diff --git "a/PMC_clustering_945.jsonl" "b/PMC_clustering_945.jsonl" new file mode 100644--- /dev/null +++ "b/PMC_clustering_945.jsonl" @@ -0,0 +1,1294 @@ +{"text": "Dear Editor,A 98-year-old male was referred complaining of a mass on his left cheek. He had never received immunosuppressive therapy. Physical examination showed a solid, dome-shaped, reddish tumor, 35\u202fmm in diameter, on his left cheek. Microscopic examination of a biopsy specimen revealed an infiltrative tumor in the dermis. The tumor was composed of sheets and trabeculae of atypical cells with scant cytoplasm, and round nuclei with stippled chromatin . Immunohvia the induction of regulatory T-cells, systemic immunosuppression may be an essential factor in the development of both conditions in a patient.Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine cancer that is known to be a highly aggressive malignancy with frequent metastasis and a high mortality rate. A previous review article revealed increased risk of a second primary cancer after the diagnosis of MCC, and cutaneous malignant melanoma (MM) is one of the most common cancers after MCC.None declared.Masato Ishikawa: Drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Toshiyuki Yamamoto: Approval of the final version of the manuscript; conception and planning of the study; critical review of the manuscript.None declared."} +{"text": "Bioengineering on \u201cStem Cell Bioprocessing and Manufacturing\u201d addresses the central role in defining the engineering sciences of cell-based therapies by bringing together contributions from worldwide experts on stem cell science and engineering, bioreactor design and bioprocess development, scale-up, and the manufacturing of stem cell-based therapies.The next healthcare revolution will apply regenerative medicines using human cells and tissues. Regenerative medicine aims to create biological therapies or in vitro substitutes for the replacement or restoration of tissue function in vivo lost due to failure or disease. However, whilst science has revealed the biomedical potential of this approach, and early products have demonstrated the power of such therapies, there is a need for the development of bioprocess technology for the successful transfer of the laboratory-based practice of stem cell and tissue culture to the clinic as therapeutics through the application of engineering principles and practices. This Special Issue of In the last few years, human pluripotent stem cell (hPSC) derivatives have emerged as promising allogeneic cell therapy products, with amazing potential to treat a wide variety of diseases and a vast number of patients globally. Brian Lee and co-authors addresseAmong the most promising hPSC derivatives, hepatic cell lineages represent a potential cell source, holding great potential for biomedical applications, such as in liver cell therapy, disease modelling, and drug discovery. Jo\u00e3o Cotovio and Tiago Fernandes assessedAlongside the development of novel bioreactor configurations for cell therapy manufacturing, efforts have also been undertaken to optimize bioreactor operating conditions. In their study focused on the manufacturing of mesenchymal stem/stromal cell (MSC) therapies, Josephine Lembong and colleagues developeAn additional key aspect towards the successful translation of cell therapy products is the need to use animal origin-free products -free) for the derivation, expansion, and differentiation of stem cells in order to minimize the risks of animal-transmitted diseases and immune reactions to foreign proteins. In this context, Valentin Jossen and colleagues developeIn addition to the increasing demand for large-scale cell manufacturing protocols, there is a critical need to establish potency assays for stem cell therapy products and their derivatives. Katharina M. Prautsch and colleagues developeExperimental culture conditions are critical for the ex vivo expansion and differentiation of stem cells. In fact, variables such as culture supplements, the purity of the initial cell population, the initial cell concentration, and the duration of culture affect the outcome of stem cell cultures and, consequently, the regenerative potential of ex vivo cultured stem cell-derived products. Sam L. Francis and co-authors focused Finally, cell-delivery methods are a key part of regenerative medicine. The delivery of stem cells and their derivatives can be performed as scaffold-free products or combined with polymer scaffolds. Traditionally, cells and biological agents are implanted into the matrix of the scaffold following electrospinning. The study performed by Nasim Nosoudi and colleagues focused"} +{"text": "In September 2017, Namibia\u2019s Ministry of Health and Social Services (MoHSS) identified an increase in cases of acute jaundice in Khomas region, which includes the capital city of Windhoek. Hepatitis E is a liver disease caused by hepatitis E virus, which is transmitted by the fecal-oral route, causing symptoms consistent with acute jaundice syndrome , development of effective communication strategies through a reformatted situation report, and supporting implementation of effective outbreak control and prevention measures.This is the third hepatitis E outbreak described in Namibia since 1983, the largest to date, and the first of nationwide scope ("} +{"text": "Defining the role of nutrients in disease prevention and control has entered a renaissance because of both breakthroughs in studying the gut associated microbiome ,2 and deFrom the earliest pen strokes in their review, Gombart, Pierre, and Maggini appropriately remind the reader of the evidence that clinical deficiencies of specific micronutrients impair immune responsiveness . A classThe role of specific micronutrients and of various combinations are painstakingly documented in , althougFood-gut microbiome-immune system interactions are an unquestionable focus of the recently released National Institutes of Health (USA) Nutrition Research Strategy ,14. The A principal focus of the Gombart, Pierre, and Maggini review is directed to infectious diseases. While this is very appropriate, it must also be considered that 60% of deaths globally are due to chronic diseases in which the immune system, as well as the gut associated microbiome, play a significant role . Whether"} +{"text": "The Role of the Lymphatic System in Lipid and Energy Metabolism, and Immune Homeostasis During Obesity and Diabetes\u201d summarizes the rapid development of the field of lymphatic vessel biology over the last two decades emphasizing its relevance to metabolism and metabolic dysregulated diseases. The Research Topic, available in Frontiers in Physiology\u2014Lipid and Fatty Acid Research, comprises 11 Reviews of the current literature, one Original Research Article, one Perspective, and one Hypothesis and Theory by experts in the field.The Research Topic \u201cXiao et al. discuss the emerging evidence that oral glucose and intestinal hormone glucagon-like peptide-2 (GLP-2) mobilize retained enteral lipid into the lymphatic system by two different mechanisms; (i) via glucose, by mobilizing cytoplasmic lipid droplets and (ii) via GLP-2, by targeting post-enterocyte secretory mechanisms. A second contribution by Zhou et al., discusses the importance of composition and properties of the matrix in the lamina propria in regulating chylomicron diffusion and their entry in the lacteals. Zhou et al. provide insights into the activation of mucosal mast cells by fat absorption and the associated metabolic consequences highlighting the link between chylomicron transport, mucosal mast cell activation, leaky gut, and the microbiome. In the Hypothesis and Theory Article, Nauli and Matin discuss a potential mechanism related to higher accumulation of abdominal visceral fat in males as compared to pre-menopausal women. The authors propose that the accumulation of abdominal visceral fat in men, a strong independent predictor of mortality, is due to the higher dietary fat uptake by abdominal visceral fat. During the post-prandial state, the larger chylomicrons observed in males congest the lamina propria and the low-pressure lymphatics, predisposing the chylomicron triglycerides to hydrolysis by lipoprotein lipase. The liberated fatty acids are then stored by the nearby abdominal visceral adipocytes, leading to the accumulation of abdominal visceral fat. These mechanisms perhaps explain the reason of bigger and higher production of chylomicrons in males.The involvement of the lymphatic system in the transport and distribution of lipids has been known for centuries . Mouse models of obesity with defective lymphatic function are summarized in Norden and Kume.The link between the lymphatic system, metabolic dysfunction, inflammation, and the metabolic syndrome is not completely understood and likely to involve multiple mechanisms and different organs. A growing body of evidence suggest that dysfunctional lymphatic vasculature might promote obesity by impairing adipogenesis and promoting inflammation. This is somehow not surprising given the adipogenic properties of lymph within the lymphatic function and progression of atherosclerosis. Another critical metabolic organ where lymphatic vessels are currently understudied is the liver. Burchill et al. review the inherent difficulties of using lymphatic markers to identify lymphatic vessels in the liver, where hepatic cells express many of the same proteins. The focus of the review, however, is summarizing newly identified roles for lymphatic endothelium in non-alcoholic steatohepatitis and hepatitis C infection.The Research Topic reviews the contribution of lymphatic biology in metabolically dysregulated diseases, including type 2 diabetes, atherosclerosis, myocardial infarction, and chronic liver disease. Zhang et al. provide a comprehensive review of the molecular regulation of LEC junctions during development, and diseases namely obesity and inflammation-associated conditions. The authors provide a comprehensive summary of lymphatic vascular phenotypes following genetic deletion of junctional proteins.Lymphatic endothelial cell (LEC) junctions are crucial for the maintenance of vessel integrity and proper lymphatic vascular function. Pawlak and Caron. The authors review five highly specialized hybrid vessel beds that adopt partial lymphatic programing for their specialized vascular functions namely (i) the high endothelial venules of secondary lymphoid organs, (ii) the liver sinusoid, (iii) the Schlemm's canal of the eye, (iv) the renal ascending vasa recta, and (v) the remodeled placental spiral artery. The authors summarize the morphology and endothelial expression pattern of these vessels and interrogate their specialized functions within the broader blood and lymphatic vascular systems (Pawlak and Caron). Finally, Azhar et al. discuss the current knowledge on the pathophysiology of lymphedema, a chronic and progressive disease arising from impaired lymphatic drainage, which causes accumulation of interstitial fluid and results in tissue swelling (Rockson, Vascular diversity and endothelial plasticity are reviewed by Rockson, . AuthorsIn conclusion, our understanding of the regulation of the lymphatic system in contributing to tissue remodeling, inflammation, and metabolic outcome during disease has greatly improved in the last two decades. However, more translational studies are needed to pave the way for novel therapeutic approaches to treat metabolically dysregulated diseases, including type 2 diabetes, atherosclerosis, myocardial infarction, and chronic liver disease, as well as lymphedema and lipedema.All authors wrote and revised the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The deformation and cracking of concrete will lead to various deterioration processes, which will greatly reduce the durability and service life of the concrete pavement. The relating previous studies and analysis revealed that the coupling action of environmental temperature, moisture, and wheel load will cause cracking and seriously affect the normal service and durability of pavement concrete. This paper presents theoretical and numerical state-of-the-art information in the field of deformation and failure of pavement concrete under coupling action of moisture, temperature, and wheel load and draws some conclusions. (a) Concrete is a typical porous material, moisture and heat transfer theory has obtained enough data to simulate the hygro-thermo properties of concrete, and the relationship between moisture and heat is very clear. (b) There are few studies on concrete pavement or airport pavement considering the coupling action of moisture, temperature, and wheel load. (c) Concrete pavement is subjected to hygro-thermal-mechanical coupling action in service, which has the characteristics of a similar period and its possible fatigue effect. (d) COMSOL software has certain advantages for solving the coupled hygro-thermal-mechanical of concrete. Cement concrete pavement is widely used in the construction of the airport runway and high-grade highway in China. More than 80% of the airport pavement in China adopts cement concrete . For pavThis paper will start from the coupling action of moisture, temperature, and wheel load that affects the deformation and failure of concrete pavement in the service life. The basic model of the multi-physical fields of concrete, research on the fatigue effect of concrete pavement, research on the deformation and failure of concrete pavement or airport pavement (except for concrete pavement or airport pavement), and the numerical simulation method of hygro-thermal-mechanical coupling deformation of concrete are discussed. This paper will provide new research ideas for the study of concrete deformation and failure of the pavement.Concrete is a typical porous medium material ,6, and iGenerally, it is assumed that the moisture transfer in porous cement-based materials is in the form of diffusion, and the humidity gradient is the driving force of humidity (liquid water and steam). According to Fick\u2019s law and mass conservation equation, the one-dimensional transmission formula is as follows :(1)\u2202\u2202x is as follows :(2). The rheological model is shown in In the formula, the For the pavement in the area with significant temperature and humidity changes, frequent takeoff and landing of aircraft or airport runway of large military multi-wheel aircraft, heavy load and frequent traffic, the pavement is more prone to deformation and damage. The problem of deformation and cracking of airport runway, highway, and urban road pavement has not been well solved because the influence factors of pavement concrete deformation and failure are not fully considered in the design stage. The above factors include temperature change, dry and wet change, and dynamic and static action of wheel load and its coupling effect. The research on the fatigue effect of airport concrete is mainly as follows: large scale airfield concrete slabs were tested by Jeffery R. Roesler in the lIn the related research on deformation and failure of airport pavement or cement concrete pavement, many researchers mainly focus on the influence of temperature, fatigue load and freeze-thaw, temperature and humidity changes on the shrinkage, and cracking of pavement concrete ,30,31,32Seongcheol. Choi et al. sMany Chinese researchers have carried out research on warpage stress. In recent years, there have been studies considering the joint effect of temperature effect and wheel load stress. Tan Zhiming et al. earlier A 3D finite element model was established for analyzing the mechanical responses of cement concrete airport pavement to multiple-gear military aircraft loadings. The test results showed that the maximum tensile stress in the pavement occurred at the bottom of the slab, the tensile stress and the deformation of the pavement under two 8-wheeled gears were smaller than that under one 8-wheeled gear. The elasticity modulus of the slab, the resilience modulus of the base and the reaction modulus of the subgrade all had significant effects on the mechanical responses of the pavement.Zheng Fei and Weng Xingzhong analyzedThe research on the hygro-thermal-mechanical coupling action analysis was previously in the field of rock engineering and had always been a research hotspot ,54. The In the research of the numerical simulation method of hygro-thermal-mechanical coupling deformation of concrete, there are four main numerical simulation methods:This method does not involve the internal heat and mass transfer mechanism and specific processes of the porous media, but only considers the relationship and cross effect between various flows and forces of heat and mass transfer. A phenomenological equation can be obtained to describe various flows. Phenomenological methods are difficult to apply in practice due to the influence of test conditions and many material parameters. Due to the lack of effective means and methods for testing moisture distribution, the moisture migration rate is slower than the thermal migration rate. In the process of solving various models, the values of some coefficients are basically based on experimental or empirical data, which affects the versatility of this method.This method considers the heat absorption or exotherm in the process of heat and mass transfer, and establishes a partial differential equation system based on the principles of mass conservation and energy conservation in the process of moisture migration. The method of numerical analysis is used to solve the equations to obtain the analytical solutions of the heat, humidity fields, and their dynamic changes ,73,74,75The finite element method is the most widely used numerical calculation method in scientific research and has become the main tool for solving scientific and technological problems. At present, many commercial finite element softwares have been developed, such as ANSYS, MSC, ADINA, ABAQUS, etc. In the finite element analysis method, the model should be established first, and then solved by self-programming ,58,63,81The analysis method of COMSOL multi-physical field coupling calculation software ,70,86 waThe studies of the coupled hygro-thermo-mechanical behavior of concrete pavement have been reviewed in this paper. The various aspects on the deformation and failure of concrete pavement under coupling action of moisture, temperature and wheel load presented in this paper could be summarized and concluded as:1. Concrete is a typical porous material, moisture and heat transfer theory had been obtained enough data to simulate the hygro-thermo-mechanical properties of concrete, and the relationship between moisture and heat is very clear.2. There has been some research on the moisture-heat-mechanical coupling of concrete materials, but most of the research focused on the performance of concrete in fire or high temperature. There are few studies on the moisture-heat-mechanical coupling deformation of concrete under normal service conditions.3. In the related research on deformation and failure of airport pavement or cement concrete pavement, many researchers mainly focused on the influence of temperature, fatigue load and freeze-thaw, and temperature and humidity changes, which lead to the shrinkage and cracking of pavement concrete. There are few kinds of literature considering the coupling action of moisture, temperature, and wheel load at the same time.4. Concrete pavement is subjected to hygro-thermal-mechanical coupled action in service, which has the characteristics of a similar period and its possible fatigue effect. In the existing moisture-heat-mechanical coupling research, the research on \u201cforce\u201d is mostly the load of a certain stress level continuously applied, but not enough attention is paid to the periodicity of wheel load and the change of temperature and humidity.5. COMSOL software has certain advantages for solving the coupled hygro-thermal-mechanical of concrete.In the later research, the deformation and failure mechanism of pavement concrete under the coupling action of moisture, temperature, and wheel load need to be studied."} +{"text": "Since its discovery in 1997, the default mode network (DMN) and its components have been extensively studied in both healthy individuals and psychiatric patients. Several studies have investigated possible DMN alterations in specific mental conditions such as bipolar disorder (BD). In this review, we describe current evidence from resting-state functional magnetic resonance imaging studies with the aim to understand possible changes in the functioning of the DMN in BD. Overall, several types of analyses including seed-based and independent component have been conducted on heterogeneous groups of patients highlighting different results. Despite the differences, findings seem to indicate that BD is associated with alterations in both frontal and posterior DMN structures, mainly in the prefrontal, posterior cingulate and inferior parietal cortices. We conclude this review by suggesting possible future research directions. To date, however, neurobiological underpinnings of the disorder are still discussed, hindering the development of new pharmacological therapies and targeted rehabilitative interventions. Findings on brain structure in BD suggest ventricular, prefrontal and temporal abnormalities but remain largely inconsistent . Particularly, rs-fMRI is used to evaluate the functional interactions among remote neural systems that occur in a resting or task-negative condition, i.e. when an explicit task is not being performed. This technique provides information about intrinsic brain activity, not dependent on specific tasks or experimental settings. Most commonly, the brain functional connectivity (FC) at rest is studied by analysing the statistical dependencies among the blood oxygenation level-dependent (BOLD) signals from multiple brain regions, which reflect the spontaneous fluctuations in the oxygenation state of blood within them seed-based analyses (SBA), which require a-priori definition of the brain network nodes, (2) blind-source separation techniques, which adopt an unbiased approach by grouping brain voxels/regions based on their latent time series the Salience Network (SN), composed of the ACC and the insula; (ii) the central-executive network (CEN) consisting of fronto-parietal regions and the posterior parietal cortex; (iii) the fronto-parietal network (FPN) that includes the cortex surrounding the intraparietal sulcus, the inferior parietal lobe, the dorsal motor cortex and the inferior frontal cortex; and (iv) the default-mode network (DMN) extending from the prefrontal medial cortex (mPFC) to the precuneus, posterior cingulate cortex (PCC) and inferior parietal cortex. The DMN is recognised as a key component of the brain functional architecture. The vmPFC composes the anterior part of the DMN and has been shown to modulate social behaviour, mood regulation, executive functioning and control processes original publication in a peer-reviewed journal between 2010 and 2020, (ii) English language, (iii) a diagnosis of BD for the patient groups and (iv) the analysis of the DMN activity patterns through rs-fMRI. After an initial screening 71 studies were identified of which 23 studies were included in the review.et al., et al., et al., et al., et al., et al., et al., et al., Overall, findings from the reviewed studies suggest that BD patients compared to Healthy Controls (HC) are characterised by marked functional alterations of both anterior and posterior hubs of the DMN, including the PFC, PCC, precuneus and inferior parietal cortex. These alterations are mostly mixed across studies, consisting of both hypo and hyper-connectivity of the anterior DMN at rest .et al., et al., et al., et al., et al., et al., et al., et al., et al., v. HC, possibly indicating specificity of the PCC alterations for the psychotic conditions showed aberrant functional activity in the posterior hubs of the DMN, of which five in the precuneus (21%) and 12 in the PCC (52%). These alterations are mostly hypo-activations of BD patients when compared with HC. Specifically, most of the studies showed FC reductions in BD compared to HC within these regions suggesting a possible relationship between the two regions without any history of medication. The authors suggest that the absence of alterations within the DMN may be due to specificity of the recruited group or on the absence of medication.Only two studies found no alterations in the DMN of BD patients , different BD populations or the lack of control for confounders that may have influenced the results compared to HC in both frontal and posterior hubs of the DMN. In particular, the evidence to date suggests that BD patients compared to HC have altered FC of the DMN in a number of regions including the PFC, the ACC and PCC and the precuneus. However, only a paucity of studies has been conducted and evidence is still sparse. The inconsistency of findings may be due (in part) to methodological issues such as heterogeneous analysis pipelines can account for the complex dynamics in the interactions between brain regions as suggested by some studies investigate the complex link between structure and function in the DMN and other networks involved in BD pathophysiology, (2) identify neurodevelopmental and maturation trajectories of FC patterns in relation to the natural course of the disease and in response to different therapeutic strategies, (3) disentangle the contributions of genetics, environment and their interaction to the large-scale functional brain network abnormalities underlying BD symptomatology.The data that support the findings of this study (search query) are available on request from the corresponding author."} +{"text": "The Industrial Internet of Things is the emerging core backbone construct for the various cyber-physical systems constituting one of the principal dimensions of the 4th Industrial Revolution. While initially born as a concept inside specific industrial applications of the generic IoT technologies, for the optimization of the operational efficiency in automation and control, it quickly became the vehicle for the achievement of the total convergence of Operational Technologies (OT) with Information Technologies (IT). Today, it is already breaking the traditional borders of automation and control functions in the process and manufacturing industry, towards a wider domain of functions and industries, embraced under the dominant, global initiatives and architectural frameworks of Industry 4.0 (or Industrie 4.0) in Germany, Industrial Internet in the US, Society 5.0 in Japan, and Made-in-China 2025 in China. As real-time embedded systems are quickly achieving ubiquity in people\u2019s everyday life and in industrial environments, and many processes already depend on real-time cyber-physical systems and embedded sensors, IoT integration with cognitive computing and real-time data exchanges is essential for real-time analytics and realization of digital twins in smart environments and services under the various frameworks\u2019 provisions ,2. In thThe ten articles in this Special Issue provide advances of real-time sensor networks and systems that are significant enablers of the Industrial IoT paradigm. In the relevant landscape, the wireless networking technologies domain is centrally positioned, as expected. Seferagi\u0107 et al. comparatively discuss various alternatives for the engineering and deployment of industrial wireless sensor and actuator networks (IWSAN) in . In thisSeveral articles in this Special Issue address important industrial IoT security and infrastructure protection issues. Tedeschi et al. analyze the integration of modern IoT and legacy industrial equipment for real-time machine condition monitoring applications, and the resulting security challenges in . The autThe real-time performance of the evolving IIoT networks and systems is increasingly considered among the major IIoT challenges, together with energy efficiency, security, and interoperability . Coming For all these reasons, we expect that the pressure for solutions will be increased with the upcoming penetration of 5G and the"} +{"text": "The importance of teamwork to improve the quality of care and overcome the complexity of health system is clear to everyone. Therefore the current study aimed to review the studies in the field of team-work assessment in hospital and pre-hospital emergency.In this review study, scientific texts with the key-words of teamwork, paramedic, emergency medical technician, emergency department and inter-professional practice were searched in Google scholar, PubMed, scientific information database(SID), and Magiran.Several studies have been found on the training and evaluation of teamwork in different parts, particularly in the treatment section. The results show that training and promotion of teamwork in health care lead to better performance and results, reducing clinical errors and reducing patient long length of stay In wards especially in the emergency department. Studies indicate that organizational support and teamwork training has the greatest impact in teamwork facilitate. In the pre-hospital emergency, there was a wide variety of teammates and less familiarity with teammates in EMS is associated with more occupational injuries. According to the aid team of pre-hospital emergency and their interaction with the hospital emergency department and other relief teams, training and evaluation of teamwork is important in EMS. However, there are few studies on teamwork in pre-hospital emergency especially in Iran. According to the importance of pre-hospital emergency mission, it is necessary to pay attention to teamwork in the emergency training curriculum and evaluation of teamwork in pre-hospital EMT. Teamwork, Pre-hospital, Emergency, Medical technician"} +{"text": "This paper presents a comparative analysis of the gross regional products (GRPs) of 85 Russian regions. Statistical methods were used to analyze datasets on regional GRP, its sectoral composition and growth rates. Many datasets have been computed for the first time, including those of gross value added per capita and per employee. The work reviews a range of evidence on the contribution of the production of goods and market and non-market services to regional GRPs. The production of goods was further analyzed by economic sectors for each region. The data used in computations were provided by the Russian Federal State Statistics Service (ROSSTAT). The authors built a typology of Russian regions based on GRP figures, GRP sectoral composition and growth rates. The data obtained make it possible to determine a set of indicators of the geographical distribution of Russia's economy and its growth rates. The findings are presented in the form of tables, maps and graphic materials , displaying quantitative measures of the economic performance of Russian regions . In this work, we performed a comparative analysis of GRP output, GRP sectoral composition and growth rates of 85 Russian regions. These indicators have been extensively analyzed in economic literature. Many authors have built their typologies of regions based on GRP per capita This work presents a comprehensive large-scale assessment of the gross regional products of 85 Russian regions. The computations characterize the level of economic development of different parts of the country: GRP measures the value of goods and services produced in a region; GRP per capita reflects the economic output of a region and the standard of living; the ratio of different economic sectors defines the sectoral composition of regional economies. Special attention was paid to the analysis of datasets for the production of goods, market and non-market services.The sectoral composition of GRP was analyzed using two datasets \u2013 on GRP per capita and GRP growth rates. This makes it possible to evaluate the economic performance of individual sectors of the regional economy and to measure labor productivity and economic growth rates.Cartographic representation of GRP helps reveal similarities and disparities in regional economic development.1)GRP per capita and employee \u2013 gross value added per sector (per type of economic activity);2)GRP sectoral composition of consolidated groups of economic activity \u2013 the production of goods per economic sector3)GRP growth rates - GRP per capita.Types and subtypes of regions were identified based on the following coupled indicators:The initial and computed statistical data are presented in three tables, two diagrams and 10 cartographic maps for all 85 regions of the Russian Federation. They illustrate GRP figures and sectoral composition in 2018 and the growth rates of GRP per capita during two periods \u2013 2004\u20132018 and 2013\u20132018.The economic differentiation of Russian regions is analyzed according to 30 indicators.The aggregated GRP and social indicators datasets on Russian regions are available in spreadsheets (Annex 1).The aggregated GRP per economic sectors in 2018 datasets on Russian regions are available in separate spreadsheets (Annex 2).Annex 3 contains tables presenting groups of Russian regions formed according to the chosen indicators see , Fig. 14Regions of the Russian Federation differ greatly in size, natural resources, the number and replacement rate of the population, GRP figures and other socio-economic indicators. For instance, Sevastopol, a city of federal importance, (territory \u2013 0.9 thousand sq. km) is 3.4 thousand times smaller than the Republic of Sakha (Yakutia) (3083.5 thousand sq. km). The population of the Nenets autonomous region is 288 times smaller than that of Moscow . In 2018, the GRP of the Republic of Altai amounted to 51 billion rubles, whereas that of Moscow to 17 882 billion rubles, which is 351 times as much. In 2018, the highest average annual growth rate of GRP per capita as compared to 2013 was 6.5% , and the largest decrease was -2.0% in the Republic of North Ossetia-Alania.The GRP of Moscow is four times that of the Khanty-Mansi autonomous region, which is the second-largest oil-producing region in Russia. The Moscow region (forming a single agglomeration with the city of Moscow) and St. Petersburg, which is often referred to as the second or cultural capital of the Russian Federation , have almost reached the GRP of Moscow.The data in We established correlations between GRP per capita of Russian regions and some other socio-economic indicators. The coefficient of linear correlation of GRP per capita with urban population figures and population density is extremely small \u2013 0.25 and 0.08 respectively.Although many highly urbanized regions of Central Russia and the Volga region have rather low GRP per capita, the Moscow agglomeration boasting a very high level of urbanization is the social and economic nucleus of the country. The St. Petersburg agglomeration also plays an important role.The correlation between these two indicators is rather low: the linear correlation coefficient is 0.14. As Of all federal districts of Russia, only the regions of the Far East saw an increase in GRP per capita.In the Siberian Federal District, GRP per capita decreased in the analyzed period. The decrease was particularly dramatic in the Republic of Buryatia (7%), which had already had very low per capita figures. In the Ural Federal District, there are two territories, the Tyumen Oblast and the Khanty-Mansi autonomous region, which belong to regions with high GRP per capita.Two regions in the Southern Federal District and three in the North Caucasus also have declining GRP figures. At least one region saw a decline in GRP per capita in the Central, Northwestern and Volga Federal Districts.Further research requires analysis of the GRP sectoral composition. The main Russian oil and gas regions have the largest share of the production of goods in their GRP structure: the Nenets (88.4%), Khanty-Mansi (83.4%) and Yamal-Nenets autonomous regions (82.7%) and Sakhalin (80.4%) , St. Petersburg (54%) and the Moscow (53%), Primorye (52%) and Novosibirsk (51%) regions. The highest percentage of non-market services (33%\u201350%) is typical of Russia's national republics \u2013 Ingushetia (50%), Chechnya, North Ossetia-Alania, the Karachay-Cherkess Republic in the North Caucasus, Altai, Tyva, Buryatia in southern Siberia, as well as of cities of national importance (Sevastopol). This can be explained by a weaker development of the other two sectors \u2013 the production of goods and market services.The Belgorod region, located in the Chernozem zone of Russia, has fertile soils and is well developed industrially. The region has the highest value added both per capita and per employee. Other regions of the Chernozem zone \u2013 Orlov, Kursk, Lipetsk, Voronezh, Tambov and Bryansk (the latter belongs to the Non-Chernozem zone and has intensive farming) are catching up.Regions of the North Caucasus , Volga regions and the Novgorod region are characterized by a relatively high GRP per capita. High per capita figures of some coastal regions can be attributed to the development of fishing and fish farming. The Primorye region also has highly developed forestry and logging. Many northern and eastern regions having relatively high gross value added figures employ more people in forestry and logging than in agriculture. Territories with the least favorable natural conditions have poorly developed agriculture. These are the Arctic coastal regions of Siberia and the Far East, regions bordering Mongolia and the regions of the Northern Urals. Crimea and some regions of the Middle Volga region, Central and North-West of the European part of Russia have low value added figures.The highest value added per capita (over 1 million rubles) and per employee (over 10 million rubles) was registered in the main oil and gas regions \u2013 Sakhalin region and the Khanty-Mansi and Yamal-Nenets autonomous regions. The Republic of Sakha (Yakutia) and the Chukotka autonomous region have high value added per capita ranging from 500 thousand to 1 million rubles, and per employee \u2013 from 5 million to 20 million rubles. All these regions, except the Nenets autonomous region, are located in Siberia and the Far East. In the Krasnoyarsk (Eastern Siberia) and Magadan regions (Far East), the Orenburg region , the Komi Republic (North-West) and the Astrakhan region , value added per capita and per employee exceeds 200,000 rubles and 5 million rubles respectively. Central Russia (except the Belgorod region), the southern part of Russia's north-west, the east of the Volga region, North Caucasus and some southern regions of Western Siberia have the lowest per capita and employee figures.The manufacturing industry of Russia employs 14% of the working population. A higher percentage is observed only in trade and the repair and maintenance of motor vehicles and motorcycles (19%). The most developed manufacturing regions having high gross value added per capita and per employee are located in Central Russia and in the south of Russia's north-west, the Middle Volga region, in the Urals, as well as in the eastern regions of the country \u2013 primarily in the Krasnoyarsk region and the Tyumen region see . Most eaNorthern and eastern regions take the lead in the production of electric energy, gas, steam and air conditioning. This can be attributed to severe climatic conditions, which require considerable investment in the production of electric energy and heat for industrial and household needs . There aWater supply, wastewater treatment, waste collection and disposal and pollution elimination are most developed in the northern regions of Russia having cold climate \u2013 in the Republic of Sakha (Yakutia), the Murmansk region, the Yamal-Nenets and Chukotka autonomous regions) and in the most economically developed and highly urbanized regions . These industries are the least developed in the republics of North Caucasus, southern Siberia and the Far East .In construction and the production of goods, value added per capita differs from region to region . There iMoscow, the Republic of Tatarstan, and the Leningrad region have the highest indicators among industrially developed regions.Among market services, the share of trade and repair of motor vehicles and motorcycles in the GRP sectoral composition is 44%; that of transportation and storage, 17%. The development of these sectors largely determines the value added per capita and per employee, which is the highest (as is the case for the production of goods) in the two capital cities, Moscow and St. Petersburg, and in the main oil and gas regions, the Nenets, Khanty-Mansi and Yamal-Nenets autonomous regions was used to form 13 groups within the 85 regions. Subdivision into subgroups was done by means of expert evaluation.The proposed classification of regions can be used for comparative analysis of the geographical distribution of economic centers in Russia and the assessment of Russia's economy.2Regions of Russia reference book. These data were used for computing average values of GRP per capita and per employee as well as chain indices of GRP growth rates. Coefficients of linear correlation between GRP and its growth rates, on the one hand, and other socio-economic characteristics of regions, on the other, were also calculated.Statistical data were obtained from the EMISS database of the Federal State Statistics Service of Russia and the The data obtained are presented in three tables, three charts and 11 cartographic maps displaying quantitative indicators.http://dx.doi.org/10.17632/n36vrd8zrp.1Transparency data associated with this article can be found in the online version at The authors declare no competing interests."} +{"text": "This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses When the body encounters harmful stimuli, such as invading pathogens, wounding or damaged cells, the immune system will be activated and an inflammatory response is triggered ] and non-steroidal anti-inflammatory drugs as a research model started in the 1950s and it was initially applied for studying embryonic development , for which guidelines have been published by the Organization for Economic Co-operation and Development . In addiFigure 2 for a schematic overview of these different methods), and we discuss how they are used for studies on the molecular mechanisms underlying the inflammatory response as well as for research aiming at the development of novel anti-inflammatory drugs, in particular novel GC drugs.The immune system of zebrafish is highly similar to that of humans. The innate branch of the immune system matures first during zebrafish development, and macrophages can be observed from 15 h post-fertilization (hpf) promoter ] gradient from the wounded site, through local activation of the epithelial NADPH oxidase Duox was found to mediate migration by inducing actin polymerization and generating membrane protrusions at the leading edge through Rac activation and polarization of F-actin dynamics (in a Rac-independent way), which is required for actomyosin-mediated tail contraction reporter line, similar to the differentiation processes that are observed in mammalian macrophages , and results in an increased expression of pro-inflammatory molecules like tnfa, il1b, il6, and il8 is known to be a potent chemoattractant for neutrophils in mammalian systems resulted in impairment of the fin regeneration, and the presence of large vacuoles in the regenerated tissue resulted in suppression of neutrophil apoptosis and reduced the level of inflammation in zebrafish larvae.In order to find new anti-inflammatory drugs from collections of existing or clinically approved drugs and cytokines -38, known to be an anti-apoptotic and anti-inflammatory factor, was reported to inhibit neutrophil migration toward the neuromasts and expression of pro-inflammatory genes (Leukotriene B4 (LTB4) is an eicosanoid released by leukocytes, acting as a pro-inflammatory mediator and enhancing leukocyte accumulation at sites of inflammation represents a group of intestinal disorders that are characterized by inflammation of the digestive tract Hanauer, . IBD is il1b, tnfa, mmp9, ccl20, and il8 was observed upon TNBS treatment has also been utilized to induce intestinal inflammation. This treatment recapitulates several aspects of TNBS-induced enterocolitis, inducing symptoms such as elevated expression of pro-inflammatory genes and neutrophil recruitment around the intestine , and was shown to result from soy saponin and not soy protein and decreased the relative number of Firmicutes (Lactobacillus group) in the composition of the larval microbiota, and these changes correlated with the severity of the enterocolitis anti-inflammatory and antibiotic drug treatments which ameliorated the response to TNBS played a critical role. Morpholino knockdown of mmp9 partially rescued the abnormal epithelial phenotype as well as the neutrophilic infiltration of the epithelium, and restored the organization of collagen fibers.To identify genes with essential functions during zebrafish skin development, a screen of mutants generated by insertional mutagenesis was performed gene was identified axis, the fish equivalent of the HPA axis (Wendelaar Bonga, irg1l, thereby inhibiting the ROS production which is important for leukocyte migration (Hall et al., il8, tnfa, and il1b and reduced the recruitment of leukocytes toward the wounded area (Kyritsis et al., Upon tail amputation in embryos, treatment with several synthetic GCs has been shown to inhibit the migration of neutrophils toward the wounded site in a Gr-dependent manner. However, GCs leave the migration of macrophages unaffected in most studies (Mathew et al., 4 immersion of larvae, GCs also caused inhibition of neutrophil accumulation (d'Alen\u00e7on et al., In the LPS-induced inflammation model, GC administration was reported to inhibit the production of ROS and NO, the expression of pro-inflammatory genes, the recruitment of leukocytes, and the mortality (Wijesinghe et al., The clinical use of GCs is severely limited by the severity of their side effects, which include diabetes and obesity, osteoporosis, and impaired wound healing. Interestingly, these effects have been modeled in zebrafish as well, opening up the possibility to evaluate both the therapeutic anti-inflammatory effect and the adverse effects. GC effects on metabolism, including increased glucose concentrations, were observed in zebrafish embryos and the global transcriptional changes underlying these effects have been characterized (Chatzopoulou et al., in vivo, mainly due to the small size and transparency of zebrafish larvae. The similarities of the immune system and inflammatory responses between zebrafish and mammals guarantee good translational value.The use of animal models is a critical part of biomedical research and crucial for the development of novel drugs. A wide range of human disease models have been established in mammalian models such as rats and mice, which have largely contributed to the remarkable progress in our understanding of the mechanisms underlying these diseases and the development of novel therapies. However, the rodent systems have limitations such as the high cost of housing and breeding and they are not suited for large-scale automated screening. The development of the zebrafish animal model in the past decades has added a complementary system, which allows the performance of automated high through-put screening 2O2 gradient is created during the onset of an inflammatory response which signals to leukocytes in the tissues (Niethammer et al., in vitro assays and rodent experiments with great potential to accelerate the preclinical phase of anti-inflammatory drug development.In order to model inflammatory diseases, three types of inflammation models have been developed in zebrafish: wounding-, chemical-, and mutation-induced inflammation. These models have enabled a detailed investigation of the cellular and molecular mechanisms underlying the inflammatory response, adding to our knowledge of the mechanisms of leukocyte behavior and the identification of potential drug targets. For example, using the zebrafish model, it was observed for the first time that a tissue-scale HAM and MS: conceptualization, resources, and supervisions. YX, AM, and MS: methodology and writing\u2013review & editing. YX: investigation and funding acquisition. YX and MS: data curation and writing\u2013original draft. MS: project administration. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Internet of Things (IoT), or Industry 4.0, represents a smart shift to more interconnected manufacturing processes where individual entities within the supply chain communicate with each other to achieve greater flexibility and responsiveness in general manufacturing and leaner manufacturing to reduce the cost of production. IoT has become instrumental in driving leaner manufacturing and more efficient systems in other industries such as transportation and logistics. Cell-based therapeutic products could potentially transform various diseases; however, the delivery of these products is complex and challenging.This study aims to understand the applicability of IoT in cell-based product supply chains and delivery.We will search Medline, EMBASE (OvidSP), Web of Science, Cochrane Library & HEED, Scopus, ACM digital library, INSPEC, ScienceDirect, and the IEEE Xplore Digital Library for studies published after 2008 using a combination of keywords and subject headings related to IoT used in cell therapies. Additionally, a Google search to identify gray literature will be conducted. Two authors will independently screen the titles and abstracts identified from the search and accept or reject the studies according to the study inclusion criteria. Any discrepancies will then be discussed and resolved. The quality of the selected literature will be assessed using the Critical Appraisal Skills Programme systematic review checklist.Data from eligible publications will be abstracted into a predesigned form to map the current and future directions of the technologies, applications, benefits, and challenges in the implementation of IoT in regenerative medicine. This study will be published in a peer-reviewed journal in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This systematic review will be executed by June 2020, and the completed review will be published in a peer-reviewed journal to inform future developments in IoT application for the delivery of cell-based therapies.This review paper will provide an overview of all technologies available in the area and inspect the current IoT applications in cell-based therapies to identify the benefits, challenges, and future directions of using IoT to allow safe and cost-effective delivery of cell-based therapies.PRR1-10.2196/16935 Internet of Things (IoT) is a concept first proposed by Ashton at a preOver the last two decades, IoT has been successfully implemented in various industries including aerospace, aviation, automotive, telecommunications, medicine and health care, independent living, pharmaceutical, retail, logistics and supply chains, manufacturing, process, environmental, transportation, agricultural and breeding, media and entertainment, recycling, and insurance ,3. VarioA survey of the trends and topics in IoT research conducted by Whitmore et al in 2015 Technology platforms for facilitating information flow and exchange have been made available by industry and academic partnerships. Vitruvian Networks, for instance, is a partnership set up by GE Ventures and Mayo Clinic to make use of biomarkers, cell therapy processes, and clinical outcome data to guide therapy development . IoT allThis paper aims to systematically review all technologies available in the area, and inspect the current IoT application in cell-based therapies to identify the benefits, challenges, and future directions of using IoT to allow safe and cost-effective delivery of cell-based therapies.The aim of this review is to understand the current available technologies for IoT, the extent of implementation in cell-based therapy delivery, and the drivers and challenges for implementation of IoT. This will allow the gaps for IoT implementation to be identified and will inform future directions in cell therapy supply chain optimization.Our research questions are as follows:What is the current state of IoT implementation in cell-based therapy delivery? What companies and partnerships are engaged in IoT ?What are the technologies available for IoT specific to cell-based therapy delivery?What are the benefits of IoT in cell-based therapy delivery?What are the challenges of implementing IoT on cell-based therapy delivery?This systematic review will be conducted following the PRISMA guidelines 20]..20].In accordance with the PRISMA-P (Protocols) checklist recommendation, the inclusion criteria of this protocol are in accordance with the PICO standards. Details of the PICO to be included in the review are described in ParticipantPatients receiving cell-based therapyInterventionAny supply chain step using or interacting with the Internet of Things (IoT) technologies/networks in a cell-based therapy delivery process, from patient cell collection (if autologous) or cell sourcing to postadministration monitoring and follow-upComparatorNo intervention, standard practice, or any other type of intervention that is not IoT such as paper-based batch recordsOutcomesBenefits and challenges of IoT implementation in tissue or cell-based therapy deliveryStudy typeAny study type (study type will not be subjected to any restrictions)Publications between 2008-2018English publicationsThe fields of both IoT and cell therapy are rapidly advancing; therefore, to ensure that studies found are up to date, only publications from 2008-2018 will be considered. Studies not published in the English language are excluded due to a language barrier. Studies relevant only to the discovery, research, and development phases of cell-based therapies are not in the scope of this review.The following databases will be searched: Medline, EMBASE (OvidSP), Web of Science, Cochrane Library & HEED, Scopus, ACM digital library, INSPEC, ScienceDirect, and the IEEE Xplore Digital Library. In addition, a search on Google to identify gray literature will be conducted. EndNote X8 software will be used for the removal of duplicates. Two reviewers will independently check each article to minimize bias using the collaboration\u2019s risk of bias tool as described in the Cochrane Handbook for Systematic Review of Interventions . All selThe eligible literature will then be described for its three-layer architecture of IoT proposed in various literature ,23. Any Current practice/company and future directions for the items belowSensing layer:Sensing devices and technologies such as radio frequency identification tagsNetwork layer:Service entities arrangement, virtual entity and information, resource modulesApplication layer:Functionalities of Internet of ThingsObserved benefits (if any)Observed challenges (if any)The study aims to provide a landscape of the application of IoT technologies in the cell therapy field and identify the gaps and challenges for IoT application. A sample search was conducted on the PubMed database, and the search strings used are described in This review paper will provide an overview of all technologies available in the area and inspect the current IoT application in cell-based therapies to identify the benefits, challenges, and future directions of using IoT to allow safe and cost-effective delivery of cell-based therapies."} +{"text": "This Special Issue is focused on measuring and characterizing the mechanical and adhesive properties of cells and membranes.Cell mechanics has an important impact on cellular functions and cell fate. The field has developed very rapidly in the last two decades, incorporating elements of cell biology, biophysics and nanotechnology. In particular, the study of lipid membranes, erythrocytes, and endothelial cells have been performed with several techniques, such as scanning force microscopy, laser pinzette, optical tweezers, and many others. Although a great advance has been achieved in recent years, the characterization of the cells properties and the understanding of the results at cellular and molecular level are still a major challenge for researchers in this area.In this issue, the principles and techniques used in studies of cell and membrane biomechanics and adhesion have been addressed. The reader will find five comprehensive experimental research articles in the oncological field, and another article dealing with cell membrane adhesion modelling, which reports the last developments in the area of adhesion and biomechanics of cancer cells. Experimentally, three of them are closely connected, since the authors used a combination of atomic force microscopy and confocal and/or fluorescence microscopy to investigate morpho-structural/cytomechanical modifications induced by anti-neoplastic drugs or proteins in cancer cells and/or the cell membrane.In one of these contributions, Mariafrancesca Cascione and co-workers , in an aOn the same line, Jagoba Iturri et al. employedIn another paper with a similar approach, Xiaoli Zhang and co-authors have invADAM17 gene found in the tissue of colon cancer patients. In order to shed light on the role of ADAM17 in cancer development, as well as into the mechanisms that regulate maturation and cellular trafficking of ADAM17, they perform overexpression investigations of four ADAM17 variants located in the pro-, membrane-proximal- and cytoplasmic-domain of the ADAM17 protein in ADAM10/17-deficient HEK cells. They found a cancer-associated point mutation within the pro-domain of ADAM17 (R177C), to be most impaired in its proteolytic activity and trafficking to the cell membrane, and discovered similar functional limitations [In an interesting study, Egor Pavlenko and co-workers characteitations . FinallyYAP1 target genes and cell proliferation [Another contribution authored by Jutamas Uttagomol et al. investigferation . The curIn the only theoretical contribution, Long Li et al. proposedFinally, we are confident that these articles will readily contribute to the progress in the area of nano/biomechanics, and will further stimulate future studies dedicated to understanding the link between the mechanical properties of cells and membranes, as well as the physico-biological mechanisms and pathways involved."} +{"text": "Besides general information including Q&As, daily case counts, and maps with disease distribution, examples of latest updates comprise: Poster: Effective hand-washing, COVID-19 - How to minimise the spread? and Considerations relating to social distancing measures in response to the COVID-19 epidemic. ECDC also publishes regular risk assessments and the The European Centre for Disease Prevention and Control (ECDC) provides regularly updated information on coronavirus disease-2019 (COVID-19) relevant to Europe on a dedicated BoxOn 31 December 2019, a cluster of pneumonia cases of unknown aetiology was reported in Wuhan, Hubei Province, China. On 9 January 2020, China CDC reported a novel coronavirus as the causative agent of this outbreak, which is phylogenetically in the SARS-CoV clade. The disease associated with the virus is referred to as novel coronavirus disease 2019 (COVID-19).As of 11 March 2020, 118,598 cases of COVID-19 were reported worldwide by more than 100 countries. Since late February, the majority of cases reported are from outside China, with an increasing majority of these reported from EU/EEA countries and the UK.The Director General of the World Health Organization declared COVID-19 a global pandemic on 11 March 2020.All EU/EEA countries and the UK are affected, reporting a total of 17,413 cases as of 11 March. Seven hundred and eleven cases reported by EU/EEA countries and the UK have died. Italy represents 58% of the cases and 88% of the fatalities (n=631). The current pace of the increase in cases in the EU/EEA and the UK mirrors trends seen in China in January-early February and trends seen in Italy in mid-February.In the current situation where COVID-19 is rapidly spreading worldwide and the number of cases in Europe is rising with increasing pace in several affected areas, there is a need for immediate targeted action. The speed with which COVID-19 can cause nationally incapacitating epidemics once transmission within the community is established, indicates that in a few weeks or even days, it is likely that similar situations to those seen in China and Italy may be seen in other EU/EEA countries or the UK.There are no vaccines available and there is little evidence on the effectiveness of potential therapeutic agents.In addition, there is presumably no pre-existing immunity in the population against the new coronavirus and everyone in the population is assumed to be susceptible. Clinical presentations of COVID-19 range from no symptoms (asymptomatic) to severe pneumonia; severe disease can lead to death. While the majority of cases (80%) are milder respiratory infections and pneumonias, severe illness and death is more common among the elderly with other chronic underlying conditions, with these risk groups accounting for the majority of severe disease and fatalities to date.The risk of severe disease associated with COVID-19 infection for people in the EU/EEA and UK is currently considered moderate for the general population and high for older adults and individuals with chronic underlying conditions, based on the probability of community transmission and the impact of the disease. The risk of healthcare system capacity being exceeded in the EU/EEA and the UK in the coming weeks is considered high. The impact and risk assessment on health system capacity can be mediated by the application of effective infection prevention and control and surge capacity measures.The risk of transmission of COVID-19 in health and social institutions with large vulnerable populations is considered high. The impact of transmission in health and social institutions can be mediated by the application of effective infection prevention and control and surge capacity.The EU/EEA and the UK are quickly moving toward a scenario of sustained community transmission of COVID19. The situation is evolving very quickly and a rapid, proactive and comprehensive approach is essential in order to delay transmission, as containing transmission to local epidemics is no longer considered feasible. A rapid shift from a containment to a mitigation approach is required, as the rapid increase in cases, that is anticipated in the coming days to few weeks may not provide decision makers and hospitals enough time to realise, accept and adapt their response accordingly if not implemented ahead of time. Measures taken at this stage should ultimately aim at protecting the most vulnerable population groups from severe illness and fatal outcome by reducing transmission and reinforcing healthcare systems.Given the current epidemiology and risk assessment, and the expected developments in the next days to few weeks, the following public health measures to mitigate the impact of the pandemic are necessary in EU/EEA countries:Social distancing measures should be implemented early in order to mitigate the impact of the epidemic and to delay the epidemic peak. This can interrupt human-to-human transmission chains, prevent further spread, reduce the intensity of the epidemic and slow down the increase in cases, while allowing healthcare systems to prepare and cope with an increased influx of patients.Such measures include:the immediate isolation of symptomatic persons suspected or confirmed to be infected with COVID-19;the suspension of mass gatherings, taking into consideration the size of the event, the density of participants and if the event is in a confined indoor environment;social distancing measures at workplaces ;measures in and closure of schools, taking into consideration the uncertainty in the evidence of children in transmitting the disease, need for day care for children, impact on nursing staff, potential to increase transmission to vulnerable grandparents;cordon sanitaire of residential areas with high levels of community transmission.Ensuring the public is aware of the seriousness of COVID-19. A high degree of population understanding, solidarity and discipline is required to apply strict personal hygiene, coughing etiquette, self-monitoring and social distancing measures. Community engagement and acceptance of stringent social distancing measures put in place are key in delaying and reducing further spread.Prevention and control of COVID-19 in hospitals and long-term care facilities is an immediate priority in order to: (1) slow the demand for specialised healthcare, such as ICU beds; (2) safeguard populations vulnerable to severe outcomes of infection (3); protect healthcare workers that provide care; (4) minimise the export of cases to other healthcare facilities and the community.Every healthcare facility should initiate training for all staff and those who may be required for healthcare provision during surge capacity. Countries should identify healthcare units that can be designated to care for COVID-19 cases, to minimise transmission to non-cases and to conserve PPE. Countries and healthcare institutions should identify additional facilities that can be used for the cohorting of cases with mild symptoms, in the event that surge capacity is exceeded by healthcare facilities. The highest priority for use of respirators (FFP2/3) are healthcare workers, in particular those performing aerosol-generating procedures, including swabbing.If resources or capacity are limited, rational approaches should be implemented to prioritise high-yield actions, which include: rational use of confirmatory testing, reducing contact tracing to focus only on high-yield contacts, rational use of PPE and hospitalisation and implementing rational criteria for deisolation. Testing approaches should prioritise vulnerable populations, protection of social and healthcare institutions, including staff.National surveillance systems should initially aim at rapidly detecting cases and assessing community transmission. As the epidemic progresses, surveillance should monitor the intensity, geographical spread and the impact of the epidemic on the population and healthcare systems and assess the effectiveness of measures in place. In circumstances with capacity shortages and strict implementation of social distancing measures, surveillance should focus on severe acute respiratory infections, sentinel surveillance in outpatient clinics or collection of data through telephone helplines.A strategic approach based on early and rigorous application of these measures will help reduce the burden and pressure on the healthcare system, and in particular on hospitals, and will allow more time for the testing of therapeutics and vaccine development.What is new in this update?Updated data on the epidemiological situation in the EU/EEA and the UKRecent findings on disease and transmissibility, including during the asymptomatic periodRisk associated with COVID-19 for people from the EU/EEA and the UKRisk of local and widespread national community transmission in the EU/EEA and UK in the coming weeksRisk to healthcare systems capacity being exceeded in the EU/EEA and the UK in the coming weeksRisk of transmission of COVID-19 in health and social institutions with large vulnerable populationsOptions for preparedness and response focused on the mitigation phase, including rational measures in case of resource constraints or shortagesUpdated surveillance objectives and methods for the mitigation phase.https://www.ecdc.europa.eu/sites/default/files/documents/RRA-sixth-update-Outbreak-of-novel-coronavirus-disease-2019-COVID-19.pdfSource: European Centre for Disease Prevention and Control (ECDC). Rapid risk assessment: Novel coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK \u2013 sixth update. ECDC: Stockholm; 12 March 2020. Available from: COVID: coronavirus disease; ECDC: European Centre for Disease Prevention and Control; EU/EEA: European Union/European Economic Area; ILI: influenza-like-illness; SARS-CoV: severe acute respiratory syndrome coronavirus; UK: United Kingdom."} +{"text": "With its roots firmly planted in the fields of CNS autoimmunity and infection, the rapidly growing field of neuroimmunology is branching out to include almost every area of neurophysiology and neurological disease to encompass brain development and function, psychiatric illnesses, inflammatory demyelinating diseases, cancer, infections, and neurodegeneration of the central and peripheral nervous systems. The nervous system is also functionally intimately interconnected, via immune mechanisms, to multiple other processes and organ systems including systemic inflammation, gut microbiome, and chronic pain, to name a few. The scope of neuroimmunology and its implications for the understanding of human health and disease, from diagnosis through therapeutics, was highlighted during the 14th Congress of the International Society for Neuroimmunology (ISNI) 2018, and the associated 2nd Global Schools of Neuroimmunology (GSNI), held together in August 2018 in Brisbane, Australia. The richness of topics covered is further illustrated through the series of related articles presented in this special issue of Frontiers in Neurology entitled \u201cUpdate on Translational Neuroimmunology Research of ISNI 2018.\u201dThe Congress highlighted the importance taking the knowledge gained from translational research and clinical experience back into the research environment to gain further understanding of immune-mediated diseases affecting the human CNS and how to overcome them. During the meeting, dedicated symposia covered diverse topics of CNS and PNS autoimmunity, immune dysfunction, and immunotherapy, covering a wide range of neuroimmune interactions in health and disease. For example, disease topics ranged from immune-mediated conditions, such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), myasthenia gravis, and autoimmune encephalopathies and neuropathies, to inflammation in conditions usually thought of as neurodegenerative, such as Alzheimer's disease (AD), Parkinson's disease (PD), motor neuron diseases, neuropsychiatric diseases, as well as traumatic injuries and infections by parasites and neurotropic RNA viruses including West Nile and Zika.McCombe et al. review the emerging evidence that the peripheral immune system contributes to motor neurodegeneration in amytrophic lateral sclerosis (ALS), and implications for therapeutic targeting to manage the disease. This parallels current thinking in AD that peripheral inflammation influences inflammation in the brain. In a similar vein, Yates et al. review the current evidence suggesting that extracellular vesicles (EVs) shed from CNS cells, cross the blood brain barrier (BBB), and play a critical role in activating peripheral immune responses to traumatic CNS injury. Vilquin et al. describe the consequences of autoimmune attack against components of the neuromuscular junction in myasthenia gravis, focusing on the response of the ultimate target in this disease, the muscle. Fujii et al. turn their attention to investigating the link between allergic inflammation and neuropathic pain, describing a possible role for spinal cord glial inflammation and autoantibodies that target sensory neurons in the dorsal root ganglia.The involvement of immune mechanisms in psychiatric diseases was introduced at GSNI on the first day of the meeting and during the main meeting in talks by Lennox and Brown. In this issue, van Langelaar et al. further discuss the types of T cell-B cell interactions that might be important for MS pathogenesis, Greer et al. report that autoantibodies to the major myelin protein, proteolipid 181\u2013230 peptides, are increased in a subgroup of MS patients and that their levels positively correlate with disease severity, while Young reviews the differential effects of antibodies to the GluN1 subunit of the glutamate NMDA receptor in pathogenesis of neurological diseases.The dramatic clinical success of B cell depleting immunotherapies in patients with MS, as well as CNS diseases that involve autoantibodies such as NMOSD, has focused research on understanding the critical roles of B cells, and their interactions with T cells, in the pathogenesis of MS and other neuroimmune diseases. B cells produce antibodies, present antigens to T cells, and produce pro-inflammatory and anti-inflammatory cytokines, and all these functions can contribute to CNS autoimmunity. At the Congress, The Immunology Lecture delivered by Vinuesa was dedicated to rare mutations that contribute to systemic autoimmunity. Focus was placed on genes that control mechanisms involved in the production, selection and elimination of memory B cells and antibody production, and specifically on the role of roquin, an E3 ubiquitin ligase, in the control of B cell-T cell interactions by T follicular helper cells (TFH) . In the Neutrophils are amongst the first immune cells to reach the CNS in the MS model experimental autoimmune encephalomyelitis (EAE) and are present in the CNS during NMOSD and severe MS, but little is known of their role in disease pathogenesis. Vallieres showed that neutrophils adopt macrophage-like properties once entering the CNS in a B cell-dependent EAE model and to promote inflammation via the neutrophil-specific protease ASPRV1 . MoreoveMS research is increasingly focused on myeloid cells and CNS-resident cells such as astrocytes, microglia, and oligodendrocytes, which contribute to disease pathology through additional mechanisms likely relevant for other neurologic diseases. One topic that remains hotly debated in the MS field is the identity of the antigen-presenting cell that is responsible for reactivating T cells in the CNS, and thereby licensing them to induce demyelinating lesions, since this is a potential target for more selective therapy. Various cell types, including dendritic cells, B cells, barrier-associated macrophages (BAM), and microglia are able to present antigen to T cells in the context of MHC class II, although which one is involved in the pathogenesis of EAE and MS still remains to be identified. Important targets are also the effector molecules communicating these interactions, as discussed by Becher for (GM-CSF) .Benmamar-Badel et al. review data regarding a unique subset of microglia that is found in development, during normal aging and in diverse diseases and discuss the possible functional significance of these cells. It is clear that much more needs to be learnt regarding the differential functions of myeloid cell subtypes before these cells can be both effectively and safely targeted for therapy.The functions of CNS-resident myeloid cell (microglia) in neuroinflammation continue to intrigue researchers. Unlike their peripheral counterparts (monocytes and macrophages), microglia perform essential functions in the CNS not only in pathologic states such as in repair of tissue damage, as discussed by Popovich, but also under normal physiologic conditions, such as shaping neuronal networks and clearing debris by phagocytosis. Loss of these functions during development has been implicated in schizophrenia and potentially in autism spectrum disorders, while loss of the same functions in the context of chronic inflammation may contribute to pathology in diseases such as MS and AD. For example, Waisman reported that selective depletion of A20 (an inhibitor of the transcription factor NF-\u03baB) in microglia, was sufficient to induce spontaneous neuroinflammation and CNS infiltration by CD8+ T cells, pointing to a homeostatic function for microglia in the brain . The TAMEvidence for inflammatory functions of CNS-resident oligodendrocyte precursor cells (OPC) was presented by Ransohoff wherein IL-17-induced Act1-NOTCH1 interactions in OPC promoted the inflammatory responses, cell proliferation and inhibited OPC differentiation into mature oligodendrocytes thereby inhibiting remyelination. Genetic depletion of NOTCH1 in OPC in mice, or administration of a decoy peptide based on IL-17RA, were sufficient to inhibit Th17-induced EAE . IncreasOur current understanding of CNS immune privilege and CNS barriers, including the blood brain barrier (BBB), blood CSF barrier (B-CSF), and brain surface barrier, was reviewed by Engelhardt at GSNI and elaborated during the congress itself, where the perivascular space at the BBB was implicated as a main entry point for immune cell infiltration in MS . Brain bJogia and Ruitenberg on the significance of gut microbiota in traumatic spinal cord injury, and from Cady et al., on the importance of dietary phytoestrogens in protection in EAE and possibly MS.Well-deserved attention was given to the gut-CNS axis and, in particular, the role of gut microbiota in immune homeostasis of the brain and in triggering CNS autoimmunity. This field developed following a landmark discovery made in the field of neuroimmunology just one decade ago. Since then the functional relationships between the gut microbiome and its effects on CNS pathology driven by peripheral and resident cells have been subject to intense investigation, as introduced at GSNI by Barazini, and updated in the Congress by Wekerle, Miyake, Weiner, Quintana and Yamamura, and by recent reviews \u201318. ThisSeveral talks highlighted the neuroimmunology of infectious diseases of both the peripheral and central nervous systems, including cerebral malaria by Idro and viral infections by Klein, Pender, Basu and Yamano.Prain et al. describe a clinically-based survey of NMOSD in Australia and New Zealand, and critically evaluate different assays for anti-AQP4 and anti-MOG antibodies used in the diagnosis of NMOSD and anti-MOG associated disease, respectively. In the case of anti-AQP4 antibody seronegative NMOSD, differential diagnosis from MS might be difficult. The current status of medical imaging research in MS and NMOSD, and its role in the diagnosis and management of these two diseases was discussed at the meeting by Stankoff and Paul, and is reviewed in this issue by Kuchling and Paul. Tea et al. together with the Australasian and New Zealand MOG Study Group, discuss data analysis tools for maximizing the diagnostic power of FACs cell-based assays that detect MOG autoantibodies. Gastaldi et al. critically report the results and main shortcomings of the 2018 Italian Neuroimmunology Association external quality assessment program (EQAP), which evaluated assays using a wide range of markers including oligoclonal bands, antibodies to intracellular and surface neuronal antigens, AQP4, MOG, and myelin-associated glycoprotein (MAG) antibodies, in different assay types used by 34 different laboratories. Jiang et al., describe improved novel biomarkers in the CSF of patients with autoimmune encephalitis for differential diagnosis between viral infections and autoimmune encephalitis. Masvekar et al. investigated whether apoptotic bodies/ apoptosomes, which are vesicles released from apoptotic cells, could represent a biomarker for MS, by measuring total and cell-specific apoptotic bodies in the CSF of MS patients by FACS using annexin V and antibodies to cell-specific markers.The search for improved diagnostic biomarkers continues, and is a particular focus of articles published in this special issue. While MS is the most common inflammatory demyelinating disease of the CNS, other rare disorders include NMOSD and anti-MOG associated disease, and the need for accurate diagnosis is stressed since prognosis and treatment of these three diseases are different. In this issue, Ottoboni et al.) and The Rita Levi-Montalcini Neurobiology Lecture delivered by Bartlett 2018, and the associated 2nd Global Schools of Neuroimmunology (GSNI), highlighting new developments in this rapidly moving field, as well as unanswered research questions and unmet clinical needs. This growing body of research sets up the stage for the upcoming ISNI/GSNI 2021 meeting in Nice, France.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "As organisms age, many changes occur to their physiology, which in turn impact the function of multiple tissues. It is therefore critical to investigate the fundamental mechanisms of how endocrine organs shape our physiology, and how changes in our physiology affect stem cell lineages, which generate new cells for maintenance and repair of tissues/organs throughout life. This symposium will highlight the research in the laboratories of Dr. Gerard Karsenty (Columbia University) on the multiple endocrine functions of bone, of Dr. Nicholas Buchon (Cornell University) on the role of host-microbe interactions in intestinal homeostasis, of Dr. Jane Hubbard on the physiological control of the germline, and of Dr. Daniela Drummond-Barbosa (Johns Hopkins University) on how diet and adipocyte factors regulate oogenesis. As research by these and other groups illustrate, the complex physiological regulation of tissue/organ maintenance and function is not only a fascinating biological problem, but it also has implications for many diseases and other conditions that are tightly linked to our endocrine state, including aging."} +{"text": "The psychosocial stress process model remains a dominant theoretical framework characterizing the transactions between factors affecting outcomes of informal caregivers of people with dementia (PWD). Despite widespread agreement that the model provides an important framework for understanding caregiver experiences and predicting caregiver outcomes, it is not sufficient to clarify the needs of caregivers. Needs are conceptualized as the skills and resources that could be used to ameliorate the negative impacts of caregiving and promote quality of life . Determining caregiver needs requires appreciation of the complex background, contextual, and stress-related variables described in the stress process model and requires empirically- and theoretically-driven understanding of the diverse resources, materials, and skills that individuals require for global health and functioning. In this study, we conducted a content analysis of existing measures of dementia caregiver needs (N = 54), content analysis of materials related to evidence-based dementia caregiver interventions and government reports and documents (N = 28), and semi-structured in-depth interviews with current caregivers of PWD (N = 12) to identify the personal and care-related needs of family caregivers of PWD. We propose a framework of five inter-related need categories that transact with the factors described in the stress process model, ultimately influencing functioning. In the future, we plan to test this model empirically with a nationally representative sample of caregivers."} +{"text": "Due to their large number of applications, the pesticides pose potential toxicity risks to the non-target organisms. In recent years, the studies on the toxic effects of pesticides on non-target organisms, based on their gut microbiome and metabolome, have been continuously reported. As a dense and diverse microbial community, the gut microbiota in the mammalian gut plays a key role in the maintenance of host metabolic homeostasis. The imbalance in the gut microbiota of host is closely associated with the disturbance in the host's metabolic profile. A comprehensive analysis of the changes in the gut microbiota and metabolic profile of host will help in understanding the internal mechanism of pesticide-induced toxic effects. This study reviewed the composition and function of the gut microbiota of host, as well as the analysis methods and applications of metabolomics. Importantly, the latest research on the toxic effects of the exposure of pesticide to host was reviewed on the basis of changes in their gut microbiota and metabolic profile. Pesticides are widely used as an important mean for agricultural production. However, the pesticide residues its excessive and unreasonable use, which seriously threatens the quality of agricultural products and the safety of ecological environment . At presIn recent years, the studies on host gut microbiome and metabolomics have attracted more attention . The hosIn this study, the composition and function of gut microbiota, and the analysis methods and applications of metabolomics have been reviewed. Importantly, the effects of pesticides on the gut microbiota and metabolic profile of host were reviewed, which further emphasized on their key role in the pesticide-induced host toxicity.Firmicutes and Bacteriodetes. In addition, Proteobacteria, Verrumicrobia, Actinomycetes, Fusobacteria and Cyanobacteria are also relative abundant in the human intestines , carbon nuclear magnetic resonance spectroscopy (13C-NMR), nitrogen nuclear magnetic resonance spectroscopy (15N-NMR), and phosphorus nuclear magnetic resonance spectroscopy (31P-NMR), of which the 1H-NMR and 13C NMR are the most widely used NMR spectroscopies in metabolomics. The NMR can detect most of the endogenous metabolites in organisms, and can obtain a wealth of information about the tested samples. It provides stable results with good repeatability. In addition, the NMR has relatively simple requirements for the pretreatment of samples, and can perform unbiased and non-destructive analysis and detection of samples and gas chromatography-mass spectrometry (GC-MS) are commonly used . These tDue to the limitations in existing analysis platforms, they are not suitable for the analysis of all metabolites in a biological sample. By combining various single analysis techniques to form a joint technique, its application range becomes wider, and provides accurate information about a specific metabolome. Therefore, in the field of metabolomics research, several analytical techniques are often used to study the metabolites. There is a continuous developmental trend in the modern analytical techniques, which will promote the metabolomics research. At present, the most common example of the combination of multiple analysis techniques is the combination of NMR and MS. This method can make the full use of the advantages of various techniques for the identification of metabolites in organisms to the greatest extent. This combined method is not only used in the pesticide environmental toxicology research, but also provides an opportunity for the integration of multiple omics in system biology .https://www.metaboanalyst.ca/), HMDB (the human metabolome database) and KEGG (Kyoto encyclopedia of genes and genomes), etc. are used to interpret the biological information of metabolites. Subsequently, the p value and pathway influence value (PIV) are used to find the significantly affected metabolic pathways, and the mechanism of toxicity can be explored in-depth through the changes in metabolic pathways.After obtaining the original data by measuring the samples through the above-mentioned analysis techniques, the data needs to be preprocessed to make it suitable for the multivariate analysis. Depending on the technique used, the processing steps are slightly different . The datMetabolomics has been playing an increasingly important role in the basic research and clinical applications, and has been widely for studying the different functional states and diseases of various organisms. Li et al. collected the blood samples of 150 patients with severe obstructive coronary heart disease (CHD) and 150 healthy controls for the metabolomics analysis using ultra-high performance liquid chromatography-quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). The study found significant changes in the metabolites of 105 CHD patients. In addition, six metabolites, including palmitic acid, linoleic acid, 4-pyridoxic acid, phosphatidylglycerol, carnitine and lithocholic acid, had a strong correlation with the CHD . Zhao et. In addition, the metabolomics technology is also widely used in the identification of food quality. As early as 2002, Brescia et al. analyzed the metabolic profile of 41 red wines from southern, central and northern Apulia, Italy, using NMR. With the help of the PCA, the wines of these three regions could be clearly distinguished. The main substances that caused differences in the wine regions were amino acids , taurocholic acid (TCA), glyco-cholic acid (GCA) deoxy-cholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholicacid (GDCA), lithocholic acid (LCA), taurolithocholic acid (TLCA), and glycolithocholic acid (GLCA) and decreased that of the \u03b2-MCA (Akkermansia, and a decrease in the abundance of Desulfovibrionaceae and Lactobacillus. In addition, the metabolites, mainly related to the metabolism of purine and BCAAs and TCA cycle in feces were changed, which ultimately led to an increase in the consumption of host energy (1H-NMR analysis showed that a total of 20 fecal metabolites, mainly including succinate, SCFAs, bile acids and trimethylamine, were affected (The increasing use of pesticides year by year has attracted more attention toward their toxic effects on non-target organisms in the environment. Interestingly, many recent studies have shown that the gut microbiota plays a key role in the toxic effects of pesticides . In addihe \u03b2-MCA . In addihe \u03b2-MCA . Studieshe \u03b2-MCA . In addihe \u03b2-MCA . The pert energy . In addit energy . Similart energy . Wu et aaffected . Moreoveaffected . CurrentIn recent years, the gut microbiota of host has received more attention. Generally, the dysbiosis of gut microbiota often occurs simultaneously with the metabolic disorder of host. The studies on the health effects of host based on the changes in gut microbiota and metabolic profile have been continuously reported. In the past few decades, the pesticides have been widely used, and their toxic effects on the non-target organisms have received increasing attention. In particular, some studies have confirmed the destructive role of pesticides on the gut microbiota and metabolic profile of host. Unfortunately, most of these studies have only established a simple correlation between the pesticides and host gut microbiota and metabolic profile, while the key roles of the gut microbiota and metabolic profile host in the pesticide-induced toxic effects are still not focused. In particular, some studies have shown that some specific bacteria in gut microbiota can regulate specific metabolites or specific metabolic pathways, further affecting the host health. However, the current studies on the toxic effects of pesticides have not established a clear relationship between the specific pesticides and specific gut microbiota or metabolites. On the other hand, the key role of the gut microbiota and metabolic profile of host in the pesticide-induced toxic effect is needed to be further confirmed either by the transplantation of microbiota or the dietary supplementation of specific metabolites. In summary, this study reviewed the studies on the toxic effects of pesticides based on the gut microbiome and metabolomics of host. This review further emphasized on the role of changes in the gut microbiome and metabolomics of host in the pesticide-induced host toxic effects."} +{"text": "Brain computer interfaces (BCI) provide a direct communication link between the brain and a computer or other external devices. They offer an extended degree of freedom either by strengthening or by substituting human peripheral working capacity and have potential applications in various fields such as rehabilitation, affective computing, robotics, gaming, and neuroscience. Significant research efforts on a global scale have delivered common platforms for technology standardization and help tackle highly complex and non-linear brain dynamics and related feature extraction and classification challenges. Time-variant psycho-neurophysiological fluctuations and their impact on brain signals impose another challenge for BCI researchers to transform the technology from laboratory experiments to plug-and-play daily life. This review summarizes state-of-the-art progress in the BCI field over the last decades and highlights critical challenges. The brain computer interface (BCI) is a direct and sometimes bidirectional communication tie-up between the brain and a computer or an external device, which involves no muscular stimulation. It has shown promise for rehabilitating subjects with motor impairments as well as for augmenting human working capacity either physically or cognitively , replace , enhance , supplement , improve , and research tool have been outlined as feasible and promising fields a comfortable and convenient signal acquisition device, (2) system validation and dissemination, and (3) reliability and potentiality of BCI the selection of the signal acquisition modality, which plays an important role in diagnosing neural states, (2) the design of feedback modality that has explicit association with the neural signal classification performance, (3) the consideration of application-specific feedback delays, and (4) the utilization of a suitable feedback modality technologies together with BCI could offer immersive experiences and have many potential applications including arts and neurofeedback experiments that involve decoding sender's cognitive intentions, translate them into commands for stimulating receiver's brain, have been explored (Pais-Vieira et al., Irrespective of the scientific breakthroughs in BCI field, there are key factors pertaining to safety, ethics, privacy protection and data confidentiality, community acceptance and socioeconomic aspects that should be considered with adequate precautions to maximize users' benefits and social impacts (Illes and Bird, Physical and mental safety of BCI users is important. Invasive procedures such as deep brain stimulation and intracortical microelectrode array may cause postoperative psychological and neurological side effects (Jotterand and Giordano, A user's expectations of achieving extended or auxiliary degree of freedom may not be fulfilled, and even the unfamiliar risk factors can diminish the accomplished advantage of using BCI Clausen, . CreatinIt is critical to introduce a suitable act for lawful utilization of BCI and preservation of privacy and confidentiality of stored data. Recent studies have demonstrated decoding of password or recognizing faces utilizing consumer-grade BCI successfully, prompting a potential concern of any illegitimate access to users' raw data and their further exploitation (Martin et al., Human Brain Project. In addition, the Brain Initiative has been announced by the White House. In our opinion, advanced understanding of basic neuroscientific phenomena will determine the structure, efficacy and applications of futuristic BCI.By creating a common networking platform for BCI researchers worldwide, the immediate proposition of a comprehensive list of universal guidelines is key to sustainable advancements of the field (Vaadia and Birbaumer, Numerous groundbreaking advances in neurosensors and computational tools herald great promise for more sophisticated and user friendly BCI systems requiring no or little maintenance. In addition to hi-fidelity signal acquisition, significant progress in signal processing and machine learning tools, their complementary roles, and high computation power and increased mobility of computers have significantly contributed in the emergence of BCI technologies. The future of BCI technology will rely greatly on addressing the following key aspects:Elucidating the underlying psychophysiological and neurological factors that potentially influence BCI performance.Designing less invasive sensors with reliable signal acquisition and resolution, while considering portability, easy maintenance, and affordability.Modeling session-to-session and subject-to-subject information transfer for the proposition of more generalized BCI models with insignificant or no calibration requirement.Establishing broad consensus on ethical issues and beneficial socioeconomic application of this technology.SS conceived the initial idea, wrote the first draft, and generated all figures and tables. KM, KA, RM, GN, and SD participated in the discussion and commented on the draft. AHK and MB provided further insight and helped SS to finalize the structure and materials. All authors read and approved the final paper.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Chinese animal industries face challenges in finding graduates with the appropriate training for the needs of a dynamic industry.The agricultural universities of China are working on methods to strengthen the specialized abilities of students to meet industry needs.The Chinese government has increased funding to encourage faculty and students to devote energy to animal science research not only in tradition field, but also in some new cross\u2013disciplinary areas, for example, artificial intelligence applications.These challenges have accelerated the formation of mutually beneficial relationships between the industries and universities but there is a long way to go.Following more than 20 years of rapid development, China is the largest producer of meat and eggs and the third-largest producer of milk in the world. Since 2016, the animal industry in China has reached a plateau in which the yields of meat, eggs, and milk increased by no more than 3% per year . MeanwhiChinese (mainland) imports of livestock and poultry products reached 36.2 billion U.S. dollars in 2019 . The SinMore importantly, animal disease epidemics heavily depress the development of a sustainable animal industry in China. For example, the spread of African swine fever (ASF) in China since 2018 caused producers to lose tens of billions (U.S. dollar) losses during 2019. In addition, hundreds of pig farms, especially mid- and small-sized farms, went out of business.To strengthen the ability of agricultural industries to withstand risk, more companies are beginning to integrate the feed industry, animal husbandry, and processing. Only powerful and integrated companies, along with some unique mid- and small- size enterprises, can survive and attain profit in China. A huge and integrated animal industry needs hundreds of thousands of employees involved in the primary and supporting industries. However, many young people prefer to move to urban areas to enjoy a convenient lifestyle rather than work on remote and isolated farms, causing a deficiency in farm labor throughout China. Considering the huge demands for qualified employees with well-trained professional knowledge, skills and interdisciplinary background, employers are willing to offer high salaries to qualified employees. Unfortunately, the candidates with a traditional background in animal science regardless of degree are at a relative disadvantage when applying for these high-salary positions due to the absence of cross-disciplinary training.To strengthen the graduates\u2019 abilities to deal with challenges and cooperate with colleagues from across branches in integrated enterprises, designing the animal science curriculum and supporting courses for the future has become a primary issue. Establishment of new courses reflecting the transformation of the industry to develop students with the following abilities would be welcomed.Application of artificial intelligence in the animal industries;Understanding experimental design, statistical analyses, interpretation of data, and scientific communication skills ;Training in biotechnology, including cell and molecular biology, genetic engineering, and fermentation engineering;Expertise and skill in nutritional strategies to keep animals healthy, minimize agricultural environmental impact and emissions, and promote production efficiency;Skills in control and prevention of infectious diseases;Animal product quality control and monitoring;Design of animal husbandry buildings and auxiliary infrastructure, including design of facilities, feed processing and conveyor systems, environmental control systems, and other engineering skills;Excellent interdisciplinary background covering animal husbandry, veterinary science, feed processing, environmental monitoring, financial accounting and analysis, and so forth.The Chinese government also annually identifies scientific issues on the frontier, including the common problems impacting the development of animal industries. They also create funding for projects addressing these priority issues through the National Natural Science Fund or other projects of national scientific programs.Issues concerning the development of animal genetic resources and breeding, control and prevention of epidemics, feed production/processing/efficient utilization, animal immunity, environmental stress and animal health, animal nutrition, application of artificial intelligent in the animal industry, animal waste processing and environmental protection, and animal behavior and animal welfare attract more financial support than has previously been available from the government and from the industries.According to the Statistical Bulletin on National Investment in Science and Technology for 2018 , the totThe government understands that investment in high-level scientific research activities of animal science and development of the full-fledged potential and ability/skills of students who will have careers in animal husbandry and related works is money well spent. Additionally, university administrators must do their best to provide facilities that encourage faculty and students to upgrade student skill sets for professional careers of the future because employment opportunities exist for well-trained graduates . To faciIn summary, it is of great importance for the university education system in China to cultivate students with professional knowledge and know-how to serve the rapidly transforming animal industry. This must be done by increasing the needed funds to promote multidisciplinary training and high-quality scientific research activities."} +{"text": "On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak as a pandemic, with over 720,000 cases reported in more than 203 countries as of 31 March. The response strategy included early diagnosis, patient isolation, symptomatic monitoring of contacts as well as suspected and confirmed cases, and public health quarantine. In this context, telemedicine, particularly video consultations, has been promoted and scaled up to reduce the risk of transmission, especially in the United Kingdom and the United States of America. Based on a literature review, the first conceptual framework for telemedicine implementation during outbreaks was published in 2015.An updated framework for telemedicine in the COVID-19 pandemic has been defined. This framework could be applied at a large scale to improve the national public health response. Most countries, however, lack a regulatory framework to authorize, integrate, and reimburse telemedicine services, including in emergency and outbreak situations. In this context, Italy does not include telemedicine in the essential levels of care granted to all citizens within the National Health Service, while France authorized, reimbursed, and actively promoted the use of telemedicine. Several challenges remain for the global use and integration of telemedicine into the public health response to COVID-19 and future outbreaks. All stakeholders are encouraged to address the challenges and collaborate to promote the safe and evidence-based use oftelemedicine during the current pandemic and future outbreaks. For countries without integrated telemedicine in their national health care system, the COVID-19 pandemic is a call to adopt the necessary regulatory frameworks for supporting wide adoption of telemedicine. On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak as a pandemic, with over 720,000 cases reported in more than 203 countries as of 31 March. This announcement followed the declaration of a Public Health Emergency of International Concern (PHEIC) on January 30. The response strategy included early diagnosis, patient isolation, symptomatic monitoring of contacts, as well as suspected and confirmed cases, and a public health quarantine. The confinement of population and the outbreak impact on health care systems is disrupting routine care for non COVID-19 patients. In this context, telemedicine, particularly video consultations, has been promoted and scaled up to reduce the risk of transmission, especially in the United Kingdom and AustTelemedicine was shown to be helpful in previous outbreaks, including former coronavirus outbreaks such as SARS-CoV (severe acute respiratory syndrome\u2013associated coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus), or PHEICs related to Ebola and Zika viruses ,7. BasedAn updated framework for telemedicine during the COVID-19 pandemic has been defined in Technological improvements and cost reduction of telemedicine solutions combined with both the high-speed internet and mass spread of smartphones makes it possible to apply this framework and quickly deploy video teleconsultations from a patient\u2019s home.Most countries, however, lack a regulatory framework to authorize, integrate, and reimburse telemedicine in their care delivery for all patients, particularly in emergency and outbreak situations . Two posWith the second largest burden of COVID-19 in the world, Italy does not include telemedicine in the essential levels of care granted to all citizens within the National Health Service. No formal input was given on telemedicine by health authorities, despite high pressure on health services during the first phase of the epidemic ; not untIn France, the Ministry of Health signed a decree on March 9, 2020, allowing the reimbursement of video teleconsultations and tele-expertise by the National Health Insurance (NHI), for patients with COVID-19 symptoms and those confirmed with COVID-19 throughout the country, without the need to know the patient beforehand . The decThe pre-existing telemedicine regulations also enabled primary care and hospital doctors to switch scheduled face-to-face consultations with known patients to reimbursed teleconsultations, when suitable. This model was activated in the largest national public academic hospital (AP-HP) in Paris, to encourage mass use of outpatient teleconsultations to reduce patient visits to the hospital March 13, 2020). This has been reinforced by the High Council of Public Health, which recommended prioritization of teleconsultations for people with risk factors for severe disease in primary care March 14, 2020) [, 2020. T, 2020 ,. Among gIn this context, several challenges remain for telemedicine to be globally used and integrated into the public health response to COVID-19 and future outbreaks:The integration of telemedicine into international and national guidelines for public health preparedness and response The definition of national regulations and funding frameworks for telemedicine in the context of public health emergenciesA strategy to quickly define telemedicine frameworks; use case scenarios; develop clinical guidelines; and standardize triage auto questionnaire and remote patient-monitoring algorithms for any outbreaks at local, national, or global scalesA strategy and operational plan guiding health care providers to switch to outpatient teleconsultations and increase tele-expertise and remote patient monitoringA communication toolkit to inform and educate the population on the recommended use of telemedicineA data-sharing mechanism to integrate telemedicine providers\u2019 data with epidemiological surveillanceA scientific evaluation framework and dedicated research funds to describe and assess the impact of telemedicine during outbreaksAll stakeholders are encouraged to address the challenges and collaborate to promote the safe and evidence-based use of telemedicine during the current pandemic and future outbreaks. For countries without integrated telemedicine within their national health care system, the COVID-19 pandemic is a call to adopt the necessary regulatory changes supporting wide adoption of telemedicine."} +{"text": "The coronavirus disease (COVID-19) outbreak is rapidly progressing globally, and Italy, as one of the main pandemic hotspots, may provide some hard lessons for other countries. In this paper, we summarize the current organizational capacity and provide a pragmatic and narrative account of strategies and activities implemented by the Department of Prevention (Dipartimento di Prevenzione)\u2014the regional entity of the Local Health Authority of the Italian National Health Service in charge of public health\u2014since the beginning of the outbreak. We conduct a preliminary analysis of general strengths, weaknesses, opportunities, and threats (SWOT) of the response strategies from a local perspective. Furthermore, we provide firsthand insights on future directions and priorities to manage this unprecedented pandemic. Our case report gives a qualitative view of the healthcare response, based on the experience of frontline professionals, with the aim to generate hypotheses about factors which may promote or hinder the prevention and management of a pandemic locally. We highlight the importance of a public health approach for responding to COVID-19 and reshaping healthcare systems. The 2019\u20132020 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, which was first identified in Wuhan, Hubei, China, in December 2019, has resulted in an ongoing coronavirus disease (COVID-19) pandemic. Exponential increases in the number of confirmed COVID-19 cases and deaths continue to be reported globally, and necessitate awareness and proactive action .On 30 January 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern, and on the same day, the Italian government banned air traffic from China ,5. The fIn Italy, only three cases were identified at the end of January, and all involved individuals who had recently traveled to China. The first case of pneumonia due to SARS-CoV-2, without history of possible exposure abroad, was diagnosed in northern Italy\u2019s Lombardy on 20 February . Within On February 21, the Ministry of Health ordered a mandatory supervised quarantine for 14 days for all individuals who had come into close contact with confirmed cases of disease. In addition, it required a mandatory communication to the Department of Prevention\u2014the entity of the Local Health Authority of the Italian National Health Service in charge of public health\u2014in identified areas from anyone who had entered Italy from areas with a high risk of COVID-19, followed by quarantine and active surveillance . The ItaThereafter, additional social distancing measures were initially enforced in Lombardy and within areas of other affected regions. Subsequently, draconian lockdown measures were extended nationwide, through several decrees enacted by the President of the Council of Ministers, closing schools (5 March), banning public events 9 March), limiting movement of people except if motivated by proven work needs or situation of necessity , and suspending all retailing and business activities, with the exception of essential goods and production activities that were strategic or relevant to the management of the crisis (22 March) March, l,13,14. TIn March, the number of cases identified in Italy had rapidly increased, predominantly in northern Italy, although all regions of the country reported ever-increasing numbers of COVID-19 cases ,17. The Nevertheless, despite the de-escalation measures that are underway, the situation is far from normal and the Italian National Health Service has faced the worst threat since its establishment more than 40 years ago. From the beginning of the crisis, professionals of the Italian healthcare system employed in all its different settings have been fully and strenuously engaged in battling the SARS-CoV-2 outbreak. In this context, the Italian public health community has been at the forefront, fire-fighting this sweeping pandemic.With this case report, we aim to provide a general and qualitative perspective on the pandemic response implemented by the Department of Prevention , which is the operative branch of the local health authorities of the INHS in charge of public health. Drawing from the hard lessons of COVID-19 in Italy, the Western country most affected by the pandemic to date, we share a preliminary epicrisis and reflections on the current situation, as well as insights and priorities for the future. Firstly, the institutional role and activities of DPs during the initial phase of the pandemic are set out. Secondly, strengths and weaknesses, threats, and opportunities are described. Thirdly, we generate hypotheses about factors which may promote or hinder the prevention and management of a pandemic locally.Italy\u2019s healthcare system comprises a regionally organized NHS. The fundamental principles of the INHS include universal coverage, social financing from general tax revenues, and non-discriminatory access to healthcare services. The system provides largely free healthcare at point of delivery, and is regionally administered, with the central government sharing responsibility with the respective regions for healthcare services planning and delivery . At presThe Ministry of Health is the main institution responsible for public health at the national level. The functioning of the Ministry of Health is supported by several established governmental agencies. At present, the most important such agency for public health, including emergency responses, is the National Institute of Health (Istituto Superiore di Sanit\u00e0), which undertakes scientific research, surveillance, and promotion of public health practices. Within each region, the responsibility for the organization and delivery of services rests on specific geographically and population-defined institutions\u2014the Local Health Authorities . The Department of Prevention, which is one of the three \u2018pillars\u2019 of the INHS (legislative decrees no. 502 of 1992 and no. 229 of 1999), is the operative branch of every local health authority in charge of preventive medicine and public health, including pandemic response.The main functions of Departments of Prevention include prophylaxis of infectious and parasitic diseases; protection from the health risks of living environments and workplaces ; veterinary safety and health ; veterinary pharmacovigilance; hygiene of livestock production, and protection of health and hygiene of food of animal origin); food hygiene and safety; nutritional surveillance and prevention; and health promotion on noncommunicable diseases . DepartmThe epidemic scenario changed rapidly, as did the response strategy and measures. From 22 January to mid-April 2020, the Italian government enacted over 160 decrees, orders, circular letters, notices, advices, or protocols related to the COVID-19 emergency . AdditioWe summarize below the practical measures, grouped into three categories that were instituted for the containment and mitigation of the epidemic and were managed directly by the DPs.(1)Membership of local crisis task force.Epidemic risk assessment and analysis of scenarios and health system capacity .Development and updating of local emergency plans.Coordination with institutions and non-healthcare bodies .Provision of information and education to healthcare workforce .Advice for vulnerable groups , schools, and businesses.Designating dedicated facilities for isolation.Support to the local health authority for coordination and management of the crisis:(2)Contingency plan: rescheduling non-urgent activities and maintaining only essential programs , telemedicine , assignment of staff to COVID-19 tasks, and protection of the workforce.Joint integrated response with primary care teams for detection, assessment, rapid reporting, and active surveillance of suspected or confirmed COVID-19 cases.Establishment of an alert system and dedicated helpline.Information system for the management and traceability of testing.Sharing practices and data with other DPs.Internal reorganization and infrastructure:(3)Active investigation of cases and clusters and contact tracing (concentric circles approach).Deciding on the necessity for quarantine and home isolation.Swabbing and testing, especially through proximity diagnostics .Active surveillance for people under quarantine and home isolation.Implementation of orders and advice on physical distancing, environmental hygiene, mortuary police, veterinary medicine, and food safety.Guidance and controls on physical distancing and other preventive measures in different community settings .Advice and support for risk assessment and health surveillance in workplaces and other community settings .Risk communication and community engagement practices .Travel advice and screenings of travelers.Collection, analysis, and dissemination of surveillance data .Blocking and tackling:We undertook a strengths, weaknesses, opportunities, and threats (SWOT) analysis to provide a quick, pragmatic, and preliminary overview of the perceived state of response strategies and operations from the DP perspective. Such a tool has been applied elsewhere for reviewing healthcare response to COVID-19 .We drew from published literature, practical experience, and consensus brought together at short notice by a group of senior members of Italian Society of Hygiene, Preventive Medicine, and Public Health. In March and April 2020, we performed two rounds of discussion linked to two online meetings of members of the extended college of operators of Prevention, Public Health. and Medical Directorates and one additional meeting of preparation of an online webinar on the state of pandemic response in Italian regions. Themes were collected and reviewed by the authors. To generate the SWOT factors, we set a limit of seven items for each factor, and we selected only items with a full consensus among professionals on priority, generalizability, and relevance.For analyzing and discussing results, we relied on available data from: the Italian Observatory on Prevention (pre-pandemic state of DPs) , a socieWe summarize below the results of the analyses of strengths, weaknesses, threats and opportunities.National event-based surveillance and analysis for public health emergencies and laboratory capacity for detecting prioritized diseases and providing real-time data .Well-functioning national influenza surveillance network that is supported by regional reference laboratories .Consolidated experience in first-line response to infectious emergencies, including the severe acute respiratory syndrome (SARS), the influenza pandemic, and Chikungunya, as well as the measles outbreaks and epidemic meningitis.National coordination and progressive strengthening of the response, consistent with risk assessments and recommendations of the World Health Organization and the European Center for Disease Prevention and Control.Key role of DP in the governance of the emergency within the Local Health Authority.Comprehensive and integrated community-based response supported by all the units of the DP .Awareness and early activation of the public health community.Inadequacy of national and regional public health emergency preparedness as well as response planning and operations, including laboratory capacity and medical countermeasures , which lRapid change, perceived inconsistency, and bureaucratic rigmarole in technical orders and clinical protocols , sometimes due to international guidance .Non-homogenous and limited operational capacity of DP and integration with primary care.Patchwork responsiveness and communication at DP level, given the time needed to implement an unprecedented organized response.Reactive and \u201clocal mindset\u201d in critical thinking and \u201chomemade\u201d solutions to support operations of DPs .Sparse availability of tools for data integration and smart technologies deployable to support contact tracing, surveillance, and other public health interventions.Greater mandate and expanded capacity for preparedness planning, surveillance, and scientific advisory support from European and Italian national authorities.Rapid upgrade of national and regional infrastructure for emergency response, including increased human resources capacity and \u201cprotected\u201d supply chains.Allocation of resources and reengineering integration models and tools for robust collaboration, particularly \u201cintra-territorial care\u201d, between public health and primary care agencies.Pragmatic and action-oriented reframing of duties and powers between healthcare and other institutional authorities and politics.Accountable response supported by exponential technologies and effective policies for real-life implementation of telemedicine.Insufficient resilience of supply chains for protective equipment and other medical countermeasures.Health consequences of prolonged interruption or delay of population-based prevention programs and clinical care.Inconsistencies between regional strategies that alter the ability to set up uniform, robust planning for future responses to support overextended health and social care.Substantial countrywide social, political, and economic disruption that impacts health and social services.A proactive and targeted public health response is fundamental for interrupting human-to-human transmission chains and preventing further spread, thereby reducing the intensity of the epidemic. Therefore, in response planning, even at the local level, it is crucial that decision makers primarily understand the pandemic as a public health problem and not as a hospital (or intensive care) issue, especially after the emergency phase is over and the necessity for the containment role of hospitals is greatly diminished. The strengths and weaknesses of the local public health response during the first pandemic phase in Italy were several and varied. Support to the local health authority for coordination and management of the crisis, internal reorganization, and infrastructure guaranteed governance and stewardship for public health action. The cooperation with primary care was fundamental for managing \u201cblocking and tackling\u201d activities.Core fieldwork and labor-intensive practices for contact tracing and quarantining might have been affected by initial delays in tailoring the emergency response, multiple systemwide organizational and technological constraints, and excessive focus on symptomatic people during the epidemic\u2019s peak. In a rapidly changing epidemiologic scenario, it was essential to adapt strategies to locally available capacity and resources and pressure on healthcare services.Until we have effective vaccines and treatments, public health work will continue to be crucial for protecting people and communities.In the 14th century, starting in 1348 during a bubonic plague outbreak in medieval Italy, physicians and public health officials started to implement some of the world\u2019s first effective practices of anti-contagion measures related to social distancing and disinfection of surfaces . CurrentEvidence to date from China, South Korea, and other Asian countries , as well as data emerging from some European countries, indicates that early decisive actions may reduce community transmission . FurtherThe comparatively high rate of critical cases and deaths observed in Italy versus some other high-income countries could be attributable to: demography and epidemiological factors ,22,43, lAt the time of writing (20 April), in Italy there were almost 81,000 people in home isolation and around 1,400,000 tests performed ,19. In IItalian regional and local responses were remarkably different. The regional structure of the Italian national health service caused diverse regional responses to the emergency .A thorough scientific comparative analysis of facts and outcomes is needed. Certainly, the COVID-19 crisis exacerbated existing fault lines and vulnerabilities that everyone in the public health community has recognized and warned about for years. What we can argue is that the response was more effective and proactive where organization, qualifications and competencies, operational capacity, and territorial capillary presence of Departments of Prevention were consistent with the current national legislation and guidance for organization, practice, and allocation of resources within the Italian National Health Service. A high level of integration of public health with primary care and hospital services is another factor hindering an effective response.An interesting Italian case study on the value of a territorial response may be provided by the Veneto Region, which probably benefited from an early but circumscribed outbreak . In thisPublic health approaches, smart social distancing policies, aggressive tactics for supporting preventive measures in the community , active surveillance, contact tracing and testing, and home care as an elective setting for early clinical treatment of mild COVID-19 patients during containment and mitigation of epidemics may reduce the growth of the contagion curve, prevent the saturation in hospital services and nosocomial viral spread, decrease the number of deaths, and enable de-escalation of control measures.To act swiftly in protecting medical personnel, to avoid loss of personnel capacity and limit nosocomial virus spread.For early and smart swabbing primarily linked to epidemiological investigations, and tracing of high-yield contacts (including home testing) and risk categories .For acute respiratory infection/influenza-like illness sentinel surveillance through sentinel general practice and telephone/app helplines.For policies and rationale for rapid point-of-care diagnostic testing and seroepidemiologic population surveys.For optimizing the use and benefits of public health interventions through real-time accessibility of data and systematic evaluation.Other lessons relevant to other countries, from the difficult but nonetheless educational episode that Italy has experienced, indicate the need:We grounded our assumptions and hypotheses about the factors which promote or hinder the prevention and management of a pandemic locally on perception and data available in an emergency and rapidly changing context. In addition, Italy has a slightly different health system compared to other developed systems, and we are aware that our analysis and suggestions may not be applicable in other settings. SWOT results and discussion relied on a pragmatic exchange and consensus process and were not based on any systematic literature review or quantitative analysis. Therefore, information gathered may be oversimplified, some data overlooked, and authors\u2019 biases introduced. Despite such limitations, we believe this case report can provide a preliminary, contextualized, and comprehensive insight into the local response of the Italian Department of Prevention and the value of certain public health measures during the COVID-19 crisis. Raising awareness of the complexity of activities to perform during an epidemic crisis may help countries and public health officials in their strategic planning and on-the-ground decision making.In moving from a strict physical distancing period (Phase 1) to a staged reopening phase (Phase 2), until an effective vaccine or treatment is available (Phase 3), public health is essential in managing risks of increased transmission of COVID-19 to the health and wellbeing of the public, society, and the economy, via measures taken to reduce the spread of the disease .Therefore, after the end of lockdown, in going back to a \u201cnew normal\u201d, public health will be the key driver for informing decision-making with the engagement of all stakeholders. Measures to phase out confinement need policies and actions at local, regional, national, and international levels . During Driving and organizing boot-on-the-ground prevention and surveillance to protect vulnerable groups and the general population.Continuing to reshape the public health risk assessment and management system to ensure optimal epidemic response capacity.Continuing education and capacity building of public health workers.Standardizing terminology, communication tools, guidelines, and actionable protocols for practice.Replacing structurally bureaucratic management and low-value interventions with pragmatic local, community-based practice and scientifically sound practice.While scientific research and biomedical innovators are tackling the virus at unprecedented speed, additional systemwide priorities are:Hopefully, we will be able to ride the wave of this dramatic health crisis, transforming it into a relevant scientific and professional opportunity for hygiene and public health, building in the post-COVID-19 period a cutting-edge, attractive, and modern discipline .The community of public health physicians, health assistants, and other prevention professionals working in DPs and in other positions within the Italian NHS are fully committed to a continued timely, professional, non-fungible, and resilient action and practice exchange. Sharing experiences in the field, in addition to research, is crucial for the better management of healthcare services during the pandemic crisis for saving lives and protecting communities.The Department of Prevention is the entity of the Local Health Authority of the Italian National Health Service in charge of hygiene and public health, including the management of epidemiologic emergencies.Since the beginning of the outbreak, the work of the Departments of Prevention was crucial in supporting coordination and management of response operations at the local level, as well as supporting and managing activities of case finding, tracing and testing, and quarantining and home isolation, as well as other public health community measures .Analysis and reporting of the local response may inform understanding of complexity of actions and challenges for controlling the COVID-19 pandemic faced by public health professionals.A community-based response to COVID-19 needs public health and primary care; regional and local differences in organization and strategies may explain different outcomes.Public health work is a key driver for a safe lifting of social distancing restrictions after the end of the lockdown."} +{"text": "Global usage of electronic nicotine delivery systems (ENDS) has been increasing in the last decade. ENDS are non-combustible tobacco products that heat and aerosolize a liquid containing humectants, with added flavorings and often nicotine. Though ENDS are promoted as a less harmful alternative to smoking, current evidence links their use to a wide range of deleterious health effects including acute and chronic lung damage. ENDS can elicit an inflammatory response and impair the innate immune response in the lungs. Exposure to ENDS flavorings results in abnormal activation of the lung epithelial cells and \u03b2-defensins, dysfunction of the macrophage phagocytic activity, increased levels of mucin (MUC5AC) and abnormal activation of the neutrophilic response (NETosis). ENDS menthol flavorings disrupt innate immunity and might be associated with allergies and asthma through activation of transient receptor potential ankyrin 1 (TRAP1). Recent studies have expanded our understanding of the relationship between the homeostasis of lung innate immunity and the immunomodulatory effect of the host-microbiota interaction. Alterations of the normal respiratory microbiota have been associated with chronic obstructive pulmonary disease (COPD), asthma, atopy and cystic fibrosis complications which are strongly associated with smoking and potentially with ENDS use. Little is known about the short-and long-term effects of ENDS on the respiratory microbiota, their impact on the innate immune response and their link to pulmonary health and disease. Here we review the interaction between the innate immune system and the respiratory microbiota in the pathogenesis of ENDS-induced pulmonary dysfunction and identify future areas of research. Global usage of electronic nicotine delivery systems (ENDS) has increased in the last decade, especially among youth and young adults . The preThe recent outbreak of electronic cigarettes, or vaping, product use-associated lung injury (EVALI) raised national concern about the harmful effects of ENDS products and constituents . SimilarThe respiratory microbiota has also shown to play a crucial role in the lung innate immunity and inflammatory response in health and disease . Recent Prevotella spp.), Firmicutes (including Streptococcus spp. and Veillonella spp.), Proteobacteria, and Actinobacteria and viral communities (Anelloviridae family) .Tropheryma whipplei in the LRT microbial immigration from the oropharynx ; (b) mic the LRT and the the LRT . A unifi the LRT .The airways epithelium provides a biophysical protective barrier and a siHaemophilus species in patients diagnosed with COPD. Thus, the respiratory microbiota interacts with the airway epithelium and phagocytic cells in a positive feedback loop to develop immunological tolerance and prevent exaggerated inflammatory responses. Further research is needed to elucidate specific mechanisms explaining immunological tolerance in the respiratory tract and to identify potential intervention targets in respiratory pathologies.According to The production of mucus and antimicrobial peptides and proteins is a key element of the innate immune system of the lung. The airway surface liquid facilitates the mucociliary transport of toxicants, microorganisms, or particulates; lubricates and hydrates the airways; and, contributes to the epithelial barrier . The muc2, immunoglobulin A, lung, and nasal epithelium clone protein, collectins (surfactant protein A and surfactant protein D), mannan-binding lectin, cathelicidins, and \u03b2-defensins in the airways (Nicotine has been shown to increase mucin production and mucus viscosity through activation of the \u03b1 airways . Nicotin airways . However airways . Inhaled airways . Further airways . Thus, nin vitro model. Moreover, ENDS flavoring chemicals play a major role on the cytotoxic effects of e-liquids and e-liquid aerosols . ExposurStaphylococcus aureus, Streptococcus epidermidis, and Micrococcus luteus (Additionally, Clapp et al. showed that exposure to cinnamaldehyde-containing ENDS might decrease the mucociliary escalator motility by reducing bioenergetic activity and may s luteus and membs luteus . ENDS mes luteus , arthrits luteus , and asts luteus . Though in vitro, animal, and human studies are increasingly showing a link between the pathophysiology of respiratory disease and the exposure to ENDS aerosols (Little is known about the short- and long-term effects of ENDS on the respiratory microbiota, their impact on the innate immune response and their link to pulmonary health and disease. Preliminary studies have expanded our understanding of the relationship between the homeostasis of lung innate immunity and the immunomodulatory effect of the host-microbiota interaction. Existing and emerging evidence from aerosols . Relatedaerosols , asthma aerosols , and cysaerosols , which aFew studies have focused on the relationship between the respiratory microbiota and the immune response to air pollutants and toxicants in the respiratory tract. in vitro and in vivo models for the realistic evaluation of the respiratory microbiota-lung innate immune response in the context of immunotoxicity studies. Further research on the pathogenesis of flavor-vaping induced lung injury must consider the respiratory microbiota as a potential mediator of the immune and the inflammatory response after exposure to toxicants.The recent EVALI outbreak in the US, coinciding with a surge in youth vaping, generated a movement in the research community to establish research priorities and address challenges to support the Food and Drug Administration and World Health Organization efforts to regulate and control ENDS . ElucidaZQT, DJO, and IR initiated the idea for writing the manuscript, reviewed the literature, and edited the manuscript. ZQT drafted the manuscript. ZQT, DJO, IR, DC, DL, and SG revised, edited, and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The therapeutic armamentarium in Systemic Lupus Erythematosus (SLE) is expanding with the introduction of novel biologic and small-molecule agents. Complementary to randomized controlled trials, registry-based studies are advantageous due to the inclusion of a wider range of patients from daily practice and the potential for long-term monitoring of the efficacy and safety of therapies. Moreover, data from registries can be used to identify disease phenotypes that best respond to biologic agents, and to correlate clinical response with parameters such as co-administered therapies and comorbidities. In this project, we will use the configuration of the Hellenic Registry of Biologic Therapies for inflammatory arthritides in order to design a dedicated SLE module with variables pertaining to global and organ-specific disease activity, severity, flares, organ damage/outcome, comorbidities and adverse events. The second stage will involve the pilot implementation of this platform for the multicentric registration of SLE patients who are treated with belimumab. The significance lies in the development of a structured registry that enables the assessment of the disease burden and the long-term efficacy and safety of existing and future biological agents in SLE. Piloting the registry can serve as a basis for establishing nationwide collaborative efforts. Although these agents are generally efficacious in controlling the disease, still, a considerable proportion of patients fails to achieve long-standing remission.2 Importantly, conventional drugs, particularly corticosteroids, are associated with excessive toxicity risks, accrual of comorbidities and irreversible end-organ damage.3Systemic lupus erythematosus (SLE) encompasses a wide range of clinical and immunological manifestations, which makes monitoring of patients and assessment of their response to therapy a challenging task.4 have led to the expansion of the therapeutic armamentarium due to repositioning of drugs administered in other medical conditions and the increasing use of approved (e.g. belimumab6) and non-approved biologic agents. Based on the findings of recently performed controlled trials,14 a number of innovative therapies in SLE, including monoclonal antibodies and small molecules , are expected to be introduced in the near future.Scientific advancements in our understanding of the immunopathogenesis of SLE, coupled with better-designed clinical studies,16Post-marketing analysis of the efficacy and safety of new drugs is important in defining their application in routine clinical practice. In addition to the results from randomized clinical trials (RCTs), a significant amount of information can be derived from patient registries that systematically assess the effects of treatments under \u201creal-life\u201d conditions. Registries are also advantageous because they allow the inclusion of a wide spectrum of patients without the stringent exclusion criteria of RCTs , and monitoring for long-term drug efficacy and safety (including rare adverse events).In the case of SLE, which is a multifaceted, systemic auto-immune disease, data from organized patient registries may be particularly useful to approach clinically-relevant issues that cannot be easily addressed through clinical trials. These may include, for instance, the definition of disease endo-phenotypes that respond better to individual treatments, and the association between drug efficacy/safety with various disease parameters . Furthermore, collected data may help to obtain unique insights into the mechanisms of action of novel therapies.20 Likewise, large SLE registries, such as the Johns Hopkins Lupus Cohort, have provided significant knowledge with regards to the dose-dependent corticosteroid toxicity and the role of hydroxychloroquine in prevention of disease flare-ups.3 Another example is the British Isles Lupus Assessment Group (BILAG) Biologics Register of SLE patients, which has described the main features of patients who are candidates for biological treatment and has investigated the short-term efficacy and safety associated with the use of rituximab.7The value of establishing registries of patients receiving biological agents has been illustrated in inflammatory arthritides . Thus, analysis of registry-derived data has shed light on topics such as the identification of clinical factors that are predictive of treatment response, the safety of biologics in terms of the risk for latent infections and malignancies, the use of sequential therapies (\u2018switches\u2019), the main causes of drug discontinuations and other.To date, there is no structured platform for registering SLE patients in Greece under biologic therapies, and, accordingly, there is paucity of data on the indications, long-term efficacy and safety of these agents in real-life clinical settings. In this study, we seek to establish and implement a pilot system for the electronic registration and monitoring of patients with SLE who are treated with existing biologic but also, future novel therapeutics agents.The aim of the present study is to establish and run a pilot study of an electronic registry for monitoring SLE patients who are treated with novel/biologic therapies. The study has multicentric, prospective design with two implementation stages.This is a prospective study that will be performed at the Rheumatology Clinic, University of Crete Medical School and University Hospital of Heraklion (involved at stages I and II of the protocol) in collaboration with the Rheumatology Units/Clinics of the \u201cAttikon\u201d University Hospital, \u201cLaiko\u201d General Hospital, General Hospital of Asklepieion Voula, Hippokration University Hospital of Thessaloniki, and \u201cSismanogleio\u201d General Hospital (involved at stage II of the protocol). The study has been approved by the Ethics Committees of the participating centers.17 following amendments to capture at each visit: the dosage of main and secondary treatments, general and organ-specific indices of SLE disease activity, flares, organ damage, health-related quality of life and functional status, comorbidities, adverse events and causes of drug discontinuation (outlined below).The first stage (0\u20136 months) of the protocol includes the design of a specialized electronic platform (registry) for patients with SLE. The development of the registry will be based on the configuration and software of the existing registry of patients with chronic inflammatory arthritides who are treated with biologic agents ,21 SLICC 2012,22 EULAR/ACR 201923) for SLE, and b) already receive or are started on belimumab, which represents the single approved biologic agent in SLE.24The second stage (7\u201330 months) of the protocol will include the pilot use of the electronic registry for the multicentric enrolment and longitudinal monitoring of patients who meet the following inclusion criteria: a) fulfil at least one of the three classification criteria , attainment of low disease activity and remission states, the co-administration of glucocorticoids and other treatments, major events (comorbidities) and adverse events (outlined below).We also plan to update the long-term efficacy and safety data of a previously published cohort of patients.http://web-new.ics.forth.gr/ceha/). This is a web-based platform with secure connection, anonymised entry of patient data, encrypted data storage in line with the General Data Protection Regulation (GDPR) and ability to export selected data for further analysis. The SLE registry module will be based on the structure and configuration of the Hellenic Registry of Biologic Therapies for patients with inflammatory arthritides.17An online software is under development at the Rheumatology Clinic, University of Crete Medical School, in collaboration with the Centre for eHealth Applications and Services (CeHA) at the Institute of Computer Science, Foundation for Research and Technology \u2013 Hellas (ICS-FORTH) Date of diagnosis21 SLICC 2012,22 EULAR/ACR 201923)SLE classification criteria based on BILAG-defined organ activity,Disease activity pattern 27 Physician Global Assessment [PhGA]28)Global activity indices Organ-specific activity indices Disease flares (SELENA-SLEDAI Index30 and remission31Definitions of Lupus Low Disease Activity State (LLDAS)32)Irreversible organ damage (SLICC/ACR Damage Index33)Functional status Comorbidities : detailed record of medications and administered forms/dosagehttps://www.meddra.org/faq/meddra-general), treatment discontinuationsAdverse reactions and events and/or at regular (6-month) follow-up intervals:Each participating centre will be granted access to the electronic platform (registry) with unique credentials in order to enter their own patient data. As this is a pilot implementation of the registry, we aim to enrol a total of 60 SLE patients under treatment with belimumab, which will allow to obtain statistically robust results.A single export of merged patient data from all centres will be obtained for statistical analysis (months 31\u201336). Descriptive results on demographics, proportion of patients with partial or complete clinical response, attainment of LLDAS and remission/flares will be calculated. Efficacy will be correlated with baseline clinical and demographic characteristics. Safety will be assessed according to occurrence of major events. Treatment survival and reasons for discontinuation will also be evaluated.Registries of patients with chronic rheumatic diseases receiving biological therapies have provided significant insights regarding their long-term efficacy and safety in \u201creal-life\u201d clinical practice. In recent years, biological agents such as belimumab and rituximab have been introduced in the treatment of SLE, and based on the results from ongoing clinical trials, it is likely that additional innovative therapies may be added in the near future. The importance of this project lies in the development and pilot use of a dedicated electronic registry of patients with SLE who are treated with novel/biologic therapies, which will enable the detailed monitoring of drug efficacy and safety by the use of validated clinical instruments . Moreover, the registry will help to assess the burden of the disease among contemporary SLE patients who are seen at large Rheumatology Centres in Greece, as well as the long-term retention rates of the biological agents used in SLE such as belimumab. Importantly, the successful pilot implementation of the registry could pave the way for establishing broader collaborative projects at a national level."} +{"text": "Sporotrix sp. He also had pulmonary involvement and therefore the disease was classified as systemic sporotrichosis, a rare form that usually affect patients infected with HIV. Chronic alcohol abuse was considered the factor of immunosuppression for the patient.A 44-year-old male patient presented with nodules that evolved with inflammation, following drainage of seropurulent secretion and ulceration. The patient had a 6 year-history of alcohol addiction and reported contact with cats. At the physical examination, the patient had skin-colored and erythematous nodules, and ulcers covered with thick, blackened crusts on the face, trunk and limbs. A culture of a nodule fluid revealed growth of Sporothrix. Approximately 80% of the affected patients present the lymphocutaneous form. However, in patients with immunosuppression, disseminated forms can occur.2Sporotrichosis is a subacute or chronic subcutaneous mycosis caused by dimorphic fungi of the genus A 44-year-old male patient, presented with subcutaneous nodules that developed inflammation, following drainage of seropurulent secretion and ulceration. The patient had a 6 year-history of alcohol addiction. He denied comorbidities, although he reported prolonged contact with cats of unknown origin.At the physical examination, the patient had skin-colored and erythematous subcutaneous nodules, and ulcers covered with thick, blackened crusts on the face, trunk and limbs .Figure 1Due to compatible epidemiological history and the evolution pattern of the lesions, the main diagnostic hypothesis was sporotrichosis.Sporotrix sp. after 5 days did not show any abnormal results, and the serology test results were negative.High-resolution chest CT revealed atelectasis, ground-glass infiltrate, hilar lymphadenopathy and pleural effusion in both lungs.The disease was classified as systemic sporotrichosis, according to the classification recommended by Orofino-Costa et al,Patient was treated with amphotericin B lipid complex for 28 days, followed by itraconazole, during 11 months and had a good response, with healing of ulcers and without relapses in a 6-month follow-up.S. brasiliensis is the main (88%) etiological agent of human and animal sporotrichosis.The feline zoonotic transmission of sporotrichosis was observed in the 1990s in the State of Rio de Janeiro, Brazil, which is currently considered to be a hyperendemic area. In the South and Southeast Brazilian regions, Systemic forms are rare and usually affect immunocompromised individuals, mostly those with HIV .Chronic alcohol abuse results in lymphopenia and chronic activation of the T-cell pool, which may alter the T-cell ability to expand and respond to pathogenic agents, inducing to an anergy state and, changing Th1 and Th2 response.S. brasiliensis is the most virulent species of this genus, due to its ability to invade tissues and lead one to death.5Th1 response is considered as the main control factor of fungal infection. In addition to patient immunosuppression, we should emphasize that The high prevalence of alcohol abuse in the Brazilian population, estimated at 13.7%, and the increasing zoonotic transmission of sporotrichosis may lead to an increase in the prevalence of disseminated forms of the disease.Our report corroborates the association previously reported by others between alcoholism and the spread of sporotrichosis.10None declared.Norami de Moura Barros: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Allen de Souza Pessoa: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Arles Martins Brotas: Conception and planning of the study; obtaining, analysis, and interpretation of the data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the literature.None declared."} +{"text": "Since the first COVID-19 case importation on January 23, Vietnam is now the only country in the world contain the epidemic with 268 confirmed cases (52 active and 216 recovered) with no deaths over the past three months. Being proactive in contact tracing and restrict quarantine of multiple clusters early are common policies that helped Vietnam efficiently control the spread of COVID-19. However, they are resource-intensive while the country has a limited capacity for massive testing. How to ensure surveillance and detection at the grassroots level, especially in rural and remote areas, is a critical question that is challenging not only Vietnam but also other low- and middle- income countries. In this viewpoint, we first summarize the roles and responsibilities of the network of village health workers over its long history of development in Vietnam. Thereafter, we discuss the functionalities of this informal taskforce in monitoring COVID-19 epidemic and delivering packages of interventions, especially in disadvantaged settings.Sharing a borderline of nearly 1400 km with China, it has been speculated that the northern mountainous region of Vietnam is at substantial risk of COVID-19 transmission . The regIn Vietnam, village health care is part of the grassroots health system and playing an important role in primary health care (Understanding the important role of village health care in primary health care in the community, Vietnamese government and Ministry of Health issued a number of decisions on strengthening and empowering the grassroots health care network, including village health services. The Health Minister's Decision No. 3653 on November 15, 1999 of the Health\u2019s Minister defined the functions and tasks of village health workers, which provided village health workers with clear guides on their functions and duties in the care and protection of people's health. The decision introduced five major responsibilities of village health workers, namely health education and communication, instruction of performing hygiene for disease prevention, maternal and child health care and family planning, first aid and basic medical care, and implementation of health programs . AccordiCOVID-19, which is caused by the new strain of coronavirus SARS-CoV-2, is an infectious respiratory disease that can result in pneumonia in humans . InfecteIn the fight against COVID-19, it is essential to mobilize existing resources and provide materials and skills as well as lean management for at-risk communities to efficiently detect early signs of localized transmissions, identify infected areas and effectively quarantine them. In order to do so, Village Health Collaborators should be quickly equipped with knowledge and skills in COVID-19 control and prevention through multilingual training materials delivered by both local and national trainers. Governors should set up mechanisms and protocols for information exchange, data synthesis, sample collection, and surveillance. It is also important to notice that some important skills are missing, including the identification of mental health symptoms, mapping most vulnerable groups, such as the elderly, the poor, etc. and community-based rapid risk assessment. Counselling and social support should also be incorporated as parts of comprehensive approaches for those living in disadvantaged areas."} +{"text": "This mini-review focuses on the emergence of locomotor-related movements in early infancy. In particular, we consider multiples precursor behaviors of locomotion as a manifestation of the development of the neuronal networks and their link in the establishment of precocious locomotor skills. Despite the large variability of motor behavior observed in human babies, as in animals, afferent information is already processed to shape the behavior to specific situations and environments. Specifically, we argue that the closed-loop interaction between the neural output and the physical dynamics of the mechanical system should be considered to explore the complexity and flexibility of pattern generation in human and animal neonates. Locomotor function bridges the entire life span but its development during fetal age and the first post-natal years of life is crucial for the acquisition of mature behavior. Where does locomotor behavior start? This question, suggesting a developmental continuity, is a central and long-standing issue , sensory signals originating in the limbs, and supraspinal signals (Grillner, During the early postnatal period, the locomotor-related movements also exhibit remarkable plasticity (Altman and Sudarshan, Based on the striking similarities in the early development of locomotion across mammalian species (Garwicz et al., More recently, Sylos-Labini et al. suggestein vitro, called fictive locomotion (e.g., Matsushima and Grillner, To date, numerous experimental paradigms examine the development and early plasticity of locomotion Even if the afferent information is used to a limited extent to adapt motor behavior to specific environmental contexts in neonates (Hadders-Algra, The first years of life represent an important phase of maturation of the central nervous system, processing of sensory information, and posture control. Also, many constraints evolve during the first year, such as the muscle-to-fat ratio in lower-limbs (Thelen et al., In particular, studies showed considerable changes in muscle activity with age. For example, agonist-antagonist muscle co-activation during stepping decreases as age increased from 1 to 12 months (Teulier et al., Such spatiotemporal reorganization of the locomotor output has already been investigated during infancy, highlighting how the rudimentary locomotor-related movements of neonates evolve into mature sophisticated ones (Lacquaniti et al., The elements observed in infancy are not discarded but instead become adapted, in parallel with changes in locomotion biomechanics (Dominici et al., The fine-tuning and reshaping of activation patterns of the multiple precursors in the first year of life stems in part from a functional reorganization of interneuronal connectivity, growing integration of supraspinal, intraspinal, and sensory control (Forssberg, Human infants also appear to be sensitive to transient changes in sensory input and respond to it appropriately (Yang et al., Less insight is available on the role of experience in the developmental process in human neonates during the postnatal period. In animals, motor experience during the prenatal and postnatal period has consequent developmental implications Provine, . Also inIn this mini-review article, we highlight the need to increase our understanding of the fine-tuning and reshaping of multiple precursors during the development of mature locomotor movements. Since motor coordination in the neonate is already punctuated by developmental plasticity, early responsiveness to environmental context could potentially be used to diagnose developmental disabilities, but also to design and test early therapies. By calling attention to experience-dependent development of the motor system, we hope this will inspire future studies on the control of movement during early development.All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Trypanosoma cruzi infection, is considered nonendemic in the United States of America , assuming that this chronic affection\u2019s epidemiology is different from that of Latin American countries. The attention is mostly focused on blood bank screening, organ donation, and vertical (mother to child) transmission [T. cruzi, particularly in the light of a recent acknowledgment about the role that vectorial transmission may have on the CD in the USA. A low awareness among physicians about CD risk besides its migratory origin can contribute to an existing underreporting rate, thus masking the accurate estimation of CD burden in the USA [Human Chagas disease (CD), caused by the smission . This apT. cruzi infections in immunocompetent individuals can pass undiagnosed and undetected among residents [Cases of autochthonous infection in the USA are not accurately tracked since it is only mandatory to report it in seven states, i.e., Arizona, Arkansas, Louisiana, Mississippi, Tennessee, Texas, and Massachusetts . Howeveresidents . In the esidents . This anAlthough imported CD cases are undoubtedly a matter of concern, there are also environmental conditions leading to autochthonous infections . New encT. cruzi infection risk components because there are parasite reservoirs among wildlife species and vectors living in contact with humans [T. cruzi transmission might resemble those of other endemic areas. Surveillance of infection prevalence among local populations of Triatominae is critical for accurate assessment of the public health risk. We attempt to contribute to this with an extensive historical literature review of records of autochthonous T. cruzi and human-related data for CD in California. This method of review provides a contemporary account of this topic\u2019s breadth of knowledge. There has been no recent review of this theme at the state level to the best of our knowledge, as has already been conducted in some other states, such as Texas [It is essential to improve our knowledge of h humans . This isas Texas .T. cruzi in triatomines, mammals and humans (CD), and human-triatomine interaction for California counties. We found 62 articles published between 1916 and 2018 encompassing 35 countries , followed by Triatoma rubida and Paratriatoma hirsuta.Between 1916 and 1930, counties , rangingThe first report of domestic incidence was recorded in the 1940s. In 38.8% of the publications reporting collection site for triatomines (19/49), at least one was collected inside human habitation. Domestic triatomine incidence was associated with dispersion from the vicinity of residences in semirural, canyon, or mountain-foothill areas ; during the monsoon, houselights are attractive to triatomines, especially while mating and/or seeking blood-meals.Twenty-two publications reported 164 triatomine bites and ensuing anaphylactic reactions among residents of 11 California counties , 80% of In publications around the 1950s, the bulk of domestic triatomines reports and human exposure came from residents\u2019 testimonies, from Kern, Riverside, Fresno, and San Diego counties, and from descriptions of clinical cases . AlthougT. protracta saliva. Along with this, human blood-meals have been found in free-roaming triatomines [Research on human-triatomine interaction in California involved two surveys conducted 50 years apart. The State Department of Health conducted a study in 1962 in Mariposa and Tuolumne counties that recorded more than 101 bite cases. In 2012, Los Angeles\u2019 residents reported bites resembling the swelling produced by triatomines, and rural residents in Santa Barbara were found with immunoglobulin G (IgG) against the atomines .In 1982, the first autochthonous human case of CD was reported for California in Tuolumne county: a 50-year-old woman from Lake Don Pedro . ThereafT. cruzi in California is the first one in more than 50 years. A temporal analysis of the publications shows an early scientific effort to compare some endemic areas; 80% of the articles were published before the early 1980s have led to an increasing encroachment upon the natural habitat of triatomines and their mammal hosts. This might raise the chances of triatomine domestic incidence due to their flexibility in habitat and host requirements, including dogs and other mammals . Examples of Triatoma sanguisuga in Louisiana came after the disruption of hurricane Katrina; there was a change of infestations in human dwellings [Socioenvironmental changes of the last five decades in California have not been followed by research on their effects on human-triatomine interaction and wellings .T. cruzi distribution in California. This is due to the scarcity/absence of records in some areas and early discovery of the association triatomine-woodrat that might be biased to the field research. An ecological niche modeling approach of the geographic distribution of vector species indicates favorable host habitat in many unsurveyed regions of California [County-level maps of reports only partially reflect the lifornia .T. cruzi and CD needs research/intervention on the:Our review in California highlights that a critical and accurate assessment of the public health risk for T. cruzi infection for further robust analysis on habitat suitability and risk due to socioenvironmental changes;Spatial modeling of pattern occurrences of triatomine and Dynamics and mechanisms of transmission: spatial variation of triatomine activity, infection levels and their reliance on humans-blood, dynamics of dispersal flights and free-roaming triatomines feeding habits;Identification of sylvatic, synanthropic, and domestic animal blood-sources and determination of infection variability;T. cruzi circulating strains and an analysis of the parasite\u2019s genetic variation;Identification of the Large-scale systematic programs of active surveillance, rigorous population-based data collection, and comprehensive assessment to determine infection prevalence and morbidity to identify factors that might inform policy and program-driven actions, especially among the vulnerable (impoverished residents living in substandard housing);Improvement of local knowledge local about epidemiology and ecology and the criteria for public health promotion to raise awareness among residents, physicians, and clinicians;Active screening of heart failure patients, hunters/campers, and pregnant women; andContinuing medical education programs on diagnosis and treatment among physicians.S1 Text(DOCX)Click here for additional data file."} +{"text": "The beneficial effects of oxytocin on infarct size and functional recovery of the ischemic reperfused heart are well documented. The mechanisms for this cardioprotection are not well defined. Evidence indicates that oxytocin treatment improves cardiac work, reduces apoptosis and inflammation, and increases scar vascularization. Oxytocin-mediated cytoprotection involves the production of cGMP stimulated by local release of atrial natriuretic peptide and synthesis of nitric oxide. Treatment with oxytocin reduces the expression of proinflammatory cytokines and reduces immune cell infiltration. Oxytocin also stimulates differentiation stem cells to cardiomyocyte lineages as well as generation of endothelial and smooth muscle cells, promoting angiogenesis. The beneficial actions of oxytocin may include the increase in glucose uptake by cardiomyocytes, reduction in cardiomyocyte hypertrophy, decrease in oxidative stress, and mitochondrial protection of several cell types. In cardiac and cellular models of ischemia and reperfusion, acute administration of oxytocin at the onset of reperfusion enhances cardiomyocyte viability and function by activating Pi3K and Akt phosphorylation and downstream cellular signaling. Reperfusion injury salvage kinase and signal transducer and activator of transcription proteins cardioprotective pathways are involved. Oxytocin is cardioprotective by reducing the inflammatory response and improving cardiovascular and metabolic function. Because of its pleiotropic nature, this peptide demonstrates a clear potential for the treatment of cardiovascular pathologies. In this review, we discuss the possible cellular mechanisms of action of oxytocin involved in cardioprotection. Our important findings highlighted the discovery of a specific OT system, including the presence of OT and the OT receptor (OTR) in the rodent and human heart . The prea neural and renaa neural . Conversa neural . Howevera neural . In facta neural .The role of OT in the regulation of blood pressure is well documented . OT reguin vitro and contain numerous cardiac progenitor cells (CPCs), which can contribute to cardiac reparative processes . Epidemiological studies have shown that death rates from cardiovascular diseases are increased in the patients with T2DM. This higher mortality rate is explained, in part, the downregulation of the pro-survival kinase pathways, disturbances in the mitochondrial permeability transition pore (mPTP), dysfunctional mitochondrial adenosine triphosphate (ATP)-sensitive potassium channel (mKATP) channels, and increased calcineurin activity, all of which are linked to loss of conditioning . The rolvia multiple mechanisms and pathways, affecting platelets, fibroblasts, endothelial cell, smooth muscle cells, and immune cells. In this regard, optimal cardioprotection likely requires the application of several combinations of additive or synergistic multitarget therapies (Coronary heart disease (CHD) in the form of acute myocardial infarction (MI) and acute coronary syndromes accounts for nearly one-third of heart disease-related deaths and disability in developed countries. Timely reperfusion of the coronary arteries after acute MI is critical for the restoration of blood flow. A reduction in infarct size can also be accomplished by subjecting the heart to repeated short periods of ischemia followed by IR . Rapid rherapies . In thisherapies . There iherapies . In rat herapies and infaherapies . Downregherapies . In addiherapies . These eherapies .1/V2 receptors) and its potential involvement on cardiac function of the G-protein coupled receptors is regulated by changes in receptor expression and resistance and local OT concentrations exposed to the OTR , which mediate the acute phase of an inflammatory response as seen in fever. The involvement of the NLRP3 inflammasome in conditions such as impaired glucose tolerance and peripheral inflammation from obesity has been reported, and evidence suggests that the inflammasome may contribute to the development of vascular and ventricular dysfunction . The mosIn addition, OT maintains the viability and morphology of CMC in the injured heart. To explain this effect, several mechanisms of action of OT in cardiac cells have been proposed. These mechanisms include decreased apoptosis, hypertrophy, and fibrosis in CMC as well as an increase in glucose uptake and oxidation. Benefits of OT also occur as a result of increased cell proliferation and differentiation of cardiac stem cells . We havein vitro model for the study of CMC in cardiac pathologies, including cardiac hypertrophy (via specific OTRs (unpublished data). This observation is consistent with the findings reported by via phosphoinositide-3-kinase (PI3K) and independent of insulin receptor signaling. This effect of OT was further increased in CMC with an uncoupler of mitochondrial oxidative phosphorylation and cGMP by NP production is a well-known mechanism that inhibits pathological hypertrophy pathway. We have reported that OT regulates this pathway in CMC hypertrophy induced by ET-1 and Ang-II. In physiological concentrations (\u223c10 nM), OT prevented hypertrophy in newborn and adult rat CMC by several mediators, including PI3K/ERK1/2/ANP-cGMP/NFAT signaling . In thisertrophy . Our worertrophy . This meIn summary, OT is produced in the cardiovascular system and is critical in the regulation of cardiac and vascular function during early development and adulthood. The major actions of OT include regulation of chronotropy and inotropy of the heart as well as vascular tone of cardiac resistance vessels. OT is also involved in blood pressure and body volume regulation via the cardiac\u2013renal axis and the release of ANP and NO. In addition to cardiovascular regulation and protection, OT exerts robust anti-oxidative and anti-inflammatory effects in CMC. In cells, OT targets mitochondria, promoting glucose uptake and reducing the effects of ROS upon reperfusion.Animal studies indicate that OT is not only a cardiovascular protective peptide but also critical for cardiovascular homeostasis and in the reduction in the severity of cardiovascular pathologies. The significance of OT in cardioprotective signaling warrants further study.MJ, TB, and JG equally contributed to the organization and writing the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dear Editor,Epidermolysis bullosa (EB) composes a group of hereditary bullous disorders in which the blisters arise spontaneously or are triggered by minimal trauma. Koebner suggested this denomination in 1886. EB is divided into four major types and several distinct clinical phenotypes, according to the level of skin cleavage, as well as clinical and molecular characteristics.2Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is an uncommon subtype of epidermolysis bullosa simplex . It is characterized by non-cicatricial blisters, mainly at the distal extremities, and progressive mottled hyperpigmentation. Until 2013, only 15 families and eight sporadic cases had been reported, according to the data from the Hospital Infantil Universit\u00e1rio Ni\u00f1o Jesus, in Madrid, which motivated this report.The patient was a 2-year-old girl, phototype III, with a history of blistering skin since birth. On dermatological examination she had desiccated blisters on the feet, as well as hyper- and hypochromic macules scattered over the tegument with mottled appearance . NormochFirst described in 1979 by Fischer and Gedd-Dahl, EBS-MP begins in childhood and has a genetic origin. It is a basal EBS caused by a mutation in the KRT5 gene that encodes cytokeratin 5. It occurs most commonly due to a punctual heterozygous p24L mutation in the non-helical V1 domain of cytokeratin 5.2The diagnosis of this dermatosis is based on typical clinical findings, family history, immunomapping, and/or transmission electron microscopy, as well as molecular/mutation analysis when possible.Clinically, it is characterized by non-cicatricial blisters, mainly at the distal extremities, as well as progressive mottled hyperpigmentation, which does not occur at the site of the blisters and often disappears in adulthood. Some cases may be accompanied by hypopigmented macules, as could be seen in this patient. There are also reports of palmar and plantar focal hyperkeratosis. Small acral verrucous papules, onychodystrophy, and mild involvement of the oral mucosa can be observed during childhood. Uncommon findings include photosensitivity and dental disorders (caries).The differential diagnosis of EBS-MP includes other types of EBS (mainly the herpetiformis type of Dowling-Meara), Kindler syndrome, Naegeli-Franceschetti-Jadassohn (NFJ) ectodermal dysplasia, other forms of dyschromia, Dowling-Degos disease, and even atypical cases of Darier's disease with mutations in ATP2A2.4Due to the clinical hypothesis of EB and to determine the level of skin cleavage, immunomapping or transmission electron microscopy should be performed. The immunomapping has diagnostic accuracy similar to transmission electron microscopy, with the advantage of simple and fast execution and reading. It is associated with the use of monoclonal antibodies and may be considered an indirect immunofluorescence technique. In the EBS, the skin cleavage occurs in the basal layer , and fluorescence deposition on the blister floor is seen with all antigenic markers , as observed in this case.Ultrastructural analysis of the pigmented areas in this form of EBS demonstrates abundant mature melanosomes within the basal cells.Thus, this report details a rare case of a possibly sporadic EBS-MP. The authors emphasize the rarity of this subtype of EBS and its remarkable clinical characteristics favoring future diagnoses, and highlight its benign character, with no scarring or deforming lesions and regression of hyperpigmentation in adulthood.None declared.Fl\u00e1via Regina Ferreira: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Carolina Fernandes Pereira: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; critical review of the literature.Juliana Carvalho Moretto: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; critical review of the literature.Mariana Patriota Naville: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; critical review of the literature.None declared."} +{"text": "Professor Daniel Noni Lantum , an AfriHe introduced several generations of doctors and public health professionals in his native Cameroon and in Africa to public health practice and directed over 500 theses. Prof Lantum is also well known for his invaluable contribution to the fight against iodine deficiency and associated disorders. His work with the World Health Organization, UNICEF, governments, non-governmental organizations (NGOs) and communities contributed enormously towards universal salt iodization, a key strategy to achieve elimination of iodine-deficiency related disorders for which he was awarded to Algepa Prize in 1996 in Paris and made him well-known in the nutrition and micro-nutrient circles. He is also known to have laid the groundwork for the creation of various faculties of medicine in Africa.Prof Lantum is also recognized for his passion for African cultural heritage. He worked tirelessly to promote African traditional medicine - that he practiced and taught unapologetically - as an important component of primary health care. Intellectual infatigable, Prof Lantum, wrote intensively in areas as diverse as education reforms, poetry, history, politics, African traditions, and religion.Prof Lantum studied Medicine at the University of Ibadan (Nigeria), graduating in 1962 with a Bachelor of Medicine and Bachelor of Surgery. He obtained a diploma in tropical medicine and hygiene at the Liverpool School of Tropical Medicine in 1965 and completed a Master (MPH) and Doctorate (DrPH) in Public Health at Tulane University (USA) in 1969 and 1970, respectively. His long and rich professional career encompasses the public sector, NGOs, and development organizations in various African countries. He was a member of numerous professional, traditional and cultural societies.In his academic career, Prof Lantum was Professor of Public Health at the Yaound\u00e9 University Centre for Health Sciences since 1970 and was appointed in 1998 as Vice Chancellor of the Bamenda University of Science and Technology (Cameroon). He received countless distinctions from various governments, organizations, and universities across Africa.Prof Lantum will be remembered for his passion to transmit knowledge and educate the younger generation, his love for people, and his enthusiasm to address protracted public health issues in Africa. His extraordinary story telling abilities - rooted in his deep knowledge of the traditions and history of his people - translated his passion for African ancestral knowledge. May his soul rest in peace.He is survived by four children and seven grandchildren.Contributions from: Dr Raoul Kamadjeu and Prof Charles Shey Wiysonge"} +{"text": "The Special Issue \u201cNon-Destructive Testing of Structures\u201d has been proposed to present recent developments in the field of diagnostics of structural materials and components in civil and mechanical engineering. The papers highlighted in this editorial concern various aspects of non-invasive diagnostics, including such topics as condition assessments of civil and mechanical structures and connections of structural elements, the inspection of cultural heritage monuments, the testing of structural materials, structural health monitoring systems, the integration of non-destructive testing methods, advanced signal processing for the non-destructive testing of structures (NDT), damage detection and damage imaging, as well as modeling and numerical analyses for supporting structural health monitoring (SHM) systems. Engineering structures are gradually destroyed over time due to the influence of atmospheric conditions, excessive loads, and processes of natural aging. Since damage in a structural element may lead to improper operation of the whole object, various damage detection and structural health monitoring (SHM) methods have thus been investigated and developed to improve reliability and safety and to solve the maintenance problems of infrastructural and mechanical structures.The term non-destructive testing (NDT) covers a wide group of measurement and analysis techniques used in the process of assessing the current state of structural materials or elements. It is a quick and effective approach, the main advantage of which is the ability to examine the material in a non-invasive manner, without damaging or changing the composition or shape of the inspected object. In recent years, there has been growing interest in the development of non-invasive methods, including in the field of civil and mechanical engineering.The Special Issue \u201cNon-Destructive Testing of Structures\u201d has been proposed to gather the experience of civil and mechanical research communities in relation to the latest advances and trends in the field of diagnostics of structures and their components. A total of 22 papers were published in the Special Issue to touch different aspects connected with novel NDT approaches, with particular emphasis on the development of single and integrated measurement techniques, damage imaging procedures, advanced signal processing as well as modeling and numerical analyses for supporting SHM systems. A brief description of the Special Issue papers is presented below.pH(y) signal of the sample under different stresses. The fracture morphology was observed by using scanning electron microscopy (SEM). The results showed how different types of grooves influenced the magnetic intensity gradient changes [A wide range of experimental and numerical studies is reported in the papers in this Special Issue ,5,6,7,8.The second group of papers has been devoted to the condition assessment of concrete and cement-based materials and structures ,15,16,17Another group of articles concerned non-destructive testing of bridge structures ,19,20. KThe diagnostics of cultural heritage structures were the subjects of interest in the last two papers from this Special Issue ,22. TomaIn summary, the papers presented in this Special Issue concern various aspects of non-invasive diagnostics and present recent developments in the field of the diagnostics of structural materials and components in civil and mechanical engineering. Both interesting practical solutions and a significant contribution to the new approaches to NDT were achieved."} +{"text": "Dear Editor,Cryptococcus neoformans is the etiological agent of cryptococcosis, an infectious disease that affects humans, domestic and wild animals. This pathogen is often found in pigeon excreta, possessing innumerable environmental sources.The diagnosis can be performed by analysis of cerebrospinal fluid (CSF), urine sediment, bronchoalveolar lavage fluid, wound exudates, floating node aspirate and suspected lesions biopsies.Treatment of cryptococcosis in immunocompetent and immunocompromised humans, consists of amphotericin B in combination with 5-flucitosin in disseminated infections; or with fluconazole or itraconazole, as an alternative for the treatment of cutaneous infections.Cryptococcus spp. The species identification and antifungal susceptibility were performed in the Vitek 2-Compact. The isolate was also identified by sequencing the D1/D2 domain of the rDNA using the primers NL1 and NL4 being identified as Cryptococcus neoformans (San Felice) Vuill (1901). Histopathology revealed numerous yeast fungal structures, best visualized by PAS staining (periodic acid-Schiff), with mucopolysaccharides capsules that stand out for Alcian Blue staining, with scarce inflammatory infiltrate in between disease.C. neoformans meningitis.Drug resistance, when using fluconazole, is likely to occur during prolonged suppressive treatments as in cases of This report presents the medical history of a patient with cutaneous and pulmonary alterations, which allowed the diagnosis of cryptococcosis and the appropriate treatment for it. Through this report we could highlight the importance of the differential diagnosis of infectious conditions in renal transplant patients.None declared.Deborah Lucena Markman: approval of the final version of the manuscript; elaboration and writing of the manuscript; effective participation in research orientation; critical review of the literature.Pamella Paola Bezerra de Oliveira: elaboration and writing of the manuscript; critical review of the literature.Daniela Mayumi Takano: approval of the final version of the manuscript; effective participation in research orientation; critical review of the manuscript.Idalina In\u00eas Fonseca Nogueira Cambuim: approval of the final version of the manuscript; effective participation in research orientation; critical review of the manuscript.None declared."} +{"text": "P \u2264 0.05. Three hundred and twenty-nine responded to the questionnaire. More than half of the respondents agreed that dental X-ray is hazardous to health (60.79%), and 68.1% were familiar with ALARA (as low as reasonably achievable) principle. However, only 34% are familiar with the recommendations of the National Council on Radiation Protection (NCRP) and International Commission on Radiological Protection (ICRP). The use of lead apron and thyroid collar for patients' protection from X-ray radiation was practiced among endodontic postgraduate students more frequently as well as those who are proactive in the academic field. Undergraduate students, endodontic postgraduate students, and endodontists in the academic field were the most aware towards radiation reduction measures. The use of the preventive measures needs to be emphasized more among general practitioners, endodontic postgraduate students, and endodontists especially in governmental hospitals and private sectors.The aim of this study is to evaluate the knowledge, attitude, and perception of radiation hazard and preventive measures among dental undergraduate students, general practitioners, endodontic postgraduate students, and endodontists in Saudi Arabia. Multiple choice questions questionnaires were distributed among undergraduate and endodontic postgraduate dental students, general practitioners, and endodontists in the colleges of dentistry in Saudi Arabia, government hospitals, and private clinics. The questionnaire included sociodemographic data, assessment of the knowledge of radiation physics and biology, assessment of the practice of dental radiography, and assessment of knowledge of radiation protection. Chi-square test was used for individual and multiresponse analysis. Level of statistical significance was set at It may rnations . It has The effects of the X-ray on the living tissue are deterministic and stochastic. Both are harmful and could lead to serious complications ; therefoWe hypothesize that the knowledge and the perception of dental undergraduate students, general practitioners, endodontic postgraduate students, and endodontists on radiographic protection is high, but the attitude towards taking precautions might be low.The aim of this study is to evaluate the knowledge, attitude, and perception of radiation hazard and preventive measures of the ionizing radiation among dental undergraduate students, general practitioners, endodontic postgraduate students, and endodontists in Saudi Arabia.The present study was approved by the Institutional Review Board of Princess Noura Bint Abdulrahman University (H-01-R-059). Dental students and clinical practitioners that deal with radiography during their clinical practice were sent questionnaires related to knowledge, attitude, and perception of radiation hazard and preventive measures of ionizing radiation. The questionnaire was distributed among undergraduate and postgraduate endodontic dental students, staff, and faculty in the colleges of dentistry at King Saud University (KSU), Princess Noura Bint Abdulrahman University (PNU), King Saud Bin Abdulaziz University for Health Sciences (KSAUHS), King Abdulaziz University (KAU), King Faisal University (KFU), Imam Abdulrahman Bin Faisal University (IAU), Umm Alqura University (UQU), King Khalid University (KKU), Taiba University (TU), Qassim University (QU), Prince Sattam University (PSAU), Hail University (UOH), Almajmaa University (MU), Riyadh Elm University (REU), and Alfarabi Colleges. Moreover, it was sent to clinicians in government hospitals including Ministry of Health Dental Clinics (MOH), Security Forces Hospital (SFH), King Abdulaziz Medical City (KAMC), Prince Sultan Medical Military City (PSMMC), and private practice.The form was electronic based and distributed online through Google Forms by Twitter and WhatsApp social media platforms.The questionnaire was in the form of multiple choice questions related to the harmful ionizing radiation and protective measures. It was developed in English and a pilot test of 25 questionnaires was performed against a checklist to determine content clarity, language development, and validity. The questionnaire was divided into three sections: sociodemographic data that consisted of gender, age range, working place, years of clinical experience, and socioeconomic status. Assessment of the knowledge of radiation physics and biology, assessment of the practice of dental radiography, and assessment of knowledge of radiation protection were asked in the questionnaire.P \u2264 0.05.Data were entered into an electronic database and analyzed using SPSS version 20 . Descriptive statistics were used. For differential statistics, the chi-square test was used for individual and multiresponse analysis. Level of statistical significance was set at P < 0.05), as undergraduate students showed most of the correct answers. On the other hand, most of the respondents (81.5%) agreed that radiation from dental X-ray accumulates over time, while 64.4% agreed that damage to living tissues by radiation is due to direct and indirect effect, and 61.1% agreed that short-term effects of radiation are due to large amount of radiation absorbed over a short period of time. Only 42.6% agreed that the cause of long-term effects of radiation is the small amount of radiation absorbed repeatedly over a long period of time. Almost half the respondents (53.2%) agreed that X-rays can be reflected from the walls of the room. In these responses, there was no statistically significant difference between the different educational levels (P > 0.05).Demographic data results are summarized in Most of the respondents use radiographs frequently in different stages of their endodontic treatment, either preoperatively for case evaluation (83%), or during treatment for verification of the procedure (78.1%), or postoperatively to evaluate treatment outcome (76%).Tables P < 0.05), where the endodontic postgraduate students and endodontists were mostly taking three and more radiographs compared to less number of radiographs taken by undergraduate students and general practitioners. These results were in accordance with previous studies, where they found that the number of radiographs taken during root canal treatment varies between three to four radiographs [Successful endodontic treatment requires adjunctive tools, such as intraoral radiographs, to be used preoperatively during endodontic examination and case evaluation, or during treatment for verification of the procedure, or postoperatively to evaluate treatment outcome. In this study, the frequency of taking radiographs during dental procedure differentiate statistically between the different educational groups away from the patient at an angle of 90\u00b0\u2013135\u00b0 from the tube head (Position Distance Rule) . In 2014This study had some limitations where the number of respondents could not be controlled. Moreover, the number of respondents varied among specialities and working sectors and not equally distributed.Within the limitations of the study, it can be concluded that the knowledge of radiation hazard and preventive measures of the ionizing radiation among dental undergraduate students, endodontic postgraduate students, and endodontists in Saudi Arabia was quite fair especially in academic field. However, the radiation protection measures need to be emphasized more among general practitioners, endodontic postgraduate students, and endodontists especially in governmental hospitals and private sectors."} +{"text": "Although oral diseases are largely preventable, they are among the most non-communicable diseases globally, and they disproportionately burden disadvantaged communities, specially within low- and middle-income nations. The COVID-19 pandemic has highlighted the social, economic, and health inequalities in our society, including the existing global oral health inequalities. There is a shortage of dentist-scientist all around the world, especially in developing countries, such as Thailand. The National Institute of Dental and Craniofacial Research (NIDCR) and Fogarty International Center (FIC), joined efforts on creating research capacity in oral health in South East Asia through the Fogarty International Center Training Program in Clinical, Public Health and Behavioral Oral Health Research for Thailand (2006\u20132016). The University of Washington (USA), Thammasat University (Thailand) and Khon Kaen University (Thailand) partnered to conduct short-, medium- and long-term training programs to build regional oral health research capabilities. Investing in research has not only impacted trainees\u2019 career development but enhanced advancement of oral health research of South East Asia. The success of partnership calls for expanding oral health research training in other low-income countries. Oral diseases are among the most common non-communicable diseases worldwide . AccordiThe number of dentists-scientists worldwide is decreasing as the new generation of dental students favor clinical paths . MotivatThe National Institutes of Health (NIH) has recognized the need to build the research training and capacity outside of the United States (U.S.) through the creation of the Fogarty International Center (FIC). FIC is dedicated to advancing the NIH mission by supporting and facilitating global health research conducted by the U.S. and international investigators, building partnerships between health research institutions in the U.S. and abroad, and training the next generation of scientists to address global health needs . By faciFIC efforts on increasing research training and capacity around the world include expanding training in policy development, implementation, and evaluation at the institutional, local, and national levels 789. Whil78The public health burden of oral diseases has influenced the development of Thai dental education. With almost 70 million inhabitants, the developing country of Thailand is an active member of the Association of South East Asian Nations interested in creating oral health research capacity and training. Since the first dental school opened in 1940, currently, there are now 12 public and 4 private dental schools offering the degree of Doctor of Dental Surgery (DDS) through 6 years of education with an additional 3 years of mandatory public service after graduating from public dental school . While gFor over 20 years, the University of Washington, School of Dentistry, has partnered with Thammasat University and Khon Kaen University to train a new generation of oral health researchers who have impacted the dental public health arena in South East Asia. As a result of this partnership, these institutions created the Fogarty International Center Training Program in Clinical, Public Health and Behavioral Oral Health Research for Thailand . By training over 200 trainees from 18 countries, this training site has brought Thailand to the international forefront of oral health research. As a result, Thai universities have become the regional resource for oral health research in South East Asia.Topics discussed in these 5-day workshops included general scientific principles in planning and carrying out clinical research projects, levels of evidence in evidence-based clinical research, study designs, principles in the design and conduct of randomized clinical trials, statistical concepts and principles in testing hypotheses, basic behavioral models and ethical issues in the conduct of research on human subjects, and research protocol writing.Junior faculty and graduate students from the two collaborating Thai institutions, as well as short-term trainees who attended previous workshops were eligible to participate in the Summer Institute in Clinical Dental Research Methods held at the University of Washington in Seattle, U.S. In addition to clinical/public health/behavioral pathways, program participants included those pursuing advanced basic sciences research and degrees. This six-week program was designed to provide a short but intensive research training program for dental school faculty and professionals interested in clinical research. Specifically, core courses included biostatistics, clinical epidemiology and study design, behavioral research in dentistry, a data analysis workshop, a short course in randomized clinical trials, and a seminar on grantsmanship.The third level of training was designed to augment and strengthen oral health research pathways in existing Ph.D. programs in Oral Science at Thammasat and Khon Kaen Universities. Trainees with English language skills spent one year in Seattle at the University of Washington to accomplish following three things: a) undertake the coursework in biostatistics, epidemiology or health services at the UW School of Public Health, that they might not have been able to access in Thailand. The kinds of coursework trainees would undertake depended on their interests, but were likely to be biostatistics courses involving design of medical studies, survival analysis, logistic regression, and analysis of correlated data; epidemiology courses on genetic epidemiology, exposure measurement, nutritional epidemiology, clinical epidemiology; and health services courses on applied community research, health program evaluation, health promotion and disease prevention, and evaluation of health program costs and outcomes; b) during the one-year stay in Seattle, trainees worked with one or more of the UW mentors on research projects they were developing to enhance their learning experiences; and c) trainees were required to plan and finalize a dissertation research project that they would work on over the period of the next year in Thailand.With the purpose to provide a perspective on the impact of the FIC and NIDCR support on creating training and research capacity in South East Asia, we conducted a survey of former trainees to inform us on their perception on how the Fogarty International Center Training Program in Clinical, Public Health and Behavioral Oral Health Research for Thailand impacted their professional paths. All the training types were rated high on a scale of 0\u20135 by the trainees Figure . Out of In Peru, the past three decades have witnessed impressive growth in biomedical research catalyzed from efforts made among local educational institutions and NIH securing international partnerships and funding through research training programs . As a reKenya is a lower middle-income Sub-Saharan country in Africa with a population of more than 48 million people. People living in poverty (36.1% of the population) have impaired overall health and are at high risk for HIV infection 13. With We aimed to provide opportunities for decreasing global oral health inequalities by investing in creating research training and capacity building in low- and middle-income countries. To this date, only one such training site has been funded by FIC targeting oral health. We need to increase our advocacy efforts to expand oral health within FIC and global health within NIDCR. With this article, we hope to provide insights on the effects of long-term investments and efforts made in building research capacity in Thailand, and to advocate to FIC and NIDCR to expand such opportunities to other low-middle-income countries."} +{"text": "The coronavirus disease COVID-19) outbreak began in Wuhan, China, in December 2019; by March 11, 2020, it was declared a pandemic by the World Health Organization (WHO) . These gSome national specialty societies have also set forth their recommendations on the management of benign and suspicious breast lesions during the COVID-19 pandemic. The Brazilian Society of Surgical Oncology considerFor symptomatic patients with palpable breast lesions, suspicious nipple discharge, breast pain, or an abscess without a prior oncologic diagnosis, the Brazilian Society of Mastology, the Brazilian College of Radiology, and the Brazilian Federation of Gynecology and Obstetrics Associations highlight the importance of estimating how clinically suspicious lesions are defined and how imaging information impacts decision-making, particularly in patients older than 60 years . These cThese recommendations provide a detailed guide for caregivers regarding decision-making and are intended to provide the best balance between morbidity and mortality from breast disease, risk of self and healthcare team exposure to COVID-19, and consumption of health resources. With a goal of guiding service flow, triage, and treatment of benign and suspicious breast lesions in low-complexity and specialty care settings, we proposed recommendations as outlined in the flowchart in These recommendations regarding the users of the public health system are predicated on the free access and availability of safe health care facilities to mitigate risks for patients and professionals . ClinicaHealth routines and surgical algorithms are currently being reviewed and updated worldwide owing to the COVID-19 pandemic. Meanwhile, early breast disease diagnosis remains a priority in the Brazilian public health system . Here, wPurcino FAC, Ruiz CA and Costa AMM were responsible for the manuscript drafting, writing, editing and review. Baracat EC and Filassi JR were responsible for study supervision and manuscript drafting, writing, editing and review. Sorpreso ICE and Soares-J\u00fanior JM were responsible for the study conceptualization and supervision, as well as manuscript drafting, writing, editing and review."} +{"text": "The Geriatrics and Aging Processes Research Branch of the National Institute of Mental Health (NIMH) supports research on the etiology, pathophysiology, and trajectory of late life mental disorders. The branch encourages research using neuroscience, cognitive and affective science, and social and behavioral science to translate basic and preclinical research to clinical research. The branch prioritizes research that investigates neuropsychiatric disorders of aging, how they interact with neurodevelopment/neurodegeneration, and how to assess, treat, and prevent them. Of particular interest is research on social isolation and suicide. Suicide prevention research is an urgent priority: NIMH\u2019s portfolio includes projects aimed at identifying those at risk for suicide, understanding causes of suicide risk, developing suicide prevention interventions, and testing the effectiveness of these interventions and services in real-world settings. In this talk, a NIMH program official will discuss the NIMH research agenda in the domain of late-life mental illness, social isolation, and suicide."} +{"text": "Papillary intralymphatic angioendothelioma (Dabska tumor) is a rarely metastasizing lymphatic vascular neoplasm that usually affects children and young adults. The majority of these cases occur in soft tissues of extremities, and to date less than 40 cases have been described. Despite the generally indolent evolution, can be locally invasive with the potential to metastasize. We describe a case of a young woman presenting with a plantar lesion, for 9 months and histological diagnosis of Dabska tumor. This neoplasm should be considered in the differential diagnosis of vascular dermatoses, allowing early diagnosis and treatment. Long-term follow-up should be performed. A 35-year-old female patient sought a dermatologist, complaining of an injury to the sole of the right foot 9 months prior. She reported feeling only a slight size increase. Upon clinical examination, there was an area of violaceous staining, with poorly defined limits, on the sole of the right foot . DermoscPapillary intralymphatic angioendothelioma (PILA or Dabska tumor) is a rare vascular neoplasm, defined as low grade malignancy tumor, with high tendency of local recurrence.10None declared.Thadeu Santos Silva: Approval of the final version of the manuscript; conception and planning of the study; obtaining, analysis, and interpretation of the data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Luciana Rebou\u00e7as de Araujo: Approval of the final version of the manuscript; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; critical review of the literature; critical review of the manuscript.Geise Rezende Paiva: Approval of the final version of the manuscript; conception and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Rodrigo Guimar\u00e3es Andrade: Approval of the final version of the manuscript; conception and planning of the study; obtaining, analysis, and interpretation of the data.None declared."} +{"text": "The COVID-19 pandemic, a singular disruptive event in recent human history, has required rapid, innovative, coordinated and collaborative approaches to manage and ameliorate its worst impacts. However, the threat remains, and learning from initial efforts may benefit the response management in the future. One Health approaches to managing health challenges through multi-stakeholder engagement are underscored by an enabling environment. Here we describe three case studies from state , national (Ireland), and international (sub-Saharan Africa) scales which illustrate different aspects of One Health in action in response to the COVID-19 pandemic. In Ireland, a One Health team was assembled to help parameterise complex mathematical and resource models. In New South Wales, state authorities engaged collaboratively with animal health veterinarians and epidemiologists to leverage disease outbreak knowledge, expertise and technical and support structures for application to the COVID-19 emergency. The African One Health University Network linked members from health institutions and universities from eight countries to provide a virtual platform knowledge exchange on COVID-19 to support the response. Themes common to successful experiences included a shared resource base, interdisciplinary engagement, communication network strategies, and looking global to address local need. The One Health approaches used, particularly shared responsibility and knowledge integration, are benefiting the management of this pandemic and future One Health global challenges. The scope and impact of the COVID-19 pandemic is unprecedented in modern times. At the time of writing, over 10 million confirmed human cases and 0.5 million deaths from SARS-CoV-2 infection have been reported projects. The approach also integrates a systems approach to project management, communication, and data integration as well as novel application of principles of social psychology to engage stakeholders and create a culture of high emotional energy vital to collaboration and creative problem solving . TherebyIn this article, we use three case studies from different world regions to discuss elements of One Health approaches in the COVID-19 response. The three case studies are based on the authors' experiences and illustrate which of the essential One Health dimensions listed above applied in practice during the crisis. They provide examples of collaboration, shared responsibility and knowledge integration and illustrate opportunities and weaknesses.In Ireland, the National Public Health Emergency Team (NPHET) was established on 27 January 2020, to provide national direction, support and expert advice on the development and implementation of a strategy to contain COVID-19 . The firNPHET was supported by a number of expert groups, including the Epidemiological Modeling Advisory Group (IEMAG), which was established on 7 March ; see Sup. IEMAG wThe requirement for a rapid response led to a broad call to action from stakeholders with various expertise to contribute, in some cases beyond the traditional human medical disciplines. The team was chaired by a veterinary epidemiologist, with interdisciplinary membership from human public health, agriculture, veterinary medicine, food safety, disease ecology, and One Health backgrounds. Initial team selection was guided by disciplinary expertise, full-time availability (at short notice) and prior working relationships. The group's diverse interests and skills were well-suited to rapidly gathering evidence, and undertaking quantitative secondary and meta-analyses, in response to the emerging threat \u201322. In tIn terms of lessons learned, the rapid community-based aggregation of skills applied to a single acute problem should be held as an exemplar of how a distributed network of expertise can contribute in an efficient and effective way toward a goal. Interdisciplinary synergies were central to progress, both between mathematics and the life sciences and, importantly, between medical and allied disciplines. One Health perspectives predominated and there was cross-pollination of ideas and skills across disciplines to achieve efficiencies and better, more dynamic, systems. Challenges included remote working while maintaining communication and ensuring there was no duplication of effort across various NPHET subgroup teams. Furthermore, given the finite resources available, the COVID-19 response led to a temporary diversion of expertise and resource from other aspects of national animal health management. This case study is an important example of new thinking, diversity of thought, and new networks of expertise within Ireland.On 21 January 2020, the Australian Chief Medical Officer (CMO) issued a determination adding \u201chuman coronavirus with pandemic potential\u201d to the Biosecurity (Listed Human Diseases) Determination 2016. As a result, the Australian Health Protection Principal Committee, the key decision-making committee for health emergencies formed by the CMO and state and territory Chief Health Officers, was convened and daily meetings activated. In addition, national coordination was also activated for responding to the health emergency through the National Incident Room, the strategic reserve of personal protective equipment through the National Medical Stockpile and the provision of clinical and academic leadership through the National Trauma Center. Meetings of state, territory and Commonwealth health ministers to discuss pandemic readiness also started. On 25 January, Australia reported its first case of COVID-19, and the Australian Health Sector Emergency Response Plan for Novel Coronavirus (COVID-19 Plan) was implemented on 7 February . The COVEarly in the response, a One Health approach was implemented through the collaborative engagement of animal health experts, including veterinarians and epidemiologists, from NSW Department of Primary Industries (DPI) and other institutions , sharing expert knowledge. This approach is pre-defined by EMPLAN, under which a Combat Agency is nominated to lead operations and able to request support from other government areas, such as the NSW DPI. Animal health specialists worked for the Public Health Emergency Operations Center, responsible for activities such as tracing, research and providing expert advice, in the epidemiology and tracing units. In addition, the Ministry of Health liaised with other government agencies to establish remote tracing capabilities, including sharing of databases, online training and debriefs (due to the travel limitations) and the need to increase contact tracing capacity. As the responsible agency for providing agriculture and animal support during emergencies (under EMPLAN), NSW DPI as the Agriculture and Animal Services Functional Area was present within the State Emergency Operations Center throughout the response, liaising with health services with respect to animal care. Furthermore, the NSW state animal laboratory provided diagnostic services to NSW Health. NSW DPI worked with Australia's Animal Health Committee (AHC) to develop science-based, nationally consistent policy on animal health issues related to COVID-19, and supported the agriculture and animal sectors in achieving continuity of their businesses to safeguard animal health and welfare and help ensure a secure food supply . AHC devAs key learning of this response, COVID-19 highlighted the importance of a well-resourced response using a One Health approach, involving a broad range of human and animal health stakeholders and shared resources, which could then be scaled back as needed. The COVID-19 situation also highlighted the need for appropriate communication and management of animal health and welfare during human pandemics.The Africa One Health University Network (AFROHUN), formerly One Health Central and Eastern Africa (OHCEA) is a University led network of 24 public health, veterinary medicine, pathobiology and environmental health institutions and 16 universities in eight countries in East, Central and West African regions . Since its inception in 2010, AFROHUN supports institutional changes in teaching and learning environments in higher institutions that promote One Health approaches.In the absence of a global workforce, most African national COVID-19 response actions relied on national health professionals to provide the much-needed workforce in the management of the pandemic. Universities were among the key institutions that supported different national response task forces. University members served on scientific task forces with evidence-based and science-based data shaping response strategy options as the mainstream health workforce within ministries were at the forefront of the response.Between 23 March 2020 and 18 June 2020, AFROHUN through its wide continental network in collaboration with the USAID-funded One Health Workforce \u2013 Next Generation (OHW-NG) consortium led by University of California, Davis, provided a platform where network members (faculty and students), practitioners in One Health, and stakeholders virtually via ECHO and we have been active in COVID-19. The club, a multidisciplinary team of students from Makerere University and Mbarara University of Science and Technology in Uganda have been raising awareness about COVID-19 to communities and providing mental health support.\u201d Muganzi David Jolly, President, Students One Health Innovation Club, Mbarara University of Science and Technology, Uganda.\u201cI was asked to lead a team that was responsible for advising the government on the design and necessity for wearing cloth face masks in crowded places such as bus stands, markets, hospitals and places of warship. Now mask use is widespread as one of the preventive actions against COVID 19. In my leadership role, I have used some of the ideas from the AFROHUN ECHO sessions.\u201d Prof. Japhet Killewo, Professor of Epidemiology at Muhimbili University of Health and Allied Sciences (MUHAS), Tanzania.\u201cAn AFROHUN internal review identified several lessons learnt from the three months of COVID-19 sessions. The power of existing platforms, strong leadership, the combination of global and in-country perspectives and the ability of leveraging networks was highlighted, with around 200 participants and experts being part of the sessions, providing valuable multi-disciplinary, global and local in-country perspectives. The tight schedules of the task force members at the frontline of the pandemic prevented engagement of mainstream ministries in the design of the sessions. Participation of representatives from government and members from different COVID-19 task forces helped bridge this gap. Their perspectives on the issues and dynamics of the pandemic helped to shape subsequent sessions. A more efficient information flow in the national response system to reach diverse users could have enhanced the design and delivery of the sessions. Official engagement of specific task forces such as the scientific committees on the ECHO sessions could have added value.The three case studies each demonstrate important benefits from the use of One Health approaches in the management of the COVID-19 pandemic. The sharing of resources, multidisciplinary engagement and communication network strategies were common across the three case studies, in support of knowledge integration and more effective response management. Each can be placed within a One Health framework , providiWith regards to the six One Health dimensions that are described at the beginning of the paper, the three case studies all had clear sharing and learning structures in place that facilitated an exchange of data, information, and knowledge, as well as accessing and generating new knowledge through collaborative processes. All case studies described working across disciplines, but remained within the boundaries of the natural sciences and did not engage either the social sciences or the humanities. Also, wider society engagement was lacking, which meant that collaborative working remained within the multi- and interdisciplinary spheres and did not reach transdisciplinary working. Holistic planning was a key feature of case study 2, which provided a strong basis for the actions implemented. Systemic organization was dominant for AFROHUN, with the existence of a large, formal network of universities that allowed prompt recruitment of scientific experts into the response. None of the case studies explicitly described systemic thinking even though it is advocated by the WHO and the The case studies have demonstrated how expertise can be mobilized and shared quickly, given appropriate support infrastructure and in the light of the pressing needs of the pandemic. It is hoped that lessons learned can be extended to \u201cpeacetime,\u201d outside the crisis. Interdisciplinary synergies, underpinned by One Health concepts, will also be needed to manage critical global challenges, including those relating to climate change and antimicrobial resistance . To harnThe original contributions presented in the study are included in the article/BH, AB, and MH-J conceived the study. AB and SM wrote the case study 1 (Ireland). MH-J and OS wrote the case study 2 . WB and AY wrote the case study 3 (AFROHUN). All authors contributed to developing, writing, editing of the paper, and approved the manuscript for publication.JW was employed by the company Novometrix Research Inc, a social enterprise which facilitates alignment of diverse stakeholders for solutions in economic, social and environmental sustainability. JW and Novometrix Research have no financial interest in any aspect of this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The national infrastructure FoodOmicsGR_RI coordinates research efforts from eight Greek Universities and Research Centers in a network aiming to support research and development (R&D) in the agri-food sector. The goals of FoodOmicsGR_RI are the comprehensive in-depth characterization of foods using cutting-edge omics technologies and the support of dietary/nutrition studies. The network combines strong omics expertise with expert field/application scientists . Human resources involve more than 60 staff scientists and more than 30 recruits. State-of-the-art technologies and instrumentation is available for the comprehensive mapping of the food composition and available genetic resources, the assessment of the distinct value of foods, and the effect of nutritional intervention on the metabolic profile of biological samples of consumers and animal models. The consortium has the know-how and expertise that covers the breadth of the Greek agri-food sector. Metabolomics teams have developed and implemented a variety of methods for profiling and quantitative analysis. The implementation plan includes the following research axes: development of a detailed database of Greek food constituents; exploitation of \u201comics\u201d technologies to assess domestic agricultural biodiversity aiding authenticity-traceability control/certification of geographical/genetic origin; highlighting unique characteristics of Greek products with an emphasis on quality, sustainability and food safety; assessment of diet\u2019s effect on health and well-being; creating added value from agri-food waste. FoodOmicsGR_RI develops new tools to evaluate the nutritional value of Greek foods, study the role of traditional foods and Greek functional foods in the prevention of chronic diseases and support health claims of Greek traditional products. FoodOmicsGR_RI provides access to state-of-the-art facilities, unique, well-characterised sample sets, obtained from precision/experimental farming/breeding along with more than 20 complementary scientific disciplines. FoodOmicsGR_RI is open for collaboration with national and international stakeholders. In recent years, there has been an increased awareness towards the evaluation of food quality and safety in relation to human health and life. Existing legislation refers to technological processes of food, safety assessment by monitoring food contaminants, characterization of food composition and the determination of characteristic food nutrients. The \u201cclassical\u201d targeted analytical procedures are still dominant; however, the holistic characterization of food products through \u201comics\u201d technologies is gaining interest and applicability. Such novel approaches can provide new indicators of food quality, i.e., geographic and/or genetic origin, processing methods, adulteration, organoleptic characteristics, freshness, and so forth. Omic technologies are increasingly employed in nutrition studies aiming to increase the marketability of food products and to demonstrate and/or monitor their beneficial effects on human health. Nutrigenomics, Nutrigenetics and Nutritional metabolomics are topics and terms that are increasingly found in the literature and the wider public media.Foodomics combinesFoodomics is applied in various R&D aspects. In the study of the origin and quality of foods, foodomics can reveal discriminatory markers and, most importantly, patterns that characterize foods according to their geographical origin or subtle pedoclimatic effects , the different legitimate or non-legitimate regimens/interventions applied by food producers . Such data are important to support marketability and branding, especially for Protected Designation of Origin (PDO) and Protected Geographical Indication (PGI) products.In food safety, foodomics research can assist in the discovery of (bio)markers and mechanisms of toxicity and facilitate the identification of potential hazards. Untargeted-holistic approaches may reveal underlying and unlooked-for mechanisms of toxicity, such as polymorphisms or sub-toxic (but increased and unwanted) concentrations of biomolecules. It can be a potential tool for the investigation of food allergies and the analysis of transgenic foods, providing further insight on the effect of unintended transformations ,3.In nutrition studies, foodomics can provide new knowledge on the effect of nutrition and the fate of nutrients in the human body; Foodomics can identify (among others) perturbations caused by certain dietary regimens and characteristic patterns that can allow the development of a personalized dietary intervention for certain groups , or patients with food-related disorders .Considering the needs for R&D in these topics, the Greek Secretariat for Research and Technology announced a call for new Research Infrastructures. To address the call, a consortium was formed and submitted a successful proposal that provided the means for the establishment of FoodOmicsGR_RI. FoodOmicsGR_RI is a distributed multidisciplinary national research infrastructure aiming to perform, assist and promote omics research in agri-food R&D fields in the Greek and international research environment. This research may have a strong impact on the Greek agri-food sector. Greece has a unique landscape at the crossroads of Europe with Asia and Africa. The land expands to distances of up to 1200 km in a mostly mountainous mainland. The country has a very lengthy coastline and close to 3000 islands. Varying types of soil , water supply and pedoclimatic conditions result in a wide array of ecosystems and landscapes that give rise to one of the highest biodiversities in Europe, especially taking into account the area of the country. Flora includes 5752 species (452 endemic subspecies); the fauna includes 23,130 animal species, of which 3956 are characterised as Greek endemics. Furthermore, 3500 marine animal species and a high number of fungi species have been recorded in the Greek marine environment. Besides, a high proportion of these species are unique worldwide and this biodiversity results in the unique composition of Greek agricultural products.Greece has been an agricultural country, where until the 1960s the majority of the population lived in rural areas as farmers, maintaining traditional habits in life, farming and cuisine. All these factors converge to create a very large collection and a very strong portfolio of unique and characteristic food products. Highlighting these characteristics through advanced technology offers a way to support quality, nutritional or health claims, increase their attractiveness and marketability, and provide added value to local products. The central scope of FoodOmicsGR_RI is to serve the needs of the agri-food producers, providing concrete, solid and comprehensive data on the composition and nutritional value of their produce.http://biomic.web.auth.gr/) with specialist groups from the same University, and groups of researchers from the Universities of Athens, Crete, the Aegean, Ioannina, the Agricultural University of Athens, the International Hellenic University and the Biomedical Research Center of the Academy of Athens. This consortium is highly complementary, comprising scientists from 17 Departments of the participating Institutes (a full list is given in the http://foodomics.gr/).FoodOmicsGR_RI is a multidisciplinary consortium that joins forces from eight Greek Universities and Research Centers. FoodOmicsGR_RI brings together BIOMIC, a new interdisciplinary analytical laboratory of the Aristotle University of Thessaloniki (FoodOmicsGR_RI core (bio)chemical analysis groups provide expertise in bioanalysis, food analysis, metabolomics, elemental metabolomics, genomics and proteomics. Central technologies include analytical separations, Mass Spectrometry , Nuclear Magnetic Resonance (NMR) spectroscopy and Inductively Coupled Plasma Spectrometry. Analytical groups collaborate with (bio)informatics groups, food (bio)chemistry groups and application-oriented researchers with expertise in fields relevant to food and nutritional sciences: animal husbandry, veterinary pathology, fishery, apiculture, plant physiology, pomology, horticulture, vine and viticulture, environmental control, natural products, nutrition biochemistry and human exercise biochemistry. The core analytical groups have the critical mass to realise cutting-edge research in their specific field. Investment in infrastructure and the As a major initiative, the governance of FoodOmicsGR_RI is a demanding task that expands at various levels. It includes the General Assembly (GA) that is composed of delegates from all involved institutions and a Steering Committee of five members from the participating institutions that manage the operation of the RI. An International Expert Advisory Board (IEAB) has been appointed with the scope to further enrich the knowledge, the experience and the network of the RI participants. The 11 IEAB members include scientists from consumer organisations, industry or other businesses, potential stakeholders, and representatives of the activities of the RI.-Consultancy services and uptake of experimental intervention for foodomics studies (food product -oriented studies) or nutritional studies.-Big Data Handling and statistical analysis by various modes and special software including bespoke scripts and algorithms.-Genomic, proteomic and metabolomic analysis of foods, food products and biological samples from nutritional studies.-Quantitative Determination of key target molecules in foods and biological samples.The facility is open for collaboration subject to the conditions detailed at the central FoodOmicsGR_RI web page with templates for access-use of infrastructure, usage policy, protocols for sampling, sample delivery, and information about the different FoodOmicsGR_RI SOPs. The services offered by FoodOmicsGR_RI can be tailor-made including all or combinations of the following:FoodOmicsGR_RI can provide support for the realization of studies on small molecules (metabolomics), and cover genetics/genomics/epigenetics and proteomic fields, offering a \u201cone stop-shop\u201d model to stakeholders and users.A detailed list of validated protocols is given in The ideas and scope of FoodOmicsGR_RI are aligned with several of Research and Innovation Strategies for Smart Specialisation (RIS3) priorities for the agri-food sector. A list of relevant priorities is given in Omic approaches can become a tool to broaden the knowledge and understanding of how biodiversity (genotypic variation) can improve food and nutrition, influencing national policies and markets. This can be achieved via the examination of other nutrient-rich crops and plant species, not yet fully utilized, or unexplored traditional cultivars , benefiting both producers and consumers.Implementation: The strategy to approach such multidisciplinary and multifaceted work is to overcome the fragmentation of research by organising paths for effective samples\u2019 analyses and, similarly, paths for data curation that combine omics approaches to provide holistic analytical results and highlight characteristic features. The outline of specific sub-projects is described in the following sections.Foodomics research requires state of the art technologies and methods but also the existence of specialists\u2019 knowledge and high-quality sample banks, which, after comprehensive analysis, can provide data for the establishment of compositional databases. Compositional databases are the best means to provide the basis for the control of real samples (food products). Our consortium started this work with an exhaustive literature review. This resulted in the publication of topical reviews on metabolomics of different foods, such as the olive drupe and olive oil ,6,7, graAdditionally, Special Issues organised by FoodOmicsGR_RI members in 2020 include the following:\u201cMetabolomics in Food Authentication: Strategies and Applications\u201d in the MDPI Molecules Journal by Prof. Thomaidis and Dr. Dasenaki (guest editors), including important foodomics-based authenticity studies.\u201cNutritional Metabolomics\u201d in the MDPI Metabolites Journal, guest-edited by Prof. Georgios Theodoridis, Dr. Christina Virgiliou and Dr. Olga Deda.\u201cMetabolomics Methodologies and Applications II\u201d, guest-edited by professor Helen Gika, in the MDPI Metabolites Journal.Following this fundamental work, the consortium works further to generate databases of the molecular and elemental composition of foods to facilitate control, stir further technological developments and discover relationships between food constituents and/or elemental signatures with properties sought by consumers and producers. The generation of such databases started by thorough data-mining and text-mining of the literature and collaboration with expert groups from the control sector. As a starting step, nine foods/food products have been studied as priority commodities: olive oil, olives, wine, milk, cheese, yogurt, honey, royal jelly and pollen. Since the scope is to generate a database of the contents of Greek foods, a filter is set to study only publications that report Greek products, and exclude publications that map products and varieties that are not found or those that do not originate from Greece. Emphasis was given to map specific varieties/types of Greek produce. To generate data for a certain food, a set of keywords was selected; i.e., for wine, this includes characteristic Greek variety names: Asyrtiko, Nemea, Xinomauro and so forth.Text mining algorithms developed in our group are used to mine the international literature for publications containing carefully selected keywords of interest. The codes seek to gather quantitative information reporting the concentration of food constituents such as elements and small molecules. This information is subsequently curated by PhD level scientists to verify its validity and relevance, with extra caution given at concentration numbers and units.The generated database is now formatted as a web-based database to be soon open to the research community. During the realization of the works of FoodOmicsGR_RI, new data will be generated from FoodOmicsGR_RI sub-projects. Sample sets are analysed by various information-rich analytical platforms. The data are fused to generate an atlas of the content of these unique samples. New analytical data will populate, control, corroborate the data in the database. This strategy improves confidence in findings, while it can also reduce the impact of confounding factors in large-scale analysis and help researchers to reach useful, statistically meaningful findings. The overall aim of this activity is to establish a curated, internet-based database hosted in FoodOmics portal, that would serve as a reference point for the search of the content of Greek food products.Regarding milk, cheese and animal tissue samples, our expert research teams have also built a reference database through the implementation of various research projects ,22,23,24The central aim of FoodOmicsGR_RI is to strengthen the existing infrastructure of its partners and facilitate basic and applied translational research. With this upgrade, the aggregate capability for capital instrumentation of the laboratories reaches five hybrid time of flight mass spectrometers Q-TOF-MS hyphenated to UPLC systems (two with ion mobility capability(TIMS-TOF-MS)), a UPLC-QTRAP 6500+ MS/MS, more than 10 triple quadrupole MS/MS instruments hyphenated to UPLC, four UPLC-Orbitrap HRMS (one with nano-LC), three HPLC-MS (High-performance liquid chromatography mass spectrometry) single quadrupole instruments, an SFC-UV/MS system, more than 8 GC-MS , and three GC-MS/MS (Gas chromatography\u2013mass spectrometry systems with triple quadrupole MS). Mass Spectrometry capabilities of FoodOmicsGR_RI include Matrix-assisted laser desorption/ionization- time of flight- mass spectrometry (MALDI-TOF MS) exploiting the potential for high molecular weight analysis, enhancing the development of rapid and reliable high-throughput methodologies for food authenticity studies. NMR spectroscopy capabilities include two 600 MHz, two 500 MHz and four 400 MHz NMR spectrometers. Elemental analysis is performed in two ICP-MS Inductively coupled plasma- mass spectrometry) and two ICP-OES instruments. In addition, virtually all necessary instrumentation is available in the laboratories of the partners including FT-IR (Fourier-transform infrared spectroscopy), NIR (near infrared spectroscopy), capillary electrophoresis (CE)-, and several HPLC and GC instruments linked with various detectors: UV, PDA (Photodiode Array Detector), fluorescence, ELSD (Evaporative light scattering detector) for LC; FID (flame ionization detector), ECD (Electron capture detector) for GC). FoodOmicsGR_RI involves strong informatics expertise and access to high computing power. Staff scientists and newly recruited researchers are working on data treatment and the implementation of fusion of data collected from the different analyses and omics platforms.Advancing and harmonising the available analytical methods is a central task. The RI partners have very strong track records in research, as evidenced by their publications/presentations and patents awarded. Partner selection provides high complementarity in methods, expertise, infrastructure and application orientation. The latter practically covers the whole Greek agri-food sector. An array of protocols for genetic/metabolomics/proteomics analysis in targeted and untargeted mode exists among the FoodOmicsGR_RI partners and a list of current protocols and methods is given in FoodOmicsGR_RI has established a multitude of methods for metabolic profiling as well as elemental, genetic and proteomic profiling. In addition, protocols exist for the analysis of nutrients and pollutants in foods and the characterization of foods by state-of-the-art technologies. These cutting-edge analytical tools are applied in the quest to reach a thorough characterization of food products with a focus on Greek products of high value and market potential, which includes but is not limited to olive oil, wine, honey, dairy products and seafood. A major concentration of analytical force is directed to the small molecule domain. Metabolic profiling or metabolomics is the largest and strongest sector of the FoodOmicsGR_RI, bringing together researchers from the mass spectrometry and the NMR spectroscopy fields. FoodOmicsGR_RI researchers have developed methods for metabolic profiling of wine, cheese, honey, royal jelly, olive oil, olives and several other foods, natural products and biological samples.Untargeted methods, combined with fit-for-purpose chemometric approaches, strengthen the breadth of traditional targeted analysis ,26 and rThe validation of findings and the development of Quality Control (QC) measures have been a major element of our research. FoodOmicsGR_RI laboratories have been central in the development of QC approaches and measures for LC-MS based metabolomics ,40,41,42As the metabolomics field is maturing, there is increased interest in the development of targeted methods . UltimatNMR spectroscopy is a method of choice for the analysis of complex mixtures as it permits simultaneous monitoring of all constituents within the inherent sensitivity limits. Numerous applications have been proposed in food classification and origin determination in combination with multivariate statistical analysis techniques.1H and 31P NMR spectroscopy, metabolomics approaches that deal with the authentication of extra-virgin olive oil against adulteration with seed oils, olive oils of low quality were developed and validated [We have used multinuclear and multidimensional NMR spectroscopy as a tool for food profiling, quality control and analysis of a variety of food products. In olive oil, the initial focus was the profiling of low molecular weight compounds that can be used as molecular markers of olive oil quality and provided information on olive oil age, degradation and storage history ,59. Basealidated ,61. Curralidated . SuccessWine analysis is another field of great interest, and we have developed and applied analysis protocols for metabolite profiling of red and white wines. For wines produced from grapes of different Cretan vine varieties on consecutive wine production seasons, we were able to classify commercial wines based on variety . We haveNMR employing 1D and 2D experiments remains the most powerful tool in unambiguous structures elucidation of small molecules . CombineThrough the acquisition of new NMR instrumentation by FoodomicsGR, the consortium has now access to a novel solid-state NMR spectrometer that offers the capability of NMR analysis of solid foods in their native state without the need for long and arduous extraction procedures. We are already working on developing suitable solid-state NMR analytical protocols, with our initial targets being foods such as cheese, seeds, olive fruits and meat, where the potential for a strong analytical impact in quality control and novel metabolomics method development is very promising.FoodOmicsGR_RI provides Genomic services through a Genetic traceability system that is based on the identification of animals and their products through the study of DNA. DNA is detectable in every cell, resistant to heat treatments, and allows for individual or species identification. The DNA molecule has the feature of being enormously variable among individuals, making it possible to distinguish among them ,71. OnceAt the species level, our research team has developed a \u201cDNA barcoding\u201d method for the genetic identification of fish species in order to detect phenomena of involuntary or deliberate mislabeling of fish products. Specifically, DNA sequencing and universal primers are used for the species determination in different fish products of various fish species . Reliable species identification is accomplished through comparison with big databases such as the BOLD Database, providing 100% accuracy in most cases . For thehttps://fishreg.jrc.ec.europa.eu/web/aquatrace). For the sea bass, the panel of the 20 most informative SNPs demonstrates assignment accuracy over 90% for natural and over 60% for farmed individuals [Furthermore, geographic traceability genetic tools are developed within the Foodomics consortium, accomplished by a large genomic reference database that our research team has built through various research projects for a number of fish species, birds, and large mammals. In particular, for the two most common commercial fishes in Southern Europe, the sea bream and the sea bass, we have developed, in the framework of FP7 project \u201cAquaTrace: the development of tools for tracing and evaluating the genetic impact of fish from aquaculture\u201d, efficient, high fidelity and cost-effective genomic traceability tools, i.e., SNP panels, for the identification of the origin stock of random individuals , we have analyzed the genome of the Chios Greek sheep breed, which is well known for its high milk yield characteristics as well as its fertility. Specifically, genome-wide association analyses (GWAS) are performed to identify specific genomic regions on the sheep genome associated with novel derived phenotypes regarding the future selection of animal producers unaffected by weather fluctuations due to climate change. In particular, genetic and genomic characterization of performance resilience to climate volatility under heat stress conditions will be presented regarding Chios dairy sheep. Indicatively, genetic correlations between performance resilience and lifetime milk production and also identification of additive SNPs spanning a region of fifth chromosome and associated with Chios resilience will be reported [https://www.smarterproject.eu/).Genomic analyses are additionally applied to livestock species , which constitute an important economic sector for our country, for their genetically assisted breeding. The genomic improvement of the species of interest regarding their products, such as milk yield and quality, meat, wool, etc., is widely performed through single nucleotide polymorphisms (SNPs), which scan the whole genome to identify regions associated with the desirable phenotypic characters. In the framework of iSAGE Horizon 2020 project: \u201cInnovation for Sustainable Sheep and Goat Production in Europe\u201d for the improvement of food quality, the prevention of food spoilage and the extension of shelf-life by limiting microbial interactions ,79. FurtElemental Metabolomics have been developed in collaboration with the University of Boston and Griffiths University . ElementFoodOmicsGR_RI includes expert application groups and end-users with deep knowledge of specific food products and large, well-controlled historic sample banks of food products produced in a controlled environment with full historic records . All manipulations were performed by specialised research scientists working under strictly controlled conditions; samples were collected from specific restricted geographical areas, and were treated and stored in the same way.Sample banks containing honey and royal jelly samples were produced by specialised Apiculture Laboratories in experimental breeds. Olive oil collection has been built through participation in research projects and national initiatives and covers specific geographical areas, e.g., the islands of Crete and Lesvos, and mainland regions. Monocultivar olive oils have been collected after thorough control that ensured universal oil production technology. In a similar way, monocultivar wines have been collected from collaborating wine makers. Regarding animal tissue/DNA samples, our research team has built through various research projects a thorough reference database for several fish species as well as other species like birds and mammals. Partner laboratories maintain various sample banks of non-genetically modified soybeans cereals, nuts, almonds and other foods. Sample collections extend to several years, to enable the generation of representative profiles. Samples are accompanied by metadata: breed, species, exact geographic location of the farm, farming/feeding modes, and so forth.As an example, the process for the collection of milk and dairy products will be described in brief: Specialist groups (veterinary scientists) organised sample collection from well-known collaborating animal farms from certain geographical regions; detailed reporting of animal feed, animal breed, age was applied along with the application of strict sample collection, transportation and storage protocols. The collection of milk was organised from specific farms in various areas of Greece. For cheese samples, all production steps, from milk sampling until the cheese making, were monitored by trained scientists and veterinarians. Specifically, the hygienic condition of the farms was examined, taking into consideration the animal breeds, the territory of origin , the quality of the milk and the seasonal variation. Milk was selected from different flocks, with different grazing and production systems, whereas all zootechnical parameters were recorded. Cheeses were manufactured according to specific recipes, in absolutely strict conditions of safety and quality, with a fixed percentage of ovine and goat milk in the feta and graviera cheeses, the single breeds used, as well as the cheese-making technology, which was also recorded before the experimental analysis. One sample bank consists of 180 different milk samples from 180 different flocks of small ruminants corresponding to six restricted geographical areas and 140 produced cheeses in total, whereas 48 single breed cheeses were produced in certain regions, generating specific profiles to understand the actual differences among breeds, production methodologies and territory influences. Eighty commercial cheese products from four different regions were also compared, based on our strategic plan to differentiate the authentic and traditional way of cheese making from the industrial methods ,93,94. IThis research line aims to study the potential of omics technologies in the control of authenticity (authentication) of agricultural products, the identification of characteristic patterns of biomarkers and/or the certification of the geographic origin of foods. An impressive array of analytical techniques has been used in the literature for this quest. Omic technologies and bioinformatics are currently being put to use, aiming to achieve unparalleled detailed food analysis, whilst providing useful information regarding the molecular content of foods. In the following section, selected examples of the work of the consortium are provided according to the analytical technology.Our consortium has extensively applied MS-based metabolic profiling to categorise foods such as wine, olive oil, olives, milk, apples grapes, Chios mastic and other foods. Authenticity studies regarding adulteration and geographical and varietal origin have been efficiently addressed by applying different MS-based screening strategies ,30,95,96One of the most challenging tasks in food research is labeling verification, mainly regarding products characterized by PDO/PGI indication. An indicative example is the discrimination of PDO Kalamon olive drupes from drupes of different geographical origin, based on their full metabolome . MoreoveThe proteome domain can also be studied and used for the assessment of geographical origin. In a preliminary study on feta cheese samples from different areas of Greece, the full protein content of feta cheese was reported for the first time. A total of 489 proteins of diverse functions were detected and were linked to the identity of the product 1H and 13C NMR spectroscopy for metabolite profiling of a series of different food products [31P NMR spectroscopy after chemical derivatization was developed and was used to profile minor glyceride components in olive oil [Consortium members have developed several analytical protocols based on products ,103,104.live oil ,59, and live oil . Using tlive oil or olivelive oil .For wine variety and region classification, FoodOmicsGR_RI members developed protocols for the analysis of the phenolic content after extraction using XAD technology resins Cheese samples were investigated by the FoodOmcsGR_RI staff for the presence of a specific type of bacteria, which can determine the quality and sensory characteristics, and they were also authenticated in four different geographical areas of Greece. Conventional approaches used to identify different types of bacteria include microbiological techniques based on the morphological, biochemical, physiological (phenotype) and genetic characteristics (genotype) of the microorganisms ,108. IdeApplications of Elemental Metabolomics within our consortium include: determination of geographical and botanical type of honey , authentThe work of the consortium aims to combine metabolomics data from different platforms NMR, LC-MS, GC-MS to comprehensively map the metabolome of the foods under study. A further plan is to combine data across omics: for example, metabolomics with elemental analysis (ICP-MS) data, genetics and proteomics analysis data, and so on. Fusion of the data will be used to provide an integrated perspective of the studied specimen. FoodOmicsGR_RI staff have coined a novel term for such holistic approaches for food analysis: \u201cTrophometry\u201d, that is, the sum of omics techniques encompassing analysis of foods. The \u201cTrophometric Fingerprint\u201d is expected to be unique for any given food sample, and can provide information regarding traceability of raw materials as well as the origin and quality of each food itself .In addition, given the ability for sensory evaluation of food products in available premises, omics disciplines will assist in the elucidation of sensory-active compounds, considering all possible stimuli of multimodal perception and including the biological perception of food as an additional analytical dimension to comprehensively assess the quality of a given product.In nutrition Research and Development (R&D), our strategy is to exploit the power of Omics technologies to assess domestic agri-food biodiversity for the consolidation of the value of Greek produce . Based oThis research line will analyse biological samples from animal models or humans after nutritional intervention. Within the facility, long expertise exists in profiling biological fluids and excreta such as urine, blood, feces, saliva ,114,115 Increased interest in foodomics is central in life/medical science towards the prevention of disease, the development of a personalised diet and the development of nutraceuticals and functional foods. In this line of research, FoodOmicsGR_RI partners realise collaborative projects with various partners from the private sector to improve the manifestation of quality claims of existing products or support R&D efforts toward the development of novel products containing bioactive ingredients from the Greek flora/marine organisms . In a recent example, functional foods containing phenolic-rich water extracts of olives generated during olive oil production, or plant extracts, were prepared, and their effect on animal and human metabolic models was evaluated . For fooMembers of the FoodOmicsGR_RI consortium have investigated the health benefits of different constituents of emblematic Greek traditional foods like olive tree polyphenols for their cardioprotective, anti-ischemic and hypolipidemic effects ,126,127 The agro-industry produces important amounts of solid and liquid by-products that are characterized, on the one hand, by high organic loading, while, on the other, by the presence of bioactive compounds. The future sustainable management of these by-products should focus on the application of management practices that achieve protection of the environment and simultaneous increases in revenues. Under this frame, the amounts of the agro-industrial wastewater that are produced in Greece will be estimated, while different physicochemical and biolFoodOmicsGR_RI members have developed value chains in the food-agricultural industry that promote recycling economy by taking into account regional needs. These value chains are based on the integration of innovative technologies for recycling and extracting fine chemicals of high added value from constituents of agricultural wastes. The recovery of natural products with valuable health benefits like anti-oxidants, etc., can be achieved from agricultural wastes at an industrial scale using state-of-the-art green technologies like XAD adsorption resins or supercritical fluid extraction and used in numerous applications in food supplements, cosmeceuticals, etc. These applications can create not only new products from the food and agricultural industry but also lead to significant reductions in environmental footprint, enabling sustainable agriculture practices. Several applications have been developed for olive-oil mills, wineries and wood treatment. Additionally, FoodOmicsGR_RI partners are highly equipped for the treatment of agriculture wastes and bioproducts in three ,136,137 FoodOmicsGR_RI focuses also on the assessment of food safety from chemical contaminants which can be present in foodstuffs due to environmental contamination, cultivation practices or production, packaging and storage processes. One major task deals with the development, application and validation of sensitive, accurate and robust analytical methods based on various extraction techniques and hyphenated quantitative techniques (such as LC(GC)-MS/MS and LC(GC)-HR-MS/MS) using state-of-the-art instrumentation for facing current and future needs of food surveillance and for identifying new aspects to be controlled. Different classes of traditional and emerging contaminants such as pesticides, biocides, pharmaceuticals, PAHs, phthalates, organohalogenated compounds, etc., as well as their metabolites and transformation products, are studied in terms of their fate, dissipation, levels in food commodities, compliance with current maximum residue limits (MRLs) and possible associated dietary risks. A greater interest is provided for the most significant food matrices of the Greek production market such as olive oil, wine, honey, milk, vegetables, aquaculture products, etc. ,144,145.In food safety assessment, strong interest also exists in the study of the effect of molecules migrating from food contact materials (FCM) to food or food simulants. As such extensive work has focused on the determination of endocrine disruptors, different approaches have been studied including migration of the potential endocrine disruptor, bisphenol A (BPA), from polycarbonate baby bottles into aqueous food simulants , as wellRegulated substances and non-intentionally added substances (NIAS) migrating into food or official food simulants have been studied by different analytical approaches covering BPA, phthalates and otheIt should be mentioned that in the framework of national and industrial food safety control, a wide range of the developed methodologies has been accredited by the Hellenic Accreditation System (E.SY.D) according to ISO 17025 and has been established for the in-depth monitoring of contaminants in different food matrices ,155,156 The establishment of the RI offers benefits for the Greek research system in conducting cutting edge research in Foodomics research topics. FoodOmicsGR_RI can provide a reference center, a center of excellence for the analysis of the molecular/elemental content of food products, with its spearhead on small molecule analysis (metabolomics). The consortium can assist and strengthen research proposals and R&D efforts of the RI partners, external researchers, private enterprises and stakeholders.Very important issues in food quality, namely fraud and authenticity, are recognised as major activities in different types of food, while the health benefits of specific nutrients attract the interest of a wide research community, as well as producers, retailers, and consumers. In this aspect, FoodomicsGR_RI can assist in the integration of major areas that are important for the development of new research in different areas: botanical-agricultural, veterinary, analytical, nutritional biological effects and food engineering and related technologies. The variety of methodologies covered within the RI permits the establishment of testing cascades for high-throughput information-rich screening methods suited for juridical proof of fraud, authenticity and quality control. This direction can offer an efficient, cost-effective strategy for surveillance and consumer protection, making it possible to harmonize future standards and guidelines for their implementation. This can attract collaboration from scientists from the regulatory bodies in the region, thus increasing the impact on the Greek society and national economy.The recent establishment of FoodOmicsGR_RI promotes agri-food and nutrition R&D in Greece, bringing the national research system in line with large European and global initiatives. The activities of FoodOmicsGR_RI promote effective networking and collaboration among the consortium partners, but also between the research and the private sector. The unique combination of facilities, controlled sample banks, databases and expertise is available to support researchers and entrepreneurs in the realisation of R&D efforts.Omics research necessitates collaborative work from different disciplines and standpoints. Apart from the infrastructure, and the portfolio of analytical methods, this activity required specialists\u2019 knowledge and high-quality sample banks, and FoodOmicsGR_RI combines these characteristics.FoodOmicsGR_RI addresses a priority for Greece because the country possesses unique biodiversity, as described above in detail. The characterization of unique traditional products, highlighting their value and the potential benefit of the Greek/Mediterranean diet, is best achieved by an evidence-based analytical description of their compositional characteristics with the application of advanced technology. This can increase the attractiveness and market value/demand for these products, thus supporting brand naming and generating higher revenue for the producers and national economy."} +{"text": "Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People\u2019s Democratic Republic, Myanmar, and Viet Nam.Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD).A malaria elimination campaign in the 1950\u20131960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the \u20181\u20133-7\u2032 surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors.Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.The online version contains supplementary material available at 10.1186/s12936-021-03672-8. Plasmodium falciparum and Plasmodium vivax in Yunnan, registered in 2015 and 2016, respectively, were also the last indigenous cases of either species in China ."} +{"text": "With cancer incidence increasing over time worldwide, attention to the burden of psychiatric and psychosocial consequences of the disease is now mandatory for both cancer and mental health care professionals. Psychiatric disorders have been shown to affect at least 30\u201335% of cancer patients during all phases of the disease trajectory, and differ in nature according to stage and type of cancer. Other clinically relevant distressing psychosocial and existential conditions not included as \u2018disorders\u2019 in the usual diagnostic and nosological systems (i.e. meta-diagnostic conditions) have also been shown to be present in another 15\u201320% of cancer patients. In this editorial, we will present a summary of the extensive literature regarding the epidemiology of the several psychosocial disorders affecting cancer patients as a cause of distress and burden to be taken into consideration and addressed in cancer care through evidence-based intervention. For example, in palliative care, a marked reduction in performance, pain and fatigue, as well as loss of a vision of the future, make it difficult to differentiate major depression from other depressive spectrum disorders , the stage of cancer and the type of assessment methods and tools used to determine caseness are common in cancer care, particularly after chemotherapy.et al., et al., v. endogenous stressors) and temporal criteria (acute stressor in PTSD v. continuing and multiple stressful events in cancer).Trauma/stress-related disorders include post-traumatic stress disorder (PTSD) and sub-syndromic forms of PTSD hat has also shown to affect 15% of cancer patients represent a frequent diagnosis at all stages of cancer, and describe the emotional reactions related to the multiple stressors linked to cancer, involving 20\u201325% of patients. Anxiety as well as depression can be also components of AD depression with intertwining effects in the manifestation of both conditions. However, several different problems emerge, not only with regards to oncology but all medical conditions, because of the low specificity of DSM criteria for the diagnosis of AD, the vagueness of the symptoms, the weakness of the concept of distress n Casey, .et al., et al., Somatisation and somatic-symptom disorders and their role in influencing patients' well-being are also important, not only because of its prevalence especially in long-survivors of cancer, but also in general for the multiple relationships between the perception of somatic symptoms and the patient's interpretation. Pain intensity, hypochondriacal concerns, disease labelling and dysfunctional interpretation of somatic symptoms, are part of a complex picture related to illness and abnormal illness behaviour; ways in which individuals adaptively or maladaptively monitor their body, experience, evaluate and respond to their state of health. All these issues have a significant role in cancer care, since somatic symptoms may magnify disability resulting from cancer, interfere with treatment adherence, decision making, cause delay in recovery, result in poor outcomes and recurrence, and reduce overall well-being and quality of life, and complicate the diagnosis of major depression cognitive impairment or acute confusional states (delirium) secondary to the disease and its treatment. Mild neurocognitive disorders can be secondary to chemotherapy or chemotherapy associated with radiation therapy which can cause impairment of neuropsychological domains, such as memory, attention, concentration, learning functions, calculation and visual-spatial perception Wigmore, . Other cet al., et al., et al., A special area of interest is represented by delirium, one of the most common cognitive disorders in cancer, particularly in the advanced stages of disease. Delirium prevalence, depending on stage of disease, ranges from 10 to 80%, including both the hyperactive-agitated and mixed forms, although hypoactive delirium is most common in advanced cancer and demoralisation (28.8%) are for example the most frequent clinically relevant psychosocial conditions diagnosable in cancer patients in different phases of illness and in improving quality of life, well-being and return to work and illness behaviour (Li psychopharm-oncology) (Grassi and Riba, et al., et al., et al., Integrated psychopharmacological intervention (et al., et al., et al.,et al., Cancer has significant psychosocial consequences for both patients and their families. Today there is scientific evidence of the benefits of providing psychosocial cancer care as part of standard care in reducing distress and psychosocial morbidity associated with cancer and in fostering a better quality of life during and after treatment, and eventually in increasing survival. The significant advances in research in the area of psycho-oncology have favoured the development, implementation and dissemination of psychosocial guidelines and evidence-based treatments for several co-morbid psychiatric disorders in cancer, such as depression (Li"} +{"text": "The COVID-19 pandemic, which began with reports of atypical pneumonia cases in the city of Wuhan in Hubei province of China, was declared a public health emergency of international significance by the WHO on January, 30 2020. The virus SARS COV2 has, to date, infected more than 16 million people around the world and over 0.6 million people have succumbed to it. The pandemic has affected more than 220 countries .The response in India, a LMIC, has focused on interrupting the transmission of infection through contact tracing, finding and isolating cases when they occur. The guidelines of the Ministry of Health recommends COVID care centers (CCC) be used for mild or very mild cases, separate dedicated COVID health centers (DCHC) for moderate cases (pneumonia without any signs of severe disease), and dedicated COVID hospitals with ICU facility (DCH) for critical cases .Though the steps taken in terms of prevention, interruption of transmission, and management of COVID-19 cases in India have been proactive, there is an urgent need to strengthen and integrate COVID care into the primary health care of the country. There exists a huge disparity between healthcare capacities among different states in India and states do not have similar capacities to and the ability to provide enough stand-alone centers like CCCs, DCHCs, or DCHs . Even inWe propose a three-tier system of community-based management of COVID-19 with a primary health care approach:Tier I : Local Self Government Tier II : CHC Tier III : District.The current practice in India focuses on the identification of suspects and confirmation of cases through RT-PCR testing. The ministry of health recommends the early segregation of cases into mild, moderate, and severe categories. The imperfect execution of segregation in many places has resulted in 77% of all patients admitted to hospitals having only mild symptoms of COVID-19 . MoreoveWe suggest that cases should be segregated based on the probability of future complications. Older patients with co-morbidities, pregnant mothers, children under 5 years of age, and patients exposed to high viral load in large closed door congregations should be admitted to dedicated COVID-19 hospitals with ICU facilities \u201312. PatiThe current practice of taking diagnosed COVID-19 patients to standalone healthcare centers promotes over-reliance on the health system, as a suspect is isolated from the community from the time of its contact tracing and quarantine through to testing, diagnosis, management, and finally, discharge (average 30 days) from the hospital. This increases the fear of disease among the population, which in turn increases the stigma not only against patients but also their family members, the recovered patients, and the health care workers who continue to stay in the community . This maThe Involvement of Community Health Centers (CHCs) the management of COVID19 will help diversify and decentralize the health care system in rural and semi-urban areas . It coulOne of the most important bottlenecks in the pandemic has been the lack of standardized, community-oriented, inclusive information, and a cohesive education and communication (IEC) strategy. A specialized IEC cell, with a community feedback mechanism under the district administration will helThe current practice of laboratory diagnosis starts with the collection of nasopharyngeal and/or oro-pharyngeal swab by laboratory personnel or healthcare workers in individual hospitals or quarantine facilities or isolation centers. The samples are then sent to the designated laboratories for rt-PCR by maintaining the reverse cold chain . This inThe pandemic provides an opportune moment to expand primary healthcare infrastructure along with a once redundant network of telemedicine at community levels in India by resurrecting village-level resource centers .The community-based management of COVID-19 cases will not only help in reducing the fear and stigma prevailing during this pandemic but also enhance community engagement through participation and an increase in healthcare capacity. This will also improve community preparedness for future re-emergence of infectious diseases and will reduce the need for drastic measures like lockdowns in the future.SP: concept, intellectual content, and manuscript editing. SM: intellectual content and manuscript preparation. AJ: literature search and manuscript preparation. SK: literature search and manuscript preparation. AG: intellectual content and literature search. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This paper reviews the evidence base for the health impacts of SIL on older adults, the risk factors, and the potential moderators and mediators of those relationships. Substantial evidence indicates that SIL are associated with physical, cognitive, and psychological morbidity; health-related behaviors; and health-related quality of life. Social isolation in particular is associated with a significantly increased risk of premature mortality from all causes. The evidence base for interventions in the clinical setting is also reviewed. Finally, the report\u2019s specific recommendations are discussed, including the need for basic science research, increased funding, key elements in the design and evaluation of interventions, and gap areas (including trends among current younger adults and approaches for specific understudied groups of at-risk older adults). Part of a symposium sponsored by Loneliness and Social Isolation Interest Group."} +{"text": "Polypharmacy remains a significant healthcare issue in the United States, resulting in drug interactions, adverse drug reactions, and potentially dangerous complications. Polypharmacy, often defined as the simultaneous use of five or more medications, may lead to adherence problems and an increased risk of hospitalizations and death, particularly in the older population. Medication management was incorporated into undergraduate nursing clinical experience in an affordable housing urban community as part of the New Jersey Geriatric Workforce Enhancement Program (NJGWEP), a 5-year grant supported by DHHS-HRSA. This paper will describe the first phase of this project, which involved the determination of the prevalence of polypharmacy and high-risk medications in this setting. The charts of sixty residents were reviewed and along with demographic information, the following data was collected: total number of medications , high-risk medications using Beers criteria and identification of common themes or issues. The average age of the residents was 72 years, with cardiovascular diseases and diabetes mellitus being the most common comorbidities. Fifty-two of the sixty residents (86%) received five or more medications daily, meeting the definition of polypharmacy. The average number of medications taken on a daily basis was 8.9. Among the residents, centrally-active agents such as gabapentin, tramadol and lorazepam were the most commonly prescribed medications. The second phase of this project will include implementation of a medication reconciliation process to identify potential issues using the Beers criteria and implement appropriate interventions to ensure safe medication practices in this high-risk population."} +{"text": "The novel coronavirus disease 2019, COVID-19, which is caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) . SARS-CoThe World Health Organisation (WHO) declared the novel coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) on January 30, 2020 . As COVIOn February 27, 2020, the Federal Ministry of Health confirmed the first COVID-19 case in Ogun State, Nigeria, making the country the third country in Africa to recognise an imported COVID-19 case after Egypt and Algeria. The index case occurred in an Italian citizen who flew from Milan, Italy to Lagos, Nigeria on February 24, 2020, and travelled on to his company site in Ogun State the same day in a private vehicle. On February 26, 2020, he presented at the company clinic with symptoms consistent with COVID-19 and was referred to the Infectious Disease Hospital (IDH) in Lagos where a COVID-19 diagnosis was confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) on February 27, 2020.A total of 216 contacts in Lagos and Ogun States, including the passengers on the February 24 air flight, were identified for 14-day follow-up, with 40 of these contacts identified as high-risk. Eleven days later, an asymptomatic contact of the index case in Ogun State was confirmed as the nation\u2019s second case of COVID-19.The epidemiology of COVID-19 in Nigeria has since evolved, with cases identified in 35 of 36 states in the country, plus the Federal Capital Territory (FCT) in order to ensure a cohesive and effective coordination of the country\u2019s preparedness efforts (Measures instituted by the NCPG included strengthening in-country diagnostic capacity for the testing of COVID-19 by leveraging and optimising three existing laboratories within the NCDC molecular laboratory network and assessing existing infectious disease treatment centres with a focus on identifying gaps and developing plans for case management. Interim protocols and guidelines for case management of COVID-19 were developed while the Nigeria Pandemic Influenza Preparedness and Response plan was reviewed for relevance to COVID-19 response. Infection prevention and control (IPC) and case management trainings were conducted for frontline health care workers in designated treatment centres.Findings from a WHO risk assessment identified 13 countries, including Nigeria, as high-risk priority zones for proactive surveillance, detection and containment of the spread of COVID-19 . ConsequFollowing the confirmation of the first COVID-19 case in Nigeria on February 27, 2020, the NCPG transitioned to a national multisectoral Emergency Operations Centre (EOC) at the NCDC. The EOC was activated at level three, the highest level of response in the country intended for public health emergencies requiring national coordination and use of all available resources for the response. The EOC comprises multiple pillars, including: coordination, surveillance and epidemiology, case management, laboratory, points of entry (PoE), IPC, risk communication, logistics, and research. POE and case management pillars are led by the Departments of Port Health Services and Hospital Services of the Federal Ministry of Health respectively. Sub-national EOCs were activated in both Lagos and Ogun states to coordinate the response in the first two affected states. National multidisciplinary rapid response teams (RRTs) were strategically deployed to the initial two states (Lagos and Ogun), plus FCT, and then to all states to strengthen coordination and response activities at the state and local government area (LGA) levels. The national RRTs, comprising NCDC staff and graduates/residents of the Nigeria Field Epidemiology and Laboratory Training Program (NFELTP), provided technical and logistical support at the state and sub-state levels.At the national level, the Presidential Task Force (PTF) on COVID-19 was established by the President of Nigeria on March 9, 2020, with an overarching mandate to coordinate and oversee the country\u2019s multi-sectoral and inter-governmental efforts both to contain the outbreak and to mitigate the impact of the COVID-19 pandemic in Nigeria. The National COVID-19 Multi-Sectoral Pandemic Response Plan was adopted by the PTF in March and serves as a blueprint for a whole-of-Government response.The PTF provided high-level strategic leadership to the national response guided by scientific evidence. Daily PTF media briefings were held to enlighten Nigerians on evolving evidence, address trending issues and provide update on the government\u2019s response. Technical evidence-based recommendations from the PTF informed the President of Nigeria\u2019s policy decisions for the various phases of the outbreak. Overall, Nigeria\u2019s response strategies were aimed at suppressing the transmission of COVID-19 by testing all suspect cases, isolating all confirmed cases, and tracing all contacts of confirmed cases, with the implementation of country-wide or regional non-pharmaceutical interventions as appropriate. The Nigerian response was characterised by robust collaborations with partners. Development and implementation of response strategies were facilitated by technical and material support from several local and international partners including the WHO, Africa CDC and philanthropic organisations. The need to generate relevant research evidence led to the formation of the Nigeria COVID-19 Research Consortium (NCRC) whose aim is to develop and implement a research agenda on COVID-19 with identified national priorities, in line with WHO\u2019s global research roadmap. NCRC also serves as the coordinating body for COVID-19 research in Nigeria.Given the novelty of the virus, the evolving nature of transmission in Nigeria from imported cases to clusters of cases to community transmission and level of response implemented, the NCDC EOC convened a mid-action review meeting on May 9, 2020, to strategically review the existing response approach, share lessons learnt, and identify key opportunities for improvement and further collaboration. The outcome and key recommendations of the meeting in line with the emerging data and global best practices have been used to improve response strategies, drive control and prevention measures against the disease, as well as focused interventions to strengthen the health system. The gaps identified include poor utilization of state level public health EOCs for coordinated responses, sub-optimal utilization of data to guide decision making, delayed turn-around-times of laboratory results, non-standardization of case management across treatment centers and poor adherence to IPC practices in health care facilities. Several intervention measures were instituted which include training and mentorship of State EOC teams on the incident management system as a tool for outbreak response coordination, development and operationalization of data management, analysis and use plans, deployment of the electronic surveillance system to laboratories to speed up the release of results, the establishment of a community of practice for COVID-19 case managers and deployment of online IPC training programme for health care workers.As of March 22, 2020, the initial 30 confirmed cases COVID-19 in Nigeria were travellers from abroad or their immediate contacts. This informed the initial international travel ban for passengers coming from countries with ongoing high transmission to minimize rising imported cases. Ultimately, land borders were closed, all international flights were banned, and mandatory institutional quarantine and testing for international returnees to Nigeria was instituted on March 23, 2020 to reduce further importation of the disease from high-risk countries in Lagos and Ogun States and FCT for an initial period of 14 days, extended for an additional 21 days in the same three states and adding Kano State. The states were selected based on a combination of the burden of disease and their risk: Lagos State was the initial epicentre of disease and had the highest number of cases; Ogun State borders Lagos State, was the source of the index case, and has a highly urban population with a high rate of travel into Lagos State; the FCT had the second-highest number of cases at that time. After the initial two-week lockdown period, incidence in Kano increased rapidly, prompting inclusion in the lockdown. The lockdown included closure of schools and workplaces, bans on religious and social gatherings, cancellation of public events, curfews, restrictions on movement, and cessation of interstate and international travel. Alongside the federal lockdown in Lagos, and Ogun States and the FCT, many states adopted measures as well, including school closure, movement restrictions, and curfews.The lockdown strategy was a drastic and temporary measure implemented with two objectives: first, to slow the spread of the virus across the country, and second, to buy time for the health system to increase its preparedness. During the lockdown period, the NCDC worked with all states to enhance contact tracing activities and increase capacity for case detection and treatment. Treatment centres were expanded from an initial single centre in Lagos with 35 beds, as of February 29, 2020, to 38 centres with 1055 beds by April 14; by May 30, 2020 Nigeria had 121 treatment centres with 6550 beds. In the four-week period, the number of laboratories able to carry out COVID-19 testing increased from the initial three to 13 laboratories in 10 states as of April 15, to 28 in 18 states by the end of May. More than 13\u2009000 health care workers were trained on IPC as well as on COVID-19 case management and personal protective equipment (PPE) and response commodities were deployed across the country to reinforce and better prepare the multi-sectoral response.Despite bans on interstate travel, the virus had already spread geographically. Ten states reported their first COVID-19 cases during the first 14-day phase of the Federal lockdown, while an additional 13 states reported index cases in the second phase of the lockdown. Index cases in several states were traced to domestically exported cases from Lagos State and FCT. Nearly three-quarters of current cases have no known epidemiological link, suggesting substantial community transmission. Cumulatively, as of May 31, 2020, 337 of Nigeria\u2019s 774 LGA have reported a confirmed case.Although laboratory capacity was scaled up rapidly, testing numbers did not increase as planned. Testing capacity in terms of PCR machines as of mid-April was approximately 2500 tests per day and increased to more than 5000 per day as three Mega PCR Laboratories were activated for COVID-19 testing in Lagos and FCT by late May. However, inadequate testing reagents, due to delayed orders, and airport closures, hindered testing scale-up. Limited numbers of sample collection teams and testing centres, as well as hesitancy among some of the population to test, have also constrained increased testing. In the first two weeks of April, on average fewer than 300 tests per day were conducted; this increased to approximately 640 per day in the last two weeks of April, 1145 per day during the first two weeks of May, and 1410 per day during the last two weeks of May.The drastic lockdown measures came with a significant economic and social cost. Crime and domestic violence reportedly increased during the period and manyGlobally, countries continue to employ diverse strategies to control the COVID-19 pandemic. These strategies are aimed at preventing, detecting, controlling, and mitigating the impact of the pandemic while taking into account the economic, social, cultural and religious factors unique to each country. Ultimately, the effectiveness of these strategies will be determined and sustained by country-level and community ownership .Nigeria has, to date, the second-highest number of confirmed COVID-19 cases in Africa, and accounts for 7% of all confirmed cases on the continent. This may be an underestimate of the actual case load given the relatively low testing rate in Nigeria. As of May 31, Nigeria had conducted 63\u2009882 COVID-19 tests, equivalent to 293 tests per million population; in comparison, Ghana had conducted 184\u2009343 (5948 per million population) and South Africa had conducted 488\u2009609 tests (8251 per million population) . The relBy the end of May 2020, all but one state, Cross River State, reported COVID-19 cases. Cases were concentrated in the two most densely populated states, Lagos and Kano, as well as the FCT. Many of the initial cases reported outside of these three states have been imported from Lagos State, the FCT, or Kano State. Meanwhile, the rising case numbers in conflict-affected areas such as Borno State pose additional concerns and require context-specific interventions to avert a looming health crisis, especially in camps for internally displaced persons ,17.Undetected imported cases may have played a key role in the beginning and accelerated the transition from clustered to community transmission in the Nigeria outbreak. This is because, as the outbreak began, prior to closure of international borders, arriving international passengers were allowed to self-quarantine (without testing) but encouraged to seek testing if symptoms developed. This may have led to multiple undetected imported cases. The rapid emergence of cases among individuals with no travel history or recognized epidemiological links to other cases despite contact tracing suggests multiple undetected cases may have been imported into the country or that potential contacts of the identified cases were missed. This guided subsequent approach such that following border closure, arriving passengers had mandatory supervised quarantine for 14 days.Nigeria\u2019s states were facing critical challenges as the number of cases continues to increase across the country. Foremost among these is the limited number of COVID-19 treatment centres. Though greatly expanded since the outbreak\u2019s start, the limited number of beds, health workers, and critical care equipment such as oxygen and ventilators may quickly lead to an overwhelmed health system unable to minimize COVID-19 mortality and contain the spread of the disease. The NCDC continues to work closely with all state governments and partners to ensure adequate infrastructure is in place for timely case detection, management of cases, and to build capacity of the public health and clinical workforce.Although national testing capacity has significantly increased with private sector engagement, testing coverage and pace is still relatively low. By the end of May 2020, 293 tests had been conducted per million population, about 5% of what Ghana had done, with an average positivity rate of 15.9% overall. Nigeria needs to rapidly scale up testing to be able to quickly identify existing cases, isolate them, and control the pandemic. Securing sufficient testing supplies and personal protective equipment for health care personnel are immediate challenges of the response.Lock down containment measures were aimed at slowing the spread of the outbreak to new states, delaying the progression to community transmission, and increasing health system capacity at the initial phase of the outbreak. Though the lockdown slowed down COVID-19 transmission, it had undesired collateral effects on social protection, security, and daily subsistence for many. It is safe to assume that these negative consequences of the pandemic disproportionately affected women, people living in poverty, petty traders and those dependent on income from small and medium enterprises. The adverse effects of the lockdown exacerbated already difficult situations for many, rendering prolonged enforcement of preventive interventions such as lockdown and physical distancing unsustainable.A systematic approach was adopted to balance economic reopening with public health concerns, demonstrated in the phased easing of lockdown alongside a whole-of-society outbreak control strategy. This approach mobilises all sectors and communities to take ownership of and responsibility for response efforts towards control of the war against COVID-19 in Nigeria. The easing of lockdown measures came at a time when confirmed cases were on the uptick; however, the immense socioeconomic impact witnessed during the lockdown period necessitated a more balanced approach to public health interventions . FurtherNigeria mounted a swift and aggressive response to COVID-19, leveraging on its existing epidemic preparedness and learning from other parts of the globe where transmission began earlier. The country\u2019s initial response included early activation of the national EOC at the NCDC, establishment of the multi-sectoral COVID-19 PTF, and decisive actions to stop international travel and impose a time-limited lockdown in highly affected areas. By rapidly implementing this set of interventions, Nigeria likely slowed down the rate of virus transmission and bought extra time to implement a robust case detection, testing, and treatment centre capacity. However, these efforts, especially testing, needs more private sector involvement to significantly ramp up COVID-19 diagnostic centres across the country. Sensitising and mobilising citizens to take responsibility by strict implementation of preventive non-pharmaceutical measures is key to flattening the curve. A rapid, holistic, cohesive, whole-of-government approach that encompasses civil society and local-communities in the response will be absolutely critical to combating the COVID-19 pandemic in Nigeria and rebu"} +{"text": "Persons with dementia (PWD) are two-three times more likely to be hospitalized as persons without dementia and comprise one fourth of hospitalized older adults. Hospitalization often has a dramatic impact upon the health and disposition of the older PWD. They are at increased risk for hospital acquired complications (HAC) such as functional decline, behavioral symptoms of distress, and delirium, all of which contribute to increased disability, mortality, and long-term nursing home stays. Despite the unprecedented number of PWD admitted to acute care, little attention has focused on their specialized needs and HAC, and how they impact functional recovery. The purpose of this symposium is to describe the incidence of common HACs, and factors that influence their occurrence and presentation in PWD. Utilizing baseline findings from the Family-centered Function-focused Care (Fam-FFC) trial, the presentations will address this objective and discuss the ramifications for functional and cognitive post-acute recovery in PWD. The first presentation will describe the incidence and pharmacologic management of pain in PWD, and its association with common HACs. The second presentation will describe physical activity in PWD on medical units and the validity of the Motionwatch8 actigraphy. The third session will describe differences in common HACs between white and black PWD. The final presentation will examine function-focused goals developed in collaboration with family caregivers and patients, and the functional outcomes associated with goal attainment. Our discussant, Dr. Lorraine Mion, will synthesize the research findings and lead a discussion of future directions for policy and practice in dementia-capable acute care."} +{"text": "Food, by nature, is a biological substrate and is therefore capable of supporting the growth of microbials that are potential producers of toxic compounds. Natural toxins include mycotoxins, marine biotoxins, plant toxins, cyanogenic glycosides, and toxins occurring in poisonous mushrooms. Natural toxins pose not only a risk to both human and animal health, but also impact food security and nutrition by reducing people\u2019s access to healthy food. The tracking and detection of natural toxins in foods back to their source is a primary responsibility of food producers, distributors, handlers, and vendors. National authorities should conduct monitoring and ensure that levels of the most relevant natural toxins in food commodities comply with both national and international maximum levels or relevant toxicological thresholds.Toxins includes some recent advances in analytical methodologies for the detection of natural toxins in food commodities and biological fluids. The collected contributions are relevant to two main analytical approaches, namely advanced liquid chromatography\u2013tandem mass spectrometry (LC-MS/MS) applications for the high sensitive and selective detection of emerging contaminants, and approaches for rapid and cost effective toxin detection based on immunoassays and cell-based assays.This Special Issue of The phytotherapeutic and nutritional use of plants and herbal-based products have increased in popularity over the last few years, however the improper usage of plants or unawareness of plant toxicity may lead to intoxication cases. Nowadays, highly sensitive and selective LC-MS/MS techniques represent a relatively easy to access and powerful tool to target plant toxins at low levels, and as a consequence, contaminants such as pyrrolizidine alkaloids and cardiac glycosides have surfaced as an issue of relevance in food safety. A method for the determination of pyrrolizidine alkaloids in honey has been set up by Hungerford et al. . The stuAmong the readily available in vitro methods, the functional assay known as the cell-based assay, which uses a neuroblastoma (N2a) cell line, is widely applied for routine surveillance of marine toxins. In their study, Viallon et al. optimized several key parameters of the cell-based assay, improving assay implementation and reliable toxin detection, making the final protocol suitable for future standardization and interlaborarory comparisons . The overall performances of immunoassays strongly depend on the quality of selected immunoreagents, first of all, of the antibody. For this reason, the development and testing of new antibodies continues to warrant considerable efforts in current research. Maragos et al. proposed a new competitive enzyme-linked immunosorbent assay (ELISA) to screen for citreoviridin and its geometric isomer, iso-citreoviridin, in white rice based upon the isolation of two novel monoclonal antibodies . The devWhen applying rapid screening tests for compliance testing, their fitness for purpose needs to be demonstrated through a validation study. The manuscript by Pecorelli et al. provides insights about the process of evaluating and comparing the performance profile of rapid methods currently applied for AFM1 screening in milk . AddressAntibodies as well as alternative receptors, such as aptamers, can be used in several biosensing platforms. The review by Zhuheng Li et al. updates the construction strategies of electrochemical biosensors such as immunosensors and aptasensors for the cost-effective determination of microbial toxins including bacterial toxins, fungal toxins and algal toxins . The papOverall, the papers included in this Special Issue have contributed to advance the state-of-art of analytical methods for the detection of natural toxins. Furthermore, a part of the published studies focused on emerging or less investigated toxins, thus providing the scientific community with new tools and/or data supporting a better understanding of related food safety issues."} +{"text": "Social approaches such as distancing measures are essential components of the public health response to respiratory-related infectious disease outbreaks. Due to socio-economic and broader peculiarities of SSA countries, social approaches that were effective elsewhere may have limited practicality in these contexts, and if practical; may yield different or even adverse results. We highlighted the effectiveness of these social approaches and their practicality in SSA.we conducted a comprehensive literature search through multiple databases, to identify articles relevant to social distancing. Findings were thematically summarized.our review found emerging and varying empirical evidence on the effectiveness of social approaches in the control and mitigation of the COVID-19 pandemic; thus, limiting its applicability in SSA contexts. Nonetheless, our review demonstrates that the effectiveness and practicality of social approaches in SSA contexts will depend on available resources; timing, duration, and intensity of the intervention; and compliance. Weak political coordination, anti-science sentiments, distrust of political leaders and limited implementation of legal frameworks can also affect practicality.to overcome these challenges, tailoring and adaptation of these measures to different but unique contexts for maximum effectiveness, and investment in social insurance mechanisms, are vital. The pandemic has since spread to more than 192 countries and territories around the world. Evidence shows that COVID-19 is readily transmissible from person to person through air droplets and aerosols [The World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a pandemic on the 11aerosols . The goaaerosols As of 21aerosols . Due to et al. [et al. is comprehensive, specific to respiratory disease pandemics and is widely cited across literature sources and publications addressing NPIs, hence highly relevant to our review. Further, the rationale for using this framework was due to its clear definition of each social approach. Based on that, we categorized the social approaches into five distinct but interrelated themes: 1) Isolation and quarantine; 2) Closure of schools; 3) Closure of workplaces; 4) Avoiding/cancellation of mass gathering; 5) Restriction of movement. We highlight in each category the evidence on the rationale and effectiveness of the interventions as well as their contextual implications within SSA.In the first prong, we reviewed the evidence on the effectiveness of social approaches to COVID-19 and respiratory disease outbreak response. To do this, we conducted a literature search of the following electronic databases: MEDLINE (via LitCOVID in PubMed), Google scholar, Cochrane Library, African Index Medicus, and EBSCOhost. To be eligible for inclusion, publications had to assess the effectiveness of social measures used in the response to COVID-19 or other respiratory disease outbreaks in SSA or other settings. Reference lists of relevant articles and documents on databases of the World Health Organization (WHO) and Africa Centres for Disease Control and Prevention (Africa CDC) were also scanned for potentially relevant articles. See et al. , to themIsolation and quarantine: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads primarily by human to human transmission through infected droplets [droplets ,8 .Hencedroplets . Empiricdroplets . Commonldroplets -12. HowePracticality of isolation and quarantine in sub-Saharan Africa: the potential health, social, and economic impacts of the spread of COVID-19 in Africa are important considerations for governments and public health authorities in SSA to take pragmatic steps towards stemming the tide of transmission. While isolating cases and quarantining those exposed are reasonable interventions that are potentially effective for controlling infectious disease outbreaks, they are resource-intensive [ntensive . Given tntensive . As COVIntensive ,14.Isolation/quarantine facilities may also be crucial for contacts residing in overcrowded housing conditions and those who are homeless. Due to overcrowded homes, particularly in urban slums and informal settlements, implementing self-isolation/quarantine may expose other persons in the household and may lead to further community transmission. In addition, these living conditions may make staying indoors and complying with isolation/quarantine for the appropriate duration unbearably uncomfortable, particularly on hot days. Furthermore, the lack of improved water supply and sanitation facilities in communities may also complicate self-isolation of cases and voluntary quarantine of contacts of cases. As such, designated isolation/quarantine facilities could be an avenue for dealing with these practical and contextual constraints. Moreover, seven out of ten Africans work in the informal sector with implications for the practicality of self-isolation/quarantine. There is a high likelihood of non-compliance with these self-isolations /quarantine if people are faced with the risks of income or job losses while absent from work . InformaWhile the limitation of rights and freedom of movement during the enforcement of isolation and quarantine may be justifiable in the interest of public health in pandemic settings, it carries the inherent risk of being abused and implemented in draconian ways; particularly in the contexts of authoritarian leadership. This would be the case if there is fear, intimidation, abuse, or victimization. Such adverse outcomes have been highlighted by numerous reports of police and military brutality, intimidation and harassment across a number of African countries during the enforcement of movement restrictions. Hence, it is important for isolation and quarantine to be enforced with fairness and within human rights standards . Lastly,Workplace closure: evidence suggests that there is a substantial risk of respiratory disease transmission in occupational settings [settings . Implemesettings ,19. A 23settings . In addisettings . Comparasettings .Practicality of workplace closures in SSA: the majority of the population in SSA lives in poverty and in rural households without social insurance policy. As discussed earlier, the informal sector makes up about 70% of the workforce, and there are many people who rely on a daily income to eke a livelihood [velihood . Withoutvelihood which isvelihood . Formal velihood .School dismissal and closure: school dismissal refers to schools remaining open to only administrative and teaching staff, vulnerable children, children of healthcare and essential workers [ workers . On the workers . These t workers . School workers . In Sing workers . Further workers -31. Howe workers . School workers . Disenta workers .Practicality of school closures in SSA: school closure results in reduced parental productivity including loss of health-care staff to childcare duties [e duties -30,32. Te duties . Most lie duties . While se duties . It has e duties . These ce duties . Though e duties -38.Avoiding/cancellation of mass gatherings: mass gathering is a planned or spontaneous event where the number of people attending could strain the planning and response resources of the community or country hosting the event [he event . Examplehe event . Avoidinhe event . It invohe event ,41. Evidhe event ,43. Evidhe event . During he event .The timihe event .Practicality of avoidance /cancellation of mass gathering in sub-Saharan Africa: in many SSA countries, avoiding/restricting mass gathering has been used as a social distancing measure in limiting the spread of the SARS-CoV-2 .There have been reports of compliance in the shutting down of sporting events, in contrast to large pockets of partial to non-compliance with regards to some cultural and religious practices/events like burials, coronation events, weddings, church/mosque services etc. In West Africa, there have been negative reactions, including riots, to the closure of places of worship and incidences of 'super spreading' events at evangelical church sessions (in Burkina Faso and South Africa) [ Africa) -49. Thes Africa) . However Africa) . Again, Africa) .Restriction of movement: lockdowns and curfews are categorized as restriction/halting of movement with the rationale of ensuring social distancing measures to delay the peak of the infection. While there is currently no consistent definition for lockdowns, we assume a rather more contextual definition to accommodate the variability in implementation. It ranges from hard or full lockdowns (active coercion with the agency of the police/army (state) in maintaining sit- at- home orders and enforcing no entry/exits into territories), to partial lockdowns . The lockdown seen in Wuhan, China is the prototype of hard lockdowns, while the one instituted in London is an example of partial lockdowns [ockdowns ,53. The ockdowns -58.et al. carried out a hierarchical cluster analysis to assess the impact of complete lockdown on total infection and death rates across 12 countries that declared lockdown [et al. reported that had a strict lockdown not been instituted in Wuhan-China, COVID-19 cases would have been 65% higher in the 347 Chinese cities outside Hubei province, and 53% higher in the 16 non-Wuhan cities inside Hubei [et al. modelling estimates by placing restrictions reduced COVID-19 transmission by a median 45% (42 to 49%) in Italy with over 200 000 hospitalizations averted as of March 25, 2020 [Ghosal lockdown . Data frlockdown . There wde Hubei ,. Simila25, 2020 . Institu25, 2020 .Practicality of restriction of movement: while effective in combating COVID-19, the WHO recognizes restricting movement as a blunt tool with social and economic costs [ic costs . The praOverall, our review suggests emerging and varying empirical evidence on the effectiveness of social approaches such as isolation, quarantine, school and workplace closures, movement restrictions and prohibition of mass gatherings, in the control and mitigation of the COVID-19 pandemic. We highlighted in each category of the social approaches the rationale for implementing the interventions and their contextual implications. To illustrate, while measures such as work, and school closures may be important for reducing the spread of COVID-19. In many SSA social contexts, these may have little practicality due to low internet penetrations to support online learning and teleworking. Similarly, contextual realities such as overcrowded living conditions and water supply deficits may constrain the practicality of the social distancing rule of staying or living at least 2 meters apart and the NPI of regular handwashing. Other challenges in the region include infrastructural deficits, limited technical capacity to undertake contact tracing and surveillance activities, inadequate or lack of social safety nets, weak legal and legislative frameworks, and mixed messages from some political leaders resulting in anti-science sentiments, and a general mistrust and low confidence in political leaders.Our review is not without its limitations. Given the very broad nature of the topic and time constraints, we were unable to conduct a systematic search of the literature. However, we minimized the risks of literature selection bias by an internal peer-review process that allowed each team member to critically appraise the literature identified by team mates. Because ours was a non-systematic review, it did not require a systematic quality assessment of included literature. As such, our quality assessment is narrative. The sources of the evidence we included in the review were mostly observational and simulation studies, thereby limiting the certainty of the evidence. Further, the certainty of this review\u00b4s evidence is limited by the ongoing and rapidly evolving nature of the pandemic, particularly with the lingering uncertainties around transmission dynamics. In addition, the integrated implementation of these social measures makes it difficult to distinguish the specific impact of each intervention from the cumulative effects of combined efforts. Nonetheless, our review demonstrates that social approaches have varying effectiveness and practicality, depending on available resources, the timing of the intervention, duration, intensity, combination with other measures, implementation monitoring, and compliance. For instance, there is substantial evidence that isolation, used together with contact tracing, quarantine and optimal testing, is beneficial in mitigating the spread of the virus .Finally, at the heart of the limited practicality of these social approaches in SSA countries are (1) fundamental challenges in equity: are the measures equitably implemented?, (2) sustainability: can the measures be implemented sustainably?; (3) financial and technical investments: do SSA countries have the economic and technical resources to implement some of these measures; are these economic resources judiciously and efficiently managed and used as planned? and (4) trust: do the citizens trust the messages from their leaders?In sum, there is emerging and varying empirical evidence on the effectiveness of the use of selected social approaches in the control of the COVID-19 pandemic in SSA contexts. There is limited practicality in implementing these social approaches due to infrastructural and economic deficits, limited technical capacity, anti-science sentiments, weak political coordination, distrust of political leaders and limited implementation of legal frameworks. To overcome these practical challenges, tailoring and adaptation of these measures to similar but unique contexts for maximum effectiveness, and investment in social insurance mechanisms, are vital.The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly across most countries of the world;Social approaches such as distancing measures are essential components of the public health response to respiratory-related infectious disease outbreaks;Controlling the pandemic is challenging as there is limited evidence on the safety and effectiveness of appropriate medicines, with vaccines currently available for prevention.This review demonstrates varying effectiveness of social approaches such as isolation, quarantine, school and workplace closures, movement restrictions and prohibition of mass gatherings, in the control and mitigation of the COVID-19 pandemic;This review contextualizes the implications of these social approaches in sub-Saharan African contexts, summarizing the evidence in one paper, thus making it easy for readers to access the information;This review establishes that the effectiveness and practicality of social approaches in SSA contexts will depend on several important factors. Including the availability of resources; timing of the intervention, effective leadership and community trust."} +{"text": "First WHO model list of essential in vitro diagnostics in 2018; the Indian Council of Medical Research followed in its footsteps and released its first National essential diagnostics list in 2019.Accurate and affordable diagnostics are central to effective health care. Quality diagnostics, when made available as part of health-care services, influence disease diagnosis and treatment outcomes in patients and improve disease surveillance. Poor investment in diagnostics, especially in low- and middle-income countries, has translated into high out-of-pocket expenses on diagnostics. Furthermore, lack of diagnostics can result in serious public health challenges, such as antimicrobial resistance due to overuse of antibiotics.India has had a long history of vertical, disease-specific programmes, which contributed immensely to the control of infectious diseases such as human immunodeficiency virus (HIV), tuberculosis and malaria.India\u2019s essential diagnostics list is comprehensive and ambitious; through this list, the Indian Council of Medical Research seeks to cement diagnostics as an important component in health care. The list should translate into improved patient outcomes and reduction in out-of-pocket expenses on diagnostics. The list was drafted through a consultative process spearheaded by the Indian Council of Medical Research. The process of reaching a consensus on which diagnostics to include in the list consisted of five consultative meetings with clinicians, microbiologists, pathologists, radiologists, representatives of civil society, managers of national programmes, representatives of the diagnostics industry and other technical experts over a period of 15 months. The consultations focused on the latest available evidence of disease burden,In 2015, the Indian government, under the guidance of the National Health Mission, launched the Free Drugs Service and Free Diagnostics Service Initiative, as part of its nationwide effort towards the government-led Health for All objective.Having a national essential diagnostics list endorsed by all major stakeholders would have several advantages, mainly homogenizing diagnostics availability at every level. States can use the list as a reference document to forecast needs and guide their procurement; the list can also help them determine the volumes of tests and mechanisms required to meet demand and negotiate diagnostics\u2019 prices. Special pricing initiatives driven by aggregated volumes have been practiced by some disease control programmes in low- and middle-income countries to improve diagnostics availability.During the consensus-building process to develop the list, the committee of experts identified several important gaps where diagnostic solutions for priority health-care conditions specific to India are needed. In the last decade, the development of point-of-care diagnostics has advanced significantly, with scientists and entrepreneurs making strides in the development of next-generation point-of-care diagnostic devices that are based on modern technologies such as smartphones and cloud-based devices. While some point-of-care diagnostics such as rapid blood glucose, digital haemoglobinometer and cardiac biomarkers have already been included in the diagnostics list, point-of-care rapid tests for the detection of infectious diseases, such as typhoid, are needed.Through the national essential diagnostics list, the Indian government seeks to make the availability of quality diagnostics an essential component of the health-care system; the list can also become a guidance document for other countries to develop a similar tool. Strengthening of diagnostics infrastructure and improving the availability of diagnostics will be key to achieving diagnostics availability across all levels of health care. Even the point-of-care diagnostics, despite their promise of simplicity, affordability and shorter turnaround time, require a functional delivery system that is supported by laboratory and clinical expertise. We hope that implementing the national essential diagnostics list, which is underway through the Free Drugs Service and Free Diagnostics Service Initiative, will increase the availability of good quality diagnostics and therefore reduce out-of-pocket expenses on diagnostics and improve patient outcomes."} +{"text": "The University of Nebraska Medical Center\u2019s Rural Patient and Stakeholder Engagement in Research project used a novel approach to patient engagement in research: just-in-time engagement. In this approach, patients were identified and matched with researchers with shared research interests without preemptive patient and stakeholder education and training. Ten research teams initiated engaged research design between August and October of 2019. In this presentation, we will share process and outcomes measures of the just-in-time approach: measures of ongoing engagement at 6 and 9 months; evidence of research productivity, and patient and stakeholder satisfaction with their research involvement. We will also address ethical challenges, including challenges to engaging a diverse population. Part of a symposium sponsored by the Patient/Person Engagement in Research Interest Group."} +{"text": "Muir-Torre syndrome is a rare, autosomal dominant genodermatosis, characterized by sebaceous neoplasms and visceral carcinomas. The authors describe the case of a patient who, 16 years after the diagnosis of colon carcinoma, presented a verrucous plaque on the pubic region, histopathologically compatible with sebaceous adenoma. The need to investigate this syndrome is emphasized, especially in cases of sebaceous neoplasms located outside the head, face, and neck. Screening for neoplasms in these patients and their families is mandatory. The authors describe the case of a 79-year-old woman, presenting a warty, erythematous, and painless plaque for two years on the pubic region . There wa)Amelanotic melanomab)Condyloma acuminatumc)Squamous cell carcinomad)Sebaceous adenomaBased on clinical and histopathological findings, the authors reached the diagnosis of sebaceous adenoma in a patient with Muir-Torre syndrome (MTS). Sebaceous tumors are rare, most commonly located on the face and neck of the elderly.The diagnosis of sebaceous neoplasia makes MTS screening imperative. This is a rare variant of Lynch syndrome, autosomal dominant, characterized by the occurrence of sebaceous gland tumors associated with visceral neoplasia. Among the sebaceous tumors related to MTS, adenoma is the most common, histologically characterized by lobular proliferation with predominance of mature sebocytes in the center and a minority of basaloid germ cells at the periphery. Colon adenocarcinoma is the most common associated visceral neoplasia, especially when proximal to the splenic flexure (unlike sporadic cases), followed by tumors of the genitourinary tract.The diagnosis of MTS is clinical, by finding sebaceous neoplasia and at least one visceral tumor without other contributing factors, such as radiotherapy or immunosuppression. Immunohistochemistry and molecular analysis are indicated in cases where there is no family or personal history of visceral neoplasms.The authors report a case of sebaceous adenoma with unusual location in the pubic region in a patient with colon and bladder cancer. The importance of investigating systemic neoplasms associated with SMT and the monitoring of these patients and their families is emphasized.None declared.Diego Henrique Morais Silva: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Anna Karoline Gouveia de Oliveira: Design and planning of the study; collection, analysis, and interpretation of data.Neusa Yuriko Sakai Valente: Approval of the final version of the manuscript, effective participation in research orientation, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, critical review of the manuscript.Thais do Amaral Carneiro Cunha: Approval of the final version of the manuscript, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases.None declared."} +{"text": "Dear Editor,Purpura annularis telangiectodes of Majocchi is a rare subtype of pigmented purpuric dermatosis. It is more common in children and young females and predominantly affects the lower limbs, with symmetrical annular reddish-brown macules.4A 6-year-old female patient, daughter of consanguineous parents, presented lesions since 2 years old. The patient had no history of systemic symptoms, allergies, or continued use of medications, except sporadic use of paracetamol. In the beginning, the lesions were erythematous, and subsequently evolved to annular and/or irregular hyperchromic macules, symmetrical in the legs, as well as in the right upper limb, and with an isolated lesion in the anterior cervical region . A skin Purpura annularis telangiectodes of Majocchi is part of the pigmented purpuric dermatoses, which manifests as annular macules that are symmetrical, reddish-brown, and generally asymptomatic. It preferably affects children and young women, and there is no predominant ethnicity.None declared.Aline Soares Garcez:; elaboration and writing of the manuscript; critical review of the literature.Vit\u00f3ria Regina Pedreira de Almeida Rego: Approval of the final version of the manuscript; critical review of the literature.Thadeu Santos Silva: Approval of the final version of the manuscript; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature, critical review of the manuscript.None declared."} +{"text": "Cardiovascular disease (CVD) has always been an important field of application for diagnostic imaging in small animal practices and, vice-versa, diagnostic imaging has greatly expanded the diagnostic capabilities of veterinary clinicians dealing with CVD. In addition to physical examination and electrocardiography, cardiac imaging offers unique opportunities to understand and investigate cardiovascular function and dysfunction. Among the different imaging modalities, each with specific advantages and disadvantages, some focus primarily on cardiac structure and anatomy and others are mainly concerned with cardiac physiology and function.For several decades in the last century, thoracic radiography and fluoroscopy, with or without the use of contrast medium , were the imaging techniques of choice to investigate dogs and cats affected by congenital or acquired CVD ,2. RadioStarting in the 1970s, the progressively increasing number of available ultrasound technologies, from M-mode via two-dimensional sector and then three-dimensional volume scanning techniques, in combination with various Doppler methods and other advanced techniques , has considerably increased understanding of normal and abnormal cardiovascular anatomy and function . With thIn the last decade, the increasing accessibility of computed tomography (CT) and magnetic resonance imaging (MRI) units in small animal veterinary practices has offered additional powerful tools for the in-depth exploration of cardiac anatomy and the assessment of cardiac function. The high temporal and spatial resolution achievable with the modern multidetector-row CT scanners, which can acquire a three-dimensional dataset of the heart and thoracic vessels in a few seconds, allows the depiction of very small or difficult to access normal or abnormal cardiovascular structures . FurtherThe heart and great vessels are very well visualized with MRI because the contrast between cardiovascular tissue and blood is more pronounced than in echocardiography and cardiac CT. Therefore, cardiac MRI is the reference imaging technique for the assessment of cardiac morphology and function and is often used for the evaluation of complex cardiovascular anomalies and specific myocardial disease processes in humans. In companion animals, the early application of MRI includes the precise assessment of cardiac morphology, volume and function, as well as the identification of subtle and challenging changes in poorly accessible cardiovascular structures such as the right ventricle, the pericardium and the heart base in animals with arrhythmogenic cardiomyopathy, mesothelioma, heart base masses and vascular abnormalities, respectively . Finally, veterinary cardiologists and radiologists have very recently started the early application of deep learning, an artificial intelligence application that uses computer-aided detection methods with the aim of helping clinicians recognize cardiac or left atrial enlargement on canine thoracic radiographs ,20.Cardiovascular imaging has witnessed an explosive expansion of available tools providing detailed information of cardiovascular structures and physiology with noticeable improvement in the diagnosis of CVD. The future directions of cardiac imaging include the increased interconnection among the different imaging techniques and their extended use, not only for diagnostic but also for prognostic purposes in animals with CVD."} +{"text": "Dear Editor,Epithelioid sarcoma (ES) is a rare histopathological subtype of soft tissue sarcoma, accounting for less than 1% of all adult soft tissue sarcomas.None declared.Maraya de Jesus Semblano Bittencourt: Approval of the final version of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.Caren dos Santos Lima: Drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.Aline de Lima Days: Approval of the final version of the manuscript; Drafting and editing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Camilla C\u00f4rrea Neri: Drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "An age-dependent decreased number of AVT-positive neurons was seen in the medial preoptic area, medial preoptic nucleus, paraventricular nucleus, rostral part , and lateral preoptic area. Trends to effects of brooder rearing were found in both anteromedial preoptic nucleus and supraoptic nucleus, with dark brooder reared animals showing higher mean counts of AVT-positive neurons in both areas. No interactions between brooder raising and age were observed in AVT-positive neuron count. CORT levels were higher in primary wing feathers from 28 week old hens than in those from 16 week hens. No main effects of rearing with dark brooders or interactions between age and treatment were found on CORT levels. The age-dependent effects seen in the hypothalamus and CORT aids in further understanding of the development of chickens around puberty. The use of brooders tended to increase AVT expression in the anteromedial preoptic nucleus and supraoptic nucleus, an indication that dark brooder rearing may affect physiological responses regulated by these areas. The lack of effect of dark brooders on CORT in feathers is at the least an indication that the use of dark brooders is not stressful; in combination with the benefits of dark brooders on injurious pecking, fearfulness and early mortality, this pleads for the use of dark brooders in on-farm situations.Chickens cannot independently thermoregulate at hatch and lack opportunity to behaviorally thermoregulate with a hen in the egg layer industry, thus barns are heated to thermoneutral temperatures. Dark brooders are low-energy-consuming hot plates, which may be environmentally advantageous while providing welfare-enhancing aspects of maternal care . Dark brooder use has been demonstrated to decrease injurious pecking and mortality well into the production period of layers. To further understand hen development around lay onset and effects of dark brooders on the brain and HPA-axis, we examined effects of rearing with dark brooders on expression of vasotocin (AVT) in the hypothalamus and corticosterone (CORT) in the feathers of in total 48 layer Isa Warren hens at 16 w and 28 w of age ( Gallus gallus domesticus) hatch with limited ability to produce warmth by thermogenesis . Brooders may also have positive effects on welfare problems in the egg layer industry. Chicks bred with broody hens are less fearful than chicks bred without mother hens . LikewisAphelocoma coerulescens; . Maternal deprivation has been reported to affect the neuro-endocrine response to stress in mammals \u201316. Morelescens; ]. In youlescens; , and strlescens; . Maternalescens; . Both felescens; and knowlescens; , 24, sugMaternal care, or lack thereof, can also lead to long-term changes in neuroanatomy visible even in adulthood in humans and rodents . PreviouGiven the impracticality of housing broody hens with chicks in industrial situations on the one hand, and the desirability of introducing aspects of maternal care to improve welfare and reduce energy use on the other hand, investigation of the effects of the use of dark brooders during rearing on physiological parameters related to stress and welfare is of strong interest. Previously published results from the present group of animals demonstrated strong positive effects of dark brooders on plumage condition, wound reduction and reduction in mortality rates . To furtAll procedures involving animals were in accordance with the Danish Ministry of Justice Law No. 382 (10 June 1987) and Acts 333 (19 May 1990), 726 (9 September 1993) and 1016 (12 December 2001). This study is part of a larger project that also evaluated the effects of brooders on welfare, including behavior, fear, injurious pecking damage, mortality and production parameters .The chickens used in this study were non-beak trimmed Isa Warren layers, obtained when 1 day old from Top\u00c6g Aps, Viborg, Denmark.2) and in whether the brooder was raised at regular intervals . DirectAge was found to affect the expression of AVT in the hypothalamus of chickens, and an age-dependent increase in CORT was seen in feathers of the hens. This information aids in further understanding of the development of chickens around puberty. The use of brooders tended to affect AVT expression in some areas of the hypothalamus. The lack of effect of dark brooders on CORT in feathers is at the least an indication that the use of dark brooders is not stressful; given previously shown positive benefits of dark brooders, e.g., prevention of injurious pecking, reduced fearfulness and lower mortality, this pleads for the use of dark brooders in on-farm situations.The datasets generated for this study are available on request to the corresponding author.All procedures involving animals were in accordance with the Danish Ministry of Justice Law No. 382 (10 June 1987) and Acts 333 (19 May 1990), 726 (9 September 1993) and 1016 (12 December 2001). This study is part of a larger project that also evaluated the effects of brooders on welfare, including behavior, fear, injurious pecking damage, mortality and production parameters .AR conceived and designed the study with RN. RN and AR drafted the manuscript with help from EZ. EZ and AD performed laboratory work, analysis of stained slides, and statistical analysis.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Nearly 59,000 human deaths worldwide are attributable to rabies annually, of which more than a third occur in Africa. In recent years, progress has been made in both action and collaboration including implementation of surveillance and prevention measures. In this review we assess the scale of surveillance, preventive, and control efforts of canine-transmitted human rabies in African countries. We reviewed literature published from 2014 to 2018, retrieved from electronic databases including MEDLINE, Global Index Medicus, BIOSIS, Science Citation Index, and EMBASE. WHO reports, national disease control program reports, and conference proceedings were also reviewed. The database search was conducted using keywords including rabies, control, and prevention. In forty countries (40/54), some level of rabies control and prevention strategy was available while in fourteen (14/54) countries, no specific national control and prevention strategy for human rabies could be retrieved. Thirty-four (34/54) countries utilized the Stepwise Approach towards Rabies Elimination (SARE) tool to monitor the national rabies control efforts\u2014five of these countries were at the lowest tier (0/5) of the SARE scoring system while no country had achieved the highest score (5/5). High burden countries need to step up the implementation of context specific national rabies control, prevention, and monitoring strategies. As a zoonosis, rabies control and elimination require coordination between human and veterinarian health sectors under the \u201cOne Health\u201d umbrella and with national master plans on the prevention and control of neglected tropical diseases ending in 2020, the time to act is now. Rabies, which is caused by viruses of the rhabdovirus family, genus lyssaviruses, has a worldwide distribution. Rabies is vaccine preventable; however, there is no cure, and it is usually fatal once symptoms appear . The neuThe Sustainable Development Goals (SDGs) of the 2030 agenda for sustainable development called for actions targeting improvements in health and education and ending epidemics of neglected tropical diseases (NTDs) in the next decade . As a deInvestigations from the past five years estimated the epidemiological and economic impact of intervention strategies strongly supporting the effectiveness of canine vaccination and equitable access to PEP in populations residing in endemic regions ,9,10,11.In this review, we assess the current control strategies, policies, programs, and actions directed at reducing canine-transmitted rabies in Africa. This summarized evidence will inform regional stakeholders, governments, and local officials to coordinate control, prevention, and elimination strategies across relevant governmental and non-governmental sectors to ensure enhanced collaboration in achieving the SDG targets. Further, the review will provide critical insight into the challenges and deficiencies related to current national policies and strategies. This will support development of informed and coordinated national and continental strategies for rabies elimination.https://www.un.org/en/member-states/index.html) (accessed on 21 January 2021). Searches were run combining the disease with each of the control and prevention related key words using Boolean words (AND/OR). Reference lists were scanned for relevant review articles and conference proceedings. English and French articles were included in the review. A scoping review of the control and prevention of canine-transmitted rabies in Africa was conducted by searching peer-reviewed articles from MEDLINE, Global Index Medicus, BIOSIS, Science Citation Index, and EMBASE published between 1 January 2014 and 31 December 2018. Search terms related to the disease , control and prevention efforts , and the region were utilized. The selection of African countries was done in reference to the 54 sovereign states which are listed as member states of the United Nations and national disease control program reports as well conference proceedings were also reviewed. Country specific data on SARE stages were retrieved through the Pan-Africa Rabies Control Network (PARACON) and Middle East and Eastern Europe Rabies Expert Bureau (MEEREB) interfaces of the Global Alliance for Rabies Control (GARC) .We also searched, retrieved, and reviewed specific rabies and generally neglected tropical diseases (NTD) national prevention and control strategies and plans through websites of Ministries of Health of each of the countries. Requests to key stakeholders for unpublished strategies, plans, and reports were also made for countries with no publicly available records. For countries with official languages other than English and French, we included literature, policy documents, and national guidelines translated into English or French.Quantitative and qualitative data were extracted from all available records in a structured data extraction tool in Microsoft Excel file. Key variables included the availability of a NTD and/or rabies national plan, whether rabies prevention and control is addressed in national plans/strategies, availability of a Stepwise Approach towards Rabies Elimination (SARE) score and human and/or animal vaccination programs. Furthermore, comprehensiveness of national strategic plans and challenges to rabies control and prevention were qualitatively evaluated against specific parameters including specific action items and monitoring plans in the extraction tool .https://rabiesalliance.org/tools/planning-tools/sare) (accessed on 21 January 2021). The SARE tool guides countries in the formal evaluation of their current status of rabies control [Blueprint for Rabies Prevention and Control\u201d [Under the umbrella of \u201cOne Health\u201d, a collaborative, multisectoral, and transdisciplinary approach including human and animal health and environmental scientists, countries are working towards elimination of canine rabies with the support of the WHO, the World Organization for Animal Health (OIE), the Food and Agriculture Organization of the United Nations (FAO), and GARC . This ef control . OperatiControl\u201d . Togethehttps://rabiesalliance.org/networks/paracon) (accessed on 21 January 2021). Another notable effort under the GARC is the Middle East, Eastern Europe, Central Asia, and North Africa Rabies Control Network (MERACON), that arose out of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB) in 2015, which unites scientific expertise and national stakeholders to inform prevention programs and complements the coverage of the African continent. PARACON, an advisory and networking initiative, was formed under the secretariat of GARC to unify all sub-Saharan African countries towards a One Health approach for rabies control and elimination . This reThe level of rabies awareness and adapted strategies for surveillance and prevention varied widely across countries. Thirty-nine African countries have implemented an official vaccination program for animal vaccination against rabies. Vaccination programs in 15 of these countries focus on dog vaccination while in 10 countries, both dog and cat vaccinations are practiced. National efforts for rabies control and prevention need to be coordinated through strategic plans, which outline specific, attainable, and measurable actions; monitoring strategies; and the financial provisions for all the planned activities. Five countries including Algeria, Angola, Ivory Coast, Kenya, and Namibia have an accessible and specific national strategic plan for the elimination of rabies . In AlgeFourteen countries 14/54, 25.9%) included rabies prevention and control measures in their NTD Masterplan . Eritrea.9% incluThe Central African Republic , DR CongThe national program against rabies of the Kingdom of Morocco targets reduction of rabies incidence by 50% in 2021 and elimination of canine-transmitted rabies by 2025 . In TuniTanzania initiated a multi-faceted project in 2010, which was supported by the WHO in 28 districts on the Tanzanian mainland and the island of Pemba and in 2017 gave impetus to the development of a National Rabies Control and Elimination Strategy aiming at control of dog rabies incidence and elimination of human rabies by 2030 ,39. SimiBotswana and Ethiopia have no national rabies plan nor integrated measures in their respective NTD master plan and for five countries including Benin, Burkina Faso, Burundi, Cabo Verde, and Cameroon, no data was publicly available .In four countries, namely, Angola, Ivory Coast, Namibia, and Sierra Leone, national plans are mentioned in peer-reviewed publications or from sources linked to national policies or by the scientific community ,44,45,46Identification of the key challenges to implementation of rabies prevention and control strategies is an essential first step to successfully achieving regional, national, and global targets. Although most of the African countries are members of one of the rabies networks such as MEEREB or PARACON, national rabies plan, stand-alone or as part of the NTD master plan are not yet implemented. Qualitative assessment of existing plans is complicated by the diversity of country-specific definitions of prevention or control measures such as monitoring and surveillance or limited simply due to lack of data . FurtherThe lack of epidemiologic data is a significant challenge in streamlining rabies control and prevention. In Mali and Nigeria, despite having more elaborate strategies within the NTD Master Plan, the scarcity of prevalence and incidence data on rabies poses significant challenges to the control and prevention efforts ,26. In cIn Ethiopia, despite not publishing a national rabies elimination plan, a surveillance network exists including the Public Health Emergency Management of the Ethiopian Public Health Institute, the Ministry of Livestock and Fisheries, and Ethiopian Wildlife Conservation Authority .Monitoring progress of national programs is at the heart of the elimination efforts. Thirty-five African countries, as well as the semi-autonomous region Zanzibar, went through the self-assessment process with SARE and shared their score with PARACON including open access of data see . GeneralThe current level of implemented programs and activities shows that rabies is still a neglected disease and surveillance, prevention and control measures are still inadequate on the African continent. It is important for national and international stakeholders to understand that rabies has the highest case fatality ratio of all infectious human diseases and, more importantly, that human death related to canine-mediated rabies could be 100% prevented by enhanced vaccine coverage in the canine population. For example, in South Africa, current surveillance for rabies was described as meagre with inadequate dog rabies vaccine coverage in many areas . The decOur findings agree with those of other reviews that identified shortages in capacity to prevent and control canine-mediated rabies in Africa . The relCanine-mediated rabies should not be recognized as a neglected tropical disease for which endemicity is regionally limited to the African continent but instead be understood as a global infectious disease problem calling for more action and coordination worldwide. As with many infectious diseases, rabies does not respect national borders and can impact any country in the world given the unprecedent air travel. A recent review investigated cases of rabies in international travelers, expatriates, and migrants and found two-thirds of identified cases in migrants from rabies-endemic low-and middle-income countries . As longThe data included in this review was retrieved from peer-reviewed journals and publicly accessible literature. We do not claim full coverage of all available information on every African country since the search was limited to data available in English and French even though most governmental portals provide English versions. Country specific regulations, practices, national strategies, or plans might not have been shared publicly or might not have been accessible and hence were not included in this review."} +{"text": "SARS-COVID-19 pandemic changed the World and urological practice. The SARS-COVID-19 pandemic has a great impact in all medical fields and because the important changes in Urology in last 3 months and due to the large volume of information and articles received, we chose to carry out this supplement. Despite these extremely difficult times, we are very happy because this supplement marks the beginning of the partnership between the Brazilian Society of Urology (BSU) and the American Confederation of Urology (CAU). Soon the International Brazilian Journal of Urology has everything to become the official information Journal of CAU reinforcing the impact of the International Brazilian Journal of Urology on the American continent.This Supplement presents original contributions with a lot of interesting papers about SARS-COVID-19 pandemic. The papers came from many different countries such as Brazil, USA, United Kingdom, Belgium, Colombia, Peru, Argentina, Germany, Netherlands, Italy, Spain, Canada, and China. As usual, the editor highlights some of them.Dr. Lauxman and colleagues from Germany performed in page 6 a nice Dr. Chen and colleagues from China performed in page 19 a nice Dr. Esperto and colleagues from Italy performed in page 26 an inteDr. Sanchez and colleagues from Spain performed in page 50 an impoDrs. Zequi and Abreu from Brazil and Uruguay performed in page 69 a nice Dr. Casco and colleagues from Spain performed in page 86 (Dr. Ibarra and colleagues from Spain Italy and Iran performed in page 104 a nice Dr. Gonzalez and Ciancio from USA and Spain performed in page 145 an impoDrs. Zampolli and Rodriguez from Brazil and USA performed in page 215 a nice The Editor-in-chief expects everyone to enjoy reading of this supplement and for sure better times will come soon around the World."} +{"text": "Tissue Engineering and Regenerative Medicine International Society (TERMIS) is the most prominent organization in the field of tissue engineering and regenerative medicine globally. TERMIS promotes education, research, innovation, clinical translation, and social responsibility within the field of tissue engineering and regenerative medicine through regular meetings, training courses, scientific and lay publications, outreach activities, and other forms of communication. TERMIS provides an international forum for informed discussion on the challenges and achievements of tissue engineering therapies.Tissue Engineering Therapies: From concept to clinical translation and commercialisation.\u201d This special issue covers all aspects of tissue engineering and regenerative medicine, including computational models for the cost efficient production of cell-based tissue engineered products ; development of media and tools for more accurate cell culture and for effectively monitoring the fate of implantable devices ; the potential of large animal models in regenerative medicine ; and clinical indication specific discussion .This special issue is associated with the TERMIS EU Chapter 2019 meeting at Rhodes, Greece, 27-31 May. The theme of the meeting was \u201cCampos et al.), gellan gum hydrogels , elastin-like recombinamer hydrogels , poly electrospun scaffolds decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) electrosprayed nanoparticles , tripolyphosphate crosslinked chitosan/gelatin biocomposite inks , inorganic calcium phosphate, chitosan, and hyaluronic acid scaffolds , polycaprolactone-polypyrrole printed conductive biomaterials ] for a diverse range of clinical targets, as well as advances in stimuli responsive materials as controlled delivery vehicles .Advancements in chemistry and engineering have made numerous new materials available and nano/micro fabrication technologies have potential in modern tissue engineering and regenerative medicine. With this in mind, this special issue discusses a range of natural and synthetic systems and of in vitro pathophysiology models for drug screening purposes .Considering that cells are the basic building blocks of tissues , contemporary tissue engineering and regenerative medicine exploits the power of cells for the development of implantable devices that will revolutionize healthcare due to their therapeutic and reparative capabilities (e.g., hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids with a photocrosslinkable methacrylamide-modified gelatin printed medium (in vitro models for the study of disease progression and to assess the potential of novel therapies. This collection of manuscripts captures the state-of-play in this field, indicating that the development of effective therapies is underway.Tissue engineering and regenerative medicine have the potential to provide effective treatments for uncurable injuries and diseases, potentially enabling the development of All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The COVID-19 pandemic, caused by the emergence of a new strain of coronavirus (SARS-CoV-2) around the end of December 2019, has caused a worldwide public health emergency and a socioeconomic crisis during 2020. The lockdown imposed to cope with the health issues caused by the outbreak of the disease has dramatically challenged and negatively affected all the economic sectors of the modern global economy. Specifically, the livestock sector and its related industries are among the most impacted sectors. This is mainly ascribed to the limitations of animal movement and the decrease of production inputs' availability. Other factors negatively affecting the sustainability of the livestock sector have been the shortage of workers due to the lockdown/curfew, the strong decrease in the purchasing power of the consumer, and the intensification of health care tasks. Such an impact is not only highly relevant because of their economic consequences, but also because of the effects of the lockdown and sanitary rules on animal care and welfare. The current review aims to offer: (a) a comprehensive overview of the impact of COVID-19 on the welfare of farm animals and on the performance of livestock farming systems, on food chain sustainability, and finally, on the global economy and food security; and (b) a prospective outline of alleviation actions. By the end of December 2019, the world awoke to a public health crisis due to the emergence of a new strain of coronavirus, which was later named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) .Globally, the COVID-19 pandemic has had a direct impact on food systems through changing the food supply-demand system, and an indirect impact through decreasing purchasing power and the capacity of food distribution and marketing, and increasing healthcare tasks . EconomiSuch a fact will cause severe effects worldwide, with larger effects seen on both the economies and sociodemographics of developing areas. The livestock sector is estimated to account for about 40% of global agricultural output value and two-thirds of the 600 million livestock keepers worldwide are women, so the current situation compromises their economic empowerment , 8. FarmThe closure of meat and milk processing plants has also contributed to the sharp disruption in the livestock supply chain, leading to substantial losses in production capacity and animal products. For instance, in the USA, the loss of production capacity due to the closure of plants have reached up to 25 and 43% for beef slaughterhouses, respectively . The porThis review discusses how the COVID-19 outbreak may affect animal welfare and livestock, the dairy and meat industry, and supply chains by using available scientific/organizational reports, and cited observations and complaints of farmers. Such data may help in taking suitable measures to improve the current status and to pose lessons for the future, avoiding the emergence of food insecurity.Homo sapiens) and other animals, including birds and mammals and laboratory animals and camels (genus Camelus), inducing diarrhea, fever, and respiratory diseases, and thus causes negative impacts on animal welfare/productivity and farm profitability (Sixty percent of emerging contagious diseases have a zoonotic origin. Coronaviruses (CoVs) were first identified in the mid-1960s and are known to infect humans , rodents (order Rodentia), civets (Civettictis civetta), cats, pangolins (Family Manidea), minks (Neovisonvison), and tigers (Panther atigris), were found to test positive for COVID-19 (Canis lupus familiaris) and cats (Sus scrofa), cattle and sheep (Family Bovidae), horses, and poultry for antibodies of COVID-19 revealed negative results or Suidae (pigs) as well as poultry are not COVID-19 reservoirs (Rhinolophus species) coronavirus HKU2, suggesting both a bat origin of the pig virus and a jumping across species the main reservoir of COVID-19 are bats; (2) some wild , farmed (mink), and domestic (cats and dogs) animals can be a reservoir; (3) there is a possibility for the transmission of COVID-19 from humans to animals, animals to humans, and human to human; and (4) livestock belonging to the family the mainservoirs . Despite species , 32. Ano species . Accordi species , 31. HenRegarding the handling and consumption of animal products, there is no direct evidence on food-borne infection, including meat and milk. Precautions and hygienic measures are advisable since there is a possibility that contamination of food materials can occur through the handling of food by infected individuals. These precautions and sanitary measures include hand washing or sanitizing following the processing of fresh and packaged animal products, avoiding contact between fresh and cooked food materials, consuming well-done cooked meat, and extending meat and meat-processed materials' freezing time by more than 2 days before consumption .It is expected that the sudden restriction on human activities and the economic crisis will affect farming and veterinary services, and therefore, affect animal health . The COVFurthermore, some associations, such as the Canadian Cattlemen's Association, has called farmers to put cattle on maintenance rations rather than finishing rations to limit feedlot placements, coping with the closure of processing plants, and limited market capacities . Also, tLivestock production farming systems and their supply chains are challenged by many logistical supply interruptions, like most other agricultural enterprises. The COVID-19 outbreak interrupted livestock chain sustainability in different areas, from the production process to marketing and consumption of animal products . The priRestrictions on import/export activities and local movements have prevented farmers from accessing livestock production inputs and given them limited marketing opportunities. The limitation of movements and the disruption of national and international trade routes drive to a substantial decrease in vital livestock farming materials and facilities, such as feed materials, replacement stocks , drugs and vaccines, feed additives, and other livestock farming inputs . For insSeveral companies working on vaccines, animal health products, feed additives, milk testing kits, and spare parts of pasteurization equipment to small-scale meat and dairy producers have indicated that the reductions in fluidity and foreign exchange were other significant factors affecting the sustainability of the livestock supply chain, specifically in developing countries . There iIt is widely believed that agricultural sectors, including meat and dairy production sectors, are heavily labor-dependent sectors. The COVID-19 outbreak has caused a severe shortage of labor numbers and workforce in both developed and developing countries, which is more problematic for countries that depend on an imported workforce, such as European countries . This shXinfadi market in Beijing's largest wholesale market facilitating the direct distribution of food/animal products to consumers and offering electronic marketing platforms (China and Morocco); (2) providing livestock production inputs, such as animal feeds, drugs, and machines ; (3) supporting the resumption of meat/milk processing enterprises (China); (4) creating agricultural, healthcare, and animal diseases control extension programs; and (5) providing direct funding support to seasonal and informal labors , 49, 55.in vitro as an eco-friendly production technique, as methane emission by farm animals will be reduced , to the food supply chain as alternatives to animal protein sources is one of the suggested strategies , 56. Ano reduced , 58. How reduced . This al reduced , 61. Fur reduced . Recentl reduced . In this reduced .The availability of animals', feed ingredients, either through foraging or concentrate ingredients, was an additional challenge confronting the sustainability of the livestock supply chain. Data presented in our overview illustrated that one of the livestock supply chain's major disruptors was the inability of farmers to access animal feed. The restriction on import/export activity has negatively impacted the availability of essential feed ingredients . AcThe experience acquired through the COVID-19 crisis may also contribute to optimizing the part of the livestock supply chain that includes processing, retail, and marketing through strengthening the connection between producers, retailers, targeted markets, and consumers . The ineUnfortunately, to date there is no particular vaccine or therapeutic protocol to control the spread of COVID-19, and forecasts predict the continuation of this pandemic for a long time. In this scenario, livestock farmers have to be aware of different measures that they can apply themselves to maintain safe and efficient livestock farming. Successful farmers should maintain farm biosafety , 15, worIn this overview, we illustrated the significant disruptions that occurred in livestock, milk, and meat supply chains due to the outbreak of COVID-19. The COVID-19 pandemic revealed that, despite the vast advancements in knowledge and informatics technologies, we still need to create innovative applications and measures that can support the world against any future pandemic disasters. It is now clear that pandemic disasters are not only a matter of human health insecurity but can also encompass food insecurity and economic recession, increasing poverty and famines worldwide.NH: creating the main idea and writing the first draft. AG-B and AR-M: reviewing and final preparation of the manuscript. All authors approved the content for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Rheumatology as a research-intensive discipline may particularly benefit from the emerging digital evaluation tools, systematic search engines, distribution platforms, and repositories. Currently, processing journal submissions through advanced online systems allows detecting major inconsistencies and mistakes in research reporting and formatting manuscripts. Such systems, linked to regularly updated reviewer instructions of global editorial associations and supported by external bibliographic searches, enable fast evaluation of the novelty, originality, methodological rigour, and implications of the manuscripts by peer reviewers.In times of information deluge, editing and publishing a scholarly journal is increasingly dependent on digital tools and artificial intelligence.Open Researcher and Contributor IDs , are now employed by most publishers to validate individual profiles at the peer review and increase visibility of their contributions post-publication. The Mediterranean Journal of Rheumatology has also encouraged its contributors to register with and submit informative ORCID iDs with biographical notes, publication lists, and other academic accomplishments. The ORCID iDs are now integrated with the the Publons platform (https://publons.com), yet another indispensable digital tool for crediting reviewers and selecting active and skilled experts for further evaluations.3 Notably, the number of academic contributors with ORCID iDs is fast approaching the level of 6 million, and more publishers and standalone journals are partnering with Publons to streamline the peer review activities and global recognition of their reviewers. With the integration of Publons with Web of Science in 2017 and further upgrades of the platform, the registered scholars are now offered automatic updates of their profiles by listing their WoS-indexed articles and tracking related citations. Publons profiles are particularly valued by emerging scholarly journals, aiming to attract scarcely available reviewers and increase the quality of peer review.5 The total number of registered reviewers on Publons is 541,093, including 571 in rheumatology . The Mediterranean Journal of Rheumatology acquired its profile on Publons this year to increase transparency of the peer review activities and give deserved academic credits to its best contributors .The author and reviewer identifiers, and particularly the Crossref, a powerful system for cross-linking references and updating individual digital profiles (http://crossref.org/). Launched in 2000, Crossref is currently run by the Publishers International Linking Association. The reference validation and formatting tools supported by Crossref permanent identifiers guarantee the accuracy of technical editing, formatting, and detecting plagiarism, to name just a few advantages of the system. With the expansion of Crossref services and integration with journal platforms , ensuring the efficiency of online publishing, navigating through myriads of scientific articles, and indexing with bibliographic databases are becoming closely interconnected. Once and for all, the concept of discoverability of scholarly items and systematic searches through online databases has shifted towards permanent article identifiers.7 Given the growing importance of the Crossref services, a decision was made to acquire DOIs for the Mediterranean Journal of Rheumatology this year to benefit from vast opportunities of improved visibility and integration with digital platforms and databases.The speed of processing and visibility of scholarly contributions are also increasingly dependent on Digital Object Identifiers (DOIs) issued by 8 The absolute majority of open-access medical journals have benefited from archiving by PubMed Central, the largest digital repository of medical articles. The editors\u2019 relentless efforts aimed to archive the Mediterranean Journal of Rheumatology by PubMed Central will widen prospects of indexing for this rapidly developing periodical.Over the past two decades, open-access publishing has increased global visibility and international recognition of journals across numerous subject categories. Various open access models have increased article views, downloads, and citations, transforming all these benefits into the scientific prestige of emerging and research-intensive fields of science.Mediterranean Journal of Rheumatology, and related links are embedded in the journal instructions: the Budapest Open Access Initiative (2002) and the Berlin Declaration on Open Access (2003).10 In line with the statements of these documents, the Open Access initiative is primarily aimed to increase the use of published items for research and education.11 Additionally, the improved visibility, one of the main achievements of the initiative, has enabled detecting and \u2018cleaning\u2019 erroneous and fraudulent literature.12 Although the main attribute of Open Access is free access to published works for readers, there are other, not less important, components related to digitization, preservation, and archiving. To meet the requirements of Open Access and satisfy indexing criteria of most bibliographic services, medical journal editors should familiarize themselves with the Journal Article Tag Suite (JATS) format of Extensible Markup Language (XML), which is employed by the National Library of Medicine of the US for encoding PubMed Central-archived items.13 The XML format enables machine-readability and makes it possible to index quality journals by most prestigious bibliographic databases and digital repositories.The basic principles of Open Access are outlined in two seminal documents, which are consulted by the editors of the Mediterranean Journal of Rheumatology to the area of medicine of the registry is an exemplary achievement for the whole field of rheumatology .While Open Access is gaining momentum and numerous journals opt for different models of open-access publishing , several global initiatives have been launched to distinguish periodicals with reliable peer-reviewed contents from spurious online platforms of wasteful publishing. The Directory of Open Access Journals (DOAJ) is one such initiative with strict scientific and technical criteria, listing 12,397 open access journals from 129 countries and offering records of 3,600,965 for systematic searches . The number of the listed medical journals is 699, with 472,913 linked items available for searches. The latest incorporation of the 14 The declared by the Mediterranean Journal of Rheumatology adherence to these principles is essential for its development and ethical promotion.Launched in 2003, the DOAJ project has passed a long way and become a \u2018whitelist\u2019 of reliable periodicals. The DOAJ collaborated with several global editorial associations to set principles of transparency in publishing.16 For medical journals, the DOAJ listing is proposed as one of the requirements for indexing by PubMed and archiving by PubMed Central.17 In 2015, the Scopus database introduced the open access indicator for separate marking DOAJ-listed journals, making it easier to navigate and search through the growing number of open-access periodicals which passed stringent quality checks.18 Notably, the SCImago Journal & Country Rank platform currently ranks 34,171 Scopus-indexed periodicals across all subject categories, including 4,504 for open access. In the field of rheumatology there are 60 Scopus-indexed periodicals, with 20 registered with DOAJ . These numbers will definitely continue to grow in the future.Acquiring the seal of DOAJ is a milestone in the journal digitization and recognition by the scientific community.International Committee of Medical Journal Editors is perhaps the most important association; offering frequently updated editorial guidance for authors, reviewers, and editors. Editors claiming adherence to the ICMJE recommendations and enforcing its points in their daily practice offer good service to their community of authors and readers. Exemplary, the editors of the Mediterranean Journal of Rheumatology registered their interest in the recommendations at the ICMJE website in 2017.19While the recent digital innovations enormously influence the speed of publishing, editorial credentials still remain precious assets for the quality of publishing and impacting science. The journal editors with connections to global and regional editorial associations are capable of establishing networks of skilled peers, share experience, and add to the scientific prestige of respective periodicals. In the field of medicine, the 20 The editorial credentials and reviewer responsibilities are currently highlighted in the documents published by the Committee on Publication Ethics, the largest association of editors with more than 12,000 members. Member-editors of the COPE are now offered a set of updated recommendations about authorship problems, conflict of interest disclosures, ethics approval, copyright issues, journal management, and retractions.21 The latest incorporation of the updated publication ethics points into the instructions of the Mediterranean Journal of Rheumatology is an exemplary move towards better quality control for disseminating reliable information for the respective regional community.Several other global associations also allow advancing scientific and publishing editors\u2019 skills."} +{"text": "This dataset presents data collected from household surveys from Upper Madi Watershed of Nepal describing the benefits of non-timber forest products (NTFPs) to people of mountain ecosystems, their perceptions of climate change, and perceived impacts of climate change on NTFPs ecosystem services. The data were collected from 278 households that were randomly selected from the four villages in the watershed during the period September to December 2019. The survey assessed socio-demographic information; collected and utilized NTFPs; perceptions of climate change, and; perceived impacts of climate change on NTFPs ecosystem services. These data are important in understanding the benefits of non-timber forest products in mountain ecosystems and the impacts of climate change as the benefits and impacts are currently not well understood. The data will be helpful in formulation and implementation of adaptation strategies to sustain the supply, protection, and management of NTFPs in mountain ecosystems. The survey data include the following sections: a) socio-demographic information of respondents including age, gender, ethnicity, educational background and occupation b) utilization of non-timber forest products by mountain communities c) perceptions of climate change d) Perceived impacts of climate change on non-timber forest products ecosystem services. The questionnaire is provided as a supplementary file. Social-demographic characteristics are presented in The details of non-timber forest product use in the Upper Madi Watershed of Nepal, number of non-timber forest plant species, purpose of NTFPs collection, respondent perceptions of climate change, perceived impacts of climate change on non-timber forest products ecosystem services are described in 2This research was based on primary data collection through a household survey Ethical approval was obtained from the faculty of Science Engineering and Built Environment Human Ethics Advisory Group, Deakin University (reference number STEC-31\u20132019-GURUNG). Respondents\u2019 participation was completely agreed, voluntary, and anonymous.Lila Jung Gurung: Conceptualization, methodology, data collection, and writing of the manuscript.Kelly Miller, Susanna Venn, and Brett A Bryan: Conceptualization, methodology, review and editing the manuscript.The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article."} +{"text": "The steppe zone is the huge area in temperate Eurasia where different grasslands form the main type of vegetation. The main part of this life zone has been transformed by human activity and used for crop cultivation (mainly wheat) and livestock. Regional and local transformations and/or climate changes can result in some shifts in species and population distribution of Orthoptera. Over this area, the climatic conditions and the dominated grasslands are suitable for numerous grasshoppers and their relatives, especially the graminivorous ones. The general level of their diversity is usually high. Many species are very abundant and may become important pests. However, there are also many rare species. The main aims of this paper are to reveal general patterns of Orthoptera distribution in the Eurasian steppes, to evaluate long-term trends of changes in distribution of taxa and populations, and to estimate the potential for population changes relative to human activity and global warming trends.Locusta migratoria, Calliptamus italicus, Dociostaurus maroccanus) is also discussed. Some notable changes of their populations\u2019 distribution and dynamics are characterized. The situation with rare Orthoptera is estimated. Retrospective and prospective of the steppe fauna of Orthoptera are discussed.The main aims of this paper are to reveal general patterns of Orthoptera distribution in the Eurasian steppes, to evaluate long-term trends of changes in distribution of taxa and populations, and to estimate the potential for population changes relative to human activity and global warming trends. The main publications concerning diversity and distribution of these insects over the steppes are analyzed. The fauna of the Eurasian steppes includes more than 440 species of Orthoptera. The general distribution of grasshoppers and their kin in the Eurasian steppes reflects their common associations with different grasslands. The species richness increases from the relatively cold forest-steppes to the semi-deserts with their warm summer. There are some endemic or subendemic taxa, including the tribe Onconotini (Tettigoniidae). The populations\u2019 distribution of Orthoptera is also analyzed. The populations of native Orthoptera extend through all the herbaceous landscapes. Under these conditions, the interrelating of colonies of each species may result in great abundance. The population distribution of three species locusts ( The steppe zone is the huge area in temperate Eurasia where different grasslands form the main type of vegetation ,2,3,4 F. The adjFrom the zoogeographic point of view, the steppe zone almost coincides with the Scythian (or Euro-Siberian Steppe) subregion of Palaearctic erected mainly on the basis of the species distribution analysis ,9,10,11.The main aims of this paper are to reveal general patterns of Orthoptera distribution in the Eurasian steppes, to evaluate long-term trends of changes in distribution of taxa and populations, and to estimate prospective of their population changes relative to human activity and global warming trends.Both qualitative and quantitative data were used. The analysis of geographic distribution was based on published and unpublished species range maps. Species data points for Eurasian Orthoptera were plotted onto base maps, usually on a scale of 1:25,000,000. My own collections, the collections of different museums, and published data were used ,9.2 (sometimes 0.5 \u00d7 0.5 m2 or 1 \u00d7 1 m2). After that, the average density was estimated for every habitat investigated. The samples were collected in the Eurasian steppe by the expeditions of Department of General Biology and Ecology (Novosibirsk State University) and the Laboratory of Insect Ecology from 1972 to 2020. Numerous published papers and books (see the next parts of the publication) describing orthopteran distribution in different parts of the steppe life zone were also analyzed. In almost all cases, I use modern names of taxa ); (3) mesophilous ), and (4) hydrophilous . Distribution patterns of two species, namely Calliptamus abbreviatus Ikonnikov and Omocestus haemorrhoidalis, were unique. The three most abundant species were also separated in time of their active life.Spatial and temporal heterogeneity and niche overlapping were also described for grasshoppers in the steppes of Inner Mongolia ,80. The In the steppes, acoustic and visual communication can serve as the very important mechanism for sharing ecological niches ,82. As aLocusta migratoria Linnaeus), the Italian locust , and the Moroccan locust (Dociostaurus maroccanus (Thunberg)), occur in the Eurasian steppe. These species have spatially structured populations with rather complicated dynamics. In some parts of their ranges, they are able to change their behavior from solitarious to gregarious and vice versa and irregularly produce devastating upsurges [Three species of locusts, namely the Migratory locust . However, these specimens mainly originated from South-East Kazakhstan , where sAchnatherum splendens (Trin.) Nevski on the lake terraces, some meadows with short mesophilous grasses along a small stream, and halophytic meadows in wide depressions near the lake. The Migratory locust was very abundant on the lake terraces; its density was up 1 ind. per m2. The locust aggregations were not observed both for adults and hoppers. The main traits were typical for the solitarious form, however, some traits of adults indicated that the population could be characterized by some level of gregarization [In 2017, a moderate population of the Migratory locust was found in Tuva (the Republic of Tyva) in the Altay-Sayan Mountains, near hypersaline Shara Lake. The discovered population inhabited several adjacent habitats: the local dry meadows with dominance of rization . The ratrization . The popThe Italian locust is a common species and the most important pest in the Eurasian steppes from their western limits up to the south-eastern parts of West Siberian Plain and East Kazakhstan. Numerous outbreaks of this species were described for these territories ,83,95,96Recently, the main data on the Italian locust distribution and ecology were summarized for the territory of the former USSR. The main part of the species range is connected with the semi-desert zone ,100,101.In the forest-steppes of West Siberia, the Italian locust is widely distributed. However, its populations are very localized and are at a low level of abundance across the overgrazed plain pastures. In the steppes, its populations occupy not only local watershed plains but the dry parts of upper flood plains and lower terraces and the stony southern slopes of hills. In this area, the specific additional optimum of this species is observed in the dry steppes of Kulunda . This opSpatial population distribution of the Italian Locust at periods between outbreaks both within the whole area and on better examining territory of the eastern parts of it range corresponds as a whole with the known rule of habitat change . In the It is important to recognize that the population dynamics within additionally infested areas differs significantly from those in the main area because Poa bulbosa Linnaeus and on undisturbed clay soils [The Moroccan locust occurs only in the European steppes and, furthermore, it is distributed over the steppes of the Crimean Peninsula and the North Caucasus . Howeveray soils . Intensiay soils . In the ay soils noted thay soils ,112. In ay soils ,111,112.Calliptamus italicus or Dociostaurus maroccanus) may be also almost extinct, but others are abundant [The fauna of the Eurasian steppes includes a few rare species. There are several implicit areas of Orthoptera diversity ,114. Theabundant ,111.Isophya boldyrevi Miram, I. doneciana, Bradyporus multituberculatus montadoni (Burr) (as a separate species\u2014M.S.). Listed as endangered (EN) are Isophya stepposa, I. zubovskii Bey-Bienko, Bradyporus macrogaster (Lefebvre), and Asiotmethis tauricus. Some forms (including widely distributed Saga pedo and Stenobothrus eurasius) are vulnerable (VU). This list does not include one of the rarest taxa of the European steppes\u2014Bradyporus multituberculatus multituberculatus. The species is on the Red Books of Russia and Ukraine [About 1500 orthopteran species are now on the International Union for Conservation of Nature (IUCN) Red List of Threatened Species , and man Ukraine . It was Ukraine ,119. ForSaga pedo, Gampsocleis glabra (Herbst), Onconotus servillei ). However, some endemic and subendemic genera, species, and subspecies occur in the central and the eastern parts of the Eurasian steppes. Some of them are known from one or several localities. Besides, populations of many orthopteran insects can decline in regions with intensive agriculture.Unfortunately, the actual version of the IUCN Red List of Threatened Species does not include the steppe species associated with the steppes of South Siberia, Kazakhstan, Mongolia, and North China or with the steppe mountain landscapes of mountains of Central Asia. There are only some widely distributed species . The distribution patterns of several species, e.g., Asiotmethis muricatus , Notostaurus albicornis (Eversmann), and Mesasippus arenosus, did not change significantly during the last decades. Two species, namely Megaulacobothrus aethalinus and Aeropedellus variegatus, were recently found near the boundaries of the region. Four species , Stenobothrus carbonarius (Eversmann), Sphingonotus coerulipes) are extremely rare now. The local populations of almost all rare species are usually associated with a few types of habitats. This means that intensification and changes of human activity may result in their extinction.Recently, distribution patterns of rare acridid species in the south-eastern part of West Siberian Plain were analyzed . The ranReconstruction of the past of many taxa and faunas is problematic. The most important problem is the shortage of appropriate fossils. This results in development of different hypotheses explaining geographic and ecological history of different taxa and faunas. In the absence of adequate fossil data, some possible approaches can be based on a complex analysis of the ecological factors, adaptations to particular living conditions, and the optimum conditions, which can be estimated by some comparative studies of species range shapes and the population distribution within the range ,60,70.Chorthippus and its relatives), the genera Podisma Berthold, Stethophyma, Podismopsis Zubovsky, etc. He also mentioned some relationships between the Angarian fauna and the faunas of the southern parts of East Asia. Bey-Bienko [The history of Orthoptera of the Eurasian steppes was discussed in a number of papers. A century ago, Uvarov ,123 and y-Bienko ,65,124 hy-Bienko ).One of the principal results of retrospective views on faunas and populations is the opportunity to forecast their possible changes in the future. If the trend of global warming continues, the steppe zone will shift northwards , and theThe steppe species will shift the northern boundaries of their ranges northwards, and some of them will be able to use numerous transformed habitats, such as clearings, roadsides, agricultural fields, and pastures . BesidesIsophya costata and also Saga pedo, Arcyptera fusca, A. microptera , and Stauroderus scalaris, due to human activityIn Hungary, B. Nagy noted siArcyptera fusca, A. microptera, Stenobothrus fischeri, Bryodemella tuberculata, Psophus stridulus Linnaeus, and Sphingonotus caerulans Linnaeus. He explained this declining by intensification and some changes of human activity. Besides, the isolated colony of Sphingonotus coerulipes was unexpectedly found on stockpiles of mining plants.In the northern steppes of Central Russian upland, A. V. Prisny showed pPodisma pedestris, Euthystira brachyptera (Osckay), Gomphocerus sibiricus, Psophus stridulus, Bryodemella tuberculata, etc., were found here in the middle of the 19th century [Dericorys tibialis , Heteracris adspersa (Redtenbacher), Sphingonotus halophilus Bey-Bienko, Ramburiella turcomana , etc.) [Glyphonotus thoracicus mainly associated with river valleys of deserts and semi-deserts was recently found in the southern parts of the steppes of Central and North-East Kazakhstan [Significant changes of orthopteran diversity were revealed for the vicinities of Lake Baskunchak in the semi-deserts of South-East Europe . Several century but disa century supposed), etc.) . The buszakhstan .Gomphocerus sibiricus significantly declined in the plain steppe habitats during the last decades [Podisma pedestris, Sphingonotus coerulipes) became very rare [Arcyptera microptera), some others crossed more than 100 km , Conocephalus fuscus (Fabricius), Dociostaurus brevicollis, Oedipoda caerulescens (Linnaeus), Oedaleus decorus, Epacromius pulverulentus) [Our published and unpublished data show conspicuous changes in distribution of several species in the south-eastern part of West Siberian Plain during the last decades. Populations in the first half of the 20th century of the widely distributed and abundant decades . Severalery rare ,114. Howulentus) ,114. Almulentus) ,131 and ulentus) . On the I can conclude that, during last decades, biological diversity, geographic, and ecological distribution of Orthoptera over the Eurasian steppes have been characterized by rapid changes due to climatic variations and changes of local human activity. In many cases, we can observe declining and elimination of local populations but, on the contrary, other species can colonize new areas and habitats. This is true for both possible pests and rare species. This means we should constantly monitor orthopteran populations and assemblages over all huge territory occupied by the steppe biome."} +{"text": "The peer review system is the soul of the Scientific journals. This process became an institutionalized part of the scholarly process in the latter half of the twentieth century . The serIn 2020 the International Brazilian Journal of Urology received more than 900 papers and the reviewers were very important to the entire process of our Journal. As a Editor-in-Chief I would like to thanks all the reviewers and specially the Doctors: Alexandre Danilovic, MD ; Ralf Anding, MD ; John Denstedt, MD, PhD (Western University Canada); Trushar Patel, MD (University of South Florida) and Gustavo Ruschi Bechara, MD who reviewed more than 5 articles during the year and strictly within the deadline.Thanks a lot!!!!!Luciano A. FavoritoEditor-in-ChiefInternational Brazilian Journal of Urology"} +{"text": "Molten salts play multiple important roles in the electrolysis of solid metal compounds, particularly oxides and sulfides, for the extraction of metals or alloys. Some of these roles are positive in assisting the extraction of metals, such as dissolving the oxide or sulfide anions, and transporting them to the anode for discharging, and offering the high temperature to lower the kinetic barrier to break the metal-oxygen or metal-sulfur bond. However, molten salts also have unfavorable effects, including electronic conductivity and significant capability of dissolving oxygen and carbon dioxide gases. In addition, although molten salts are relatively simple in terms of composition, physical properties, and decomposition reactions at inert electrodes, in comparison with aqueous electrolytes, the high temperatures of molten salts may promote unwanted electrode-electrolyte interactions. This article reviews briefly and selectively the research and development of the Fray-Farthing-Chen (FFC) Cambridge Process in the past two decades, focusing on observations, understanding, and solutions of various interactions between molten salts and cathodes at different reduction states, including perovskitization, non-wetting of molten salts on pure metals, carbon contamination of products, formation of oxychlorides and calcium intermetallic compounds, and oxygen transfer from the air to the cathode product mediated by oxide anions in the molten salt."} +{"text": "In 2018, the government of the Republic of Korea (ROK), South Korean life science companies, and a group of international funders led by the Bill & Melinda Gates Foundation launched a new and innovative funding agency to support neglected-disease research and development (R&D). The new venture is known as the Research Investment for Global Health Technology (RIGHT) Fund. At the end of the Korean War in 1953, ROK was a devastated nation and ranked among the poorest in the world. A decade later, in response to its high prevalence rates of poverty-related neglected diseases, including soil-transmitted helminth infections, malaria, and tuberculosis, the ROK government in collaboration with a Korean Association for Parasite Eradication (KAPE) began programs of infectious and parasitic disease control . In someToday, the ROK boasts the 11th largest economy globally and one of the most advanced economies in Asia, with a gross domestic product (GDP) of 1.7 trillion USD . RecogniA key element of the ROK\u2019s economic success is its vigorous and productive life sciences and pharmaceutical industry, with advanced capabilities for drug, diagnostics, and vaccine development. The ROK has also well positioned to lead the convergence and integration of biotechnology, information and digital health, and communication technologies (ICT) for disease prevention, diagnosis, and treatment. These features afford a unique opportunity for the ROK to leverage and incorporate R&D into its programs of ODA.Recognizing the ROK\u2019s dual capacity to both contribute ODA at a high level and pursue a vigorous R&D agenda, the Bill & Melinda Gates Foundation pursued a partnership with both the ROK government and South Korea\u2019s life sciences industry for developing an innovative fund for neglected-disease technologies. Such activities built on a previous success in Japan where the Global Health Innovative Technology (GHIT) Fund was established in 2013 . HoweverIn July of 2018, a new Research Investment for Global Health Technology (RIGHT) Fund was created as a three-way nonprofit partnership between the Ministry of Health and Welfare (MOHW) of the ROK government, South Korean life science companies, and the Gates Foundation, in addition to other international funders 6]..6].Central to the RIGHT Fund is an innovative platform for the Korean partners to expand their contributions to global health and neglected-disease R&D projects, with a long-term objective to develop and deliver new neglected-disease drugs, diagnostics, and vaccines .An overall project goal of the RIGHT Fund is \u201cto advance the discovery and development of new health technologies to meet the needs of Low and Middle Income Countries (LMICs) by leveraging the intellectual, technological, and financial resources of the ROK\u201d . The FunThe RIGHT Fund operates through a management team that includes an Executive Director, together with individuals who lead operations in three areas\u2014strategy, investment planning and management, and government relations. The RIGHT Fund management works with an independent selection committee and reports to a Board of Directors composed of representation from the Korean MOHW and Korean Centers for Disease Control & Prevention (CDC), in addition to an ex officio observer from the Gates Foundation, and members at large. Also overseeing the entire RIGHT Fund is a Council with representation from the Korean MOHW, National Institute of Health, IVI, Gates Foundation, and the leadership of the five major South Korean life sciences industries.The technologies advanced by the RIGHT Fund are driven by the needs of the low-resource countries, typically measured through years of life lost or years lived with disability; their potential for impact; and whether they leverage the current strengths of life sciences R&D within ROK. An applicant should involve at least one Korean research organization or company. Another criterion is the potential of the technologies selected to expand the invovlement of Korean life sciencies organizations in the global health space and ecosystem. Fairness and transparency are also paramount. The three major technological areas include vaccines, therapeutic drugs, and diagnostics, with each area considering new approaches and constructs, product improvements, or patient access 6]. Req. Req6]. Haemophilus influenzae type b (Hib) vaccine. The therapeutic is a low-cost manufacturing process for a new antimalaria drug from the product development partnership (PDP) Medicines for Malaria Ventures (MMV), together with the Korean life sciences company SK Biotek. The two diagnostics are (1) a second-generation test for glucose-6-phosphate dehydrogenase (G6PD) from the Seattle-based PDP, PATH, and the Korean life sciences company SD Biosensor and (2) a point-of-care diagnostic for detection of Mycobacterium tuberculosis and multidrug-resistance mutations from a PDP with diagnostics expertise, Foundation for Innovative New Diagnostics (FIND), and Bioneer, another Korean company [In its first year of operations, investments have been made in five technologies: two vaccines, one therapeutic agent, and two diagnostics. The two vaccines include (1) a novel conjugate cholera vaccine under joint development by Harvard Medical School, Massachusetts General Hospital, IVI, and EuBiologics (a Korean life sciences company) and (2) a hexavalent vaccine produced by LG Chem, another Korean life sciences company, which combines diphtheria whole-cell pertussis-tetanus toxoid vaccine, inactivated polio vaccine, recombinant hepatitis B vaccine, and The concept of \u201cblue marble health\u201d finds an unexpected level of neglected-disease burden among the poor living in the Group of 20 (G20) nations ["} +{"text": "To strengthen the fight against malaria, it is imperative to identify weaknesses and possible solutions in order to improve programmes implementation. This study reports experiences gained from collaboration between decision-makers and researchers from a World Bank project . The objectives of this paper were to identify bottlenecks in malaria programme implementation as well as related research questions they bring up.Questionnaire addressed to National Malaria Control Programme managers and prioritization workshops were used as a medium to identify research questions. The bottlenecks in malaria programme implementation were identified in seven thematic areas namely governance, human resources, drugs, service provision, use of prevention methods, monitoring and evaluation (M and E), and public support or buy-in. The first five priority questions were: (1) compliance with drug doses on the second and third days during the seasonal chemoprevention (SMC) campaigns, (2) the contribution of community-based distributors to the management of severe cases of malaria in children under 5\u00a0years, (3) the SMC efficacy, (4) artemisinin-based combination therapy (ACT) tolerance and efficacy according to existing guidelines, and (5) the quality of malaria control at all levels of the health system.This work showed the effectiveness of collaboration between implementers, programmes managers, and researchers in identifying research questions. The responses to these identified research questions of this study may contribute to improving the implementation of malaria control programmes across African countries. More often than not, local social determinants of health are hidden or overlooked by funding agencies, institutional researchers, and health systems, yet they may be slowing down or reducing programme implementation and impact. In addition, many of the physical constraints that impede the regular and effective delivery of health interventions to those who need them are much more pronounced in Low-to-Middle-Income Countries (LMIC) than in high income countries . Hence bIndeed, despite recent trends showing a reduction in malaria mortality rates in Africa generally, and in the region in particular , mortaliThis study reports experiences gained from collaborations between decision-makers and researchers, a part of a project undertaken in the framework of the regional World Bank funded project titled: Malaria and Neglected Tropical Diseases in the Sahel (SM/NTD). The objLocal and primary providers along with malaria programme managers were approached in the 15 countries of the Economic Community of West African States (ECOWAS), including eight French-speaking, five English-speaking and two Portuguese-speaking countries using two approaches, namely: a questionnaire survey and regional validation workshops were held as part of the activities of the SM/NTD project. This study only focuses on malaria.The questionnaire translated into the three official languages of ECOWAS, namely English, French and Portuguese, were sent to the malaria control programmes managers in the last semester of trimester of 2016. The questionnaires were divided into two (2) parts: (i) Bottlenecks in malaria programme implementation (ii) Priority research questions on malaria programme. Each part covered seven thematic areas: governance, human resources, drugs, service provision, use of prevention methods, monitoring and evaluation (M and E), and public support or buy-in. Questionnaires were thereafter sent through electronic messages (Email) to National Malaria Control Programme (NMCP) managers/coordinators of the 15 ECOWAS countries, with instructions on how to fill the questionnaires.Follow up actions were undertaken for two months to obtain a satisfactory response rate. Even though the countries have similarities as well as differences regarding their governance structure, epidemiological trends, and public health research, the authors conducted an initial in-depth analysis country by country. They then split bottlenecks recorded and questions into the seven \u201cECOWAS regional topics of interest\u201d according to the thematic areas mentioned above. This analysis was then presented at the ECOWAS malaria regional workshop.A two-day regional workshop was organized in Bamako by the West African Health Organization (WAHO), the ECOWAS specialized institution dealing with health concerns, such as malaria as well as NTDs programmes in West Africa. Participants included malaria programme managers, NTDs programme managers, Directors of Public Health of the various Ministries, monitoring/evaluation officers, countries project management unit coordinators, technical and financial partners . The results of the questionnaire survey were analysed, presented, and discussed in two plenary and two breakout sessions.The first breakout session on malaria was organized with two groups of 12 people each. The breakout sessions brought together malaria programme coordinators, researchers, partners, and the regional project team. These teams worked to validate the research problems and questions. The two breakout teams were tasked to review, complete the problems, prioritize, and justify the research questions. The two breakout teams reviewed the survey results using individual and average ratings. For the first plenary session, each group was instructed to choose the top 20 research questions. On the second plenary session, the representative of each group shared the top 20 research questions they have selected. The questions selected by the participants clarified some research questions and allowed to finalize list related to malaria management.The second breakout session focused on individual countries\u2019 participants. The participants worked together to select three priority research questions from the list of questions established during the plenary session. Representatives of each country were asked to prioritize the three questions they selected and to address them over a three-year period. Finally, a third plenary session allowed each country\u2019s team to share their key questions to address and prepare a plan for the subsequent years, 2017, 2018 and 2020.The workshop was moderated by a expert in parasitology and malaria research from West Africa and at the end, the moderator reformulated some of the questions and justifications in accordance with the adopted guidelines.Out of the 15 ECOWAS countries, 11 responded to questions related to malaria and Table In all seven thematic areas, there were challenges that limited the effectiveness of programme implementation. In the area of governance, issues of coordination and collaboration with partners in the field came up as well as weaknesses in the managerial capacity at the regional and district levels. The human resources problems identified were mainly related to capacity, competence, motivation of community health workers, weaknesses in research skills and capacity of programme actors. There were also difficulties in the area of management of medicine logistics, from ordering commodities to the distribution to patients, and also difficulties in pharmacovigilance. In service provision thematic area, difficulties of direct observed treatment were pointed out, especially for the second and third day doses of SMC, while for prevention, low uptake of vector control measures, the absence of insecticides for the impregnation of protective materials, and the low use of protective means were the major problems mentioned. In terms of monitoring and evaluation, challenges of access to quality data, especially from the community level, and inadequacy in the dissemination of research results were reported.Finally, in terms of public support, refusal or reluctance to participate in mass drug distribution during SMC campaigns, failure in adopting preventive measures and behaviour were reported by programme managers.Table The first five priority questions were related to (1) compliance with drug doses for the second and third days of SMC campaigns, (2) contribution of community-based distributors to severe malaria cases management in children under 5\u00a0year, (3) SMC efficacy, (4) ACT efficacy and tolerance of ACT under current guidelines, and (5) quality of malaria cases management at all health system levels.The prevention theme was ranked first with five questions, followed by the governance and medicines with four questions, and the monitoring and evaluation (M and E) with three questions. The five prevention questions were related to the effectiveness and non-use of long-lasting insecticidal nets LLIN), the level of use and effectiveness of indoor residual spray (IRS), conducting a study on the effectiveness of mosquito soap, and the possibility of using two insecticides to impregnate nets. Governance issues were related to the best strategy for the implementation of SMC campaigns, quality of malaria case management at all health system levels, the place of information and communication technology in data quality management and the type of collaboration framework between the Ministry of Health and partners. For the medicines theme, the four priority questions focused on the efficacy and tolerance of ACT under current guidelines, the side effects of ACT, the efficacy of traditional medicines and the comparative advantage of the dihydroartemisinin (DHA)-piperazine combination over sulfadoxine\u2013pyrimethamine (SP)\u2009+\u2009amodiaquine (SP-AQ). Regarding M and E, questions related to adherence for the second and third dose during seasonal chemoprevention campaigns, the performance and use of rapid diagnostic tests. In terms of human resources, the two priority issues were related to the contribution of community health workers in severe malaria case management and the supervision of the second and third doses during SMC campaigns. At the service delivery level, both issues were related to the quality and performance of the drug supply and management chains. Finally, in terms of public support, the questions were related to communication channels, media and strategies to ensure behavior change. Table It was noted that the research questions related to factors influencing adherence to second day (day 2) and third day (day 3) doses of SMC were highlighted as first priority by Mali and Niger participants. The same questions were flagged as second priority by Burkina Faso participants. It was followed by questions related to the contribution of community health workers in the supervision of the second and third doses of drug during the SMC campaigns in Burkina and Niger. The final ones were in order of importance, the questions on the most efficient strategy in the implementation of SMC in Burkina Faso, the toxicological effects of administering multiple doses of SP-AQ in children, the impact of communication interventions in 2nd and 3rd days in Mali, and the therapeutic effectiveness of SP-AQ in Niger.This work allowed the identification of key challenges limiting the implementation of NMCP in West Africa. Priority research themes in malaria has helped to highlight similarities between countries regarding malaria control programmes. Most of the bottlenecks highlighted by this work are related to the poor coordination and collaboration with partners, the skills and motivation of community health workers responsible for drug distribution during mass treatment. In addition, the bottlenecks were also due to weaknesses in the supply and distribution chain, poor use of prevention measures, difficulties in accessing quality data, especially at community level, and the population buy-in and acceptance of strategies. The problems that have emerged in malaria control programmes in this work have already been reported by some authors in Africa \u201311. The This work was designed to assess the implementation, operational bottlenecks, and success of public health practice in West Africa. Furthermore, this study evaluated the relationship between programme implementing actors, African researchers, and the constraints they face in their respective countries. Local researchers should work in coordination with programme actors to address local problems. The New Partnership for Africa\u2019s Development (NEPAD)\u2019s Consolidated Plan of Action 2005\u20132014 (CPA) and the Science Technology Innovation Strategy 2024 attempteThe landscape of global health keeps changing because new innovations and new discoveries are being implemented in interventions against emerging diseases (infectious and non-communicable). New discoveries either technically or \u201cprocess, are not easy to incorporate in public health interventions since they require drawing new strategic plans and other logistics. Hassan has repoPlasmodium falciparum carriage rate in the SMC implementing areas; on adverse toxicological effects of multiple administration of SP-AQ, and on potential factors affecting adherence to mass drug administration (MDA) in nomadic population.After the identification of research priority questions, the project funded some research activities taking into account these priorities. For instance, a regional research was commissioned in the three countries related to the factors that influence adherence to day 2 and day 3 doses during SMC. The research started in 2018 and the primary result will be obtained in 2020. The overall results will be validated in the countries and published in 2021. Still at the regional level, a second research was conducted to analyse all communication interventions and impact on malaria programmes. Currently the preliminary results on the mapping of communication interventions are being finalized and the impact study is ongoing. Between 2018 and 2020, a lot quality assurance sampling survey (LQAS) was conducted in Burkina Faso and Mali in order to analyse the performance of the SMC campaign. Further research work is needed to on research questions not addressed in this study. In Mali, three studies were conducted including the prevalence of This study showed the effectiveness of collaboration between policy makers and researchers in identifying and funding research needed to improve malaria control programmes. The research questions identified can be adapted to other ongoing research to improve malaria control in different countries."} +{"text": "The endocannabinoid system (ECS) is a complex signaling system that includes cannabinoid receptors, their endogenous ligands (endocannabinoids), and biosynthetic and hydrolytic enzymes . ECS conThis Special Issue of the International Journal of Molecular Sciences is a collection of eight review articles and five original research articles, and offers an updated overview of current knowledge on ECS in both physiological and pathological conditions. An update on the epigenetics of the ECS has been reported in the review article by the group of Pierantoni, with focus on its emerging role in reproduction and fertility. ECS undergoes epigenetic modulation by life style and environmental factors, with consequences on health and disease. Nevertheless, the modulation of ECS induces epigenetic changes, to different extents, of target genes, with possible trans-generational effects in the off spring through the transmission of deregulated epigenetic marks in the gametes .Cnr1-/- knockout mice, the authors demonstrate the requirement of CB1 activity, in driving the formation of inter-/intra-protamine disulphide bridges, and in histone removal in a mechanism involving the hyper-acetylation of histone H4, once again confirming the need of CB1 activity for the production of high-quality spermatozoa [The activity of cannabinoid receptors, CB1 and CB2, in male germ cell development\u2014from gonocyte up to mature spermatozoa\u2014has been reviewed by Barchi et al.; interestingly, new roles in paternal epigenetic trans-generational inheritance and testis cancer are also discussed . Furtherrmatozoa .Moving toward female reproduction, Cecconi and coworkers report the expression of major endocannabinoid-binding receptors at different stages of mouse oocyte maturation, and investigate the effects of specific receptor antagonists, revealing a new possible role for GPR55 and potentially offering new targets for the therapy of female reproductive alterations . The involvement of CB1 in the hypothalamic control of food intake and reproduction has been investigated by Zuccarini et al., through the pharmacological and genetic manipulation of CB1 in zebrafish. The CB1-dependent effect on the guidance, fasciculation and routing of GnRH3 (Gonadotropin Releasing Hormone 3) and AgRP1 (Agouti-related peptide 1) axons has been demonstrated, suggesting the need of CB1 signaling in the correct development of neuroendocrine function related to food intake and reproduction . In this respect, the gut\u2013brainaxis represents a key regulator of the hypothalamic neuronal networks related to food-sensing and appetite. Therefore, the review article by Forte et al. summarizes the emerging role of an \"expanded ECS\", or endocannabinoidome (eCBome), encompassing endocannabinoid-like mediators in the modulation of the communication between microbiota and gut\u2013brainaxis, with consequences on host metabolism and a critical role in obesity onset .ECS may be a therapeutic target for the treatment of disease, and the modulation of endocannabinoid tone by the fatty acid hydrolyzing enzyme (FAAH) is a key step in ECS signaling. In this respect, the research article by Giacovazzo et al. compares different administration routes to in vivo inhibit FAAH activity in mouse brains. Interestingly, the authors demonstrate the efficacy of intranasal FAAH inhibition, and suggest this delivery model as a suitable alternative to enhance the tone of endocannabinoids within the brain, for the treatment of neurodegenerative disorders and the improvement patients\u2019 compliance .The functional participation of the ECS in neurodegenerative disorders has been analyzed by Bhatia-Dey and Heinbockel, who focused a review article on the endocannabinoid-mediated neuromodulation in the olphactory bulb, a brain region in which neurogenesis continues throughout the life span, suggesting possible therapeutic interventions in decelerating neurodegenerative pathology . -/-Cnr2 mice, suggesting different signaling mechanisms for basal and damage-induced neurogenesis [In spite of the known involvement of CB2 in the neuorogenesis in both neuroinflammatory conditions and in response to pathophysiological stimuli, Mensching et al. demonstrate that stable adult neurogenesis occurs in the hyppocampus of ogenesis .The Interplay between the ECS, epilepsy and cannabinoids has been reviewed by the group of Mitchell. The deep involvement of ECS in neuroinflammation points out the possible use of cannabinoids-based treatments to modulate ECS, as alternatives to more conventional pharmacological therapies, but also underlines the need for further research in the field to sustain the use of therapeutic cannabis .The review article by Argenziano et al. analyzes the role of ECS in the pathogenesis and onset of pediatric inflammatory and immune diseases, like immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel and celiac disease, obesity and fatty liver disease, neuroinflammatory diseases, and type 1 diabetes mellitus .Cannabis sativa, of particular interest for clinical application. In this respect, the review article by Kis et al. summarizes the anticancer effects of CBD in vitro and in vivo, and its main pharmacological and toxicological aspects [As reviewed by Laezza et al., ECS can exert anticancer activity, modulating several signaling pathways involved in cell proliferation, differentiation, migration and angiogenesis , but the aspects . Taken together, this Special Issue provides a very updated overview on ECS activity and modulation in physiological and pathological conditions, through the presentation and integration of data from experimental animal models and clinical observation. The deep involvement of ECS in the control of biological functions is far from fully clarified, but all the submitted manuscripts expand the knowledge in the field of ECS involvement in both health and disease, with a particular attention to the possible therapeutic exploitation. Lastly, the Editor hopes this Special Issue of the International Journal of Molecular Sciences may be useful for basic and clinical scientists working in the field, and deeply thanks all the authors who contributed with excellent works, and the reviewers engaged for the peer-review process."} +{"text": "Military service and exposure to war may influence the development of depression, leading to disparities in the condition among veterans and non-veterans. This study included 10,512 older men from the 1996 to 2014 waves of the Health and Retirement Study (HRS). We estimated Center for Epidemiology Depression (CESD) score trajectories among veterans and non-veterans and veterans of different war cohorts in growth curve models, controlling for early, mid, and late life characteristics. CESD score trajectories were lower among veterans and war veterans than non-veterans and non-war veterans, respectively. The highest levels of depression were among war veterans who served in more than one war. Veterans demonstrated lower levels of depression than non-veterans, calling into question the health advantage of veterans and selection mechanisms into the military and out of HRS. Multiple war veterans showed the highest levels of depression, representing the greatest mental health threat to veterans in the study. Part of a symposium sponsored by the Aging Veterans: Effects of Military Service across the Life Course Interest Group."} +{"text": "The issue of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has created enormous threat to global health. In an effort to contain the spread of COVID-19, a huge amount of disinfectants and antibiotics have been utilized on public health. Accordingly, the concentration of disinfectants and antibiotics is increasing rapidly in various environments, including wastewater, surface waters, soils and sediments. The aims of this study were to analyze the potential ecological environment impacts of disinfectants and antibiotics by summarizing their utilization, environmental occurrence, distribution and toxicity. The paper highlights the promoting effects of disinfectants and antibiotics on antibiotic resistance genes (ARGs) and even antibiotic resistant bacteria (ARB). The scientific evidences indicate that the high concentration and high dose of disinfectants and antibiotics promote the evolution toward antimicrobial resistance through horizontal gene transformation and vertical gene transformation, which threaten human health. Further concerns should be focused more on the enrichment, bioaccumulation and biomagnification of disinfectants, antibiotics, antibiotic resistance genes (ARGs) and even antibiotic resistant bacteria (ARB) in human bodies. As the coronavirus disease 2019 (COVID-19) epidemic worsens, various disinfectants and pharmaceuticals have been actively used to control the spread of the virus. Disinfectants, such as alcohols, chlorine, formaldehyde, glutaraldehyde, ortho-phthalaldehyde, hydrogen peroxide, iodophors, peracetic acid, phenolics, and quaternary ammonium compounds were recommended to use alone or in combinations on public health by authorities. The Chinese Center for Disease Control and Prevention (China CDC), United States Environmental Protection Agency (US EPA) and World Health Organization (WHO) successively released the guidance for disinfectant utilization to against the virus, while the lack of necessary training program for public could raise the adverse effects of disinfectant on human health . TherefoIn the times of COVID-19 panic, disinfectants and antibiotics were overused for the coronavirus disease control and treatment, since the effective treatment measures and medications are not yet determined. Until 2020 March, China has dispensed at least 2000 tons of disinfectants in the city of Wuhan alone . Bacteria, only carrying antibiotic resistance genes (ARGs), can survive and persist in these contaminated environments. A disinfection by-products study reported that disinfection by-products can select strain with high-level resistance via broadly conserved cellular functions and pathways at the minimal inhibitory concentrations .In fact, ARGs and antibiotic resistant bacteria (ARB) can be target selected in disinfectants and antibiotics contaminated environments.. The ARGBesides HGT, ARGs and ARB can also be transferred from environments or microorganisms to higher trophic levels through drinking water, food and respiration . Human hCOVID-19 has threatened the global health remarkably. High concentration and high dose of disinfectants and antibiotics used during the COVID-19 pandemic, which entered into environments, are definitely accelerating the target selection of AMR in environments . HGT amo"} +{"text": "Jiangsu was one of the first four pilot provinces to engage in comprehensive health care reform in China, which has been on-going for the past 5\u2009years. This study aims to evaluate the equity, efficiency and productivity of health care resource allocation in Jiangsu Province using the most recent data, analyse the causes of deficiencies, and discuss measures to solve these problems.Data were extracted from the Jiangsu Health/Family Planning Statistical Yearbook (2015\u20132019) and Jiangsu Statistical Yearbook (2015\u20132019). The Gini coefficient (G), Theil index (T) and health resource density index (HRDI) were chosen to study the fairness of health resource allocation in Jiangsu Province. Data envelopment analysis (DEA) and the Malmquist productivity index (MPI) were used to analyse the efficiency and productivity of this allocation.From 2014 to 2018, the total amount of health resources in Jiangsu Province increased. The G of primary resource allocation by population remained below 0.15, and that by geographical area was between 0.14 and 0.28; additionally, the G of health financial resources was below 0.26, and that by geographical area was above 0.39. T was consistent with the results for G and Lorenz curves. The HRDI shows that the allocated amounts of health care resources were the highest in southern Jiangsu, except for the number of health institutions. The average value of TE was above 0.93, and the DEA results were invalid for only two cities. From 2014 to 2018, the mean TFPC in Jiangsu was less than 1, and the values exceeded 1 for only five cities.The equity of basic medical resources was better than that of financial resources, and the equity of geographical allocation was better than that of population allocation. The overall efficiency of health care resource allocation was high; however, the total factor productivity of the whole province has declined due to technological regression. Jiangsu Province needs to further optimize the allocation and increase the utilization efficiency of health care resources.The online version contains supplementary material available at 10.1186/s12939-020-01320-2. Health care resources are the basis for the development of health services, and the rationality of their allocation not only affects residents\u2019 health level but also plays an important role in the sustainable development of medical and health services , 2. TherIn recent years, due to economic development, an ageing population, the prevalence of chronic diseases and the improvement in health concepts, higher standards have been established for the allocation of health resources. The equity and efficiency of health resource allocation and health service utilization are attracting increasing attention in China , 7. To eJiangsu was one of the first four pilot provinces to engage in comprehensive health care reform in China. Jiangsu is located in the eastern coastal area of China and has 13 prefecture-level cities, such as Nanjing, Zhenjiang, Suzhou and Huaian . JiangsuJiangsu Province has implemented comprehensive health care reform for the past 5\u2009years, and the year 2020 is also the last year of the Healthy China 2020 strategy . This stData were extracted from the Jiangsu Health/Family Planning Statistical Yearbook (2015\u20132019) and Jiangsu Statistical Yearbook (2015\u20132019), which cover 13 cities in Jiangsu Province. The series of longitudinal data were used to analyse the equity and efficiency trends in Jiangsu from 2014 to 2018.On the basis of the economic development level, geographical position and the Jiangsu Statistical Yearbook, the 13 cities in Jiangsu Province were divided into three groups: the most economically developed southern zone , the moderately developed middle zone and the less economically active northern zone . Health care institutions included hospitals, primary health institutions, professional public health institutions and other health institutions.Considering representation, stability, availability and independence, capital, labour and financial investment are deemed to be important input variables in the delivery of health services. The number of institutions and beds represents the capital, the number of health workers represents labour, and the government financial subsidy and total expenditure represent financial investment. Health workers include physicians, registered nurses, assistant physicians, medical personnel, other technical personnel and health administrative staff. They were chosen as input indicators to measure equity. The annual numbers of outpatient visits, the hospitalization rate and general income represent output indicators.The Gini coefficient is the optimal tool to assess the equity of health resource allocation in terms of demographic and geographical aspects . The GinXi: cumulative percentage of health resources in the ith city of Jiangsu Province after ranking according to the per capita or regional average share of health resources.Yi: cumulative percentage of population or geography in the ith city of Jiangsu Province after ranking according to the per capita or regional average share of health resources.k: total number of cities.G: value of the Gini coefficient.The Theil index is used to analyse the inequity of resource allocation. The advantage of the Theil index is that it can measure the contributions of intra- and inter-regional differences to total inequity . FormulaPi: percentage of population or geography of each city in Jiangsu Province.Ei: percentage of health resources of each city in Jiangsu Province.T: value of the total Theil index.The total Theil index can be decomposed into the intra-Theil index and inter-Theil index . FormulaTintra: value of the intra-Theil index. In this study, it represents the intra-different distribution of health resources in southern, central and northern areas of Jiangsu Province.Tinter: value of the inter-Theil index. In this study, it represents the inter-different allocation of health resources among southern, central and northern areas of Jiangsu Province.Pg: proportion of population or geography of three regions for the overall number of Jiangsu Province.Eg: proportion of health resources of three regions for the overall number of Jiangsu Province.Tg: value of the Theil index of three regions .Tintra and Tinter can be calculated by dividing the total Theil index [The contribution rates of il index .The HRDI displays the influence of population and geographical factors on the agglomeration of health resources while avoiding bias caused by a single population or geographical aspect. Formula is used HRi: health resource quantity of the ith region.Ai: geography of the ith region.Pi: population of the ith region.HRDI: value of the Health Resource Density Index.DEA is a nonparametric method that evaluates the performance of mathematical planning models, including the relative efficiency of decision-making units (DMUs), using multiple input and output indicators , 19. TheIn the BCC model, technical efficiency (TE) can be disassembled into pure technical efficiency (PTE) and scale efficiency (SE). Formula is used TE expresses the production efficiency of DMU, which is based on input resource. PTE reflects the advance in productivity resulting from the efforts of managers and workers and the effective combination of production factors. SE indicates different levels of changes in DMU\u2019s economies of scale . Values Whereas DEA measures relative efficiency for a period of time, TFPC measures dynamic changes in productivity from time t to time t\u2009+\u20091 . TFPC caValues of TFPC, TEC, TC, PTEC and SEC above 1 indicate improvement. The DEA and TFPC were calculated using DEAP V.2.1.From 2014 to 2018, the total amount of primary health resources increased in Jiangsu Province. In a general sense, the primary resources include capital and labour . In termFor financial resources, we counted government financial subsidies and total expenditures. From 2014 to 2018, government financial subsidies continued to grow to 37.3 billion yuan , South K , South Although we use a variety of methods to evaluate the equity and efficiency of health care resource allocation in Jiangsu Province, there are still some limitations to this study. First, although the selection of indicators is commonly used in similar research and indicators for health workers are included, we did not further subdivide these workers into doctors, nurses and other personnel. Second, this study mainly analyses the fairness of health care resource allocation from the perspective of population and geography, without considering the actual health status and health service needs of different regions. Third, due to the limitations of the basic DEA method, there are no bias adjustments for efficiency and productivity scores.In the past 5 years, the total amount of health resources in Jiangsu Province has increased steadily, and the overall equity of health care resource allocation has been good. The equity of basic medical resources was better than that of financial resources, and the equity of geographical allocation was better than that of population allocation. However, there were great differences among regions: health care resources in southern Jiangsu were plentiful, while those in central and northern Jiangsu were relatively lacking. The overall efficiency of health care resource allocation was high, but some cities faced low efficiency. In addition, the total factor productivity of the whole province has declined. Therefore, to ensure the sustainable development of medical services, the government should further optimize the allocation of health resources, comprehensively consider geographical and demographic factors, and strive to narrow the gap in medical resources in different regions. In addition, to increase the utilization efficiency of limited medical resources, technical efficiency needs to be improved by developing the service ability of basic medical institutions, strengthening cooperation among medical institutions at all levels, and improving training and incentive mechanisms for doctors.Additional file 1:Fig. S1.The Lorenz curves of health care resources in Jiangsu Province from 2015 to 2017. A-F show the Lorenz curves of primary resources allocated by geographical area (A-C) and population (D-F). G-L show the Lorenz curves of financial resources allocated by geographical area (G-I) and population (J-L). A, D, G, J are in 2015; B, E, H, K are in 2016; C, F, I, L are in 2017."} +{"text": "Pearl River Declaration, emanated from the symposium, called for establishing a One Health Cooperation Network in the Southeast Asia\u2013Pacific region with a vision to strengthen regional health security through sharing each other\u2019s knowledge and experience, and making investments in workforce development, scientific innovations such as vaccine research and development, sharing epidemic intelligence, risk identification, risk communication and appropriate response measures against emerging health threats.The Second International Symposium on One Health Research (ISOHR) was held in Guangzhou city, China on 23\u201324 November 2019. A transdisciplinary collaborative approach, One Health (OH), was the central theme of the symposium which brought together more than 260 experts, scholars and emerging researchers from human health, veterinary health, food safety, environmental health and related disciplines and sectors. More than 50 organizations including World Health Organization, Centers for Disease Control (USA), and Queensland Government participated in the symposium. Scholars, experts and emerging researchers, policy-makers and practitioners in their respective fields delivered over 50 presentations at the symposium, highlighting the collective vulnerability to some of the emerging health challenges the region was combating. These included emerging infectious diseases, antimicrobial resistance, climate change, food safety and the growing burden of non-communicable diseases. The Emerging infectious diseases, antimicrobial resistance, climate change, food safety and security, and the growing burden of non-communicable diseases were identified as some of the most pressing challenges to global health security at the Second International Symposium on One Health Research (ISOHR) held in Guangzhou, China on 23\u201324 November 2019. The symposium was jointly organized by Sun Yat-sen University (China), Griffith University , South China Agricultural University (China) and Guangzhou Medical University (China). A transdisciplinary collaborative approach, known as One Health, was identified as a key opportunity to promote human, animal and environmental health within and between countries around the world [The ISOHR brought together more than 260 experts, scholars and emerging researchers from China and around the world in as diverse areas as public health, clinical medicine, veterinary medicine, laboratory science, food safety, environmental health, agricultural science, military medicine, health systems and policies. More than 50 organizations including multiple Chinese Government departments and research institutions, and representatives from World Health Organization, Centers for Disease Control (USA), and Queensland Government participated in the symposium.Over the past two centuries the world has witnessed spectacular innovations and successes in public health and medical science. The most notable among those were the invention of vaccines (1796\u2009AD) and antibiotics 1928), the eradication of small pox (1979) and the introduction of a simple, low-cost oral rehydration therapy for treatment of dehydration caused by diarrhea. Collectively, these innovations have saved tens of millions of lives 8, the er. These aInternational Health Regulations 2005 [The novelty of the virus, the nature and speed of the interspecies and cross-border transmission of COVID-19 prompted World Health Organization to declare it a \u2018Public health emergency of international concern\u2019 , whereasons 2005 .The ISOHR observed with a great concern that over the past five decades, the world has witnessed the emergence of about 40 new diseases including Legionnaires\u2019 disease, HIV/AIDS, hepatitis C, mad-cow disease, SARS, Middle East Respiratory Syndrome (MERS), Nipah and Ebola virus diseases. Twenty of these diseases were found in China alone . Many ofThe ISOHR acknowledged the role of economic globalization in the twenty-first century and the associated growth in tourism and trade. These and other developments have significantly increased the mobility of populations and trade in goods worldwide and increased the risk of infectious disease spread across regions and countries. In some areas this has resulted in a continuing epidemic and pandemic threat. The impact of global climate change, agricultural intensification, rapid economic growth combined with population growth and urbanization, further complicate public health challenges globally and more specifically in LMICs . Today, In the recent past, the region has experienced some of the deadliest epidemics resulting in formidable losses not only to health but also impacting heavily on their economies with substantial sociological and political repercussions . For exaCountries increasingly recognize the value of working collaboratively and sharing knowledge, expertise and resources for the protection of their own country and to address the collective vulnerability in today\u2019s globalized world. This recognition is evidenced by the Australian Government\u2019s regional health security initiative known as \u2018Indo-Pacific Centre for Health Security\u2019 established in 2017 . The iniThe ISOHR noted with concern that the growing antimicrobial resistance (AMR) was a significant threat to the core of modern medicine as it seriously hampers the efficacy and sustainability of an effective public health response to infectious diseases. The complex root of the problem and the process of widespread, systematic misuse of antibiotics in human and animal medicine, and in food production, demands systematic and coordinated action involving multiple sectors, and disciplines beyond health . The unrInfectious diseases and AMR are not the only causes of concern for the global health security. Similarly, the scope of OH is not limited to infectious disease only. The growing burden of chronic disease, the double burden of malnutrition which is defined as the coexistence of overnutrition (overweight and obesity) and undernutrition (stunting and wasting) , climateInfectious disease transmission occurs at the human-animal-environment interface. The magnitude of the impact of disease and its transmission is influenced by many factors including human behavior, and society, the environment, and the culture of the community. Thus, a broad-based, holistic approach, known as One Health (OH), has received prominence in recent years. Countries increasingly recognize the collective vulnerability to emerging health security threats such as epidemics and pandemics and seek to forge joint effort for mutual benefit. One example of such collaboration effort is the Australian Government\u2019s regional health security initiative, the \u2018Indo-Pacific Centre for Health Security\u2019. EstablisLooking through the lens of etiology, infectious diseases are not only caused by bacteria, viruses and parasites. They are also influenced or shaped by social, economic, political, legal and cultural conditions. Thus, the breadth of emerging health issues and the application of OH to address those will go much farther than the traditional health outlook.In line with its fast-paced economic development, China remains focused on combating emerging health threats including emerging infectious diseases such as SARS and the coronavirus disease (COVID-19), and controlling the spread of antimicrobial resistance , 29. HavIn line with this acknowledgement, the Pearl River Declaration Table 11 called The process of initiating such a regional collaboration by Griffith University, a co-convener of the ISOHR, began as early as 2016 with the establishment of the Global Research Consortium on Risk Communication, Emergency Management and Adaptation to Climate Change for Health (REACCH). This was undertaken in partnership with 15 institutions including government departments across the region. REACCH members have contributed to joint research, policy advocacy and capacity-building to improve health systems and address collective vulnerability to emerging health threats.(i.)The One Health Research Network, established in 2016\u2013\u2013a collaboration with One Health networks in China and Indonesia, focusing on diseases that occurs at human-animal-environment interface.(ii.)The country programs network for Bangladesh, China, Indonesia, Mongolia, the Philippines and Vietnam, consisting of many institutional members from these countries guided by a Memorandum of Understanding of each with Griffith University, having been gradually expanded since 2006. These collaborations focus on health system policies and operational capacity building in the region, as well as emerging health challenges including climate change adaptation, disaster risk reduction, zoonotic and vector-borne disease control.The establishment of a cross-disciplinary Research and Policy Advocacy Hub for Global Health Security at Griffith University, Australia in 2019 further supports this overall regional objective. The Hub hosts two broad networks:Among many tangible outcomes achieved through the establishment and function of these networks has been the delivery of over 10 public health leadership programs that have successfully nurtured more than 120 Fellows across the region. Many of these Fellows have gone on to leadership of the COVID-19 pandemic response in their respective countries over recent months .Addressing emerging health challenges is the collective responsibility of nations as they are collectively vulnerable in the globalized world. If health is for all, as it is often heard being said, then all should be working for health. The resounding message of the Pearl River Declaration was the need for greater commitment and collaboration among nations across the mountains and seas under the umbrella of OH for a future healthy global community. As important regional development partners in health in the Indo-Pacific region, countries such as Australia, China, Thailand, Singapore and international bodies such as Asian Development Bank and WHO can play a pivotal role in country-capacity building through sharing knowledge and experience, as well as making investments in workforce development, scientific innovations such as vaccine research and development. These can be better achieved through establishing a regional One Health Cooperation Network."} +{"text": "Annular epidermolytic ichthyosis is a rare subtype of epidermolytic ichthyosis that is characterized by erythematous, polycyclic, and migratory scaly plaques accompanied by palmoplantar keratoderma. This report presents the case of an 8-year-old girl who developed migratory, erythematous, scaly plaques associated with palmoplantar keratoderma. The initial hypothesis was erythrokeratodermia variabilis et progressiva; however, the finding of epidermolytic hyperkeratosis in histopathological examination led to the diagnosis of annular epidermolytic ichthyosis. Annular epidermolytic ichthyosis (AEI) is a rare phenotypic variant of epidermolytic ichthyosis (EI), also known as congenital bullous ichthyosiform erythroderma, an autosomal dominant disorder characterized by extensive erythroderma and formation of blisters in early life.4An 8-year-old female patient was attended at the pediatric dermatology outpatient clinic of the Hospital Santa Casa of Porto Alegre with a report of diffuse dermatosis that began in the first months of life. Upon examination, the patient presented erythematous, scaly, hyperkeratotic plaques with prominent borders, affecting the mesogastrium, cubital fossae, popliteal fossae, and inguinal and cervical regions, as well as palmoplantar hyperkeratosis and yellowish hyperkeratotic plaques on the scalp and nasal introitus . No assoThe patient denied any symptoms and there was no background of family history of similar cases and consanguinity. After one month, she was reassessed and the appearance of the plaques changed, increasing the extension of the affected areas; however, the polycyclic aspect disappeared B.Skin biopsy in the extensor portion of the forearm showed acanthosis, papillomatosis, and hyperkeratosis with marked epidermolysis in the granular layer .Figure 4AEI was first described in 1992 by Sahn et al.10In the histopathology, the hyperkeratotic lesions of the AEI revealed hyperkeratosis, acanthosis, and a thickened granular layer. Keratinocytes in the spinous layers and superior granulosa of the epidermis demonstrated cytoplasmic vacuolization and prominent keratohyaline granules.5The main differential diagnosis of annular epidermolytic ichthyosis is with erythrokeratodermia variabilis et progressiva (EKVP),Treatment options in the small number of patients reported included topical medications such as retinoids, topical corticosteroids, propylene glycol, calcipotriene, and keratolytic agents, and little response was observed.None declared.Emanuella Stella Mikilita: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript.Irina Paipilla Hernandez: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature.Ana Let\u00edcia Boff: Drafting and editing of the manuscript; collection, analysis, and interpretation of data.Ana Elisa Kiszewski: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "This article describes priority areas for research on the impact of the Covid-19 pandemic on older adults that have been identified by the CIHR Institute of Aging (CIHR-IA). The process used by CIHR-IA consists of several iterative phases and thus far has resulted in identification of three key areas for Covid-19 research needs and four cross-cutting thematic areas. The key research priority areas are as follows: response of older adults to disease, vaccination, and therapeutics; mental health and isolation; and supportive care environments. The four cross-cutting themes are equity, diversity, and inclusion (EDI); ethical/moral considerations; evidence-informed practices; and digital health technologies. The priorities outlined in this article will inform CIHR-IA\u2019s responses to Covid-19 research needs. On March 11, 2020, the World Health Organization announced that Covid-19 had reached pandemic status.The mission of the Canadian Institutes of Health Research Institute of Aging (CIHR-IA) is to support research, to promote healthy aging, and to address the causes, prevention, screening, diagnosis, treatment, support systems, and palliation for the complex health challenges that can be present in older individuals.CIHR-IA focuses on the entire trajectory of life while specifically addressing the health challenges of older individuals and is a national leader in addressing health research priorities related to aging. Initiatives led by CIHR-IA not only link and support researchers across the country, but also bring together a broad group of stakeholders, including different levels of government, practitioners, health charities, voluntary health organizations, and older adults themselves. At the start of the Covid-19 crisis, CIHR-IA mobilized quickly to identify research priority areas related to this pandemic and its dramatic effects on older adults. The goal of this article is to describe the approach implemented by CIHR-IA to rapidly understand Covid-19 research needs for older adults in Canada. These priorities will be used to shape future actions of CIHR-IA within the context of Covid-19.The process initiated by CIHR-IA consists of a number of actions and consultations as illustrated in In early February 2020, CIHR launched the Canadian 2019 Novel Coronavirus (Covid-19) Rapid Research Funding Opportunity. A total of 100 grants were funded in this competition for a Government of Canada investment of $55.3 million, with the primary focus on medical countermeasures research and social and policy countermeasures research. At this early stage in the identification and investigation of the health impacts of Covid-19, older adults had not yet been recognized as an especially vulnerable population. Thus, no funded projects focused on Covid-19 consequences on the health, wellness, and welfare of older adults. Given this outcome and the rapidly evolving situation related to Covid-19 and older adults, CIHR-IA mobilized to identify research priorities to respond to the needs of the aging population in preparation for the Institute\u2019s participation in funding opportunities coming forward from CIHR and partners.With review of the available published literature and emerging data, CIHR-IA identified initial areas of research need related to Covid-19\u2019s impact on older adults. This was followed by the initiation of a fast-track process to engage stakeholders and gain insight into the impact and implications of Covid-19 on research in aging in Canada. In April 2020, CIHR-IA sent a survey to the more than 4,000 mailing list subscribers; over 600 responses were received from researchers, trainees, decision-makers, health care administrators, public servants, health care providers, older adults, and caregivers. The survey comprised eight questions designed to obtain both quantitative and qualitative responses. Qualitative responses were analysed using a thematic approach and classified by emerging themes. In early June, CIHR-IA engaged in targeted consultations with key stakeholders, including the Institute of Aging Advisory Board members and the directors of the 35 Canadian Research Centres on Aging. Information from these consultations was collated with data obtained from the survey, resulting in the identification of several key research priorities.The CIHR-IA priority identification process resulted in three key areas and four cross-cutting themes for research on the impact of Covid-19 on older adults and aging, as illustrated in Aging is a multifaceted process involving numerous cellular and molecular mechanisms in different organ systems. This can include functional and structural alterations in the immune system that can manifest as a decreased ability to fight infection and constitutive low-grade inflammation (inflammaging) homes.Equity, diversity, and inclusion (EDI)CIHR has implemented a range of strategies and solutions to foster equity, diversity, and inclusion in the research ecosystem.Ethical/moral dilemmas around end-of-life care in pandemic situations or emergenciesEthical and moral considerations in research on older adults are critical within the Covid-19 crisis. Research related to illness, resource rationing, palliative care, and isolation are of critical importance.Trials informing best practices for care of older adults with covid-19 and translation and implementation of knowledge for best practices in emergency preparednessCIHR-IA supports the inclusion of older adults in trials that inform best practices that involve Covid-19 care. Historically, older adults have been omitted from trials that will impact their own care.Digital health technologies supporting health services and care delivery, including drug discovery and vaccine production, and monitoring and social interventionsCIHR-IA is a co-lead of the CIHR eHealth Innovations initiative. This initiative supports exceptional national and international digital health research to develop solutions to maintain and improve the lives of older adults. Research that brings together a diversity of stakeholders will enable enhanced collaboration through the entire health research continuum from basic research to public health.Four important cross-cutting themes are also identified that intersect with the aforementioned three key research areas.Soon after the start of the Covid-19 pandemic, it became apparent that older adults were the most at-risk group to develop complex symptoms and had the greatest risk of mortality. To advance our mandate to improve the health and lives of older adults, CIHR-IA reacted rapidly, including by consulting stakeholders and experts, to identify priority research needs related to older adults and Covid-19. The key research areas laid out in this article, ranging from the response of older adults to disease, vaccination, therapeutics, and clinical trials, to mental health and supportive care environments, will continue to inform the responses made by CIHR-IA over the longer term.In parallel with the consultation process and identification of priority research needs, CIHR-IA rapidly mobilized to partner on two important CIHR funding opportunities; Covid-19 May 2020 Rapid Research Funding Opportunity and the Covid-19 and Mental Health (CMH) Initiative, as well as a funding opportunity initiated by the Canadian Frailty Network (CFN) to fund research projects focused on the interaction between frailty and Covid-19 in older adults. Research carried out in these three programs has the potential to begin to address the priority needs in each of the key areas identified. CIHR-IA will continue to seek opportunities to develop and partner on research programs that will address the needs of older adults in this area.The four cross-cutting themes identified through the consultation process pinpoint crucial elements to be included in research on the impact of Covid-19 on older adults. As with all health research, considerations related to equity, diversity, and inclusion of under-represented populations must be integrated into the research plan and, in particular, older adults must be engaged meaningfully in all aspects of the research. With regard to the specific situation of older adults during the Covid-19 pandemic, considerations related to mental health issues and ethical/moral dilemmas around end-of-life care in a pandemic or emergency situation should be carefully integrated into the research. This is an opportunity to rethink the status and role of older adults in our society and to specifically address the impact and influence of ageism in decision-making and the delivery of care. Research leading to public policies that reduce social exclusion of seniors and fight ageism and stigma associated with end of life, frailty, and vulnerability, is needed now more than ever. The inclusion of older adults in trials to inform best practices for Covid-19 care is of the utmost importance. At this time of evolving tools and techniques, digital health research should be harnessed to bring solutions to maintain and improve the lives of older adults.CIHR-IA seeks to ensure that research needs on aging in Canada are met and so is committed to fostering research programs to find approaches to support the health and wellness of older adults during the Covid-19 pandemic and in the post-pandemic recovery period."} +{"text": "The burden of sickle cell disease (SCD) is greatest among African nations. Effective scalability of evidence-based interventions screening) is urgently needed particularly in these settings for disease management. However, Africa is constrained by limited resources and the lack of capacity to conduct implementation science research for proper understanding of context, and assessment of barriers and facilitators to the uptake and scalability of evidence-based interventions (EBI) for SCD management.We outline implementation science approaches to embed EBI for SCD within the African context and highlight key implementation research programs for SCD management. Building implementation research capacity will meet the major need of developing effective life-long and accessible locally-tailored interventions for patients with SCD in Africa.This commentary communicates the importance of the application of implementation science methodology to scale-up evidence-based interventions for the management of SCD in order to reduce pain, prevent other morbidities and premature death experienced by people with SCD in Africa, and improve their overall quality of life. These studies were conducted exclusively among pediatric and adults populations in clinical settings in Nigeria (n=2), and Jamaica (n=1). Findings suggest that adoption is low, as observed through reported provider practices and patient adherence, in part shaped by misinformation and fear of side effects among patients, provider beliefs regarding affordability and organizational challenges with procuring the medicine [Effective scalability of health interventions is urgently needed particularly in low-and middle- income countries (LMICs), considering the constraints these countries bear, and the lack of capacity to conduct implementation science research. For Africa, sickle cell disease (SCD), the inherited blood disease characterized by anemia, severe pain and other vasoocclusive complications, and early mortality, has significant financial, social, and psychosocial impacts and burdens individuals, families, and health systems. Currently it is projected that over 300,000 individuals are born annually with SCD in Africa , 2. Compmedicine . This coacceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability [PARIHS , etc.) [Implementation science, defined as the scientific study of methods to promote the systematic uptake of research findings and other evidence-based practice into routine practice guided bnability are not ), etc.) , 14 and ), etc.) , 16, to ), etc.) , 18, andWhat is currently lacking within Africa is a comprehensive multicomponent implementation strategy that explores for example, the reach, uptake, and long-term sustainability of EBIs for SCD. This strategy, would ideally incorporate patient /provider/ community/ policy engagement for the EBIs needed to manage SCD exist. The American Society of Hematology Sickle Cell Disease Guidelines provide SCD management recommendations including broad pain management approaches, pharmacological and nonpharmacological interventions and analgesic delivery blood trThis commentary highlights the need for EBIs for SCD management across Africa. It also outlines key implementation research programs that should employ implementation science strategies and capacity building activities for SCD management. We note the success of EBIs in high-income countries that have reduced childhood SCD-related deaths but yet resource-constrained settings, including Africa lack access to EBIs. We acknowledge the critical importance of investigators implementing clinical trials in Africa for SCD management to plan for sustainability at the onset and throughout the implementation process, considering the tremendous amount of resources required to implement these trials. We, therefore advocate for a comprehensive multicomponent implementation strategy with strong patient and community stakeholder engagement, and the need to build capacity at the provider and health systems level to conduct implementation science research for proper understanding of context, and assessment of barriers and facilitators to the uptake, sustainability, and scalability of EBIs for SCD management within the African context."} +{"text": "Although significant progress has been made in understanding mental health issues, racial/ethnic minorities are disadvantaged in terms of knowledge, attitude/stigma toward mental illness, and access to treatment. Older Koreans and Korean Americans are high-risk groups with great prevalence of stigma and limited access to mental services. The two groups share similarities as well as differences. For example, Older Korean Americans, a first-generation immigrant group, tend to share traditional values and beliefs with older Koreans. However, differences in social and cultural contexts, availability of social networks and resources, and access to health care systems present unique challenges and strategies. The purpose of this symposium is to enhance the understanding of critical issues in mental health among older Koreans and Korean Americans and identify challenges and strategies to promote mental health and well-being. Five studies conducted in Korea and the US will explore a variety of personal, social, and cultural factors related with mental health, based on quantitative and qualitative approaches. The diverse topics cover the mediating role of self-esteem in the relationship of stigma to emotional well-being, the effect of stress and coping on well-being, loneliness and negative family interactions, the relationship of life stressors and social capital on mental distress among older Korean Americans compared with other older Asian Americans, and community leaders\u2019 attitude toward depression. The issues of vulnerabilities and resources will be discussed from the cultural perspectives as well as implications for future research and practice."} +{"text": "P. purpureum because of higher adherence between the particles and mucous covering of the algae. Silica NPs caused significant inhibition of microalgae growth-rate predominantly produced by mechanical influence.Nanoparticles (NPs) have various applications in medicine, cosmetics, optics, catalysis, environmental purification, and other areas nowadays. With an increasing annual production of NPs, the risks of their harmful influence to the environment and human health is rising. Currently, our knowledge about the mechanisms of interaction between NPs and living organisms is limited. Additionally, poor understanding of how physical and chemical characteristic and different conditions influence the toxicity of NPs restrict our attempts to develop the standards and regulations which might allow us to maintain safe living conditions. The marine species and their habitat environment are under continuous stress due to anthropogenic activities which result in the appearance of NPs in the aquatic environment. Our study aimed to evaluate and compare biochemical effects caused by the influence of different types of carbon nanotubes, carbon nanofibers, and silica nanotubes on four marine microalgae species. We evaluated the changes in growth-rate, esterase activity, membrane polarization, and size changes of microalgae cells using flow cytometry method. Our results demonstrated that toxic effects caused by the carbon nanotubes strongly correlated with the content of heavy metal impurities in the NPs. More hydrophobic carbon NPs with less ordered structure had a higher impact on the red microalgae The growing industry of nanotechnology inevitably results in an increase of risks associated with the nanomaterials (NMs) and nanoparticles (NPs) to affect living organisms including humans. Carbon- and silica-based NPs could be highlighted among the variety of engineered NPs ,2. Due tThe consumer products, large-scale manufacturers producing NMs, synthesizing, and research laboratories could be highlighted among the main sources leading to the release of NPs in the environment ,27. DespThe difficulty of risk assessment in nanotoxicology is complicated by the variety of factors that could significantly change the properties and, therefore, the toxicity of NPs. Moreover, much uncertainty still exists about the relation between different parameters such as size, form, surface area, zeta potential of NPs, protein corona formation, and transformation of NPs inside of organisms and in the environment or combinations of these parameters and toxic properties of NPs ,33,34,35Attheya ussuriensis (Bacillariophyceae), Chaetoceros muelleri (Bacillariophyceae), Heterosigma akashiwo (Raphidophyceae), and Porphyridium purpureum (Rhodophyceae).The aim of this study was to evaluate and compare the toxic level and biochemical effects caused by the influence of different types of carbon nanotubes, carbon nanofibers, and silica nanotubes on four marine microalgae species, namely In this research, we used two types of multiwalled carbon nanotubes , two typHeterosigma akashiwo [Carbon nanotubes and nanofibers were synthesized and characterized in the Boreskov Institute of Catalysis . The strakashiwo .Silicon nanotubes were kindly provided by the Department of Chemistry, Inha University Republic of Korea . The samCharacteristics of NPs used in this research are represented in Marine biobank of the National Scientific Center of Marine Biology, Far Eastern Branch of the Russian Academy of Sciences (NSCMB FEB RAS). The toxicity bioassay of NPs was carried out on four marine microalgae: two types of diatom species Attheya ussuriensis [Chaetoceros muelleri [Heterosigma akashiwo [Porphyridium purpureum [Microalgal cultures were provided by The Resource Collection uriensis and Chaemuelleri , a raphiakashiwo , and a rurpureum . Culturiurpureum with minurpureum ,59.The microalgae species were selected based on its abundance among the microalgae of the Sea of Japan , and itsThe samples of NPs were added to filtered seawater to obtain the working suspensions with a concentration of 1000 mg/L. Before each series of bioassays, the working suspensions of NPs were sonicated with ultrasound homogenizer Bandelin Sonopuls GM 3100 using maximal intensity for 30 min.The exposition of microalgae cells to the suspensions of NPs was carried out in 24-well plates. Each well was filled with 2 mL of microalgae cell aliquot and the corresponding volume of the working suspension to obtain the final concentrations 1, 10, and 100 mg/L. The filtered seawater without NPs was added to the control group. The exposure of each used concentration and control group was performed in four biological replicates.6) [Microalgae cell counting and registration of morphological and biochemical changes during the experiment were carried out with flow cytometer CytoFLEX with the software package CytExpert v.2.0. The changes of microalgae cells after exposure to NPs were evaluated using specific fluorescent dyes. Microalgae growth-rate inhibition was determined by staining with propidium iodide (PI) according to the standard bioassay protocol . Esteras6) ,68. To dPrior to the assessment of growth-inhibition, esterase activity, and membrane potential of each microalgae species, we made a series of preliminary measurements to determine the optimal concentration of fluorescent dyes and the optimal duration of staining as described in our previous report . The reg50) are one of the most common values used for evaluation cytotoxic effects in macroalgae bioassay [Growth-rate inhibition and changes in the size of microalgae cells should be estimated as a benchmark of direct cytotoxic effects or as an indicator of mortality. The 96\u2009h and 7 days half maximal effective concentration .p \u2264 0.05 was considered statistically significant.Statistical analyses were performed using the software package GraphPad Prism 7.04 . The one-way ANOVA test was used for analysis. A value of 50 concentrations of microalgae growth-rate, FDA fluorescence intensity (esterase activity), and DiOC6 fluorescence intensity compared to control. The calculated mean EC50 concentrations and 95% confidence limits are given in For all the samples of NPs, we calculated ECFor visualization of calculated data and analC. muelleri and P. purpureum.Silica nanotubes SNT-1 and SNT-2 demonstrated the most pronounced influence on the microalgae growth rate. The level of toxicity increased for all microalgae species after seven days of exposure except for the samples SNT-1 and SNT-2 after 96 h of the treatment affected growth-rate only for A. ussuriensis, C. muelleri, and H. akashiwo both after 96 h (acute toxicity) and seven days (chronic toxicity) of the treatment. Carbon nanofibers CNF-1 and CNF-2 also did not reveal any significant influence on the growth rate of these three species in acute toxicity assessment but chronic toxicity and growth-rate inhibition was detected for A. ussuriensis and H. akashiwo. Moreover, all the carbon NPs caused significant inhibition of esterase activity and depolarization of membranes for A. ussuriensis, H. akashiwo, and C. muelleri. However, the nanofiber sample CNF-2 did not affect the esterase activity of diatomic algae A. ussuriensis and stimulated esterase activity of diatomic algae C. muelleri.Carbon nanotubes CNT-1 and CNT-2 had almost no influence on the growth rate of P. purpureum significantly differed from three other microalgae species. P. purpureum was the only species responded by growth-rate inhibition to the influence of carbon NPs. At the same time, the red algae had the lowest changes in esterase activity and membrane potential.The toxicological profile of the red algae The data of flow cytometry analysis indicated the changes in the size of microalgae cells after the treatment of NPs as demonstrated in A. ussuriensis after the treatment with the samples CNT-1 and CNT-2 at the concentration of 100 mg/L and after the treatment with silica nanotubes at the concentrations of 10 and 100 mg/L on esterase activity and membrane potential, we can conclude that the main mechanism of toxic action of these samples on the red microalgae was a physical damage caused by adhesion of clusters of NPs with extracellular mucopolysaccharides of P. purpureum [The current statement correlated with the results of the structural and surface analysis of the samples of carbon NPs . It was urpureum .A. ussuriensis, H. akashiwo, and C. muelleri was probably caused by the lower mechanical interaction between microalgae cells and the NPs. However, observed esterase activity inhibition, membrane depolarization, and size changes of microalgae cells might be produced by the influence of metal impurities containing in carbon NPs silica NPs did not affect the esterase activity and membrane potential of the cells of all four microalgae species even at higher concentrations but caused significant inhibition of growth-rate, which indicated predominance of mechanical damage as a mechanism of toxicity for used samples of silica nanotubes.In this study, the aim was to assess the level of toxicity and the mechanisms of toxic action of carbon nanotubes, carbon nanofibers, and silica nanotubes using four microalgae species as the objects of aquatic toxicity bioassay. The results of this investigation show that (1) carbon nanotubes samples CNT-1 and CNT-2 had non-significant toxic effect on the growth rate of all four microalgae species but caused a high inhibition of esterase activity and depolarization of cell membranes, which was most probably caused by heavy metal impurities in NPs; (2) more hydrophobic carbon NPs with less ordered structure had a higher impact on the red microalgae The findings of this research provide insights for the formation of the principles of safe design, production, and utilization of NPs . We beli"} +{"text": "Post-workshop self-assessment (completed by 21 participants) noted significant median gains in knowledge domains related to NGS targeted sequencing, bioinformatics for genome assembly, and sequence quality assessment. The participants also reported that the information on study design, sample preparation, sequencing quality control, data quality assessment, reporting, and basic and advanced bioinformatics analysis were the most useful information presented in the training. While longer-term evaluations are planned, the training resulted in significant short-term improvement of a laboratory\u2019s self-reported wet lab and bioinformatics capabilities. This framework can be used for future DoD laboratory development in the area of NGS and BI for infectious disease surveillance, ultimately enhancing this global DoD capability.Epidemics of emerging and re-emerging infectious diseases are a danger to civilian and military populations worldwide. Health security and mitigation of infectious disease threats is a priority of the United States Government and the Department of Defense (DoD). Next generation sequencing (NGS) and Bioinformatics (BI) enhances traditional biosurveillance by providing additional data to understand transmission, identify resistance and virulence factors, make predictions, and update risk assessments. As more and more laboratories adopt NGS and BI technologies they encounter challenges in building local capacity. In addition to choosing the right sequencing platform and approach, considerations must also be made for the complexity of bioinformatics analyses, data storage, as well as personnel and computational requirements. To address these needs, a comprehensive training program was developed covering wet lab and bioinformatics approaches to NGS. The program is meant to be modular and adaptive to meet both common and individualized needs of medical research and public health laboratories across the DoD. The training program was first deployed internationally to the Basic Science Laboratory of the US Army Medical Research Directorate-Africa in Kisumu, Kenya, which is an overseas Lab of the Walter Reed Army Institute of Research (WRAIR). A week-long workshop with intensive focus on targeted sequencing and the bioinformatics of genome assembly ( Development of Next-Generation Sequencing (NGS), or High-Throughput Sequencing (HTS), has revolutionized life sciences, dramatically increasing the variety of questions that can be answered using genomic sequence data. With this continuously evolving and growing field, the need for adequate computational hardware resources, software, and expertise to analyze large and complex data is also increasing. The field of bioinformatics has thus experienced substantial growth and advancement in recent years, and the requirement for highly skilled and specialized personnel has surged.Staphylococcus aureus (MRSA); pathogens that have the ability to negatively impact United States force readiness and mission goals (Within the Department of Defense (DoD), NGS and bioinformatics are routinely used to answer many scientific and research questions that ultimately aid in protection of the armed forces, as well as the general population . Infection goals , 2019. Ion goals . The DoDon goals . Unsurpron goals . Howeveron goals . TherefoIn 2017, GEIS created a Consortium to address the increasing needs and challenges associated with NGS and bioinformatics at DoD medical research and public health laboratories. The vision of the Consortium is to rapidly detect and characterize known, emerging, and novel infectious disease agents through establishment of a harmonized DoD laboratory NGS and bioinformatics capability to inform force health protection decision making. The Consortium today represents a network of DoD laboratories that use NGS and bioinformatics for infectious disease surveillance. A baseline assessment and initial training effort was led by GEIS and three DoD core sequencing and bioinformatics laboratories: WRAIR-VDB , NMRC-BDRD , and USAMRIID-CGS . The Consortium performed an assessment of the GEIS DoD laboratory partners with access to Illumina MiSeq or other NGS instrument(s), in order to evaluate existing laboratory capabilities in NGS and bioinformatics, and to map gaps and needs in laboratory utilization of these tools to meet their mission goals of infectious disease surveillance. Limited access to experienced and knowledgeable NGS and bioinformatics personnel was one of the main gaps, making basic and advanced bioinformatics analyses a common challenge across the network. Another challenge was the restrictive and limited informatics infrastructure, especially in some of the participating laboratories located in low-and-middle income countries (LMICs). However, the challenge of finding personnel with sufficient training in NGS and bioinformatics was not only observed in laboratories located in LMICs, it was also apparent in domestic laboratories, thus highlighting the need to develop a structured NGS and bioinformatics training for the specific needs of DoD biosurveillance programs. Such training would have to be standardized across the Consortium network, as well as made agile enough to meet different levels of needs and computational resources of the participating DoD laboratories. Using the baseline information from the assessment, desired sequencing capabilities for DoD research and public health laboratories were divided into three tiers . Here weSamples used for the NGS hands-on training included dengue virus 2 (DENV-2) and chikungunya (CHIKV) and were provided on-site. Controls for library preparation, MiSeq sequencing and TapeStation for both DENV-2 and CHIKV were validated and prepared at VDB-WRAIR in the months prior to the planned NGS&BI training in Kenya. Prior to shipment of controls to Kenya, the control concentrations were measured and documented and the information was sent to MRD-A. Coordination of the reagent and control shipment from VDB-WRAIR to Kisumu, Kenya started a month prior to the training. Four Linux laptops and two Linux servers were prepared for hands-on bioinformatics training. A list of software was prepared by the Consortium and sent out to MRD-A Lab for installation onto the training computers. The software list included ngs_mapper, IGV, Geneious, MEGA7, EDGE (servers only) . Three wLectures and theory included: History of sequencing, overview of NGS, library preparation, quantification, validation and pooling. In detail: (i) List of library preparation kits used by core DoD for different projects and specimens were highlighted; (ii) Several topics on types of kits for viruses, bacteria and parasite work were heavily discussed throughout the lecture; (iii) Specific library preparation kits were highlighted including TruSeq, QIASeq Fx, Kappa, NexteraXT, RNA Access and DNAFlex; (iv) AmpureXP Beads clean up after PCR reactions and library preparation was emphasized as preferred method; (v) Different library validations, including qPCR, Qubit and TapeStation were highlighted as essentials for quality control (QC); (vi) Library pooling based on TapeStation and Qubit were introduced; (vii) Two exercises of how to calculate amount of each library for pooling were conducted. Preparations were made for the upcoming bioinformatics training.Hands-on training for NGS wet lab was performed with 24 participants. The participants were separated into two groups based on their NGS background and interests for hands-on performance. Group 1 prepared the NexteraXT library from the amplicons and assessed amplicons using both Qubit and TapeStation prior to NexteraXT library preparation. The NexteraXT libraries were validated using both Qubit and TapeStation. Group 2 validated the pooling based on the controls from the shipment and prepared sample sheets, the MiSeq instrument and PhiX controls. The libraries were loaded onto the Miseq. Bioinformatics training dataset was prepared on each computer. Server performance was tested for running the pipelines and tools needed for the training, and the training dataset analyses were executed to test functionality prior to the hands-on bioinformatics training.Hands-on wet lab activities from Day 2 were summarized and any questions and concerns were addressed. Lectures on laboratory project experimental design (to include bioinformatics), bioinformatics data cleaning and pre-processing, and genome assembly through reference mapping were performed, as well as exercises in experimental design and genome consensus calling. For hands-on bioinformatics training, the 24 participants were divided into six different groups, each group utilizing one training computer or server. Ngs_mapper was used as the example of a reference mapping pipeline. The first training was performed on the DENV fastq dataset, including training on usage of different stages of the pipeline, setting a desired reference genome and running the pipeline. After ngs-mapper jobs were completed, interpretation of the output, how to utilize data quality scores and depth of coverage, how to assess the performance of the sequencing and the genome assembly were performed. Manual QC and genome curation were performed. The second training dataset consisted of CHIKV fastqs and was used for training on multiple reference usage and reference selection, in addition to repeating the above steps for dataset one.de novo genome assembly, assembly of bacterial genomes, and troubleshooting and maintenance of the MiSeq platform.Bioinformatics hands-on training was continued by evaluation of the CHIKV runs for reference genome selection. Based on the best reference choice, the reference mapping run was repeated. The repetition was incorporated on purpose to ensure better knowledge retention. Following reference mapping, the output of CHIKV assembly was evaluated and its genome curated. The data that were used for this training were purposefully chosen to be of lower quality, so that different challenges of genome assembly curation were highlighted, as well as the importance of QC and what consequences a lack of QC might result in. The last reference mapping analysis was performed on CHIKV data but now the participants learned how to change different pipeline thresholds, picking their own requirements for minimum base quality, consensus type output and the like. In addition, lectures were conducted covering theory of A summary of wet lab activities and library pooling to obtain optimal cluster density was presented. An exercise aimed at the evaluation of several MiSeq runs was performed. Management of sequencing libraries and data, and prevention of chimeric sequence data generation and mislabeling were discussed. Bioinformatics training on the influenza dataset was performed separately since influenza virus has a segmented genome and bioinformatically, full genome assembly is slightly more complicated. How to recognize presence of influenza reassortment was covered. A workshop survey was distributed and the A comprehensive training curriculum was constructed that consisted of standardized wet lab and bioinformatics theory modules as well Based on the results of the initial laboratory assessment, training was recommended for the GEIS partner US Army Medical Research Directorate \u2013 Africa (MRD-A) laboratories in Kenya. For MRD-A\u2019s initial needs, which mainly cover sequencing and analyses of known pathogen outbreaks and epidemics in the region, a 1 week on-site workshop was constructed where the wet lab targeted sequencing was covered in both lectures (specific assembled modules) and hands-on practice, followed by bioinformatics theory (specific assembled modules) and hands-on practice of pathogen genome assembly and curation . This apWe undertook a rapid evaluation of participants\u2019 self-reported baseline and post-workshop knowledge across ten skill domains related to genomic sequencing . We alsoThere were substantial gains in self-reported knowledge across all skill domains , with thThe participants were also asked in which topics they felt they would like more training and experience and how The rapid growth and utility of NGS and bioinformatics for research and biosurveillance has resulted in the emergence of DoD requirements for implementation of sequencing and computational technologies, as well as access to highly trained and knowledgeable personnel in the fields of NGS and bioinformatics. Specifically the latter point remains one of the major challenges across the DoD, and even though bioinformatics programs have more recently gained larger momentum in academia, lack of workforce with early-on and/or specialized bioinformatics training is still palpable in the government settings, particularly in government labs outside the continental United States. Therefore, NGS and bioinformatics training programs for infectious disease surveillance have recently been developed by many government agencies or non-governmental organizations. Within the United States Government, Canada, and the European Union, there is movement towards training and coordinated promotion of standardized quality assurance and quality control practices for pathogen genome sequencing using NGS technologies . Some reOur experience in deploying a comprehensive yet customizable classroom and hands-on training in NGS and bioinformatics in Kenya was overall successful (see caveats of assessment below) and is a potential model for future training programs in similar environments. This training program consisted of foundational material in sequencing theory and experimental design which formed a basis for more applied modules in targeted sequencing and metagenomics. Additionally, hands-on NGS wet lab and bioinformatics modules were further tailored to meet the needs of the laboratory participants using information obtained from a baseline landscape assessment. This training shows that a highly modular and deployable set of NGS and bioinformatics workshop components can be used within the DoD network of medical research and public health laboratories to improve sequencing wet lab capability, and analysis and interpretation of pathogen genomic data gathered using NGS and bioinformatics.Embedded within this training workshop was a post-self-assessment questionnaire to gauge immediate improvements in knowledge gained from the workshop materials. It is important to note that this questionnaire has several limitations including a small sample size, the immediate nature of the assessment tool which does not allow one to measure long-term benefits, and the fact that the assessment was only delivered through written evaluation and self-report. Further, more objective measurements of knowledge and skill gains after workshops may not directly translate into effective implementation and retention of these skills. The latter requires medium and longer term evaluations in an implementation science framework . HoweverFollowing this workshop a mechanism to facilitate reach back support with embedded long-term training and mentorship has been instituted to overcome challenges associated with long-term sustainability of a sequencing capability at MRD-A. Included in this 5-year NGS and bioinformatics implementation plan for MRD-A are: (i) continuous contact and support by the core DoD sequencing laboratories, (ii) repetition of training with focus on real data and troubleshooting, (iii) additional hands-on training in other wet lab and bioinformatics approaches to achieve capability diversification, (iv) development of local computational infrastructure for bioinformatics, and (v) regular assessments of wet lab and bioinformatics knowledge retention. Laboratory-level assessments of proficiency and skill retention 1\u20132 years post-training have included external review of raw sequence data and consensus genomes generated from GEIS funded surveillance projects. We also anticipate deploying periodic blinded panel of samples or data files for follow-up assessments of knowledge retention and capability development. At the end of this period, the goal is to achieve a high quality diversified portfolio of NGS and bioinformatics capabilities at the site, which then may serve as a central DoD hub for sequencing and advanced characterization of Force Health Protection (FHP) relevant pathogens in Africa.The current COVID-19 pandemic has further highlighted the importance of access to the NGS and bioinformatics in laboratories throughout the world. This makes the need of workshops such as ours even greater. However, the pandemic has also made travel and in-person learning a challenge, and therefore, GEIS is planning on development of virtual versions of the workshops to continue development of this important DoD-wide capability. In addition, Oxford Nanopore\u2019s MinION platform has increasingly been used in pathogen outbreak studies for real-time in-field analyses throughout the world, including analyses of SARS-CoV-2 . AlthougMore broadly, the Consortium goal is the establishment of basic proficiencies and adopted norms in quality assurance and quality control in targeted (hybridization- or amplicon-based) and metagenomic sequencing for viral and bacterial pathogens leading to more reliable results which will ultimately improve DoD public health surveillance and response. An additional objective is the development and maintenance of advanced genomics and bioinformatics capabilities in the United States and priority overseas locations, in order to enhance global health surveillance and facilitate faster response to infectious disease outbreaks. Development of these capabilities with GEIS DoD laboratory partners will require sustained commitment and global coordination. The end results will be the ability to reliably and rapidly sequence, identify, and characterize pathogens of public health importance in order to improve biosurveillance efforts and inform FHP measures throughout the world.All datasets presented in this study are included in the article/IM, WR, KB-L, LM, and RJ designed the training modules and the workshop modules. IM, WR, LV, LM, KP, RJ, JW, SP, and RC prepared and instructed the workshop. IM, WR, LV, KP, SP, RC, JK, KB-L, LM, JW, and RJ performed workshop post-assessment and wrote the manuscript. All authors contributed to the article and approved the submitted version.The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of the Navy, Department of Defense, or United States Government. Several of the authors are United States Government employees. This work was prepared as part of their official duties. Title 17 U.S.C. \u00a7105 provides that \u201cCopyright protection under this title is not available for any work of the United States Government.\u201d Title 17 U.S.C. \u00a7101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person\u2019s official duties.LV and RC were employed by company Leidos, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Mycobacterium leprae, an acid-fast bacillus that mainly affects the skin and peripheral nervous tissue. Many of the clinical manifestations of leprosy can mimic connective tissue diseases. The authors present the case of a 49-year-old woman who had been treated for four years for systemic lupus erythematosus in a rheumatological service. Skin biopsy of a plaque on the inguinal region was compatible with borderline lepromatous leprosy associated with a type 1 lepra reaction. The patient is undergoing treatment with multibacillary multidrug therapy, showing clinical improvement.Leprosy is an infectious disease with chronic evolution, caused by A 49-year-old woman reported pain in the interphalangeal joints and lower limbs, a skin rash, and alopecia; all symptoms persisted for four years. She was being treated for systemic lupus erythematosus with hydroxychloroquine, azathioprine, methotrexate, and prednisone. On physical examination, she presented generalized erythematous plaques, and infiltrated areas on the trunk, on the ears, and fingers, as well as diffuse non-healing alopecia .Figure 1She presented 24-hour proteinuria within normal limits, positive ANA , positive anti-cardiolipin IgM antibodies, and anti-SM and anti-double helix DNA, both negative.a)Subacute lupusb)Dermatomyositisc)Lepromatous leprosyd)Diffuse eosinophilic fasciitisShe also presented paresthesia of the lower limbs, and thickening and pain on palpation of the left ulnar and left external sciatic popliteal nerves.The bacilloscopy of the ear and two trunk lesions was positive (smear index: 3.33). Histopathology of the plaque in the inguinal region showed an epidermis with hyperkeratosis; in the dermis, edema and a perivascular, periadnexal, and interstitial mild inflammatory infiltrate composed of lymphocytes, histiocytes, plasmocytes, epithelioid cells, and sparse giant Langhans cells, involving the subcutaneous tissue, adipocytes and septa. Wade staining showed a large number of intracellular acid-fast bacilli, grouped in globi, fragmented and granular A and 3 BMycobacterium leprae, an acid-fast bacillus, with tropism for Schwann cells and the reticuloendothelial system. The bacillus mainly affects the skin and peripheral nervous tissue.M. leprae to regulate cytokine production and induce Th1 or Th2 responses contributes to the variety of clinical presentations of the disease.Leprosy is a chronic contagious infectious disease, caused by Rheumatological manifestations are observed in 64% to 77% of patients with multibacillary leprosy, especially when presenting lepra reactions.Positive ANA can be observed in 3% to 34% of leprosy patients. Titers are generally low, and the speckled and homogeneous patterns are the most common.The different clinical manifestations of leprosy pose a diagnostic challenge, since they can mimic other diseases, including autoimmune disorders. The difficulty of diagnosing leprosy early can increase the chance of transmission and cause deformities secondary to peripheral nerve involvement.None declared.Larissa Daniele Machado G\u00f3es: Elaboration and writing of the manuscript; critical review of the literature; critical review of the manuscript.Juliana Alves Scrignoli: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Patr\u00edcia Morais: Statistical analysis; approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Patr\u00edcia Morais: Statistical analysis; approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Indomethacin (IND) is a drug which after successful clinical trials became available for general prescription in 1965 and from that time is one of the most widely used anti-inflammatory drug with the highest potencies in the in vitro and in vivo models. However, despite its high therapeutic efficacy in relieving the symptoms of certain arthritis and in treating gout or collagen diseases, administration of IND causes a number of adverse effects, such as gastrointestinal ulceration, frequent central nervous system disorders and renal toxicity. These obstacles significantly limit the practical applications of IND and make that 10\u201320% of patients discontinue its use. Therefore, during the last three decades many attempts have been made to design novel formulations of IND aimed to increase its therapeutic benefits minimizing its adverse effects. In this review we summarize pharmacological information about IND and analyze its new lipid formulations and lipid bioconjugates as well as discuss their efficacy and potential application. This compound is one of the most useful antirheumatic drugs and prime drug recommended for the treatment of gout, collagen diseases, ankylosing spondylitis, osteoarthritis, and acute shoulder pains. Indomethacin was discovered in 1963 and two years later has been approved by the Food and Drug Administration (FDA) as a drug with anti-inflammatory, analgesic, and antipyretic properties for use in the United States . The. The2]. ammation . In 2002ammation . In termammation .Indomethacin belongs to the group of non-selective non-steroidal anti-inflammatory drugs. Similarly, to acetylsalicylic acid, diclofenac or ketoprofen, indomethacin also acts on the way of additional mechanisms of formation of pain and inflammation demonstrating the ability to inhibit the passage of leukocytes through the vascular walls to the site of inflammation in the tissues . AccordiThe relative potency of NSAIDs increases in the following order: aspirin < phenylbutazone < ibuprofen < naproxen < indomethacin both in the in vitro and in vivo models. This indicates the potent anti-inflammatory effect of indomethacin compared to other NSAIDs and partially is responsible for the popularity of the first three drugs . IndometO-demethylation, N-deacylation, or both reactions (O-desmethyl-indomethacin (DMI), O-deschlorobenzoyl-indomethacin (DBI), O-desmethyl-N-deschlorobenzoyl-indomethacin (DMBI), and their conjugates with glucuronides . Du. Du64]. In the next years the effect of lipid composition and size on the targeting potential of liposomes encapsulated IND in arthritic rats as well as methods for increasing their circulation time have been extensively studied by Srinath and coworkers ,70,71. MThe enhancement of absorption of IND by increasing the retention time at the absorption site and reducing the distance to the blood was reported for liposomes modified with chitosan . In fastThe safety of liposomal formulation of IND was evaluated in a pregnant mouse model ,74. RefuBioconjugation of therapeutics is an effective method for targeted drug delivery and reduction of their undesired side effects. Linkage of drug with other biomolecule via covalent bond offers many clinical benefits like enhanced disease-specific targeting, reduced toxicity, optimized pharmacokinetics, and improved efficacy, safety, and tolerability. Especially bioconjugates are attractive which include lipids as the building blocks. As hydrophobic compounds, lipids after passing through the intestinal walls, penetrate into the lymphatic system through which they connect with the circulatory system at the level of the thoracic vein. This way of transporting lipids in the circulatory system distinguishes them from hydrophilic compounds, which, after penetration into the intestinal walls, reach the blood vessels, and then are transported through the portal vein to the liver, and then to the general circulation. Giving a lipid character to drugs after their conjugation with lipid molecule increase their concentration in the body, prolong release and blood circulation . Active sn-2 position of triacylglycerol (TAG) skeleton, which ensured the appropriate level of salicylates in the blood excluding the occurrence of gastric irritation ..2 enzymeThis work presents an overview of the literature data about indomethacin developed during the past few decades, methods of reduction of its gastrotoxicity, and targeted delivery by formation of lipid formulations and bioconjugates. The study summarized in this review established lipid bioconjugates of indomethacin as promising candidate for future clinical studies and proved that lipids protect against acute intestinal epithelial injury caused by indomethacin and effectively increased the therapeutic efficiency of this drug.Application of phospholipids and nanotechnology is a promising approach for further development of innovative formulation for indomethacin and other drugs from the group of NSAIDs and is expected to grow in the near future."} +{"text": "Amphiphilic Polymer Co-networks: Synthesis, Properties, Modelling and Applications is a new and very interesting book published by the Royal Society of Chemistry and edited by Prof. Costas S. Patrickios (University of Cyprus). Herein, a brief review of the most important features of the book and its contents is provided from a personal perspective. The presence in these materials of the hydrophobic segments, in addition to the hydrophilic ones, allows only limited water absorption , rendering them less fluid-like and mechanically stronger than classical hydrogels. Provided that the hydrophobic components come in segments of several consecutive hydrophobic units, these hydrophobic segments aggregate and the APCNs undergo self-organization in water, a process analogous to surfactant aqueous micellization. Upon APCN deformation, these hydrophobic pockets dissipate mechanical energy, rendering these materials stronger. The hydrophobic pockets can also solubilize hydrophobic solutes, such as drugs to be subsequently delivered, or sequester oils or other hydrophobic pollutants for environmental remediation. Polymeric hydrogels are crosslinked hydrophilic polymers which are capable of absorbing water, having the characteristics of both a solid and a fluid. Their higher water content makes hydrogels more fluid and transparent but also more fragile. Polymeric materials consisting of crosslinked hydrophilic and This book Figure is aboutN-vinylimidazole), poly(ethylene glycol), poly[(2-dimethylamino)ethyl methacrylate], polysaccharides or poly(ethylene glycol)s, among others, and hydrophobic domains derived, for instance, from poly(tetrahydrofuran), polyisobutylene, poly(\u03b5-caprolactone), four-armed star poly(ethyl glycidyl ether)s and poly(dimethylsiloxane)-based crosslinkers. Important properties discussed throughout different chapters include aqueous swelling, thermophysical and mechanical properties, self-assembly mechanism, morphological features, external stimuli responsiveness, , degradation and protein adsorption. In addition, useful comparisons between the properties of these materials and those of common polymeric hydrogels are provided for important examples. Applications described in the book chapters include, for instance, the use of APCNs in soft contact lenses, drug delivery, tissue engineering, heterogeneous biocatalysis , and for the fabrication of membranes of controllable permeability and antibacterial hybrid materials. Furthermore, an important theory chapter on the simulation of the self-assembly of APCNs, focusing on microphase separation and order\u2013disorder transitions, is also included.The book\u2019s 15 chapters are written by experts in the field, coming from four continents and 12 countries, and are organized into four sections that include synthesis, properties, modeling and applications. The chapters describe and discuss new developments in the field, while the history of APCNs since their origin in 1988 is summarized in the Foreword by Prof. J. P. Kennedy of the University of Akron and in Chapter 1 by the editor of the book. A brief outlook for the field is provided at the end of Chapter 1. The co-network architectures discussed in this book are mainly derived from hydrophobic macromolecular crosslinkers which represent the classical approach; however, more modern designs as well as the use of more efficient coupling chemistries are also presented. Among different APCNs, the book emphasizes those based on the combination of hydrophilic components such as poly(Professor Costas S. Patrickios obtained his PhD in 1993 at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts in the USA. Between 1994 and 1996, Dr. Patrickios worked as a post-doctoral researcher at the University of Sussex in the UK. Then, he served as a Lecturer at the University of Manchester Institute of Science and Technology (UMIST) (1996\u20131997), also in the UK. In 1998, he joined the Department of Natural Sciences (now Department of Chemistry) at the University of Cyprus (Republic of Cyprus), where he has remained since then. His main research has been focused on the synthesis and characterization of amphiphilic polymer co-networks based on interconnected amphiphilic block copolymers prepared using the living/controlled polymerization techniques group transfer polymerization (GTP), atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. He is currently the Chair of the Polymer Networks Group (PNG), an international organization promoting research on polymer networks and gels.In conclusion, this is a timely and decisively important book with well-articulated content, which invites the hydrogel research community to consider adding a hydrophobic block/segment to their materials in order to convert them into amphiphilic gels and examine whether the resulting properties are improved for the particular application compared to those of the original hydrogels. The book\u2019s style and its content diversity make it appropriate for graduate students and researchers interested in hydrogels, polymer chemistry, polymer networks, self-assembly and nanomaterials. Certainly, this is a must-read book for all those who are passionate about engineering new functional hydrogels that can contribute to solving real-world challenges."} +{"text": "Improving food and nutritional diversity based on the diversity of traditional plant-based foods is an important dietary strategy to address the challenges of rapidly emerging diet- and lifestyle-linked noncommunicable chronic diseases (NCDs) of indigenous communities worldwide. Restoration of native ecosystems, revival of traditional food crop cultivation, and revival of traditional knowledge of food preparation, processing, and preservation are important steps to build dietary support strategies against an NCD epidemic of contemporary indigenous communities. Recent studies have indicated that many traditional plant-based foods of Native Americans provide a rich source of human health\u2013relevant bioactive compounds with diverse health benefits. Based on this rationale of health benefits of traditional plant-based foods, the objective of this review is to present a state-of-the-art comprehensive framework for ecologically and culturally relevant sustainable strategies to restore and integrate the traditional plant food diversity of Native Americans to address the NCD challenges of indigenous and wider nonindigenous communities worldwide. Loss of plant-based food diversity and subsequent changes in dietary patterns closely associated with higher daily intake of more hyperprocessed and calorie-dense foods have partly contributed to the rapid rise of diet- and lifestyle-linked noncommunicable chronic diseases (NCDs) across different communities worldwide , 2. The Most public health reports from last 2 decades have suggested that Native American communities and Alaska Natives of the United States are facing increasing health challenges due to the NCD-linked epidemic of type 2 diabetes (T2D) and cardiovascular diseases (CVDs) , 8. A naThe framework and strategies suggested in this review are to revive and revitalize the traditional plant-based food diversity of Native Americans and to integrate such foods into contemporary healthy dietary patterns as part of overall public health solutions for NCD epidemics. Kuhnlein and Receveur defined The foundations of life, such as food resources, medicines, cultures, rituals, and spiritual integrity, of indigenous Native American communities have long been rooted and associated with their respective native and localized ecosystems . DiverseTherefore, a resilient native ecosystem with high species biodiversity, including plant-based food diversity, is essential for the sustainability and well-being of dislocated Native American communities . The negPrior to developing sound food diversity and nutritional intervention strategies to advance public health policies addressing NCD-linked health disparities of Native American communities, it is important to understand and recognize significant dietary and lifestyle changes and what has happened in the socioeconomic and ecological domains in these communities. Until the early 20th century, most Native American tribes farmed, hunted, or fished on their own lands and wetlands or gathered foods and medicinal plants from the woods and forests . The traHowever, in the last century the growth of industry and technology triggered a general shift from home cooking to higher consumption of commercially produced food products from a few calorie-dense food plants and rise in commercial animal farming that led to the development of multiple popular food chains across the United States . To suppNCDs such as obesity-linked T2D and CVDs are rapidly increasing in prevalence and becoming the leading cause of death in different communities, including indigenous and wider nonindigenous populations worldwide . HoweverThe latest report of the National Center for Chronic Disease Prevention and Health Promotion indicates the highest prevalence of diagnosed diabetes in Native American and Alaska Natives, with 14.9% in men and 15.3% in women . HoweverTraditional wisdom, invention, and continuous observation guided early humans to adopt and incorporate plant-based foods in their diet and for medicinal uses depending on their availability and nutritional properties relevant to human well-being , 12. MesIn this context, many plant-based foods from very specific and localized ecosystems such as wild rice of the Great Lakes region or cranberry from North-Eastern America were widely used in traditional Native American diets , 37. FurSeveral traditional food plants and wild edibles of Mesoamerican origin are rich sources of phytochemicals relevant to human health, such as phenolic bioactives, with diverse health benefits . These tTherefore, traditional plant-based foods of Native Americans, with their rich source of natural phenolic antioxidants, can be incorporated in dietary intervention strategies to counter chronic oxidative stress and other metabolic dysfunctions commonly associated with T2D, CVDs, and GDM , 38, 40.Squash is also a rich source of phenolic antioxidants and has natural angiotensin-converting enzyme (ACE) inhibitors, which are important for T2D-linked hypertension management . High phOverall, the average consumption of traditional and ethnic plant-based foods by Native American communities is <10%, and many living in the reservations do not even have access to traditional foods . TherefoEarly human migration and settlement, such as the migration of Native American tribes across North America, was partly guided by the quest for food and based on the availability of diverse plant and animal food resources in their respective ecosystems . HoweverTherefore, it is important to revive the knowledge of traditional food systems of Native Americans and restore information about traditional food plants, wild edibles, and other relevant natural food resources . To achiScreening and comparing human health\u2013relevant nutritional profiles and diverse health benefits of traditional plant-based foods is essential for building more resilient and robust dietary intervention strategies, especially to counter the diet-linked NCD epidemic of indigenous communities , 47. OveRevival of traditional knowledge of indigenous culture-specific cultivation practices is as important as understanding the nutritional qualities and associated health benefits of the native food plants. Appreciation of natural food and nonfood resources and their spiritual connection with native ecosystems is a significant part of the ethos of indigenous Native American tribes . The traSimilar to different traditional cultivation practices, food preparation, processing, and preservation practices of traditional food plants and wild edibles also have significant relevance in determining optimum nutritional qualities and associated health benefits of traditional Native American foods . AnotherTo address the NCD-linked health disparities of Native American communities, it is also important to integrate nonindigenous food plants and plant-based foods rich in human health\u2013relevant bioactives into traditional Native American diet models . Such inActive participation and continuous engagement of Native American communities in decision processes around food and health policy are extremely important for successful outcomes of any intervention strategies , 37. SucRestoring indigenous food sovereignty is essential to address the severe public health challenges linked to food and nutritional security of contemporary Native American communities. However, challenges related to indigenous food sovereignty are extremely complex due to interlinkage of different cultural, ecological, social, political, and economic factors. Therefore, to address such complex indigenous food sovereignty issues, it is important to develop more sustainable and community-oriented strategies based on a systems approach by understanding the ecological, cultural, social, and economic contexts of traditional foods of Native Americans. Additionally, such resilient and robust strategies to improve food and nutritional diversity based on traditional food plants and native medicinal plants of Native Americans should also have enough flexibility to adjust and evolve based on the needs of Native American communities and their contemporary cultural and ecological relevance. Therefore, restoration of traditional food systems of Native Americans and integration of nonindigenous healthy foods from contemporary American diets into traditional food systems to enhance nutritional diversity can have a profound impact on advancing nutritionally linked health outcomes of Native American communities, especially to combat the rapidly increasing NCD epidemic. However, most importantly we have to recognize that access to nutritionally balanced traditional foods is not a privilege but a right of indigenous people of North America and worldwide. Overall, acknowledging and accepting this simple fact can help to develop and advance more effective and sustainable policy measures to enhance traditional food and nutritional diversity in contemporary diets for improving the health, livelihood, and well-being of Native American communities and wider nonindigenous communities."} +{"text": "Abrupt industrialization, urbanization, and the emergence of the nuclear family have contributed to the increase of single-person households, placing an emphasis on individualization in society. Because of such changes, more people are living alone and feeling lonely, alienated from society and family. This research examined the association between loneliness and age-friendly environment, a community equipped with policies, settings, services, and structures that promote active ageing and aging-in-place, with the mediating roles of social support and sense of community. The study analyzed a total of 590 respondents aged 45 and above using data from the age integration survey conducted by the OO Research Institute of South Korea. Structural equation modelling and the bootstrapping method were applied. Age-friendly environment was positively associated with social support and sense of community . Social support was negatively associated with loneliness . The full mediation effect of social support was observed in the pathway from age-friendly environment to loneliness . Social support was fundamental in lowering loneliness, and age-friendly environment could only reduce loneliness by following a pathway that enhances social support. In other words, despite how well an age-friendly environment is established, it would not decrease an individual\u2019s loneliness unless it also enhances social support level. This finding sheds importance in maintaining satisfactory relationships that enable sharing of feelings, and fulfilling emotional and social needs in lowering loneliness. Measures to increase social support level within community are suggested."} +{"text": "Functional polymers show unique physical and chemical properties, which can manifest as dynamic responses to external stimuli such as radiation, temperature, chemical reaction, external force, and magnetic and electric fields. Recent advances in the fabrication techniques have enabled different types of polymer systems to be utilized in a wide range of potential applications in smart structures and systems, including structural health monitoring, anti-vibration, and actuators. The progress in these integrated smart structures requires the implementation of finite element modelling using a multiphysics approach in various computational platforms. This special issue presents six scientific report articles.The Special Issue opens with work from Eindhoven University of Technology in a joint study with Bernal Institute, University of Limerick, Ireland, in which the researchers developed a finite element method (FEM) for representing the microstructural behaviour, particularly the swelling of hydrogel beads . As the In the second article, Zhang and colleagues from Northeast Agricultural University, China, designed a novel hierarchical metamaterial with a tuneable negative Poisson\u2019s ratio by re-entrant representative star-shaped unit cells . In thisZolfagharian and Kaynak from the School of Engineering in Deakin University, Australia, worked on the fracture resistance analysis of three-dimensional 3D) printed polymers in collaboration with Khoshravani from the University of Siegen in Germany [D printedIn the fourth article, , Carleo The Special Issue closes with the work of international researchers from the UK, USA, and Egypt in which Atif and colleagues developed a computational fluid dynamics (CFD) model to investigate characteristics of high-speed submicron polyvinylidene fluoride (PVDF) fibres as they are expelled from a blow spinning (SBS) nozzle . The aut"} +{"text": "This commentary describes the creation of the Zika Virus Individual Participant Data Consortium, a global collaboration to address outstanding questions in Zika virus (ZIKV) epidemiology through conducting an individual participant data meta-analysis (IPD-MA). The aims of the IPD-MA are to (1) estimate the absolute and relative risks of miscarriage, fetal loss, and short- and long-term sequelae of fetal exposure; (2) identify and quantify the relative importance of different sources of heterogeneity for the risk of adverse fetal, infant, and child outcomes among infants exposed to ZIKV in utero; and (3) develop and validate a prognostic model for the early identification of high-risk pregnancies and inform communication between health care providers and their patients and public health interventions . By leveraging data from a diversity of populations across the world, the IPD-MA will provide a more precise estimate of the risk of adverse ZIKV-related outcomes within clinically relevant subgroups and a quantitative assessment of the generalizability of these estimates across populations and settings. The ZIKV IPD Consortium effort is indicative of the growing recognition that data sharing is a central component of global health security and outbreak response. Aedes-aegypti endemic areas in Asia and Africa [While the world has turned to face COVID-19, recent epidemics are re-emerging . Even asd Africa . Despited Africa ,6. IdentBMJ Open (https://bmjopen.bmj.com/content/9/6/e026092).In February 2017, a group of researchers formed the ZIKV Individual Participant Data (IPD) Consortium to conduct an individual participant data meta-analysis (IPD-MA) of ZIKV-related longitudinal studies of pregnant women and their children. The ZIKV IPD Consortium initiative arose from a meeting of international organizations and Ministries of Health in June 2016 to coordinate and harmonize ZIKV-related research efforts . The resAs of August 2020, 52 cohort studies and country-level active surveillance system sites from 28 countries and territories have agreed to contribute de-identified data to the ZIKV IPD Consortium IPD-MA. The use of participant-level data from diverse geographies and populations will allow the team to better identify the clinical, virological, environmental, and individual-level factors that predict severe ZIKV-related fetal effects or adverse neurocognitive or neurodevelopmental outcomes in the child, several of which can only be measured after two years of age . For exaThe global response to ZIKV has been characterized by unprecedented levels of collaboration between countries, research organizations, universities, and surveillance systems . The ZIKWomen living in and travelling to countries with ongoing or recent ZIKV transmission face a tremendous burden from the fear and uncertainty around the risks associated with ZIKV infections during pregnancy, guidance from public health authorities to avoid or delay pregnancy, and the lack of economic and social support for the challenges of raising infants with congenital Zika syndrome (CZS) and other ZIKV-related disabilities and developmental delays ,18. ReseDespite the persistent threat of ZIKV infection to pregnant women and women of reproductive age worldwide, investment in critical areas of ZIKV research is waning. Leveraging existing investments through collaboration will accelerate the development of effective prevention, harm reduction, and control strategies. Best practices and lessons learned from the research response to ZIKV can be used to improve the coordination and speed of the global research response to emerging pathogens.Global travel, trade, urbanization, and climate change have all facilitated the development of novel hosts and exte"} +{"text": "Caregiving is often considered stressful, even more so if the care recipient has been diagnosed with dementia. The current study examines the rate of cognitive decline of spousal caregivers of persons with dementia (CG-D) when compared to spousal caregivers of persons without dementia (CG) before and after the death of the care recipient. Health and Retirement Study (HRS) data from 1998-2016 were used to examine cognitive trajectories of CG-D (n=364) and CG before and after the care recipient death. Cognition was measured through the HRS\u2019s shortened Telephone Interview of Cognitive Status and separated into measures of total cognition and memory. Covariates included age, education, sex, race, ethnicity, care hours, frailty, socioeconomic status, nursing home placement of the recipient, and whether the death was expected. Piecewise mixed models were constructed to examine two two-year periods of decline leading up to the death of the care recipient, and two two-year periods of decline after the death of the care recipient. CG-D and CG declined at equivalent rates on measures of total cognition and memory (ps > .05). In all caregivers, total cognition and memory declined at a stable rate before the death of the care recipient. However, an accelerated decline was evident after the death of the care recipient (ps < .001). Our results suggest that cognitive decline is not differentially affected by care recipient dementia diagnosis. We find evidence that the death of a spousal care recipient is accompanied by hastened cognitive decline in our population-based sample."} +{"text": "The author has undertaken multiple echocardiographic studies during his academic career; most of these were published in peer-reviewed journals. These studies include an evaluation of the role of echocardiography in the estimation of left-to-right shunt in isolated ventricular septal defects, an examination of the utility of contrast echocardiography in the diagnosis of anomalous connection of the right superior vena cava to the left atrium, a description of pitfalls in M-mode echocardiographic assessment of the aortic root in left ventricular hypoplasia syndromes, reviews of echocardiographic evaluation of left ventricular function, study of the role of contrast echocardiography in the evaluation of hypoxemia following open heart surgery, a quantification of left ventricular muscle mass by m-mode echocardiography in children, an examination of race and sex related differences in echocardiographic measurements in children, study of cardiac size and function in patients with sickle cell disease, an examination of afterload reduction in the management of primary myocardial disease, study of the utility of echo-Doppler studies in the evaluation of the results of balloon pulmonary valvuloplasty, study of the usefulness of Doppler in the prediction of pressure gradients in valvar pulmonary stenosis, a review of Doppler echocardiography in noninvasive diagnoses of heart disease, echo-Doppler studies of the evaluation of the results of balloon angioplasty of aortic coarctation, study of the value of Doppler in the prediction of pressure gradients across coarctation of the aorta, and a characterization of foramen ovale and transatrial Doppler velocity patterns in the normal fetus. When the author was named as Interim Director of Pediatric Echocardiography Laboratory at Children\u2019s Memorial Hermann Hospital/University of Texas-Houston Medical School, Houston, Texas in 2006, some of the staff critiqued this appointment, as the author was considered to be an interventionist pediatric cardiologist. The author responded to this critique by sending them a list of the his echo publications ,31,32,33At the time of the author\u2019s fellowship training in 1969/1970 at Stanford University Medical Center, Palo Alto, California, there were only two echocardiography recording machines in the United States: one was at University of Indiana, Indianapolis, Indiana and the other at Stanford University. The author was exposed to echocardiography to evaluate mitral valve motion and pericardial effusion on M-mode tracings. During subsequent fellowship training at Case-Western Reserve University and the University of California at Los Angeles, the echo machines had not yet arrived at the respective institutions. By 1972, when the author joined the Faculty at the Medical College of Georgia, Augusta, Georgia, there were indeed echocardiography facilities at that institution. Shortly thereafter, Dr. Wesley Covitz joined our faculty at Georgia and provided the author with additional understanding of the principles and practice of M-mode echocardiography, thereby adding to the author\u2019s knowledge base. This resulted in the author\u2019s active participation in echocardiography research at that time ,4,5. Twop < 0.01) than those of control subjects , we compared the cardiac catheterization data with echocardiographic values (echo performed within 24 h of cardiac catheterization) in 35 babies; 35 children with normal hearts by physical examination and ECG were used as controls ) in the modified Bernoulli equation. Duration-related measures of Doppler flow signal distal to the coarctation site, namely, acceleration time (AT) and antegrade flow time (AFT) , were al2) peak instantaneous and catheterization-measured peak-to-peak gradients resulted in a correlation coefficient of 0.757. (22 \u2212 V12]) in the modified Bernoulli equation (r = 0.763). A comparison of the catheterization data with antegrade flow time (r = 0.82) and antegrade flow time fraction (r = 0.737) showed marginal, if any, improvement in the correlation coefficients following balloon angioplasty of native aortic coarctation; this was similar to reduction in peak-to-peak pressure gradients by catheterization. A discussion of possible reasons for the lack of correlation between Doppler and catheter gradients included peak-to-peak vs. peak instantaneous gradients and possible collateral vessel flow in aortic coarctation. It was concluded that (i) the magnitude and duration related Doppler velocity recordings are helpful in estimating coarctation gradients, and (ii) Doppler is useful in demonstrating the relief of obstruction by balloon angioplasty [It was further noted that the Doppler flow velocity magnitude and calculated gradients improved in fetal circulation, the size of and shunt velocity patterns across the FO in the fetus had not been thoroughly investigated as of the mid-/late-1980s. Therefore, we endeavored to define the normal size of FO and the Doppler velocity patterns across the atrial septum in the normal fetus. Normal human fetal ultrasound studies in 48 consecutive fetuses were examined and the size of FO, foramen flap angle , its motThe maximal FO diameter was similar to the diameter of the Ao at all gestational ages ; there wOur study showed that the size of normal foramen ovale is similar to aortic root diameter, and that the foramen flap angle reaches 30 degrees or greater. Right-to-left flow is as anticipated for fetal circulatory physiology; the left-to-right flow documented in this study was unexpected and may be related instantaneous pressure difference between atria, as previously shown in patients with tricuspid atresia . These fThe author\u2019s contributions to the echocardiography literature from 1991 to the current date will be detailed in Part II of this review."} +{"text": "Genital lesions are an unusual presentation of American cutaneous leishmaniasis. Conditions such as disseminated cutaneous leishmaniasis and HIV infection may be associated with genital involvement. The authors present five cases of American cutaneous leishmaniasis with genital lesions and discuss the clinical and epidemiological aspects observed in this case series. Leishmania transmitted by the bite of infected female sandflies, insects of the genus Lutzomyia.3American cutaneous leishmaniasis (ACL) is an infectious disease caused by protozoa of the genus DL constitutes up to 2% of ACL cases and probably occurs due to the lymphatic or hematic spread of the parasite from the bite site.4Genital lesions are an unusual presentation of ACL and suggest hematic dissemination in patients with DL or direct inoculation of the parasite in patients with isolated genital lesions who sleep naked outdoors or perform bodily functions in endemic areas of ACL without sanitary facilities.Leishmania (Viannia) braziliensiss, as all patients were inhabitants of the state of Rio de Janeiro with no recent history of travel.Although Sexually Transmitted Infections (STIs) are the main causes of penile ulcers, other conditions such as fixed drug eruption erythema, autoimmune bullous dermatoses, psoriasis, Beh\u00e7et's disease, Reiter's syndrome, pyoderma gangrenosum, lichen planus, and squamous cell carcinoma can also cause genital ulcers.ACL should be considered in the differential diagnosis of chronic genital lesions in patients who reside in or travel from endemic areas, especially when associated with mucosal lesions in UADT and multiple, polymorphic skin lesions. Furthermore, the presence of genital lesions can aid in the differential diagnosis of granulomatous diseases with similar clinical presentation, such as paracoccidioidomycosis, histoplasmosis, and disseminated sporotrichosis.Genital involvement in ACL probably occurs due to hematic dissemination in patients with DL. Therefore, ACL should be included in the differential diagnosis for patients from endemic areas with genital ulcers, especially in the presence of mucosal lesions in UADT and multiple skin lesions.Instituto Nacional de Infectologia Evandro Chagas (INI).Marcelo Rosandiski Lyra: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Alan Bittencourt da Silva: Elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; critical review of the literature; critical review of the manuscriptCl\u00e1udia Maria Valete-Rosalino: Approval of the final version of the manuscript; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Maria In\u00eas Fernandes Pimentel: Approval of the final version of the manuscript; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Statistical models are increasingly being used to estimate and project the prevalence and burden of asthma. Given substantial variations in these estimates, there is a need to critically assess the properties of these models and assess their transparency and reproducibility. We aimed to critically appraise the strengths, limitations and reproducibility of existing models for estimating and projecting the global, regional and national prevalence and burden of asthma.We undertook a systematic review, which involved searching Medline, Embase, World Health Organization Library and Information Services (WHOLIS) and Web of Science from 1980 to 2017 for modelling studies. Two reviewers independently assessed the eligibility of studies for inclusion and then assessed their strengths, limitations and reproducibility using pre-defined quality criteria. Data were descriptively and narratively synthesised.We identified 108 eligible studies, which employed a total of 51 models: 42 models were used to derive national level estimates, two models for regional estimates, four models for global and regional estimates and three models for global, regional and national estimates. Ten models were used to estimate the prevalence of asthma, 27 models estimated the burden of asthma \u2013 including, health care service utilisation, disability-adjusted life years, mortality and direct and indirect costs of asthma \u2013 and 14 models estimated both the prevalence and burden of asthma. Logistic and linear regression models were most widely used for national estimates. Different versions of the DisMod-MR- Bayesian meta-regression models and Cause Of Death Ensemble model (CODEm) were predominantly used for global, regional and national estimates. Most models suffered from a number of methodological limitations \u2013 in particular, poor reporting, insufficient quality and lack of reproducibility.Whilst global, regional and national estimates of asthma prevalence and burden continue to inform health policy and investment decisions on asthma, most models used to derive these estimates lack the required reproducibility. There is a need for better-constructed models for estimating and projecting the prevalence and disease burden of asthma and a related need for better reporting of models, and making data and code available to facilitate replication. Resources are limited and health system planners need to make investment decisions based on available evidence of disease prevalence, associated morbidity and health care utilisation, mortality and costs, how these are likely to have the potential to change over time and their amenability to interventions -8. ModelFocusing specifically on estimates of asthma prevalence and burden, we observe that varying estimates have been reported in the published literature at national, regional and global levels, which are not consistent over the years and published in any language. Our outcomes of interest were the prevalence of asthma and different components of the disease burden of asthma. The components of disease burden were direct and indirect costs of asthma , disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), potential years of life lost, healthy years of life lost, active life expectancy, disability-free life expectancy, disability-adjusted life expectancy, and healthy life expectancy (HALE).We identified relevant published and unpublished studies through searching electronic databases, hand-searching of pertinent journals and checking reference lists of all the eligible papers for studies published between January 1980 and September 2017. The following electronic databases were searched: Medline, Embase, World Health Organization Library and Information Services and Web of Science Core Collection. Journals that were hand-searched included The Lancet, BMJ (1980-2017), European Respiratory Journal (1988-2017), Lancet Respiratory Medicine (2013-2017), Lancet Global Health (2013-2017) and Journal of Global Health (2011-2017). We ran the last searches on 16 September 2017. We included papers published in any language and translated the papers that were not in English with the help of fluent or native speakers.Comprehensive search strategies were developed for all the aforementioned databases in consultation with a senior medical librarian at The University of Edinburgh to identify both published and unpublished (grey literature) primary studies as well as reviews. The search terms used included but were not limited to asthma, wheeze, epidemiology, prevalence, burden, morbidity, mortality, DALY, QALY, HALE, primary health care, emergency service, hospitalisation, absenteeism, cost of illness, model, estimate, projection. The detailed search strategies used to search each database are given in Appendix S1 in the Two reviewers independently checked and screened the titles and abstracts of identified articles against the inclusion criteria. Full-text copies of potentially eligible studies were obtained and assessed by two independent reviewers (MRB and MAI) on the basis of the inclusion criteria. Discussion between the two reviewers resolved the majority of discrepancies; a third reviewer (BIN) arbitrated in the case of any disagreements.We developed a data extraction form and used it to extract relevant data from included studies. The data extraction form was piloted on 10 included studies and was then refined accordingly prior to full use in the review. Data extraction was performed independently by two reviewers (MRB and MAI). Any discrepancies in data extraction were resolved through discussion between the reviewers, with arbitration by a third reviewer (BIN) if a decision could not be reached.The following data items were extracted from each paper: 1) study identification ; 2) aims and methods of the study ; 3) model information .As this review mainly focused on the properties of models rather than quantitative measures, we did not perform any quantitative synthesis of the data.We produced a tabular summary of the data to summarise the overall evidence. Descriptive statistics and graphical presentation were used to summarise the results. A detailed critical narrative synthesis of the models was undertaken regarding their strengths, limitations and reproducibility.To our knowledge, there is no existing quality appraisal tool to assess the quality of the components of models for estimating the prevalence and burden of diseases. We therefore developed our own model evaluation checklist by adapting relevant sections from pertinent critical appraisal checklists ,23, repoOur checklist consists of 13 quality criteria that a model should possess. We present the checklist by a pyramid in This systematic review is reported following the guidelines of the Preferred Reporting Items for Systematic review and Meta Analysis (PRISMA) checklist .Our electronic search of the databases yielded a total of 23\u2009571 references. After removing duplicates, 18\u2009502 study titles and abstracts were screened against our inclusion criteria. Among these, 287 full-text articles were assessed in detail. Finally, 92 papers met the inclusion criteria. An additional 16 papers identified from hand-searching of journals and scrutinising reference lists of included studies met the inclusion criteria. Therefore, a total of 108 studies were included in the systematic review. The PRISMA flow diagram of the selected papers is presented in We identified 94 studies that estimated the prevalence and burden of asthma at a national level; two at a regional level; seven at both global and regional levels; and five at global, regional and national levels ; two models were used to derive regional level estimates; four were used for global and regional estimates; and three models were used to derive global, regional and national estimates studies ,35-127 pMost studies failed to fulfil two internal model quality criteria and all the external criteria. Sixty-two 57.4%) studies ,127-129 .4% studiWe found only 20 (18.5%) studies ,117,122 Further analysis, assessing whether the included studies adhered the new Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) showed tThis systematic review of the international literature has found that a variety of models are used to estimate disease prevalence and burden; most models, however, suffer from methodological limitations, in particular, lack of reproducibility and sub-optimal reporting.Almost all the studies provided a clear statement about the questions that the models aimed to answer. The majority of the studies described the structure of the models explicitly; mentioned the methods used to fit the models or used to estimate model parameters; and applied appropriate modelling tools to deal with the nature, distribution and type of input data. These were the strengths of the models. However, these models had substantial limitations. We observed a lack of clarity in reporting the models. The majority of the studies did not provide any information on the model assumptions, methods of model building, methods of model diagnosis, methods of handling missing data, model validation and sensitivity analysis. In addition, many studies did not adequately present the final model parameter estimates, standard errors and confidence intervals. Moreover, most of the models could not be reproduced as the studies did not provide input data , computer coding, a model fitting manual or complete information about the process of model formulation.The main strengths of this review include the comprehensive search strategy employed, the use of established methodology and the inclusion of studies from all over the world including studies published in any language. Critical appraisal of identified models and expert involvement in developing model assessment tools further strengthened the credibility of this review. However, this review has a number of potential limitations. As with any systematic review, we may have missed some studies. Although risk factor based models or association models are particularly essential to assess determinants of a disease, we did not include studies that used models to estimate risk factors or to assess association rather than estimating prevalence and disease burden using model. The use of a self-developed customised model evaluation tools, due to the lack of appropriate critical appraisal checklist, may be considered to be a further limitation of this review. There is a need for the development of an internationally standard tool that will be used for the purpose.This systematic review is the first to synthesise models for prevalence and burden of asthma in the context of national, regional and global estimates and projections. Previous systematic reviews on disease modelling studies were mainly undertaken on other domains, such as prediction models -139, ecoExisting estimates are heavily reliant on modelling studies due to lack of data on direct measurements of asthma cases in many countries and regions. Whilst these modelling studies have advanced better understanding and appreciation of the burden of different diseases, the lack of reproducibility of the models, as highlighted in this review, requires concerted effort from researchers and decision makers to set in place platforms that will ensure that estimates of disease burden produced can be reproduced. Policymakers should thus be aware of the transparency of modelling processes and the reliability of the input data when making decisions on the basis of these model-based estimates.The findings of this review suggest that models should be carefully designed to incorporate all the necessary methodological components required to develop a robust model, including an explicit statement about the purpose and structure of the model; statement of necessary model assumptions; variable selection applying appropriate techniques; model diagnostic accuracy checking; assessing goodness-of-fit; addressing missing data by applying suitable techniques; applying optimum methods of parameter estimation; carrying out sensitivity analysis; and performing both internal and external model validation. Besides, a highly complex model usually lacks understanding, usability, reproducibility and, hence, credibility. While publishing models, sufficient information about the complete modelling process, therefore, should be reported to facilitate its understanding and usability for non-technical audiences. For example, a model development manual should be made publicly available, including input data and necessary computer code, to describe the step-by-step process of model development with illustrative examples. Although the perspectives of this review are prevalence and disease burden of asthma, these recommendations also apply to the modelling prevalence and burden of other chronic diseases.Future research could potentially be undertaken to develop consensus guidelines for developing or fitting and reporting models for prevalence and burden of diseases. Moreover, developing a critical appraisal checklist for assessing the quality of models for prevalence and burden of diseases is another key area for future research.Of the available approaches, we found the Bayesian meta-regression method- DisMod-MR, DisMod-MR 2.0, DisMod-MR 2.1 and CODEm ,9,14,17 Amidst data types and their sources, modelling remains indispensable for estimating the prevalence and burden of disease. This evidence synthesis has shown that existing models that have been applied to estimate the prevalence and burden of asthma suffer from methodological limitations, in particular, suboptimal reporting and lack of reproducibility. There is a need to enhance the reportage of models used for estimating and projecting the prevalence and disease burden of asthma and making data and code available to facilitate replication. Moreover, there is also a need for developing better-constructed asthma-specific models in an attempt to produce more accurate and consistent estimates. In the interim, we suggest using Bayesian meta-regression models and cause of death ensemble models for estimating national, regional and global prevalence and burden of asthma, and Box-Jenkins regression- autoregressive integrated moving average (ARIMA) model to make projections in relation to these estimates. We also suggest to validate the Bayesian meta-regression models against their alternative frequentist or classical models to check which modelling approaches generate better estimates of prevalence and burden of asthma than the others."} +{"text": "Aedes aegypti. Especially in the tropics, inefficacy of mosquito control causes arboviruses outbreaks every year, affecting the general population with debilitating effects in infected individuals. Several strategies have been tried to control the proliferation of A. aegypti using physical, biological, and chemical control measures. Other methods are currently under research and development, amongst which the use of nanotechnology has attracted a lot of attention of the researchers in relation to the production of more effective repellents and larvicides with less toxicity, and development of rapid sensors for the detection of virus infections. In this review, the utilization of nano-based formulations on control and diagnosis of mosquito-borne diseases were discussed. We also emphasizes the need for future research for broad commercialization of nano-based formulations in world market aiming a positive impact on public health.Arboviruses such as yellow fever, dengue, chikungunya and zika are transmitted mainly by the mosquito vector Aedes aegypti and Aedes albopictus are the most important global vectors of arboviruses, such as dengue, yellow fever, chikungunya, and zika viruses is often late, ineffective, and dependent on the clinical symptoms. The final decision on the infection generally requires a long waiting time, collection of samples from suspected patients , transportation and preservation, and laboratory procedures by trained health staff.Rapid diagnosis of important arboviruses-borne diseases such as dengue, chikungunya, zika, and yellow fever is essential in order to reduce and avoid further dissemination of the infections within the general population Sethi, . These rSeveral recent studies have used mainly LFAs as the basis for the construction of ASSURED biosensing devices. These assays can be performed using microfluidic technologies such as paper-based miniaturized devices that combine several recognition steps in a small area for naked-eye detection and quantification of compounds in complex mixtures, with the sample being collected on a test device and the results being displayed in real time bound covalently to the surface of one or more carbon nanotubes and/or metal nanoparticles present on part of a microelectrode surface, together with an electrically conducting part where a transduction system (sensor) converts the biochemical response into an electric signal . Encapsulation also protects the active agent against premature degradation caused by the effects of light, temperature, oxidation, and humidity, among others , average size around 100\u2013200 nm, zeta potential around\u221240 mV. Both encapsulated EOs reached lethal dosages within 24 h of exposure and total mortality of the tested pests , with the chitosan-based formulations having the best effects. These findings demonstrated the potential of polymeric nanoparticles containing essential oils for use as eco-friendly larvicidal products for the encapsulation of essential oils (geranium and bergamot). Evaluation was also made of the acute and residual larvicidal activities of the formulations against Piper aduncum L. and Piper hispidinervum C. in gelatin nanoparticles, with evaluation of the biological effects against Aedes aegypti. The encapsulation efficiencies exceeded 80%, and the particles were spherical, monodispersed, and smaller than 100 nm in size. Both of the encapsulated essential oils provided lethal effects within 24 h of exposure, with Aedes aegypti mortality greater than 80% and nanoemulsions containing citronella and neem oil, for the control of insects such as Aedes aegypti. The results showed that both the nanoemulsions and the NLCs loaded with the essential oils caused 100% mortality of A. aegypti larvae during the first day of exposure, while the NLCs without essential oil induced 100% mortality after 10 days of exposure. Both carriers showed satisfactory efficacy in the control of A. aegypti larvae synthesized using an aqueous extract of Euphorbia hirta leaves against the larvae of Aedes aegypti (LC50 = 13.2 mg/L) and Culex quinquefasciatus (LC50 = 6.89 mg/L) (Udayabhanu et al., Recent studies have reported the synthesis of various nanoparticles using different natural extracts, with demonstration of the larvicidal, ovicidal, and mosquiticidal activities of these nanoparticles. Udayabhanu et al. observed the larvicidal effect of titanium dioxide nanoparticles (TiOQuisqualis indica plant showed high toxicity against the vectors of filariasis, zika virus, and malaria. In addition, toxicity tests employing three non-target organisms indicated low toxicity of these systems (Govindarajan et al., Another study proposed the green synthesis of Ag NPs for use as an environmentally-friendly alternative to pyrethroid and carbamate larvicides. Silver nanoparticles synthesized from extracts of the The patent databases include inventions that describe methods of green synthesis of metal nanoparticles and metal oxides, with broad applications in consumer products, medicines, pharmaceuticals, and other biomedical products (Hoag et al., The potential application of nano-based formulations in the field of arboviruses management was investigated by analyzing the number of publications in the last ten years. The results revealed that around 1000 articles were published worldwide, which an exponential trend in publication numbers after 2016, mainly for researches related to zika and chikungunya. Overall, many publications have shown that nanotechnology has led to rapid advancements in the development of pesticides, repellents, drug delivery system and diagnostic devices for arboviruses management. However, the clinical translational of nano-based formulations has some bottlenecks that hinders the broad acceptance and commercialization of these products (Hua et al., Much debate still exists regarding the legislation of nanomaterials, which is in an early stage of development. In addition, there is a lack of a clear definition of nanomaterials, lack of standard methods for assessment of pharmacology, toxicology and efficacy evaluation of nano-based formulations and lack of worldwide network for gathering and sharing pertinent information. According to Schnell-Inderst et al. 12% of tAlso, economic issues can limiting the broad commercialization of nano-based formulations Ventola, . In compAedes aegypti-borne diseases.As conclusion, as indicated in this review, it is important to learn and appreciate the great potential offered by nanotechnology in relation to the development of new and more efficient tools and products. In this regard, it is extremely important that ongoing research involves all sectors: academia, industries, research centers, and government agencies, in order to turning this technology into a sustainable commercial reality and to create alternatives for detection and control of EC, JO, and LF proposed the structure of the manuscript. EC, JO, DA, CR, CB, VM, and RM wrote the manuscript. EC and LF revised the manuscript. All authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Addressing the psychological mechanisms and structural inequalities that underpin mental health issues is critical to recovery following disasters and pandemics. The Asia Pacific Disaster Mental Health Network was established in June 2020 in response to the current disaster climate and to foster advancements in disaster-oriented mental health research, practice and policy across the region. Supported by the World Health Organization (WHO) Thematic Platform for Health Emergency and Disaster Risk Management , the network brings together leading disaster psychiatry, psychology and public health experts. Our aim is to advance policy, research and targeted translation of the evidence so that communities are better informed in preparation and response to disasters, pandemics and mass trauma. The first meetings of the network resulted in the development of a regional disaster mental health agenda focused on the current context, with five priority areas: (1) Strengthening community engagement and the integration of diverse perspectives in planning, implementing and evaluating mental health and psychosocial response in disasters; (2) Supporting and assessing the capacity of mental health systems to respond to disasters; (3) Optimising emerging technologies in mental healthcare; (4) Understanding and responding appropriately to addressing the mental health impacts of climate change; (5) Prioritising mental health and psychosocial support for high-risk groups. Consideration of these priority areas in future research, practice and policy will support nuanced and effective psychosocial initiatives for disaster-affected populations within the Asia Pacific region. Disasters create an environment of disruption, trauma and grief, with potential for sustained mental health impacts. Heightened stress during pandemics and disasters can impair individual wellbeing , cognitive function , high-risk behaviours and behavioural outcomes ,2. The mThe Asia Pacific region records the highest frequency of hazards and greatest number of people affected by disasters annually ,10. The In response, the Asia Pacific Disaster Mental Health Network was established in June 2020 to create a collaborative platform for rigorous research, evidence-based practice and tailored policy designed to support improvements in mental health among disaster-affected communities. The network is supported by the World Health Organization (WHO) Thematic Platform for Health Emergency and Disaster Risk Management and its research network . At its The Asia Pacific Disaster Mental Health Network comprises fifteen representatives , selected for their expertise in responding to health emergencies and natural disasters, and work with trauma-affected communities within the region. The network is open to all Asia Pacific nations and currently includes representatives from Australia, Japan, China, Nepal, Sri Lanka, India and the USA. The purpose of the network\u2019s early meetings was to establish a collaborative platform for future research and policy development and set overarching priorities in line with the goals of the WHO Thematic Platform for Health EDRM and its research network. Monthly meetings are conducted via videoconference. The selection of research priorities was conducted through open consultation within the network. An iterative-generative reflective method was adopted, whereby experiential knowledge of network members gleaned through their immersion with affected communities allowed for iterative debate . As reflLarge-scale climate disasters, severe wildfires and the COVID-19 pandemic have drawn renewed global attention to disaster response this year. The COVID-19 pandemic has amplified the structural injustices of race, faith, gender, age, migration and economic inequality within and across societies, with significant implications for mental health (e.g., ,16,17,18Reinforcing local social networks, social solidarity and engagement with community groups in responding to disasters and other mass trauma events will enhance psychosocial outcomes ,25,26. CDisasters create multiple waves of healthcare need. Early response requires a focus on physical injuries, bereavement and re-establishing critical infrastructure for survival . EstabliThe COVID-19 pandemic has fast-tracked the development and widespread adoption of technology in mental healthcare in many settings. Digital mental health services include treatment sessions conducted via video call, telephone helplines, clinical text messaging services, digital health applications and platforms, online streaming and therapy services and mass dissemination of mental health resources on social media ,46. EnabClimate change has increased the frequency and severity of natural disasters in the Asia Pacific region, with resulting risks for mental health problems ,56,57. THigh-risk groups, including those disadvantaged or discriminated against due to the characteristics and intersection of age, gender, sexuality, ethnicity, faith, ability, migration and economic status, may be at greater risk of mental health difficulties during and after disasters ,64. In aThe Asia Pacific Disaster Mental Health Network was established to foster advancements and coordination of psychosocial supports and mental health service delivery, policy development and collaborative research in the region. In line with the priorities of the WHO Thematic Platform for Health EDRM and its research network ,72, the"} +{"text": "Despite the recent advances in treatment, antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) are among the rheumatic diseases with the highest morbidity and mortality. These outcomes are affected by a variety of factors apart from the disease itself, and are driven by infections, cardiovascular disease and drug toxicity. Even after the induction of remission, patients and their treating physicians are challenged by frequent relapses, accrual of chronic damage and impaired quality of life. Given their rarity along with their heterogeneous disease spectrum, patient registries are of utmost need for the study of all aspects of AAV. Already established AAV registries have a significant contribution in the apprehension of these diseases outside the strict context of clinical trials, and are becoming increasingly important as new drugs and treatment strategies are about to be introduced in daily practice. We here describe the design of a contemporary, web-based and easy-to-use patient registry specifically for patients with AAV, including all the necessary domains suggested by international working groups. This project is anticipated to contribute in better understanding of AAV in our country, with a future prospect of contributing to and sharing data with other international registries. B-cell depletion (rituximab) is considered a first line therapy for induction and maintenance of remission in patients with GPA and MPA today.5 However, new issues have emerged, given the similar rates of serious infections with cyclophosphamide-based regimens,4 optimal (regular versus biomarker-tailored) dosing, and the management of patients who relapse while on treatment. Significant research projects on AAV are ongoing or recently completed and published, investigating the role of the novel oral, selective C5a receptor inhibitor avacopan as a steroid-sparing agent6 or clarifying the exact role of plasma exchange and lower dose corticosteroids during induction of remission.7Antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) and carry the highest mortality and morbidity among systemic vasculitides. Even when aggressively treated with glucocorticoids (GCs) and traditional immunosuppressives, mortality is still high (~25% at five years).2 especially in patients with lung involvement, positive PR3 autoantibodies, and high damage index, while it has been shown that the number of relapses correlates with the development of chronic lesions. Prevention, early diagnosis and management of vasculitis-associated damage have been recognised as of paramount importance. Damage in ANCA vasculitis occurs early in the course of the disease, varies according to the type of vasculitis, is correlated with both the disease itself and the treatment the disease itself and the treatment, and significantly affect prognosis.8Nevertheless, the impact and uptake of these promising strategies will need to be studied in real-life settings outside the strict boundaries of clinical trials. Although current therapeutic regimens induce remission in the great majority of patients (70\u201390%), disease relapses are quite common (~40% in 5 years),There are limited data in the literature regarding the long-term prognosis, comorbidities and mortality of patients with AAV in daily clinical practice, outside randomised trials and their extensions. Moreover, the complexity of these diseases in terms of differential diagnosis, the need for interdisciplinary collaboration, the treatment and assessment of outcomes and the long-term vigilance for relapses makes the management of AAV patients quite cumbersome. Due to the rarity of the disease, establishment of patient registries are crucial for the better understanding of the natural course of AAV and, interestingly, registries are one of fields of interest of the EUVAS Research Council along with disease assessment, biomarker studies, epidemiology and aetiology, clinical trials, genetics, toxicity and infection, database, and histology.9 Furthermore, the working group proceeded in the development of AAV-specific patient-reported outcome (PRO) after taking into account and incorporating patients\u2019 perceptive of the impact of the disease on quality of life (AAV-PRO)10 and the implementation of these tools in registries of real-life patients is imperative. Recently, patient registries across Europe and the United States have provided useful information in that direction. Most of these registries are web-based, and this design enables easy access and data entry of participating centers.11The OMERACT (Outcome Measures in Rheumatology) Vasculitis Working Group has recently proposed a core set of outcome measures in AAV research in order to align data collection and assure homogeneity of different datasets. This set includes at least assessment of disease activity, damage, patient-reported outcomes and mortality.To design and establish a Greek Registry, where patients with AAV will be registered and prospectively followed. Candidate participating centres will be rheumatology, nephrology and pulmonary clinics or departments with an expertise in the clinical care of patients with AAV.The registry will include patients with GPA, MPA and EGPA that fulfil 2012 Chapel Hill Consensus Conference Disease Classification Criteria. Patients will be registered irrespective of their age, in order for rare cases of paediatric patients with ANCA vasculitis to be included. Informed consent will be obtained from all study subjects. Patients will be retrospectively and prospectively registered and evaluated at baseline, then every 6 months or at relapse (confirmed or suspected), and data will be entered into an electronic web-based platform. For any new registration, the user will be asked to enter epidemiologic data, a clinical assessment of disease activity and severity/chronicity (VDI), patient-reported outcomes (AAVPRO), comorbidities, hospitalisations (except from those caused by infections), infections (irrespective of severity), laboratory measurements, biopsy and imaging reports and medications. Especially for hospitalisations, infections and medications, universal coding is used to assure optimal data entry. In addition, biologic samples storage (Biobank) is designed, including information on storage of peripheral blood, serum, PBMCs, mRNA in order to enable future biomarker- or basic research projects.AAV are a diverse group of diseases that, although rare, carry high mortality and morbidity and several unmet needs. This study is anticipated to reflect the current clinical and laboratory spectrum of patients with AAV in Greece, to describe treatment regimens currently used and compliance of treating physicians with guidelines, to document rates of chronic lesions and complications related to disease itself or immunosuppressive therapy, to assess efficacy, tolerance and complications of novel biologic agents, and create a biobank of biologic samples from different phases of the disease. Finally, a significant prospect of this study includes the future incorporation of this registry with similar international ones and its participation in multicentre studies held by the vasculitis community."} +{"text": "Generalized Structural Equation Modeling (GSEM) in prediction of injury leading to motorcyclist hospitalization: a case-control study Abstract Background and Objectives: Given that the SEM model includes both structural and measurement models, It is also a method for the exact test of theoretical models and is very useful for causal modeling. The purpose of the present study is to investigate the predictors of injuries caused the hospitalization of motorcyclists using a Generalized Structural Equation Modeling (GSEM) with mediator in a case-control study.In this case-control study, 300 cases and 156 controls were selected from 150 clusters using a cluster random sampling in Tabriz, Iran. Using of motorcycle-riding behavior questionnaire (MRBQ), Attention-deficit/hyperactivity disorder (ADHD). The GSEM model was used to examine the linear direct and indirect linear relationships of variables in the conceptual model and considering the binary response variable of the model. Also, MRBQ were considered as a mediator variable for the underlying and ADHD and Data analysis was performed by STATA14 software.The predictors of injury were: MRBQ, ADHD and Demographic, The results indicated significant linear and direct relationships between odds of injury and cell phone answering , hyper active child , dark hour riding and MRBQ , while significant inverse relation between injury and being married, academic education .Based on the results GSEM model, Due to the significance of the variables, having intervention programs, on the ADHD, and those who answer their cell phones while driving, and dark hour riding is highly recommended.SEM, GSEM, Traffic, Injury, MRBQ, ADHD"} +{"text": "Staphylococcus aureus (MRSA) across the human, animal and environmental compartments in East Africa.The emergence and spread of antimicrobial resistance (AMR) present a challenge to disease control in East Africa. Resistance to beta-lactams, which are by far the most used antibiotics worldwide and include the penicillins, cephalosporins, monobactams and carbapenems, is reducing options for effective control of both Gram-positive and Gram-negative bacteria. The World Health Organization, Food and Agricultural Organization and the World Organization for Animal Health have all advocated surveillance of AMR using an integrated One Health approach. Regional consortia also have strengthened collaboration to address the AMR problem through surveillance, training and research in a holistic and multisectoral approach. This review paper contains collective information on risk factors for transmission, clinical relevance and diversity of resistance genes relating to extended-spectrum beta-lactamase-producing (ESBL) and carbapenemase-producing Enterobacteriaceae, and Methicillin-resistant blaCTX-Ms (45.7%), SCCmec type III (27.3%) and IMP types (23.8%), respectively.The review of the AMR literature (years 2001 to 2019) was performed using search engines such as PubMed, Scopus, Science Direct, Google and Web of Science. The search terms included \u2018antimicrobial resistance and human-animal-environment\u2019, \u2018antimicrobial resistance, risk factors, genetic diversity, and human-animal-environment\u2019 combined with respective countries of East Africa. In general, the risk factors identified were associated with the transmission of AMR. The marked genetic diversity due to multiple sequence types among drug-resistant bacteria and their replicon plasmid types sourced from the animal, human and environment were reported. The main ESBL, MRSA and carbapenem related genes/plasmids were the The high diversity of the AMR genes suggests there may be multiple sources of resistance bacteria, or the possible exchange of strains or a flow of genes amongst different strains due to transfer by mobile genetic elements. Therefore, there should be harmonized One Health guidelines for the use of antibiotics, as well as regulations governing their importation and sale. Moreover, the trend of ESBLs, MRSA and carbapenem resistant (CAR) carriage rates is dynamic and are on rise over time period, posing a public health concern in East Africa. Collaborative surveillance of AMR in partnership with regional and external institutions using an integrated One Health approach is required for expert knowledge and technology transfer to facilitate information sharing for informed decision-making. Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase (ESBL)-producers. For instance, MDR invasive non-typhoidal Salmonella (iNTS) disease poses a major challenge to the clinical management of infections in resource-limited settings especially as alternative more effective antibiotics remain either unaffordable or simply unavailable for majority of patients , ESBL and MRSA , ESBL (13.1%), and MRSA (24.25%) were reported in studies conducted from 2013 to 2016, 2009\u20132012, and 2013\u20132016 respectively. The rise of ESBL, CAR, and MRSA carriage rates in East Africa pose a threat to public health particularly in the geographical areas where the rates are very high. A limitation of this analysis is the fact that these data were collected from unlinked cross-sectional studies conducted in different geographical areas in East Africa; consequently, some important information may have been missed.Figure\u00a0The genetic diversity at antibiotic resistance loci could determine a population\u2019s capacity to cope with future challenges of the antimicrobial drugs used for infection control . The genThe high MRSA carriage rates among patients and health workers in the East Africa is a concern given poor infection prevention and control measures in our settings . In KenyE. coli in humans, animals and their environments are conducted by postgraduate students of the SACIDS Foundation for One Health at the Sokoine University of Agriculture and Muhimbili University of Health and Allied Sciences in Tanzania. This work is attempting to understand the transmission dynamics of AMR genes and their virulence [The World Health Organization, the Food and Agriculture Organization of the United Nations and the World Organization for Animal Health has advocated for a holistic and multisectoral approach to address the AMR problem. This has been strengthened by the collaboration of regional consortia involving local and regional academic and research institutions in Africa, and a joint dedication of efforts to fight against infectious diseases in animals, humans and their environments. Regional consortia such as the SACIDS Foundation for One Health in collaboration with the London School of Hygiene and Tropical Medicine, London International Development Centre, Royal Veterinary College, Chatham House of the Royal Institute of International Affairs in the United Kingdom and the American Society of Microbiology of the United States, have partnered to address AMR problem through research and training. Strategically, surveillance is being supported by phenotypic and genomic data, to understand the flow of resistomes across human, animal and environmental compartments. For instance, research programs focused on genomic epidemiology of ESBLs producing irulence , and wilThe implementation of effective and sustainable AMR surveillance programmes in Africa is hampered by a lack of infrastructure and other resources required to perform optimal surveillance . Most laThe high genotypic diversity of the AMR genes among the bacterial isolates might suggest possible exchange of strains or a flow of genes among different strains due to transfer by mobile genetic elements or multiple sources of resistance bacteria. Such levels of diversity prompt the calling for immediate interventions, including guidelines concerning antibiotics use and regulations governing their importation and sale. However, antibiotic use and regulation is likely to be a very complex system because other factors such as cultural and ecological conditions favour transmission of bacteria. There is a high likelihood that people will have AMR bacteria irrespective of how antibiotics are used. Therefore, control strategies against AMR need to be tailored, beyond antibiotic use and availability, to local practices that affect bacterial transmission. Moreover, the trend of ESBL, MRSA and CAR carriage rates is dynamic and are on rise over time period, posing a public health concern in East Africa. In addition to that, phenotypic and genotypic drivers of AMR should be investigated within an integrated One Health framework. Such investigations will inform transmission dynamics of resistomes across compartments, and facilitate information sharing for informed decision making; ultimately, reducing the spread of AMR genes in bacteria. Further, the application of advanced techniques such as whole genome sequencing for detection of AMR could cut a bridge between clinical research and care, so that case management and treatment decisions can be informed and personalised."} +{"text": "Cells show an impressive range on the pathophysiological relevance of ROS and RNS, including the relevance of second messengers of free radicals like 4-hydroxynonenal, allowing us to assume that the future will reveal even more detailed mechanisms of their positive and negative effects that might improve the monitoring of major modern diseases, and aid the development of advanced integrative biomedical treatments. Our common knowledge on oxidative stress has evolved substantially over the years, being focused mostly on the fundamental chemical reactions and the most relevant chemical species involved in human pathophysiology of oxidative stress-associated diseases. Thus, reactive oxygen species and reactive nitrogen species (ROS and RNS) were identified as key players in initiating, mediating, and regulating the cellular and biochemical complexity of oxidative stress either as physiological (acting pro-hormetic) or as pathogenic (causing destructive vicious circles) processes. The papers published in this particular Special Issue of Cells is to cover broad aspects of these important scientific areas, still focusing on the cellular level. However, since many disorders are based on altered cellular functions involving interactions of reactive oxygen species (ROS) and reactive nitrogen species (RNS) with macromolecules, in this Special Issue we also try to tackle physiological and pathological aspects of cellular ROS and RNS related to specific cellular processes affecting the entire organism.For decades, free radicals were mostly considered as harmful molecules that contribute to the toxic, mutagenic, and carcinogenic bioactivities of different chemical and physical stressors. However, after hydrogen peroxide and nitric oxide were found to have multiple, often cell-type and dose-dependent effects, the new era of interdisciplinary molecular biosciences and translation medicine made significant progress in studies on the pathophysiology of oxidative stress and associated disorders. Therefore, the major goal of this Special Issue of .), known for its ability to damage almost any biomolecule, induce lipid peroxidation, and cause DNA strand breaks i) and the secretion of vonWillebrand factor (vWF) in human umbilical vein endothelial cells (HUVECs), and on the relaxation of rat aorta in response to histamine. They found that VAS2870 attenuated histamine-induced secretion of vWF, although it did not inhibit its basal secretion. However, VAS2870 did not change the degree of histamine-induced relaxation of rat aortic rings constricted by norepinephrine. In accordance, the authors suggest that NOX inhibitors might be useful as a tool for preventing deep vein thrombosis induced by histamine release from mast cells without affecting vasorelaxation, which, of course, requires intense additional studies, both in vitro and in vivo.The association of inflammatory factors, such as histamine, and the onset of oxidative stress affecting the blood vessels was studied by P. Avdonin et al. . In partThe association between oxidative stress and the functional activities of blood vessels is usually addressed in terms of tackling the onset and progression of atherosclerosis. Therefore, S. Fiorelli et al. analyzed the oxidative stress from the aspects of the Nrf2/HO-1 axis in monocyte-derived macrophages (MDMs) obtained from healthy subjects and from patients with coronary artery disease (CAD), in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT) . They fo2+ imbalance and mitochondrial membrane depolarization was attenuated by IH, which also reduced the I/R-induced Ca2+ overload. Moreover, IH increased the expression of superoxide dismutase (SOD), notably of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase, suggesting that IH may indeed protect the cardiomyocytes against H2O2- and I/R-induced oxidative stress, maintaining Ca2+ homeostasis as well as the mitochondrial membrane potential and upregulation of antioxidant enzymes.The frequent consequences of atherosclerotic changes affecting coronary blood vessels are ischemia and reperfusion of the heart, i.e., induced oxidative stress of the cardiac muscle cells. However, there are indices suggesting that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could be beneficiary, and even cardioprotective. This phenomenon was focused on in the research produced by K.T. Young\u2019s group . Aiming Cells deals with novel and challenging topic of oxidative stress modulation as an option to regulate the healing of soft-tissue wounds or even bone fractures [The last paper of this Special Issue of ractures . Thus, Eractures . The autractures . Thus, tractures . In the ractures . Cells show an impressive range on the pathophysiological relevance of ROS and RNS, including the relevance of second messengers of free radicals like 4-HNE, allowing us to assume that the future will reveal even more detailed mechanisms of their positive and negative effects that might improve the monitoring of major modern diseases and the development of advanced integrative biomedicine treatments. Observed together, the papers published in this particular Special Issue of"} +{"text": "Sodium hyaluronate eye drops are frequently prescribed for dry eye disease in South Korea.This study analyzed the trends in the utilization of sodium hyaluronate eye drops and evaluate the impact of the introduction of high-priced disposable forms in the South Korean market.The yearly claims data for sodium hyaluronate eye drops from 2002 to 2015 were retrieved from the National Health Insurance Service-National Sample Cohort. Prescriptions of sodium hyaluronate eye drops were sorted by the characteristics of patients and health care institutions.The number of prescriptions has continuously increased and the share of disposable forms in total prescriptions reached 37% in 2015. Particularly, the prevalence of prescriptions has increased during the study period from 2,562/100,000 persons in 2002 to 14,732/100,000 persons in 2015, while the incidence of prescriptions (new users) has remained steady during the study period, approximately 3,500/100,000 persons. More female patients were noted in terms of general users and new users, and the proportion of male patients was higher in new users than in general users. The average age of general users increased during the study period, while that of new users slightly decreased. Finally, the distribution of prescription category was significantly different between sex and age groups in frequently prescribed users.Eye drops in disposable forms, which are safe and more convenient to use, have expanded the market in South Korea and caused equity issues in utilization. Thus, the utilization of eye drops should be closely monitored from the perspectives health equity. Dry eye disease (DED) is the most common ocular disease causing patients to visit ophthalmology clinics . DED is The management of DED is complicated due to the multifactorial characteristics of DED, and the aim of DED management is to restore the homeostasis of the ocular surface and tear film . Thus, aIn South Korea, sodium hyaluronate eye drops are prescribed for patients with corneal epithelial disorders caused by endogenous and exogenous diseases and are reimbursed under the National Health Insurance Services (NHIS). Endogenous diseases include Sj\u00f6gren's syndrome, cutaneous mucosal syndrome (Steven-Jones syndrome), and dry eye syndrome, while exogenous diseases are caused by surgery, chemicals (including drugs), or the wearing of contact lenses. The majority of these patients are prescribed eye drops for dry eye syndrome . CurrentOphthalmic preservatives have been recognized as a risk factor for corneal and conjunctival inflammation, indicating that preservative-free eye drops reduce iatrogenic dry eye . Thus, cThis study has two aims. First, we will analyze the trends in the utilization of sodium hyaluronate eye drops in South Korea from a large-scale population-based dataset. With this analysis, we could approximate the prevalence of DED in South Korea. Second, we will evaluate the impact of the introduction of high-priced disposable forms in the South Korean market from the perspective of health financing and equity in utilization. To this end, we will analyze prescriptions including sodium hyaluronate eye drops, patients who were prescribed medicines, and health-care institutions prescribing medicines to understand for whom, under what conditions, and how eye drops in disposable forms are prescribed.The National Health Insurance Service-National Sample Cohort (NHIS-NSC), a population-based cohort established by the NHIS, was used for this study . The NHIThe NHIS-NSC consists of four databases, including information on participants and their medical treatments and health examination, and information on health-care institutions, for the period from January 2002 to December 2015. The database on participants includes demographic and socioeconomic characteristics of participants, such as the age, sex, level of income, and types of health insurance. The database on medical treatments covers prescriptions, such as the date and duration of the prescription, the prescribed drug's international nonproprietary name, the dosage, and the prescribing health-care institution. The database on health-care institutions includes types and locations of health-care institutions.Currently, two types of eye drops are available on the market: disposable and multiuse forms. Disposable eye drops were defined as medicines with packing specifications less than 1 ml without the presence of ophthalmic preservatives, while multiuse forms were defined as medicines with packing specifications greater than 1 ml with the presence of ophthalmic preservatives. With these definitions, separated information on prescriptions, patients, and health-care institutions was obtained. Additionally, frequently prescribed users were categorized into two groups: the disposable user group and the multiuse form user group.Descriptive statistics were used to examine the characteristics of prescriptions, patients , and health-care institutions. At the patient level, information on the sociodemographic characteristics of the patients, including sex, age, and types of health insurance, were collected. Types of health insurance included the NHIS for the population and the Medical Aid Program for low-income household. Members of the NHIS were categorized into two types: self-employee and the employee. In South Korea, the premium that the member of NHIS pay are calculated based on their income and assets. Thus, the premium was used to proxy their income level, and separated into quintiles. The first quintile indicates the lowest income, while the fifth quintile indicates the highest income.At the health-care institution level, information on the location and type of institution were obtained. First, the location was divided into several regions based on the administrative district. In the end, four regions were created, including Seoul, metropolitan excluding Seoul, city excluding metropolitan, and rural. Second, the health-care institutions were categorized as primary-, secondary-, tertiary-, and quaternary-care institutions : primaryA deidentified secondary dataset was used for this study, indicating that the study was exempted from review by the Institutional Review Board (IRB) of Ewha Woman's University (IRB No ewha-201903-0005-01).No patients were involved in developing or conducting the research. Thus, the dissemination of the results of the research directly to the eligible participants is not required.The proportion of category IV users (or disposable users) has increased, while that of category I users (or multiuse form users) has decreased during the study period. The proportion of disposable user and multiuse form users in 2013 was 27% and 57%, respectively, indicating that the number of multiuse form users was still higher than that of disposable users among frequently prescribed users. Then, frequently prescribed users in 2005 and 2010 were selected to examine the odds ratio between demographic variables and prescription categories. In this study, we evaluated the trends in the utilization of sodium hyaluronate eye drops in South Korea from a large-scale population-based dataset and analyzed prescriptions, patients, and health-care institutions, which were separated by disposable and multiuse forms, to discuss the impact of the introduction of expensive disposable forms from the perspective of health financing and equity in utilization.et al. (2014) reported that the overall prevalence of DED diagnosis and the prevalence of dry eye symptoms in South Korea were 8 and 14.4%, respectively, in 2010\u201311 USD and 1.7 million (65%) USD for multiuse and disposable forms, respectively. Furthermore, the proportion of disposable users among frequently prescribed users is increasing, indicating that the utilization of disposable forms might be an additional burden for the insurer from the perspective of health financing. For instance, the proportion of expenditure for sodium hyaluronate eye drops in total benefits, including medical service and prescription drugs, increased from 0.06% in 2002 to 0.34% in 2015. Thus, understanding for whom, under what conditions, and how eye drops in disposable forms are prescribed is essential to address their impacts on health financing.Furthermore, introducing disposable forms of eye drops caused equity issue in utilization. In this study, we demonstrated that sex and age of users were associated with utilizing eye drops in disposable forms. Particularly, female users and users under 30 years old (reference more than 60 years old) are more likely to be prescribed eye drops in disposable forms. DED is closely related to wearing contact lenses and eye makeup , which aSodium hyaluronate eye drops are prescription drugs that should be prescribed at health-care institutions. In this study, we found that the majority of eye drops (approximately 90%) were prescribed by primary-care institutions, indicating that DED was the most common disease causing patients to visit ophthalmology clinics. Furthermore, we found that the proportion of the prescription of disposable forms and their speed of adoption were different among various types of institutions. For instance, the proportion of the prescription of disposable forms was in the order of quaternary- tertiary-, secondary-, and primary-care institutions, which might imply that physicians at quaternary-care institutions were more likely to prescribe eye drops in the disposable form to their patients, including patients with glaucoma and patients who need multiple eye drops. However, note that the number of total prescriptions involving disposable and multiuse forms from quaternary-care institutions is much less than that of prescriptions from primary-care institutions, where the majority of eye drops are prescribed. Thus, the total impact of the introduction of disposable forms on health financing is greater in primary-care institutions.We also found an interesting result in variance among four regions, including Seoul, metropolitan excluding Seoul, city, and rural area, for the prescription of disposable forms. The proportion of the four regions in prescriptions involving the disposable form was in the order of Seoul (38%), rural (26%), city (20%), and metropolitan excluding Seoul (15%) in 2004. However, the proportion of the Seoul area slightly decreased, while that of the rural area slightly increased during the study period. Finally, the proportion of the four regions in prescriptions involving the disposable form were converged to 25% in 2015. Similarly, we presented the proportion of disposable forms in the total prescriptions for the publication of any potentially identifiable images or data included in this article.K-BS developed the concept of the paper, undertook the analysis, and wrote the manuscript.The author disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Taejoon Pharmaceutical Co., LTD. However, the funding source was not involved in the study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the article for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dirofilaria (Nochtiella) repens and Candidatus Dirofilaria (Nochtiella) Honkongensis Provide Evidence for Presence of Cryptic Species. The title contains spelling errors and should be corrected to: The Mitochondrial Genomes of the Zoonotic Canine Filarial Parasites Dirofilaria (Nochtiella) repens and Candidatus Dirofilaria (Nochtiella) hongkongensis Provide Evidence for Presence of Cryptic Species.The title currently is The Mitochondrial Genomes of the Zoonotic Canine Filarial Parasites th author, Tran Anh Le, is currently Department of Parasitology, Viet Nam Veterinary Medical University, Ha Noi, Viet Nam. The correct affiliation of the 10th author, Tran Anh Le, is Department of Parasitology, Vietnam Military Medical University, Hanoi, Vietnam.The affiliation of the 10In the manuscript, there is reference to canine blood samples used to amplify partial mitochondrial DNA sequences of the putative species Dirofilaria sp. \"Thailand II\". This is incorrect. It should be noted that the samples came from cats and not dogs."} +{"text": "Most of these applications are still at an early stage of development and have technological challenges and a lack of fundamental comprehension. Furthermore, the functional memristive properties of TiO2 thin films are heavily dependent on their processing methods, including the synthesis, fabrication, and post-fabrication treatment. Here, we outline and summarize the key milestone achievements, recent advances, and challenges related to the synthesis, technology, and applications of memristive TiO2. Following a brief introduction, we provide an overview of the major areas of application of TiO2-based memristive devices and discuss their synthesis, fabrication, and post-fabrication processing, as well as their functional properties.Titanium dioxide (TiO Owing to an appropriate combination of physical and chemical properties, environmental compatibility, and low production cost, polycrystalline TiO2 has found a large variety of applications and is considered to be a promising material for future technologies. One of the most distinctive physical properties of this material is its high photocatalytic activity , biohybrid systems, and sensors, as schematically shown in 2-based memristors. A special focus is placed on the relationships between the synthesis and deposition methods, the effects of post-synthesis treatment, and the resistive switching properties.Currently, the development of TiO2 . Alternatively, TiO2 thin films may serve as an interface material in various biohybrid devices. The bio- and neurocompatibility of a TiO2 film has been demonstrated in terms of its excellent adsorption of polylysine and primary neuronal cultures, high vitality, and electrophysiological activity capacitors the synthesis of a nanostructured material, (ii) deposition of the functional layer, (iii) arrangement of the electrodes, and (iv) post-processing annealing at an elevated temperature under a suitable atmosphere. The first stage is required for traditional chemical synthesis routes, while the first two stages take place at the same time for physical deposition methods.The fabrication of a TiOVT), retention time, switching time, and the resistive switching ratio (ROFF/RON). The main technological, topological, and exploitative characteristics of typical memristive devices are summarized in The choice of fabrication route is thus a trade-off in complexity, cost, scalability, desirable topology , threshold electroforming voltage , the solvent type, and the temperature or TiCl4 have been used as precursors have also been reported have been demonstrated . In these methods, Ti-based precursors are decomposed in the presence of an oxidizer gas mixtures under vacuum (Schmidt et al., 2 thin films that have often been addressed as prototype oxide memristors for many research applications. Numerous recent achievements highlighted in this mini-review demonstrate the rapid development of TiO2-based memristors in various application fields, while the growing interest in these devices is seemingly far from saturation.The current renaissance of the resistive switching phenomenon over the last 12 years has been intimately associated with studies on TiO2 memristors have been outlined in several previous reviews and remain essentially unsolved. Technologically, the emerging properties of memristive systems concern the operational stochasticity, number of distinguishable states, switching energy, switching speed, endurance, retention, and feature size. Their relationship in various types of modern memristive systems has been comprehensively addressed in a recent topical review (Zhang et al., 2 polymorphs (Scanlon et al., 2 memristors by choosing appropriate electrodes and an appropriate operating voltage regime or by affecting the phase ratio, defect structure, and microstructure of the synthesized materials using post-processing annealing under ambient or inert atmospheres (Goren et al., 2. Meanwhile, only a few studies have systematically addressed the effect of thermal annealing at reduced oxygen partial pressures on the resistive and resistive switching properties of TiO2 thin films (Lai et al., The major challenges of TiO2-based memristors, we can expect an increasingly large role of chemical approaches to device fabrication, lowering of the production costs, rapid development of neuromorphic computing systems, and further convergence of artificial electronic neurons with biological cells based on TiO2 thin films.In view of the current trends and challenges of TiOAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In recent years the popularity and application of both research- and consumer-grade wearable physical (PA) activity monitors have witnessed substantial growth in large observational studies and clinical trials. For example, the NHANES and UKBiobank, have collected accelerometry data on thousands of participants contributing to the reputation of wearable technology overall as well as in aging-oriented research. As a result, more aging-focused studies including the Baltimore Longitudinal Study of Aging, Maastricht Study, Finnish Retirement and Aging study, and the National Health and Aging Trends Study, along with clinical trials have introduced accelerometry protocols into their design. The symposium focuses on challenges in the implementation of the objective measurements of PA into large studies on older adults. We will discuss the design of successful projects held and/or completed in the United States and Europe including: (1) types of devices, (2) size of datasets, (3) steps necessary for the successful device implementation, (4) data management and (5) statistical analyses. We will also present primary, PA-related findings in each study, together with funded or planned follow-up work. Collectively, these presentations will improve understanding of the technology and effort necessary for the successful application of objective PA monitoring and the resulting data analysis, providing a better context for investigators in the field of aging who want to introduce wearable devices into existing and upcoming research. The discussion will focus on the future of these technologies in the context of geriatric medicine and gerontology and the consequent steps essential for their best utilization and further expansion."} +{"text": "Incorporating geographic information science and technology (GIS&T) into COVID-19 pandemic surveillance, modeling, and response enhances understanding and control of the disease. Applications of GIS&T include 1) developing spatial data infrastructures for surveillance and data sharing, 2) incorporating mobility data in infectious disease forecasting, 3) using geospatial technologies for digital contact tracing, 4) integrating geographic data in COVID-19 modeling, 5) investigating geographic social vulnerabilities and health disparities, and 6) communicating the status of the disease or status of facilities for return-to-normal operations. Locations and availability of personal protective equipment, ventilators, hospital beds, and other items can be optimized with the use of GIS&T. Challenges include protection of individual privacy and civil liberties and closer collaboration among the fields of geography, medicine, public health, and public policy. Incorporating geographic information science and technology (GIS&T) into COVID-19 pandemic surveillance, modeling, and response enhances understanding and control of the disease.Applications of GIS&T include developing spatial data infrastructures for surveillance and data sharing, incorporating mobility data in infectious disease forecasting, using geospatial technologies for digital contact tracing, integrating geographic data in COVID-19 modeling, investigating geographic social vulnerabilities and health disparities, and communicating the status of the disease or status of facilities for return-to-normal operations.Protections for individual privacy and close collaboration among the fields of geography, medicine, public health, and public policy to use GIS&T are imperative.The spread of infectious disease is inherently a spatial process; therefore, geospatial data, technologies, and analytical methods play a critical role in understanding and responding to the coronavirus disease 2019 (COVID-19) pandemic. Geographic information science and technology (GIS&T) is the academic field centered on geospatial data and analysis. The field encompasses geographic information systems (GIS), spatial statistics and visualization, and location-based data derived from global navigation satellite systems and remotely sensed imagery. Opportunities for incorporating GIS&T into COVID-19 pandemic surveillance, modeling, and response include 1) developing spatial data infrastructures (SDI) for surveillance and data sharing, 2) incorporating mobility data in infectious disease forecasting, 3) using geospatial technologies for digital contact tracing, 4) integrating geographic data in COVID-19 modeling, 5) investigating geographic health disparities and social vulnerabilities, and 6) communicating the status of the disease or status of facilities for return-to-normal operations. Locations and availability of personal protective equipment, ventilators, hospital beds, and other items can be optimized with the use of GIS&T.Current surveillance of COVID-19 at the national and global levels is built on lessons learned from maintaining previously developed databases of contamination and disease, such as FluNet . The assAn important aspect of monitoring the spread of infectious disease is spatial data infrastructure (SDI), composed of the human resources and institutions that create and maintain the foundation to which additional spatial data can be attached and used. Key components of an SDI include geospatial culture and awareness, resources for information and communications technology, common standards for data integration and interoperability, a legal framework for data security and privacy, a common lexicon, the use of robust statistical and epidemiological methods, and interdisciplinary collaboration and partnerships . Along wMaps play a key role in communicating the risks and spread of COVID-19 . InteracThe GIS&T community has long worked toward development of the National Spatial Data Infrastructure (NSDI) for the United States , an effoAlong with handwashing and social distancing, perhaps the foremost mitigation strategy for reducing person-to-person contact and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the absence of pharmaceutical intervention is regulation restricting mobility . Consequently, one key role for geospatial technologies in responding to the COVID-19 pandemic is monitoring population distribution and mobility through the use of social media and location-tracking applications embedded in mobile telephones that employ GNSS, cell phone tower connections, and/or wireless connections .Modeling population distribution and mobility has a long history in GIS&T and focuses on fine-scale estimations of population distribution and mobility ,12, mostMonitoring mobility at the individual level, in addition to the population level, has also emerged as an important use of geospatial technologies, particularly in its application to digital contact tracing. Conventional contact tracing, involving identifying, contacting, and encouraging quarantine for the people with whom an infected person has had close contact to mitigate disease transmission, is labor intensive. The process can be made more efficient and scaled up to large populations by exploiting individual digital mobility data, as well as data indicating proximity among mobile telephones using Bluetooth or related technologies, to computationally show close proximity among individuals . Such loAdvances in GIS&T have been made in modeling the geographic trajectories of individuals throughout their daily lives, their interactions with other people, and their immediate environment using geographic and computational constructs such as activity space and space\u2013time prisms \u201320. HoweA strength of GIS is the ability to integrate diverse spatial data sets based on georeferencing, facilitating the integration of health data with contextual characteristics. Descriptive modeling research that leverages this capability has examined the spatial associations of COVID-19 with socioeconomic and environmental characteristics. This research found, for example, that lower income and income inequality , higher Computational infectious disease models are widely used to predict or forecast the spread of COVID-19 disease and the effects of intervention strategies. Predictive modeling approaches can be generally categorized as SEIR/SIR , agent-bSpatial transportation and mobility data can play an important role in forecasting disease prevalence, where, for example, the effect of nonpharmaceutical interventions on city-level transmission of COVID-19 in China was analyzed using mobility data harvested from mobile telephone location-based services. This method allows one to parameterize the local contact rate and forecast the geographic distribution of disease prevalence under different intervention timing scenarios . RelatedIndices of social vulnerability are place-based variables that incorporate factors such as race/ethnicity and socioeconomic status to encode the vulnerability to adverse health outcomes and other types of hazards . CommuniResources for investigating COVID-19-related social disparities include publicly available data on COVID-19 cases by small areas, such as zip codes , althougThe multidimensional social, economic, and health consequences of the COVID-19 pandemic are geographically inequitable: some places and populations have greater social, economic, health and other effects than other places and populations. Beyond the need to identify such factors as lack of access to resources or the prevalence of pre-existing health conditions is the need to recognize and understand the mechanisms of vulnerability that have been in place and led to the exacerbation of the COVID-19 crisis in some communities. Community recovery from the COVID-19 pandemic requires incorporation of social, economic, and health components and an emphasis on investigating how place shapes the uneven effect of COVID-19.www.ucgis.org/covid-19-resources), the OGC (www.ogc.org/resources-for-COVID-19-from-ogc), and the National Alliance for Public Safety GIS Foundation (www.napsgfoundation.org/resources/covid-19).We have outlined how GIS&T can be used for understanding and responding to the COVID-19 pandemic and future infectious disease epidemics and pandemics. Central to this understanding and response is a commitment for the use of GIS and geospatial technologies as the platform for collecting, integrating, and analyzing georeferenced data on the locations and characteristics of individuals and the spatial distribution of socioeconomic, health, and built and natural environmental characteristics. Geospatial resources for COVID-19 response are available through several organizations, including the University Consortium for Geographic Information Science (Leveraging GIS&T for responding to the COVID-19 pandemic requires a close and extensive collaboration between researchers in the fields of geography, medicine, public health, and public policy. The field of GIS&T has a long history of research in data synthesis, statistical modeling, and computational simulation for spatial data and applications. Recognizing that GIS&T is a theoretical and scientific approach rather than simply a set of analytical tools will facilitate transdisciplinary collaboration. Advances in preserving individual privacy and civil liberties in the age of big spatial data, where geospatial technologies generate massive repositories of individual-level data on movement, health, and behavior widely available, are also necessary. These advances will likely require enhanced government regulations, corporate policies, and technological innovations in data sharing and privacy protection.The COVID-19 pandemic is still in the beginning phase, and the research community is continuing to learn and revise the best way to respond to this global public health crisis. Geospatial data, methods, and technologies have a crucial role to play in understanding and responding to the pandemic, and the lessons learned on the use of GIS&T for pandemic response at this time should enhance preparedness and response for future public health crises."} +{"text": "The burden of substance use disorders in sub-Saharan Africa has been projected to increase by an estimated 130% by 2050. Despite this, little is known about the substance use disorder treatment and prevention systems in the region.The objective of this review is to describe the public sector substance use disorder treatment and prevention systems in Kenya guided by the World Health Organization health systems framework model, with the aim of informing decision-making.We reviewed official government documents obtained from hand-searching the websites of relevant governmental organizations including: Ministry of Health, National Authority for the Campaign Against Alcohol and Drug Abuse, Parliament of Kenya, Ministry of Treasury & National Planning, National Law Reporting Council, Kenya National Bureau of Statistics, the National Non-Governmental Organization (NGO) Coordination Board and the 47 County Governments. We augmented those searches with official documents that the authors were aware of by virtue of being practitioners in the field. Draft and retired documents were excluded. The findings of the search are presented as a narrative review.Mental Health Act 1989, the main legislative framework governing substance use disorder treatment and prevention, focuses on institutional care only. While there are only three public health facilities offering substance use disorder treatment in Kenya, several non-public sector actors are involved in SUD treatment and prevention activities. Unfortunately, there is limited cross-sector collaboration. The Ministry of Health has no specific budget for substance use disorder treatment and prevention, while the National Authority for the Campaign Against Alcohol and Drug Abuse has an annual resource gap of about US$ 5,000,000. The substance use disorder workforce in Kenya has not been characterized.The Mental Health (Amendment) bill 2018. (2) Integration of substance use disorder treatment and prevention into primary health care to increase access to care. (3) Utilization of money from taxation of alcohol, tobacco and betting to increase funding for substance use disorder treatment and prevention. (4) Characterization of the substance use disorder workforce to inform planning. (5) Enhanced collaboration between the government and non-state actors in order to increase access to SUD treatment and prevention.We propose five key strategies for strengthening substance use disorder treatment and prevention systems in Kenya including: (1) Enactment of the The burden of substance use disorders (SUDs) in sub-Saharan Africa has been projected to increase by an estimated 130% by 2050 . In AfriThe World Health Organization (WHO) defines health systems strengthening as the process of improving the six health system building blocks namely service delivery, workforce, health information, medical products, financing and governance in order to achieve optimal health outcomes . A well-Mental Health Act 1989 [Unfortunately, the existing SUD treatment and prevention systems in Kenya are inadequate. The main legislative framework governing SUD treatment and prevention, the Act 1989 is outdaAct 1989 . MoreoveAct 1989 , 16 (ii)Act 1989 , and tarAct 1989 .Since our aim was to describe the public sector SUD treatment and prevention systems, we reviewed official government documents. We hand-searched the websites of relevant governmental organizations for documents and web pages that had content on SUD treatment and prevention. The organizations whose websites were searched include: MOH, National Authority for the Campaign against Alcohol and Drug Abuse (NACADA), Parliament of Kenya, National Council for Law Reporting, Kenya National Bureau of Statistics (KNBS), National Non-Governmental Organization (NGO) Coordination Board, each of the 47 County Governments.The Vision 2030 , Kenya\u2019sMental Health Act, 1989 [Constitution of Kenya, 2010 which devolves health functions to the county governments [Mental Health Act, 1989 [Unfortunately, the ct, 1989 which prct, 1989 . Moreovect, 1989 however ct, 1989 .Mental Health (Amendment) Bill, 2018 [Mental Health Act, 1989 [Constitution of Kenya, 2010 [The proposed ll, 2018 , currentct, 1989 . In addrMental Health (Amendment) Bill, 2018 [Importantly, this bill is aligned with Vision 2030 , and guill, 2018 will theMental Health Act 1989, several other laws contain provisions that seek to address SUD treatment and prevention in Kenya. The Health Act, 2017 [,The Tobacco Control Act, 2007 [, The Alcoholic Drinks control Act, 2010 [and The Narcotic Drugs & Psychotropic Substances (Control) Act, 1994 [Other than the ct, 2017 ,The Tobact, 2007 , The Alcct, 1994 all mandThe Alcoholic Drinks Control Act, 2010 [and the Narcotic Drugs & Psychotropic Substances, Act 1994 [Narcotic Drugs & Psychotropic Substances Act, 1994 [Alcoholic Drinks Control Act 2010 [Act 1994 specificct, 1994 providesAct 2010 , 60.Alcoholic Drinks Control Act 2010 [and the Narcotic Drugs & Psychotropic Substances Act 1994 [Unfortunately, The Act 1994 mandate Act 1994 . In a joAct 1994 . This haWorkplace policies on SUD treatment and prevention are an integral part of SUD management at the institutional level and are an International Labor Organization (ILO) requirement . Such poSUD treatment and prevention services are delivered within the health sector by the MOH, and the County Government Departments of Health; and outside the health sector by the NACADA and various County Government Departments.The key responsibilities of the MOH include developing health policies, managing five national referral health facilities as well as oversight of service delivery at the County level. The County Departments of Health are in turn tasked with the delivery of facility and community based health care at the county level, and report to the MOH . In realThe health sector SUD services however remain scarce and inaccessible. Out of 5800 health facilities run by the MOH and County Departments of Health in Kenya, only three offer SUD rehabilitation services and all are located in urban centers . FurtherThe NACADA is a State Corporation in the Ministry of Interior and Coordination of National Government. Its role centers on SUD prevention . The NACIn the 2019/2020 financial year, 70% of the Counties had their SUD programs under various departments including Public administration, Education, Social services and Youth empowerment Capacity building of faith based organizations, community based organizations and mutual self-help groups by the government in order to make them potential means for SUD treatment and prevention at the grassroots level. (ii) Accreditation of private SUD treatment facilities by the National Hospital Insurance Fund (NHIF) to increase access to specialized SUD treatment. Currently, only three private rehabilitation facilities are accredited .The MOH had no specific budgetary allocation for SUD treatment and prevention . At the The cost of interventions for alcohol use disorders has been estimated and could serve as a guide during planning. For example, public awareness campaigns to prevent harmful alcohol use have been approximated to cost US$ 0.2\u20130.8 per person in the population per annum, and that of brief interventions offered within the health sector US$ 0.4\u20131.8 per person in the population per annum . StrategGlobally, the SUD treatment and prevention workforce is diverse comprising of peers, teachers, counselors, social workers and nurses , 70. CerKenya has a number of sources of information on substance use that could inform interventions. The KNBS in collaboration with various stakeholders conducts several national household surveys. The Kenya Demographic Health Survey collects data on the patterns of alcohol consumption among other health indicators and has been conducted twice so far (in 2003 and 2014) . The GloThe MOH through its health sector indicator manual providesThe WHO recommends that at the minimum, health systems must have nicotine replacement therapy and methadone for the management of SUDs . The KenA limitation of this review is that it describes the SUD treatment and prevention systems in Kenya based on documents and information that was available online. Information unavailable on the internet such as some County government budgets and implementation levels of planned programs was therefore missed out. A future study obtaining data from key informant interviews and review of hard copies of government documents, and guided by a structured tool such as the World Health Organization-Assessment Instrument for Mental health Systems (WHO-AIMS) could prMental Health (Amendment) bill 2018. (2) Integration of substance use disorder treatment and prevention into primary health care to increase access to care. (3) Utilization of money from taxation of alcohol, tobacco and betting to increase funding for substance use disorder treatment and prevention. (4) Characterization of the substance use disorder workforce to inform planning. (5) Enhanced collaboration between the government and non-state actors in order to increase access to SUD treatment and prevention.The SUD treatment and prevention systems in Kenya are under-resourced. We propose five key strategies for strengthening SUD treatment and prevention systems in Kenya: (1) Enactment of the"} +{"text": "The Support at Home pilot program provided financial support for the purchase of home care services by middle-income adults with disabilities in San Francisco to support aging in place. Enrollees had income below the area median and made copayments based on household income. The mixed-methods evaluation of the program incorporated administrative records, surveys of clients and comparison group members, surveys of unpaid caregivers, surveys of paid care providers, and focus groups with clients and unpaid caregivers. Outcome measures included the Older People\u2019s Quality of Life Questionnaire, Patient Health Questionnaire-2, an adapted Burden Scale for Family Caregivers, and self-reported falls, emergency department visits, and hospitalizations. Analyses included pre-post chi-squared and t-test comparisons between client and comparison groups and multivariate regressions. An economic analysis was conducted to learn whether changes in costs associated with reduced health care utilization were greater than the costs of the program. Results indicated statistically significant positive changes in client ratings of personal and financial stress, but not in the composite quality of life score. There were statistically significant reductions in attendance at medical appointments, falls, emergency department visits, and hospitalizations. Similar changes were not found in the comparison group. The focus group data supported the findings regarding personal and financial stress and indicated that clients and their caregivers perceived quality of life benefits. The economic analysis indicated substantial cost savings from the program due to reduced use of medical services. Due to its positive impacts, San Francisco has made Support at Home a permanent program."} +{"text": "Current pathology practice is being shaped by the increasing complexity of modern medicine, in particular of precision oncology, and major technological advances. In the \u201cnext-generation technologies era\u201d, the pathologist has become the person responsible for the integration and interpretation of morphologic and molecular information and for the delivery of critical answers to diagnostic, prognostic and predictive queries, acquiring a prominent position in the molecular tumor boards. In 1953, Crick and Watson\u2019s discovery of the DNA double-helix , Giovanni Battista Morgagni placed anatomo-clinical correlations at the heart of modern medicine [The performance of autopsy has been widely recognized for several decades as a fundamental part of routine pathology practice. In 1761, with the publication of medicine . The lesmedicine .However, since the last decades of the twentieth century, the rate of autopsies has decreased significantly, due to increasing confidence in ante-mortem diagnosis, more complex legislations regarding human tissues procedures and also insufficient priority given to autopsies by pathologists themselves, burdened with increasing workloads of surgical resections, biopsies, and cytology .The declining autopsy rate should be a source of concern among the scientific community, given its great potential for the advancement of medical knowledge and improvement of clinical practice. As demonstrated by the COVID-19 experience, the post-mortem examination, together with state-of-the-art molecular diagnostics, plays a central role in the diagnosis and clinical management of newly emerging diseases .Current pathology practice is being shaped by the increasing complexity of modern medicine and major technological advances . In the However, traditional organ, tissue and cellular pathology lays the foundation for the development of molecular pathology and, as demonstrated by the on-going COVID-19 pandemic, still provides essential tools to greatly enhance clinical practice.Current practicing and future pathologists are called on to actively incorporate molecular knowledge into their diagnostic armamentarium and deeply transform laboratory frameworks and pathology educational training programs.We are facing an epochal evolution of the figure of the pathologist who must necessarily find fertile ground both in laboratories, thanks to economic availability and mental openness towards innovation, and also in the training programs of young pathologists. Studies aimed at new technologies will be a fundamental background for the pathologist\u2013in-training.Collaboration between different professional figures must acquire more and more importance in the context of the MTB. The first experiences of multidisciplinary teams in the molecular field are demonstrating how an integration between different knowledge in specialized fields such as clinical, molecular and surgical pathology and engineering can lead to an increasingly targeted therapy, to an increasingly personalized follow-up and a more precise cancer risk stratification."} +{"text": "Many countries within the European Union report significant difficulties in retaining and recruiting healthcare workers and are facing increasing levels of predicted staff shortages over the long term summarize the accepted papers in this special issue and discuss how they relate to the concept of Healthy Healthcare; and (iii) to present a new research agenda, drawing on occupational health psychology research to further advance our understanding of the concept of Healthy Healthcare.This editorial, therefore, aims to: (i) introduce the concept of Healthy Healthcare\u201d refers to a new interdisciplinary system-based perspective of healthcare practices encompassing three main pillars: (1) quality of patient care; (2) worker health and well-being; and (3) the organization and practices of healthcare organizations. It recognizes that healthcare systems must be organized, managed, and financed in balance with the health and performance of available workers in mind can potentially disadvantage another pillar. Ultimately a system-based perspective considering the dynamics between the patient(s), the worker(s), and the complex healthcare system will lead to a more resource-efficient delivery of high-quality healthcare services.\u201cHealthy Healthcare. The inter-disciplinary nature of Healthy Healthcare aligns well with the discipline of occupational health psychology given that the latter is also inherently multidisciplinary and draws on occupational health and psychology as well as being inclusive of public health, human factors, organizational studies, economics, industrial engineering, and more the organization of healthcare; (ii) workers' health and well-being; and (iii) the quality of care provided.The complexity of a system-based perspective of Broetje et al.). It also includes two different two-wave longitudinal panel studies examining age-related factors among aging healthcare workers . There is a cross-sectional study investigating the relationship between job autonomy, self-leadership, work engagement, and health among healthcare workers , and a process-evaluation qualitative study among hospital executives about the key process factors in implementing health-related work design interventions . The issue also includes a qualitative study exploring the emerging psychosocial risks of healthcare accreditation in workplaces .In total, six papers were accepted. The special issue includes a systematic review examining the influence of psychosocial work characteristics in explaining the mental health of nursing staff for different types of healthcare practices and contexts among a variety of healthcare workers, but also includes insights about the interrelation of the main pillars from the perspective of current systems. This includes healthcare assistants, nursing workers, upper and middle managers within a hospital, different levels of seniority as well as different levels of organizational practices. Moreover, the research questions of these papers address diverse issues related to Healthy Healthcare through different theoretical frameworks such as the JD-R Model and theory , the full concept of Healthy Healthcare remains theoretically as well as empirically untested, and further research is needed to develop and examine the core concepts postulated by it. Emphasis needs to be placed on linking different antecedents of its three core pillars, including the mechanisms that explain these relationships to possible outcomes among patients, healthcare workers, and organizations. These will contribute to developing and refining the overarching theoretical model presented in Multilevel study designs. Occupational health researchers typically neglect the fact that relationships are situated within a wider context, with important factors at the organizational, sectoral, societal, and national level all influencing the three pillars of Healthy Healthcare .Van der Heijden et al.; de Lange et al.), gender, ethnicity, and immigrant workers . These potential interventions aim to ensure employee health and well-being can also give voice and provide insights on how individuals make sense of the healthcare system developing an overarching theory and concepts of Healthy Healthcare expanding our focus of well-being to include more positive manifestations; (vi) focusing on primary and organizational-level interventions; and (vii) embrac different research methodologies and paradigms.A system-based perspective is needed to address the challenges faced in healthcare and to increase the uptake of knowledge from occupational health psychology into healthcare. The All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The widely-cited failure within the Millennium Development Goals to adequately reduce infant deaths and reverse maternal health inequalities prompted incorporation of new goals in the 2016 UN Sustainable Development Goal (SDG) three to \u2018ensure healthy lives and promote well-being for all at all ages\u2019 . With amAnnually, the placental disorders of pregnancy are associated with 46,000 maternal and 2.5 million perinatal deaths [While placental disorders of pregnancy are well investigated in HICs, this is not so in LMICs. LMIC-based placental disorder research is under-represented in the global portfolio. Moreover, the pathways to disease within a resource-constrained setting in sub-Saharan Africa are likely to differ from pathways in HICs where much of the research has been conducted. For example, synergistic challenges of malnutrition, rural settings underserved by transport infrastructure and health facilities, high burdens of infectious diseases, and other adverse social determinants of health may contribute to pathways of disease in ways that are currently not captured by HIC research. Understanding the interactions between placental complications and contextual factors may provide a critical step towards the development of precision healthcare to optimise maternal, fetal and infant outcomes.The PRECISE Network is a new and interdisciplinary group of research scientists and health advocates from sub-Saharan Africa, Europe, Canada and the USA, that is investigating the origins and outcomes of the placental disorders in sub-Saharan Africa. Funded by the UK Research and Innovation Global Challenges Research Fund (GCRF), PRECISE aims to develop a robust clinic-based research infrastructure, database and biobank that will catalyse formative research describe the pathways to placental disorders and their complications in sub-Saharan Africa, and inform the design of effective interventions. Importantly, this programme will provide essential information about the impact of placental disorders on women\u2019s lives and their communities.The five papers in this supplement introduce the scientific scope and vision of this ambitious programme of work and describe the development of key components of PRECISE: the study protocol, clinical database, biorepository, qualitative work plans, and partnership and capacity-building elements. The first three papers describe the design of the prospective pregnancy cohort study and the research platform to collect epidemiological data and biological samples from approximately 10,000 pregnant Gambian, Kenyan and Mozambican women, 1500 of whom we anticipate will have a pregnancy complicated by at least one placental disorder. In addition, we will recruit 1800 non-pregnant women of reproductive age as a control group to provide representative regional data and biological samples. The unified data collection platform of the PRECISE database and the biorepository links together sociological, clinical and discovery bioscience research. The second and third papers in this series describe the issues and challenges around their creation, development, management and scientific uses. PRECISE takes a 360\u00b0 approach to understanding both individual-level co-exposures and contextual factors associated with the placental disorders. The fourth paper in the series describes the value of qualitative research in helping to understand quantitative and biological data. The fifth paper in the series brings the picture of the PRECISE Network together with capacity-building in research infrastructure, strengthening emerging leaders in reproductive science and supporting advocacy for research. Together, the papers in this supplement describe a vision and the developmental journey of research platform that seeks to fill current knowledge gaps related to placental conditions in sub-Saharan Africa, and strengthens capacity for research and health improvement related to placental disorders."} +{"text": "Percutaneous Transforaminal Endoscopic Discectomy (PTED) offers an exceptional visualization of foraminal anatomy. Dorsal root ganglion and adjacent foraminal structures are satisfactorily visualized, thereby minimizing the risk of their intraoperative injury. Percutaneous Transforaminal Endoscopic Discectomy (PTED) offers an exceptional visualization of foraminal anatomy. Dorsal root ganglion and adjacent foraminal structures are satisfactorily visualized, thereby minimizing the risk of their intraoperative injury Percutaneous Transforaminal Endoscopic Discectomy (PTED) represents a novel minimally invasive method for surgical treatment of lumbar disc herniation (LDH). PTED provides access to the underlying pathology through Kambin's triangle, a right angle triangle located at the lower portion of lumbar intervertebral foramen (LIF). This triangle defined by the exiting nerve root as the hypotenuse, the posterolateral edge of superior endplate of underlying vertebra horizontally and the superior articular facet vertically.Authors have no conflict of interest to declare.KS: involved in conception and design, acquisition of data, analysis and interpretation of data, critical revision of manuscript, general supervision, and final approval. GN: involved in acquisition of data, drafting of manuscript, and critical revision of manuscript. TT and GM: involved in acquisition of data, analysis and interpretation of data, and critical revision of manuscript.Conduction and publication of this specific article was approved by Institutional Review Board and Ethics Committee of Interbalkan European Medical Center, Thessaloniki, Greece."} +{"text": "The AFU global initiative begin with a collaborative agreement by Arizona State University (ASU), Dublin City University (DCU), and the University of Strathclyde in 2012. The vision was to spur other universities to be fully inclusive of all generations. In 2013, ASU and DCU created a Trans-Atlantic Catalyst Fund to spur AFU initiatives at each institution, with an early focus on research in on dementia, technologies for \u201caging in place,\u201d challenges of caregiving, healthy and active aging, and retirement community design. Since then, ASU has embedded Age Friendly practices throughout the institution via creation of a new foundational charter , creation of ASU-wide Center for Innovation in Healthy and Resilient Aging, a re-purposed Osher Lifelong Institute, construction of the Mirabella community (twenty-story gateway for older adults into ASU), new inter-generational learning platforms, and implementation of universal learning systems."} +{"text": "Diseases related to Coronavirus-19 and their consequences APS , b are fThese conditions may also provide us with a unique opportunity to engage in studies that may be able to provide important and crucial information to understand the various ways and the extent to which the COVID-19 and its consequences may be impacting on language function and cognition, development of linguistic categories, cross-language learning, language-specific concept formation, memory and retrieval of specific events, the role of emotions on language production, etc.Semantic analysis of medical misinformation on social media during the Covid-19 pandemicUsing public figures as case studies for how language has changed during the course of the pandemic. Using their social media posts over time to provide linguistic data.Analysis of pandemic narratives. Asking people to speak about their experience of being isolated, how their memory (for what category) may be affected, what gives them comfort, changes in perceptions and language expression, etc.Linguistic content analysis of individuals with or without a previous history of traumaIssues related to differential effect of increased emotional concern on language learning and language performance in children, young adults, and the elder populationsImpact of change in attentional preoccupation on language functioningImpact of COVID-19 on specific mechanism involved in reading, writing, concept formation, abstract thinking, etc.Difference and quality of metaphor and changes in dimension of metaphor in general population, children, elderly in relation to the Coronavirus experienceMetaphor interpretation and reading abilityOrganization in speech eventsSpeech perception in its multilevel processing systemCoding and sentence retrievalChanging in propositional reasoning with or without propositionDevelopment of young children\u2019s awareness of words, syntax, grammatical structures, etc.Children\u2019s conversational repairsParsing strategies and discourse contextChanges in comprehension of complex sentences: A Developmental analysisFunction of stages in the acquisition of syntaxImpact of emotional conflicts in voluntary and involuntary component of speechProcessing of idioms with multiple meaningsEffect of gender and topic on speech processing, production, stylesSemantic and syntactic processing in monolingual and bilingualsConditional reasoning and semantic contextUnderstanding and processing linguistic time sequenceChildren\u2019s Knowledge of propositional phrase structureChildren\u2019s concept of wordIdentifying deception in language communicationChanges in electrophysiological correlates of semantic featuresImpact of increased emotionality and ambiguity in Dyslexic individuals\u2019 reading and language processing/productionImpact of ambiguity on language perception and judgment of intentionality in normal and paranoid subjectsChanges in linguistic markers: Concepts of health, illness, and diseaseSemantic and pragmatic factors in the representation of near and far or spatial dimensionsLanguage acquisition and children\u2019s representation of knowledgePerception of stress contrasts in semantic and nonsemantic contexts by children and adultChanging in mentalism and language productionBilingual frequency encodingInput/output switch in bilingual code-switching of ordinary and emotionally-laden contentEffect of stress on linguistic generalization in bilingualsLanguage processing and language organization in bilingual populationSpeed perception: Word recognition in foreign languageProcessing of COVID-19 experience among the deaf and mute populationsSemantic and phonemic verbal fluency in blindsEtc.In response to this challenge, we are launching a call for specialized contributions meant to help address some of these challenges. We are accepting contributions in a form of special issues or individual manuscripts focusing on research and theoretical constructs geared at advancing and guiding research methodology for a variety of topics related to psycholinguistics. Below are some of the themes to consider:For any questions about the special issue or suitability of a manuscript, please feel free to contact the Editor-in-Chief at javierr@stjohns.edu or initiatives@stjohns.eduWe are requesting a brief abstract of no more than 500 words clearly stating the specific relevance of the manuscript in addressing the contribution of psycholinguistic science in advancing our understanding of the impact of COVID-19 on language processing and production, neurolinguistic issues likely to be affected, impact on psycholinguistic research, etc. We welcome innovative linguistic models likely to encourage new ways of fulfilling our scientific responsibility in virtual contexts while protecting the scientific integrity of the academy. Those submitting a special issue topic should include a brief abstract for each of the contributions to be included in that special issue with the information listed below.Please, include a cover letter providing names, email addresses and other relevant contact information for three independent reviewers . Reviewers from different career stages, institutions, and countries are encouraged. It should also include the following to be submitted to the Editor-in-Chief, Rafael Art. Javier (javierr@stjohns.edu and initiatives@stjohns.edu).Abstract submission: June 1, 2020.Submission of complete manuscript: October 1, 2020.Title of the manuscript (s)List of author (s) and affiliation (s)Abstract (s)Estimated time of completionWhen submitting your proposal (s), include the following for each manuscript, in addition to the cover letter:Accepted manuscripts will be electronically published on an ongoing basis. The first special issue is expected to be published by June 2021. Subsequent special issue publications will follow, if appropriate."} +{"text": "Francisella tularensis, isolated from diverse sources, have been reported in recent years. In this announcement, we present the complete sequence of the circular chromosome of one of the closest neighboring genera of Francisella, the type strains of Allofrancisella inopinata and Allofrancisella frigidaquae.Near neighbors to the causative agent of tularemia, Francisella tularensis, isolated from diverse sources, have been reported in recent years. In this announcement, we present the complete sequences of circular chromosomes of one of the closest neighboring genera of Francisella .Near neighbors to the causative agent of tularemia, Francisellaceae, named Allofrancisella, was published, with three different species and of the type strain of Allofrancisella frigidaquae SYSU 10HL1970 , in addition to the already published complete genome sequence of the type strain of Allofrancisella guangzhouensis . Short-read sequencing libraries were prepared using a Nextera XT 600-cycle kit and sequenced on an Illumina MiSeq sequencer, followed by trimming using Trimmomatic under the accession no. CP038017, SRR11853073, and SRR11853074.These complete genome sequences are the first versions and have been deposited in GenBank/SRA. Genome and read sequences for SYSU YG23 (FSC1302) are available under the accession no."} +{"text": "Multiple sclerosis (MS) is a chronic inflammatory/demyelinating disease of the central nervous system (CNS) animal models of MS etiopathology, (ii) cellular processes in MS pathophysiology, and (iii) tools and biomarkers enabling investigation of Titus et al. and Sen et al. summarized the most updated models supporting either the outside-in or the inside-out theory of MS. In particular, the first study concluded that, due to the heterogeneous manifestation of MS pathology, a combination of both paradigms, rather than one of the two, may better explain the origin of MS. Conversely, the second article supported the value of more recently developed models, like the cuprizone (CPZ) mouse, to investigate primitive changes occurring in MS brains. Interestingly, CPZ models seem ideal to reveal the mechanisms involved in MS origin before the immune attack intervenes, and to study MS progression in conditions of immune reaction and protection.Ferr\u00e8 et al. provided an update of genetic factors associated with MS onset, progression and treatment response. At present, the majority of genes and biological processes associated with a higher MS risk are implicated in immune functions enables identification of focal demyelination in white matter and cortical lesions already from the earliest phases of MS. Lesion burden was associated with serum neurofilament light chain (sNfL) levels, a biomarker of axonal injury. Moreover, the 2-year longitudinal changes of cortical and white matter lesion burden correlated with the cognitive performances of MS patients. This underlined the relevance of MRI biomarkers and sNfL to identify from the earliest disease phases reliable markers of neurodegeneration, disease severity and progression.Pathological studies and experimental models are the gold standard approaches to investigate MS pathophysiology. However, recently, several laboratory, neuroradiological and neurophysiological tools have been applied to define reliable biomarkers for understanding MS development and progression Frontiers in Cellular Neuroscience, -Immunology, and -Neurology provides an integrated overview of the \u201chot topics\u201d in the field of MS cause. Emerging from the article collection is a complex picture where a dichotomy between outside-in/inside-out theories is replaced by a more integrated vision where both theories might equally apply according to the specific condition. The studies published in this issue emphasize the need for a re-evaluation of cellular processes, previously regarded as pure indicators of immune attack , in combination with the individual (genetic) variability of MS patients, and the development of highly predictive experimental models/accurate biomarkers to unravel the unknown cause of the MS in the coming years.In conclusion, this issue of AL, PP, and B'tH wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Neglected tropical diseases (NTDs) are a group of infections that are prevalent in many of the tropical and sub-tropical developing countries where poverty is rampant. NTDs have remained largely unnoticed in the global health agenda. There is a substantial gap between the burden of disease for NTDs in cardiovascular diseases (CVD) and research devoted to the affected populations. We created a Latin-American initiative with emerging leaders (EL) from the Interamerican Society of Cardiology (IASC) with the objective to perform multiple systematic reviews of NTDs and other infectious diseases affecting the heart: The NET-Heart Project.To describe the rationale and design considerations of the NET-Heart project.The NET-Heart Project is a collaborative work of the IASC EL program. The main objective of the NET-Heart project is to systematically evaluate the available evidence of NTDs and other infectious diseases and their cardiovascular involvement. As a secondary objective, this initiative aims to offer recommendations and potential diagnostic and therapeutic algorithms that can aid the management of cardiovascular complications of these infectious diseases. After an expert discussion 17 initial infectious diseases were selected, for each disease we created one working group. The project was structured in different phases: Systematic review, brainstorming workshops, analysis and results, manuscript writing and recommendations and evaluation of clinical implications.The NET-Heart project is an innovative collaborative initiative created to assess burden and impact of NTDs and other infectious diseases in CVD. NTDs can no longer be ignored and must be prioritised on the health and research agenda. This project aims to review in depth the evidence regarding cardiac compromise of these serious conditions and to propose strategies to overcome barriers for efficient diagnosis and treatment of cardiovascular complications. NTDs are a group of bacterial, parasitic, viral and fungal infections that are prevalent in many of the tropical and sub-tropical developing countries where poverty is rampant affecting more than one billion people . By contAccording to the last meeting of the Strategic and Technical Advisory Group for NTDs, the World Health Organization (WHO) has in its portfolio a diverse group of heterogeneous diseases, such as: Chagas disease, Buruli ulcer, Rabies, Soil-transmitted helminthiases, Trachoma, Schistosomiasis, Snakebite envenoming, Scabies and other ectoparasites, Taeniasis/Cysticercosis, Dengue and Chikungunya, Dracunculiasis (guinea-worm disease), Leishmaniasis, Leprosy (Hansen\u2019s disease), Echinococcosis, Foodborne trematodiases, Human African trypanosomiasis (sleeping sickness), Onchocerciasis (river blindness), Lymphatic filariasis, Mycetoma, Yaws (Endemic treponematoses), chromoblastomycosis and other deep mycoses . NTDs haNTDs cause a significant portion of disease. In the 2010 Global Burden of Disease Study, NTDs accounted for 26.06 million disability-adjusted life years (DALYs) . MoreoveCVD is the leading cause of mortality worldwide . More th9There is a substantial gap between the burden of disease for NTDs in CVDs and research devoted to the affected populations. Furthermore, considering the difficulties to access healthcare services that exist in many regions affected by NTDs, the usual recommendations may not be easy to implement so alternative strategies might be necessary. We created a Latin American initiative with the EL program from the IASC with the objective to perform multiple systematic reviews of NTDs and other infectious diseases affecting the heart: The NET-Heart Project.The purpose of this paper is to describe the rationale and design considerations of the NET-Heart project.The NET-Heart project is a collaborative work of the IASC EL program.The EL program is comprised of a group of enthusiastic, talented and creative young cardiologists, residents, pre-grad students and fellows from different countries of north and south America Figure .The main objective of the NET-Heart project is to systematically evaluate the available evidence of NTDs and other infectious diseases and their cardiovascular involvement. As a secondary objective, this initiative aims to offer recommendations and potential diagnostic and therapeutic algorithms that can aid the management of cardiovascular complications of these infectious diseases.After consulting experts in tropical diseases and cardiologists, we chose the infectious diseases that presented major impact on the cardiovascular system. We selected 17 infectious diseases: human immunodeficiency virus, dengue, zika, chikungunya, tuberculosis, African trypanosomiasis, malaria, Chagas, schistosomiasis, Lyme, cysticercosis, echinococcosis, fascioliasis, leishmaniasis, coronavirus disease 2019, rabies and toxoplasmosis.For each disease we created one working group led by a principal investigator with a co-investigator, an expert on the infectious disease to be investigated, and a supervisor. Globally they had a director (AB) and coordinator (CS) Table .The project was structured in four main phases.Systematic review: It includes studies evaluating the infectious disease and its cardiovascular involvement. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in conducting and reporting the systematic reviews .\u201cBrainstorming\u201d Workshops: Based on the systematic review research results, workshops were held with the experts to determine the focus and design of the study .Analysis and results.Manuscript writing and recommendations and evaluation of clinical implications.All initial meetings and workshops were conducted through video conferences. Currently, the vast majority of the project\u2019s working groups are starting phase 3.The NET-Heart project is an innovative collaborative initiative to assess burden and impact of NTDs and other infectious diseases in CVDs. Considering that the burden of traditional risk factors cannot fully explain the increase in CVDs in LMICs, and that there is lack of information about the contribution of NTDs to CVD, we aim to review in depth the evidence regarding cardiac compromise of these serious conditions. We also intend to propose strategies to overcome barriers for early diagnosis and efficient treatment of cardiovascular complications."} +{"text": "This study examined the effect of registered nurse (RN) staffing level, work environment, and education on adverse events experienced by residents in nursing homes. A cross-sectional study was conducted with 216 RNs working in nursing homes who were selected using random stratified sampling by location and bed size. Self-reported questionnaires regarding staffing level, work environment, education level, adverse events, and nurse characteristics were administered. Data from the National Health Insurance Service were used to describe nursing home characteristics. Both multiple and multinomial logistic regressions were used to control for the characteristics of nurses and nursing homes, and investigate the effects of nursing staffing level (number of older adults assigned to a nurse), work environment , and level of nursing education on the adverse events experienced by residents. An increase of one resident per RN was significantly associated with a higher incidence of pressure ulcers . Poor work environment increased the incidence of adverse events such as pressure ulcers and sepsis . Compared to RNs with a baccalaureate or higher, RNs with diplomas reported increased incidence rates of pressure ulcers . RN staffing, work environment, and education level affect the incidence of pressure ulcers, and the work environment affects the incidence of sepsis among residents in nursing homes. Policy-wise, improving the level of nurse staffing, nursing work environment, and nursing education will improve health outcomes of residents."} +{"text": "The use of ultrasound (US) in emergency departments (ED) has become widespread. This includes both traditional US scans performed by radiology departments as well as point-of-care US (POCUS) performed by bedside clinicians. There has been significant interest in better understanding the appropriate use of imaging and where opportunities to enhance cost-effectiveness may exist. The purpose of this systematic review is to identify published evidence surrounding the cost-effectiveness of US in the ED and to grade the quality of that evidence.We performed a systematic review of the literature following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies were considered for inclusion if they were: (1) economic evaluations, (2) studied the clinical use of ultrasound, and (3) took place in an emergency care setting. Included studies were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards checklist.We identified 631 potentially relevant articles. Of these, 35 studies met all inclusion criteria and were eligible for data abstraction. In general, studies were supportive of the use of US. In particular, 11 studies formed a strong consensus that US enhanced cost-effectiveness in the investigation of pediatric appendicitis and 6 studies supported enhancements in the evaluation of abdominal trauma. Across the studies, weaknesses in methodology and reporting were common, such as lack of sensitivity analyses and inconsistent reporting of incremental cost-effectiveness ratios.The body of existing evidence, though limited, generally demonstrates that the inclusion of US in emergency care settings allows for more cost-effective care. The most definitive evidence for improvements in cost-effectiveness surround the evaluation of pediatric appendicitis, followed by the evaluation of abdominal trauma. POCUS outside of trauma has had mixed results. Ultrasound (US) is well established as a safe and effective imaging modality for the rapid diagnosis and management of emergency conditions. At the bedside, it also improves success and patient safety during invasive procedures \u20135. In thThere is a common assumption that US is cost-effective in emergency care settings as it is diagnostically valuable, rapid, and less expensive than other imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) . HoweverCost-effectiveness analysis is a tool that combines economic and health outcome data to produce standardized ratios of costs and benefits. The outputs of CEAs allow for comparison of diagnostics that vary by both price and clinical utility, and generate important data to support decisions related to health policy and investment. The validity and reliability of CEAs are highly dependent on the rigor with which they are conducted. In 2013, health economists developed consensus-based guidelines on the conduct and reporting of health economic evaluations, called the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist .We present a systematic review of the published evidence surrounding the cost-effectiveness of US in emergency care settings. Our aim is to characterize the existing knowledge regarding the costs and benefits of emergency US, to examine the quality of cost-effectiveness studies using the CHEERS checklist, and to provide guidance for future research efforts.A systematic review of the literature was performed using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines . The revwww.covidence.org), an online platform for systematic review. Studies were considered for inclusion if they were: (1) economic evaluations that assessed costs and outcomes of comparative strategies; (2) studied the clinical use of US; and (3) took place in an emergency care setting. Two reviewers with experience in reading, writing and reviewing economic evaluations independently assessed titles and abstracts for inclusion in a blinded fashion. Studies progressed to a full-text review if both reviewers agreed on the relevance based on the research question. Studies then underwent full text reviews for eligibility by each reviewer. Disagreements were resolved by consensus. The following information was extracted from each of the studies in the review: country, year of publication, intervention, comparator, time horizon (the time over which the costs and effect are measured), discount rate (the rate at which future costs and benefits are discounted), perspective (which costs are included or excluded), health outcome, sensitivity analyses (an assessment of the level of uncertainty in the modeling), and findings.All studies were collated and screened for eligibility through Covidence , biliary, venous, and renal applications. A small group of studies also evaluate general US processes and impact in the emergency department (ED). Tables We identified 11 studies that assessed the cost-effectiveness of US in the evaluation of acute appendicitis \u201328. The Six studies examined US in the setting of acute trauma \u201334. TheySix studies examined US in the setting of renal, biliary, or venous pathology \u201340. The Three studies assessed US in the evaluation of emergency OB/GYN complaints \u201343. One Four studies assessed echocardiography in the emergency care setting \u201347. ThreFinally, we identified a collection of studies evaluating the downstream impact of emergency US on resource utilization \u201352. One While we tailored our search criteria to identify formal attempts at CEA, considerable variability remained in the quality of the economic evaluations conducted in the studies we identified. Most studies received about half the possible points on the CHEERS checklist. Inadequacy in the performance or the reporting of study perspectives, preference-based health outcomes , modeling assumptions, transparency of costs, characterization of uncertainty, and incremental cost-effectiveness ratios contributed to the majority of downgrading. For example, only nine of the 35 studies presented any characterization of the uncertainty surrounding their cost-effectiveness results, only seven presented an incremental cost-effectiveness ratio, and only 11 explicitly stated the economic perspective from which they were calculating costs.To our knowledge, this is the first systematic review to broadly evaluate the cost-effectiveness of US in the emergency care setting across all applications, including both radiology-performed and POCUS exams. The body of literature identified through this systematic review is fairly consistent in supporting the increased cost-effectiveness of integrating US in emergency care settings across a variety of applications. Healthcare systems have begun to focus on value-based approaches throughout the hospital including the ED , and theOf the studies identified in this systematic review, those pertaining to the cost-effectiveness of US in the ED evaluation for pediatric appendicitis were the most plentiful and consistent in demonstration of cost-effectiveness gains, particularly when used in conjunction with clinical decision rules \u201328. ThreUse of POCUS evaluation of trauma is ubiquitous and recommended by the American College of Surgeons . The sixCost-effectiveness of consultative ED US was demonstrated across a variety of applications, including echocardiography, appendicitis, venous thromboembolism, renal, and obstetric. This is consistent with a prior narrative review that demonstrated increased cost-efficiency of US across the spectrum of clinical medicine .The studies identified in this review generally support the cost-effectiveness of POCUS, although some reach the alternative conclusion. The aforementioned studies evaluating POCUS in trauma consistently demonstrated cost savings. Additionally, multiple studies demonstrated potential cost savings in POCUS for biliary and OB/GYN applications , 37, 42.None of the studies included in this systematic review specifically address the widely-inferred cost-effectiveness of POCUS due to increased efficiency and patient throughput, or the decreased adverse iatrogenic events due to US guidance of procedures \u201359. ThisThis systematic review sought to identify all relevant articles by searching five databases without language or date restrictions; however, it remains possible that pertinent articles were missed. Multiple independent reviewers were utilized at each step of the study selection and data abstraction process to minimize the likelihood of excluding relevant studies. Additionally, the mixed quality of methodology and reporting surrounding the economic evaluations conducted in these studies is notable. Most authors did not frame their analysis as a formal cost-effectiveness study, which may have led to the lack of robust methodology. Both past and recent reviews of cost-effectiveness studies in radiology have highlighted the need for standardized approaches , 61. ThiIn summary, the body of existing evidence, though limited, is generally supportive of the cost-effectiveness of US in the emergency care setting. The strongest evidence of cost-effectiveness of ultrasound in the ED exists in the evaluation of pediatric appendicitis and of abdominal trauma. Further study, using established best-practice standards in the methodology of cost-effectiveness analysis, is needed to definitively establish the cost-effectiveness of consultative and POCUS across a variety of applications in emergency care settings."} +{"text": "To develop a clinical technique for objective estimation of exact location and degree of participation of face and neck soft tissues in age-related deformations for determine effective mini-invasive treatment techniques.Ultrasound examination was performed in 2017-2019 at 63 patients with age-related face changes. Examination was done in the vertical position for determine the role, exact location and participation degree of different soft tissues of the face and neck in age-related changes.Great diagnostic value of ultrasound examination of involutional changes in soft tissues of lower third of face and neck was noted to determine all causes of contour age-related deformities. These results were used to choose effective minimally invasive methods for correction.Ultrasound examination is a non-invasive, harmless, clinically available, inexpensive examination that allows to determine exact localization and degree of participation of different soft tissues of face and neck in age-related changes. That is very important for planning and use different minimally invasive techniques for facial and neck rejuvenation. As the people\u2019s life in the world has increased, they want to stay longer healthy, active, young and look good.Historically, in plastic surgery, methods for objective assessment of deformities in the lower third of the face and neck are not so important for open surgical techniques, when a surgeon can correct his actions based on intraoperative situation. Good visualization of tissues is impossible during minimally invasive correction, but it is very important for objective evaluation of tissues causing the deformation and for correct planning the actions of plastic surgeon. The first report on facial muscle imaging using ultrasonography was published in 1988.The aim of our research was to develop a clinical technique for objective estimation of exact location and degree of participation of face and neck soft tissues in age-related deformations for determine effective mini-invasive treatment tactics.The prospective analysis of examination and treatment of 137 patients with aged-related involutional changes in soft tissues of lower third of face and neck was performed in Federal Research Clinical Center of the FMBA in the period from 2017 to 2019. The stages of the study were approved by the Ethics Committee of the N.I. Pirogov Russian National Research Medical University . We have obtained the patent \u2018Method for choosing treatment techniques for age-related involutive changes in the face and neck soft tissues\u2019 RU 2710671 30.12.2019. Written consent of all patients to use the results of research and photos was obtained.The age of patients was from 38 to 62 years. Among them, women were 121 (88.3%), men \u2013 16 (11.7%). The average age was 49 \u00b1 0.5 years (\u00b1 standard deviation average). Presurgery ultrasound examination was done to 63 patients. The examination was performed using an ultrasound device Voluson E8Voluson E8 (Austria), a linear sensor 9 L, with a radiation frequency of 3-8 MHz. Ultrasound examination was done in the vertical position of patient to determine the maximal point of soft tissues ptosis of lower third of the face and submandibular area. Then tissue composition was determined using ultrasound without compression in this position. Parameters were measured: surplus subcutaneous and subplatysmal adipose tissue and its thickness, the thickness of platysma and the level of divergence of the edges of platysma from the mandible edges, ptosis platysma strands. Composition of tissue disturbing the contour of lower jaw from both sides was defined in the same position of patient. The thickness of the skin, subcutaneous fat and ptosis of muscles were assessed, i.e. the degree of participation of each tissue in age-related deformities.During our work we noted great diagnostic value of ultrasound examination of involutional changes of soft tissues of the lower third of the face and neck to determine all the causes of contour deformities and to define minimally invasive methods for their correction. Some clinical cases are present for illustration.Patient H, 45 years old, complained of ptosis of soft tissue face and neck, violation of aesthetic. Clinical diagnosis: Age-related soft tissue atrophy of lower third of the face and neck. During examination we found slight sagging of soft tissues in the lower third of the face and submandibular area. There were slight excess skin and wrinkles with possibility of correction without excision and formation of deforming relief .On ultrasound examination accumulations of adipose tissue was found in the lower third of the face, neck and chin (73% of the thickness of soft tissue that violated contours of the lower jaw and the neck-submandibular angle). There were no atrophic age-related changes in platysma .Result of ultrasound examination showed that the local removal of excess subcutaneous fat in areas of disturbed contours of lower jaw and submandibular area was enough to correct the aesthetic lines of these areas, it was confirmed by the results of treatment of the patient .Patient G., 54 years old, complained of soft tissue ptosis of the face and neck. Clinical diagnosis: Age-related soft tissue atrophy of lower third of the face and neck. During examination we found slight sagging of soft tissues in the submandibular area and platysma strands, painless and moderately displaced by palpation. There were excess skin and wrinkles with possibility of correction without excision and formation of deforming relief .On ultrasound examination in the vertical position of the patient we found ptosis of platysma strands from both sides, causing deformation of the contours of neck-submandibular angle, accumulation of fat tissue over platysma was inconsiderable and did not exceed the thickness of subcutaneous fat in adjacent regions. It was found that 68% of the thickness was determined by excessive deposition of subcutaneous fat.Result of ultrasound examination showed that violation of contours of the neck-submandibular area was caused by age-related involution of tissues of subcutaneous neck muscle (platysma) and was not caused by local excessive accumulations of subcutaneous fat or skin ptosis. Violation of contours of lower jaw was mainly by local excessive accumulation of subcutaneous fat, with secondary unexpressed ptosis and excess skin . Thus, cPatient K., 58 years old, complained of ptosis of soft tissue face and neck, problems of aesthetic. Clinical diagnosis: Age-related soft tissue atrophy of lower third of the face and neck. Visually, there was a sagging of soft tissues in the submandibular and cervical area, excessive accumulation of adipose tissue, violation of the contour of the lower jaw, and a smoothed neck- submandibular angle .On ultrasound examination in the vertical position of the patient we found excessive accumulation of adipose tissue above the platysma in the chin and neck area problems of lower jaw contour due to accumulation of fat, ptosis of medial platysma was diagnosed. There were not determined either visually on palpation during physical examination .Based on the results of ultrasound, it was concluded that age-related problems were caused by local excess deposition of subcutaneous fat and ptosis of platysma cords. Thus, liposuction and platysmotomy was performed with intraoperative ultrasound control which were sufficient to correct age-related changes in this area for our patient .Success of aesthetic surgery considerably depends on understanding of mechanisms of each specific deformity formation, skills to evaluate them in planning and making surgical correction as well as rehabilitation measures in postoperative period.8Aging process affects all parts of the face and neck. Deformation in neck area can be determined by several factors: weakness of skin and platysma, appearance of platysma bands, ptosis of submandibular glands, lipodystrophy and even jaw resorption. Changing of face and neck proportions, quality and structure of skin, volume and location of fat make some interventions more difficult and may limit to obtain positive results.11Analysis reveals that only few studies have been performed for objective diagnosis of involutional changes caused in lower third of face and neck. Unfortunately, practically all authors rely on subjective assessment of clinical situation. At the same time, based on anatomical studies, it is evident, that it is necessary to differentiate specific anatomical structures of soft tissue deformations. It is also difficult in many cases on general physical examination, especially in patients with thick skin and expressed subcutaneous fat cellular.For example, it is not rare situation in such patients, when liposuction eliminate excess fat, but contours of neck-submental angle were deformed by platysma bands that became visual after surgery, on ptosis of all platysma.Many authors in their works note the importance of accurate assessment of causes of neck contour disorders. Nevertheless, they often neglect to use diagnostic methods. Only lately publications in the world literature appeared about role of instrumental examinations in planning surgical correction of facial and neck tissue atrophy.Japanese authors tried to use computed tomography for objective visualization and evaluation of age-related soft tissue changes of face and neck. Okuda I. et al. in their study (57 women aged 21-57 years), in which they used multi-detector row computed tomography (MDCT) for diagnostic.Alfen N. V. was one of the first to use ultrasound to examine facial muscles in patients with myotonic dystrophy, and proved that this is perspective non-invasive method of diagnostics and monitoring in neuromuscular disorders. Ultrasound can be used for detecting early or subclinical face muscles lesion in Duchenne muscular dystrophy and Moebius syndrome to determine certain facial muscles are absent or atrophic.13Volk G. F. et al. in their research described diagnostic value of ultrasound in lesions of facial nerve after injuries and tumors, that lead to atrophy of face muscles. Ultrasound was used to control regeneration and sizes of face muscles after reconstructive surgery, thickness and intensity of echo in patients with chronic peripheral facial paralysis at different stages of denervation and reinnervation. This method simultaneously presented functional and structural information about muscle state.15Safran T et al. noted the importance of using ultrasound in cosmetology. They measured muscle thickness after botulism toxin injection, skin thickness after implantation of polylactic acid filaments and before eyelid and face surgeries. Their research indicated the importance of patients\u2019 anatomy visualizing in real time for low complication rate without radiation exposure.16X. Wortsman, and colleagues have described in detail the ultrasound anatomy of face for non-invasive cosmetic and plastic surgery, pointed to the importance of ultrasound examination of facial structures in various deformities, paresis muscles and bruxism.G. Mashkevich et al. used ultrasound examination of the submandibular area in 10 patients. It helped to identify, which of this area components mainly caused deformation, especially in patients with so-called \u201cheavy\u201d necks.18Analysis of works reveals that ultrasound is a non-invasive, not inexpensive method in clinical practice that can visualize in detail the anatomy of soft tissues of face. However, it was not previously used in clinical practice for diagnostic involute changes of face lower third and neck to determine treatment tactics.New idea and finding of our work are the use of ultrasound examination for age-related changes of soft tissues of the lower third of face and neck in the vertical position of the patient. Different ptosis tissues and the degree of their participation in age-related changes are visible in different anatomical areas. It significantly help in determination of effective minimally invasive treatment methods in a number of clinical situations.Ultrasound examination is non-invasive, harmless, clinically available, inexpensive examination that allows to determine exact localization and degree of participation of different soft tissues of face and neck in age-related changes. It is very important for planning of use different minimally invasive techniques for facial and neck rejuvenation.VS: Conceived, designed the study, data collection, editing of manuscript, review and final approval of manuscript.SA, AT, LS: Did statistical analysis, data collection and manuscript writing."} +{"text": "Dysfunction of the autonomic nervous system has been implicated in the pathogenesis of cardiovascular disease, including congestive heart failure and cardiac arrhythmias. Despite advances in the medical and surgical management of these entities, progression of disease persists as does the risk for sudden cardiac death. With improved knowledge of the dynamic relationships between the nervous system and heart, neuromodulatory techniques such as cardiac sympathetic denervation and vagal nerve stimulation (VNS) have emerged as possible therapeutic approaches for the management of these disorders. In this review, we present the structure and function of the cardiac nervous system and the remodeling that occurs in disease states, emphasizing the concept of increased sympathoexcitation and reduced parasympathetic tone. We review preclinical evidence for vagal nerve stimulation, and early results of clinical trials in the setting of congestive heart failure. Vagal nerve stimulation, and other neuromodulatory techniques, may improve the management of cardiovascular disorders, and warrant further study. The autonomic nervous system regulates all aspects of cardiac function, including chronotropy, inoptroy, dromotropy, and lusitropy . In the via C7 to T6 rami to the superior cervical, middle cervical, stellate, or cervicothoracic ganglia, and acts though norepinephrine and neuropeptide Y (The anatomy of the cardiac nervous system is complex and has been categorized into: (1) central components, (2) intrathoracic extracardiac components, and (3) intrinsic cardiac components . The inteptide Y . Affereneptide Y . These aeptide Y initiatieptide Y . The ICNeptide Y . These geptide Y . Contrareptide Y . Moreoveeptide Y . For exaeptide Y . Similareptide Y . Given tIn this review, we provide a brief foundation for understanding the structure of, and organization of the cardiac autonomic nervous system and highlight neural control of cardiovascular function, emphasizing the roles of the sympathetic, parasympathetic, and ICNSs. Based on this scientific foundation, an overview of current neuromodulatory therapies is presented, focusing on cardiac sympathetic denervation and VNS . We highAutonomic control of the cardiovascular system is mediated through afferent and efferent pathways and neural networks involving the brain stem, spinal cord, peripheral ganglia, and ICNS . FeedbacCanonical organization of the sympathetic nervous system traditionally considers two sets of neuronal projections, defined by location of cell bodies and neurotransmitters mediating cell to cell communication. Preganglionic neurons with cell bodies in the intermediolateral cell column of the cervical and thoracic spinal cord (C7-T6) project to the superior, middle, cervicothoracic or stellate ganglia, and the remainder of paravertebral chain, with fibers running through ventral horns . Postganin vivo surrogate for action potential duration evaluated the adjunct use of the Demipulse VNS system for left or right cervical vagal nerve stimulation in a cohort of patients with heart failure with reduced ejection fraction and New York Heart Association functional class II-III symptoms . ImproveTwo other major studies have explored the impact of VNS on cardiovascular outcomes in the setting of heart failure, with mixed results . The NEuThe INcrease Of VAgal TonE in Heart Failure (INOVATE-HF) trial randomized 707 patients with HFrEF (LVEF \u2264 40%) with NYHA class III symptoms to medical therapy or medical therapy and VNS using an R-wave triggered pulse . Of noteOur prior work has described the concept of the neural fulcrum \u2013 an equilibrium point between activation of afferent and efferent vagus nerve pathways, resulting in a null heart response to stimulation with intact neural circuits . TitratiMultiple cardiovascular disorders including myocardial infarction and congestive heart failure result in excessive sympatoexcitation and a withdrawal of central parasympathetic tone . The majJH and JLA contributed to writing, reviewing, and editing of the manuscript. Both the authors approved the submitted version.University of California, Los Angeles has patents developed by JLA relating to cardiac neural diagnostics and therapeutics. JLA is a co-founder of NeuCures, Inc.The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dear Editor,Mastocytosis is a heterogeneous group of disorders whose signs and symptoms are characterized by mast cells infiltrate in tissues.peau d\u2019orange appearance , abdominal symptoms, respiratory symptoms, hypotension and even anaphylaxis.DCM is a rare condition that usually manifests with erythema, dermal thickening, skin folds accentuation, and edema with a typical leather or peau d\u2019orange appearance.4A review of DCM cases concluded that the majority were congenital and that even in cases of high tryptase the prognosis was good.Reliable prognostic criteria are still lacking to predict the risk of systemic involvement in DCM and maculo-papular mastocytosis. Most cases of DCM resolve spontaneously in childhood or adolescence, however these patients are at a greater risk of complications such as hypotension, anaphylaxis and diarrhea and they should be monitored regularly.None declared.Julia Marcon Cardoso: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; critical review of the literature; critical review of the manuscript.Camila Angelico S. Cabral: Conception and planning of the study; critical review of the literature;Rute Facchini Lellis: Approval of the final version of the manuscript; obtaining, analysis, and interpretation of the data.None declared."} +{"text": "The development of medicines designed for children can be challenging since this distinct patient population requires specific needs. A formulation designed for paediatric patients must consider the following aspects: patient population variability; dose flexibility; route of administration; patient compliance; drug and excipient tolerability. The purpose of this Special Issue entitled \u201cPaediatric Formulation: Design and Development\u201d is to provide an update on both state-of-the-art methodology and operational challenges in the design and development of paediatric formulations. It aims at re-evaluating what is needed for more progress in the design and development of age-appropriate treatments for paediatric diseases, focusing on: formulation development; drug delivery design; efficacy, safety, and tolerability of drugs and excipients. This editorial, briefly, summarizes the objects of nine original research and review papers published in this Special Issue. When designing and developing paediatric medicines, the route of administration, dosage form, and dose of the active ingredient (API) are decided on the basis of the expected duration of the therapy, the disease affecting a patient and his/her age, size, physio-pathological condition, API organoleptic and physicochemical properties , its pharmacokinetic and pharmacodynamic properties, and stability during manufacture, storage, and use of the chosen formulation ,2,3,4.The paediatric population is a heterogeneous group ranging from preterm newborn infants to adolescents with wide physiological and developmental differences regarding organ and skin maturation, metabolism, and other factors that impact on the pharmacokinetics and pharmacodynamics of a drug .It is a challenge to formulate one dosage form appropriate for this heterogeneous group of the human population. The goal should be to safely cover as wide an age range as possible with one specific dosage form. The guiding principle for choosing paediatric formulations should be the equilibrium of risks and benefits, taking into account the specific needs of these vulnerable patients. Key aspects in paediatric formulations involve the design and development of novel dosage forms, which should be adjustable for age and size, acceptable and palatable, easy to administer, and, at the same time, safer and effective ,3,4.Current use of medicines for paediatric patients reflects the full range of dosage forms and routes of administration used for adult medicines. There is, however, limited information on the acceptability of different paediatric dosage forms in relation to age and therapeutic needs and on the safety of excipients in relation to the development of the child ,3,4,6,7.Since its establishment, the biopharmaceutical classification system (BCS) has facilitated the development of oral drug formulations designed for adult patients. Theoretically, the BCS tenets could be applied also to paediatrics. Children\u2019s peculiarities and physiological differences from adults justify the need for a specific paediatric biopharmaceutics classification system (PBCS). Several scientific works attempted to provisionally classify oral drugs listed on the latest World Health Organization\u2019s Essential Medicines List for Children into age appropriate BCS. Validating a PBCS would provide a valuable tool to apply in specific paediatric formulation design by reducing time and costs and avoiding unnecessary paediatric experiments restricted by ethical reasons. Additionally, PBCS could minimize the associated risks to the use of adult medicines on pharmaceutical compound formulations for children. Moreover, developing a PBCS classification might be helpful in the process of harmonizing extemporaneous oral formulations in the hospital setting ,9.As a result of the great interest in developing age-appropriate dosage forms for children, this Special Issue, entitled \u201cPaediatric Formulation: Design and Development\u201d, was programmed to highlight the need of formulating safer and effective medicines for paediatric patients. A total of nine papers were accepted for publication in this issue: four reviews and five primary data manuscripts, focusing on (1) the design, characterization, and safety evaluation of orodispersable formulations for paediatric tuberculosis pharmacotherapy; (2) development and palatability assessment of ritonavir powder for the paediatric population; (3) development of new praziquantel paediatric formulations in schistosomiasis treatment; (4) tridimensional retinoblastoma cultures as a vitreous seeds model for live-cell imaging of chemotherapy penetration; (5) preparation and characterization of dasatinib/cyclodextrin complex for the potential treatment of paediatric neuromuscular disorders; (6) efficacy, safety, and tolerability of tyrosine kinase inhibitors in the treatment of paediatric chronic myeloid leukaemia; (7) technologies and modern approaches to modify drug release in paediatric dosage forms; (8) challenges in formulating neonatal medicines; (9) efficacy, safety, and tolerability of anti-interleukin-1 (anti-IL-1) treatment in paediatric autoinflammatory diseases.Palatable orodispersible film formulations are ideal for patients with swallowing difficulties such as babies and children because they are stable and dissolve rapidly within the oral cavity in the presence of saliva, without the need to chew or drink water. In this Special Issue, Matawo and co-workers investig\u00ae oral powder (NOP) was developed to replace the oral solution, which provided reasonable bioavailability but exhibited taste-masking challenges and required the use of solvents with potential paediatric toxicity. In this study, the authors provided an overview of the development of NOP and palatability assessment strategy. In summary, NOP provided dose flexibility, enhanced stability, eliminated solvents, and maintained consistent bioavailability, with reduced bitterness and improved palatability via administration with common food products.In this Special Issue, Morris and colleagues presenteHere, Albertini and co-workers evaluateRetinoblastoma is the most common intraocular tumour of childhood ,14. ThisFor the first time, in this issue, a new inclusion complex of dasatinib, the first-choice oral drug in the treatment of chronic myeloid leukaemia and the excipient hydroxypropyl-beta-cyclodextrin (HP-\u03b2-CD), was described and fully characterized by Cutrignelli and co-workers for the Recently, tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib have been approved for the treatment of chronic myeloid leukaemia in children, even though the studies that were concerned with efficacy and safety toward this population are still awaiting defined and more accurate data ,18,19. IIn pharmaceutical technology, the paediatric population still represents the greatest challenge in terms of developing flexible and appropriate drug dosage forms. In their review article published in this issue, Trofimiuk and colleagues elucidatIn this Special Issue, O\u2019Brien at al. publisheThe safety profile of treatment is of paramount importance when children with autoinflammatory disorders are managed, since it may affect adherence to treatment and overall clinical efficacy ,24,25. IThe high number of articles published in this Special Issue entitled \u201cPaediatric Formulation: Design and Development\u201d highlights the significant amount of research being conducted on the development of medicines designed for paediatric patients.Formulating an appropriate dosage form is a challenge when considering chronic diseases that affect children and minimizing the dose frequency. Key aspects in paediatric formulations involve the design and development of novel dosage forms, which should be adjustable for age, palatable, easy to administer, and, at the same time, safer and effective."} +{"text": "Due to the exceptionally high transmissibility and robust infectiousness of the underlying virus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] was first identified in Wuhan, China, in December 2019. It was then declared a public health emergency of international concern on 30Since no vaccine is far available for containment of this virus, thus unprecedented large-scale quarantine measures are one of the best ways to prevent the chain of events leading to transmission of SARS-CoV-2. In many countries, mandatory requirements for social isolation, including stay-at-home orders, banning social contacts, canceling public events, and closing mass transit systems have been ordered by governments , 5. AlthIn social animals, positive social interactions are fundamental for increasing cognitive ability, promoting brain development, and maintaining mental and physical health, ultimately contributing to survival and reproduction , 10. LonStress due to social isolation accounts for one of the most common sources of chronic stress in humans. Previous studies have shown that chronic social isolation correlates with a higher risk of morbidity and mortality . ChronicThe brain is a vital organ that is vulnerable to influence by the external environment. Regulation of social behavior and emotion depends on complex neural circuits within the brain . PreviouExposure to social isolation stress induces a variety of endocrine changes, and dysregulation of the neuroimmune-endocrine system has been shown to be one vital mechanism for the development of psychological disorders . StudiesFurthermore, social isolation stress has also been shown to alter levels of neurotransmitters and receptor sensitivities in many regions of the central nervous system (CNS) , 39. IntSocial isolation stress can also alter neurotrophin levels. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors, which are key regulators of synaptogenesis, neuronal plasticity, and adult neurogenesis , 44, creFor many countries, the COVID-19 pandemic may necessitate long-term and wide-ranging social isolation. This social isolation will not only change the reaction norms of daily activities, but may also create dramatic adverse psychological effects, including loss of freedom, isolation from friends and family, and feelings of loneliness and uncertainty. Unfortunately, chronic stress-induced neurochemical and neuroendocrine disorders are often neglected until they become psychological illness. Given that a mandatory quarantine of confirmed and suspected cases is the best way to avoid spread of COVID-19, a series of measures are needed to avoid the negative physiological and psychological effects induced by chronic social isolation, including potential neurochemical and neuroendocrine system disorders. First, national public health emergency systems should provide fundamental and explicit guidelines for prevention of mental illness induced by mandatory social distancing and thereby mitigate physiological and psychological stressors. These guidelines should include recommendations for positive social interactions and maintenance/development of social supports, including online communication with relatives and friends . Second,In conclusion, both governments and citizens must recognize the important neurochemical and neuroendocrine changes induced by the chronic social isolation stress of the COVID-19 pandemic to help prevent potential psychological and mental illnesses that are often invisible and easy to neglect.LW: literature searched and wrote the original draft. GN: literature searched and wrote the original draft. TZ: manuscript revised. DL and YW: study designed. DL: wrote the final manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China to DL and the Natural Science Foundation of China of Hebei Province (C2020205005) and China Postdoctoral Science Foundation (2020M670685) to LW.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Preterm birth is associated with a significantly increased risk for childhood and adolescent psychopathology relative to full-term birth, with an inverse relationship between gestational age at birth and later risk for psychopathology. The manifestation of symptomatology and comorbidity profiles of emotional and behavioral adjustment problems in this high-risk group have been shown to be distinct from the broader pediatric population. Acknowledging these differences, a preterm behavioral phenotype has been proposed and increasingly recognized, highlighting the unique, frequent co-occurrence of symptomatology associated with attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety disorders. The current state-of-the-art review provides a comprehensive characterization of this phenotype to date and further highlights key knowledge gaps primarily regarding the evolution of symptoms, co-occurrence of disorders and/or symptomatology within the phenotype, and associations of the phenotype with chronological age and degree of prematurity. Preterm birth (<37 weeks gestation) affects approximately 15 million infants and their families around the world, annually, with vast improvements in survival reported in recent times , 3. PretDiagnostic and Statistical Manual of Mental Disorders (DSM) Third Edition Revised (DSM-III-R), Fourth Edition (DSM-IV), or the International Classification of Diseases 10th Revision (ICD-10) in children, adolescents, and young adults aged 10 to 25 years and born preterm or with low birth weight (LBW) compared to full-term peers , and if they made explicit reference to the preterm behavioral phenotype in the background or discussion of the study when interpreting findings. Studies were excluded if they investigated only one of the three phenotype clusters or if they exclusively recruited a medically high-risk preterm sample , due to these groups being less representative of the larger preterm population. In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , a systeLoe et al. investigDSM-IV disorder, there were significantly more ELBW adolescents meeting criteria for three or more disorders (n=10 vs. 1). In contrast, ELBW adolescents self-reported lower scores on all measures compared to normal birth weight adolescents, with significant differences for item ratings of oppositional defiant disorder and rates of inattentive ADHD and conduct disorder. From ELBW self-reports, there were also no significant differences in the rates of one or more, or three or more, co-occurring disorders. While a strength of this study is the comparison between parent and adolescent reports, a limitation in the current context is the failure of the study to focus specifically on the co-occurrence of disorders within the phenotype. This information would have provided support for the proposed unique pattern of behavioral and emotional difficulties. Methodologically, findings may be further limited by reliance on clinical cutoff thresholds as applied to ratings rather than on clinical psychiatric diagnoses.Taylor et al. is the fKorzeniewski et al. describeFollowing on from this, Samuelsson et al. investigUnlike the previous studies reviewed above, Johnson et al. investigated the comorbidity of cognitive and behavioral outcomes in late to moderate preterm (LMPT) born toddlers in the United Kingdom . This isAnother investigation of the comorbidity of symptoms comprising a potential preterm behavioral phenotype was conducted by Burnett et al. . This stMaintaining the theme of cluster-based approaches, Lean et al. identifiSince the conceptualization of the preterm behavioral phenotype, seven studies have investigated two or three symptom clusters characteristic of ADHD, ASD, or anxiety, with explicit reference to the phenotype in the study rationale or interpretation of findings. Research has increased knowledge of the variable pattern of behavioral and emotional difficulties in the preterm population and of the co-occurrence of symptom clusters within the phenotype. Despite these advances, there are several methodological challenges that continue to hamper our knowledge in this area. The first challenge is the substantial heterogeneity of outcome measures administered in follow-up assessments of preterm samples. As shown in A prevailing limitation of the existing literature is that the manifestation of the preterm behavioral phenotype is very rarely described in relation to underlying etiological mechanisms. Therefore, it remains unclear if the unique comorbid nature of the phenotype has a distinct neurological or psychosocial basis precipitating its development.The impetus to conduct more research on neurological alterations associated with the preterm behavioral phenotype is growing with the increase in magnetic resonance imaging studies of preterm samples. In the preterm population, ADHD has been associated with reduced volumes in total cerebral and frontal areas , 41, venMaternal mental health is another factor that may underlie the unique development of comorbid psychopathology in preterm children . MothersThe primary mechanisms of the preterm birth experience and the resultant maternal mental health can both negatively impact parenting behavior and mother\u2013child relationships , 61, whiEight systematic reviews and meta-analyses have been published since the preterm behavioral phenotype was proposed in 2011 \u201368, eachDSM-IV/V\u2013based conceptualization of the preterm behavioral phenotype is needed in view of the vast variability in the preterm population in etiology, symptom presentation, and comorbidity.Enhancing understanding of the preterm behavioral phenotype will require further investigation of the neonatal, neural, and psychosocial antecedents of the types and comorbidity of behavioral and emotional problems in preterm children. Longitudinal studies are needed to address questions regarding influences on developmental precursors of psychiatric disorders and identification of risk and resilience factors. Finally, critical review of the current The objective of this state-of-the-art review was to comprehensively synthesize and describe the studies characterizing the preterm behavioral phenotype since conceptualization in 2011. Findings confirm the suggestion that children born preterm are at significantly increased risk for symptoms of ADHD, ASD, and anxiety disorders. Although there is some additional support for comorbidity of these three symptom clusters, few studies have investigated the extent to which these clusters occur conjointly as a unitary phenotype, in isolation, or in combination with other behavioral, cognitive, or learning impairments. The pattern of comorbidities associated with preterm birth has implications for neurodevelopmental assessment of children born preterm and for addressing their clinical needs. As profiles of impairment may vary with age, knowledge of comorbidities may be useful in improving early identification of children at the highest risk for ongoing psychiatric disorders. Identification of profiles of comorbidity may also be useful in guiding more individualized approaches to intervention.The corresponding author, SB, had full access to all of the study data and is primarily accountable for all aspects of the work, including the decision to submit for publication. GF conceptualized and designed the review protocol, acquired data, interpreted the results, drafted and revised the initial manuscript, and approved the final manuscript as submitted. GT substantially contributed to the oversight of the conceptualization of the review, interpreted the results, critically reviewed and revised the initial manuscript, and approved the final manuscript as submitted. SB acquired funds and resources, conceptualized the review, supervised the designing of the review protocol and data acquisition, interpreted the results, critically reviewed and revised the initial manuscript, and approved the final manuscript as submitted.This work was supported by a Mater Foundation Principal Research Fellowship to SB and the University of Queensland Research Training Program and Frank Clair scholarships to GF. The funding sources had no role in the writing of the manuscript or in the decision to submit it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The functional consequences of the aging brain include several aspects of physical and cognitive decline that ultimately cause loss of mobility and dementia. Although in certain individuals, the cognitive and physical correlates of the aging brain occur in parallel, others show decline in one of these functional parameters. Underlying mechanism of this complex process that lead to different manifestations is not well understood. Proposed mechanisms include brain structural changes, tau pathology, specific white matter degeneration, metabolic derangement mostly including lipids metabolism and others. This symposium aims to address the complexity of the aging brain by showcasing studies that span the continuum from normal aging to dementia using data from the Baltimore Longitudinal Study of Aging (BLSA). The wealth of neuroimaging and phenotype data from the BLSA provides the unique opportunity to investigate neural substrates and predictors of aging phenotype, and mechanisms of age-related neurodegeneration and pathology, such as dementia, and loss of mobility. First, we identify multimodal neuroimaging predictors of important aging phenotypes of gait decline (Sargent/Tian) and memory decline (Bilgel). Second, using advanced quantitative MRI technology, we investigate underlying mechanisms of age-related white matter degeneration through potential oligodendrocyte metabolism (Bouhrara). Third, we demonstrate unique cognitive and neuroimaging profiles of dual memory and gait decline (Tian) and neural substrates for bile acids, the primary cholesterol breakdown products (Varma) in relation to dementia. We seek to generate discussions of mechanisms of the aging brain that connect the age-related phenotypes, such as decline of mobility and cognition, to the development of dementia."} +{"text": "Thyroid hormone has effects on the skin. Patients with hypothyroidism have changes such as dry, scaly and rough skin. Increase carotene in the dermis becomes a yellowish tone to the skin of the patient with hypothyroidism. There is an increase in capillary cycle (anagen phase) and nail growth and a reduction in eccrine gland secretion. It is a case of primary hypothyroidism with nail manifestations associated with dermatologic disorders and successful treatment with levothyroxine. Receptors for thyroid hormone have already been found in keratinocytes, fibroblasts, hair follicles and sebaceous glands. Genes responsive to thyroid hormones and elements of the hypothalamic\u2013pituitary\u2013thyroid axis were identified on the skin. This report highlights the importance of cutaneous manifestations as markers of thyroid disease. Thyroid hormone effects on the skin.4Male, 58-year-old, seller, referring nail dystrophy in all the quirodactyls and firsCutaneous manifestations are important as external markers of thyroid disease. Thyroid hormone receptors have been found in keratinocytes, fibroblasts, hair follicles and sebaceous glands. Genes responsive to thyroid hormones and elements of the hypothalamic\u2013pituitary\u2013thyroid axis were identified on the skin. Hypothyroidism reduces the activity of enzymes in the cholesterol sulfate cycle, causes changes in the skin barrier, affects the development of lamellar granules (Odland bodies),None declared.Thadeu Santos Silva: Conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; critical review of the manuscript.Gustavo Baptista de Almeida Faro: Elaboration and writing of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.M\u00e1rcia Gabrielle Bonfim Cortes: and planning of the study; obtaining, analysis, and interpretation of the data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.Vit\u00f3ria Regina Pedreira de Almeida Rego: of the final version of the manuscript; elaboration and writing of the manuscript; effective participation in research orientation; critical review of the literature.None declared."} +{"text": "In Europe, discussions are currently ongoing to harmonize front-of-pack nutritional labelling, while some countries have adopted or are considering implementing the Nutri-Score. However, its adaptability to multiple nutritional contexts in Europe requires further investigation. This study aimed to evaluate the applicability of the Nutri-Score in various European countries, regarding its ability to discriminate the nutritional quality of foods and its consistency with national dietary recommendations. The European Food Information Resource (EUROFIR) nutritional composition databases from eight European countries were used. The distribution of foods across the Nutri-Score classes within food groups was assessed, as well as the discriminating performance of the label, and the adequacy of nutritional recommendations. The Nutri-Score demonstrated high discriminating ability for all food groups, with similar trends in the eight countries, and consistency with nutritional recommendations. For instance, fruit and vegetable products were mainly classified in the two healthiest Nutri-Score categories, while sugar and animal fat products were mainly classified in the two less healthy categories of the Nutri-Score. Our results support the fact that the Nutri-Score would be a relevant tool to discriminate the nutritional quality of products within and across relevant food groups in different European countries, with consistency with nutritional recommendations. In 2017, the European region was the most affected World Health Organization (WHO) region by non-communicable diseases , accounting for approximately 77% of the burden of disease and 88% of deaths . In thisHowever, in view of the plurality of FoPLs on the European market, potentially leading to confusion for consumers, the European Commission has launched discussions among member states on the potential reopening of the INCO regulation , includiMore specifically, the Nutri-Score is a color-coded graded scale of five letters based on the United Kingdom\u2019s Food Standards Agency (FSA) nutrient profiling system (NPS), adapted to the French context by the French High Council for Public Health (HCSP), namely the FSAm-NPS ,19. The Data were retrieved from the European Food Information Resource (EUROFIR), an international non-profit association created to promote international cooperation in the nutrition field, in particular through the collection of validated national nutritional databases . FollowiFood products were categorized according to the EUROFIR classification, grouping foods with similar use and nutritional characteristics . Herbs aThe following elements in the nutritional composition table of each country were required for the calculation of the FSAm-NPS score and thus the Nutri-Score of each food: energy, sugars, fats, Saturated Fatty Acids (SFA), proteins, fiber, and sodium. In order to limit the number of missing data, the content of some nutrients was recalculated using usual equations with other data available in the tables = total protein (g) * 17 + total carbohydrates (g) * 17 + total fat (g) * 38 + alcohol (g) * 29 + total dietary fiber (g) * 8). Moreover, in order to verify the quality of the nutritional composition data, control procedures were performed on variables of interest for the FSAm-NPS calculation, including verification on the total energy content. The analyses were finally carried out on the eight following countries, for which all necessary data were available: Finland, France, Norway, Poland, Portugal, Slovakia, Sweden, and Switzerland. Finally, 11,347 foods and beverages from the eight countries contained data on food composition and classification and were thus used for the analyses. The number of food products available in each group or subgroup varied across countries. In total, 2075 food products were included in the database for Finland, 2309 for France, 1101 for Norway, 919 for Poland, 921 for Portugal, 1183 for Slovakia, 1990 for Sweden and 849 for Switzerland. The flowchart of the food databases used in the present study is described in Based on the nutritional composition for 100 g of food (or 100 mL of beverage), the FSAm-NPS assigns positive points for the amounts in elements that should be limited, including energy (kJ), total sugars (g), SFA (g), and sodium (mg) (0 to 10 positive points for each). Negative points are then attributed to the amount in elements that should be promoted, including fruits, vegetables, legumes and nuts , fibers (g) and protein (g) (0 to 5 negative points for each). The FVLN component was not available per se in the composition tables. Thus, values were estimated for each product, using French generic food composition databases for which FVLN amounts had been estimated ,35,38,39For each main food group and subgroup, the distribution of foods and beverages in the different classes of the Nutri-Score was computed . This distribution was assessed across and within the eight countries. Further, within each main food group and subgroup, the modal class and the percentage corresponding to the predominant Nutri-Score class were calculated. The ability of the Nutri-Score to discriminate the nutritional quality of products within main food groups and subgroups was assessed using the number of available colors in each group. Discriminating performance was considered satisfying when at least three classes of Nutri-Score were available in the food group. In addition, the overall distribution of foods in the different classes of the Nutri-Score was compared with the food-based dietary guidelines from the different countries included in the study and the general guidelines from the WHO . Thus, fOverall, a final sample of 11,347 foods and beverages was used, including 1800 fresh or processed fruits, vegetables and nuts, seeds or kernels; 1898 breads and cereal products; 2506 meat, fish and egg products; 906 milk and dairy products; 336 fats or oils; 2655 composite products; 614 sugar or sugar products; and 632 beverages.Overall, for the eight countries combined, the distribution of the different Nutri-Score classes for each main food group and subgroup is displayed in Overall, in the eight countries combined, at least three classes of the Nutri-Score were observed for all main groups and subgroups, except in the \u201cpulse and pulse product\u201d subgroup, where only two classes of the Nutri-Score (\u201cA\u201d and \u201cB\u201d) were represented. The results on the overall discriminating performance of the Nutri-Score in each country are displayed in In this study, the distribution of foods within the Nutri-Score classes showed a good performance of the FoPL to discriminate the nutritional quality of products within main food groups and subgroups, and across relevant food groups in terms of purchase, use or consumption, with high consistency with official dietary guidelines in the eight countries tested\u2014Finland, France, Norway, Poland, Portugal, Slovakia, Sweden and Switzerland. These results are consistent with other studies using food composition databases of manufactured foods from the French and German markets, therefore validating the ability of the Nutri-Score to discriminate the nutritional quality of products in various sociocultural contexts ,35. A scThe validation of the ability of the Nutri-Score to discriminate the nutritional quality of products in different markets using the FSAm-NPS profile is particularly important to assess its transferability given the current European context. Beyond the country-specific food database, the concordance of our results confirms the performance of the Nutri-Score system in achieving product discrimination in various European countries ,21. OnlyDietary guidelines and FoPLs such as the Nutri-Score are complementary and synergic measures, based on different approaches and principles. Dietary guidelines aim to provide consumers practical guidelines to adopt a healthy diet, by helping them identifying the food groups that should be encouraged and those that should be limited . NeverthThe use of the EUROFIR database, including both generic and specific food and beverages of multiple European countries, is the main strength of the present study. Indeed, it allowed us to perform cross-cultural comparisons of the discriminating performance of the Nutri-Score, particularly important in the current European context of front-of-pack nutritional labelling harmonization. This comparative study across eight European countries remains the first study in terms of the validation of the NPS underlying the Nutri-Score in different sociocultural contexts on a large variety of generic foods. These findings are complementary to studies conducted in other food databases such as Open Food Facts providing data on multiple industrial foods of different brands. However, some limitations should be acknowledged. First, data from EUROFIR were retrieved from different sources and did not allow us to analyze the representativeness of the sample of foods collected in our database. Nevertheless, our objective was to assess the discrimination capacity of the Nutri-Score; we did not need to be exhaustive and the EUROFIR database provided a large number of food products for each country. In addition, some disparities were observed between countries regarding the number of foods available, or even the composition of foods or both. Given these heterogeneities of the database structures, we elected not to perform statistical tests to determine the significance of the intercountry differences. However, only a few countries were concerned, and their results remain consistent with the literature mentioned above. Moreover, several procedures were applied to verify the validity of the data and optimize the number of products in each database. In addition, results on the distribution of foods in the different Nutri-Score classes depended on the EUROFIR classification that was used in the present study. Another limitation of the present study remains the somewhat arbitrary aspect of the measurements of the discriminating performance of the FoPL and the consistency with dietary guidelines. Nevertheless, in the absence of a consensual indicator to which to compare the performance of nutrient profiling, we used a similar methodology to previous studies ,35. FinaOur results provide additional evidence of the relevant application of the Nutri-Score and its adaptability to the European context, particularly in Finland, France, Norway, Poland, Portugal, Slovakia, Sweden, and Switzerland, with regard to discrimination within main food groups and subgroups. This FoPL is notably strongly supported by European consumer associations who launched a petition (\u201cPRO-NUTRISCORE\u201d) in order to encourage the European Commission to change the regulation and make the label mandatory. This study supports the Nutri-Score as an interesting alternative for European countries wishing to implement complementary nutrition labelling on the front of food packaging, and ultimately avoid confusion among consumers through the coexistence of several systems on the European market."} +{"text": "Canine Morbillivirus is the causative agent of one of the most important diseases in domestic dogs and wild fauna. It belongs to the Paramyxoviridae family, order Mononegavirales, which has a non-segmented, single-stranded linear negative polarity RNA genome , CDV infects multiple species within the Order Carnivora, including several wild species as Canidae, Felidae, Procyonidae, Mustelidae, Hyaenidae, Ursidae, and Viverridae families. CDV infection has also been reported in other Orders such as Rodentia (rodents), Primates, Artiodactyla, and Proboscidea with neurological signs . Both of these belong to the Myrmecophagidae Family , family Choloepodidae, order Pilosa, was reported with clinical signs that included hyporexia, lethargy, mucopurulent nasal discharge, and oral and facial ulcers confirmed as CDV South America/North America-4 lineage and wild and domestic dogs in the United States (North America) , white-lipped peccary (Tayassu pecari), collared peccary (Pecari tajacu), white-tailed deer (Odocoileus virginianus) and the Central American red brocket deer (Mazama temama), carnivores such as the jaguar (Panthera onca), puma (Puma concolor), and ocelot , and insectivores like the giant anteater (Myrmecophaga tridactyla); all of them are mostly forest specialists ranging from ungulates to carnivores and even insectivorous species, and CDV has been reported to infect most of those species , margay (Leopardus wiedii), jaguarundi (Herpailurus yagouaroundi), Jaguars (Panther onca), ocelots , jaguarundis (Puma yaguaroundi), pampas cat (Leopardus colocolo), and other wild canids such as the maned wolf (Chrysocyon brachyurus), crab-eating fox (Cerdocyon thous), hoary fox , striped hog-nosed skunk (Conepatus semistriatus), and coati (Nasua nasua), among others contribute more than 75 % of biomass to the observed diet of the jaguar (Panthera onca) in the Cerrado, central Brazil , another species that has been commonly been reported as being at risk of infection with CDV (Noon et al., In the Mesoamerican and South American areas, CDV has been described as infecting the cougar (Our understanding of the circulation of CDV in the Americas allows us to speculate on the number of critical factors. These factors include the presence of specific viral lineages in large geographical areas, and the susceptibility of circulating species in interconnected regions which favors viral exchange across the continent and represents a risk for wild endangered populations. For this reason, it is imperative to establish not only the dynamics but also diverse aspects of the circulation of CDV among wildlife in the Americas, such as prevalent linages and their associations that would enable us to elucidate the main circulating stains.There is a great possibility that there is an underreporting of CDV infection and that the published cases only represent the tip of the iceberg in the epidemiology of CDV in wild populations in the Americas.We recommend enhancing the monitoring of CDV among wildlife corridors and to evaluate the CDV dynamics among different target populations regardless of whether clinical signs are observed. Moreover, we encourage the implementation of an interdisciplinary approach that would enable us to understand the critical role of high impact/mortality diseases such as CDV on the wildlife conservation. Also we encourage the assessment of the impact of CDV circulation and vaccine coverage of domestic dogs on wildlife epidemics, as this topic has not been evaluated in the America corridor areas.JR-S conceived the study. SR-M, MM-G, JS, and JR-S were involved in all other aspects of the study, including data collection, data analysis, drafting and editing the paper. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Coronavirus disease 2019 (COVID-19) has accelerated the adoption of telemedicine globally. The current consortium critically examines the telemedicine frameworks, identifies gaps in its implementation and investigates the changes in telemedicine framework/s during COVID-19 across the globe. Streamlining of global public health preparedness framework that is interoperable and allow for collaboration and sharing of resources, in which telemedicine is an integral part of the public health response during outbreaks such as COVID-19, should be pursued. With adequate reinforcement, telemedicine has the potential to act as the \u201csafety-net\u201d of our public health response to an outbreak. Our focus on telemedicine must shift to the developing and under-developing nations, which carry a disproportionate burden of vulnerable communities who are at risk due to COVID-19. The novel coronavirus disease COVID-19) emerged at the end of 2019 in Wuhan (People's Republic of China) and the viral outbreak was declared as a pandemic by World Health Organization (WHO) on March 11, 2020 9 emerged\u20136. The gPandemics challenge the preparedness of health systems-exposing the structural barriers . Amidst Existing telemedicine frameworks and policies of various countries/regions and their implementation stage are analyzed using Gladhart and Pan The existing telemedicine framework/s across various regions/countries, status or maturity of telemedicine implementation, and various developments or changes that have been adopted during the COVID-19 are summarized. A comparative analysis of existing telemedicine frameworks using Gladhart and WHO/PAHO hat models, their stage, and recommendations from this consortium on improving telemedicine uptake during and beyond COVID-19 have been provided in A 2016 multi-country study by Suzuki et al. assessed the possibility of introducing telemedicine services in several developing Asian countries . IndicatAsian telehealth platforms are reporting drastically increased usages, such as Indonesian telehealth platforms Alodokter, Halodoc, and GrabHealth, driven by government support and recommendation . The DocSingapore is a front-runner in Asia in terms of telemedicine adoption and healthcare system efficiency. In 2018, the Singapore Ministry of Health launched a regulatory sandbox to facilitate innovation and form relationships between the government and telehealth partners . There aFederated National Health Information System.\u201d It proposes to link systems within private- and public-health provider organizations across primary-, secondary-, and tertiary-care value chains , Department of Information Technology, Ministry of External Affairs and MoHFW . HoweverSome of the national projects undertaken by the Ministry of Health and Family welfare are Integrated Disease Surveillance Project (IDSP), National Cancer Network (ONCONET), National Rural Telemedicine Network, National Medical College Network, and the Digital Medical Library Network . The fraCurrently, no national telemedicine framework in Bangladesh exists; and current systems suffer from lack of technological infrastructure, healthcare inequities, and poor treatment quality . The curChina has a sizeable urban-rural health gap, which major telehealth networks such as the International MedioNet of China network, Golden Health Network, and the People's Liberation Army Telemedicine Network have not been able to rectify . In SeptDevelopment of telemedicine in rural health care,\u201d was launched in 2005 within the framework of the state program in 2004 . Its pur program . During ormation . As a paormation . At presormation . This ex country . KazakhsSub-Saharan Africa is a region of swift telehealth development, as program implementation increases, and smartphone penetrance is expected to reach 66% by 2025 . This reTelemedicine is still in its infancy in Africa due to ongoing conflicts and war, inadequate information communication technology (ICT), and lack of funding and political support for technology diffusion and policy . In lighLatin America has one of the fastest-growing elderly populations worldwide and has a big divide in access to healthcare providers between rural and urban regions . A 2019 Targeted government support of telemedicine is needed in this region, as telemedicine in countries such as Mexico falls under the standard practice of medicine regulations, instead of being governed by a focused telehealth department . In 2018Telehealth in the Caribbean is in a relatively early stage, with a lack of cohesive telehealth strategies and policies. The National Health Authority in the Bahamas announced a new Electronic Health Record (EHR) system at the end of 2019 , which rAustralia is in the process of making telehealth implementation more accessible for providers since the COVID-19 outbreak . New MedThe Ministry of Health in New Zealand has released an advisory on available teleconsultation technologies for health care practitioners and best practices around patient privacy . The MedFrench Doctolib and Qare, Swedish LIVI, UK's Push Doctor, and Germany's Compugroup Medical SE have all seen considerable increases in European uptake numbers , telecommunication companies such as BT, Virgin Media, and Sky in the United Kingdom have agreed to support the National Health Services (NHS) in rolling out telehealth for healthcare practitioners . PrimaryIt has been reported that many Italian hospitals lack the infrastructure for effective telehealth platforms, due to supply-chain breakdown and insufficient internet capabilities . Italy avia video or phone consultations by nurses were provided. This was expanded to include teleconsultations by speech therapists on March 25, 2020.The telemedicine regulations in France developed before COVID-19 allowed tertiary and primary care physicians to switch scheduled in-person consultations to teleconsultations, as and when appropriate . All vidDenia Marina Salud Hospital have reported a rapid switch to telemedicine for outpatients and staff conferences to good effect consortium is formed to champion the safety of healthcare workers, policy development, and advocacy for global pandemic preparedness and action.SBh devised the project, the main conceptual ideas, including the proposal for a new telemedicine workflow, the proof outline, and coordinated the writing and editing of the manuscript. SBh and SBr wrote the first draft of the manuscript. SBh encouraged SBr to investigate and supervised the findings of this work. All authors discussed the results and recommendations and contributed to the final manuscript.SP is the Vice President of Immersive Medicine at Luxsonic technologies, a medical technology company specializing in virtual/augmented reality for medical education, collaboration, and training. AAt is the Scientific Founder and Board Member of Rx.Health, and founding chair of NODE.Health . The opinions expressed in this article are those of the authors and do not necessarily represent the decisions, official policy, or opinions of the affiliated institutions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Cellular senescence, the decline of cellular function due to aging, causes gradual loss of physiological functions and induces some chronic diseases, which negatively affect the quality of human life. Intervention in the cellular senescence process may reduce these incidences and delay the progression of age-related diseases, thereby contributing to the longevity of human lifespan. The budding yeast, Saccharomyces cerevisiae, is a model system that can provide significant insights into the genetics and molecular biology of senescence and is a suitable cellular model for research on mammalian cells. In the 2019 GSA meeting, we had revealed that the prolongation of yeast cell lifespan was induced by the addition of immature pear fruits extracts (iPE). In this study, we have focused on investigating the anti-senescence effects of hydrophilic (WiPE) and hydrophobic (OiPE) components of iPE on yeast cells and their genes and their possible application in extending human lifespan. The anti-aging effects of iPE were investigated using a chronological lifespan assay on S. cerevisiae cells. The chronological lifespan of the yeast was significantly extended in those treated with both WiPE and OiPE at 1% (v/v). The expression of sirtuin-related genes, which regulate cellular senescence, was examined by RT-PCR. Interestingly, gene expression was found to be significantly increased only in WiPE treated cells. The results suggested that the different polarity components from iPE exhibited anti-aging effects on the cells via different mechanisms. Research on the identification of useful components in iPE and the possibility of application to mammalian cells is ongoing."} +{"text": "Each year, billions of ornamental young plants are produced worldwide from cuttings that are harvested from stock plants and planted to form adventitious roots. Depending on the plant genotype, the maturation of the cutting, and the particular environment, which is complex and often involves intermediate storage of cuttings under dark conditions and shipping between different climate regions, induced senescence or abscission of leaves and insufficient root development can impair the success of propagation and the quality of generated young plants. Recent findings on the molecular and physiological control of leaf vitality and adventitious root formation are integrated into a systemic perspective on improved physiologically-based control of cutting propagation. The homeostasis and signal transduction of the wound responsive plant hormones ethylene and jasmonic acid, of auxin, cytokinins and strigolactones, and the carbon-nitrogen source-sink balance in cuttings are considered as important processes that are both, highly responsive to environmental inputs and decisive for the development of cuttings. Important modules and bottlenecks of cutting function are identified. Critical environmental inputs at stock plant and cutting level are highlighted and physiological outputs that can be used as quality attributes to monitor the functional capacity of cuttings and as response parameters to optimize the cutting environment are discussed. Facing the great genetic diversity of ornamental crops, a physiologically targeted approach is proposed to define bottleneck-specific plant groups. Components from the field of machine learning may help to mathematically describe the complex environmental response of specific plant species. Plant propagation is the initial process of producing ornamental crops that already sets the first benchmark for the whole cultivation process by determining the quality of the young plant. Many ornamental plant species are propagated vegetatively by rooting of shoot tip cuttings. Depending on the plant genotype, the developmental stage of the cutting, and specific constellation of environmental factors, impaired vitality of cuttings or insufficient adventitious root (AR) formation in the stem base can cause leaf losses and dying of cuttings or failures in rooting and delayed or uneven root formation among individuals that impairs synchronous subsequent growth. Furthermore, the increasing demand on sustainability of young plant production requires improved propagation protocols that should provide maximum utilization of the genetically determined endogenous potential of the crop.Propagation of ornamental plants by cuttings can be characterized as follows:(1)It involves control of plant development in highly equipped ecosystems, that are mainly determined by technically controlled environmental inputs, for example in greenhouses, growth and storage rooms etc. I propose the term \u201ctechnoecosystems\u201d for such systems.(2)Environmental inputs are highly dynamic, because propagation involves a complex chain of subsequent processes that occur in different environments. Stock plant cultivation and harvest of cuttings occurs in diverse climatic regions far remote from the market of young plants and is followed by packaging, storage, transport, sticking and cultivation of cuttings close to the market.(3)The chain is continuously changing, because new priorities in the society and developing technologies provide new demands and options. Examples are the increasing demand for saving energy and reducing pollution, the changing lighting technology and the up-coming rooting systems that are compatible with transport logistics and sticking robots.(4)Chrysanthemum varieties were submitted to the Community Plant Variety Office , which determines the specific developmental stage as well as the source-sink and hormonal status of the cutting tissues at time of harvest.Important functional modules are the stem base (SB) as zone of root regeneration and of C and N utilization, the upper stem (US) as transport unit for all compounds and as intermediate storage unit of C and N, the fully developed leaves (FL) as source organs for providing C, N and possibly auxin, and the developing leaves (DL) and shoot apex (SA) as competitive utilization sinks for C and N and as potential source (DL) or sink (SA) of auxin.hormone homeostasis, signaling and function control the dedifferentiation (Dediff), induction, initiation and expression of adventitious roots, with Aux/IAA proteins, auxin responsive factor (ARF) transcription factors, GH3 proteins, and cell fate regulating transcription factors (CTF) such as GRAS, AP2/ERF and WOX as important components. Sink establishment and C and N utilization provide building blocks, energy and metabolic signals. Wound-induced accumulation of ethylene (ET) and jasmonic acid (JA), a decrease in levels of root-sourced cytokinins (CK) and strigolactones (SL) due to isolation from the stock plant, and accumulation of IAA contribute to dedifferentiation and induction of ARs. IAA accumulation in the stem base is dependent on auxin re-mobilization from the upper shoot, with DL and FL as potential auxin sources and polar auxin transport (PAT) as important process of translocation.In the SB, leaf retention and greenness by affecting leaf senescence and abscission, with ethylene (ET) and cytokinins (CK) as classical trigger and inhibitors of leaf senescence or abscission, respectively. Whether the principally known agonistic effects of jasmonic acid (JA) and strigolactones (SL) on leaf senescence have relevance to cuttings, requires further investigation. High sugar levels, particularly of glucose can counteract leaf senescence/abscission, possibly via depressed ET signalling.Depending on the sensitivity of the leaves, systemic effects of the changed plant hormone homeostasis may control establishment and the strength of the new utilization sink in the stem base as compared to the competing sink in the upper shoot limits the influx of C and N resources into the stem base. Activity of cell wall invertase (INVcw) as crucial driver of initial sink activity may be under positive control by IAA and JA.The earliness of C and N re-mobilization from the upper shoot, particularly from fully developed leaves is an important process for the delivery of sugars and amino acids (AA) to the utilization sink in the stem base, with sucrose (Suc), asparagine (Asn) and glutamine (Gin) as important components of phloem transport (PT).gross)of gross photosynthesis (P and respiration in the light and in the dark (RLD) determines the carbon gain or loss of the leaf and thus its carbohydrate pool, with starch (Sta) and Suc as intermediate storage and main export fraction, respectively, while glucose (Glu) and Fructose (Fru) are locally utilized.The balance assimilation of nitrate and ammonium, that have been initially delivered from the root system of the stock plant, determines one influx of N into the AA and protein (Prt) pools, while competing with the sugar pool for C skeletons. Under prolonged dark conditions of whole cuttings that deplete the carbohydrate pool of leaves, leaf metabolism is readjusted towards a survival strategy, resulting in accumulation of AA, while proteolysis contributes to this process. If the released AAs are further catabolized to free ammonium, this may trigger leaf senescence.Light-dependent Depending on the plant genotype and configuration of environmental inputs at stock plant and cutting level, different processes may constitute the bottleneck (B) of cutting function .Rosa or Hydrangea macrophylla, can exhibit low rooting capacity in dependence on the specific genotype , no or few ARs will be formed. Cuttings, particularly of woody ornamentals such as genotype or when genotype . The undgenotype . In somegenotype , 2019. Ipulation . However factors requiresIf AR source cells require dedifferentiation before AR induction, early wound induced accumulation of ET and JA, together with CKs may contribute to this process by enhancing auxin responsiveness (see B1)If AR source cells are root competent , AR induction is dependent on local accumulation of IAA and further supported by a decrease in levels of the antagonistic CKs and SLs. Cutting off from (a) the root-ward auxin-drain and (b) the root-sourced delivery of CKs and SLs initiates these changes which may be supported by local IAA biosynthesis or release from auxin conjugates .In intact plants, IAA is synthesized in young expanding leaves and is in the stem either transported root-ward by polar auxin transport (PAT) in xylem parenchyma and cambium cells or co-transported in the phloem associated with assimilate transport (AT) , while iInitiation and expression of ARs requires a decrease of IAA and probably also of the physiologically active conjugate of JA after the induction phase. Obviously, upregulation of specific GH3 proteins that function as acyl acid amido synthetases conjugating IAA or JA to specific AAs has an important role for this dynamic . IAA levTemporal courses of carbohydrates and amino acids (AA) in the stem base of cuttings during rooting and the B7a) or N source (B7b) may limit rooting (If the sink in the SB is sufficiently high to attract resources (B6), their influx can be limited by the source capacity of the upper shoot, with the fully developed leaves (FL) as main source organs . Dependi rooting . The ava rooting , while c rooting . The lev rooting .Senescence or abscission of leaves can impair the visual quality and vitality of cuttings and may finally cause decay and loss of whole cuttings. Changed concentrations in cuttings particularly of ET, JA, and CK in response to their excision have consequences for leaf senescence and/or abscission when the changed hormone homeostasis meets the respective responsiveness of the leaf . Both, t2 on the C gain of cuttings, distinct effects of light spectrum may involve changes of auxin homeostasis and signaling (Serendipita indica (former Piriformospora indica) at stock plant or cutting level on leaf vitality and AR formation may involve changed C source and hormone signaling in cuttings. However, effects of such inoculations are highly variable and even include negative effects on AR formation, when comparing different environmental conditions, modes of inoculation and plant genotype on rooting of cuttings are unclear , monitorcuttings . In addicuttings . Howevergross. One of the most frequently used non-invasive tools for chlorophyll analysis in plant leaves is the Soil Plant Analysis Development (SPAD) chloropht (SPAD) . This tot (SPAD) . Very hit (SPAD) . Howevert (SPAD) . Digitalt (SPAD) is one at (SPAD) and are t (SPAD) .Infrared gas analyzers can be used to determine the current carbon gain of cuttings or cutting leaves under the condition of measurement, which may, however, differ from the real conditions of rooting depending on the used measuring system . Use of Considering that sugars and of AA in source tissues of cuttings reveal important fractions for the crucial C and N re-mobilization, analysis of their levels provides important information about the C and N source limitation of rooting . The N sARF and GH3 genes (Since hormone levels in the cutting tissues have decisive functions in leaf senescence and AR formation, their analysis can discover important bottlenecks of cutting function. Whereas commercial systems are available to measure ET emission by plants in closed environments such as storage packages or boxes , analysiH3 genes , RNA-basThe high complexity of highly dynamic environmental inputs in young plant production by cuttings and responding metabolic and hormonal pathways is a chaAll datasets generated for this study are included in the article/UD wrote the article.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The discovery of COVID-19 was linkedto the Huanan seafood market in Wuhan, China. As of February 27, 2020, there have been 82\u2009294confirmed cases globally with the first case in New Zealand.Because Samoa is an international tourism destination and, coupled with her conservativenature, is highly susceptible to an outbreak of COVID-19 if strict public health regulationsare not enforced. This is imperative considering the extent of spread and rapidity of virustransmission, especially among vulnerable populations. The rise of COVID-19 brought back thehorror of the last measles epidemic in Samoa and some Pacific Island countries. The gradualdecline in the measles epidemic trend was met with a sedulous approach toward case diagnoses,detection, and confirmation. It further stresses the importance of having well-equippedstate-of-the-art diagnostic health facilities, public health disease control centers, andhighly trained infectious disease personnel. This is a necessity for early disease detectionand diagnosis to prevent the occurrence of an epidemic of COVID-19 in Samoa.2 The successful implementation of this action plan is determined by many factors inindividual countries, and it mostly involves a cohesive teamwork between the local Ministry ofHealth and the Joint IMT composed of representatives from WHO and regional donor partners suchas Australian Department of Foreign Affairs and Trade (DFAT), New Zealand Ministry of ForeignAffairs and Trade (MFAT), Pacific Community (SPC), and the United Nations Children\u2019s Fund (UNICEF).2 The establishment and activation of Samoa\u2019s Health Emergency Operations Centre (HEOC)through the Ministry of Health (MOH) is a step forward for Samoa in preparation for COVID-19to enhance health sector surveillance, coordination, and provision of situational analysisupdates.It suffices to reason that the small Pacific Island countries could defeat an outbreak ofCOVID-19 by benchmarking and collaborating with both regional and internationalmultigovernment institutions for technical and financial support. The COVID-19 Joint IncidentManagement Team (IMT), coordinated by the WHO office in the Pacific, has developed and isimplementing a 6-month Pacific Action Plan for COVID-19 Preparedness and Response.2 The MOH has also put in place some public health measures against COVID-19 on theministry\u2019s website to ensure the general public is updated about the ongoing pandemic and, most important, to beaware of prevention and management strategies against COVID-19.Similarly, ongoing are campaigns on epidemic preparedness via leveraging on availableresources, capacity building; procurement of laboratory packaging and personal protectiveequipment (PPE); appropriate identification of isolation and quarantine facilities; anddeveloping case management protocols and strengthening communications to raise publicawareness and counter rumors and misinformation."} +{"text": "The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the \u201cworkforce\u201d) and the harnessing of the heterogeneity of thought (the \u201cthinkforce\u201d) to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Projects Programs and discussed barriers identified by new and early-stage investigators that limit effective career development, as well as potential solutions to overcome such obstacles. This report also proposes potential alignments of professional development activities, targeted goals and common metrics to track productivity and success. Achieving long-term health and wellness in communities that suffer disproportionately from racial, ethnic, environmental, and social and/or economic inequalities and inequities demands building institutional capacity and enhancing infrastructure on many levels. Particularly at institutions of higher education and health-professions schools, a major component of this infrastructure is the professional development of diverse teams of academic and community scholars (the \u201cworkforce\u201d), who understand the challenges faced by underserved and vulnerable populations because of shared life experiences (the \u201cthinkforce\u201d), to collaboratively explore and identify the causes of health disparities, to design and test the best measures and methods for studying health disparities, and to develop and implement the most effective and culturally appropriate interventions for reducing and eliminating health disparities ,2,3. FunHouse Report 98-911, attached to H.R. 6028 , provided the original language to establish research centers in predominantly minority institutions, which offered doctoral degrees in the health professions and/or the health-related sciences to individuals from underrepresented, underserved, and minority populations [Originally administered by the National Center for Research Resources (NCRR), of the National Institutes of Health (NIH), the RCMI Program provided support to two inaugural institutions: Florida Agricultural and Mechanical University (FAMU) and Ponce School of Medicine (PHSU). The next cohort, in 1986, included Clark Atlanta University, Meharry Medical College (MMC), University of Hawaii at Manoa (UHM), and University of Puerto Rico Medical Sciences Campus (UPR-MSC), followed in 1987 by Howard University (HU) and Morehouse School of Medicine (MSM). The annual operating budget of the fledgling RCMI Program, initially less than $1 million, has grown to more than $74 million in FY2020. Such growth has been justified by the successful leveraging of RCMI funds by RCMI grantee institutions and supported through strong congressional advocacy.As part of the NIH reorganization to create the National Center for Advancing Translational Sciences (NCATS), NCRR was dismantled in 2011 , and theA principal goal of the RCMI Specialized Centers is to create environments conducive to career enhancement for all investigators, and particularly women, persons with disabilities, and those from racial and ethnic groups which are underrepresented in biomedical research, as defined by the National Science Foundation . These environments are designed to assist investigators in becoming more successful in obtaining competitive extramural funding for basic biomedical, behavioral, clinical and/or population health research on diseases and conditions that disproportionately affect the health and well-being of ethnic minority and other underserved and marginalized communities, including the poor, homeless, rural persons, sexual and gender minorities, and recent immigrants. Another goal of the RCMI Centers is to strengthen and sustain partnerships with community-based and other non-academic organizations that reach the intended underserved populations to collaborate on the dissemination and implementation of culturally appropriate and contextually relevant interventions for health promotion and disease prevention. In short, the RCMI Centers are meant to diversify the workforce, enhance the quality of scientific inquiry, and promote collaborative research that improves minority health and reduces long-standing health disparities.As instructed in the funding opportunity announcements RFA-MD-17-003, RFA-MD-17-006, RFA-MD-18-018, issued by NIMHD, each RCMI Specialized Center had to be structured with four distinct cores: Administrative Core (AC), Community Engagement Core (CEC), Investigator Development Core (IDC), and Research Infrastructure Core (RIC). The primary goal of the IDC is to create a supportive career development milieu for post-doctoral fellows, junior faculty, and other early-stage investigators to conduct hypothesis-driven basic biomedical, behavioral, and/or clinical research that results in significant return on investment, as measured by peer-reviewed publications in high-impact journals and successful NIH grant applications, among other metrics. The IDC is also expected to develop and implement a Pilot Projects Program to provide funding on a competitive basis to new and junior investigators.The shared goals and expected functions of the RCMI IDC provide an unparalleled opportunity to improve coordination, increase efficiency and leverage resources for professional development across all RCMI Centers. Accordingly, the primary objective of the RCMI IDC Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019, was for IDC Directors to meet each other and to learn first-hand about the professional development activities and Pilot Projects Program at each RCMI Center with the goal of stimulating problem-solving discussions around common challenges to strengthen each RCMI Center and the collective RCMI Program. The near-term desired outcome was relationship building to facilitate the development of an IDC Consortium, comprising RCMI IDC Directors, which would meet regularly to enhance resource sharing to build a diverse workforce and thinkforce to reduce health disparities.The logistics and organization of the IDC Workshop were handled by the Research Coordinating Center, of the former RCMI Translational Research Network ,5, and tThe workshop started with an Information-Sharing Session to allow each Center to present a brief summary of their IDC activities, focusing primarily on professional development activities and on the Pilot Projects Program. Because the RCMI Centers have different project start dates, and because some RCMI Centers were transitioning from funding through the prior G12 funding mechanism while other RCMI Centers had no previous RCMI funding history, some Centers had data about the number of Pilot Projects Program project proposals received and reviewed, whereas other Centers were limited to presenting their plans. Nevertheless, the final slide of each presentation was devoted to articulating challenges and barriers to effective execution of IDC activities.Next, during the Problem-Solving Session, the IDC Directors and other workshop participants discussed the challenges and barriers encountered in implementing mentoring efforts and the Pilot Projects Program. Participants also shared potential solutions, and discussed milestones and common metrics to better track progress and to arrive at best practices and harmonization.Both the Information-Sharing Session and the Problem-Solving Session were informed by data collected from RCMI Investigator Needs Assessment Surveys, previously performed by the RTRN Research Coordinating Core. That is, the barriers and obstacles to optimal mentoring and professional development, as well as potential solutions, were those articulated by basic biomedical, behavioral, and clinical researchers at all academic levels, including junior investigators, who played a significant role in providing input through their real-life experiences.Finally, during the Networking and Evaluation Session, participants completed an evaluation survey about the workshop and were allowed time for unstructured interactions and relationship building to form the basis for the establishment of the envisioned IDC Consortium and sustained engagement of IDC Directors to achieve shared goals.The IDC Workshop was well attended, with active participation from 14 RCMI Centers: FAMU, FIU, HU, MMC, MSM, MSU, PHSU, SDSU, Tuskegee University (TU), UCR, UHM, UPR-MSC, University of Texas at El Paso (UTEP), and Xavier University of Louisiana (XULA). Each Center provided an overview of their mentoring and investigator development activities, as well as Pilot Projects Program.Common features were evident in the IDC of each RCMI Center. Specifically, the IDC provided personalized mentoring in scientific and career development to junior and early-stage investigators, as well as senior postdoctoral fellows. The IDC Directors acknowledged that effective mentoring was a key factor to successful career development. However, the process of identifying promising junior investigators and matching them with mentors who are compatible in terms of their personality, temperament, scientific knowledge, history of NIH funding, and mentoring skills is not fool proof and requires thoughtful, personalized attention. Research networking tools, such as the open-source Profiles Research Networking Software originally developed by Harvard Medical School and enhanced by the University of California San Francisco , can proInvestigator development activities at nearly all RCMI Centers consisted of developing mentoring teams, providing grant writing workshops, and arranging seminars, featuring internal and external researchers speaking about their research and topics related to health disparities and professional development. Importantly, junior investigators were provided opportunities to meet with speakers to foster mentorship and collaboration.The HU IDC presented a systematic and methodological program to fast track the development of junior faculty and early-stage investigators, using a tri-faceted approach that involved providing pilot seed-grant support, coordinating comprehensive career mentoring that included both discipline-specific research and professional advancement mentoring, and offering professional development trainings relevant to early-stage investigators .At FIU, mentoring activities were largely outcomes-driven and closely linked with the Pilot Projects Program. Recipients of pilot funding met regularly with RCMI faculty and other awardees for advice and support, with linkages to RCMI research training, RCMI research opportunities, RCMI community connections, and career development activities through the RCMI and other university-wide programs.Similarly, the FAMU IDC and MMC IDC focused mentoring efforts and other professional development activities and resources on recipients of pilot funding. MMC investigators were able to request a Studio ,9, whereThe SDSU IDC provides two avenues for career enhancement: a year-long program to awardees of pilot project funding, and open-forum career enhancement activities for all interested parties. For pilot project awardees, the SDSU IDC offers highly structured monthly mentoring sessions that cover wide-ranging topics, including individual development plans, project management, data management and safety, and optimizing success. The open-forum career enhancement activities generally focus on a specific topic or skill, such as how to select an appropriate electronic data capture system, how to effectively partner with external organizations on minority health and health disparities research, among others.The MSM IDC was built on the foundation of their well-developed Mentoring Academy that worThe MSU IDC provided a summer mini-sabbatical for its RCMI investigators to build collaborations at partnering institutions in Baltimore, such as the University of Maryland and Johns Hopkins University School of Medicine.The PHSU IDC provided a two-year program, known as Strategic Academic Research Training (START), to approximately six scholars per year. Emphasis was placed on enhancing the diversity that their scholars brought to the scientific workforce.At TU, mentoring and professional development activities were focused on early-stage investigators. In addition, the IDC was intent on supporting senior or established investigators, who were transitioning into research on the science of health disparities from non-biomedical fields or biomedical fields not directly related to minority health and health disparities.The UCR IDC\u2019s Big Feasible and Fundable Seminar Series was linked with the AC\u2019s Interdisciplinary Research Workgroups to create pipelines for identifying and recruiting junior investigators and to facilitate their acquisition of essential skills in communicating and collaborating across disparate disciplines. That is, Individual Multidisciplinary Mentorship Teams comprised mentors from within the trainee\u2019s discipline and from complementary disciplines.At UPR-MSC, IDC mentoring activities included informal meetings, rehearsal of scientific presentations, discussion of topics relevant to successful transition to running a lab (using the best-seller book: \u201cAt the Helm: Leading your Laboratory\u201d), and mock study sections. Trainees regularly review their five-year plans for grants, publications, and promotion.At UTEP, the IDC uses a \u201csynergy = success\u201d model, which incorporated the commitments of multiple stakeholders at the university, programmatic, and external levels to ensure sustained support of RCMI investigators. Apart from intensive training on grant writing, course release was offered to investigators in exchange for preparing and submitting grant applications, and senior postdoctoral fellows and senior investigators were provided opportunities to secure short-term starter funds and bridge funds, respectively.At XULA, the matching of junior investigators with collaborators and mentors occurred even before new faculty were officially recruited and multiple activities linked early-stage investigators, mid-career faculty and research scientists to RCMI and non-RCMI resources.Professional development activities for new and early-stage investigators at RCMI Centers can be generally grouped into three categories: Professional Conduct, Research Resources, and Career Skills and Knowledge. As an illustration, Through input from junior faculty at their institutions, the IDC Directors reported multiple barriers and obstacles to professional development . Among tIn addition to needing compatible mentors, junior faculty frequently mentioned other barriers to professional development, including their lack of knowledge about finding funding and training opportunities; the lack of pre-award grant application preparation; the lack of internal grants review system; the lack of bridging funds to continue while awaiting funding decisions.Apart from individual barriers to professional development, there were institutional obstacles that limited the growth of a diversified workforce for research on the science of minority health and health disparities at RCMI Centers. For example, institutional hiring freezes, limited institutional start-up funds for newly recruited faculty, insufficient grants development support, high administrative leadership turnover, and lack of positions for postdoctoral fellows in the absence of training grants, both individually and collectively, stifle the growth of a critical mass of investigators in specific research areas. In addition, broken promises and unfulfilled commitments by institutional leadership have occurred because of changes in organizational structure and/or changes in administration, as well as downturn in financial wellbeing.For each barrier and obstacle, potential solutions and enablers were identified to optimize mentoring and professional development of new and early-stage RCMI investigators . A possiCoordinating and leveraging the IDC infrastructure of the RCMI Centers, as well as engaging non-RCMI programs, including the Clinical and Translational Science Awards (CTSA), Institutional Development Award (IDeA), Centers for AIDS Research (CFAR), and Transdisciplinary Collaborative Centers (TCC), to serve on mentoring teams will accelerate attainment of research independence of early-stage RCMI investigators. Intensified engagement with the RCMI IDC Directors and the formation of an IDC Consortium would facilitate better alignment of professional development activities across the RCMI Centers . For exaThe IDC of each RCMI Center is expected to develop and manage a Pilot Projects Program to provide funding through a competitive process to RCMI investigators. Inherent in this approach are the expected outcomes of accelerating the pace of scientific discovery, heightening research productivity, increasing competitiveness for mainstream extramural funding, and ultimately improving the health of the nation. Currently, the awards for such pilot projects have ranged between $30,000 and $50,000 per year. For most RCMI Centers, the funding period for pilot projects was one year, but in the case of UPR-MSC, XULA, and SDSU, two or more years of support were granted. More than one year of funding was deemed especially necessary for community-engaged research projects. Thus far, the number of awards has varied from two to five pilot projects per year. However, insufficient data were available from many of the Pilot Projects Programs to assess success or return on investment.The FIU Pilot Projects Program planned to fund up to five pilot projects per year, with a goal of up to 20 projects during the five-year funding cycle. To date, eight FIU junior faculty have been funded, and each is preparing an NIH grant application .The UCR Pilot Projects Program provides support through four mechanisms: (1) Fostering Interdisciplinary Research-early STage Awards (FIRST Awards) serve as transition awards aimed at increasing competitiveness at obtaining external funding; (2) Pilot Interdisciplinary Collaborative grants (PIC Grants) seek to support goals of interdisciplinary research working groups; (3) Interdisciplinary Research Work Group Awards (IRWG Award) funds problem-focused interdisciplinary health disparities research; and (4) Continuity Collaborative Fellowships are awarded twice a year to fill gaps in research and database management in ongoing community-based research projects, conducted by graduate students or postdoctoral fellows.The XULA Pilot Projects Program, which focuses on early-stage investigators engaged in clinical and population research involving cancer health disparities, solicits applications jointly with the Louisiana Cancer Research Center (LCRC) and Project Pathways, of the Building Infrastructure Leading to Diversity (BUILD) program. Of 16 pilot applications submitted in 2019, three were funded through RCMI, three with LCRC, and six by BUILD.The MSM Pilot Projects Program involves a letter-of-intent. In 2019, full applications were invited from five of 11 investigators who originally submitted a letter-of-intent, and two awards were made. Applicants who were not funded were encouraged by the IDC to revise and resubmit their applications to the next round or to submit to other funding agencies.The UHM Pilot Projects Program also has a two-phase process. In the first phase, one-page abstracts and NIH Biosketches of the applicant(s), mentors and collaborators are reviewed by the principal investigators and core directors. In the second phase, invited full applications are evaluated by outside reviewers. Over three funding cycles, 83 abstracts were received and 37 full applications were invited, from which 15 pilot awards were made, resulting in 71 publications and 34 new grants .The HU Pilot Projects Program has had similar outcomes from seven pilot awardees, who have been responsible for 31 publications and 11 new grants, with a return on investment of 6.4 over two funding cycles.The RCMI Centers identified multiple barriers to the effective implementation of the Pilot Projects Program . Among tPotential solutions were identified to optimize the implementation of the Pilot Projects Program at RCMI Centers . As in mHeavy teaching loads for junior faculty and insufficient protected time for clinicians served as major deterrents to preparing proposals for Pilot Projects Programs. Finding solutions to these barriers is not a simple matter. Institutional investments are required at the department and college or school level. Particularly for newly hired basic scientists, a one- or two-year postponement of teaching obligations, coupled with intensive mentoring, would heighten the probability of grant success. Similarly, providing several months-long periods of protected time for clinical faculty would likely boost the number of grant proposals submitted and the likelihood of success, and once such faculty garner grant support, their mentors and IDC Directors should serve as strong advocates to negotiate reductions in teaching loads and clinical assignments.Alignment or harmonization of the processes and procedures of the Pilot Projects Programs at RCMI Centers would result in the achievement of specific goals each year . For exaContinued assistance to RCMI investigators whose applications were not selected for funding would constitute another way to align Pilot Projects Programs. That is, the professional development function of the IDC Consortium should be inextricably linked with the Pilot Projects Program function. The annual outcomes and goals in The opportunity for IDC Directors to meet face-to-face, nearly all for the first time, and to share their experiences, as well as to discuss their challenges at the IDC Workshop, has laid the foundation for the creation of an IDC Consortium, comprising the IDC Directors from RCMI Centers, to work collaboratively to overcome obstacles in professional development activities and to promote greater efficiency in the review process of pilot project proposals. The newly funded RCMI Coordinating Center will serve as a communications hub to facilitate the scheduling of regular meetings of the IDC Consortium and to coordinate continued interactions, resource sharing and problem solving to achieve the collective goals of advancing the careers of underrepresented minority investigators and those conducting minority health and health disparities research.By leveraging the leadership, expertise and talent of the RCMI IDC Consortium, there is every expectation that performance outcomes will improve and productivity measures will increase at individual RCMI Centers and in the overall RCMI Program. Although there are institution-specific barriers to building research capacity , there aJunior RCMI faculty do not typically encounter institutional racism, discrimination and/or bias, in large part because all RCMI grantee institutions serve predominantly racial and ethnic minorities and individuals from disadvantaged socio-economic backgrounds, and because many senior RCMI faculty and IDC Directors have themselves experienced hardships and barriers and understand the challenges faced by junior faculty. The lack of generational pipelines and access to academia is a well-known barrier to success. While not mentioned or discussed during the workshop, persistent barriers to professional development in the Science, Technology, Engineering, Mathematics, and Medicine (STEMM) pipeline perpetuate racial disparities in academia. Solutions lie in earlier exposure and access to resources, supportive mentoring networks, and comprehensive training programs for racial and ethnic minority students and trainees at each career stage . MultiplIn addition to monthly IDC Consortium-wide meetings, periodic regional meetings based on geography and time zones might further strengthen relationship building, enhance resource sharing, and facilitate and expedite the review of pilot project proposals. Currently, there are 21 RCMI Centers, distributed in 12 states, the District of Columbia, and Puerto Rico. Each regional sub-consortium could comprise four or more RCMI IDC , and theProfessional development activities are also enhanced through resources within the RIC and CEC of each RCMI Center, as well as leveraged through considerable resources available in collaborations and partnerships with other NIH-funded infrastructure programs, such as CTSA, IDeA, CFAR, and TCC, at non-RCMI grantee institutions ,23. MoreCommunity-driven and culturally relevant solutions to eliminating health disparities necessitate the creation of a supportive mentoring milieu to accelerate the career development of diverse and multidisciplinary teams of scholars (the \u201cworkforce\u201d) and to harness the heterogeneity of their thought and thinking (the \u201cthinkforce\u201d). That is, only by embracing and celebrating the power of different perspectives, tempered by unique lived experiences and influenced by cultural and indigenous beliefs, as well as age-old community practices and norms, can one expect to pose previously unasked research questions and to design distinctly alternative approaches that lead to innovative interpretations of data and sustainable strategies for disease prevention and health promotion for underserved populations and marginalized communities. The IDC Consortium provides an exciting platform for productive interactions that foster the sharing of research resources and human capital across the RCMI Centers to hasten the acquisition of new knowledge to improve minority health and to reduce health disparities. Such interactions are also likely to strengthen and sustain inter-institutional collaborations and partnerships with non-RCMI grantee institutions ,23."} +{"text": "The 9th Conference of the International Society for Integrated Disaster Risk Management (IDRiM) was held in Sydney on 2\u20134 October 2018. The event was hosted by Data61, the data innovation hub of Australia\u2019s National Science Agency CSIRO. The IDRiM annual conference series traditionally brings together researchers and practitioners across all disciplines of disaster risk management (DRM) and the Australian instalment was no exception. More than 120 participants from 20 countries attended the congress, representing all sectors of DRM including academia, industry, and governmental agencies, to exchange on ideas and best practices through a mix of plenaries, presentations, panel discussions, and poster sessions.Data-Driven Approaches to Integrated Disaster Risk Management, mirrors the overarching theme of the 2018 IDRiM conference, which set out to explore the ever-increasing role of data in all areas of disaster risk and emergency management. The articles included in this special issue have been selected to represent the diversity of data-driven approaches under active development for DRM. They are also illustrative of the multidisciplinary nature of DRM, its applications ranging from natural hazards to man-made disasters or even a combination of the two. All four phases of DRM, namely prevention (or mitigation), preparedness, response, and recovery are covered in this volume, and many of the themes that were extensively discussed during the conference are further explored here.This special issue, entitled In the prevention phase, data science and analytics can inform us on the potential impact of both natural hazards and man-made disasters to help protect the ecological diversity of our environment and make better long-term choices and investments, which in turn will improve the safety and welfare of our communities, as discussed in Liu et al. In this context, the ability to access extensive databases is a critical element of building evidence-based strategies for prevention and preparedness purposes . Important challenges remain, however, when dealing with heterogeneous sources of data and several of the technologies presented in the special issue aim to address the issues of data collection, data curation, and data sharing to dramatically improve such cross-disciplinary collaboration .Digital technologies such as smartphones have become ubiquitous in modern life, but their application to DRM has yet to be fully realized. An example of such application is discussed in Yamori and Sugiyama, where a smartphone app was developed to increase the preparedness of the local community by simulating tsunami evacuation drills. Another example of the potential application of digital technologies is the development of evidence-based decision support systems both for planning and operational (response) purposes. As the volume and accuracy of available data increase, a number of initiatives around the world have been focussing on developing such systems in recent years to help emergency coordinators make informed decisions. Two of the articles in this special issue discuss these concepts as applied to storms, floods, and landslides in Japan (Takenouchi and Yamori) and debris flows in Indonesia .Improved resilience is achieved through risk assessment and risk reduction, which in turn implies understanding and reducing various sources of uncertainty in the data and in the processes at play. Two articles propose methodologies to address these important issues in the context of hurricane vulnerability and post-earthquake lifeline systems recovery (Deelstra and Bristow). This last article in the volume also exemplifies that perhaps one area where the unrealized potential of data-driven approaches is the most evident is in fact in the post-disaster recovery phase. The premise here is to help communities regain a sense of stability and rebuild faster after being struck by a disaster.Each of the articles in this special issue may be briefly summarized as follows:Variability in Regional Ecological Vulnerability: A Case Study of Sichuan Province, China by Yimeng Liu, Saini Yang, Chuanliang Han, Wei Ni, Yuyao Zhu. The authors developed a data-driven method to assess the vulnerability of ecological systems to external stress factors such as natural hazards and human activities. They found that for the case study of Sichuan Province, anthropogenic construction activities increased ecological vulnerability more than any other factors considered, including natural hazards.Seismic Policy, Operations, and Research Uses for a Building Inventory in an Earthquake-Prone City by Ken Elwood, Olga Filippova, Ilan Noy, Jacob Pastor Paz. A building inventory database integrating datasets from multiple sources was created for the city of Wellington, New Zealand to manage the risks associated with earthquake events. The multiple uses of such a database discussed in this article, ranging from planning to response, highlight the importance of easily accessible data in the decision-making process.Disaster Risk Management through the DesignSafe Cyberinfrastructure by Jean-Paul Pinelli, Maria Esteva, Ellen M. Rathje, David Roueche, Scott J. Brandenberg, Gilberto Mosqueda, Jamie Padgett, Frederick Haan. This article presents a cloud-based cyber-infrastructure platform designed to address the challenges associated with collecting, curating, sharing, and analyzing heterogeneous datasets for disaster risk management purposes. The article discusses the application of this multi-disciplinary tool to several cases including soil liquefaction, seismic risk analysis, and hurricane recovery.Extracting Natech Reports from Large Databases: Development of a Semi-Intelligent Natech Identification Framework by Xiaolong Luo, Ana Maria Cruz, Dimitrios Tzioutzios. This contribution explores the use of machine learning algorithms to extract information about natural hazard-triggered technological accidents from large databases for risk management purposes. It provides an example of using state-of-the-art computing technologies to realize the potential of available data for disaster risk management.Development and Social Implementation of Smartphone App Nige-Tore for Improving Tsunami Evacuation Drills: Synergistic Effects between Commitment and Contingency by Katsuya Yamori and Takashi Sugiyama. Nige-Tore is a smartphone app that allows the user to participate in a tsunami evacuation drill. Participants take actions and choose escape routes based on real-time updates of a simulated tsunami displayed on a map. The authors discuss at length the benefits and challenges of the human-digital technology interactions brought about by this app, and explore how these new technologies may be useful resources to improve our preparedness for natural hazards and disasters.Synergistic Integration of Detailed Meteorological and Community Information for Evacuation from Weather-Related Disasters: Proposal of a \u201cDisaster Response Switch\u201d by Kensuke Takenouchi and Katsuya Yamori. The importance of high-resolution meteorological data and weather forecasting models is discussed in the context of several common hazards in Japan, namely storms, floods, and landslides. From the results of this study it is apparent that the development of data-driven decision support systems is critically needed to assist local authorities develop appropriate and evidence-based emergency response, and to determine the timing of an evacuation.Na\u00efve Bayes Classifier for Debris Flow Disaster Mitigation in Mount Merapi Volcanic Rivers, Indonesia, Using X-Band Polarimetric Radar by Ratih Indri Hapsari, Bima Ahida Indaka Sugna, Dandung Novianto, Rosa Andrie Asmara, Satoru Oishi. A debris flow disaster warning system for a volcanic region in Indonesia is presented. The method estimates debris flow susceptibility through a simple data mining approach. The study also highlights the need for higher-resolution data to improve the robustness of the model.Uncertainty Reduction through Data Management in the Development, Validation, Calibration, and Operation of a Hurricane Vulnerability Model by Jean-Paul Pinelli, Josemar Da Cruz, Kurtis Gurley, Andres Santiago Paleo-Torres, Mohammad Baradaranshoraka, Steven Cocke, Dongwook Shin. This contribution discusses the issue of epistemic uncertainty and approaches for uncertainty reduction with hurricane vulnerability as a case study, in the context of insurance claims. By integrating various sources of data augmented claims may be constructed, which then facilitate the development of a vulnerability model.Characterizing Uncertainty in City-Wide Disaster Recovery through Geospatial Multi-Lifeline Restoration Modeling of Earthquake Impact in the District of North Vancouver by Andrew Deelstra and David Bristow. The authors studied, through a data-driven modeling approach, the recovery of lifeline systems in the earthquake-prone area of the district of North Vancouver. One of the uses of their model is to determine which systems are more likely to be restored first following a disaster and to allocate resources accordingly to accelerate the overall recovery process.Following the 2018 IDRiM conference in Australia, the next congress was held in Nice, France, in October 2019 and focused on \u201cknowledge-based disaster risk management\u201d thus expanding on the notions of information and data science applied to risk reduction, resilience, and sustainable development. Two major events in 2019-2020 dramatically illustrated the relevance of these two themes of data- and knowledge-based approaches for disaster risk management.The first was the catastrophic bushfire season that occurred across six states in Australia between the second part of 2019 and ended in May 2020. This event caused 34 direct fatalities and in excess of 400 indirect fatalities and affected almost three billion animals, not to mention the economic and broader ecological costs that are both yet to be fully estimated. Following this major disaster, it became clear that in order to become more resilient to such large-scale events as a society, better data analytics, artificial intelligence (AI) solutions, and new digital innovations were needed. The Australian government thus invested a further AUD 88.1 million over the next 10\u00a0years in the Bushfire and Natural Hazards Cooperative Research Centre, with space monitoring and predictions of natural hazards, development of new digital technologies, and AI solutions all at the heart of the center\u2019s mission.As catastrophic as the Australian bushfires had been, they were almost eclipsed in the media by the global COVID-19 pandemic that developed worldwide in 2020. Again, the role of data-driven science in the fight against the spread of the virus was abundantly clear. Many governments based their decisions to implement lockdown measures on predictive scientific models that utilized the latest available data to help assess the effectiveness of potential mitigation strategies in slowing down the spread of the virus. Moreover, geospatial monitoring has been used worldwide to manage this crisis, firstly through the development of smartphone apps to improve the enormous task of contact tracing, and secondly to understand the effect of restrictions on the mobility of individuals put in place by authorities.Now more than ever, the world has therefore become acutely aware of the key role that data-driven approaches play in disaster risk management, and we hope that this special issue will provide the reader with an overview of some of the important initiatives currently pursued in this area.Vincent Lemiale, Mahesh Prakash, and Ana Maria CruzGuest Editors"} +{"text": "Epidemiological evidence has demonstrated the association between dietary factors and non-communicable diseases. Great attention has been payed to the Mediterranean dietary pattern, given its richness in anti-oxidant and anti-inflammatory molecules. Numerous reports from the SUN (Seguimiento Universidad De Navarra) cohort have shown that higher adherence to the Mediterranean dietary pattern may be inversely associated with mortality, type 2 diabetes and cardiovascular diseases. Likewise, a link with mental health outcomes, such as depressive symptoms, cognitive status and quality of life was also found, suggesting its beneficial effects toward brain health. Non-communicable diseases are the leading causes of premature mortality and disability in developed countries ,2. ObesiThe SUN (Seguimiento Universidad De Navarra) study represents one of the main cohorts in the European Mediterranean area aiming to explore the association between dietary factors and non-communicable diseases. It involves individuals aged 20 years and over who have previously graduated from the University of Navarra, as well as from other different Spanish universities; the cohort has adopted an open continuous recruitment of highly educated participants, which is supposed to reduce the potential risk of bias. The project has contributed for over 20 years to evidence on the importance of traditional dietary patterns, such as the Mediterranean diet, as an ideal dietary choice for the prevention of chronic diseases . The artAnother line of research investigated within the context of the SUN cohort has been the role of the Mediterranean diet on mental health, including depressive symptoms, cognitive status and quality of life. Higher adherence to the Mediterranean and other healthy dietary patterns has been associated with a lower risk of depression . SimilarA traditional Mediterranean diet characterized by (i) high intake of plant-derived foods ; (ii) use of olive oil, nuts and fish as the main sources of fats; (iii) low consumption of meat and processed foods; and (iv) moderate alcohol intake (mostly wine) during meals, and is a dietary pattern that provides an ideal content of healthy nutrients (such as poly- and monounsaturated fatty acids) and bioactive components exerting anti-inflammatory and antioxidant properties (such as vitamins and polyphenols) , many ofThe contribution of the SUN cohort to nutritional science was crucial in making modern knowledge on the role of certain dietary factors, among which the Mediterranean diet is the core research question of this cohort, in human health. The results obtained are in line with those reviewed in two umbrella reviews of meta-analyses of the role of the Mediterranean diet in preventing non-communicable diseases ,37. The"} +{"text": "Investigators from the Soroka University Medical Centre, The Hebrew University of Jerusalem, and Tikun Olam Ltd. in Israel studied the safety and efficacy of medical cannabis treatment on 188 patients with autism spectrum disorder (ASD) for six months. Investigators from the Soroka University Medical Centre, The Hebrew University of Jerusalem, and Tikun Olam Ltd. in Israel studied the safety and efficacy of medical cannabis treatment on 188 patients with autism spectrum disorder (ASD) for six months. The study examined the efficacy of cannabidiol (CBD) through a quality-of-life assessment, global assessment rating, and an ASD symptom severity assessment looking at restlessness, rage attacks, agitation, speech impairment, cognitive impairment, anxiety, incontinence, depression, and more. The safety of CBD was examined by assessing physiological and cognitive side effects. The largest national provider of medical cannabis in Israel employed several of the authors and sponsored this study. [COMMENTARY. ASD is a developmental disorder with two clusters of symptoms: 1. persistent deficits in social communication and social interaction, and 2. restricted, repetitive patterns of behavior, interests, or activities and effeSafety was assessed by analyzing the frequency of side effects, while efficacy was analyzed using the ASD symptom severity assessment. Many of the same symptoms were reported as both side effects of the treatment and comorbid symptoms of prior diagnoses, making it difficult to interpret the results. The safety of medical cannabis was assessed within a one-month, and six-month follow up. Progress of patients who received extra THC doses was not differentiated from the remainder of patients.Long-term safety from prolonged usage could not be determined from this study. Patient outcomes and side effects were only recorded at months one and six; the selection of this specific follow-up period is not clearly explained. Observational studies, such as this one, are essential in identifying the short-term safety and efficacy of medications; CBD's long-term safety for ASD spectrum patients is unclear.Subjective self-reporting by parents of patients was used as the basis of this study. Parents' expectations likely influenced their reporting. Assessment of parental perceptions and expectations of safety and efficacy at baseline could have elucidated these potentially confounding factors. Furthermore, this study was sponsored by a large local CBD manufacturer and the study population was using the product, which could have added an extra layer of parental reporting bias. Prospective, independent, placebo-controlled clinical trials are required to determine more accurate long-term efficacy and dosing guidelines for CBD in ASD.The authors have declared that no competing interests exist."} +{"text": "In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China.From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces.School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends differed among provinces. Compared with Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as the local transmission of COVID-19 declined, switching the focus of measures to the testing and quarantine of inbound travellers may have helped to sustain the control of the epidemic.Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database containing these indicators and information regarding control measures is a useful resource for further research and policy planning in response to the COVID-19 epidemic. The coronavirus disease 2019 (COVID-19) outbreak was first reported in Wuhan City, Hubei Province, China in late December 2019 . From laThe Imperial College London COVID-19 Response Team initiated data collection activities in mid-January 2020 to understand the epidemic in China. Together with volunteers, the Imperial Team made considerable efforts to collate aggregated data and individual patient information from publicly available, national, and local situation reports published by health authorities in China. Individual case or death reports are considered crucial for informing the determinants of disease severity and fatality during the emergence of the epidemic , but theThe data we extracted from Chinese official reports may also be useful for the wider research community by building on other existing data collection activities . In the https://github.com/mrc-ide/covid19_mainland_China_report.Daily situation reports of the COVID-19 epidemic were extracted from mid-January to 31 March 2020 in 31 provinces/municipalities of mainland China. We downloaded these reports from the websites of local health commissions and used Google translate to obtain English versions for each province/municipality. In addition, reports from the National Health Commission website and Wuhan City Health Commission website were included. We extracted aggregated numbers of cases, deaths, recoveries, contacts, and details on disease severity and case importation from the official reports released each day . The quaWe reviewed the timing of implementation and subsequent lifting of the following control measures: i) cancellation of cross-province public transportation; ii) temperature checks for inbound travellers at provincial borders; and iii) community-level lockdown that reported the highest numbers of confirmed cases up to the end of March 2020. These provinces accounted for 90% of the total COVID-19 cases in mainland China. Hubei alone accounted for 80% of the total number of reported cases .Figure 1We first calculated the proportion of recoveries from 15 January to 31 March as: results .To investigate the disease severity across provinces, we obtained the crude case-fatality ratio (cCFR) as: eporting , but it According to the guidelines for contact investigation published by the On 26 January 2020, In addition to school closures, In addition to the key dates for initiating and lifting the three most common control measures, We explored the association between the epidemic trend and health care burden based on the time-varying proportions of the total confirmed cases who recovered . Most prA wide variation in cCFRs was reported in each province by 31 March 2020 . Most ofProvincial differences in disease severity were also demonstrated by the analysis of hospitalised cases , where HFinally, we investigated the scale of contact tracing for infection control at the national and provincial levels by using the ratio of total contacts relative to total cases by the end of March . On averIn this study, we conducted data collation and descriptive analyses of the COVID-19 epidemic trends and control measures in mainland China between mid-January and March 2020. In most provinces, the local epidemics peaked in early February and declined in early March, but they were not completely eliminated because the number of imported cases increased. School closures, travel restrictions, contact tracing, and other control measures were enforced at a similar time from late January across provinces. However, in Hubei where the origin of the COVID-19 pandemic was reported, increased levels of case fatality and severity were reported compared with the other five most badly affected provinces analysed. Based on the descriptions of the epidemic trends and timings of interventions, we observed the potential effects of early implementation and timely adjustment of the control strategies on containing the COVID-19 epidemic in mainland China. The collated data have been made available and they may provide a useful resource for further research into epidemic control and policy planning.Domestic travel restrictions were implemented at similar times across provinces in China , althougThe timing of school reopening in China depended on the local epidemic situation , but theA particularly high cCFR was reported in Hubei compared with the other provinces according to our analysis. This difference in disease severity was also consistently demonstrated by the proportion of critical and severe cases over the last few months. Another study that accounted for right-censoring when estimating the true case fatality demonstrated a similar discrepancy across provinces to that we determined based on the cCFRs . This siThe indicators comprising cCFR and proportions of currently critical and severe cases exhibited different relationships across the provinces in China . Henan pContact tracing was implemented nationally at the beginning of the epidemic in China as a key strategy coupled with case management . We founA major limitation of our descriptive analysis is the use of aggregate cases, deaths, recoveries, and contacts data. These indicators are convenient for monitoring and comparing the epidemic trends by province, but further inferring the effects of risk factors on the transmission dynamics is not possible. Patient characteristics such as age and comorbidities are essential for understanding the heterogeneity of disease severity. Estimations of the setting-specific incubation period, reporting delay, and disease progress also rely on the date of symptom onset and care-seeking pathways for individual cases . AnotherMany containment measures have been implemented in the different provinces of China since the beginning of the COVID-19 outbreak in Wuhan City, Hubei Province. Similar control measures were also introduced in other countries, such as Singapore and South Korea, although the practical implementations varied . Social HF, HW, XX, NI, and SB conceptualised and conducted the analysis. HF, HW, XX, AB, YW, SLvE, and NI set up the data collation framework and maintained the quality of the data sets. HF, HW, XX, AB, YW, WH, KJF, RM, DOM, JS, AL, TD, AD, KECA, LC, GC, ODE, NS, HAT, HJTU, and LKW extracted the data. HF wrote the first draft of the manuscript. All authors contributed to the revised version of the manuscript and agreed with its submission.UK Medical Research Council and Department for International Development [grant number MR/R015600/1]. This study was also supported by the National Institute for Health Research Health Protection Research Unit in Modelling Methodology, the Abdul Latif Jameel Foundation, and the EDCTP2 programme supported by the 10.13039/501100000780European Union.We acknowledge Joint Centre Funding from the The authors declare that they have no conflicts of interest.This study did not require ethical approval because aggregated publicly available data were used."} +{"text": "Zea mays genes were expressed with various expression levels in the tested development stages, including dough stage, fruit formation, anthesis, inflorescence formation, stem elongation, seedling stage and germination (In the The Expression Profile During Different Development Stage and Different Tissues of the RNA Helicase Genes in Four Species Under Normal Growth Conditions subsection of the Results, there is an error in the first sentence of the third paragraph. The correct sentence is: Approximately 108 mination .There are errors in the number of RNA expression profiles in the captions of The image for"} +{"text": "The time trend of prevalence and mortality of major cancers is the result of three competing processes: changes in the incidence rate, stage-specific survival, and ascertainment at early stages. Partitioning approach allows for evaluating the relative contribution of each of these competing processes to the overall trend. In this report we applied the partitioning methodology developed for the SEER registry data for prostate, colorectal, lung, female breast, bladder, ovarian, stomach, pancreas, kidney, liver cancers and melanoma. The analysis involves the design and estimation of four models for each cancer site: i) incidence rate using the Armitage-Doll model with individual predisposition modeled by the gamma distribution, ii) probability of relative survival after cancer diagnosis using the Weibull model for time after disease onset, iii) frequencies of stage at onset, and iv) mortality in the general population using the Gompertz model. B-splines are used to fit the time patterns of model parameters obtained for each year Relative contributions of the partitioning components were evaluated for individual cancers , improved survival (29%), and improve stage ascertainment (12%)) and compared among all considered cancers. The results were discussed in the light of the effect of the accumulation of survivors occurring in early years and their higher mortality in later years ."} +{"text": "This presentation will share examples of arts-based and creative interventions serving people and their families living with dementia representing evidence-based and promising practices in the United States. Such interventions offer effective non-pharmacological approaches to dementia care including use of the visual arts and performing arts ; literature and writing including reminiscence, biographical approaches, and life story work; photography and Photovoice; and dance and movement as intervention modalities. Current evidence will be presented that demonstrates the effectiveness of arts-based interventions as a form of psycho-social and self-care to alleviate the effects of dementia and enhance the quality of life. Recommendations for future research will be discussed. Strategies will be proposed to develop interprofessional health humanities networks between universities, healthcare systems, libraries, museums, and the arts community to collaborate on the creation of arts-based programs in communities currently without the benefit of such programs."} +{"text": "The COVID-19 epidemic is still spreading globally. Contact tracing is a vital strategy in epidemic emergency management; however, traditional contact tracing faces many limitations in practice. The application of digital technology provides an opportunity for local governments to trace the contacts of individuals with COVID-19 more comprehensively, efficiently, and precisely.Our research aimed to provide new solutions to overcome the limitations of traditional contact tracing by introducing the organizational process, technical process, and main achievements of digital contact tracing in Hainan Province.A graph database algorithm, which can efficiently process complex relational networks, was applied in Hainan Province; this algorithm relies on a governmental big data platform to analyze multisource COVID-19 epidemic data and build networks of relationships among high-risk infected individuals, the general population, vehicles, and public places to identify and trace contacts. We summarized the organizational and technical process of digital contact tracing in Hainan Province based on interviews and data analyses.An integrated emergency management command system and a multi-agency coordination mechanism were formed during the emergency management of the COVID-19 epidemic in Hainan Province. The collection, storage, analysis, and application of multisource epidemic data were realized based on the government\u2019s big data platform using a centralized model. The graph database algorithm is compatible with this platform and can analyze multisource and heterogeneous big data related to the epidemic. These practices were used to quickly and accurately identify and trace 10,871 contacts among hundreds of thousands of epidemic data records; 378 closest contacts and a number of public places with high risk of infection were identified. A confirmed patient was found after quarantine measures were implemented by all contacts.During the emergency management of the COVID-19 epidemic, Hainan Province used a graph database algorithm to trace contacts in a centralized model, which can identify infected individuals and high-risk public places more quickly and accurately. This practice can provide support to government agencies to implement precise, agile, and evidence-based emergency management measures and improve the responsiveness of the public health emergency response system. Strengthening data security, improving tracing accuracy, enabling intelligent data collection, and improving data-sharing mechanisms and technologies are directions for optimizing digital contact tracing. The COVID-19 epidemic is still spreading rapidly worldwide. Tens of millions of people have been infected, and the number of infections is still growing rapidly. Most countries or regions are still in states of public health emergency. Although China, the United States, and other countries have successfully developed COVID-19 vaccines, the production and application of the vaccines still have large gaps. Moreover, effective drugs for treatment of COVID-19 have not been successfully developed. Therefore, quickly identifying and tracing individuals infected with COVID-19 and their contacts and adopting active emergency management measures, such as travel restrictions, health monitoring, and home-based quarantine, are necessary for all countries and regions to overcome the COVID-19 epidemic [Contact investigation has always been an important public health strategy and a key process in epidemic emergency management. The scale of COVID-19 infection poses a major challenge to contact investigation . TraditiDigital contact tracing uses electronic information to identify exposures to infection; it has the potential to address the limitations of traditional contact tracing, such as scalability, notification delays, recall errors, and contact identification in public spaces ,11. CurrThe data storage and processing models of digital contact tracing adopted by some countries and regions are generally divided into centralized and decentralized models . In the applet to collect residents\u2019 self-reported health characteristics and travel history and to combine the location information generated by the users\u2019 specific quick response (QR) codes to trace infected persons and contacts for individual risk assessment. A health code is generated for the identification of personal infection risk; this code serves as a voucher for passage, work resumption, and school resumption [South Korea and China have adopted the centralized model for digital contact tracing . Korea\u2019ssumption ,16. The The decentralized model was adopted by countries and regions such as Europe, North America, and Singapore . Google,App-based digital contact tracing in a decentralized mode can only be effective when used by 40%-70% of smartphone users . The earAn empirical study showed tTherefore, this study aimed to overcome the insufficient use and objectivity of existing digital contact tracing\u2013related practices and provide new solutions to further improve the effectiveness and reliability of digital contact tracing. Hainan Province, China, was selected as the case in this study. Hainan Province adopted a centralized model to conduct contact tracing during the COVID-19 epidemic. Moreover, the model gathered multisource epidemic data that relied on the government\u2019s big data public service platform, which enabled government agencies to apply graph database algorithms, data visualization, and other digital technologies to determine and trace contacts from hundreds of thousands of epidemic records. This study describes the organizational process, technical process, application prospects and possible obstacles of digital contact tracing in Hainan Province, which may provide a more effective solution and technical support for other countries and regions.Hainan Province is one of the most popular tourist destinations among Chinese and even global tourists because of its tropical island scenery. Due to the massive influx of tourists, the flow rate of the population of Hainan Province is very large. Additionally, due to the geographical location of the island, the influx of infected individuals is the main challenge in the emergency management of the COVID-19 epidemic. As of August 7, 2020, Hainan Province reported a total of 171 confirmed individuals infected with COVID-19 [Hainan Province issued the \u201cRegulations on the Development and Application of Big Data in Hainan Province\u201d in October 2019 , which cWe conducted semistructured interviews in collaboration with the project manager and technical staff of the Big Data Administration who were in charge of Hainan\u2019s COVID-19 epidemic digital contact tracing project to understand the details of the whole process. We explained the purpose and content of the interview to the interviewees before the interview, recorded the outlines during the interview, and transcribed the voice recording to text format after the interview.Under the leadership and coordination of the Command of Hainan Provincial Epidemic Prevention and Control, the Hainan Provincial Big Data Administration collected epidemic data from different agencies, including epidemic investigation records, confirmed infected individuals\u2019 information and their spatiotemporal trajectory, high-risk population information, information on close contacts and patients with fever, and the mobile phone signaling data of imported residents or travelers with a history of residence in Hubei Province . The information in the specific databases is shown in A graph database is a new type of database system based on graph theory and algorithms that efficiently processes complex relational networks. A graph database can efficiently process large-scale, complex, interconnected, and changeable data, and its computational efficiency is far higher than that of a traditional relational database . A graphMost graph databases provide a query language that is suitable for representing graph structures and graph query. Neo4j is a Java-based open-source graph database with high performance, high reliability, and strong scalability . The graOur research used the Cypher algorithm of Neo4j version 3.4.15 to construct an association graph among the high-risk population, the general population, vehicles, public places, and other key information; reveal the hidden network of relationships; and identify the risks in the relationships to identify and trace the contacts of COVID-19 cases.ECharts (Apache Software Foundation) is an open-source visualization tool based on JavaScript that can run smoothly on personal computers and mobile devices and is compatible with most current web browsers. The bottom layer relies on a vector graphics tool, ZRender, to provide intuitive, interactive, and highly personalized data visualization . EChartsOur research used ECharts to visualize basic data and the results of the graph database algorithms as well as to develop web portals and interactive operating systems to intuitively and dynamically query and analyze epidemic data.Based on the data planning, data collection, data storage, data analysis, and data application processes involved in the data life cycle, we used interview data to summarize the activities performed by various participants in the digital contact tracing process of the COVID-19 epidemic in Hainan Province. The specific organizational process is as follows.Data planning includes organization, assessment of the situation and demand, and the formulation of strategic goals. This project was initiated by the Hainan Provincial Command of COVID-19 Epidemic Prevention and Control on January 29, 2020. The governor of Hainan Province, as the person in charge, instructed various government departments to cooperate with the Big Data Administration to apply big data technology to COVID-19 epidemic emergency management\u2013related work. That is, the Hainan Provincial Command of COVID-19 Epidemic Prevention and Control played a leading and coordinating role, the Hainan Big Data Administration played a leading role in implementation, and other government departments played cooperative roles. Thus, an integrated and flat organizational structure and coordination mechanism were formed.The Hainan Big Data Administration immediately assessed the COVID-19 epidemic situation and emergency management measures, coordinated communication with the Command of COVID-19 Epidemic Prevention and Control and other relevant government departments, and organized epidemiologists and big data technicians to formulate an implementation plan. The plan determined the specific implementation details of using multisource epidemic big data for digital technology tracing and submitted achievable data requirements to the Command of COVID-19 Epidemic Prevention and Control. Then, the COVID-19 Epidemic Prevention and Control headquarters coordinated the cooperation of work by relevant departments and provided the specified data.Hainan Provincial Big Data Management collected the first batch of data in Excel format (Microsoft Corporation) from the Command of COVID-19 Epidemic Prevention and Control, Public Security Department, Health Commission, communication operators, and other departments on February 10, 2020.The technicians of the Hainan Provincial Big Data Administration cleaned and merged the data under the guidance of officials and epidemiologists, uploaded all databases to Hainan\u2019s big data public service platform, and used the hive data warehouse tool to manage, extract, query, and analyze the data.The data technicians of the Hainan Provincial Big Data Administration retrieved data from Hainan\u2019s big data public service platform; used the graph database Neo4j algorithm to perform association analysis on key populations, vehicles, and public places; and then used ECharts to visualize the data analysis results and determine contacts and high-risk public places.The Hainan Provincial Big Data Administration regularly writes COVID-19 epidemic contact tracing reports based on the results of data analysis and reports them to the Command of COVID-19 Epidemic Prevention and Control. The Command of COVID-19 Epidemic Prevention and Control promptly releases early warning information to the public; strengthens cross-departmental sharing of information; and guides the Health Commission, CDC, medical and health institutions, and grassroots residents\u2019 committees in the implementation of measures, such as isolation, health monitoring, and nucleic acid testing of contacts. Measures are also implemented to limit the flow of people and close high-risk infected public places.The technicians of the Hainan Provincial Big Data Administration took confirmed, suspected, and asymptomatic infected individuals, as well as individuals with a history of residence in Hubei Province, as the nodes of population; private cars, trains, and flights as the nodes of transportation; and communities and shopping malls as the nodes of public places. The technicians defined a relationship as appearance in the same public place or vehicle at the same time. Based on these nodes and relationships, the Neo4j Cypher algorithm graph database was applied to build an association graph to analyze and display the associations among key populations, vehicles, public places, and other key pieces of information. The core algorithm of the graph database used in our research is shown in The representative analysis results of the graph database algorithm are shown in The Hainan Provincial Big Data Administration applied ECharts data visualization tools to compute and visualize the distribution of the population with a residence history in Hubei Province in all cities of Hainan Province. As shown in The Hainan Provincial Big Data Administration applied the graph database algorithm to rank the frequency of confirmed, suspected, and asymptomatic infected individuals and their contacts appearing in shopping malls and communities. The results were used to infer and predict public places with high risk of infection.The Hainan Provincial Big Data Administration used ECharts to visualize the basic data and analysis results and also designed an interactive operating system that can be accessed through a web page on a browser. The system interface is shown in The Hainan Provincial Big Data Administration identified 61,439 analysis objects from hundreds of thousands of records and identified 10,871 contacts. The authorities took measures to isolate, transport, and monitor these contacts. Hainan provincial digital contact tracing identified 378 individuals with the highest infection risk , including 106 close contacts and 154 second-degree contacts who traveled on the same vehicles, 110 contacts within the same communities, and 8 contacts within the same malls. The Hainan Provincial Big Data Administration identified 6 high-risk communities and a number of high-risk shopping malls. According to the list of the highest-risk infected individuals and high-risk shopping malls and communities, the Command of Hainan Provincial COVID-19 Epidemic Prevention and Control directed health committees, the CDC, medical and health institutions, grassroot governments, and community residents\u2019 committees to take mandatory measures for the highest-risk infected individuals and to implement emergency shutdown measures for high-risk public places. As a result, a patient who was not detected by traditional contact tracing was discovered through digital contact tracing, which provided vital information support to comprehensively curb the spread of the COVID-19 epidemic from the source.We summarized the organizational process, technical process, and main achievements of the graph database algorithm in tracing the contacts of COVID-19 cases in Hainan Province, China. This approach has practical importance in overcoming the limitations of traditional emergency management measures and existing digital contact tracing methods. From the perspective of the organizational process, our research found that Hainan Province formed a scientific and effective organizational structure and operating mechanism for digital contact tracing during the COVID-19 epidemic. The success of the organizational process is attributed to (1) the establishment of a special high-level administrative leadership agency to coordinate the entire process, namely, the Hainan Provincial Command of COVID-19 Epidemic Prevention and Control; (2) the clarification of the rights and obligations of relevant emergency management agencies in the digital contact tracing of the COVID-19 epidemic; (3) the formation of a flat and integrated organizational structure and operating mechanism for multiple agencies to communicate effectively in a timely manner and achieve collaborative governance; (4) the establishment of a dedicated big data management department to provide technical support required for data lifecycle management; and (5) the establishment of a government big data public service platform that supports the storage, recall, and analysis of multisource data according to the centralized model, and the application of the platform in digital contact tracing during the COVID-19 epidemic.From the perspective of the technical process, our research is based on the use of the Neo4j graph database algorithm and ECharts data visualization tool to mine and analyze multisource COVID-19 epidemic big data. Hidden contacts and public places associated with confirmed patients, suspected patients, and asymptomatic infections were discovered and traced so that contacts and high-risk public places could be accurately identified. The results show that the digital contact tracing in Hainan Province is compatible with multisource heterogeneous epidemic big data; it can quickly and accurately find close, second-degree, or third-degree contacts, and it can identify public places with high risk of infection. Visualization technology is of great importance in optimizing public decision-making . In our Our research is expected to overcome the main difficulties faced in emergency management of the COVID-19 epidemic in different countries and regions due to their unique political, cultural, and civic concepts ,19,28-31The main limitation of our research is the small coverage and insufficient information of COVID-19 epidemic data. Thus, tracing high-risk infected populations among the entire population of Hainan Province and their contacts is impossible. The participants in digital contact tracing in Hainan Province are limited to people with a history of residence in Hubei Province. This selection greatly reduces the scope of digital contact tracing. In addition, WeChat positioning\u2013based GPS data, UnionPay consumption data, and railway and flight passenger information, which can accurately reflect the trajectory of residents, are owned by enterprises. These enterprises did not agree to provide users\u2019 spatiotemporal trajectory data to the Hainan Provincial Big Data Administration to protect the privacy of their users.Hainan Province needs to further improve the accuracy of data contact tracing using a graph database algorithm. Authorities need to adopt more comprehensive, accurate, and dynamic population spatiotemporal trajectory data to combat the epidemic. These data are the key to improve the accuracy of digital-based tracing. In addition, when confirmed, suspected, and asymptomatic infected individuals come into contact with the general population, the distance and duration of exposure are the main indicators for assessing the risk of cross-infection . Hainan Furthermore, security issues in the process of digital contact tracing of epidemics based on a digital government platform under the centralized model need to be properly resolved in two aspects: governance and technology. In terms of governance, the law, system, and data management structure must be improved for the government to obtain citizens\u2019 personal information in public health emergencies. Data sharing standards, authority management, and data security management in the process of epidemic data analysis and application, as the bases for the government to adopt useful data to respond to epidemics under the premise of ensuring the privacy of citizens, should be clarified. In addition, the government\u2019s use of data from enterprises, social organizations, and other nongovernmental organizations to respond to the epidemic needs to be further clarified and improved. In terms of technology, data security technologies, such as cryptography methods, data encryption technologies, system vulnerability monitoring and repair technologies, virus-killing technologies, and automatic data deletion technologies, must be comprehensively used in the digital platform for epidemic emergency management.Finally, the methods of collecting epidemic data were not sufficiently intelligent. For example, epidemiological investigation data were mainly collected by health personnel through face-to-face interviews with the cooperation of community resident committees. These data were manually entered into the information system by the staff of the CDC or medical institutions. This data collection method was relatively inefficient and requires substantial staffing. Furthermore, onsite investigation by staff increases the risk of cross-infection. Therefore, for digital contact tracing, it is necessary to develop more intelligent means of completion. Therefore, authorities should follow the development trend of governance in the digital age; develop an epidemic emergency management big data platform with the aid of governmental big data platforms; and fully use cloud transmission, cloud storage, and cloud computing technology to realize the real-time and dynamic collection of epidemic data from the transaction information systems of public and private agencies through a network interface to replace the traditional methods of collecting multisource epidemic data.Hainan Province, China, was selected as the case for this study. The use of a graph database algorithm and ECharts visualization tools in Hainan Province to trace contacts and identify high-risk public places was summarized in a centralized model during the process of emergency management of the COVID-19 epidemic. Moreover, the organizational and technical processes of the case we studied can help government agencies to implement precise emergency management measures and provide agile, evidence-based decision support to improve the responsiveness of the public health emergency response system. The organizational arrangements and technology involved in our research can be applied in different countries and regions to respond to the COVID-19 epidemic and can be applied at different stages of the COVID-19 epidemic. Future research should focus on solving the problems of insufficient data coverage information, insufficient contact tracing accuracy, insufficient intelligence of data collection methods, security concerns, and insufficient real-time performance of data sharing caused by the tradeoff between citizen privacy and public health security to optimize digital contact tracing."} +{"text": "To the Editor:1 The reasons for the decision were multifactorial, including the opportunity for medicalschools to develop and implement educational programs to fully educate all their students, toensure medical student and patient safety, and to conserve personal protective equipment.Due to the COVID-19 outbreak, the Association of American Medical Colleges (AAMC) recommendedthe suspension of all direct patient contact for clinical rotations by medical studentseffective immediately on March 17, 2020.2 Endorsed by the AAMC, Abraham Flexner later influenced medical education throughrecommendations of science-based programs in university departments linked to teaching hospitals.2 With COVID-19 being the first pandemic to affect the United States in the modern era,the outbreak resulted in the first immediate cessation of clinical education for medicalstudents in the United States.Apprenticeship on clinical rotations remains as relevant today in the education of medicalstudents as it did when Sir William Osler, FRS, FRCP, established clerkships a century ago,giving students a role on clinical services.3 The HMS organizational framework was shared with multiple medical schools across theUnited States.With no precedent, medical students with and without faculty oversight across the countryacted through the development of both social connectedness and wellness, but more importantlycommunity service, to assist patients in the general population. Locally, medical students atthe University of Cincinnati College of Medicine developed a free service program throughwhich student volunteers provided free delivery of groceries, medications, and meals topatients at risk for COVID-19-associated complications if they acquire the viral infection.Moreover, a group of medical students at Harvard Medical School (HMS) implemented a team of500 volunteers to develop a student-led organization to optimize mobilization of interestedstudents in the COVID-19 response, both clinically and in the community, and to serve as aliaison between administration for the needs and efforts of these engaged students.4 During this unprecedented time when medical students are removed from clinical servicesat US teaching hospitals, they do not have to feel powerless as noted by the HMS students.Medical students can empower themselves through sustaining the quality of health of the mostvulnerable in the broader community.Our job as physicians is to heal the sick, especially when patients are at their mostvulnerable. The innate characteristics of physicians to heal patients is developed beforegraduation from medical school. Many students develop optimistic and altruistic behavior and asense of morality patients during their medical education.University of Cincinnati, Cincinnati,OHCincinnati Children\u2019s Hospital Medical Center, Cincinnati,OHDon Hayes Jr, MD, MS, MEd"} +{"text": "Cofilin is an actin-binding protein that regulates filament dynamics and depolymerization. The over-expression of cofilin is observed in various cancers, cofilin promotes cancer metastasis by regulating cytoskeletal reorganization, lamellipodium formation and epithelial-to-mesenchymal transition. Clinical treatment of cancer regarding cofilin has been explored in aspects of tumor cells apoptosis and cofilin related miRNAs. This review addresses the structure and phosphorylation of cofilin and describes recent findings regarding the function of cofilin in regulating cancer metastasis and apoptosis in tumor cells. Once cofilin is activated by dephosphorylation, it servers actin by translocating into the nucleus with binding to actin and slingshot phosphatases (SSH). Phosphorylation on Ser3 deactivate cofilin, while dephosphorylation works in the opposite way. In addition, the phosphorylation status of Ser3 also affects the ability of cofilin to translocate to the mitochondria and Thr505 (LIMK2) threonine residue, whereas upstream effectors are Rho GTPases, including RhoA, Rac1, and Cdc42 . EMT can dissolve cell\u2013cell adhesion and alter the cell morphology to fibroblast-like forms as a consequence of actin reorganization, which collectively translate into metastasis properties , such as miR-342, miR-429, miR-182-5p, act as inhibitors of cofilin activity and upstream effectors of proliferation and migration in cancer cells and phosphatases (SSH1) can change the activation of cofilin, and LIMK1 and SSH1 have been extensively studied as regulators in cofilin-mediated pathways in cell motility and cancer metastasis. However, there are contradictory results and data regarding the expression of cofilin in tumor cells, effects of dephosphorylation of cofilin and the expression level of LIMK1 on cell migration and invasion. Further studies are needed to explore the potential mechanisms behind these contradictory results. The effect of cofilin on apoptosis is a new focus of studies on tumor development, and a growing body of research has found that cofilin is involved in apoptosis under the regulation of AITC, UA, etoposide and arnidiol in various leukemia cells and breast cancer cells. Active (dephosphorylated) cofilin induces apoptosis by translocating to the outer membrane of mitochondria and promoting the release of cytochrome C. Therefore, cofilin can be developed as a new anti-tumor target. The regulation of apoptosis by cofilin in cancer cells can be a very promising research direction. With further study of the pathway linking cofilin and apoptosis, cofilin may be not only a biomarker and prognostic indicator of cancers but also a therapeutic target for various cancers.JX, YH, and JZ: wrote-original draft preparation. LW, QQ, YL, GL, and JL: wrote-review and editing. HL and HW supervised and approved the final submitted version. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dear Editor,Although onychomadesis secondary to hand-foot-and mouth disease (HFM) is an an uncommon clinical manifestation; it threatens parents and child caregivers. In a case series of 145 Thai patients, it occurred in 5\u201337% of cases, depending on the virus.None declared.Juliana Polizel Ocanha Xavier: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analysis, and interpretation of the data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Jos\u00e9 C\u00e2ndido Caldeira Xavier Junior: Approval of the final version of the manuscript; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Scientific Reports 10.1038/s41598-017-15839-y, published online 13 November 2017Correction to: Bram Van den Bergh was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.The Author Contributions section now reads:CC designed the experiments with CWM, executed the experiments, analyzed the data, and wrote the manuscript. CL and VvN conducted the in silico analysis of Ger receptor genes in 152 gIICb strains. BVdB performed the bioinformatic analysis of the genome sequence of the gerBAC deletion mutant. CWM conceived the study and finalized the manuscript. All authors discussed and interpreted the data."} +{"text": "Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Sorafenib remained the main stay treatment for patients with advanced HCC for over a decade ,2. In thA minority of patients have locoregional disease at the time of presentation and are candidates for potentially curative options. Surgical resection remains one of the cornerstone curative strategies but, given the underlying liver disease, is not an option for many. Ju et al. review the advantages and disadvantages of anatomical resection (AR) over non-anatomical resection (NAR) in HCC patients and outline outcome measures of both the techniques . AR can Limited models exist for studies of prevention and rationally done studies with tolerable therapies, when given long term, are much needed to design chemoprevention trials. In the woodchuck model of hepatitis B related hepatocellular cancer, Iyer et al. demonstrate the chemo prevention potential, tolerability and immunomodulatory role of low dose sorafenib. High doses of sorafenib upregulated nuclear factor of activated T cells 1 (NFAT1) signaling, and were associated with an immunosuppressive phenotype, with reduced T cell proliferation and enhanced PD-1 expression . Dose reThis issue contains four original research reports examining novel therapies in preclinical models (n = 3) and patients (n = 1). Chen et al. show that magnolol, a compound extracted from the bark of Magnolia officinalis, enhances the therapeutic efficacy of sorafenib via protein kinase B (AKT) inactivation . Co-admiSeveral papers in the issue comprehensively review different therapies under development. Jiang et al. review the role of AMP-activated protein kinase (AMPK) in HCC . DownregThe lack of or limited available tumor tissue in hepatocellular cancer patients poses a challenge in biomarker development. To this end, various groups have suggested using readily available non-invasive laboratory values, to aid patient selection and prognostication. Ueshima et al., demonstrate the effect of baseline liver function in terms of the Child-Pugh score and ALBI grade on efficacy and adverse event outcomes of patients treated with lenvatinib . AntkowiThe plethora of treatment modalities available to manage HCC patients, many showing efficacy compared to placebo but not compared head to head, present unique challenges in patient selection and sequencing. Standardized approaches are lacking, due to the differences in biological characteristics, patient comorbidities and the paucity of data regarding the appropriate sequencing of novel therapies. In a review by Gholam et al., the authors highlight the importance of multidisciplinary teams to maximize the outcomes of HCC patients, especially in the setting of unresectable disease, and the important roles various subspecialists will play to ensure optimal patient outcomes . In rapidly fatal cancers like HCC, the goal of therapy is an improvement in the quality of life (QoL), in addition to prolonging survival. This has been challenging in the HCC space, due to multiple factors, including absent or lack of standardized quality of life reporting in clinical trials, as well as worse liver function and performance status of real-world patients. Zhou et al. summarize the efficacy and safety outcomes of systemic treatment options, along with QoL data, and provide a reference for management of treatment toxicities . Li et aIn conclusion, despite the recent additions to our armamentarium of drugs, HCC remains an area with unmet need. Although more therapy options exist than before, determination of optimal sequencing of therapies, combinations and the impact of these decisions on patient-reported QoL, and on cost of overall care delivery are new challenges that we face. This Special Issue illuminates further understanding into the biology of this aggressive disease and provides innovative solutions for development of new therapies and biomarkers, as our collective efforts towards improving the survival and quality of life outcomes of HCC patients continue."} +{"text": "We recently adapted the published National Institute for Health and Care Excellence (NICE) Attention deficit hyperactivity disorder (ADHD) diagnosis and management guideline to the Saudi Arabian context. It has been postulated that adaptation of evidence-based clinical practice guidelines to the local healthcare context rather than de-novo development will improve their adoption and implementation without imposing a significant burden on resources. The objective of this paper is to describe the adaptation process methodology utilized for the generation of the first national guideline for management of people with ADHD in Saudi Arabia.We used the KSU-Modified-ADAPTE methodology for the guideline adaptation process. We describe the full process in detail including the three phases of set-up, adaptation, and finalization. The process was conducted by a multidisciplinary guideline adaptation group in addition to an external review for the clinical content and methodology.The group adapted ten main categories of recommendations from one source CPG (NICE). The recommendations include: (i) service organisation and training, (ii) recognition, identification and referral, (iii)\u00a0diagnosis, (iv) support, (v) managing ADHD, (vi) dietary advice, (vii) medication, (viii) maintenance and monitoring, (ix) adherence to treatment, and (x) review of medication and discontinuation. Several implementation tools were compiled and developed to enhance implementability including a clinical algorithm, quality measures, coding system, medication tables, translations, patient information, and online resources.The finalized clinical practice guideline provides healthcare providers with applicable evidence-based guidance for the management of people with ADHD in Saudi Arabia. The project also demonstrated the effectiveness of KSU-Modified-ADAPTE, and emphasized the value of a collaborative clinical and methodological expert group for adaptation of national guidelines. Adaptation of guidelines is a valid alternative to de novo development for generation of evidence-based guidelines.The \u2018King Saud University (KSU)-Modified-ADAPTE\u2019, as a formal methodology for guideline adaptation, is less resource-intensive than de-novo development without losing the methodological rigor.Balanced clinical and methodological expertise in the guideline group is essential for the success of similar projects.We describe the process and outputs of a comprehensive national guideline adaptation initiative with multidisciplinary contributions for management of people with ADHD.These findings contribute to the work to enhance adaptation or customization of clinical practice guidelines and highlight implementability issues for ADHD.Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders that affects cognitive, emotional, social, academic, and occupational functioning . It is cThere were\u00a0no standardized clinical guidelines for ADHD management in Saudi Arabia. There is, however, a large volume of internationally published CPGs for ADHD that may create a dilemma for relevant healthcare providers and clinicians who care for people with ADHD in Saudi Arabia during the processes of sharing healthcare decisions and care provision. Furthermore, although some initiatives have targeted the management of ADHD in primary care, they are in their infancy; ADHD is mainly diagnosed and treated in tertiary care and the private sector and managed in a variety of settings, sometimes inappropriately or ineffectively. This results in significant variability in clinical practice, and suboptimal quality of care \u201310.As part of its strategy to improve access to care for people affected by ADHD in Saudi Arabia, the Saudi ADHD Society formed a multidisciplinary team to remedy this situation. The resulting clinical practice guideline (CPG) was adapted from the National institute for Health and Care Excellence (NICE) guideline entitled, Attention deficit hyperactivity disorder: diagnosis and management (NG87) , to imprClinical Practice Guidelines (CPGs) are defined as \u2018statements that include recommendations intended to optimize patient care, which are informed by a systematic review of evidence and an assessment of the benefit and harm of alternative care options . CPGs haAdaptation of CPGs is a valid and efficient alternative to de novo development of CPGs especially in resource-limited healthcare settings. It was proposed to avoid duplication of efforts, to use the available resources in a cost-effective manner, and to encourage trans-contextual customization of the CPG prepared for different economic and healthcare settings reflecting the local context and system \u201316.Given that there were\u00a0no published CPGs for ADHD management in Saudi Arabia, the presented evidence-based CPG is proposed as a National CPG using an evidence-based and formal CPG adaptation methodology. The aim of this study was to adapt the international clinical practice guidelines\u2019 recommendations for people with ADHD to fit the healthcare setting in the Saudi Arabian context including primary, secondary, and tertiary care settings.We utilised the \u2018King Saud University (KSU)-Modified-ADAPTE\u2019 adaptatiThe two main reporting standards for CPGs recommended by the EQUATOR Network are the Appraisal of Guidelines for Research and Evaluation (AGREE) II reporting checklist and the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement \u201320. DespIn phase one, Attention deficit hyperactivity disorder (ADHD) was identified by the Saudi ADHD Society as the health topic for this CPG adaptation project. An initial exploratory search regarding ADHD CPGs was conducted to identify whether there were existing CPGs related to this topic. The guideline adaptation working group (GAG) was formulated at the outset to include a child psychiatrist, two pediatric neurologists, a developmental pediatrician, a clinical neuropsychologist, a clinical pharmacist, a general pediatrician and CPG expert methodologist, a project manager, and a patient advocate. Participation of the patient advocate in the GAG and all of its meetings was intended to capture the patients\u2019 or public\u2019s views and preferences in addition to the support and insight from the networks and resources of the Saudi ADHD Society. The results of the preliminary search for ADHD Source CPGs encouraged us to proceed and officially launch this CPG adaptation project with a national scope. Capacity building sessions were conducted by the CPG methodologist for the rest of the GAG on concepts of evidence-based healthcare including the CPG adaptation process methodology and its associated toolkit , 14, 17.The target patient population for the adapted CPG is children and adults suspected of having or diagnosed with ADHD. The identified target intended users include physicians, clinical psychologists, other behavioral health clinicians, nurses, occupational therapists, pharmacists, social workers, dieticians, medical students, and health sciences students.The healthcare settings include primary, secondary and tertiary care dealing with assessment, treatment and management of ADHD in Saudi Arabia.In phase two, we identified specific health questions using the PIPOH model, relevant inclusion and exclusion criteria, and a full search strategy including a list of keywords. The elements of the PIPOH model include the target patient population (P), intervention(s) (I), professionals and clinical specialties (P), outcomes (O), and healthcare setting or context (H) that were reported earlier , 12. We Based on the results of the AGREE II appraisal and in-dWe decided not to conduct further assessment of the certainty of the body of evidence and the strength of recommendations and relied on the high standardized domain score of domain 3 (rigour of development) of the AGREE II appraisal and the evidence-base of the NICE source CPG based on its provided Grading of Recommendations: Assessment, Development, and Evaluation (GRADE) evidence profiles .Moreover, the GAG identified, revised, and discussed all the recommendation statements through successive focus group discussions against the local and national healthcare system in Saudi Arabia. Drafting the first version of the adapted CPG was the last step of this phase.In phase three, the first draft of the adapted CPG full document was finalized including assessing the recommendations for acceptability and applicability in the local Saudi Arabian healthcare settings. This adapted CPG draft was then disseminated to a selected national panel of external reviewers of specialized healthcare providers, topic experts, and methodologists from relevant healthcare sectors. The feedback of reviewers was revised and discussed within the GAG and was reflected in the final version of the adapted CPG. A set of CPG implementation (CPGI) tools was included in the final CPG full document.th of January 2017 till 30th of May 2019. Seven meetings were conducted for planning, reviewing, and focus group discussions including two training sessions with ongoing hands-on advisory on the CPG appraisal and adaptation tools.The overall duration of this CPG adaptation project was two years and five months from 4This work marks the first national CPG adaptation project for the management of people with ADHD using the \u2018KSU-Modified-ADAPTE\u2019.The aforementioned GAG was formulated in January 2017 as a multidisciplinary group with expertise in ADHD and evidence-based CPGs (YA). ADHD was selected as a high priority health topic with clear practice variation and lack of national CPGs for its management. The necessary resources and skills were identified and allocated. All of the GAG members signed declaration of conflicts of interest statements.The feasibility of the CPG adaptation process was confirmed by conducting a preliminary search for published CPGs. The working plan was drafted and discussed at the outset using the relevant CPG adaptation working plan template from the KSU-Modified-ADAPTE , Table 3For the first and second phases, a systematic review for the recently published ADHD Source CPGs was conducted and published in a separate report, which included the PIPOH model, eligibility criteria, results of the search and screen for Source CPGs, in addition to the results of the ratings and commentary of the AGREE II appraisal .Six source ADHD CPGs were reviewed and critically appraised including those developed by the American Academy of Pediatrics, Canadian ADHD Resource Alliance, National Health and Medical Research Council, National Institute for Health and Care Excellence (NICE), Singapore Ministry of Health, and University of Michigan Health System .The NICE CPG was superior in all of the six standardized domain scores of the AGREE II Instrument and it addressed all care options for ADHD across the lifespan. The AGREE II ratings of the NICE CPG were 100% (domain 1: scope and purpose), 96% (domain 2: stakeholder involvement), 93% (domain 3: rigour of development), 89% (domain 4: clarity and presentation), 92% (domain 5: applicability), 92% , and 100% [Afterwards, we assessed the currency of the NICE Source CPG to ensure the validity and currency of its recommendations and their evidence-base using the related assessment of the CPG currency from the KSU-Modified-ADAPTE , Table 4The GAG reviewed and discussed the AGREE II assessment standardized domain scores and decided to adopt all of the recommendations of the NICE CPG. Relevant customization of the recommendations was conducted after several focus group discussions of facilitators and barriers to CPGI especially regarding variable health systems, medications, or healthcare provider positions.https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-guidelines/making-decisions-using-nice-guidelines in addition to further explanation in, Chapter 9: writing the guideline of, \u2018Developing NICE guidelines: the manual\u2019: https://www.nice.org.uk/process/pmg20/chapter/writing-the-guidelineWe have followed the same format or presentation of recommendation statements developed by NICE that relied on the \u2018wording\u2019 of each recommendation rather than highlighting a quality of evidence and grade of recommendation like other CPG developers may opt for. The rationale for this format has been clearly stated in the NICE website: The GAG decided to adopt the CPGI tools provided by the NICE Source CPG, i.e. baseline assessment tool and quality standards. Additional CPGI tools were included by the GAG based on and relevant to the adapted ADHD recommendations including: (i) two medication tables; one for treatment of children and young people and the other for treatment of adults with ADHD (a summary medication table has been provided in this article), (ii) a clinical algorithm for management of ADHD Fig.\u00a0, (iii) tThirteen members participated as the external review panel from the target audience of the CPG based on their expertise in caring for people with ADHD and in methodologies of evidence-based CPGs (HAA and SA) in addition to their representation of multiple relevant healthcare sectors in Saudi Arabia. Two international experts with local experience were invited to contribute to the external review of the clinical content as well (MG and MJN).The external review comments were compiled using a template , revisedThe customization or adaptation of recommendations was conducted with regards to the differences in the health systems and delivery of healthcare services especially for people with ADHD between the United Kingdom (UK) and the Kingdom of Saudi Arabia. The similarities in the health systems in both countries being nationalized healthcare systems where the government provides the majority of healthcare services, in addition to the similarity of income levels, facilitated the process of adaptation of recommendations to the local context . FurtherHealth benefits, side effects, and risks were evaluated in the Source CPG (NICE) as part of the AGREE II assessment and wereThe values and preferences of the target patient population was considered and discussed throughout the CPG adaptation process through the input of the patient advocate. Moreover, reports from the patient and public encounters during related services were provided by the society.As a part of quality assurance, the finalized adapted CPG from the Saudi ADHD Society was then critically reviewed and endorsed by the Saudi Health Council as well as five national professional societies: the Saudi Pediatric Neurology Society, the Saudi Pediatric Association, the Saudi Pharmaceutical Society, the Saudi Psychiatric Association, and the Saudi Society of Professional Psychology. The adapted CPG included recommendation statements organized into ten sections including: (i) Service organisation and training, (ii) Recognition, identification and referral, (iii)\u00a0Diagnosis, (iv) Support, (v) Managing ADHD, (vi) Dietary advice, (vii) Medication, (viii) Maintenance and monitoring, (ix) Adherence to treatment, and (x) Review of medication and discontinuation.The Saudi ADHD Society contacted NICE, the Source CPG developer, and finalized an official end user license agreement in line with the original NICE terms and conditions and the NICE UK Open Content license.https://cpg.adhd.org.sa/.A summary of the key recommendations is provided in Table The GAG recommended for the next review of this adapted CPG to be after four years from its publication (2020) which should be on (2024) after checking for updates in the Source CPG, consultation of expert opinion on any suggested updates needed according to the newest evidence and recommendations published in this area in addition to the implementation and evaluation results at relevant healthcare organizations in the Kingdom of Saudi Arabia. The Checklist for the Reporting of Updated Guidelines (CheckUp) is recommended by the EQUATOR network to report the updating of CPGs .A full set of CPGI tools was an integral component of the adapted CPG full document Fig.\u00a0, 2. SeveThe GAG recommends using this adapted CPG as a core tool within regular Plan-Do-Study-Act (PDSA) healthcare quality improvement cycles to support and promote quality and safety of healthcare services and best practice for people with ADHD.Several potential facilitators and barriers to implementation were identified during the CPG adaptation process.Facilitators include the relevant national strategies, committees, initiatives, and new healthcare services that are expected as a part of the new model of care, to support implementation. Contribution of representatives of multiple local healthcare sectors are designed to facilitate early dissemination and implementation. Furthermore, leadership engagement and support from the organizing society and from the contributing and endorsing national organizations played a major role in the success of this CPG project.Identified barriers and challenges that require a pro-active intervention to address them as a part of planning for implementation include, but are not limited to, the following: (i) medication availability, access, and sustainability; (ii) dissemination of the adapted CPG; (iii) lack of awareness of the primary care regarding the updated evidence-based recommendations of ADHD; (iv) lack of seamless integration between different national healthcare sectors; and (v) poor transition from pediatric to adult healthcare services.https://cpg.adhd.org.sa/development/).An overall decision support record for the ADHD CPG adaptation group (GAG) using the KSU-Modified-ADAPTE methodology is provided in The aim of this study was to adapt the international CPGs and their recommendations to the Saudi healthcare context for the comprehensive management of people with ADHD across all local healthcare sectors.The iterative process of the ADHD CPG adaptation reveals the nature of intensive work and capacity building that was an integral component of this project, and the specialized expertise required for such a process irrespective of the clinical or methodological expertise. The long timeline observed was not unique to this CPG adaptation project and was reported in other local CPG adaptation projects as well .The GAG did not experience a shorter timeline for this CPG adaptation project compared to the 2\u20133-year period often suggested for de-novo development of CPGs . This coNevertheless, the adaptation of CPG recommendations is a good and valid alternative to de-novo developing a CPG for people with ADHD, especially given the lack of relevant local high-quality systematic reviews and randomized controlled trials.A strength of this study is the use of the \u2018KSU-Modified-ADAPTE\u2019 method because it is clearly structured and easy to follow with a set of tools to support the process.Another noted strength was the inclusion of a patient advocate in the GAG with major contributions and input to the finalized adapted CPG.There are increasing initiatives and projects related to knowledge translation in general and CPGs in particular nationally and regionally , 30, 31.For the medication recommendations and monitoring for both children and adults, we have minimal concerns about stimulant abuse in the local population since medication prescription has strict regulations in the country and has a clear system for controlled drugs regulations.Conducting the needs assessment, that had a significant impact, is by default part of the set-up phase of adaptation and this is consistent with the experience of the GAG, which coincides with published evidence. This is an essential prerequisite of such a CPG adaptation project to practically determine the expected workload, resources, expertise, and the need for dedicated leadership and project management.The \u2018KSU-Modified-ADAPTE\u2019 methodology for CPG adaptation is a rigorous, practical, and intensive tool that\u2014along with the AGREE II instrument as a major component of the adaptation process\u2014has been demonstrated to be particularly feasible for national CPG projects.Our experience with this adaptation methodology provides useful insight into its utilization on a national level in Saudi Arabia, and further demonstrates its potential suitability for the Eastern Mediterranean region. Additional modifications to the adaptation process and tools as per the context are recommended and accepted , 17.Participation of a large number of healthcare sectors through multi-disciplinary groups in the CPG adaptation process aims at increasing the future uptake of the recommendations of this CPG. We anticipate an increase in the level of collaboration and integration of ADHD-related healthcare services as a result of the adoption of this adapted CPG.Availability of a national CPG is essential but not sufficient to guarantee ultimate standardization of patient healthcare. The degree of positive impact on people with ADHD will highly depend on the effectiveness of dissemination and implementation strategies in addition to other quality improvement and safety interventions.A formal cost-analysis is suggested to decide whether the process of CPG adaptation is cost-effective. Research evidence is required as well to determine the effectiveness of CPGI tools and strategies for ADHD, as well as effectiveness of the adapted CPG in the following areas: (i) early identification and referral of children and adults with ADHD, (ii) appropriate transition of care from child to adult healthcare services for ADHD, (iii) parent training programs, (iv) initiation of drug treatment with dose adjustment as indicated, (v) regular assessment of the response to medication, and (vi) annual review of drug treatment.Additional file 1. AGREE Reporting Checklist"} +{"text": "Metabolomics which deals with the biological metabolite profile produced in the body and its relation to disease state is a relatively recent research area for drug discovery and biological sciences including toxicology and pharmacology. Metabolomics, based on analytical method and multivariate analysis, has been considered a promising technology because of its advantage over other toxicogenomic and toxicoproteomic approaches. The application of metabolomics includes the development of biomarkers associated with the pathogenesis of various diseases, alternative toxicity tests, high-throughput screening (HTS), and risk assessment, allowing the simultaneous acquisition of multiple biochemical parameters in biological samples. The metabolic profile of urine, in particular, often shows changes in response to exposure to xenobiotics or disease-induced stress, because of the biological system\u2019s attempt to maintain homeostasis. In this review, we focus on the most recent advances and applications of metabolomics in toxicological research."} +{"text": "Management of CHF involved multifaceted programs that included the participation of multiple health care professionals, patient and physician education, promotion of intensive drug therapy and lifestyle modifications, and close patient monitoring. The most common CHF management strategies were case management and physician education, with an emphasis on close patient monitoring. Hypertension and hyperlipidemia-CAD intervention programs focused on chronic outpatient management and regular follow-up, with an emphasis on self management skills. These programs were managed through regular and periodic interventions, including pharmacist-managed clinics and automated provider notices. Many of the studies employed \"before-after\" comparisons in the absence of a truly experimental design and posed significant limitations due to variations in the outcomes measured, lack of transparent disease severity stratification, and variation across types of managed care organizations.A number of cardiovascular disease management strategies in the literature reported promising results. Many of the multidisciplinary CHF disease management programs were more complex than were programs for hypertension and hyperlipidemia-CAD, due, at least in part, to the nature and severity of the disease. A lack of agreement on appropriate economic and clinical outcomes for evaluating the effectiveness of cardiovascular disease management strategies is readily apparent."} +{"text": "Early in 2021, India embarked on the uphill journey of the COVID-19 vaccination of the largest population group in the world in a prioritized manner and in the shortest possible time. Considering the endless variety of geography and diverse socio-economic demographic, religious, and community contexts, there was a high likelihood of certain population subgroups with known vulnerabilities facing inequities, which were anticipated to be further accentuated by a digital divide. This necessitated devising solutions for such communities in a localized manner to aid the local government in breaking the service access and uptake barriers with an inclusive approach. To bridge this vital gap, the Momentum Routine Immunization Transformation and Equity project implemented a three-tiered collaboration, viz., government, non-governmental organizations (NGOs), and a wide range of vulnerable and at-risk communities, utilizing knowledge exchange and use of data. The project implemented localization strategies through the NGOs for community engagement in conjunction with government vaccination teams to universalize COVID-19 vaccination uptake up to the last mile. The collaboration resulted in reaching close to 50 million beneficiaries through messaging and facilitated the administration of more than 14 million vaccine doses, including 6.1 million doses for vulnerable and marginalized communities in 18 States and Union territories in India, along with suggesting implications for public health practice and research. The Indian Government launched its COVID-19 vaccination drive in January 2021, with the objective of vaccinating the world\u2019s largest national population group of 1.06 billion people . Within According to the \u2018UN Women,\u2019 adolescents, teenagers, children, women, the elderly, people with disabilities, indigenous people, refugees, migrants, and minorities face the highest social and economic marginalization . MarginaCollaboration is integral to the success of any public health program. The fundamental assumption underlying collaborative participation is that addressing complex problems involves a combination of diverse resources owned or managed by different organizations . CollaboIn August 2021, the MOMENTUM Routine Immunization Transformation and Equity (M-RITE) project, supported by the U.S. Agency for International Development (USAID) and led by John Snow India Pvt. Ltd. under the guidance of the Ministry of Health and Family Welfare (MoHFW) of the Government of India, pioneered multiple pathways for scaling solutions for reaching the most vulnerable with COVID-19 vaccination\u2014particularly through successful collaboration with the community-oriented non-governmental organizations (NGOs), community influencers, religious leaders, and associations of people. The model presented in this paper introduces a novel case of innovation in collaborative management with a strategic focus on vulnerable and at-risk communities through collaborations with local NGOs. The learning and experiences shared in this paper provide considerations for public health managers to work beyond the boundaries of specialization and management style in forming and convening collaborations and providing a framework applicable to emergency and routine health scenarios.World Health Organization (WHO), in its operational planning guidelines to support country-preparedness and response to COVID-19, has prioritized risk communication and community engagement by recommending collaborating with civil society as an important approach to dealing with the impact of the pandemic . SimilarAn extensive literature search for possible collaboration approaches did not yield results for a comprehensive collaborative approach suitable for vaccine delivery in emergency situations like COVID-19, but did provide insights for developing a collaborative model. For example, Solana EF\u2019s public\u2013private not-for-profit partnerships (PPNP) model (2014) suggests equitable allocation of tasks among partners to maximize value generation . G\u00f3mez JThe project team assisted the MoHFW of India at the national, state, and district levels to develop a collaboration mechanism that utilized the strengths of NGOs specializing in working with vulnerable and marginalized populations in 18 states and union territories (UTs) and 298 districts, as shown in The collaboration followed a four-step consultative process between the government, donors, and project implementation team:Step 1: Need-assessment for identification of areas of collaborative support and geographies for intervention.Technical assistance (TA) for vaccine planning and prioritization for equitable delivery, including supply chain and vaccine safety;TA for catalyzing service delivery and use, including innovative delivery modalities, health workforce expansion, capacity building, community engagement, demand generation, and risk communication;Identification of intervention geographies for addressing gaps in last-mile delivery based on the COVID-19 vaccination coverage up to August 2021. Eighteen states, including seven in the northeastern part of India, known for its hard-to-reach terrain, were identified for technical support and on-the-ground interventions;Concluding that the high-priority vulnerable populations, as the key target group, included, but were not limited to, the elderly age group, differently-abled people, remote and/or tribal communities, truckers, and migrants. Priority groups also included pregnant and lactating women, transgender people, people with disabilities, adolescents in childcare institutions, etc.The project team underwent multiple rounds of discussions with the MoHFW of India, as well as the project funders, to finalize the areas of intervention as indicated below:A detailed account of activities under each intervention area has been discussed at length in the forthcoming sections.Step 2: Identification, onboarding, and capacity building of NGOs to address last-mile delivery gaps.The project collaborated with NGOs, which had a significant role in implementation, particularly at the district level and below, to support last-mile service delivery and social mobilization and community engagement activities for equitable vaccine coverage. The selection criteria included: local NGOs ; active presence in the low-vaccine-coverage districts; valid Foreign Contribution Regulation Act (FCRA) certification; prior experience of working in USAID projects; understanding of local issues; the organization\u2019s vision being aimed towards marginalized and vulnerable populations in the area; and strong history of financial management, administration, and compliance with laws.Step 3: Devising risk-communication strategies for effective community-based collaboration with the flexibility to customize demand-generation activities.The on-the-ground communication strategy was designed in accordance with the national government\u2019s COVID-19 Vaccine Communication Strategy, and focused on managing vaccine eagerness, hesitancy, and crises with respect to fear of adverse events following immunization. The project team supported state and district governments with demand-generation activities for cohorts for social mobilization and increasing awareness across project states and districts.The team emphasized collaboration with the local governments, as well as in workplaces, community-based organizations (CBOs), and faith-based organizations (FBOs) to customize interventions to meet the objectives of demand generation and target and reach specific population groups . Activities included mapping and reaching out to vulnerable populations, raising awareness, mobilizing communities, and connecting beneficiaries to the health system. Aligning with the national and state government needs, the NGOs customized the delivery of messages during the \u2018Har Ghar Dastak\u2019 (knock every door) campaign of the national government.Step 4: Devising a monitoring, evaluation, and learning (MEL) framework for reporting collaborative efforts.The project identified requirements for project monitoring, evaluation, and learning for the data collection and management system, and developed a system, in collaboration with the USAID Strategic Information Team, to ensure maximum efficiency in data reporting.The team also developed standardized data-capturing and reporting formats for NGOs. To ensure the quality of data reported by the NGOs, the project state teams and supervisory-level staff of the NGOs collated details of beneficiaries from the reported line lists and checked the status of vaccination of the beneficiaries . Around 5% of reported vaccinations were subject to back-checks on a monthly basis.The collaboration model was designed and implemented with a three-tiered approach, viz., collaboration with the government, NGOs, and the community, as depicted in The project\u2019s efforts were complementary to the efforts of the national and state governments in multiple ways, such as the provision of technical assistance, catalyzing program implementation, monitoring, and evaluation, and knowledge exchange.Technical assistance: The project team collaborated with the national government on capacity-building, vaccine supply-chain management, data analysis of vaccination coverage, communication strategies, adverse events following immunization (AEFI), and most importantly, designing various vaccine delivery approaches. Support was also seconded to the Government Medical Store Departments (GMSD) to facilitate a regular and uninterrupted supply of vaccines and syringes, and the tracking of vaccines from manufacturers to regional and state stores in coordination with supply-chain personnel. On many occasions, the collaboration allowed the generation of crucial evidence, such as shortages of vaccines, hesitancy issues, expiring vaccines, etc., which led to the re-alignment of efforts that enhanced the vaccination program. This was especially important when the vaccination staff and healthcare workers were overwhelmed in mitigating the effects of the second COVID-19 wave. Notably, the project team advocated for and facilitated the redistribution of near-expiry vials to districts with low coverage.Catalyzing project implementation: The project teams at the sub-national level identified barriers to vaccination service uptake and demand, and concurrently provided information to district administrations to advocate for organizing special camps tailored to their community\u2019s needs. One such example of facilitating vaccination among daily wage workers is shared in Box 1state of Jammu & Kashmir is home to manymigrant laborers. Health staff observed that it was difficult to vaccinatethem during the working hours of the day. The project team, along with thesub-awardee, organized a rapid coverage survey, followed by an awarenessdrive and vaccination camp lasting three days, and running into the lateevenings. Night camps were organized at three different sites, which resultedin the successful facilitation of vaccine doses at times convenient to thecommunity. The state of Maharashtra, the tribal populationof Nandurbar (district) is occupied in daily wage work. Due to the workers\u2019busy daytime schedules, they were unable to make time for vaccination.Successful advocacy by the project team with the district administration ledto the organizing of night awareness-and-vaccination camps in the tribalsettlements, resulting in outreach to 15,000 people with messages and nearly1450 people with vaccination. In the Punjab,Rajasthan, and Chhattisgarhx.Similar initiatives were taken in other states such as Monitoring & evaluation: The state project teams supported government officials with their data management systems to ensure consistent data collection, systematic data cleaning, and sufficient analytics. Using the CO-WIN data portal which has been developed by the Government of India, the project team supported state governments with management information system (MIS) based factsheets for better decision-making, informing strategies to address low vaccine coverage and assessing the effectiveness of NGO-led interventions.The state dashboards were automated for all 18 project states; the one presented in Knowledge sharing is imperative to collaboration. For uninterrupted functioning of the project collaboration, all partners under the project met with donors at the national level each month to discuss synergy in all critical areas of work. The project also conducted reviews/knowledge-sharing meetings with the NGOs and government at the sub-national level to share best practices and key learnings on the engagement of marginalized and vulnerable groups at the field level and share the support received from the local administration in all project regions, especially hard-to-reach areas, for vaccine supply.To increase the demand for, distribution of, and uptake of COVID-19 vaccination, particularly among vulnerable and marginalized populations, it was important to build public trust in vaccines and seek public participation. The project team, therefore, identified NGOs for partnership in districts that had low COVID-19 vaccination coverage in discussion with the state governments and were highly ranked in the priority list of state governments. The main objective of the collaboration was to identify low coverage and/or inaccessible areas; engage in the prioritization of these areas; and support vaccine delivery planning and supply-side interventions, demand generation through community engagement, and social mobilization. The project team and collaborating NGOs joined hands to support the physical mobilization of the elderly and persons with disabilities to vaccination centers; establish referrals, link-up beneficiaries for enhancing vaccine access and conducting follow-ups, and conduct need-based assessments to understand misconceptions regarding COVID-19 vaccination and combat vaccine hesitancy. The state project teams facilitated training for the onboarded NGOs\u2019 human resources on project implementation activities. For effective counseling and outreach efforts, a detailed set of reference materials, including interpersonal communication (IPC) for rapport-building and frequently asked questions (FAQs) were used to allay fears and mitigate negative messaging in the community. The NGOs brought different forms of expertise and helped reach various marginalized and neglected groups, as depicted in Box 2The project team collaborated with ground-based NGOs withdiverse areas of specialization to mitigate the varied set of projectchallenges:Church\u2019s Auxiliary for Social Action (CASA), an organization specialized in working with hard-to-reachcommunities in the northeastern region of India, has a strong presence amongthe faith-based community, and works closely with them to address commonmisconceptions and/or misinformation which cause vaccine hesitancy.HelpAge India, withits expertise in providing elderly care, aided the project in overcomingresistance, mobility restrictions, and the digital divide among the elderly.Samarthan-Centre for Development Support, with its deep-rooted presence in tribal populations inChhattisgarh, helped build trust in COVID-19 vaccination among hard-to-reachpopulations.Shanta Memorial Rehabilitation Centre (SMRC) worked strongly to implement the \u201cNear to homevaccination\u201d advisory by MoHFW for all individuals who were unable to leavetheir homes for a variety of reasons, including illness and disabilities.Transport Corporation of India Foundation (TCIF) supported the vaccination of the truckercommunity and allied populations.Gilmore et al. in 2020 identifiBox 3North India: Theproject team worked closely with the Sikh Gurudwara Prabandhak Samiti (SGPC)in the state of Punjab. It conducted awareness generation activities andbeneficiary counseling, shared a written appeal in favor of COVID-19vaccination, and facilitated regular announcements from gurudwaras, whichhelped build vaccine confidence and enhance community engagement among thepopulation of the state. The team also facilitated vaccination near theplaces of worship.Central India: Theproject team worked closely with religious and community leaders of TajjulMasjid (one of the biggest mosques in Asia), which is located in Bhopal, thecapital city of Madhya Pradesh. The project team, under the leadership of thestate government, sensitized and facilitated vaccination for around 400religious leaders from various parts of the state, who in turn pledged tosupport COVID-19 vaccination from various mosques in the state. As a resultof sensitization, the Masjid undertook intensive community-engagementactivities to spread awareness, such as sharing messages through amplifiedannouncements and local television.North East India: In northeastern states,the project team collaborated with churches to create awareness among andmobilize people for vaccination by organizing vaccination camps on churchpremises, which helped to build vaccine confidence among the masses. Thereligious leaders were facilitated with vaccination on a priority basis sothey could motivate community members to become vaccinated. The strategy adopted by the project team was guided by inclusivity\u2019, and \u2018equity\u2019, and was well-aligned with the government\u2019s strategy for COVID-19 vaccination. However, achieving this strategy necessitated improved access, awareness, and demand generation among the most vulnerable and marginalized groups. Since the project NGOs are deeply entrenched in the project geographies and trusted by the target communities for their health-related needs, they were instrumental in identifying \u2018influencers\u2019 from the community, making for an impactful initiative.Among the transgender community in Chhattisgarh, the team identified and engaged two influencers who were members of the Third Gender Welfare Board constituted by the State Government of Chhattisgarh. Similarly, the team collaborated with a local community in Manipur to create and disseminate socially-inclusive messages and social media posts on vaccine uptake among the targeted marginalized communities of lesbian, gay, bisexual, transgender, intersex, queer/queer-questioning, asexual people (LGBTQI+); people living with HIV/AIDS (PLHIV); individuals who were homeless; orphans; and older adults. The case has been depicted in Box 4The project team identified the \u2018transgender community\u2019as a sub-group that was vulnerable to COVID-19, but that remainedmarginalized and could not access vaccination campaigns. The transgendercommunity in the state of Chhattisgarh was hesitant to take the vaccine becausemany of them were receiving hormone replacement therapy (HRT), and believedthat the vaccine would be unsuitable for them. Moreover, with the highprevalence of STDs and the widespread use of HRT, the community believed themyths that vaccination would adversely affect their health due to druginteraction. To increase vaccine uptake among this community, the projectteam identified a key influencer/ leader from the group who was receptive tovaccination messaging. The team conducted interpersonal counseling sessionswith the leader, and developed and showed videos of positive behaviourregarding the safety of vaccines to the community leader. The receptiveleader in Chhattisgarh received the first vaccine dose, which motivated theremaining transgender community to take their own vaccinations.Community engagement was made possible by unconventional partnerships that contributed to improving COVID-19 vaccine uptake. Some of these are detailed below.The project team engaged \u2018Persons with disabilities\u2019 using collaborative efforts and connected them to benefits provided by the social welfare departments. The team also collaborated with NGOs, which organized awareness generation activities by using sign language among teenagers with visual and hearing impairments and cerebral palsy. \u2018Drug users\u2019, often situated away from the mainstream, were apprehensive about vaccination due to misconceptions related to the safety of vaccines and fear of side effects. With the support of the Medical Officers at rehabilitation centers, NGOs organized special awareness sessions for drug users and discussed the benefits of the COVID-19 vaccine. The team engaged \u2018older adults\u2019; and \u2018pregnant and lactating women\u2019 with the help of government systems, including frontline health women workers, Community Health Officers (CHO), Gram Pradhans (village heads), and Panchayat Development Officers (PDO) (who monitor and supervise the work of Gram Pradhans), through counseling and building trust in vaccine safety. The project team mapped \u2018tribal villages\u2019 with low COVID-19 vaccination rates in states like Jharkhand, Odisha, Chhattisgarh, and Maharashtra. The project team and NGO staff covered long distances to interact with the communities through folklore activities, in which storytelling was done through acting.The project, with its prompt and proactive on-ground implementation, reached approximately 50 million beneficiaries (January\u2013December 2022) through IPC, mid-media , hard-copy prints , and telephonic reminders (on the due date of vaccination and publicizing upcoming camps). The administration of more than 14 million vaccine doses was facilitated between January and December 2022 through ground-based activities by local NGOs and project teams, including mobilizing, facilitating hard-to-reach populations to ongoing camps, and organizing special vaccination camps. Since, the modalities were culturally acceptable to the target communities, they had a significant contribution in bringing the marginalized communities to the public health mainstream. A significant proportion of doses were facilitated for vulnerable populations (6.1 million). The results are listed activity-wise below.Apart from mobilization and camp facilitation, this success can also be attributed to the IPC efforts of the project. Since the funding mandate prevented the project\u2019s communication activities from using mass media such as social media, TV, radio, etc., the outreach workers utilized innovative communication methods such as folklore, engagement of FBOs, street shows, engagement through community champions etc. Considering the rapid nature of the COVID-19 vaccination initiative and the inaccessibility of the target group, the 14.1 million doses made a significant contribution to reaching the unreached.To ensure the fulfillment of one of the key objectives of reaching marginalized and vulnerable population groups, the project team organized special camps to ensure adequate participation of target beneficiaries. During the 18 months of project planning and execution, the team gained several learnings regarding the effectiveness of the activities and interventions. State and demographic-wise data can be obtained upon request. The detailed results of MEL activities are outside the purview of this document. The current focus is on highlighting the structured collaborative approach for replication and adaptation in research and practice. The results have been shared briefly to indicate the contribution of the project to COVID-19 vaccination of individuals at an overall and demographic level.Engagement of government stakeholders: Involving government staff at all levels facilitates the timely implementation of interventions in hard-to-reach areas and catalyzes feedback and action.Involvement of local NGOs: Engaging with local NGOs is an effective mechanism for accelerating social and community mobilization. Local NGOs with a strong ground presence and footprint help to quickly map and reach out to target audiences and seek the support of local stakeholders such as village heads, FBOs, self-help groups, elected representatives, etc.Contextualization of information, education, and communication (IEC) materials: The development and adaptation of available IEC materials in local languages and local formats ensures quick vaccine acceptance and community action.Customized demand generation approaches: Tailored approaches\u2014such as night camps, and collaborations with community and religious leaders to suit local needs and raise awareness of COVID-19 vaccination\u2014help in targeting specific subpopulations that might be more likely to miss vaccinations due to the fear of wage loss and other competing work and family commitments.All the approaches to vaccination were instrumental in achieving the project\u2019s objectives. Some activities that were of particular importance were:The project\u2019s collaborative approach clearly met the necessary conditions of \u2018collaborative rationality\u2019 set forth by Innes and Booher : (1) TheSeveral considerations were critical to the success of this collaborative approach, including understanding the needs and limitations of the NGOs; working directly with communities to identify appropriate outreach and engagement strategies; prioritizing strategies that supported a multi-directional exchange of information; and adapting strategies based on grounded realities and internal lessons learned. Strategies evolved over time, and the level and quality of community participation increased during planning and implementation. Real-time data analysis facilitated quick and timely decisions; constant effort helped establish collaborations between corporates, funding organizations, and senior team members, which developed mutual confidence because of timely and planned knowledge-sharing sessions. The team overcame many barriers; however, in the process, new obstacles emerged, ones which were then addressed by preemptive approaches. Experiences gained from the project can be used to encourage the consideration of collaborative participation in routine immunization, new vaccine introductions, and other public health programs and decision-making processes.The limitations faced during the project span bring forth certain considerations for community health practices. The challenges, limitations, and lessons from the project\u2019s implementation suggest the following considerations:\u2212A strategic orientation with a clearly determined target group and implementation approach is important to keep the activities of collaborators aligned and prevent confusion among the partners.\u2212Collaboration partners must be chosen wisely through a rigorous vetting process. In the current project, we ensured the recruitment of local Indian NGOs that specialize in dealing with specific vulnerable populations.\u2212The current project deployed the M&E indicators to keep policy partners informed and aligned with the ground realities on vaccine uptake. However, in the future, the monitoring and evaluation efforts must also be designed according to research priorities.\u2212Specific requests must be shared with collaborative partners and discussed during follow-up meetings. Achievable plans must be prepared for the next period in tandem with the capacities and potential of collaborative partners.\u2212Managerial capacities of the collaborating partners must be upgraded periodically.\u2212The management of collaborations must aim towards convening rather than commanding and constraining partners. Mutual and respectful cooperation must be fostered by sharing management responsibilities with ground-level partners.\u2212Community participation by involving religious and community leaders, CBOs, and FBOs, and facilitating a sense of ownership among them must be contemplated in the initiatives targeting marginalized, vulnerable, and hard-to-reach people. The global strategy to ensure maximum inclusion in immunization programs advocates the usage of community-based organizations in strengthening accountability and ownership for immunization at the ground level. The same could be leveraged for reaching out to \u2018zero-dose\u2019 vulnerable communities.Public health initiatives targeted at sizable populations are complex due to a combination of behavioral, psychosocial, political, and cultural factors. The conditions at the ground level (particularly in pandemics) require decision-making and the rollout of activities on a war footing. Therefore, it is important to identify and enroll people and agencies who can bring ground-level insights to the initiative and act swiftly to implement changes. Eventually, most program implementation partners enter a collaborative mode, but such collaborations are often unplanned and need-based, therefore, there is a lack of strategic orientation and trustworthiness among partners. Such arrangements often result in overlapping work, non-clarity as to objectives, and fragmentation. The authors propose that a collaborative approach must be at the heart of any vaccination or public health program of this scale. The project activities align with the Immunization Agenda 2030 (IA2030) , which eThe need to disseminate research results of public health programs beyond academic and clinical audiences has been expressed repeatedly , but limOverall, the project has devised ways to strengthen the existing healthcare system by identifying and filling existing gaps in equiBox vaccination programming. Efforts to curb vaccine-preventable diseases have, in both the past and the present, recognized the importance of collaborative partnerships which can be utilized to extend routine immunization services to regularly reach \u201czero dose\u201d and under-immunized children and communities. Engaging community-level partners and ground-based institutions broadens the horizon of public health practice. The local NGOs have a deep understanding of underlying problems in their respective communities. They hold positions of high trustworthiness and receptivity among the communities. The learnings of the project have applicability in the routine immunization program management for the equitable distribution of vaccines by prioritizing efficient storage and redistribution. The coordination between district officials and NGOs was remarkable in this project.The geographical reach and experiential attributes of these NGOs are well-positioned to be leveraged for reaching the unreached in national primary healthcare programs, with a special focus on routine immunization, strengthening of data systems, appropriate messaging, and emergency response."} +{"text": "Worldwide efforts to standardize instruments measuring quality in psychiatric care are rare. The international project \u201cQuality in Psychiatric Care\u201d (QPC) is a large research programme aiming at adapting the versions of the QPC instrument for patients and staff to different international settings.The aims were to test the psychometric properties and equivalence of dimensionality of the different language versions of QPC and also to describe and compare the quality of psychiatric out-patient, in-patient, forensic in-patient and psychiatric care across different countries.The QPC is a family of instruments based on a definition of quality of psychiatric care from the patients perspective with adapted versions for staff. In this project, we used different language versions in three areas for patient and staff: psychiatric out-patient (QPC-OP/OPS), in-patient (QPC-IP/IPS), and forensic in-patient (QPC-FIP/FIPS).Patients in out-patient psychiatric care in Brazil rated the quality of care higher than Swedish patients. Comparisons of forensic in-patient care (QPC-FIP/FIPS) patients were more critical of the care they received while staff were generally more positive on the quality of care provided in both Denmark and Sweden. Quality of in-patient care (QPC-IP/IPS) in Spain show staff rating lower quality of care than patients and lowest in the secure environment, which the Swedish staff rated low as well. In Indonesia the patients rated lower quality than staff and lowest in the discharge dimension, followed by the participation dimension. Generally, staff and patients were similar in their perceptions of the low quality of participation. Several studies in Turkey, Indonesia, Spain, Faroe Islands and Norway is ongoing.The psychometric test and validations of the instrument QPC in different language and country versions will assist countries to compare quality of care, quality improvement and permits benchmarking. Since there are few standardized instruments for measuring quality of care in the psychiatric care, the QPC is expected to make an important contribution to the development in the field.None Declared"} +{"text": "Editorial on the Research TopicSport as a tool for social inclusion, employment, and improved healthCurrently, sports are well-known as a prominent means to address a wide spectrum of social goals. This acknowledgement of sports' social impact has been achieved through international acts and advocacy actions involving the United Nations (UN), the International Olympic Committee (IOC), sport federations, national governments and civic society over time . A recenAs a consequence of the identification of sports as catalysts for diverse social outcomes on the global and national agenda, the sport for development and peace (SDP) movement has emerged. SDP encompasses a wide range of actions, programs and studies wherein sports are utilised and investigated as means to promote non-sporting and peace building goals . SDP stuDespite the richness of studies in the field, some open questions remain concerning the efficient use of sports as a tool for social and developmental purposes. First, the literature lacks frameworks and models guiding efficient sport-based program planning, structuring and management to maximize social outcomes \u201324. SecoMost of the researches of the Research Topic draw upon data from diverse sport-based interventions aimed at various social goals and implemented in different geographical areas, ranging from southern Africa to China, and from northern and southern Europe to Latin America. Despite the variety of social goals promoted by the programs analyzed in these studies and their geographical diversity, the articles provide similar evidence-based insights guiding: (i) the development of theoretically grounded sport initiatives; (ii) effective action planning; and (iii) efficient monitoring and evaluation of these initiatives.Burnett demonstrates that engaging in such an initiative provided the participants with a high level of soft skills transferable to the working environment. The study advocates for a robust monitoring, evaluation, and learning (MEL) framework capable of capturing the nuances of the different contexts of program implementation.Analyzing the results of a 6-month government-funded sport-for-development program implemented in Africa, with a focus on youth employability, Gozzoli et al. describe the participatory development of a training framework aimed at promoting sport coaches' awareness of their role in enhancing employability skills. The authors highlight the lack of clarity regarding the theoretical and methodological assumptions that guide the design of training courses and propose a constructivist approach to structure effective training programs for coaches.In their contribution, Commers et al. analyze a program in Flanders aimed at transferring job skills to young people through sports. The research underscores the absence of clear definitions and theoretical operationalization of program outcomes, leading to gaps in efficiently monitoring and evaluating the participants\u2019 progress within the intervention. The authors advocate for theory-based program planning, which could help outline the desired outcomes and impacts of the sport-based interventions more effectively.Gadais et al. describe the experiences of Colombian youth from disadvantaged backgrounds and program managers who participated in an SDP intervention that took them from a local community sports club to the Olympic Games. The authors recommend the intensification of evaluation research on SDP programs, including close collaboration between academics, community-based organizations, donors, and the international community.Kunlun et al. study the spatio-temporal distribution and evolution pattern of Chinese Go League Clubs and emphasize their cultural and economic impact at the local level.Finally, Commers et al. advocate for grounding and planning sport-based programs based on the principles of the theory of change. Employing the theory of change offers the advantage of anticipating desired outcomes and impacts, providing a logical sequence of actions and inputs to achieve specific social changes. On the other hand, Gozzoli et al. suggest adopting less top-down approaches and promoting participatory methods for program development, involving local stakeholders and beneficiaries at all stages of the planning process. Future research should analyze and compare the opportunities and challenges of both approaches to advance the understanding of this field.The comprehension of programme components, structure, planning and effective management remains a fundamental area for analysis to advance research and implementation in SDP . The artBurnett and Gadais et al. underscore the need to enhance M&E research in SDP. Future M&E investigations should encompass the nuanced impact of these interventions from various stakeholders' perspectives and should consider not only the individual effects of sport-based programs but also their broader economic and cultural implications .Effective program planning in sport-based initiatives is not only crucial for action delivery and impact but also has significant implications for monitoring and evaluation (M&E). There exists a circular relationship between planning, program implementation, and M&E."} +{"text": "Natural products derived from herbal medicine are a fruitful source of lead compounds because of their structural diversity and potent bioactivities. However, despite the success of active compounds derived from herbal medicine in drug discovery, some approaches cannot effectively elucidate the overall effect and action mechanism due to their multi-component complexity. Fortunately, mass spectrometry-based metabolomics has been recognized as an effective strategy for revealing the effect and discovering active components, detailed molecular mechanisms, and multiple targets of natural products. Rapid identification of lead compounds and isolation of active components from natural products would facilitate new drug development. In this context, mass spectrometry-based metabolomics has established an integrated pharmacology framework for the discovery of bioactivity-correlated constituents, target identification, and the action mechanism of herbal medicine and natural products. High-throughput functional metabolomics techniques could be used to identify natural product structure, biological activity, efficacy mechanisms, and their mode of action on biological processes, assisting bioactive lead discovery, quality control, and accelerating discovery of novel drugs. These techniques are increasingly being developed in the era of big data and use scientific language to clarify the detailed action mechanism of herbal medicine. In this paper, the analytical characteristics and application fields of several commonly used mass spectrometers are introduced, and the application of mass spectrometry in the metabolomics of traditional Chinese medicines in recent years and its active components as well as mechanism of action are also discussed. Exploring the safety and effectiveness of herbal medicine, such as traditional Chinese medicine (TCM), is the key to its modernization and internationalization . It is oTerminal downstream products of the genome are known as the metabolome , which iAt present, there are four main analytical instruments to analyze and identify the structure of compounds, which are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, ultraviolet-visible (UV) spectroscopy and mass spectrometry (MS). NMR spectroscopy has the characteristics of the same sensitivity to all detected substances, simple sample processing and non-invasiveness, so it can be applied in isotope labeling to trace metabolic pathways . HoweverHigh-resolution mass spectrometers such as Orbitrap, time of flight (TOF) and Fourier transform ion cyclotron resonance (FT-ICR) can attain a mass resolution of nearly 10 million and are suited for correctly determining the precise molecular mass and molecular structure of substances. Although high-resolution mass spectrometry is better at quantifying chemicals, the costs of both its purchase and maintenance are substantial . The mosThe quadrupole mass spectrometer (QMS) is the most classical mass spectrometer with outThe most common multistage tandem MS system is a three-stage tandem mass spectrometer--QQQ. In three-level tandem quadrupole mass spectrometry, three quadrupole analyzers are connected in series to form a QQQ sequence, which can also be called TQMS . This alin vivo metabolites of TCM can also be identified and characterized by UPLC-QTOF/MS that adds auxiliary radiofrequency to the QQQ can do selective excitation and provide the functional advantage of multistage serial for the QQQ and contemporary digital technology were combined to create Fourier transform mass spectrometry (FT-MS), also known as Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). FTICR-MS has the highest resolving power and is often used as equipment for high-end scientific research, and its unique analytical characteristics make it an essential tool for studies on proteomics, metabolomics and complex mixtures. A common method for micromolecule and proteomic analysis uses FTICR-MS in conjunction with ion preselection and fragmentation equipment and its bonding with reversed-phase LC. The high fidelity of detection linearity and frequency determination are inherent properties of FTICR-MS, which can realize the resolution, mass accuracy and dynamic range . Since iIn the traditional MS, the new separation and measurement factor of ion mobility is added, thus constituting the IM-MS system. IM-MS has multidimensional separation, which increases peak capacity, shortens analysis time, separates structural analogues or isomers, and has multiple fragmentation modes and acquisition modes. Experimental data that cannot be provided from MS alone when IM is coupled with MS. Ion-size isomers can be measured by adding an ion migration cell to the MS. Isobaric lines and conformational isomers are separated, and chemical noise is decreased, which are characteristics of IMS. Additionally, ions with a similar charge state and those with structural similarities can be grouped into categories according to the lines where their mass-mobility relationships appear . At presin vivo and in vitro studies, the effectiveness of TCM was scientifically expressed, and the overall pharmacodynamic action process of TCM was efficiently analyzed under the premise of effectiveness. Effectiveness is a fundamental property of a drug. Despite the fact that TCM is frequently used in clinical settings, it is still challenging to demonstrate its usefulness through science . FurtherIn the clinical setting, the effectiveness of TCM is crucial. Contrary to modern medicine, TCM\u2019s multiple active ingredients are affected by a variety of parameters, including the source, provenance, and processing methods of medicinal ingredients . The nonThe quality marker of TCM is the basis of a modern TCM research system that combines macroscopical and microscopic aspects and includes the study of compatibility law of TCM compounds, the basic study of chemicals and the modern pharmacological study from the molecular point of view. The determination of TCM quality markers is based on the overall view of \u201cpharmacodynamic components,\u201d, that is, those that have clear chemical structure and biological activity. It is conducive to carrying out layer-by-layer analysis of the pharmacodynamic components that play an important role in TCM, and gradually elucidating its pharmacological effects and mechanism of action, which is the premise for traditional Chinese medicine to carry out subsequent research.TCM formula has always been the most common type of medication in clinical research, and it is a group of drugs that are properly compatible according to the composition principle after selecting the appropriate dosage of drugs after determining the treatment method based on syndrome differentiation examination. TCM formulas containing two or more medicinal herbs tend to obtain better efficacy and fewer side effects than the single herbs . Jun-Chein vivo, that is, the effects of TCM compatibility on in vivo processes such as absorption, distribution, metabolism, and excretion, and finally reflect the synergistic or resistant biological effects in TCM compounds through effect indicators, bioavailability, and target recognition.The research on the chemical constituents of Chinese herbal compounds alone is not enough to clarify the compatibility law of Chinese herbal compounds and their basic efficacy and mechanism of action. As a result, using mass spectrometry, it is necessary to analyze the qualitative or quantitative changes in active ingredients of drugs before and after compatibility, study the pharmacokinetic interactions Although there is only one drug, single herbs contain a variety of active ingredients. While TCM formulas are composed of several herbs and dozens of components, these components are decomposed into countless chemical molecules, so elucidating the mechanism of action of TCM is a very difficult thing . Metabolvia integrating UPLC-QTRAP-MS, GC-MS, Western blotting and molecular docking techniques. Ultimately, it was discovered that the main targets of the QRKSG for the therapy of NS were AKT1, MTOR, CASP3, and BCL2L1. Hydroxysaffloryellow A in the treatment of traumatic brain injury, as PTGS2, XDH, NOS1 and ACHE. Many studies showed that the main active components of TCM can target one or more specific molecules and thus perform a variety of clinic treatment functions . ExploriA large number of research studies have shown the utility of metabolomics in discovering the pharmacodynamic material basis of TCM and TCM formulations . The phaMetabolomics, as a science that can comprehensively analyze the metabolome, can elucidate the mechanism of action and the change rule of action of TCM by specifically comparing the changes in metabolic profile. It provides a powerful grasp of \u201cmulti-component-multi-target\u201d for TCM, and provides a more scientific and reasonable comprehensive explanation for elucidating TCM. As the most important instrument for the analysis and identification of compound structure, MS lays the foundation for the scientific elaboration of the metabolome change contour, pharmacodynamic material basis, mechanism of action, safety, and compatibility principles of TCM. Metabolomics also emerged as a result of the development of MS. With the addition of high-tech and more MS databases, the characterization and identification of metabolites are also more accurate.With the advancement of science and technology and the passage of time, the types of MS and MS-based analysis technology have been continuously updated, reformed and broken through, and the sensitivity, scope of application, throughput and identification technology of instruments have been greatly improved. The development of MS has contributed to the promotion of metabolomics applications, giving researchers a more comprehensive understanding of small molecule metabolites. Although mass spectrometry has the traits of high resolution, good precision, and maximum throughput, the research progress of metabolomics is still slow due to the complexity of organisms, the huge number of metabolites, and unrepeatable experimental protocols in different laboratories. Different types of MS have their own advantages, and appropriate mass analyzers are selected according to different sample characteristics and requirements. Compared with the acquisition of data, the subsequent processing and mining of data are the bottleneck problems facing metabolomics. Although the existing metabolome database has shortcomings in terms of scale, the open MS database and shared metabolome dataset provide convenience for the qualitative identification of metabolomics. Introducing the quick algorithms of computers into the field of metabolomics is of great help to the annotation as well as the accuracy of the data. The research direction of multi-omics conforms to the root of the overall regulation of organisms, and multidisciplinary cross-fusion can promote the development of metabolomics."} +{"text": "According to current diagnostic systems, affective symptoms do not represent a fundamental criterion for the diagnosis of DD. However, numerous studies have highlighted frequent comorbidity between DD and Mood Disorders and have elucidated the importance of the affective state in the development and persistence of delusions. Thus, some factor analysis studies have identified the existence of a depressive dimension in DD, suggesting a substantial psychopathological heterogeneity in DD. However, these important affective features have not evaluated from a phenomenological point of view and in their relationship with delusions.The aim of the present study is to investigate the relationship between personality, trait affectivity and severity of delusions in patients with Delusional Disorder (DD).Thirty-two outpatients affected by DD were administered the Structured Interview for DSM-IV-TR Personality Disorders (SIDP-IV), the Pathological Narcissism Inventory (NPI), the Positive and Negative Affect Schedule (PANAS) and the Psychotic Symptom Rating Scale (PSYRATS). Next, we analysed the prevalence of personality disorder in our sample of patients with DD and studied the correlations between the severity of delusions and the different affective variables. Finally, we obtained a multivariate explanatory model of the severity of the delusions.The severity of delusions was directly associated with \u201cGrandiose Fantasy\u201d item of narcissistic personality and inversely related with the feelings of shame, fear and guilt. In the multivariate model, the feeling of shame was the only independent variable capable of accounting for the severity of the delusions, that, in in DD patients, would lie on an affective core of shame.The severity of delusional beliefs in DD patients would lie on an affective core of shame upon predisposing personality traits. These findings could help to develop a psychotherapeutic approach for delusional patients focused in the feeling of shame.None Declared"} +{"text": "Dear Editor,Bruton's tyrosine kinase (BTK) is essential for the development and maturation of B-lymphocytes. These cells do not mature in individuals with mutations in this enzyme, and they have X-linked agammaglobulinemia, the most common type of congenital agammaglobulinemia.BTK is also expressed in tumor cells, and its inhibition is gaining increasing importance in the treatment of B-lineage neoplasms.Ibrutinib is a potent irreversible BTK inhibitor and was the first inhibitor of this enzyme approved by the FDA for the treatment of the following diseases in adults: 1) Chronic graft-versus-host disease, after the failure of one or more systemic therapy lines; 2) Chronic lymphocytic leukemia/small cell lymphocytic lymphoma (CLL/SCLL); 3) CLL/SCLL in adults with 17p deletion; 4) Mantle-cell lymphoma in adults who have received at least one prior therapy; 5) Relapsed/refractory marginal zone lymphoma, in adults who require systemic therapy and have received at least one prior anti-CD20-based therapy; and 6) In Waldenstr\u00f6m's macroglobulinemia.The described side effects are fatigue, diarrhea, peripheral edema, cardiac arrhythmia , bleeding, and infections (respiratory tract).6Ibrutinib can have cutaneous adverse effects, with a peak incidence in the first year of treatment. The most common manifestations are skin rash, petechiae and ecchymosis. Also, urticaria, herpes simplex and herpes zoster reactivation, panniculitis, and Stevens-Johnson syndrome may occur.7Despite the specificity for BTK, some skin effects are similar to those produced by EGF inhibitors,in natura with scanning electron microscopy. At medium magnification, discreet longitudinal channels were observed in the hair shafts (A 72-year-old patient who had received ibrutinib for six months to treat mantle lymphoma unresponsive to conventional therapy was assessed. The patient reported a slight alteration in his hair, with a change in its curling . Some har shafts A and B, r shafts C. At higr shafts .Figure 1The authors did not find any reports in the literature of an examination of hairs shafts with scanning electron microscopy showing alterations caused by ibrutinib. There are some reports with EGF inhibitors, in which channels were also described in the hair shafts,The findings of this patient demonstrate, on ultrastructural examination, a similarity between the alterations of EGF and BTK inhibitors.BTK inhibition is an expanding concept in the treatment of hematologic malignancies, with 22 drugs under development, and the emergence of drugs with less systemic and cutaneous toxicity is possible in the near future.12None declared.Hiram Larangeira de Almeida Jr: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Debora Sarzi Sartori: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Douglas Malkoun: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Carlos Eduardo Pouey Cunha: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Neural plasticity promotes the reorganization of language networks and is an essential recovery mechanism for poststroke aphasia (PSA). Neuroplasticity may be a pivotal bridge to elucidate the potential recovery mechanisms of acupuncture for aphasia. Therefore, understanding the neuroplasticity mechanism of acupuncture in PSA is crucial. However, the underlying therapeutic mechanism of neuroplasticity in PSA after acupuncture needs to be explored. Excitotoxicity after brain injury affects the activity of neurotransmitters and disrupts the transmission of normal neuron information. Thus, a helpful strategy of acupuncture might be to improve PSA by affecting the availability of these neurotransmitters and glutamate receptors at synapses. In addition, the regulation of neuroplasticity by acupuncture may also be related to the regulation of astrocytes. Considering the guiding significance of acupuncture for clinical treatment, it is necessary to carry out further study about the influence of acupuncture on the recovery of aphasia after stroke. This study summarizes the current research on the neural mechanism of acupuncture in treating PSA. It seeks to elucidate the potential effect of acupuncture on the recovery of PSA from the perspective of synaptic plasticity and integrity of gray and white matter. Poststroke aphasia (PSA), a language-acquired disorder, is one of the most devastating symptoms after stroke. PSA affects approximately one-third of stroke patients, and 30\u201343% of them suffer from long-term effects of aphasia , 2. PeopAcupuncture promotes the process of repairation of the nervous system by regulating neuroplasticity. As one of the ordinary means for PSA treatment, acupuncture has unique advantages in alleviating PSA. Acupuncture has the characteristics of evident efficacy, low price, flexible use, and few adverse reactions. According to traditional Chinese medicine theory, acupuncture applied to specific acupoints can dredge meridians, reconcile Yin and Yang, strengthen the body resistance, and dispel blocked energy by acupuncture on specific acupoints. Thus, acupuncture is one of the alternative methods that has been a favorable choice for PSA patients who need long-term treatment .In this study, we summarize the effects of acupuncture that promoting the recovery of PSA patients and review the language processing of PSA and its regulation at the cellular and molecular levels to provide a complementary perspective, and promote neuroplasticity.PSA is mainly related to infarction in language function-related areas, especially in the middle cerebral artery (MCA). Lesions, such as hypertension and ischemia, cause arterial stenosis or occlusion in these related areas, reducing blood perfusion and blood flow in the penumbral area, and thus affecting the corresponding language function \u201314. The 2+-ATP pump) on the cell membrane. Then, excessive neuronal depolarization, excitatory neurotransmitter release, and reduced neurotransmitter reuptake occur in the extracellular space, resulting in an increased intracellular calcium ion (Ca2+) concentration. Accumulation of calcium ions causes a downstream neurotoxic cascade, including calcium-dependent enzymes and hyperactivation of signaling, causing impaired neuronal function and irreversible damage . NM. NM51]. Evidence has demonstrated the exact efficacy of acupuncture therapy on CNS plasticity. Acupuncture-induced neuroplasticity is associated with neurotransmitters and NTFs, which may be the potential molecular basis for promoting aphasia recovery. Neuroplasticity is an important bridge to promote the recovery of neurodegenerative lesions . Almost Although the increasing number of neuroimaging studies on PSA have significantly advanced the knowledge on the mechanisms of PSA recovery, many issues remain unresolved regarding the mechanism of acupuncture on PSA. We analyze the literature and propose that the language recovery mechanism under acupuncture may involve two points: (1) glutamate receptors and neurotransmission of neurotransmitters may play a key role in the normal physiological process of language and the transmission of language information; (2) astrocytes exert an effect on neural plasticity through cellular homeostasis, and therefore intervene in the recovery of language function. This cellular homeostasis improves the outcome of PSA by promoting synaptic reconstruction and remodeling nerve conduction pathway. This study emphasizes the effect of acupuncture, and how can glutamate receptors, neurotransmitters, and astrocytes shed light on the biological mechanisms of acupuncture and neuroplasticity, and increase our understanding how acupuncture affects specific language disorders by regulating dysregulation of neurotransmitters/astrocytes."} +{"text": "Editorial on the Research TopicSex differences in adiposity and cardiovascular diseaseSex Differences in Adiposity and Cardiovascular Disease was proposed a few months before the COVID pandemic by AJ from the University of Mississippi Medical Center (USA) and ROM from the Universidad Nacional de Tucuman (Argentina) with the goal to aid the understanding of the role of the body fat constitution as a cardiovascular risk factor, and whether this risk is similar for men and women. In addition to this, to determine if sex steroids play a specific role either in the health of females and males.The Research Topic Today, although there is progress in the study of the effect of sex hormones on the adipocyte\u2019s metabolism and distribution, its role is still unclear in cardiovascular and metabolic diseases. Controversial evidence suggests that different fat types contribute to the high risk of cardiovascular events . Thus, vZhao et al. examines the association between hypertension and its control with atrial fibrillation and how the biological sex affects this association. The original research study by Khatami et al. explored whether iron biomarkers mediate sex differences in NT-proBNP levels. Authors investigated, using linear regression analyses, the association of sex and iron biomarkers with NT-proBNP levels, independent of adjustment for potential confounders. Another original research study by Li et al. examined the effects of age and sex on outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with the three-vessel disease (TVD) and the interaction between treatment and age or sex in NSTE-ACS and TVD. Finally, the cohort study by Huang et al. showed the sex difference temporal trends of short-term and long-term mortality after CAD admission in China. It was based on 11 years of data from a sample of 24,432 people in the largest cardiovascular disease center in South China.In our proposal, we received six original research manuscripts that indirectly fill the aim of our topic and contribute to the leading journal Frontiers in Global Women\u2019s Health. Of 100% of the manuscript submitted to our topic, 67% were accepted, and 33% were rejected. The case-control study by In this experience, we learned to manage different situations involved during the publication process, where, in the present day, the offer to publish and review manuscripts is increasing. The limitation was finding reviewers for the specific field."} +{"text": "Over the last decade, there has been an increase in research surrounding the specific pathologies related to gene mutations in ALS and FTLD. It has long been recognized that familial forms of these diseases can show hallmark pathologies related to mutations, e.g., ALS-FUS or FTLD-MAPT. This has been expanded recently by the identification of the C9orf72 expansion and its characteristic pathology . HoweverHenderson et al. discuss the evolution of the frontal lobes, metabolic adaptations during human evolution, and the consequences of aging on neuronal processes, linking them to known ALS/FTD pathomechanisms, mainly those related to RNA/protein turnover. The authors propose that neurodegenerative processes affecting the frontal lobes, specifically ALS and FTD, may result from a mismatch between cellular and metabolic pathways and increasing lifespan within an evolutionary framework.We have therefore collected, in this Research Topic, a number of papers that cover various aspects of neuropathology, pathophysiology, biomarkers, and genetics related to ALS and FTD. Butchbach and Scott. They offer their perspective on novel conceptual frameworks which could help find common therapies for MNDs. They point out how research has so far mainly focused on investigating the pathomechanisms linking mutations in a gene to a certain MND and propose an alternative system biology approach to understand early-onset MNDs, paving the way for new therapeutic possibilities for these diseases.A general overview of biological networks and complexity in early-onset Motor Neuron Diseases (MNDs) is given by Scarian et al. report recent findings on the role of the valosin-containing protein (VCP) gene, an ATPase involved in many different biological functions including protein degradation, autophagy, and lysosomal and mitochondrial homeostasis. The authors report evidence of possible therapeutic approaches targeting the VCP pathway, describing the use of many different drugs already developed for the treatment of other diseases, such as VCP inhibitors able to: (i) prevent muscle cell death and restore muscle integrity and mitochondrial size in VCP mutants; (ii) increase the oxygen consumption rate of patient's fibroblasts; and (iii) reverse the mislocalization of TDP-43 and FUS in mutant motor neurons.This Research Topic also concentrates on the role of causative genes shared in ALS and FTD, highlighting possible therapeutic approaches for these gene mutation-linked diseases. Zhang et al. investigate the correlation between serum NfL levels and the severity of lower motor neuron (LMN) axonal degeneration in patients with ALS, particularly in the early stages of the disease. The authors show that the use of NfL blood levels reflects the extent of limb LMN axonal damage but not upper motor neuron involvement among ALS patients, indicating that the use of this biomarker may have a profound effect on patient selection and efficacy monitoring of treatment in disease-modifying clinical trials.Additionally, the field shows interest in studying the role of neurofilament light chain (NfL) as a biomarker in ALS that can provide a deeper understanding of the pathophysiological mechanisms and potentially effective therapies for this disease. In their prospective cross-sectional study, The four articles included in this Research Topic provide an overview of the current state-of-the-art research on the role of gene mutations in the neuropathology of ALS and FTD, ranging from characterizing the pathomechanisms related to a specific genetic variation to re-evaluating biomarkers useful for the stratification of patients and directing the search for disease-modifying therapies. Much has been done and much needs to be done to better describe the gene-linked pathology in ALS and FTD. Traditional and new technologies still show many limitations, for example, in detecting the correct size of large expansions of C9ORF72, and better biomarkers are needed. The next decade promises to shed light on new aspects of the relationship between gene mutations, disease pathology, and clinical manifestation in ALS and FTD, enabling improvements in treatment and the finding of effective cures for these devastating diseases.Both authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "In the age of neural networks and the Internet of Things (IoT), the search for new neural network architectures capable of operating on devices with limited computing power and small memory size is becoming an urgent agenda. Trends in the development of artificial intelligence (AI) applications in the field of the Internet of Things include smart healthcare services ,2,3,4,5,AI technologies for IoT devices and edge computing are demanded in mobile healthcare , as well as in close application domains. Ambient intelligence (AmI) environments are constructed in IoT domains to provide smart services based on real-time analysis of human cognitive and motion functions. This Special Issue focuses on recent developments in the constantly growing application field of computing technologies and artificial intelligence algorithms. It includes new approaches to the organization of artificial intelligence on edge devices, as well as the organization of modular, feed forward, distributed, reservoir, recurrent, convolutional, and deep neural networks for various IoT-enabled smart applications. The guest editors are Andrei Velichko (Institute of Physics and Technology), Dmitry Korzun (Institute of Mathematics and Information Technology), and \u0438 Alexander Meigal ; they are all from Petrozavodsk State University, Russia.The Special Issue collects eleven papers to provide a multi-domain overview of the trends and developments in the edge computing and starts with the illustration of achievements in smart healthcare services. The digitalization of healthcare driven by the IoT and AmI leads to the effective use of sensors, when various parameters of the human body are instantly tracked and processed in daily life ,2. The cAn IoT-enabled system to monitor gait in subjects with Parkinson\u2019s disease is presented in study . ParkinsSmart healthcare applications, the Internet of Things (IoT), and artificial intelligence are arguably the most appropriate customized solutions for such shortcomings of traditional healthcare systems, such as long waiting times, unnecessary long trips to health centers, high costs, and mandatory periodic doctor visits. The comprehensive literature review determinAnother illustration of the effective application of neural networks in healthcare is presented in study . Speech The realm of smart object-recognition applications of AI systems is presented in the subsequent articles ,7,8. DriFor the IoT-enabled smart applications, point clouds are one of the most widely used data formats created by depth sensors. Research on feature extraction from disordered and irregular point cloud data has advanced recently. The overview of the dThe research direction of smart environment monitoring is presented by the study , in whicSmart disaster rescue is presented by an interesting development of a wearable device for search dogs that recognizes the behavior of a dog when a victim is found, using deep learning models . With thIn conclusion, this Special Issue illustrates advanced cases of using the AI technology for IoT-enabled smart applications. Each case demonstrates a promising trend for applying AI in IoT environments, making a step towards the effective use of modern technologies in our everyday life."} +{"text": "On 19 April 2022, in order to overcome a succession of recent global food health and agriculture safety (FHAS) incidents, the Taiwanese government instituted and announced 20 comprehensive Articles under the Taiwanese Food and Agricultural Education Law (TFAEL) for regulating the Taiwanese FHAS in order to completely construct the international strategies under the current global food security challenges of the FAHS. As a result, this research study firstly employs the learning community model (LCM) of the learning theory to measure the implementing depth of the international sustainability practice of the 20 Articles of the Taiwanese FHASE from a learning performance analytical perspective. Then, the social learning theory (SLT) of the educational theory is applied to consolidate the individual behaviors of the relative stakeholders, the organizational management of the relative industries and the socialized consent of the multilateral organization performance assessment network (MOPAN) of the Food and Agriculture Organization (FAO) of the United Nations (UN). After completing quantitative and qualitative analyses, the two most valuable conclusions and findings were as follows: (1) Not only Article 12, but also Articles 3, 4 and 5 of the new law can empirically facilitate strategic management for supporting and promoting the Taiwanese FHAS educational policy dialogue at a global, regional and country scale in order to effectively advance the international sustainable compatibility of the TFAEL. (2) Articles 6, 11 and 16 of the new law can completely construct operational management for building normative and standard-setting Taiwanese FHAS educational works in order to efficiently advance the international sustainable compatibility of the TFAEL. Therefore, beyond the analytical results of this research, the international sustainable compatibility of the TFAEL provides a direction for the development of sustainable food systems, food policies, agricultural food markets and food chains in order to overcome the various contemporary global food security challenges. For a long time, governments have paid attention to stabilizing the supply and volatility of food prices and crops, and to technical guidance and marketing promotion on the agricultural production side. Further, most people have deemed that the food health and agriculture safety (\u201cFHAS\u201d) issue is the government\u2019s responsibility , which rRecent incidents of the Taiwanese food health and agriculture safety (\u201cTFHAS\u201d) include the contaminated soy sauce and starch food safety incident in 2013, the rancid cooking and feed oil that was used as edible oil in 2014, the \u201cMin Dou\u201d pesticide residue food safety incident of schools\u2019 nutritious lunches in 2014, the pesticide residues in tea beverages in hand-shaken beverage shops in 2012 and 2015, the presence of antibiotics in honey in 2015, the high fipronil content in eggs in 2017, the pudding powder and other products made with expired additives in 2018, and in 2019, a high fipronil content was once again detected in eggs. Therefore, the Taiwanese public has started to break their silence by expressing their own opinions on FHAS. They strongly request more TFHAS regulations and rules in nutrition, housekeeping, health, food health, agriculture safety and ecological education. In order to effectively reflect these public requirements, the Taiwanese government has specially integrated not only the TFHAS standards, but also educational concepts and behaviors into the legislation source design of the 20 Articles of the Taiwanese Food and Agricultural Education Law (\u201cTFAEL\u201d) on 19 April 2022 to overcome the current global food security challenges. Firstly, the TFAEL has officially declared the Executive Yuan, at the Council of Agriculture, as the main authority responsible for the entire TFHAS. Secondly, new goals and principles were incorporated into the TFAEL in order to bring positive benefits to the expansion of domestic ingredient use for local production and public consumption ,7,8.However, it is difficult to make a comprehensive survey on the international sustainable compatibility of the TFAEL ,10,11 afIn order to extensively consider the educational sustainability of these 20 Articles of the TFAEL, the public, democracy and pursuing excellence philosophies of the learning community model (LCM) from theIn In order to statistically measure the interplays, the factor analysis (FA) approachSignificantly, the 20 Articles of the TFAEL can be refined based on .Articles 1 to 4 legislatively institute the power and responsibility of the TFHAS to the relative competent authorities to effectively facilitate the participation of the Taiwanese public in promoting the developed sustainability of the TFAHS.Article 3 firstly defines the empirical implemented terms of the educational activities of the TFAHS. Its content is described as follows: \u201cTFHAS is to refer to the use of educational methods to cultivate citizens\u2019 understanding of national basic agricultural production, agricultural product processing, friendly environment, friendly production and breeding and animal husbandry, animal welfare, food selection, knowledge and practice of catering preparation, leftover food disposal, and enhance the connection between food, the environment and agriculture\u201d .Articles 4, 5 and 6 legally point out that each level of the central, municipal and local Taiwanese government must set the TFHAS-related competent authorities, responsible agencies or departments to facilitate the planning, supervision, awards and professional labor training of the TFHAS. Furthermore, these TFHAS-related competent authorities have the direct duty to organize professional committees to advance the implementation, performance, development and gathering resources for the administrative guidance of the TFHAS.Article 5 directs each TFHAS-related competent authority, responsible agency or department to take the legal rights and responsibilities to dominate the direction of international development and social needs, formulate promotion policies and set up specific implementation indicators for comprehensively developing sustainability.Article 8 states that each TFHAS-related competent authority, responsible agency or department has to regularly hold two meetings per year to update the amendment-related policies by inviting various experts, scholars and non-governmental representatives.Article 11 directly empowers each TFHAS-related competent authority, responsible agency or department to have the legal priority to expropriate local agricultural products or foods to all national government agencies (departments), public institutions, administrative legal persons, schools, kindergartens and foundations in order to sustainably develop TFHAS-related industries.(1) First session of the TFAEL:In order to improve the labeling regarding the place of production or origin, Articles 12 and 16 currently regulate that primary food staples consumed by Taiwanese people such as egg, rice, chicken, soybean, etc., must be clearly labeled to identify the origins of these primary food and agricultural products.Article 12 regulates that each TFHAS-related competent authority, responsible agency or department has to guide cater and food businesses to use local ingredients; label the origin of the ingredients according to the municipality, county (city) or township name; promote the consumption of local agricultural products; reduce food waste; reduce the amount of ingredients and reduce leftovers. Thus, Article 12 not only effectively encourages food and catering industrialists to use local ingredients while labeling the original production location and to reduce leftovers in the operation, but it also efficiently guides consumers to think about the sources of necessary ingredients by giving priority to domestic and local ingredients sourced in Taiwan.Article 16 regulates that each TFHAS-related competent authority, responsible agency or department has to set up not only a network platform to integrate relevant information, but to also construct a food and agriculture education information integration platform to strengthen consumption channel information, promote local agricultural products and labels, and integrate food and agriculture education teaching materials, teaching plans, professionals, teachers, volunteers and publicity materials.Articles 12 and 16 manifestly rule that each TFHAS-related competent authority, responsible agency or department has to design and offer the appropriate rewards to the TFHAS-related industrialists and institutions that provide outstanding contributions.(2) Second session of the TFAEL:As Taiwan is a part of the global economy, these 20 Articles of the TFAEL must not only be considered, but they must also be measurable in order to comprehensively develop the internationalization and sustainability of the TFHAS, because the international sustainable compatibility can effectively advance the legitimacy, effectiveness, implemented performance and international sustainability of the TFAEL through the international sustainable compatibility.In order to achieve the research goal, the institutional theory (IT) was applied to emphasize the impact of institutions on the international convergence of the TFHAS. It can be argued that the TFHAS system and the TFAEL rules shape the country\u2019s overall individual behaviors and organizational cooperation model and drive all Taiwanese people to adopt and abide by common legal standards through institutional norms and constraints. The institutional theory (IT) originally emerged in the late 19th and early 20th centuries to be formed as a prominent sociological perspective used to examine the role of institutions and society in shaping individual and collective behavior. The core concepts were (1) the significance and role of normative, regulative and cognitive institutions in regulating individual behaviors and organizational policies, and (2) the role of rational\u2013legal authority and formal organizations in society. Comprehensively, the institutional theory (IT) continues to evolve, incorporating insights from other disciplines such as economics and political science. It has expanded to study fields beyond organizations, including international institutions, healthcare, education and sustainability. Continuously, a lot of researchers began to utilize the institutional theory (IT) to examine how multiple institutional logics or socially constructed systems of values, norms and beliefs coexist and influence organizations and society. This perspective emphasizes the tension and conflicts that arise when individuals and organizations are subjected to different institutional pressures. Overall, the institutional theory (IT) can not only evolve, incorporating insights from other disciplines such as economics and political science, but it can also be used to extensively study fields beyond organizations, including international institutions, healthcare, education and sustainability.In order to effectively advance the legitimacy, effectiveness, implemented performance and international sustainability of the TFAEL, the democracy philosophy (DP), pursuing excellence philosophy (PEP) and public philosophy (PP) of the learning community model (LCM) have further been employed to assess the legal educational performance and effectiveness of the TFHAS on the entire Taiwanese society, as shown in In detail, firstly, the democracy philosophy (DP) of the learning community model (LCM) can demoSecondly, the pursuing excellence philosophy (PEP) of the learning community model (LCM) can illuThirdly, the public philosophy (PP) of the learning community model (LCM) can presIn order to comprehensively assay the interactions and dependences among the democracy philosophy (DP), pursuing excellence philosophy (PEP) and public philosophy (PP) of the learning community model (LCM), the social learning theory (SLT) was further applied, as shown in Significantly, the individualism characteristic of the social learning theory (SLT) can explore both the democracy philosophy (DP) of the learning community model (LCM) and the normative considered role of the institutional theory (IT) in the TFAEL. Each Taiwanese citizen has equal rights and duties to speak and attend the various TFHAS activities and political campaigns. Particularly, the individual concepts and behaviors of the TFHAS-related stakeholders directly affect the organizational measures of the TFHAS-related industries . ReciproAt the same time, the TFHAS public consent regarding the multilateral organization performance assessment network (MOPAN) of the Food and Agriculture Organization (FAO) of the United Nations (UN) can also reversely disturb the organizational measures of the TFHAS-related industries . Critically, the TFHAS public consent of the TFHAS regarding the multilateral organization performance assessment network (MOPAN) of the Food and Agriculture Organization (FAO) of the United Nations (UN) can also directly impact the individual concepts and behaviors of the TFHAS-related stakeholders and the organizational measures of the TFHAS-related industries . MeanwhiHence, the officers and staffs of the TFHAS-related competent authorities have to accomplish a series of relative classes of the FHASE and then must report the completed learning outcomes and performances in connection with the international sustainability practice. Measurably, the first session of Articles 3, 4, 5, 6 and 11 were defined as the pursuing excellence philosophy (PEP) of the learning community model (LCM) for assessing the organizational management of TFHASE-related industries and the second the Article 12 and 16 were classified as the democracy philosophy (DP) of the learning community model (LCM) for apprIn terms of the achievement of research reliability, representativeness, validity and accuracy, this research cross-employs the factor analysis (FA) of quantitative analysis to condiariables ,32,33.XStep 1: Standardize the intersection of variance to be 1 (maximum).If maximization occurs:, the interaction-compared measurements of the \u201cdiscrete probability connections\u201d in the interactive dependences were completely computed in the entropy triangular weight ((3) from .(3)H\u00a0YXSignificantly, the interplays and dependences among the individual behaviors of the TFHAS-related stakeholders, organizational management of the TFHAS-related industries and TFHAS socialized consent of the multilateral organization performance assessment network (MOPAN) of the Food and Agriculture Organization (FAO) of the United Nations (UN) were comprehensively assessed by systematically analyzing the structure of the evaluated mode of the international sustainable compatibility of the TFHAS through the effective assessments of the triangle entropy method (TEM) of qualitative analysis.As shown in (1)The first step: We concretely explored the most core determinants of the international sustainable compatibility of the TFAEL under the current global food security challenges to achieve the main goal of this research by cross-employing the institutional, learning community and social learning theories and statistical analyses of the factor analysis (FA) and triangle entropy method (TEM).(2)The second step: We not only extensively explored the literature about the main concept of the FAHS and TFAEL, but also systematically reviewed the literature about the institutional, learning community and social learning theories as well as comprehensively integrated the statistical analyses of the factor analysis (FA) and triangle entropy method (TEM).(3)The third step: We implemented the factor analysis (FA) of quantitative analysis in detail to empirically deal with the large-scale questionnaire data with a higher research validity and representativeness, as well as used the triangle entropy method (TEM) of qualitative analysis to practically execute the expert\u2019s weighted questionnaire results with a higher research reliability and exactness.(4)The fourth step: Based on the systematic measurements and assessments of the statistical analyses of the factor analysis (FA) and triangle entropy method (TEM), we induced the valuable conclusions and contributive findings in order to academically resupply the interdisciplinary research gap and empirically provide the most effective recommendations for the international sustainable practice of the Taiwanese Food and Agricultural Education Law under the current global food security challenges.In According to With reference to the methodological measures of the factor analysis (FA) of quantitative analysis , the conEssentially, the larger the number of samples selected, the higher the accuracy of the inference of the statistical analysis results to the actual situation, which can help to avoid the effective detection of differences caused by too few samples. Significantly, the authors of addresseIn detail, there were 199 interviewees that had previously taken related courses regarding the international sustainable compatibility of the TFHAS. This induces that approximately 86.15% of the interviewees have experience with regard to the international sustainable compatibility of the TFHAS. Fifty-seven (57) out of the 231 interviewees (or 24.68%) were not willing to support the international sustainable compatibility of TFHAS, even if they were knowledgeable on the contents of Article 5 of the TFAEL. In addition, with respect to the expert\u2019s questionnaires, clearly Furthermore, Particularly, the majority of the entire commonalities of the appraised, assessed and evaluated criteria were higher than 0.6 and close to 0.7, which means there was a higher associated interplay among each criterion through measuring the 231 valid large-scale questionnaires in the FA approach of quantitative analysis.After executing the FA of quantitative analysis, the entire communalities among these four appraised, five assessed and two evaluated criteria in the 231 valid interviewed questionnaires were integrated into the computation of Equations (2) and (3) of the TEM of qualitative analysis for achieving the higher research validity and representativeness. Furthermore, the 30 valid experts\u2019 weighted questionnaires were conducted into Equations (2) and (3) of the THM of qualitative analysis through the statistic entropy method with the communalities of the FA of quantitative research. Continuously, Finally, In view of Continuously, they also agreed that the OM-BNSW of the Food and Agriculture Organization (FAO) of the United Nations (UN), the cognitive institutions role of the institutional theory (IT), public philosophy (PP) of the learning community model (LCM) and the socializationism of the social learning theory (SLT)) was affected by Article 16 , democracy philosophy (DP) of the learning community model (LCM) for the individualism of the social learning theory (SLT)) and Article 11 , pursuing excellence philosophy (PEP) of the learning community model (LCM) and the organizationism of the social learning theory (SLT)).(1)Not only Article 12 , democracy philosophy (DP) of the learning community model (LCM) for the individualism of the social learning theory (SLT)), but also Articles 3, 4 and 5 , pursuing excellence philosophy (PEP) of the learning community model (LCM) and the organizationism of the social learning theory (SLT)) can empirically facilitate the strategic management for supporting and promoting the TFHAS policy dialogue at the global, regional and country levels in order to effectively advance the international sustainable compatibility of the TFAEL. The TFHAS has instituted the source of law that the central, municipal and local levels of the Taiwanese government must set the TFHAS-related competent authorities, responsible agencies or departments to facilitate the planning, supervision, awards and professional labor training of the TFHAS. Particularly, the central, municipal and local governments also have the direct duty to organize the professional committees to facilitate the implementation, performance, development and gathering resources for the administrative guidance of the TFHAS.(2)Article 16 , democracy philosophy (DP) of the learning community model (LCM) for the individualism of the social learning theory (SLT)) as well as Articles 6 and 11 , pursuing excellence philosophy (PEP) of the learning community model (LCM) and the organizationism of the social learning theory (SLT)) can completely construct the operational management for building normative and standard-setting TFHAS works in order to efficiently advance the international sustainable compatibility of the TFAEL. Each TFHAS-related competent authority, responsible agency or department has to guide cater and food businesses and industries to use local ingredients, label the origin of the ingredients according to the municipality, county (city) or township name, and promote the consumption of local agricultural products, reduce food waste, reduce the amount of ingredients, and reduce leftovers by giving priority to domestic and local ingredients sourced in Taiwan.Since the continuous appearances of a succession of the recent global FHAS incidents, a majority of people have commenced to realize that the FHAS is not only a governmental responsibility, but that they also have a public duty. Facing the development trend of the world\u2019s FHAS, the Taiwanese government instituted the comprehensive 20 Articles of the TFAEL on 19 April 2022 for overcoming various current global food security challenges of the FAHS. In order to cross-evaluate the legitimacy, effectiveness, implemented performance, international compatibility and educational sustainability of the 20 Articles of the TFAEL, the three role considerations of the institutional theory (IT), the three essential philosophies of the learning community model (LCM) and the three basic characteristics of the social learning theory (SLT) were cross-employed to measure the large-scale and experts\u2019 weighted questionnaires through the factor analysis (FA) of quantitative analysis. As a result, the most two valuable conclusions and findings are concluded as follows:Therefore, beyond the analytical results of this research, the international sustainable compatibility of the TFAEL is a direction towards sustainable food systems, food policies and agricultural food markets and food chains for overcoming the various contemporary global food security challenges. However, as for the limited research resources, there are more measured methodologies of the quantitative and qualitative analyses to be utilized to detect the key determinants of the evaluation and construct the assessed model in the future."} +{"text": "Conductive anaesthesia of the nerves around the head is one of the methods of intraoperative pain relief (under deep anaesthesia but before proceeding with the procedure). Performing this procedure on primates is especially challenging for the veterinarian, due to their cranial anatomy and topography, which has more in common with the human skull than with the skulls of other animals. Knowledge of key bony structures, including cranial foramina, is essential for effective anaesthesia of the cranial nerves.Colobus angolensis), Celebes crested macaque (Macaca nigra), L\u2019Hoest\u2019s monkey (Allochrocebus lhoesti), baboon , buff-bellied capuchin (Sapajus xanthosternos), black-and-white ruffed lemur (Varecia variegata), crowned lemur (Eulemur coronatus), and a ring-tailed lemur (Lemur catta) coming from the Wroclaw Zoological Garden (Poland). The cranial nerves running through the foramina have also been described and their anaesthesia techniques against bone points have been tested to relieve post-operative pain in the area of the head supplied by these nerves.In this study, the differences in the topography of the cranial foramina in eight selected species of primates were examined: Angola colobus (The tests carried out show differences in the topography of the cranial foramina, and therefore also differences in the methods of injection, so the results obtained in this study may be useful in veterinary medicine, especially for practising veterinarians. Camelus dromedarius) [Sus scrofa) [Bos taurus) [Macaca mulatta) [Cranial nerves that originate in the brain pass through openings in the skull and they innervate various tissues and organs of the head and its surroundings. The foramina differ in their structure, topography and size depending on the animal species and individual characteristics and they are a reference point for the veterinarian to perform perineural injections, for example, to relieve pain while reducing the dose of systemic anaesthetic. This reduces the risk of complications and the patient\u2019s recovery time \u20133. Regioedarius) , Eurasia scrofa) , domesti taurus) , New Zea taurus) . In addimulatta) . This memulatta) . When itmulatta) , 11. It mulatta) . Anothermulatta) . Accordimulatta) . For themulatta) , 14\u201318.The basic problem with conduction anaesthesia (nerve blocks) is the fact that the anaesthetic should not be administered into the nerve trunk itself - this can lead to serious complications, including permanent nerve damage. In addition, perineural injections carry the risk of hematoma, peripheral neuritis, or abscess . DependiThe research aimed to learn the topography of the skull of primates, paying attention to the foramina from which the cranial nerves exit. Knowledge of bone structures is necessary for the effective use of anaesthesia because some injections used in other animal species are not applicable in primates precisely because of the characteristic structure of the skull. The skull publication is only the first in a series. Part II will concern the use of anaesthesia with attention to the anatomical structures of soft tissues, i.e. major salivary glands, lymph nodes, blood vessels and nerves. Knowledge about the anatomy of above mentioned structures and the described procedures will allow veterinarians to apply the appropriate method of anaesthesia block to the appropriate nerve. Such data on exotic primates, while not necessarily of use to a general practitioner, is especially important for veterinarians practising in zoos, primate sanctuaries and national parks, and with primate researchers. However because a limited number of individuals were available in some instances the proposed routes for and placement of needles should be interpreted as guidance and less as a directive.Collection of Specimen and Conservation status. The study material compared eight adult captive species of primates: yellow Angola colobus (Colobus angolensis), Celebes crested macaque (Macaca nigra), L\u2019Hoest\u2019s monkey (Allochrocebus lhoesti), baboon , buff-bellied capuchin (Sapajus xanthosternos), black-and-white ruffed lemur (Varecia variegata), crowned lemur (Eulemur coronatus), and a ring-tailed lemur (Lemur catta) coming from the Wroclaw Zoological Garden (Poland). These animals were collected in the years 2016\u20132022 in the Division of Animal Anatomy of the Department of Biostructure and Animal Physiology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences . The thermal dissection was completed when the remains of soft tissues were imperceptible on the bones. The skulls were then cleaned in clean running water and left in a ventilated room to dry completely [mpletely . After ampletely . Values Topography of the cranial foramina.foramen jugulare) is located on the border of the basilar part of the occipital bone and the temporal bone on both sides of the foramen magnum. In the centre of the jugular opening is the intracervical process (processus intrajugularis), which divides it into two parts. The medial part - relatively smaller - contains the glossopharyngeal nerve (nervus glossopharyngeus), the lateral part \u2013 relatively larger \u2013 contains the vagus nerve (nervus vagus) and the accessory nerve (nervus accessorius) [The jugular foramen (ssorius) \u201327. In bforamen infraorbitale) is located on the anterior surface of the maxillary body below the infraorbital margin and there may be more than one foramen. From it comes the infraorbital nerve - a branch of the maxillary nerve. The infraorbital nerve gives off the superior alveolar branches responsible for the innervation of the maxillary teeth and the terminal branches innervating the skin and mucosa of the nose, upper lip and lower eyelid [The infraorbital foramen is present in the posterior part of the palatal surface of the horizontal plate of the palatine bone, and the greater palatine nerve emerges from it [The greater palatine foramen is located on the medial side of the mandibular branch and is the beginning of the mandibular canal. The inferior alveolar nerve runs through it, originating from the mandibular nerve (nervus mandibularis), which passes into the mental nerve and exits through the mental foramen . There may be more than one mental foramen and more than one mental nerve [The mandibular foramen is located between the jawbone and the sphenoid bone. It connects with other cranial spaces through numerous openings and canals: sphenoid-palatine foramen, inferior orbital fissure, circular foramen, pterygoid canal, palato-vaginal canal, and greater palatal canal. The pterygopalatine fossa is bounded: superiorly by the body of the sphenoid bone, anteriorly by the body of the maxilla and the orbital process of the palatine bone, posteriorly by the pterygoid process of the sphenoid bone and the greater wing of the sphenoid bone, laterally by the pterygopalatine fissure , medially by the vertical plate of the pterygopalatine bone. It passes from below into the greater palatal canal. The most important nerve structures present in the pterygopalatine fossa are the pterygopalatine ganglion and the maxillary nerve (nervus maxillaris) [The pterygopalatine fossa (illaris) , 25, 33.foramen ovale) is located on both sides of the skull in the greater wing of the sphenoid. The mandibular nerve (nervus mandibularis) emerges from the oval foramen and runs nasally-inferiorly giving branches to the masticatory nerve (nervus masticatorius), lingual nerve , auricle-temporal nerve , mandibular-hyoid nerve (nervus mylohyoideus), and inferior alveolar nerve [The oval foramen (nferior) , 25, 34.Anaesthesia of the infraorbital nerve. The infraorbital nerve gives off the superior alveolar branches responsible for the innervation of the maxillary teeth and the terminal branches innervating the skin and mucous membrane of the nose, upper lip and lower eyelid.Intraoral method. The needle is inserted into the vestibule of the oral cavity, between the first and second incisor, and moved upwards and outwards, towards the pupil of the eye looking ahead [ng ahead . Baboon Anaesthesia of the greater palatine nerve. The greater palatine nerve is responsible for innervating the mucous membrane of the hard palate. The needle is inserted at the level of the last molar [st molar . It is dAnaesthesia of the mental nerve. The mental nerve is responsible for the sensory innervation of the skin of the chin and the mucous membrane of the lower lip. The needle is inserted through the skin after palpating the mental foramen with a finger. This method can be applied to all monkey species tested . Thus our proposed routes for and placement of needles should be interpreted as guidance and less as a directive."} +{"text": "Artificial intelligence (AI) has made an indelible contribution to the progress and development of human society, which has major applications in the fields of national defense, transportation, finance, logistics, education, etc. As a branch of computer science, AI has made significant breakthroughs in machine translation, intelligent control, language and image processing, automatic programming, and storage computing. Artificial intelligence-driven healthcare technologies are rapidly evolving into solutions that are applicable to clinical practice. AI has greatly helped improve health outcomes by using patient-relevant clinical data for early diagnosis of symptoms and better prognosis. Therefore, there is reason to believe that AI can make greater contributions to the prevention and diagnosis of mental disorders.There have been relevant representative studies based on AI technology that have made breakthrough contributions in the prevention, diagnosis, and treatment of other diseases. In order to improve the applicability of AI technology in the mental disorder field, it is necessary to propose new theories, technologies, architectures, algorithms, and mechanisms. The goal of this Research Topic is to bring together relevant researchers from industry and academia to share their latest findings and developments in the application of AI in medicine, especially in the prevention and diagnosis of mental disorders. It was our unexpected pleasure to have 4 papers in this topic which reported new exciting findings and cutting edge methodologies.In this Research Topic, four articles focus on the performance of artificial intelligence in the field of mental disorders, such as symptom diagnosis, adjunctive treatment, and model optimization.Depression recognition model:Xie et al. explored the application of the depression recognition model (DR model) based on AI machine learning (ML) in the diagnosis of depression. They explored the rhythms of adrenocorticotropic hormone (ACTH) and cortisol in depressed and anxious patients and their effects on mental status, and extracted data features based on electroencephalo-graph (EEG) data from different patients to construct a DR model for diagnosis .AI-based chatbot micro-intervention for parents:Entenberg et al. investigated the effectiveness of intelligent chatbots to help parents with parenting. The authors recruited a sample of 170 parents with at least one child to participate in the chatbot intervention. Parents can learn skills for parenting such as effective praise techniques. This study analyzed the effectiveness of parenting chatbot micro-interventions, the learning gained by participants from pre to post-intervention, and the user characteristics of parents. According to the experimental results, mental health chatbots are a promising method for busy parents of children and adolescents to enhance parenting skills .Point of interest (POI) recommendation based on preference perception: Graph embeddings and graph neural networks are fail to capture deep graph structure information in point-of-interest recommendation tasks, resulting in unsatisfactory representation results. To address the above issues, Shu et al. proposed a general framework based on the diffusion of preference-aware graphs to capture the deep structural information neglected in most existing methods for POI recommendation.Understanding psychiatric illness through natural language processing: The diagnosis of mental disorders is mainly based on the level of experience of each psychiatrist and often lacks objectivity. To this end, Kishimoto et al. created a large Japanese speech dataset, used natural language processing to quantify the linguistic features of mental disorders and neurocognitive disorders. Finally, objective and easy-to-use biomarkers were developed. These biomarkers quantify the linguistic features of mental disorders, allow more detailed examination of their correlation with other clinical indicators, and improve the accuracy of disease prediction .These typical research efforts are artificial intelligence for the adjunctive treatment of psychiatric conditions, diagnosis and optimization of neural network models, which are important for the development of novel network models and intelligent diagnostic techniques. The development of artificial intelligence provides new ways of diagnosis and treatment in medicine. We look forward to closer interaction as well as breakthroughs between AI and the field of mental disorders. Finally, we thank all contributing authors for their novel research works and publishers, as well as the editorial team for their efforts in organizing this Research Topic.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "The hit-to-lead optimization, which represents a crucial step in the early drug discovery process, aims at improving the drug-likeness by modifying physicochemical properties, improving pharmacokinetic/pharmacodynamic (PD) profiles, and reducing off-target activities. Increasingly, lead optimization may benefit from the support of dictions and the dictions by adopthemistry . Howeverhemistry .Streptomyces aureofaciens, artemisinin from Artemisia afra, doxorubicin from Streptomyces peucetius, cyclosporine from Tolypocladium inflatum, and so on , Khandazhinskaya et al. describes the synthesis of a new series of 5\u2032-norcarbocyclic fleximers bearing an artificial sugar fragment with a pyrazole-containing heterocyclic base, and the inhibitory properties in respect to purine nucleoside phosphorylase (PNP). Today, fleximer analogues of nucleosides are in the crossroad of heterocyclic and nucleoside chemistry, and this class of compounds is very promising because of a wide spectrum of biological activities. Specifically, the design with the fleximer aza/deazapurine bases can ensure additional conformational freedom in order to maximize structural interactions in the active site of the target enzyme while maintaining the structural similarity with a normal nucleoside substrate. Thus, helping with better understanding of enzyme specificity. The new compounds interact with the active site of the PNP of E. coli like natural heterocyclic bases, showing weak, non-competitive inhibitory activity.The second article by VNN1 gene. The main effect of vanin-1/VNN1 is related to its pantetheinase sulfhydrylase activity, which can hydrolyze pantetheine into pantothenic acid and cysteamine. The enzymatic activity of vanin-1/VNN1 has been found to be essential in the development of many diseases. Wang et al. used fluorescent and bioluminescent probes to establish a series of visual screening methods and evaluate the inhibitory activity of a number of novel VNN1 inhibitors with different backbones. The authors demonstrated that VNN1 has a role of a pro-inflammatory agent during the onset of inflammatory bowel diseases (IBDs). Thus, the development of VNN1 inhibitors can provide a new avenue for effective IBD treatment to alleviate suffering.Pantetheinase is an enzyme that in humans is encoded by the Tamatam et al. describes methodologies and mechanistic insights for the synthesis of nitrogen-containing heterocyclic quinazolines via transition metal-catalysed reactions, paying attention to the advantages, limitations, and future perspectives of quinazoline synthesis via such reactions.Finally, the review article by In conclusion, this Research Topic of articles demonstrates the importance of the heterocycles of natural or synthetic origin in molecules with therapeutic properties and recent advances in the preparation of the quinazoline scaffold."} +{"text": "Optimal resource allocation within national health systems represents the ultimate challenge in diverse countries worldwide. Major part of the literature points that health systems decentralization potentially address the challenge. The present commentary focuses on the debate referring to effects of health systems decentralization, based on the evidence of the study of Arianna Rotulo and colleagues. Studies on the subject emphasize the role of path dependence and the influence of choice of indicators for measurement of effects in the assessment of health systems decentralization. Acknowledging the complexity of the phenomena, the results of the study of Rotulo et al on health system decentralization in Italy are highlighted through the analysis of recent evidence from the literature. The present commentary shows that there are diverse indicators adopted in the literature on the subject, pointing to mixed results, depending on country characteristics and selection of indicators in the analysis. The synthesis of indicators gathered in recent studies also indicate that health system indicators are sensitive to path dependence, thus, requiring additional attention to assumptions of studies on health systems decentralization. Thus, studies should consider the influence of path dependence on organizational practices and institutional structures involved in decentralization processes, in addition to acknowledging that assessments on decentralization vary substantially according to indicators adopted in the analysis, and their links with previous decisions within health systems. The present commentary focuses on the debate regarding effects of health systems decentralization, based on evidence from the study of Arianna Rotulo and colleagues.4 Optimal resource allocation within national health systems represents the ultimate challenge in diverse countries worldwide. Major part of the literature points that health systems decentralization potentially address the challenge, particularly in countries with substantial intervention of the public sector, considering that the provision of merit goods may benefit from supply at local level due to in-depth knowledge of population needs and preferences.1 showed that fiscal decentralization may negatively impact health services due to intensification of existing inequalities in the distribution of resources within the country, through decrease of healthcare availability, accessibility, and utilisation. According to the authors,1 the allocation of pooling and expenditures to local governments aggravated disparities among Italian regions from 2001 until 2017, showing decrease in access and availability of resources in public hospitals, whilst increasing resources in private healthcare settings. Yet, evidence from studies assessing health systems decentralization during recent decades identifies mixed results, depending on country characteristics and selection of indicators. Rotulo et al1 Acknowledging the complexity of decentralization phenomena, Rotulo et al1 highlight negative effects of fiscal decentralization of the Italian health system through the analysis of selected indicators in the context of Italy, a high-income country. Considering elements in the literature of health systems decentralization, authors should ponder the influence of path dependence and choice of indicators for assessment of decentralization effects.Servizio Sanitario Nazionale) was intended towards promotion of universal healthcare access , funded through federal taxes and operationalized at local level. Fiscal decentralization occurred in 2001, including services restructuration and additional financing at local level with co-payment.1 First, concerning path dependence, authors emphasize historical inequalities among country regions, and underscore that the design of the Italian National Health Service or increase in unplanned readmissions . Healthcare utilization was represented by hospitalizations in public and private hospitals, potentially including premature discharges, which may lead to negative health outcomes, including complications, unplanned readmissions, and higher mortality.1 should consider interactions with other variables, since it is important to acknowledge that prevention represents lower costs and higher quality of life for individuals and populations, whilst curative tertiary level interventions result in higher costs and potential detrimental impacts on individuals\u2019 health and wellbeing. Therefore, part of the indicators in the study of Rotulo et al1 may be linked to either lower costs or higher quality of private healthcare (in comparison to public sector), or to higher public sector expenditures in prevention strategies in high-income regions, leading to improvements in population health outcomes. Finally, the potential effects of decentralization referring to expansion of private sector in low-income regions1 Costa-Font and Turati6 showed that inequalities in outcomes and outputs in Italian and Spanish health systems were associated to differences in design and management of health services by local governments, instead of healthcare decentralization processes. However, the authors adopted different measures of regional inequality output and health system outcome with different empirical strategy, based on concentration indexes, for the analysis of pre- and post-decentralization inequalities within national health systems. Contradicting the results from Rotulo et al,7 indicated potential opportunistic behaviour of local governments to benefit from spillovers from public expenditures of neighbour regions in the process of decentralization in Italy from 1996 to 2010. In addition, authors point to economies of scale, shift of demand to the private sector, and movement of individuals to regions with higher income due to unsatisfaction with local health services. The authors focused on levels of public expenditures in three sectors using spatial Durbin model to assess the impact of decentralization on spillover effects.7 De Siano and D\u2019Uva8 Evidence from studies on health system decentralization in other countries reinforce divergences according to country characteristics and type of indicator. Health system decentralization has been usually associated with beneficial results in primary healthcare in developed and developing countries,10 which are related to health promotion and disease prevention at lower costs, and associated with long term beneficial health outcomes for the population. Major part of studies on health systems decentralization focuses on indicators of responsiveness, efficiency, and effectiveness in healthcare delivery.11 showed that decentralization of governance, financing, and healthcare delivery generally present positive effects, whilst resource management decentralization may have negative effects. According to evidence from 30 European countries from 1996 to 2015, the effects of decentralization of healthcare expenditures were negative on populations\u2019 perceptions of healthcare quality.12 Cobos Mu\u00f1oz et al13 performed a systematic review of literature, showing mixed results regarding the effects of decentralization on health system indicators, although effects on indicators of system performance and health outcomes were generally positive. However, it is important to highlight that the authors assessed the quality of studies included in the systematic review, considering only 10 studies with low risk of bias. Dwicaksono and Fox14 synthesized quantitative and qualitative evidence on the effects of health systems decentralization in low-, medium- and high-income countries, indicating mechanisms and contextual factors at institutional, socioeconomic, and geographic levels influencing decentralization results on equity, efficiency, and resilience in healthcare. In addition, the decentralization process may present different effects in developing countries compared to developed countries, emphasizing the role of path dependence in the evolution of organizational practices and institutional arrangements within diverse structures of incentives. Abimbola et al14 The authors emphasize the complexity of the decentralization phenomena, showing that national and local government characteristics may influence the results of health systems decentralization. Therefore, decentralization may generate competition, cooperation, or coopetition (competition and cooperation) among organizations and governments through creation of multiple governance centres with vertical and horizontal relations amongst themselves.1 the decentralization process in the Italian health system follows the path of aggravating previous patterns of inequities through the mechanism of \u2018voting with feet,\u2019 phenomena based on the migration of individuals and resources from low- to high-income locations.13 In relation to the study of Rotulo et al,9 Recent evidence indicates that the process of decentralization may present important trade-offs between economies of scale, transaction costs and agency costs due to bureaucracy. In addition, lack of public sector accountability may support the capture of political power by local elites, jeopardizing efficiency, efficacy, and outcomes in local health systems. Thus, previous inequities in distribution of resources among local governments play important role in determining the capacity of provision of public services, contributing to divergences in results of health system decentralization.15 On the one hand, decentralization may generate disproportionate bureaucracy whilst pursuing improvements in quality, safety, and efficiency of healthcare delivery; on the other hand, health system centralization may lead to imposition of ineffective patterns for provision of health services at national level, depending on country characteristics.16 argue that health systems decentralization comprises diverse processes referring to various models of delegation or distribution of activities regarding organization, financing, management, and delivery of healthcare within different socioeconomic, cultural, and political backgrounds. Consequently, assorted degrees of responsiveness, efficiency, and effectiveness should be expected accordingly, especially considering the fundamental role of organizational practices and institutional structures in determining incentives and accountability to achieve optimal performance whilst minimizing risks of principal-agent problems.17 In fact, Costa-Font and Greer16 is supported by the synthesis of evidence on indicators gathered from studies previously discussed, reinforcing the requirement for careful consideration on the assumptions adopted in studies assessing health systems decentralization ."} +{"text": "The grading of recommendations assessment, development and evaluation (GRADE) method was adopted for the development of evidence, evidence classification, and recommendations that can be systematically evaluated. For evidence lacking clinical research support, the quality of evidence was evaluated and recommended based on the evidence level standard of ancient books of traditional Chinese medicine, and The Appraisal of Guidelines for Research and Evaluation II (AGREE II) and The Reporting Items for Practice Guidelines in Healthcare (RIGHT) were referred to. This guideline plan mainly introduces the guideline formulation process of constructing clinical questions and selecting outcome indicators, evidence retrieval, generation of recommendations, Acute primary headache causes pain in the organism, and long-term, persistent headache is a trigger and aura manifestation for many highly disabling diseases,3 The current treatment for acute primary headache is primarily analgesia. As no clinical practice guideline exists specifically for the treatment of acute primary headache using Traditional Chinese Medicine (TCM), this guideline was developed to recommend TCM treatments for acute primary headache aimed to relieve pain and standardize clinical behaviors of physicians, and allied health professionals who treat or care patients with acute primary headache in outpatient/emergency/in-patient care. It aims to recommend TCM for the treatment of acute primary headache, and improve the management, clinical efficacy, and quality of life in patients with headache.Headache is either a disease or a clinical symptom of multiple diseases.Syndrome differentiation and modification are critical in improving the efficacy of TCM in treating acute primary headache. However, such clinical evidence is difficult to obtain through randomized controlled trials (RCTs) or systematic reviews. Ancient literature is a treasure trove of TCM, an important basis for decision making in TCM clinical practice, and has a wide range of guidance for the treatment of acute primary headache using TCM. Therefore, the ancient TCM literature was also used as a major element of clinical evidence in the development of this guideline.This guideline focuses on acute primary headache and provides recommendations for their treatment using TCM, which can be used as a guide and reference for clinical practice by physicians in TCM internal medicine, neurology, and other related departments, and it will be revised according to clinical practice and advances in evidence-based medicine. The guidelinedoes not function as a medical code of conduct or a legal basis. Clinical practice based on this guideline may have different benefits for different patients and may produce different clinical outcomes.guidelines-registry.org/), with registration number IPGRP-2021CN156.The guideline proposals were registered on the practice guideline registration for transparency (PREPARE) , guideline secretary group, and guideline review group. The working group members are multidisciplinary experts, not only involving clinicians and methodologists but also due consideration on the values and wishes of potential conflicting parties and patients.The guideline steering committee comprises 10 to 15 experts. It has two chairpersons: professional and methodological chairpersons. All experts signed a conflict of interest statement, and at least one of the chairpersons did not have a conflict of interest related to this guideline. The main responsibilities of the guideline steering committee are as follows: (1) determine the topic and scope of the guideline; (2) approve the guideline proposals; (3) manage its conflict of interest statement; (4) oversee the guideline development process; (5) approve the guideline recommendation; and (6) approve the guideline publication.Guideline development groupThe GDG is composed of multidisciplinary clinical experts and methodologists. The main responsibilities of the GDG are as follows: (1) identify population, intervention, comparative measures, and outcome indicators and determine the scope of the guideline; (2) draft the guideline proposal; (3) collect and select clinical questions and outcome indicators, and construct clinical questions according to patient/population problem, intervention, comparison or control, and outcome (PICO) principles; (4) assess the importance of clinical questions and outcome indicators; (5) develop systematic reviews, evidence grading, and decision tables; (6) investigate patients\u2019 wishes; (7) determine quality grading of evidence and reach consensus on recommendations; (8) write the full text of the guideline, complete the coordination of the external review of the guideline, and handle the external review comments; (9) document the whole process of guideline development; and (10) manage matters related to guideline development.The external review group contains relevant experts and stakeholders, and its main task is to review the developed guideline recommendations.A conflict of interest statement form was made. All members of the guideline steering committee and guideline development group are required to fill in the form and agree to present the conflict of interest statement and the results of its handling as an annex to the guideline. For those who have a conflict of interest, the guideline steering committee decides whether or to what extent they would participate in the development of the guideline after discussion; those who do not have a conflict of interest could participate in the whole process.The purpose of this guideline is to recommend TCM treatment for acute primary headache, to guide clinicians and nursing staff to standardize the use of TCM for the treatment of acute primary headache with the main purpose of pain relief, and to improve the management of patients with headache, clinical efficacy, and the quality of life of patients. Users of the guideline include physicians and nursing staff of TCM internal medicine, neurology, and other related departments. The target population of the guideline is patients who were diagnosed with acute primary headache. which includes a class of diseases with headache as the main clinical feature caused by external factors and internal injury resulting in constriction or loss of nourishment of the veins and channels or by unfavorable clearing of the orifices. Western medicine diagnosis is based on the International Classification of Headache, Third Edition. Primary headache includes migraine, tension-type headache, trigeminal autonomic headache, and other primary headaches. This guideline does not cover secondary headaches, painful cranial neuropathy, other facial pain, or other types of headaches. This guideline applies to the pharmacological treatment of ongoing headaches and does not apply to the prevention of headaches during remission in patients with headache. Interventions include oral and topical TCM treatments.The clinical questions covered in this guideline relate to the TCM treatment of acute primary headache. The diagnosis of headache is based on the diagnostic criteria of headache disease in the Development of Internal Medicine of Traditional Chinese Medicine, The selection of clinical problems will be completed through multiple rounds of questionnaires.The working group investigates the importance of the collected and summarized PICO clinical questions and outcome indicators after reviewing relevant guidelines and surveying clinicians, multidisciplinary experts, and patients. The survey respondents are multidisciplinary experts and patients/guardians who rate the importance of clinical questions and outcome indicators. The importance of the outcome indicator is assessed through the method recommended by the GRADE working group. and a retrieval report will be produced. The National Library of Medicine (PubMed), the Cochrane Library, and the Cochrane CENTRAL database , Guideline International Network (GIN), National Guideline Clearinghouse (NGC), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guide Network , World Health Organization (WHO) database, Wanfang, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (SinoMed), and Chinese Sci-tech Journal Database (VIP), Baidu Xueshu (https://xueshu.baidu.com/), Yimaitong (https://www.medlive.cn/), and Zhonghua Yidian (TCM Dictionary) version 5.0 will be searched. Specific retrieval strategies are developed based on the characteristics of different databases using a combination of subject terms and free words. The development of retrieval strategies and the literature retrieval are conducted under the guidance of a literature retrieval specialist. No language limitation is applied. In addition, references from included studies are traced to gain access to relevant literature. Information such as relevant retrieval strategies and results are reported in a formal guideline document.In this guideline, published relevant guidelines, systematic reviews, and related literature published domestically and internationally in the past 3 years are retrieved based on the questions covered. Evidence evaluation will be performed based on the results of systematic reviews if the evidence in existing guidelines is not sufficient to answer the clinical questions posed in this guideline; relevant literature will be retrieved by the guideline development group to produce systematic reviews if high-quality systematic reviews in the past 3 years are not retrieved. Evidence from ancient sources lacking clinical studies is retrieved by an antiquarian literature agency based on the Classification Standard of Evidence in Ancient Books of TCM, The evidence quality will be categorized as \u201chigh\u201d, \u201cmoderate\u201d, \u201clow\u201d, or \u201cvery low\u201d. The evaluation process is completed independently by at least three people, and the coefficient of internal consistency among the evaluation team members is calculated. The methodological quality of the included systematic reviews re-review, systematic reviews, meta-analyses, and network meta-analyses were evaluated using the AMSTAR scale. The evaluation of the ancient evidence is completed by the guideline development group according to the TCM ancient evidence standards. The evaluation process is completed independently by two members, and if there is disagreement, it is discussed together, or a third party is consulted to resolve it. If no systematic reviews related to the clinical questions is retrieved, GDG will make a new round of systematic reviews to answer the clinical questions.The methodological quality of the included guidelines is evaluated using the GRADE approach.The guideline development group develops a \u201cProblem-Recommendations-Evidence\u201d decision form, sets the expert opinions as \u201cAgree, Disagree, and Uncertain,\u201d and submits it to the expert steering committee. The expert steering committee will reach consensus on the recommendations by telephone, email, or face-to-face method.The guideline recommendations will be submitted to the external review team for feedback, and the feedback will be reviewed by the guideline steering committee to determine and publish the final version of the recommendations of the guideline.After the guideline is reviewed and revised by the expert steering committee based on the external review, the full text of the guideline will be published in relevant journals, popular science journals, and other relevant mass media. Dissemination will be performed by holding relevant conferences and training courses.The guideline is planned to be updated every 5 years.The development group of TCM Guidelines for Acute Primary Headache will raise clinical questions through the real needs of clinicians in the practice of TCM for acute primary headache. The group raises clinical questions, performs evidence retrieval, quality evaluation, and recommendations, and formulates high-quality and practical clinical practice guidelines, considering the opinions of relevant experts, the wishes of patients with headache, and economic factors, to guide the clinical TCM treatment of acute primary headache and improve clinical outcomes of patients."} +{"text": "Dear Editor,3, but without treatment for hepatitis C. He complained of cutaneous lesions with two years of evolution, and significant worsening in the last months, with local pruritus. On examination, erythematous, infiltrated papules and plaques were observed in the gluteal region bilaterally, as well as in the left abdominal, cervical and upper dorsal regions , non-reactive rheumatoid factor, proteinogram with no monoclonal peaks. A skin biopsy was performed, which showed abundant mucin deposits in the upper and middle dermis and hepatitis C virus (HCV) infection three years before. He was undergoing regular treatment with antiretroviral therapy , and had an undetectable viral load, with a CD4 cell count of 534 cells/mm regions . He undee dermis .Figure 1a)Lichen amyloidosus;b)Lichen myxedematosus;c)Eruptive collagenoma;d)Granuloma annulare.The diagnosis of lichen myxedematosus was confirmed through clinical-pathological correlation. The patient was instructed to maintain antiretroviral therapy and to start treatment for hepatitis C.Lichen myxedematous (LM) is a rare, chronic subtype of mucinosis that clinically manifests as papules, nodules, or plaques restricted to the skin. It is characterized by fibroblast proliferation, with varying degrees of fibrosis, and mucin deposition in the dermis, in the absence of thyroid disease.7The current classification of mucinoses was proposed by Rongioletti et al. and divides the papular mucinoses into scleromyxedema, a variant with systemic involvement and associated with paraproteinemia, and localized papular LM. Localized LM is divided into 5 subtypes: discrete papular mucinosis, persistent acral papular mucinosis, self-healing cutaneous mucinosis, juvenile papular mucinosis, and nodular papular mucinosis.Diagnostic criteria include papular rash, mucin deposition, and variable degree of fibroblast proliferation on histopathological examination, as well as the absence of gammopathy, thyroid disease, or systemic involvement.There are no well-defined treatments reported in the literature, and the recommended approach is clinical observation alone.None declared.Nathalia Hoffmann Guarda: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Renan Rangel Bonamigo: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Renata Heck: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Activation of regeneration upon tissue damages requires the activation of many developmental genes responsible for cell proliferation, migration, differentiation, and tissue patterning. Ample evidence revealed that the regulation of chromatin organization functions as a crucial mechanism for establishing and maintaining cellular identity through precise control of gene transcription. The alteration of chromatin organization can lead to changes in chromatin accessibility and/or enhancer-promoter interactions. Like embryogenesis, each stage of tissue regeneration is accompanied by dynamic changes of chromatin organization in regeneration-responsive cells. In the past decade, many studies have been conducted to investigate the contribution of chromatin organization during regeneration in various tissues, organs, and organisms. A collection of chromatin regulators were demonstrated to play critical roles in regeneration. In this review, we will summarize the progress in the understanding of chromatin organization during regeneration in different research organisms and discuss potential common mechanisms responsible for the activation of regeneration response program. Particularly, the combination of single-cell chromatin profiling techniques ("} +{"text": "The advent of machine learning and its subsequent integration into small interfering RNA (siRNA) research heralds a new epoch in the field of RNA interference (RNAi). This review emphasizes the urgency and relevance of assimilating the plethora of contributions and advancements in this domain, particularly focusing on the period of 2019\u20132023. Given the rapid progression of deep learning technologies, our synthesis of recent research is paramount to staying apprised of the state-of-the-art methods being utilized. It not only offers a comprehensive insight into the confluence of machine learning and siRNA but also serves as a beacon, guiding future explorations in this intersectional research field. Our rigorous examination of studies promises a discerning perspective on the contemporary landscape of machine learning applications in siRNA design and function. This review is an effort to foster further discourse and propel academic inquiry in this multifaceted domain. Enveloped within the expansive discipline of RNA interference (RNAi) , the intMachine learning employs algorithms that improve automatically through experience . It is eIt is this synthesis of machine learning and siRNA, an emergent and vital topic, that captures our academic interest. As the landscape of machine learning continues to diversify and mature, and siRNA\u2019s influence in genetic research and therapeutic innovation becomes more profound, our review serves as a catalyst for fostering academic dialogue and nurturing exploratory research. Herein, we have carefully investigated studies published between 2019 and 2023 through Web of Science (WoS) using keywords of machine learning and siRNAs. The utilization of the WoS platform stems from its comprehensive incorporation of solely peer-reviewed journal articles of high quality. The specific timeframe of 2019\u20132023 was chosen not solely based on the quantity of research produced, but also due to the significant advancements in machine learning techniques, particularly deep learning methodologies, during this period.This academic landscape is mirrored by a discernible gap in research studies focusing on machine learning applications for siRNAs, as shown in In the course of our comprehensive review of recent developments in the application of machine learning for siRNAs, it is observed that an intriguing distribution of machine learning models were implemented in the examined studies. The predominant model of choice was the Neural Network (NN), utilized in a total of 10 studies, illustrating a preference for its ability to model complex non-linear relationships and its inherent aptitude for handling high-dimensional data typical in siRNA research. The Support Vector Machine (SVM) model was adopted in five studies, reflecting its well-regarded robustness and efficacy in dealing with both linear and non-linear classification problems. Meanwhile, the Random Forest (RF) model was employed in three studies, underscoring its suitability for managing multi-dimensional datasets with its ensemble-based approach and inherent feature selection mechanism. Lastly, the Partial Least Squares (PLS) model was applied in two studies, illustrating its utilization in situations where predictors are highly correlated, a common occurrence in biological data. The majority of studies employed correlation and least squares as performance metrics in their analyses. Notably, some studies deployed multiple models, acknowledging the unique strengths of each model and adopting a more holistic, hybrid approach to tackle the multifaceted complexities inherent in siRNA design and analysis.Machine learning has emerged as a crucial tool in the field of siRNA research, facilitating nuanced investigations into the complex dynamics of siRNA. Two particularly salient areas of exploration are the prediction of siRNA efficacy and the elucidation of off-target effects. A comparative analysis of the studies by in silico prediction of siRNA ionizable-lipid nanoparticles\u2019 in vivo efficacy. The authors adopted an array of machine learning techniques, including Artificial Neural Networks (ANNs) and SVM, for Quantitative Structure-Activity Relationship (QSAR) modeling, signifying a broader perspective of machine learning implementation. Notably, their model successfully predicted the siRNA dose, with ANNs delivering the most robust performance.On the other hand, Exploring off-target effects and RNA production regulation, in vivo efficacy of siRNA nanoparticles. Further, machine learning proved to be instrumental in understanding off-target effects and RNA production regulation, demonstrating the versatility and potential of these techniques in decoding the complexities of siRNA.Both the methodological approaches, i.e., GNN and ANNs/SVM, show significant potential in siRNA research, albeit in different contexts. While GNN exhibited a superior ability in siRNA-mRNA interaction analysis, the versatility of ANNs/SVM was beneficial in predicting The integration of high-throughput screening in siRNA studies has ushered in a new era of comprehensive insights into cellular behavior and mechanisms under the influence of genetic modification. These following articles underscore this trend, showcasing how machine learning techniques are employed to delve deeper into proteome regulation, cellular delivery, and phenotype expression.On the other hand, Two recent studies provided insights into the usage of machine learning for precision delivery and phenotype assessment in siRNA studies, respectively. These studies underscore the significant potential of machine learning, from neural networks to principal component analysis, in advancing siRNA research. Whether it is the identification of new cellular pathways, the precise delivery of functional molecules, or the high-throughput screening of phenotypes, machine learning methodologies emerge as vital tools, showcasing the increasing intersection between computational and biological sciences.Biomedical research has witnessed the transformative potential of machine learning, catalyzing breakthroughs in disease diagnosis and prognosis. Two notable applications of these technologies involve the identification of prognostically significant genes in cancer and the discovery of diagnostic gene biomarkers. In these contexts, the incorporation of deep learning methods has yielded significant insights.The study by in vitro. This study is a compelling example of how machine learning can drive novel insights in diagnostic biomarker discovery and influence therapeutic strategies.On the other hand, Both studies demonstrate the profound potential of machine learning in the exploration of disease genetics, either in a prognostic or diagnostic capacity. However, the approaches vary in their specificity. The approach by 2, encapsulating both curcumin and Bcl2 siRNA. The promising results obtained underscore the potential of deep learning models in predicting siRNA delivery and release patterns, thus potentially revolutionizing the design of more effective siRNA delivery systems.The convergence of deep learning and machine learning techniques is propelling siRNA research, particularly in designing efficient delivery systems and accelerating the drug discovery process. As exemplified in the study by On the other hand, The rise of machine learning techniques has brought about a significant paradigm shift in siRNA research. Recent investigations have successfully harnessed both traditional machine learning and deep learning approaches to address challenges and answer pivotal questions in the field. This subsection provides the recent trend of emerging machine learning methodologies in siRNA studies, focusing on their unique applications, effectiveness, and particular roles in advancing siRNA research.In relation to nanopore technology, Penguin and SequMeanwhile, In conclusion, the application of machine learning, from traditional algorithms to deep learning methods, is proving vital in various aspects of siRNA research, including structural profiling, prediction of vsiRNAs, cellular uptake prediction, and identification of mRNA cleavage sites. Although the methods and applications vary, the overall advancement in the field signifies the transformative potential of machine learning in this area. The comparison further highlights the benefits of non-linear and deep learning models over traditional linear models in terms of predictive accuracy and versatility, leading to valuable discoveries in the field of siRNA research.The confluence of machine learning and siRNA research has already brought to light numerous applications and technological advancements. From predicting siRNA efficacy and off-target effects, to uncovering cellular processes involving siRNA and elucidating the role of siRNA in diseases, the combination of these fields has opened up new avenues for scientific exploration and innovation. However, similar to all emerging fields, it comes with its own set of unique challenges and limitations.The application of machine learning techniques in siRNA research is hampered by the lack of expansive, high-fidelity datasets. This is a common problem in many machine learning applications, but it is particularly pronounced in the field of biological research, where experimental data can be costly and time-consuming to generate. However, as techniques such as high-throughput screening continue to advance, the availability of high-quality datasets for siRNA research is expected to increase. Moreover, strategies such as transfer learning and data augmentation could be leveraged to overcome the scarcity of data and enhance the learning capacity of machine learning models. As an alternative approach, the high-content screening techniques proposed by Another significant challenge is the inherent complexity of biological systems. The multitude of interacting factors and the non-linear nature of biological processes pose significant difficulties for the construction and optimization of machine learning models. However, novel machine learning methods, such as GNN and deep learning , have deFinally, the lack of interpretable machine learning models in this field is a crucial area that needs to be addressed . DespiteWhile challenges and obstacles lie ahead, the potential rewards of integrating machine learning and siRNA research are vast. It is our hope that this review will provide a useful roadmap for future researchers navigating this exciting and rapidly evolving field.In conclusion, the fusion of machine learning and siRNA marks a promising Frontier in the realm of RNA interference. Although faced with challenges, such as the need for large, high-quality datasets and the intricate nature of biological systems, the continued development of advanced machine learning models and feature engineering techniques offers an optimistic outlook on the field\u2019s future.The rapidly evolving landscape of machine learning necessitates frequent and thorough investigation of recent studies, particularly when coupled with the emergent field of siRNA. This review has thus aimed to provide a comprehensive, timely exploration of these two intertwined fields, bridging the gap between computational advancements and biological complexities. It is our fervent hope that this work will serve as a foundation for future explorations and will inspire novel, cross-disciplinary endeavors."} +{"text": "Value in Healthcare, defined as the relationship between outcomes and costs , includiThe objective of this Research Topic was to contribute to the existing body of knowledge with a clear picture of the current scenario of the Value-Based approach in oncologic clinical practice to deliver sound experience on its impact, potential benefits, challenges to address, and future research needs.A total of 21 manuscripts were submitted, eleven of which were accepted.Most of the contributions aimed at evaluating the economic efficacy or the financial impact of single/combined treatments of cancer diseases with a particular public health burden.Bigi et al.); they analyzed a new tool to combine reported quality experiences and patient-reported outcomes .In other cases, authors shared the results of their research on the impacts of the application of effective models of value-based care ; a Value-Based approach to untangle the full benefit of HPV-related cancers elimination strategies and identify priority and best practices have been reported, respectively.Also, organizational and financing implications from reshaping the delivery of healthcare services according to a Value-Based care approach have been published. For example, studies on the experience of involving patients and professionals in a co-constructed therapeutic pathway , thus various conceptual frameworks have been proposed , and we tried to orient publishing according to validity, rigor, and relevance .We also tried to challenge the public health research community to address future research needs, such as refinement of performance indicators to include patients' perspective (PROMS/PREMS); implementation of shared decision-making as routine in clinical practice; reshaping of logistics and operations to respect the values of \u201cgreen\u201d care delivery; digital support for the implementation of Value-Based approaches; reshaping of reimbursement systems to bundled payments based on clinical outcomes.Indeed, we received a few feedbacks on some of these items.Value-based healthcare in oncology to improve the quality of care on an individual level and consider patients' concerns and needs; reduce unwarranted duplications and wastes in care provision via more regular or systematic assessment of the effectiveness of care and monitoring of disease progression; increase patient information, communication, and shared medical decision-making, thus paving the way for precision and personalized medicine.Thus, from a public health perspective and by considering the great expansion of the research community, particularly from emerging countries and low-income countries, it will be crucial for healthcare organizations to use AB: Writing\u2014original draft, Writing\u2014review and editing."} +{"text": "The biomedical application of optical spectroscopy and imaging is currently an active, developing area of research, supported by recent technical progress in the development of light sources and detectors. Furthermore, the development of portable and low-cost optical imaging systems shows strong potential for the implementation of these technologies in everyday life and the daily practice of clinicians. In recent years, many studies have demonstrated that the use of modern optical imaging methods in conjunction with a priori data, as well as advanced data mining approaches, can significantly improve the quality of the medical diagnostic services provided ,2.The probing radiation of optical diagnostic methods is scattered due to random spatial variations in tissue morphology. Detection of diffuse reflected or transmitted light can provide information on the scattering and absorbing components of biological tissue. Changes in tissue morphology, including hyperplasia, collagen degradation in the extracellular matrix, and an increase in the nuclear\u2013cytoplasmic ratio associated with the progression of various diseases, can affect the scattering signals. In addition, changes in hemoglobin-absorbing properties can assist with angiogenesis processes, the presence of tissue hypoxia and ischemia, etc. At the same time, incident radiation can excite biological tissue molecules, causing fluorescent radiation. Most endogenous fluorophores are associated with the morphology of the tissue or with various metabolic processes responsible for the functional state of the tissue. Mitochondrial function is an important parameter of tissue viability. According to indicators of respiratory chain activity, it is possible to predict cell death, diagnose tissue ischemia, or, on the contrary, talk about its malignant activity. Additionally, the dynamic change of scattering centers of biological tissues probed by laser radiation leads to the formation of speckle fields, the study of which makes it possible to obtain perfusion (blood flow) maps in various anatomical areas. Thus, biophotonic methods can provide unique opportunities for structural and functional analysis of biological tissues, as well as for early and non-invasive diagnosis and monitoring of the effectiveness of therapy in various diseases .Biophotonics has broad prospects for development, since relatively cheap optical technologies allow images to be obtained and human tissues and organs to be influenced in real time with micron resolution and without the use of ionizing radiation. These technologies have found numerous applications in scientific research and clinical practice: dynamic light scattering methods . The speJ. Sachs et al. evaluated the possible impact of dual-energy computed tomography (DECT) on cataract formation . The aut2) as a reference standard. The high correlation coefficients were shown between the measurements of the perfusion parameters using IOFF and TcPO2. This study demonstrates that the IOFF method allows the identification of patients with a critical decrease in TcPO2 < 20 mmHg with sensitivity and specificity of 85.7% and 90.0%, respectively.P. Glazkova et al. studied the possibilities of incoherent optical fluctuation flowmetry (IOFF) to analyze the perfusion of foot tissues in patients with diabetes mellitus . PerfusiThe work of E. Zharkikh et al. focuses on studying microcirculation features in patients who underwent COVID-19 using novel wearable laser Doppler flowmetry (LDF) devices . In patiIn a study by E. Cinotti et al., the use of line-field confocal optical coherence tomography (LC-OCT) for the diagnosis of skin cancer was demonstrated . LC-OCT in vivo experiments in human skin. The new method showed high stability to instrumental disturbances introduced into the source and detection channels, while the traditional single-slope approach demonstrated stability only to perturbations in the source channels.Two studies were devoted to the use of diffuse reflectance spectroscopy (DRS). V. Perekatova et al. reported on the comparative study of self-calibrating and single-slope DRS in terms of stability against various measurement disturbances . The autIn another study A. SelifFinally, I. Zlotnikov et al. demonstrated the use of confocal laser scanning microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR) to study the interactions of antibacterial drugs with bacterial cells . More spThus, this Special Issue contains new developments and advanced ideas pertaining to optical spectroscopy and imaging for active translation to biological and clinical practice. The published manuscripts provide new insight into state-of-the-art modern methods of biomedical optics and expand readers\u2019 knowledge of the possible areas of their application.The peculiarity of biophotonics is that it combines physics, biology and medicine. The interdisciplinarity of biophotonics allows scientists from different fields to unite and collaborate to solve complex problems. Biophotonics and related fields are continuously developing and will undoubtedly become the main avenue for the development of biomedical engineering in the coming decades."} +{"text": "Broadly speaking, forensic psychiatry is the scientific study of the relationship between mental disorders and criminal behavior in a forensic context, and the application of psychiatric knowledge to crime, criminal and civil law, and the impact of law on human behavior. Psycho-criminology (or simply as psycho-criminology) is generally concerned with the use of psychological knowledge and skills in explaining, describing, and potentially preventing deviant, delinquent, and offending behavior \u20136. More The emphasis of this Research Topic (RT) focuses on the application of psycho-criminological approaches and constructs to criminal behavior and mental health in forensic settings. There are six articles included in this RT, which explored various features of crime and delinquent/criminal behavior through the application of psychological and criminological concepts and theories. Contributions to this RT are geographically diverse, with topics covering Africa (Nigeria), Asia (Hong Kong and mainland China), Europe (the UK), and the Middle East (Iran). More importantly, the collection of these articles addresses varied features of deviant and criminal behavior , delinquency and crime , and in the forensic settings .Shek et al.. This article examines the relationship between family functioning and adolescent delinquency, and the mediating role of positive youth development (PYD) attributes on this relationship. Analyzing a two-wave short-term longitudinal data (6 months apart) collected from 4,922 mainland Chinese adolescents, findings are that family functioning at the initial period (Wave 1) were negatively associated with the level of and change in delinquent behavior at the subsequent period (Wave 2), and PYD attributes (Wave 2) are found to mediate this relationship. Also, the general strain theory was tested by Wang et al. by surveying 687 mainland Chinese inmates recruited from 60 prisons, who were former public officials convicted of corrupt behaviors. They aim to explore the potential mediating effect of strain on the public officials' corrupt behaviors. Their findings indicate that clerks (a higher rank) and non-clerks (a lower rank) tended to have different experiences of status-related strain and personal financial strain, but it is the work-related strain that significantly distinguishes them. Compared to non-clerks, the work-related strain has more significant impact on clerks.The first article in this RT is an empirical study of family functioning and adolescent delinquency in a large sample of mainland Chinese adolescents by Chan recruited a nonclinical sample of 863 young people aged 17\u201320 years to examine the psychosocial risk factors of low self-control, risky sexual behavior (RSB), and paraphilic interests. Men are found to have significantly higher levels of threat of sexual assault and of general as well as of 12 subtypes of paraphilic interests than women, while women have a higher level of paraphilic interest on transvestic fetishism than men. Low self-control and more RSB and paraphilic interests are generally significant predictors of sexual assault threat issuance and perpetration of both penetrative and nonpenetrative sexual assault. Next, Ghazanfari et al. recruited a randomly selected sample of 259 male prisoners in Iran to examine their psychological wellbeing, family cohesion, and purposeful life. They found that the inmates' psychological wellbeing is significantly positively associated with their family cohesion, but both psychological wellbeing and family cohesion are not significantly correlated with their sense of a purposeful life.Examining the dynamics of sexual offending among youth in Hong Kong, Lilley et al. sampled a group of 108 jury-eligible university students to partake in one of nine identical 12-person mock trial simulations depicting a videotaped stage-setting of an intimate partner rape trial. Investigating the role of jurors' traits of psychopathology, crime-specific attitudes, sexual victimization experience, and demographic characteristics, the authors found that rape myth beliefs and juror ethnicity are positively associated with verdict decisions both pre- and post-deliberation. Besides, a diminished affective responsiveness (empathy) and experience of sexual victimization significantly predicted guilty verdict selections by the participants in the post-trial deliberation. Similarly, from a legal perspective, Ogunwale et al. critically examined the insanity plea in the Nigerian legal system. Adopting reform-oriented and fundamental legal research and psycho-legal formulated illustrative cases, the authors contend that there is a misalignment between the subjective experience of the mentally ill defendant and the objective judicial unawareness of the defendant's psychiatric conditions in some cases in Nigeria. As a result, a potential miscarriage of justice can occur. Hence, the authors argue for a reform based on current multidisciplinary knowledge whereby mental health professionals should be involved in all insanity plea cases.In the UK, Based on studies conducted in different countries, this RT collectively demonstrate the significance of applying psycho-criminological knowledge to advance our understanding of the fundamental mechanisms related to offending behavior in the intersections of mental health and the law, especially in the forensic setting. In this emerging subdiscipline of psycho-criminology, it is utterly imperative to continue moving forward with more international research to advance our knowledge and contribute to the repertoire of literature, which can have implications for research, practice, and policy development or refinement. Importantly, given the geographically diversified studies in this RT, it is noteworthy to acknowledge the importance of cultural influences wherein culturally adapted psychiatric and psychological interventions should not be neglected .The author confirms being the sole contributor of this work and has approved it for publication."} +{"text": "Mouse models have improved our understanding of mammary gland growth and development under the control of endocrine signals.Micro RNAs (miRNAs) can influence the effects of hormone axes and protein families in the mammary gland.Due to the presence of miRNAs in exosomal vesicles, miRNAs can be exported from the mammary gland to peripheral and central tissues of the animal or to suckling offspring.It is necessary to identify the biological effects of milk miRNAs in the offspring but also in human consumers of dairy products, the latter can be considered a critical issue of food safety.The insulin-like growth factor (IGF) system represents an important effector of mammary gland growth and development. Notably, in the mouse mammary gland, the IGF system integrates signals from growth hormone (GH) and prolactin. Within the cell, the IGF system impacts the pathway activating protein kinase B (AKT) and mammalian/mechanistic target of rapamycin (mTOR), which also mediates metabolic signals . AccordiIn the absence of the GH/IGF system, virtually no postnatal growth is observed in vertebrates. Accordingly, this system represents the most important endocrine system for controlling somatic growth. Under the control of GH and IGF, both cell size and cell number can be increased, thus defining the central parameters of tissue size. GH is produced in the pituitary gland and has direct effects on its target cells or tissues. In addition, GH can induce gene expression of IGF1 and thus impact growth by IGF-dependent mechanisms. Furthermore, tissue specificity is due to differential expression of IGFBPs, IGFBP-proteases, inhibitors of IGFBP-proteases, and calcium, as we rule out further down. In mice, IGFs, IGFBPs, and IGF1R are expressed in the virgin and the developing mammary gland, and cell-specific expression patterns have been described for IGFBPs . The perThe origins of life can be attributed to the inherent feature of RNA molecules to form comparably stable RNA/RNA structures . AccordiRNAhybrid (https://bibiserv.cebitec.uni-bielefeld.de/rnahybrid/), interactions of miRNAs also with exonic mRNA can be postulated, which is provided as an example for different IGFBP4 RNA transcripts (https://www.ensembl.org/). Except for IGFBP1 and IGFBPL1, the members of the expanded IGF system are putative targets of several miRNAs, and several miRNAs regulate multiple members of the expanded IGF system. The greatest degree of interaction between miRNAs, published by Wang et al. (Intricate interactions of both systems during mammary gland development in mice can be deduced from the study of Wang et al. , demonstnscripts extracteg et al. , and theg et al. . Notablyg et al. .In contrast to classical hormones, the specificity of miRNAs is expressed on a much lower level since miRNAs can have thousands of putative gene targets . The lacIn the signature of 11 miRNAs regulated during mammary development in mice , mmu-miRA direct link from miRNA to mTOR signaling has also been established for two additional members of the miRNA signature provided in Finally, the effects of regulated miRNAs on the IGF system might not only affect the development and function of the mammary gland in female mice but also have implications for distant tissues . Indeed,A crucially missing piece of the puzzle of IGF-dependent control of mammary growth and development was provided by the integration of the metzincin family members PAPPA1 and 2 into the current concept of an expanded IGF system. It is thus possible to describe the interactions of IGFs and IGFBPs and longitudinal control of IGF-related activity by PAPPAs and STCs during growth and involution of the mammary gland in mice. Since metzincins can bind zinc and calcium , we need"} +{"text": "The Fort McMurray wildfire (2016) was one of the most expensive and devastating natural disasters that ever happened in the history of Canada. According to the Insurance Bureau of Canada (2016), the cost of this disaster was estimated at USD 3.6 billion in insured losses. Despite the fundamental role of resilience in the daily functioning of individuals in the form of a protective shield that ameliorates the devastating impact of disasters on their mental well-being, to date, the long-term impact of wildfires on resilience and its associated predictors of low resilience has not been well studied and evaluated.The study aimed to enhance the understanding of the psychological impact of wildfires through the evaluation of the prevalence and predictors of resilience among the affected residents of Fort McMurray five years after the devastating wildfires.This study applied a cross-sectional survey design which was used to gather quantitative data through an online-based self-administered questionnaire. The surveys included standardized rating scales for resilience (BRS), depression (PHQ-9), anxiety disorder (GAD-7), and post-traumatic stress disorder (PTSD) (PCL-C) was used to measure the prevalence of resilience and its demographic, clinical, as well as wildfire-related predictors. The data collection spanned between April and June of 2021. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 25 and univariate analysis with done using a chi-squared test and binary logistic regression analysis.A total of 249 residents accessed the online survey and 186 completed the survey. Therefore, there was a response rate of 74.7%. Most of the respondents were females , above 40 years of age , employed , and in a relationship . The study identified two variables, thus having PTSD symptoms , and the age of respondents significantly predicted low resilience in our sample. The prevalence of low resilience in our sample was found to be about 37.4%.The study finding demonstrated that age and the presence of PTSD were the independent significant risk factors associated with low resilience in the affected population of Fort McMurray five years after the devastating wildfire disaster. This result further provides new information about the association between resilience, demographic, and clinical characteristics while adding to the rising body of evidence on the benefits of resilience in individuals during and after disasters. However, further research is needed to enhance understanding of the pathways toNone Declared"} +{"text": "Cardiac involvement results in an infiltrative cardiomyopathy that leads to progressive heart failure and carries a high rate of morbidity and mortality , 2. The The prevalence of ATTR-CA in the Middle East, and particularly in the largest country that is Saudi Arabia is significantly underrepresented in the literature. What is clear is that this condition remains underdiagnosed, and the vast majority of patients go undiagnosed. Recent studies conducted in the Middle East and the Gulf region demonstrate significant shortcomings regarding the diagnostic modalities and therapeutic approaches for cardiac amyloidosis, mainly due to a lack of awareness among health care professionals , 11. SucThe objectives of this manuscript are to highlight the magnitude of the under/misdiagnosis of ATTR-CA in Saudi Arabia and neighboring Gulf countries and to explore the barriers that impede the proper diagnosis and management of ATTR-CA in the region.2.2.1.In order to highlight the magnitude of the underdiagnosis of ATTR-CA in the Middle East and Gulf region, we extrapolated the projected prevalence of ATTR-CA in Saudi Arabia. Published epidemiological studies in Saudi Arabia indicate a case burden for chronic heart failure of approximately 455,222 cases, and thus a prevalence of 1%\u20132% in the general population , 13. WitThe estimation of ATTR-CA case burden in Saudi Arabia has several shortcomings. First, our approximation does not take into account the gender preponderance of ATTR-CA among males or the influence of age as the disease increases in incidence with age, since the HEART registry did not factor in either parameter. Second, the projected estimation does not include the prevalence of ATTR-CA amongst patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Several studies have previously highlighted an association between ATTR-CA and severe aortic stenosis in elderly patients being relatively common with an estimated prevalence of 8%\u201315% , 17. HowTo our knowledge, there are no published studies that have evaluated the incidence or prevalence of cardiac amyloidosis in Saudi Arabia. Furthermore, our search results utilizing Pubmed and Medline databases have not yielded any current population or cohort-based studies relating to ATTR-CA within the region. We hypothesize that the discrepancy in the expected prevalence of ATTR-CA when compared to the literature emerging from the region is likely due to shortcomings in the diagnosis of cardiac amyloidosis rather than lower rates of prevalence.2.2.This section addresses the possible shortcomings and barriers regarding the diagnosis of ATTR-CA and highlights the practical applications to overcome these issues within the region. ATTR-CA is a disease with a high misdiagnosis rate up to 34%\u201357% of patients . MoreoveTwo recent physician surveys have investigated the barriers to the diagnosis of cardiac amyloidosis in the Middle East , 11. FinMultidisciplinary education campaigns and meetings are essential to familiarize physicians with the clinical, biological, and imaging clues that should prompt further investigations for the disease. Additionally, subgroups of patients such as those with left ventricular hypertrophy, HFpEF, and those with low flow low gradient aortic stenosis requiring TAVR should be identified and further screened for ATTR-CA. A recent scientific statement from the American Heart Association (AHA) has identified clinical and imaging clues that should prompt further investigation(s) for CA can be uAnother significant barrier to the diagnosis of ATTR-CA lies in the utilization of appropriate investigative tools. According to guidelines published by the AHA and European Society of Cardiology (ESC), patients with suspected ATTR-CA and without monoclonal gammopathy should undergo screening by cardiac radionuclide scintigraphy imaging , 9. HoweTTR gene that requires proper investigation (TTR gene mutations causing ATTR-CA (TTR variants in the region (TTR mutations, three TTR variants known to be associated with ATTR-CA and three novel variants were identified. However, the data identified in the study requires further clinical correlation.Since the hereditary form of ATTR-CA arises from a mutation in the tigation , an addi ATTR-CA , 20. Mor ATTR-CA . The fine region . Using dTTR variants associated with hereditary ATTR-CA and to detect the individuals carrying these genetic variants who are at risk of developing the disease. Moreover, individuals with confirmed hereditary ATTR-CA should receive counseling and their family members should be offered genetic testing in line with AHA and ESC guidelines. Hence, a multidisciplinary effort is required to provide access to genetic testing sites that are equipped with appropriate resources and are adequately staffed. Additionally, this setup would allow for the conduction of further genomic studies to identify potentially pathogenic TTR variants and simultaneous clinical investigations to validate the findings from these genomic studies.Based on the above data, collaborative efforts within the region among specialists in cardiology and genetic medicine are required to identify A pertinent approach towards overcoming the underdiagnosis of ATTR-CA in the region is underpinned by the utilization of regional patient registries and the subsequent establishment of nationwide screening programs. The use of national/regional patient registries may facilitate improved awareness of disease prevalence and incidence, enhance collaborative efforts and communication amongst clinical specialists, improve knowledge and awareness of the disease, facilitate the generation of referral and screening pathways, and enhance the cost-effectiveness of managing patients with ATTR-CA . PatientThe underdiagnosis of ATTR-CA in the region has resulted in significant shortcomings in the management of the disease. Physician surveys emerging from the region highlighted deficiencies in the awareness of the management modalities for ATTR-CA . The recThe application of AHA and ESC guidelines regarding the diagnosis and management of cardiac amyloidosis in the Middle East and Gulf region is likely to lead to significant advances in understanding the epidemiology and clinical features of the disease in the region, while concomitantly improving patient outcomes. However, the application of the aforementioned guidelines may prove challenging due to potential barriers. 3.Limited data are available regarding the prevalence, incidence, and clinical features of ATTR-CA in the Middle East and Gulf region. Based on international epidemiological studies, the majority of cases of cardiac amyloidosis in this region remain undiagnosed. Physician surveys conducted in our region identified key areas for improvement, particularly relating to awareness regarding the diagnosis and treatment of ATTR-CA. Collaborative efforts are required to promote disease awareness and improve physician knowledge regarding the epidemiology, clinical features, and management of ATTR-CA. Moreover, appropriately staffed national and regional specialized referral centers equipped with the relevant diagnostic modalities ought to be established within the region. Multidisciplinary teams consisting of clinical experts from various backgrounds should collaborate to develop clinical pathways to identify and investigate patient groups with high suspicion for cardiac amyloidosis. Implementing these measures would improve the diagnosis and management of cardiac amyloidosis in the region, thereby allowing for disease detection at an earlier stage and the utilization of targeted disease-modifying therapies."} +{"text": "Planetary health education focuses on the climate and ecological crises and their adverse health effects. Given the acceleration of these crises, nationwide integration of planetary health education into undergraduate and graduate education, postgraduate training and continuing education for all health professionals has repeatedly been called for. Since 2019, planetary health education has been promoted by several national initiatives in Germany that are summarized in this commentary:1. National Working Group Planetary Health Education,2. Manual for planetary health education,3. Catalog of National Planetary Health Learning Objectives in the National Competency-Based Catalog of Learning Objectives for Medical Education,4. Working Group Climate, Environment and Health Impact Assessment at the Institute for Medical and Pharmaceutical Examinations,5. Planetary Health Report Card, and6. PlanetMedEd study: planetary health education in medical schools in Germany.We hope these initiatives promote collaboration across institutions involved in educating and training health professionals, inter-professional cooperation as well as rapid implementation of planetary health education. Planetary health education focuses on the climate and ecological crises and their adverse health effects . Given tThe inter-professional working group, jointly hosted by the German Alliance on Climate Change and Health and Health for Future, was founded in February 2021 to provide a platform for knowledge exchange targeting all health professionals involved in planetary health education. The working group focuses on different aspects of planetary health education including presentations of innovative modular teaching materials and syllabi of elective courses as well as journal clubs covering seminal contributions to the field of planetary health education. The WeChange platform is used to network and to collect material pertinent to planetary health education.https://www.klimawandel-gesundheit.de/ag-lehre-mailingliste/]Sign up to the mailing list: [https://wechange.de/project/ag-planetary-health-lehre/]Sign up to the WeChange platform: . The latest version of the manual is available online . The catalog comprises learning objectives on clinical competencies for climate adaptation and climate-sensitive anticipatory guidance as well as skills supporting physicians in initiating and implementing change processes outside patient care that contribute to climate mitigation and sustainability. To promote the integration of planetary health education in all areas of medical education, the catalog contains cross references to the main chapters of the Competency-Based Catalog of Learning Objectives for Medical Education. The planetary health learning objectives can guide, inter alia, the development of longitudinal planetary health curricula or focus areas within medical curricula stipulated in the current version of the updated medical licensing regulations for Germany.The Catalog of National Planetary Health Learning Objectives was deveThe Institute for Medical and Pharmaceutical Examinations, developing and administering centralized state examinations for medicine, dentistry, pharmacology, and psychotherapy in Germany, founded the working group in January 2021. The inter-professional working group comprises external experts and aims at adding aspects of planetary health education to the syllabi of the state examinations.In this international initiative, medical students evaluate their medical schools based on standardized planetary health indicators covering the following areas: planetary health curriculum, interdisciplinary research, institutional support for student-led initiatives, community outreach and advocacy, and campus sustainability. https://phreportcard.org/]. While previously restricted to the USA, Canada, UK and Ireland, several medical schools in Germany have been evaluated based on the report card since 2021. The extension of the report card to curricula of other health professionals is currently prepared by the international PHRC team. The results of the assessment are published online on Earth Day every year: , , .The authors declare that they have no competing interests."} +{"text": "Assuring the quality of medical products manufactured, imported or distributed in francophone sub-Saharan Africa remains a challenge, despite positive signals like the growing engagement in the benchmarking of regulatory authorities and -particularly- in the establishment of the African Medicines Agency. In this short report, we describe the existing activities to prevent, detect and respond to substandard and falsified products (SF) in this region, either through African multilateral organizations and initiatives led by the World Health Organization, or through the contribution of other stakeholders, such as local universities and procurement agencies. We underline that these emerging local stakeholders may play a pivotal role to guide and inform the national regulatory authorities about the prevalence and patterns of SF medical products, complementing the market surveillance and control, and building awareness of the importance of pharmaceutical quality assurance for public health. Substandard and falsified products (SF) , 2 causeAfrican Union (AU) and the World Health Organization (WHO) started in 2009 the African Medicine Regulatory Harmonization (AMRH) Initiative; and in 2021, following the Treaty ratification by 15 member states, they started the establishment of the African Medicines Agency (AMA). Second, the Economic Community of West African States (ECOWAS) endorsed the West African Health Organization (WAHO) Strategic Plan 2016\u20132020 [West African Economic and Monetary Union [Medicrime Convention[Pharmaceutical quality assurance (QA) is high on the agenda of continental organizations, with important aspirational objectives. First, the 016\u20132020 , a Techn016\u20132020 promptedry Union . Finallyonvention.Member State Mechanism was established to tackle SF medical products from a public health approach [Global Benchmarking Tool (GBT) [Global Surveillance and Monitoring System [The approach . It is gol (GBT) . Currentg System , throughg System . HoweverUniversity of Senegal Cheikh Anta Diop and the University of Douala in Cameroon are among the first implementers of a curriculum guide on SF medical products, developed by WHO, International Pharmaceutical Federation, and others, targeting undergraduate pharmacy students [(West) African academics can contribute to the fight against SF medical products by educating future specialists and policymakers. The students .University of Kinshasa (UniKin) in the Democratic Republic of Congo built this capability by investing in academic partnerships, particularly with the University of Li\u00e8ge, Belgium. The UniKin QC laboratory, LACOMEDA, is accredited by the Ministry of Public Health for QA and QC of Health Products. It conducts high-quality research, based on a four-phases analytical methodology: a rapid field screening; a second screening in the vicinity; full chemical analysis at central level; and standardized findings\u2019 compilation. For the screening, the program uses portable vibrational spectroscopy tools, chosen based on performance, costs and field feasibility, and suitable for post-marketing surveillance and border screening. This model, where academia builds local capacity through international networks and produces rigorous research to guide policy-makers [Universities can also play a pivotal role to understand the prevalence and patterns of SF medical products. For instance, the y-makers \u201319, coulProcurement agencies may engage in surveillance. The Ecumenical Pharmaceutical Network (EPN), an independent, non-profit, Christian organisation committed to provide quality-assured pharmaceutical services, started in 2010 the Minilab project , and thePreventing, detecting and responding to SF medical products remains a challenge in Francophone sub-Saharan Africa, despite positive signals like the growing engagement in the WHO GBT process and the construction of AMA. The NRAs already engaged in the AMA should prioritize participation in technical committees, e.g., the AMQF-TC for market surveillance and control. Academic institutions and procurement agencies can effectively support surveillance, and they should systematically share their findings with NRAs. All activities should be framed in universal health coverage, as access to essential medicines will eliminate the demand for illegal markets."} +{"text": "Recent studies report a prevalence of comorbid anxiety disorder of 38% and 80% of sleep disorders in schizophrenia. Insomnia has been associated with worsening of psychopathological symptoms and increased hospitalization rates.The aim of our work was to review mechanisms of action and the use of benzodiazepines, GABAergic drugs and melatonin for the treatment of anxiety and insomnia in schizophrenia.We carried out a narrative review of studies focusing on the treatment of anxiety disorders and insomnia in schizophrenia through PubMed and Google Scholar (2002-September 2022). The use of benzodiazepines, GABAergic drugs and melatonin in schizophrenia are discussed, illustrating them with case reports.A total of 32 studies were included. (A)Benzodiazepines (BZD) work facilitating the inhibitory actions of gamma-aminobutyric acid (GABA) by binding GABA type A receptors. The beneficial effect of combined use of antipsychotics and BZD is controversial . (B)GABAergic drugs: gabapentin (GP) and pregabalin (PG) , have no direct GABAergic action and act inhibiting voltage-gated calcium channels. The efficacy of GP and PG in the treatment of anxiety symptoms in schizophrenia is understudied. Positive effects of GP in schizophrenia suffering from restless legs syndrome receiving clozapine. (C )Melatonin, an hormone produced in the pineal gland has been used to treat insomnia. Positive effects on metabolic syndrome and cardiovascular risk factors have been reported. Several works considered it an alternative in schizophrenia.Few evidence is available on the use of BZD, GP, and PG in schizophrenia. Melatonin is a promising compound to treat insomnia.None Declared"} +{"text": "The process of initiating and completing clinical drug trials in hospital settings is highly complex, with numerous institutional, technical, and record-keeping barriers. In this study, we independently developed an integrated clinical trial management system (CTMS) designed to comprehensively optimize the process management of clinical trials. The CTMS includes system development methods, efficient integration with external business systems, terminology, and standardization protocols, as well as data security and privacy protection.The development process proceeded through four stages, including demand analysis and problem collection, system design, system development and testing, system trial operation, and training the whole hospital to operate the system. The integrated CTMS comprises three modules: project approval and review management, clinical trial operations management, and background management modules. These are divided into seven subsystems and 59 internal processes, realizing all the functions necessary to comprehensively perform the process management of clinical trials. Efficient data integration is realized through extract-transform-load, message queue, and remote procedure call services with external systems such as the hospital information system (HIS), laboratory information system (LIS), electronic medical record (EMR), and clinical data repository (CDR). Data security is ensured by adopting corresponding policies for data storage and data access. Privacy protection complies with laws and regulations and de-identifies sensitive patient information.The integrated CTMS was successfully developed in September 2015 and updated to version 4.2.5 in March 2021. During this period, 1388 study projects were accepted, 43,051 electronic data stored, and 12,144 subjects recruited in the First Affiliated Hospital, Zhejiang University School of Medicine.The developed integrated CTMS realizes the data management of the entire clinical trials process, providing basic conditions for the efficient, high-quality, and standardized operation of clinical trials. Clinical trials of drugs are an important stage in drug research and development and are means to improve the development of medical science and technology \u20135. StandIn recent years, owing to the increase in clinical trial projects in our hospital, professional and standardized information systems were urgently needed to assist in the management of clinical trials throughout the hospital. At present, the need for a centralized clinical trial project management platform reliant on the clinical data system of the hospital itself is intensifying. Based on the local area network (LAN) security architecture of our hospital, we have constructed a CTMS, which organically integrates the clinical trial organization management office, ethics committee, clinical trial center pharmacy, and clinical professional departments. The management system covers the entire process of clinical trials, including trial project establishment, ethical review, signing of agreements, trial implementation, trial conclusion, sponsor management, subject management, follow-up management, and centralized management of pharmacies supporting medication trials. The personnel involved include clinical departments, institutional management offices, central pharmacies, and ethics committees. With the help of the information system, a large number of personnel and complicated work processes are organically integrated to realize information sharing and collaborative work. With the help of this CTMS, the implementation of clinical trials can be standardized and the entire process can be traceable. As a site of clinical trials, hospital management involves multi-party collaboration, as well as study project management, subject management, investigational product management, quality control, financial management, and other complex business processes. Hospitals must develop dedicated systems to assist the entire process management of clinical trials to ensure their efficient and high-quality operation. The main objectives of this study are as follows. We aim (1) to develop an integrated CTMS as a dedicated database for clinical trials; (2) to achieve efficient data integration of CTMS with hospital business systems , laboratory information system (LIS), clinical data repository (CDR), picture archiving and communication systems (PACS), and electronic medical record (EMR), etc.); (3) to facilitate standardization and consistency of terminology in the development of database models and business processes; and (4) to ensure the safety and security of clinical data as well as protect patient privacy to comply with relevant regulations.The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU) has six campuses with approximately 5,000 beds. In 2020, the institution recorded over 4.2 million outpatient and emergency visits, and 236,100 discharges. As one of the pioneering and earliest-founded National Drug CTIs in China, the first batch of clinical pharmacology bases under the Ministry of Health was established in 1998. As a first-class integrated service platform for clinical research in China, it operates 24 specialized groups and depends on an internationally recognized and independent ethics examination system, and has undertaken more than 2000 items of foreign and domestic clinical trials since its establishment, including both Phase I\u2013IV drugs and medical devices.The development of an integrated CTMS began in March 2014, and after 18\u00a0months, the first version of the CTMS was launched in FAHZU in September 2015. The complete system development process was carried out in four stages, including two months of requirement analysis and problem collection, four months of system design, six months of system development and testing, and six months of system operation training and pilot runs. Based on the feedback from the use of the first version of CTMS and the continuous in-depth exploration of the business, the system\u2019s functionality and user experience continue to be iteratively updated. By March 2021, the updated version 4.2.5 was launched. Through the construction of an integrated CTMS, the entire process of clinical trial data management is realized, which provides the basic conditions for the efficient, high-quality, and standardized operation of clinical trials in the hospital.The collection and analysis of CTMS requirements defined the existing problem set to be solved. This stage is the most critical and determines the final goal direction of the system. The collection of requirements started in March 2014, and the participants included the CTI office director, CTI office secretary, ethics committee (EC) members, EC secretary, principal investigator (PI), sub-investigator, study nurse, clinical research associate (CRA), clinical research coordinator (CRC), investigational product custodians, financial officer, quality control expert, statisticians, data manager, pharmacovigilance associate, and information technology expert. After two months of formal and informal interviews, as well as an analysis of the collection requirements, the design goal of CTMS was determined. The overall goal of the CTMS is to realize the entire process of clinical trial management, including study project approval, ethical review, subject recruitment, subject management, investigational product management, financial management, and quality management. Table In the second stage, the CTMS design process included the definition of the system architecture and data interchange mechanisms, selection of storage media, database modeling and standardization, user interface (UI) and user experience (UX) design, and development of security and privacy policies based on analyzing and categorizing the requirements collected in the first phase, referring to Good Clinical Practice (GCP) and the guidance documents of the National Medical Products Administration (NMPA). The functions and data required by each participant in the clinical trial are determined. Figure\u00a0The third stage focused on the development and testing of the CTMS. This was divided into two steps according to the definition of the design stage. The first step realizes clinical trial approval and review management, and the developed subsystems include CTPMS, CTEMS, and PMMS, which focus on the process management of the study project application and review stage, and do not involve data integration with external systems. The second step realizes clinical trial operational management. The developed subsystems include CTSMS, CTIPMS, CTFMS, and CTQMS, which complete internal function development and data integration with external systems, and realize the entire process of data management. The CTMS was developed based on the distributed architecture of the Java programming language, and its database is Oracle Database 11\u00a0g Release 2 on a server running the Linux CentOS 7.6 operating system; data integration with external systems is managed through an interface services unified management platform. The system adopts browser/server architecture and supports current mainstream browsers, such as Google Chrome, Internet Explorer, and Firefox Browser for encrypted access via hypertext transfer protocol secure (HTTPS). System testing mainly includes verification of functional effectiveness, data security, system reliability, and the efficiency of data integration with external systems.This stage involved CTMS deployment and system operation training. In November 2014, CTPMS, CTEMS, and PMMS were officially launched, realizing clinical trial approval and review management in FAHZU. In March 2015, the development of CTSMS, CTMMS, CTFMS, and CTQMS was completed. Considering that the clinical trial operational management involves data integrity verification and data integration with external systems, a new pilot run phase was needed. By selecting a certain number of clinical trials in Phases I\u2013IV, the operating results were used to verify the compatibility of the system with different types of clinical trials. The CTMS pilot run system first selects Phase I clinical trials and runs a total of 20 projects. Through continuous updating of functions during operation, it can fully meet the needs of Phase I clinical trial operational management. Subsequently, it selects clinical trials in Phases II\u2013IV. A total of 10 projects have been run, and the functions have been stable and meet the requirements of various types of clinical trials. However, training hospital staff in the use of CTMS is critical. Through a variety of methods including face-to-face training and offline data learning, all staff related to clinical trials have been trained. The first version of CTMS was fully launched in FAHZU in September 2015.FAHZU is the first hospital in China to independently develop an integrated CTMS; the system has been successfully implemented in the hospital since September 2015. As of March 2021, the hospital now runs an updated version of CTMS known as V4.2.5. The data management of the entire process of clinical trials from project approval and review management to operational management has been fully realized. The FAHZU CTMS operates independently by design as a fully functional system at the application level (not as a component of the HIS), establishes a dedicated clinical trial database at the data level, and completes data integration with external systems through a unified interface system, to achieve process continuity and data integrity. Through the construction of an integrated CTMS, the flow of multi-party collaboration tasks is optimized, and non-research matters such as finance and data processing are simplified, to effectively improve the efficiency and quality of clinical trials. The results shown below are based on the latest stable version of FAHZU CTMS, V4.2.5.The first level involves clinical trial project approval and review management, and its functions cover the rationality review of clinical trial study projects and related affairs management by CTI and EC. Table The second level comprises clinical trial operational management, which is a complex and continuous management process. Table The third level is backstage management, which is indispensable for the stable operation of the CTMS. Table FAHZU CTMS realizes the entire process management of clinical trials through the organic combination of project approval and reviews management, clinical trial operational management, and backstage entire process management, which is further categorized into 59 internal processes by combining user and authority management Fig.\u00a0. ClinicaTo use the CTMS as a dedicated database for clinical trials, data integration with external systems is indispensable. Figure\u00a0Data security and privacy protection ensure that a mature process is developed and maintained throughout the design life cycle. Data security primarily involves data storage and data access security. Privacy protection focuses on ensuring data security while complying with laws and regulations to de-identify sensitive patient information.Data security mainly includes the two aspects of data storage security and data access security. Interms of data storage security, FAHZU CTMS adopts two strategies: (1) multi-node storage of data to achieve high availability of data services and a data backup strategy to ensure that data will not be lost in case of failure, and (2) encrypted storage of sensitive data . Policies for data access security are (1) security at the network level, through safety equipment , to implement access control and prevent illegal access, (2) security at the application level through multiple roles of authority management system access controls on data content, especially including rules to ensure no open access to prescriptions (such as CRC non-prescription issuance authority) as well as finding and repairing the vulnerabilities of the application through penetration testing and completing the information security technology-evaluation requirement for classified protection of cybersecurity\u2014Level 3, and (3) maintaining a detailed data change log can be useful in tracing the record of the process of data recovery.Subject privacy protection aims to protect sensitive patient information through a series of de-identification processes, which are explicitly required in the GCP. The FAHZU CTMS strictly implements the requirements of subject privacy protection in the GCP guidelines and refers to the Information Security Technology Personal Information Security Specification issued by the Standardization Administration of China and the HIPAA Regulations issued by the U.S. Department of Health. Final compliance with HIPAA\u2019s Protected Health Information Disidentifiability Requirements Implementation Specifications excludes 18 personal health identifiers (PHIs) from the CTMS to comply with international and national laws. For CTMS users to identify subjects, we used the clinical trial protocol number, subject screening number, and subject name initials to uniquely identify them. At the level of data interaction, the patients\u2019 medical record numbers in the hospital are systematically encrypted and stored in the CTMS database, which is linked to the data of external business systems for automatic data transmission.The evaluation of the CTMS is ongoing and mainly conducted at two levels: clinical trial project approval and review management, and clinical trial operational management. The former focuses on the convenience of multi-party collaboration and the efficiency of project approval, whereas the latter focuses on the evaluation of subject-centered data management throughout the process and the improvement of the quality of clinical trials.The improved clinical trial project approval and review management after applying the FAHZU CTMS, compared with that before the system was implemented, mainly embodies the following advantages: (1) It realizes process automation management based on task and combined with workflow technology, cooperates with user authority management systems, realizes automatic triggering of node events, and performs automatic assignment of processing personnel and message notifications such that personnel only need to process their personal to-do lists according to the message reminder, reducing the complexity of system use under multi-party collaboration. (2) Clinical trial project approval supports remote application, electronic document management enables online submission of project approval materials as well as online review and summary of revision opinions in the review process, which reduces the workload of project approval materials review and improves the efficiency of project review. Since CTMS began to operate in the hospital in December 2014, 1,388 study projects have been accepted and 43,051 documents have been submitted through CTMS as of March 31, 2021.The focus at the clinical trial operational management level is centered on patient outcomes to achieve full-cycle data management. Here, the advantages are more significant. The core advantages are summarized as follows: (1) The CTMS requires that the research plan must be entered before the recruitment of subjects, and the visit content of the current visit cycle can be automatically correlated during the subject visit. It is transformed into to-do tasks in the current research stage, with timely reminders, reducing deviations from the protocol. (2) An independent billing model is adopted for clinical trial-related inspection and treatment expenses so that subjects can be exempted from expense reimbursement and be marked in the hospital business system to meet non-clinical trial diagnosis and treatment reminders and clinical trial inspection green special requirements such as channels. (3) The CTMS contains the data on each subject, including newly generated data during operation and data collected in the hospital business system. Through strict authority classification, the scope of the data queries, such as those issued by the CRC and other data query authorities, are limited to subjects who are responsible for the project. (4) Clinical trial drugs are label-based full-cycle closed-loop managed, and transfers are completed through label scanning, and support some special properties of clinical trial drugs, such as open, single-blind, and double-blind studies, and situations with other prescriptions, where drugs need to be random, and when the serial numbers and medicine need to be recalled.The clinical trial operational management of CTMS began a pilot run at FAHZU in March 2015. Pilot runs are conducted to validate and improve the effectiveness of system functions and compatibility with different types of clinical trials. Since September 2015, all newly initiated clinical trials on the site have been managed through CTMS. According to statistics, as of March 31, 2021, a total of 12,144 subjects have been included in the management of CTMS, across 472 study projects. Figure\u00a0Informatization is an inevitable trend in clinical trial management . At presThe protection of private information is a more important consideration than the system construction \u201312. The Compared with the traditional paper CRF, e-CRF allows researchers to enter the CRF electronically based on the source data rather than fill it in manually . HoweverIn future, we also want to utilize the data in the clinical trial management platform to realize intelligent subject recruitment and improve the efficiency of subject recruitment. Recruiting subjects for some clinical trials is difficult, especially those involving rare diseases, stringent admission criteria, and special subgroups. Owing to information asymmetry, researchers only know the condition of the patients they are treating, and patients do not know that their disease may be under research at the hospital, which can seriously affect the progress of clinical trials \u201319. To fSince the outbreak of COVID-19, many jobs around the world have been stalled to a certain extent. In the event of a major public health emergency, carrying out clinical trials and ensuring the smooth implementation of monitoring work has become a problem for clinical trial practitioners, and remote monitoring has therefore been put on the agenda. The U.S. Food and Drug Administration has long encouraged more centralized monitoring, where inspectors perform inspections in the office using relevant information tools rather than at research institutions . The development trend of clinical trial monitoring is to replace on-site monitoring with centralized monitoring . Remote Compared with other information systems, CTMSs are more professional and personalized. The realization of the effectiveness of a CTMS requires a significant amount of time, and the more clinical trials undertaken, the more significant the effect. Compared with the system design, the comprehensive and efficient application of the system takes longer to achieve. With the digitization of clinical research, the sharing and integration of research data will bring many management advantages, such as an increase in available management resources, scientific and data support for major decisions, the convenience of remote management, pertinacity, and pre-operation. The CTMS developed by our hospital will be constantly updated and upgraded, and its functions will constantly improve. The system update will keep pace with developments in international drug clinical trial management, promote the development of clinical trials in a more standardized direction, and promote the disciplinary status of the hospital regarding high-level clinical trials.The FAHZU CTMS, as the first integrated CTMS independently developed by a hospital in China, can better adapt to the institutional needs for individualized, whole-process, and dynamically comprehensive evaluation and supervision of clinical trials. The integrated CTMS contains three levels and seven subsystems, which fully realizes the whole-process data management of clinical trials from project approval and review management to operational management. Through the unified interface system, the developed CTMS provides a variety of access methods to complete efficient data integration with the clinical business systems, and applies multiple security policies combined with privacy protection methods to effectively ensure the security of data and the privacy of subjects during clinical trial operation. The operation results based on the integrated CTMS show that it can effectively control the risks in the clinical trial process, so as to improve the science, safety, and timeliness of the new drug development process."} +{"text": "Within FAR SEAS, a multi-component evidence-based community intervention was implemented and evaluated in Mazovia (Poland), with the aim of preventing alcohol-exposed pregnancies, and therefore preventing FASD.n = 441) to groups for low- (70%), moderate- (23%), or high-risk (7%) of alcohol exposed pregnancy, to provide interventions tailored to their needs. The non-parametric sign test, testing differences between pairs of observations before and after intervention was used to evaluate the outcomes.Multi-disciplinary professionals from different services , recruited women of child-bearing age (pregnant and not pregnant) in local communities, screened them for alcohol risk, and allocated participants (Follow-up data (collected from 93% of participants) indicated positive changes in the key outcome variables: risky alcohol consumption dropped by 81%, contraception use increased by 15% and visiting a gynecologist increased by 39%; as well as in associated psychosocial risk factors . No changes were noted in frequency of other service use . The most prominent changes were observed in the moderate-risk group.Changing risky behaviors to prevent alcohol exposed pregnancies is feasible at the local level, even without engagement of medical professionals. Key challenges, related to engaging professionals and local authorities, must be addressed; and procedures should be adapted to local contexts and needs. Alcohol consumption during pregnancy may result in a series of adverse effects to the fetus including congenital anomalies and behavioral, cognitive and adaptive deficits, collectively known as Fetal Alcohol Spectrum Disorder (FASD). FASD is preventable by abstaining from drinking alcohol during pregnancy but effective prevention is complex and requires activities at various levels, targeting general population, women of childbearing age, women with alcohol problems and postpartum . For thiThe region chosen for the pilot was the Mazovian voivodeship in central Poland due to: relatively high prevalence of alcohol consumption reported by Polish pregnant women .The small number of pregnant participants in the study does not allow conclusions to be drawn on the effectiveness of the FAR SEAS approach during pregnancy specifically . However, our findings do suggest positive influences of the interventions on the participants taken as a whole, especially those who drink alcohol at risky level and/or present other psycho-social risk factors of drinking alcohol during pregnancy, and therefore at higher risk of giving birth to a child with FASD .Given the importance of being able to target the intervention to the group most in need of support, i.e., women most at high risk of alcohol exposed pregnancy, the result indicating significant reductions in risky alcohol consumption among the high-risk subgroup is very promising. It is also important that the interventions offered to this group within the FAR SEAS project had positive effects on their domestic situation (reduced violence) and mood (depressive symptoms). However, more intensive or different interventions, or the engagement of other specialists are needed to improve their reproductive health , and to reduce other psychoactive substance use in pregnancy.The improvement of some health behaviors in the low-risk group, suggests a need for basic health education for the general Polish population, especially among women in childbearing age.The applicability of the study results to different populations and contexts may be limited by the uneven spread of participants across the different geographical and urban sites. An unstable social and medical situation at the time of the study made the recruitment of local stakeholders and individual specialists very difficult. Out of the six local teams that signed up for the project, only 4 teams were active, including 2 which were active only at a minimal level. In two other locations of the project (P\u0142ock and Radom), interdisciplinary teams of specialists were established to implement all the planned activities. Both highly active teams were led by people evidently well predisposed to this role: engaged, well organized, oriented to problem-solving and communicative , 57. In One other limitation of the study, which is encountered in many alcohol prevention interventions, is the reliance on self-reported data for alcohol use, which may result in a social desirability bias . In addition, the freedom of local staff in selecting the project participants, although reflecting natural context of their work, may be considered a limitation of the study. It is possible that, consciously or subconsciously, they introduced a bias by inviting women they feel they can more easily work with, who may not be those most in need of the intervention. This indicates the need of more rigorous training and enforcement of research experiment standards in future studies.The positive results of the pilot project indicate the feasibility and validity of implementing multi-center regional FASD prevention through inter-disciplinary teams at the community level. The most prominent changes in the prevalence of risky alcohol consumption were observed in the moderate risk group indicating potentially high returns on investment of addressing FASD prevention and interventions to this group; which should not be overlooked, despite the priority of focusing on women at high risk of alcohol exposed pregnancies. The results suggest an opportunity to build on the receptivity of women in the moderate risk group to prevention and advice, and that delivering timely interventions may prevent women from developing more risky behaviors leading to alcohol exposed pregnancies. Dissemination of FASD prevention at the local level requires the involvement of local authorities and directors of key institutions and coordinated work in a multidisciplinary team, which is one of the key facilitators of good implementation and sustainability of FAS/FASD prevention.The main learning points and findings from the FAR SEAS pilot study have been fed forward into the FAR SEAS Guidance, which comprises 22 evidence-based recommendations, validated through international expert consensus, aimed at reducing alcohol consumption in women of childbearing age, particularly in pregnant women.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study involving humans was approved by the Ethics Committee of State Agency for Prevention of Alcohol Related Problems (Poland). The study was conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants\u2019 legal guardians/next of kin.KO-K, LS-G, FB, CG, and ES contributed to conception and design of the study. KO-K and MZ-S organized the database. KO-K, SG, and MZ-S performed the statistical analysis. KO-K, FB, LS-G, and CB wrote the first draft of the manuscript and sections of the manuscript. FB, SM, KO-K, and LS-G supervised the project implementation. FB and SM administered the project. FB, SM, and KO-K acquired funding for the project. All authors contributed to manuscript revision, read, and approved the submitted version."} +{"text": "The aim of this article review is to analyze some models and clinical issues related to the implementation of accelerated diagnostic protocols based on specific cardiac biomarkers in patients admitted to the emergency department (ED) with symptoms compatible with acute cardiac disorders. Four specific clinical issues will be discussed in detail: (a) pathophysiological and clinical interpretations of circulating hs-cTnI and hs-cTnT levels; (b) the clinical relevance and estimation of the biological variation of biomarkers in patients admitted to the ED with acute and severe diseases; (c) the role and advantages of the point-of-care testing (POCT) methods for cardiac-specific biomarkers in pre-hospital and hospital clinical practice; and (d) the clinical role of specific cardiac biomarkers in patients with acute heart failure (AHF). In order to balance the risk between a hasty discharge versus the potential harms caused by a cardiac assessment in patients admitted to the ED with suspected acute cardiovascular disease, the measurement of specific cardiac biomarkers is essential for the early identification of the presence of myocardial dysfunction and/or injury and to significantly reduce the length and costs of hospitalization. Moreover, specific cardiac biomarkers are useful predictors of mortality and major adverse cardiovascular events (MACE) in patients admitted to the ED with suspected acute cardiovascular disease. To guide the implementation of the most rapid algorithms for the diagnosis of Non-ST-Elevation Myocardial Infarction (NSTEMI) into routine clinical practice, clinical scientific societies and laboratory medicine societies should promote collaborative studies specifically designed for the evaluation of the analytical performance and, especially, the cost/benefit ratio resulting from the use of these clinical protocols and POCT methods in the ED clinical practice. In September 2021, a systematic review by the Agency for Healthcare Research and Quality U.S. Department of Health and Human Services (AURQ Report) showed that (a) overall diagnostic accuracy in the emergency department (ED) is high, but some patients receive an incorrect diagnosis (~5.7%); (b) about 2.0% of these patients suffer an adverse event because of the incorrect diagnosis; and (c) about 3.0% of adverse events are serious (~0.3%) .,49.26,49Norman et al. assessedDawson et al. analyzedIn the last 5 years, three POCT hs-cTnI methods have become commercially available worldwide ,26,36,37\u00ae IM High-Sensitivity Troponin I (hs-cTnI) assay, Siemens Diagnostics, Marburg, Germany) for the rapid rule-out of AMI, using a single hs-cTnI measurement at presentation in patients presenting to an ED. Authors enrolled 1171 patients, including 97 (8.3%) with AMI, 78.3% of which were type 2 AMI providedThe implementation of hs-cTnI POCT methods requires not only a careful education of the personnel responsible for biomarker measurement, but also an accurate evaluation of analytical, clinical, and organizational issues related to the routine use of the POCT methods in the ED ,36,37,74HF represents a relevant public health burden in European and North American countries, considering the high risk of morbidity and mortality, particularly among patients \u2265 65 years ,75,76. IThe 2015 consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine, and the Society of Academic Emergency Medicine Acute Heart Failure has defined AHF as the new onset or worsening of symptoms and signs of HF with associated elevated circulating levels of natriuretic peptides . AHF is Several recent studies and two meta-analyses confirmed the relevance of the measurement of cardiac-specific biomarkers in patients presenting to the ED with acute dyspnea or AHF ,93,94,95The most important limitation of the clinical studies concerning the role of cardiac NPs in patients admitted to the ED with AHF is that these studies have commonly enrolled relatively small, selected patient cohorts. Specific clinical characteristics are prevalent in AHF patients ,78,79,80In 2022, a meta-analysis evaluated the NT-proBNP concentrations of 10,368 individual patients with AHF, with the purpose to develop and validate a decision support tool combining biomarker concentrations and clinical characteristics . In thisIn patients admitted to the ED with suspected ACS, including those with AHF, the measurement of hs-cTnI and hs-cTnT should be considered the first-line biomarkers, in order to identify the presence of myocardial injury and to quickly rule out ACS, leading to a significant reduction in the duration and costs of hospitalization ,101,102.According to the most recent clinical studies, high levels of both cardiac-specific biomarkers in AHF patients are consistently associated with an increased risk of morbidity and mortality, due to the combined presence of a severe reduction in cardiac function and myocardial injury (or even ACS) ,102,104.In order to balance the risk between a hasty discharge versus the potential harms caused by a cardiac assessment in patients admitted to the ED with suspected acute cardiovascular disease, the recent expert documents and guidelines recommend the measurement of specific cardiac biomarkers (NPs and hs-cTn) for the early identification of the presence of myocardial dysfunction and/or injury and to significantly reduce the duration and costs of hospitalization ,100,101.The very recent development of some POCT methods capable of measuring hs-cTnI (as well as NPs) represents a fundamental advance because these methods can significantly reduce the TAT of biomarker measurement ,26,36,37To guide the implementation of the POCT methods, capable of measuring both the specific cardiac biomarkers, into routine clinical practice, clinical scientific societies and laboratory medicine societies should promote collaborative studies specifically designed for the evaluation of the analytical performance and, especially, the cost/benefit ratio resulting from the use of the rapid algorithms for the diagnosis of NSTEMI and the use of POCT methods in the ED clinical practice."} +{"text": "Objective\u2003To compare the effects of expectant versus interventionist care in the management of pregnant women with severe preeclampsia remote from term.Data sources\u2003An electronic search was conducted in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature , World Health Organization's International Clinical Trials Registry Platform (WHO-ICTRP), and OpenGrey databases. The International Federation of Gynecology and Obstetrics , Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG), andColombian Journal of Obstetrics and Gynecology(CJOG) websites were searched for conference proceedings, without language restrictions, up to March 25, 2020.Selection of studies\u2003Randomized clinical trials (RCTs), and non-randomized controlled studies (NRSs) were included. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of the evidence.Data collection\u2003Studies were independently assessed for inclusion criteria, data extraction, and risk of bias. Disagreements were resolved by consensus.Data synthesis\u2003Four RCTs and six NRS were included. Low-quality evidence from the RCTs showed that expectant care may result in a lower incidence of appearance, pulse, grimace, activity, and respiration (Apgar) scores\u2009<\u20097 at 5\u2009minutes and a higher average birth weight . Very low quality evidence from the NRSs suggested that expectant care might decrease the rates of neonatal death , hyaline membrane disease , and admission to neonatal care . No maternal or fetal differences were found for other perinatal outcomes.Conclusion\u2003Compared with interventionist management, expectant care may improve neonatal outcomes without increasing maternal morbidity and mortality. Preeclampsia is one of the most important causes of maternal morbidity and mortality,Pregnant women with severe preeclampsia remote from term can receive expectant or interventionist care.Two recent systematic reviews with meta-analysesThe purpose of the present review was to compare the effects of expectant and interventionist care in the management of pregnant women with severe preeclampsia remote from term. We included RCTs and NRSs in which women with severe preeclampsia between 24 to 34 weeks of gestation were recruited. Expectant care was defined as a policy of delayed-interval delivery until a specific maternal or fetal indication or 34 weeks of gestation. The maternal primary outcomes included: death; eclampsia; HELLP syndrome; and placental abruption. The primary fetal outcomes were stillbirth; neonatal death; intraventricular hemorrhage (IVH); and small-for-gestational-age fetuses. For the women, the secondary outcomes were: an increase in the rate of Cesarean section; pulmonary edema; renal failure; and prologation of the pregnancy; for the newborns, they were low appearance, pulse, grimace, activity, and respiration (Apgar) score (at five minutes); respiratory distress syndrome; low birthweight; admission to neonatal intensive care unit (NICU); and bronchopulmonary-dysplasia.Colombian Journal of Obstetrics and Gynecology(CJOG) was hand-searched, and citation searches of included studies were screened for additional references. The experts in the field were contacted. No language or date restrictions were applied, and the search was conducted until 25 March 2020.An electronic search was conducted in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), and Latin American and Caribbean Health Sciences Literature databases. Furthermore, searches were conducted in the OpenGrey, International Federation of Gynecology and Obstetrics , Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG) websites for dissertations, theses, and conference proceedings, and in the World Health Organization's International Clinical Trials Registry Platform (WHO-ICTRP) for ongoing studies. TheThe authors of the present study independently screened all titles and abstracts for eligibility, extracted the data, and assessed the risk of bias. Disagreements were solved through consensus. Two authors (MAQ-O and CFG-A) entered the data into the Review Manager software and checked them for accuracy. The risk of bias was evaluated in accordance with the criteria proposed by the Cochrane Bias Methods group for RCTs and NRS .2) test and the I-squared (I2) statistic, and it was considered substantial if thep-value was lower than 0.10 in the \u03c72test, or if the I2was greater than 40%.The statistical analysis was performed with the RevMan software, using the Mantel-Haenszel fixed-effect model for dichotomous data and the inverse of the variance for continuous data, in which the trials were judged sufficiently homogeneous.The publication bias was to be explored through an assessment of funnel plot asymmetry and formal tests. However, because the present review included fewer than 10 RCTs and NRSs in the meta-analysis, this analysis was not performed. \u201cSummary of findings\u201d tables were prepared using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence.The searches yielded 2,098 references; after removing duplicates, 2,059 studies were screened. From these studies, 45 had their full texts reviewed. A total of 10 studies met the inclusion criteria: 4 were RCTs,The RCTs were conducted between 1990 and 2013, and they included studies from Egypt, South Africa, and the United States. One study recruited participants from different Latin American countries. The studies included 430 women with single or multiple pregnancies, regardless of parity, and with gestational ages at admission between 28 and 34 weeks. Three trialsExpectant management was characterized by bed rest and treatment with magnesium sulfate, antihypertensives, and glucocorticoids, followed by delivery only for specific maternal/fetal indications or completion of 34 weeks of gestation. The maternal indications for termination of pregnancy were uncontrollable hypertension, abruptio placenta, renal failure, HELLP syndrome, persistent severe headache or visual changes, or epigastric pain; the fetal indications for delivery were non-reassuring fetal status, and fetal growth restriction. Interventionist care consisted of induction of delivery from 24 to 48\u2009hours after complete fetal pulmonary maturation. For both groups, fetal wellbeing was assessed through the non-stress test, a doppler evaluation, and periodic ultrasound .The NRSs were retrospectiveExpectant care involved bed rest, daily recording of maternal weight, fluid balance, monitoring of the maternal blood pressure and of the urine output every four hours, the administration of magnesium sulfate or anticonvulsants ,For the generation of random sequences and allocation concealment, three trialsThe NRSs were judged to be at high risk for the confounding bias and selection bias domains. The cohorts were prone to exclusion of some eligible participants, and one or more prognostic variables could have predicted the intervention received. Regarding the classification of interventions, all NRSs were assessed as having a low risk of bias; it is unlikely that bias will be introduced by the differential or non-differential misclassification of the intervention status. The NRSs included were judged as high-risk for bias due to deviations from the intended interventions; there were some systematic differences between experimental interventions and comparator groups in terms of the care provided (such as corticosteroid administration). For the biases due to missing data and due to measurement of the outcome domains, all NRSs were appraised as low-risk. No individuals with missing data were included in the cohorts, and because the outcomes were objectively assessed, differential or non-differential errors in the measurement of the outcome data are unlikely. Finally, the protocols of the NRSs were not available, making the risk of bias for selective reporting unclear.2\u2009=\u2009not estimable), of HELLP syndrome , of pulmonary edema , or of stillbirth , because the quality of the evidence for these outcomes was low , of intraventricular hemorrhage , of hyaline membrane disease , and of admission to the NICU , and may not have any effect on maternal morbidity , but the quality of the evidence was low, and the results were imprecise.Expectant care may not decrease the rates of neonatal death and higher average birthweight . On average, expectant care may extend pregnancy by 1 week , and increase the risk of small-for-gestational-age newborns , with little or no effect on the rates of cesarean section .The newborns in the expectant care group may have a lower incidence of appearance, pulse, grimace, activity, and respiration (Apgar) scores\u2009<\u20097 at 5\u2009minutes , HELLP syndrome , and pulmonary edema . Expectant care had no clear effect on the incidence of placental abruption , or renal failure .Very low quality evidence from the NRSs showed that it is uncertain whether expectant care may increase the rates of: maternal mortality , the incidence of Apgar scores\u2009<\u20097 at 5\u2009minutes , and may result in a small increase in small-for-gestational-age newborns . Interventionist care may not reduce the incidence of stillbirth , but, once again, the results were imprecise.Evidence from the NRSs suggested that, compared with interventionist care, expectant management may not decrease the frequency of intraventricular hemorrhage and be effective in decreasing the rates of neonatal death , of hyaline membrane disease , and of admission to the NICU , with little or no effect on the rates of caesarean section .Very low quality evidence from the NRSs showed that expectant care may increase birthweight (MD: 144.2\u2009g; 95%CI: 20.7 to 267.8; 4 cohort studies; 285 newborns; IThe management of the women with severe preeclampsia remote from term is a challenge for the obstetrician, and requires weighing maternal and fetal risks and benefits.Some findings of the present review differ from those reported in other publications. One reviewAnother reviewThe present systematic review has some strengths,Despite its limitations, the present systematic review has some implications for the clinical practice. Low quality of evidence from the RCTs showed that expectant care may result in a lower incidence of Apgar scores\u2009<\u20097 at 5\u2009minutes and a higher average birthweight. Very low quality evidence from the NRSs suggested that expectant care may decrease the rates of neonatal death, hyaline membrane disease, and admission to the NICU. No maternal or fetal differences were found for other perinatal outcomes. More studies with higher methodological quality and with adequate sample sizes are required."} +{"text": "The foundations of Artificial Intelligence (AI), a field whose applications are of great use and concern for society, can be traced back to the early years of the second half of the 20th century. Since then, the field has seen increased research output and funding cycles followed by setbacks. The new millennium has seen unprecedented interest in AI progress and expectations with significant financial investments from the public and private sectors. However, the continual acceleration of AI capabilities and real-world applications is not guaranteed. Mainly, accountability of AI systems in the context of the interplay between AI and the broader society is essential for adopting AI systems via the trust placed in them. Continual progress in AI research and development (R&D) can help tackle humanity's most significant challenges to improve social good. The authors of this paper suggest that the careful design of forward-looking research policies serves a crucial function in avoiding potential future setbacks in AI research, development, and use. The United States (US) has kept its leading role in R&D, mainly shaping the global trends in the field. Accordingly, this paper presents a critical assessment of the US National AI R&D Strategic Plan and prescribes six recommendations to improve future research strategies in the US and around the globe. The roots of Artificial Intelligence (AI) as a research field are usually traced back to a workshop held in 1956 on the campus of Dartmouth College knowledge discovery from multi-modal, noisy, and big data; (ii) perceptual capabilities of AI systems via sensors and other means; (iii) understanding of theoretical limitations of AI concerning available hardware; (iv) general-purpose artificial intelligence that is capable of performing different kinds of tasks like humans do; (v) coordination of multi-AI systems; (vi) human-like AI that can learn from small sample sizes, and that can explain itself; (vii) robotic technologies; (viii) hardware specialized for AI; and (ix) AI for improving hardware design. This strategy mentions several vital concepts such as perception and attention, commonsense and probabilistic reasoning, combinatorial optimization, knowledge representation, natural language processing, and human-machine interaction as prioritized areas for fundamental AI research.The second strategy is concerned with developing effective methods for human-AI collaboration. The strategy suggests that many applications of AI will not be completely autonomous. Instead, a combination of AI and human systems will work together. An effective and efficient human-AI collaboration requires additional R&D. The strategy highlights some development challenges: (i) human-aware intelligent systems that are capable of intuitive interaction with humans; (ii) AI techniques that enhance human capabilities, for instance, through wearable devices; (iii) human-AI interfaces to present increasingly complex data in a human-understandable manner; and (iv) better language processing systems that overcome current challenges such as noisy surroundings, heavily accented speech, impaired speech, and real-time dialogue with humans. The strategy also argues that trust in AI is necessary for human-AI collaborations, which is related to fairness, explainability, and transparency.The third strategy is concerned with understanding and addressing AI's ethical, legal, and societal implications. This strategy focuses on fundamental concepts such as trustworthiness, fairness, transparency, accountability, explainability, and ethics. The strategy presents three subsections to explore critical challenges: (i) incorporating fairness, transparency, and accountability in the design of AI systems, (ii) building ethical AI; and (iii) designing system architectures incorporating ethical reasoning.The fourth strategy is concerned with ensuring the safety and security of AI systems. The strategy emphasizes the vital role of safety and security in achieving robust and trustworthy AI systems. The strategy presents several challenges: (i) developing AI systems that are capable of explaining the reasons behind the outputs they produce; (ii) building trust in AI; (iii) enhancing verification and validation of AI systems by meeting formal specifications and user's operational needs, respectively; (iv) robustness against cyber-attacks; and (v) developing self-monitoring architectures for the safety of self-modifying systems.The fifth strategy involves developing shared public datasets and environments for AI training and testing. The strategy presents three critical areas of importance: (i) developing a wide variety of accessible datasets for the needs of the whole spectrum of AI applications; (ii) ensuring responsiveness of training and testing resources to public and commercial needs; and (iii) open-source software for making AI technologies more accessible. The strategy further stresses the importance of findability, accessibility, interoperability, and reusability principles for datasets and potential privacy and bias issues in datasets. Moreover, the need for computational resources to process data is underlined.The sixth strategy is concerned with measuring and evaluating AI technologies based on well-established standards and benchmarks. The strategy highlights several areas as needing further progress: (i) developing AI standards for the broad spectrum of AI; (ii) establishing benchmarks for evaluating AI and its compliance to the standards; (iii) increasing the availability of testbeds in all areas of AI; and (iv) engaging users, industry, government, and academia in standards and benchmarks. Further, the strategy calls attention to measuring and evaluating AI systems to assess and assure safety, security, privacy, robustness, explainability, transparency, and fairness.The seventh strategy is to understand better the national AI R&D workforce needs. It highlights the increasing demand for AI expertise and calls for improving the existing efforts for advancing the AI R&D workforce. The strategy explicitly mentions enhancing instructional capacity from K-12 to graduate level, nurturing computer scientists and experts from other fields such as cognitive science, economics, linguistics, and others.The last strategy concerns expanding public-private partnerships to accelerate advances in AI. The strategy explicitly states government, universities, and industry entities for public-private partnerships. The benefits of such collaboration include leveraging resources to push innovation, supporting the practices based on these innovations, and enhancing the training for future researchers and practitioners.The increasingly decisive role of AI in people's lives necessitates a sociotechnical viewpoint improving fairness, transparency, and accountability by design, (ii) building ethical AI, and (iii) designing architectures for ethical AI. However, as described in the Plan, these three challenges largely overlap without clear and intuitive distinctions. Also, explainability is discussed in the fourth strategy, which is concerned with the safety and security of AI systems. In contrast, this paper argues that it is more appropriate to discuss explainability concerning the other components of the third strategy and within its scope.Recommendation: The third strategy may be rewritten to present notions and challenges concerning social implications and accountability of AI systems, which include concepts such as responsibility, explainability, robustness, and fairness. It should also contain references to other related strategies, such as the second strategy on human-AI collaboration, the fourth strategy on privacy and security of AI systems, and the sixth strategy on developing methods, metrics, benchmarks, and standards to evaluate AI systems.VI. The trust to be placed in AI and its expanding role in society depends not only on the benefits of AI but also on its risks, potential harms, and remedies (Knowles and Richards, Recommendation: The Plan should support research initiatives that tackle questions related to understanding and operationalizing the risks and harms of AI systems so that risk ratings, certifications, and insurance become feasible for AI systems. This recommendation relates to Strategies 3, 4, and 6.V. The seventh strategy addresses the increasing demand for AI researchers and practitioners. While it acknowledges that the AI workforce is not composed only of computer and information scientists and engineers but also includes multidisciplinary teams, it appears to present the other fields and domains as areas \u201cin which AI may be applied.\u201d We suggest that multidisciplinary work where people from different disciplines work together is insufficient. Instead, an interdisciplinary and transdisciplinary approach (van den Besselaar, Recommendation: Considering the emerging intertwined nature of AI and human lives, the importance of cultivating an interdisciplinary and transdisciplinary AI workforce should be emphasized.VI. The eighth strategy supports expanding public-private partnerships focusing on government-university-industry research and development partnerships. Given the social implications of AI, civil society organizations play a relevant and valuable role in representing the expectations of the broader society.Recommendation: The eighth strategy should be expanded to include collaboration with civil society organizations, particularly concerning future developments regarding the societal implications of AI.The US is leading in shaping AI research and development trends globally. Such trends are highly relevant for the future of the field, especially to direct resources to prevent another AI Winter, improve social good, and ensure the safe progress of the society toward the new sociotechnical paradigm. Given this pressing issue, this paper investigates the official AI R&D strategies of the US government with a critical lens. It offers six recommendations to improve AI research strategies in the US and beyond.The first recommendation calls for more fundamental research on causality in AI. The second recommendation calls for a better understanding of and mechanism design for human oversight of AI. The third recommendation calls for a clear and comprehensive presentation of accountable AI to guide future research. The fourth recommendation calls for further efforts to facilitate risk ratings, certifications, and insurance for AI systems. The fifth recommendation calls for more interdisciplinary and transdisciplinary research. Finally, the sixth recommendation calls for the participation of civil society actors in AI research collaborations.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.FG and IK contributed to conception and design of the study, contributed to manuscript revision, read, and approved the submitted version. FG wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet.The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation.The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.The online version contains supplementary material available at 10.1186/s40249-023-01124-w. The One Health approach, centered around holistic thinking at the interface of humans, animal, and the environment, aims to promote the health and sustainable development of these sectors through multi-sectoral, interdisciplinary, and cross-border collaboration . It is aIn October 2022, the Food and Agriculture Organization of the United Nations (FAO), the United Nations Environment Programme (UNEP), the World Health Organization (WHO), and the World Organization for Animal Health (WOAH) jointly released the One Health Joint Plan of Action (OHJPA) [Supported by Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed by Shanghai Jiao Tong University in Shanghai China, with the aim of promoting the understanding, contribution and real-world implementation of the One Health approach towards the Sustainable Development Goals (SDGs). In order to strategize the construction of this academic community, a Scientific Steering Committee (SSC) was jointly formed up with a wide engagement of more than 26 experts and institutions over 18 countries and regions Providing high-quality scientific evidence through collaborative research, joint publications, and conferences on issues such as (re-)emerging infectious diseases, climate change, and antimicrobial resistance (AMR).(ii)Distilling local experiences and analyzing current One Health practices to prioritize national strategies and international collaborations.(iii)Fostering an interconnected One Health community, where partners have visibility of resources and policymakers have access to One Health solutions.The academic community can contribute to achieving the goal by:The academic community will develop a research agenda for global partners working in One Health and promote information sharing by providing a collaborative body for members. The academic community will also connect different disciplines and stakeholders at national, regional, and global levels to promote innovation in implementation and increase the impact of One Health work, including through cooperation with international organizations such as the WHO and the World Bank.The academic community also serves as an international exchange and cooperation platform for One Health solutions tailored for the diverse socio-ecological settings within the networks, which also provides an additional benefit to the inter-governmental collaborations that extend beyond the realm of One Health.Finally, the academic community will advocate for awareness of the links between human, animal, and environmental health and engage with policy makers at both national and international levels to promote the inclusion of One Health measures. The academic community will also collaborate with non-governmental organizations, academic institutions, and others in the public and private sectors to promote education and public awareness of One Health.The organizing structure of the academic committee has been proposed. A Strategic Consultancy Committee (SCC) and a Scientific Steering Committee (SSC) will be constructed to form the leadership of the academic community. The SCC, composed of high-level key opinion leaders, is responsible for developing strategic plans and action guides for the academic committee, supervising the work of SSC and secretariat and leveraging resources to catalyze the implementation of workplans. The SSC is composed of top-ranking academic experts, who have been selected from the One Health information database based onUnder the three goals of the academic community, six objectives have been developed: conducting collaborative research project (objective 1), expanding interconnected research network (objective 2), identifying and disseminating local cases (objective 3), promoting knowledge- and data- sharing platform (objective 4), fostering One Health culture and mindset (objective 5), and engaging broader partnership (objective 6). The workplan to achieve these objectives and goals is shown in Fig.\u00a0Based on overarching goals of the academic community for One Health action, research priorities to support the community will focus following five areas, including One Health governance, control of zoonotic infections, food security and food safety, control of AMR, and impact evaluation of climate changes on health.One Health governance refers to the development, implementation, and oversight of policies that support the One Health approach. It encompasses eight dimensions, including public participation, rule of law, transparency, responsiveness, consensus orientation, fairness and inclusivity, effectiveness and efficiency, and policy support . An effeA major challenge is the lack of coordination between different sectors and stakeholders . Many coTo address this issue, the academic community should facilitate the development of effective One Health governance frameworks that span multiple sectors and disciplines, drawing from lessons learned towards best practices. The academic community will also advocate for the establishment of a global governance framework for One Health, providing an international reference point for countries aiming to improve their own One Health governance.Zoonotic diseases are a high-priority target for the One Health approach. Zoonotic diseases are challenging for global surveillance, prevention, and control measures. One of the main factors is the emergence of these diseases, which highlights the need for a better understanding of the dynamics of pathogen spillover and transmission between animals and humans so that intervention strategies could be developed to zoonoses more effectively . AdditioTo address these challenges, the academic community will facilitate research to identify the drivers of zoonotic disease emergence and enhance surveillance and prevention strategies. This will require interdisciplinary collaboration among public health, veterinary medicine, wildlife ecology, and the social and economic sciences. The academic community will also strengthen countries\u2019 capacities to detect, report, and respond to zoonotic disease outbreaks by three activities: (i) expanding laboratory capacity, including improving laboratory professional level, building reference laboratory networks, standardizing standard operating procedures, etc.; (ii) improving disease surveillance efficiency, including applying innovative surveillance tools, enhancing surveillance and response systems, improving the surveillance evaluation approaches, etc.; and (iii) strengthening animal health systems, including enlarging animal surveillance networks, developing animal disease alarming system, optimizing animal health management, etc.Food security and food safety is a complex issue that affects all aspects of human life. It involves ensuring that people have access to sufficient, safe, and nutritious food that is appropriate for their culture and lifestyle . One of Currently, over 820 million people worldwide suffer from chronic hunger, while an additional 2 billion people suffer from malnutrition due to a lack of essential micronutrients in their diets . ClimateTo improve food security, the academic community will promote sustainable agricultural practices, enhance the resilience of supply chains to climate change and other shocks, reduce food waste, improving food safety, and enhance food accessibility. The One Health approach will address these objectives by working with organizations and governments to incorporate the interdependence of human, animal, and environmental health in their initiatives.AMR is a major public health threat and another key focus of the academic community. AMR occurs when bacteria, viruses, fungi, or parasites develop resistance to antimicrobial drugs, making it more difficult to treat infections . The misOne of the main challenges in addressing AMR is the lack of awareness and understanding among the public who access drugs over the counter, and healthcare professionals who administer them in bulk, both behaviors that contribute to resistance. Additionally, developing new antimicrobials is slow and costly, and even newly developed drugs can quickly become ineffective if they are similarly misused .To combat AMR, the academic community targets at educating the public and healthcare professionals about the risks of AMR and the importance of appropriate antimicrobial use, as well as improving access to diagnostic tests to ensure that antimicrobials are only used when necessary.In addition to these efforts, the academic community should work to improve surveillance and monitoring of AMR in various One Health components including wild life and migratory birds along with development of better methods for tracking the spread of resistant pathogens between animals, humans and ecosystems. The academic community also supports the development of rapid and cost-effective point-of-care testing AMR diagnostic technologies, alternative treatments, and vaccines to mitigate the impact of AMR. Through these efforts, the academic community hopes to slow the spread of AMR and preserve the effectiveness of crucial drugs.Climate change is one of the most pressing global challenges of our time. Its impacts are vast and far-reaching, affecting not only the natural world but also human health and well-being. Disadvantaged and vulnerable populations are disproportionately affected. Climate change exacerbates existing health problems and poses new risks, such as increased frequency and severity of extreme weather events, changing patterns of infectious diseases, and food and water insecurity . AddressThe One Health approach provides an essential framework for addressing the health impacts of climate change . Key strTo build an academic community for One Health action, four approaches have been proposed as follows.The academic community connects resources to support interdisciplinary research in the field of One Health. This includes advocating funding agency to put One Health on their high profile and linking funding opportunities to research projects that investigate the links between human, animal, and environmental health. Meanwhile, the academic community supports joint research programs and collaborations across different sectors and countries and also cultivate the research competitiveness for professionals in One Health to improve their capabilities to obtain funding and resources.The academic community serves as a bridge to translate scientific knowledge from research to evidence-based solutions for policy makers. Through applying both bottom-up and top-down approaches, the academic community supports implementation science to identify local needs and real gaps, and builds up dialogues between local practitioners, scientists, funders and policy makers. Meanwhile, the academic community can also contribute to developing innovative mechanisms to connect the local with the regional, and to scale up regional experiences to global policy agenda.The academic community supports training programs and other capacity-building initiatives to strengthen the research capabilities of individuals and organizations working in One Health fields. This includes training in research paradigms, methods, experimental practices, and data analysis, as well as the development of One Health related disciplines and research networks, with an emphasis on early career researchers and researchers from low- and middle-income countries.The academic community develops communication and engagement strategies to promote public awareness of One Health, and encourages diversity of the participants in One Health initiatives. It also coordinates stakeholders from around the world, together with representatives from the governments, non-governmental organizations, academic institutions, and the private sector, to promote One Health policies and practices.This article proposes to foster an academic community for One Health action, which is expected to incorporate the experience of a diverse variety of experts and stakeholders, who will be organized under the structure of SCC and SSC. Overarching research agenda followed by specific workplans and activities has been elaborated in this article, based on the exchanges and consensus of SSC. Multifaceted approach, that involves systematic thinking, evidence-based activities, transparent mechanisms, education, and communication, should be adapted profoundly in building up the community.With the tasks of promoting wider and deeper collaboration in research and practice, the community will contribute to producing novel scientific evidence, facilitating dialogues among different stakeholders, and advising for national and international policy, in its efforts to tackle global public health security at the human-animal-environment interface.Additional file 1: Table S1. The list of geographic distributions and research areas of Scientific Steering Committee (SSC) members of the proposed academic community"} +{"text": "The research area of adolescent health corresponds to the summary of a wide range of scientific interests and investigations, focusing on the first years of life of an individual . It has Health, and in particular adolescent health, are inexorably tied to the levels of physical activity and fitness; thus, a number of publications focused on this topic. Specifically, based on the 2018 Chinese National Student Physical Fitness Standard Test data, Tong et al., used a multi-scale approach to investigate the spatial heterogeneity and regional clustering of factors influencing Chinese adolescents\u2019 physical fitness, providing a national-level view . FurtherPhysical activities, such as the ones described above, are often identified as the visible expression of emotional adolescent health. Therefore, a few publications focused on emotions and emotional health. Using cross-sectional, survey-based data from Norway between 2017\u20132019, the association between physical activity organized in sports clubs, non-organized physical activity, other organized leisure-time activities, and depressive symptoms among adolescents were investigated . A diffeThe concepts affecting behaviors and perceptions were investigated further by four separate studies. In particular, the prevalence and predisposing factors related to self-medication among medical and pharmacy students in Serbia, as attitudes towards conventional and complementary medicine among future healthcare professionals can impact their future pharmacotherapy practice . A crossA third group of submitted manuscripts involved the perspectives of food and nutrition, in particular the teen-identified indicators of targeted food marketing, with a particular focus on the aggressive marketing of unhealthy foods . Two revThe fourth and final thematic group that emerged in the papers published as part of this Special Issue had a biological and molecular focus. This included two cross-sectional studies: one of ocular changes in adolescents with diabetes mellitus in health facilities in Ghana , and oneTaken together, the above provide a successful collection of research studies on adolescent health and highlight the necessary interdisciplinarity of the work required to address current scientific questions. The COVID-19 pandemic has acted as a catalyst , bringin"} +{"text": "The last decade has seen a noticeable upsurge in the use of biologics, including platelet-rich plasma (PRP), for applications in musculoskeletal regenerative medicine. Clinical trials, case series, systematic reviews and meta-analyses have shown the safety and efficacy of PRP for the management of several musculoskeletal disorders . Additio2) to tissues and carbon dioxide (CO2) from tissues to the lungs [2 and CO2. The typical life cycle of an RBC is 120 days, and RBC senescence is responsible for their removal from circulation by macrophages. The shear forces involved in whole-blood phlebotomy procedures or imperfect PRP concentration practices can cause damage to RBCs in PRP formulations. This results in the disintegration of the RBC membrane and the secretion of noxious hemoglobin, appraised as plasma-free hemoglobin, iron and hemin [RBCs are anuclear, comprise protein-bound heme, and transport oxygen , a potent cytokine . MMIF caIn addition, the function of RBCs in tissue regeneration is yet to be determined. There are no pre-clinical or clinical investigations assessing the efficacy of RBC-rich PRP compared to RBC-poor PRP. Thus, until the role of RBCs is established and the pros of including RBCs in a PRP formulation outweighs its cons, it is essential to reduce or eliminate the content of RBCs in PRP formulations to avoid the damaging effects of hemolysis and eryptosis on musculoskeletal tissues."} +{"text": "Disorders of sex development (DSD) are characterized by an atypical development of chromosomal, gonadal, and anatomic gender. DSD are divided to three classes with male normal, female normal and abnormal karyotypes and have an incidence at birth of approximately 1 in 5000. DSD patients are exposed during their long-term follow-up to severe psychological stress.The aim of our study was to determine the behavioral concerns of adults with DSD and to identify the major factors that may influence their emotional and psychological well-being.We explored, through our genetic counselling reports at the medical University of Sfax, the quality of life and the psychological concerns of all adults patients assessed for DSD with and without chromosomal and/or molecular genetic abnormalities. We also assessed their need of psychological support.During the last two decades of our genetic counselling experience, 46 adult patients (age superior to 18 years) were selected for this study. The analysis of data revealed that the major psychological concern in our DSD patients was related to their reproductive capacity. In contrast, they have poor subjective norms of communicating sexual and reproductive issues with their partners. Patients who presented non-corrected ambiguous genitalia were in the majority anxious and depressed with a constant feeling of social shame.Sex development plays a fundamental role in determining the physical attributes of the body, the structure of the brain, behavioral tendencies, and the self-concept. The clinical and social approaches of DSD conditions in our society need to be improved. Genetic and psychological counselling should thorough a deep medical education regarding reproductive and sexual health in each particular case of DSD. We emphasis, that early genetic diagnosis, involvement of patients and families in a patient-centered decision-making process, and consideration of long-term health-related quality-of-life outcomes should be considered in DSD.None Declared"} +{"text": "Negative symptoms has been classically associated with cognition, psychosocial functioning and quality of life in patients with schizophrenia. But negative symptoms are not a unitary construct, encompassing two different factors: diminished expression, and motivation and pleasure. Few works have studied the relationship between these two different negative symptoms factors and cognition , psychosocial functioning and quality of life, jointly, in patients with a first psychotic episode of schizophrenia.The objective of the present work was to study, in a sample of patients with a first psychotic episode of schizophrenia, the relationship between the negative symptoms (diminished expression and motivation and pleasure) and neurocognition, social cognition, functioning and quality of life.The study was carried out with 82 outpatients with a first psychotic episode of schizophrenia from two Spanish hospitals . The patients were assessed with the Clinical Assessment Interview for Negative Symptoms (CAINS) for evaluating diminished expression (EXP) and motivation and pleasure (MAP) symptoms, the MATRICS Consensus Cognitive Battery (MCCB) for evaluating neurocognition and social cognition, the Social and Occupational Functioning Assessment Scale (SOFAS), and the Quality of Life Scale (QLS).A negative correlation was found between neurocognition and the two negative symptoms subscales: CAINS-EXP and CAINS-MAP ; but with social cognition only CAINS-EXP was correlated . Also, it was found a high negative correlation between SOFAS scores and CAINS-MAP ; and a medium negative correlation with CAINS-EXP . Finally, QLS score was high correlated with both CAINS subscales: CAINS-EXP and CAINS-MAP .This study found a relationship between negative symptoms and neurocognition, social cognition, functioning and quality of life in a sample of patients with a first psychotic episode of schizophrenia. But the two different negative symptom factors, diminished expression, and motivation and pleasure, are associated differently with psychosocial functioning, but especially with social cognition where the relationship was only found with diminished expression symptoms.None Declared"} +{"text": "The situation that has been going on in Ukraine for the past six months has led to catastrophic consequences. This forces neuroscientists and, including psychiatrists, to turn to the study of the impact of all these events on the mental health of the population of Ukraine. In 90th of XX Russian psychiatrist Y. A. Alexandrovsky expressed opinion of presence the group of so-called social-stress disorders (SSD) that was determined like psychogenic-actual for most people in definite social, economic and political situation. Most of the people in Ukraine now experience both SSD and post-traumatic stress disorder (PTSD).Most of the people in Ukraine now experience both SSD and post-traumatic stress disorder (PTSD).The method of clinic-psychopathological interview with patients who applied out-patient consultation on the chair of psychiatry.The main changes in psychic state include following behaviors and clinical implications: loss of the value of human life, which is manifested in indifference to death in lowering caution when hazardous situations, willingness to sacrifice lives without any ideals. There is unrestrained lost for pleasure and moral promiscuity, exacerbation of personality typological traits, development of hyperstenic reactions (to self-destructive non-expedient behavior), hypostenic disorders, panic reactions, depression, dissociative and conversive irregularities, loss of communicational plasticity, loss of the ability to adapt to what happens with the preservation prospects of targeted actions, manifestations of cynicism, the tendency to antisocial actions. Patients had complaints on increase anxiety, pessimistic attitudes, existential vacuum, sense of uselessness and loss of perspectives, tendency to irrational perception of reality with including mechanisms of autistic and archaic thinking.Thus, psychological status of the population of Ukraine is a model of complicated combination of SSD plus PTSD can be considered like a basis which leads to the decreasing of the individual barrier of mental adaptation with the next manifestation of different forms of psychopathological syndromes and needs further in-depth and detailed research.None Declared"} +{"text": "The contributions in this Research Topic collectively explore the nature of functional brain connectivity and its relation to cognition, emphasizing shared mechanisms and brain complexity. Results presented here reveal common themes in how the brain dynamically reorganizes and adapts to task- and disease-related perturbations.Stylianou et al.), a dimensionality reduction technique to facilitate comparisons of oscillatory patterns across task paradigms and modalities , a new adaptation of the dynamic causal modeling (DCM) approach to capture connectivity changes during more ecological tasks such as movie watching (Nag and Uludag), a new connectivity method based on the Kuramoto model of coupled oscillators applied to network-level fMRI data , and a framework to study the relationship between functional connectivity and complexity (Das and Puthankattil).Some of the contributions present a variety of theoretical and methodological approaches to studying the relationship between connectivity, dynamics, and complexity. The articles include a novel multi-fractal functional connectivity estimation to track changes during visual pattern recognition , changes in individual differences along the language network hierarchy and their potential as biomarkers , the adaptation of the dorsal attention network to demands of a spatial attention task , the relationship between memory, depression, and inter-network connectivity , and the recovery of cognitive functions and related task networks after anesthesia .From an application perspective, contributions focus on the study of the large-scale cortical networks supporting cognition, in health and disease, including navigation subnetworks representing different types of spatial relation representations (We consider that the integration of these studies has the potential to advance our understanding of common principles governing the dynamic and complex relationship between brain connectivity and cognition.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "A chronic illness exerts a profound impact on an individual's physical and mental wellbeing, while also influencing their identities, familial relationships, and social responsibilities. Managing a chronic condition is a lifelong endeavor that demands substantial lifestyle adjustments, strict adherence to medication and treatment regimens, and the implementation of preventive measures. Informal caregivers, typically partners, spouses, family members, and friends, play a pivotal role in this experience: they are tasked with a range of complex and demanding responsibilities, such as responding to emergencies, mediating disagreements between patients and physicians, participating in treatment decisions, and addressing patients' emotional and practical needs. Promoting and supporting both patient and caregiver engagement is therefore vital for effective management of the disease.This Research Topic (RT) delves into the complex interplay between individuals facing chronic health conditions and their caregivers. The contributions included emphasize the intricate dynamics of patient-caregiver relationships and the interdependence between their actions and outcomes, encompass diverse populations such as patients and caregivers facing cardiac diseases, multiple sclerosis, amyotrophic lateral sclerosis, hemodialysis, and multimorbidity. The studies presented shed light on the theme of engagement by delving into the topic of caregiver burden and by presenting psychological interventions health education programs, and self-care programs aimed at increasing engagement.Golan and Vilchinsky; Rapelli, Giusti, Tarquinio, et al.; Rapelli, Giusti, Donato, et al.) explored the relationship between patient and caregiver wellbeing and different aspects of cardiac disease management. The study by Rapelli, Giusti, Tarquinio, et al. offered a scoping review of the existing psychological couple-oriented interventions conducted for patients with heart disease and their partners. The review collected 11 studies with heterogeneous designs, theoretical backgrounds, types of intervention, personnel involved, intervention formats , number of sessions, and duration. Results indicated high variability among couple-based interventions, lack of adequate details regarding the training of professionals delivering them, the contents of the interventions, and the theoretical models informing these programs. Interventions for patients with cardiovascular disease and their partners were found to moderately improve psychosocial outcomes. Furthermore, in most studies, only the patients' psychological strategies and outcomes were considered. Current contributions also revealed the stress experienced when a transplant or the implantation of an external device such as the Left Ventricular Assist Device (LVAD) is needed. The qualitative study by Rapelli, Giusti, Donato, et al. utilizes a phenomenological hermeneutic approach to understand the experience of six patient-caregiver dyads undergoing cardiac rehabilitation Four were the main themes: Being between life and death, Being human with a heart of steel, Sharing is caring (and a burden), and Being small and passive. Finally, Golan and Vilchinsky reflect on the necessity of applying a dyadic approach in the context of Left Ventricular Assist Device transplantation to enriching the understanding of patients' coping with this disease.Three of the studies included in the present RT considered the issue of care burden in informal caregivers of patients with multiple sclerosis (MS), given the risk of impaired quality of life, physical, and mental wellbeing of this population. The authors illustrate the Family-Centered Empowerment Model and compared it with TAU , showing that the intervention proposed does not have a favorable effect in reducing the care burden among caregivers of patients with MS. Another article contributed to the literature about caregiver-focused interventions. The authors aimed to evaluate the effectiveness of a health education program based on the \u201cTiming it Right\u201d framework (IG) on the caregivers' care ability, emotions, and health-related quality of life in the context of haemodialysis. However, the intervention had no significant effect in alleviating care burden. Similarly, the study protocol by Gomes de Souza e Silva et al. aims to investigate the effects of a self-care education program via telerehabilitation on the burden and quality of life of caregivers of individuals with Amyotrophic Lateral Sclerosis. This program has the potential to be widely disseminated among health professionals, increasing remote monitoring of individuals with difficulty performing practical care activities.One study and overlapping cognitive assessments of the circumstance emerged as higher-order factors from the quotations. Second, relationship-related tactics, such as striking a balance between autonomy and equity in the couple, were frequently highlighted. Third, some couples discussed the advantages of individual strategies that focus on developing partners' resources outside of their romantic partnerships (such as creating relationships with their grandchildren or spending time in nature).Care coordination and distress increase in case of multimorbidity , the physical, psychosocial, and relational changes and aspects of threats elicited by multimorbidity also provoke significant emotional responses. The qualitative study by This Research Topic underscores the significance of recognizing chronic illness management as a collaborative experience shared by patients and informal caregivers. The studies presented shed light on the complexities of patient-caregiver relationships, offering insights into the effectiveness of interventions and the evolving needs of those navigating chronic illnesses. By adopting a dyadic perspective, healthcare professionals can better support individuals facing chronic illnesses and their caregivers and tailor care approaches to their needs. Future research should continue to explore dynamics within these partnerships and develop tailored interventions that address the multifaceted challenges they encounter.GR: Writing \u2013 original draft. CA: Writing \u2013 original draft. EG: Writing \u2013 original draft. SD: Writing \u2013 original draft."} +{"text": "The 1978 Italian reform of psychiatric services initiated the closure of psychiatric hospitals encouraging the development of community mental health. However, there is wide variability across regions in the amount of resources devoted to community-based psychiatric care, and the range of services provided still is cause of concern.To evaluate the quality of mental health care delivered to patients with schizophrenia and related disorders taken-in-care by mental health services in four Italian regions .Thirty-one clinical indicators concerning accessibility, appropriateness, continuity, and safety were defined and estimated using healthcare utilization (HCU) databases, containing data on mental health treatments, hospital admissions, outpatient interventions, lab tests and drug prescriptions.A total of 70,586 prevalent patients with schizophrenia treated in 2015 were identified, of whom 1,752 were newly taken-in-care. For most patients community care was accessible and moderately intensive. However, care pathways were not implemented based on a structured assessment and only half of the patients received psychosocial treatments. One patient out of ten had access to psychological interventions and psychoeducation. Activities specifically addressed to families involved a third of prevalent patients and less than half of new patients. One patient out of six was admitted to a community residential facility, and one out of ten to a general hospital psychiatric ward (GHPW); higher values were identified in new cases. In general hospitals, one-fifth of the admissions were followed by readmission within 30 days of discharge. For two- thirds of patients continuity of community care was met, and six times out of ten a discharge from a GHPW was followed by an outpatient contact within two weeks. For cases newly taken-in-care the continuity of community care was uncommon, while the readiness of outpatient contacts after discharge was slightly more frequent. Most of the patients received antipsychotic medication, but their adherence to long-term treatment was low. Antipsychotic polytherapy was frequent and the control of metabolic side effects was poor. The variability between regions was high and consistent.The Italian mental health system could be improved by increasing the accessibility to psychosocial interventions, improving the quality of care for newly taken-in-care patients, focusing on somatic health and mortality, and reducing regional variability. Clinical indicators demonstrate the strengths and weaknesses of the mental health system in these regions, and, as HCU databases, they could be useful tools in the routine assessment of mental healthcare quality at regional and national levels.None Declared"} +{"text": "As of November 2022, over 417 397 confirmed cases and 2631 deaths related to coronavirus disease (COVID-19) were reported in Pacific island countries and areas (PICs). Most PICs have faced challenges accessing therapeutics recommended for the treatment of COVID-19 due to their high demand worldwide and supply chain constraints.The World Health Organization (WHO) coordinates and provides tailored technical and operational support to 21 PICs. Since the start of the pandemic, WHO has worked with partners to establish a mechanism to ensure equitable access to three novel COVID-19 therapeutics for lower-income countries, including 11 eligible PICs.WHO coordinated the requests, procurement and distribution of the three novel therapeutics. In addition, WHO supported PICs by providing trainings in clinical management of COVID-19, developing critical supply needs estimates, and facilitating regulatory approval of clinical therapeutics, including emergency use authorization.The main barriers to procurement of novel COVID-19 therapeutics were identified as prolonged negotiations with licence holders, sourcing funding, the high cost of therapeutics and limited capacity to provide safety monitoring.Uninterrupted supply and availability of essential medicines in the Pacific region is dependent on external and local sourcing. To overcome procurement barriers and ensure access to novel COVID-19 therapeutics in PICs, WHO\u2018s pandemic support to Member States focused on strengthening regulatory requirements, safety monitoring and supply chain activities. The first case of coronavirus disease (COVID-19) in the Pacific was reported in March 2020 in French Polynesia. . , which collectively are home to 3.2 million people spread across an ocean that covers 30% of Earth\u2019s surface. coordinates and provides tailored technical and operational support to 21 PICs Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Therapeutic Goods Administration of Australia, as well as the New Zealand Medicines and Medical Devices and Safety Authority (MEDSAFE). At the time of writing, only tocilizumab, molnupiravir and nirmatrelvir/ritonavir were available for WHO procurement under the emergency use listing. . The webinars covered topics such as indications for use, storage conditions, care pathways, therapeutic management of severe and non-severe cases, and safe and appropriate use, as well as country experiences. Trainers comprised experts and clinicians from WHO DPS, the WHO Regional Office for the Western Pacific, the Australian Therapeutic Goods Administration, the Central and Northern Adelaide Local Health Networks the Royal Alfred Hospital , the University of South Australia , New Zealand MEDSAFE, the WHO Global Outbreak Alert and Response Network, Fiji, the Marshall Islands, FSM and Palau. More than 150 health-care professionals including nurses, medical doctors, pharmacists and health advisers attended the webinars. Attendees represented 12 PICs \u2013 Fiji, Kiribati, the Marshall Islands, FSM, Nauru, Niue, Papua New Guinea, Solomon Islands, Tokelau, Tonga, Tuvalu and Vanuatu. The webinars provided a platform not only for participants to learn lessons from countries such as Australia and New Zealand , but also for neighbouring countries to share information and their experiences of therapeutics and clinical management of COVID-19 cases.In the Pacific, the level of regulatory systems development for medicines is either non-existent or very limited. . and corticosteroids, (Several PICs experienced difficulties in procuring an adequate supply of some essential medicines required for treatment of moderate-to-severe COVID-19, in particular dexamethasone, (In addition to supply chain issues, the COVID-19 pandemic highlighted the limited capacity of PICs to conduct safety monitoring activities for novel therapeutics. Although existing data suggest that newly introduced COVID-19 therapeutics were generally well tolerated, (Finally, the pandemic phase focused attention on the potential risk to public health posed by the general absence of robust quality control and assurance systems for medical products that exist across the Pacific. The identification of batches of falsified COVID-19 therapeutics in countries of neighbouring regions (This report has some inevitable limitations. As it describes the experience of PICs, due to the huge diversity in social systems, health-care provision, economic factors and geography, the findings might not be generalizable to all countries in the Pacific. Likewise, each PIC is unique in its culture and customs, and therefore even within the group of PICs, the responses and lessons learned may not apply universally. Nevertheless, in a field with a paucity of literature, this report not only contributes to new knowledge but also provides some important lessons for countries that share similar characteristics, namely geographical isolation and limited regulatory systems, in terms of the management of future infectious disease outbreaks in which novel therapeutic interventions are required.Throughout the COVID-19 pandemic, WHO DPS, in collaboration with partners, has delivered tailored support to PICs. This support has taken the form of assistance with procurement and emergency use authorization of novel therapeutics; provision of clinical management guidance and technical support; and regulatory system strengthening, in particular building capacity in safety monitoring and quality assurance programmes. Looking ahead, WHO DPS support should continue to be focused on strengthening regulatory requirements, safety monitoring and supply chain activities to ensure access to and implementation of novel COVID-19 therapeutics in all PICs. To ensure sustainable access to quality-assured therapeutics in the event of future pandemics, it will be important to continue to develop methodologies to estimate critical supply needs and demands."} +{"text": "Studies have explored the correlates of insecticide-treated nets in Nigeria. The few studies that focused on Northern Nigeria mostly examined individual correlates, but largely ignored the community correlates. Also, the persistence of armed insurgencies in the region calls for more research attention. This study examines the utilization and the associated individual and community factors of insecticide-treated nets in Northern Nigeria.The study adopted a cross-sectional design. Data were extracted from the 2021 Nigeria Malaria Indicator Survey (NMIS). A weighted sample size of 6873 women was analysed. The outcome variable was the utilization of insecticide-treated nets. The explanatory variables selected at the individual/household level were maternal age, maternal education, parity, religion, sex of head of household, household wealth, and household size. The variables selected at the community level were the type of place of residence, geo-political zone of residence, the proportion of children under five who slept under a bed net, the proportion of women aged 15\u201349 who heard malaria media messages, and the community literacy level. Two variables, namely, the number of mosquito bed nets in the household, and the number of rooms used for sleeping were included for statistical control. Three multilevel mixed-effect regression models were fitted.The majority of childbearing women (71.8%) utilized insecticide-treated nets. Parity and household size were the significant individual/household characteristics associated with the utilization of insecticide-treated nets. The proportion of under-five children in the community who slept under mosquito bed nets, and the geopolitical zone of residence were significant community correlates of the use of insecticide-treated nets. In addition, the number of rooms for sleeping, and the number of mosquito bed nets in the households were significantly associated with the utilization of insecticide-treated nets.Parity, household size, number of sleeping rooms, number of treated bed nets, geo-political zone of residence, and proportion of under-five children sleeping under bed nets are important associated factors of the utilization of insecticide-treated nets in Northern Nigeria. Existing malaria preventive initiatives should be strengthened to target these characteristics. Anopheles gambiae, Anopheles arabiensis, and Anopheles funestus [The transmission of malaria is endemic in most low-and-middle-income countries \u20133. In Nifunestus \u20136. Globafunestus . In addifunestus , 9. Amidfunestus \u201313, whicThe malaria preventive interventions being implemented seek not only to achieve malaria control but also to ensure the elimination of malaria in the country. These preventive interventions rest largely on the scaling-up of existing preventive initiatives, such as Indoor Residual Spraying (IRS), the universal coverage of Insecticidal-Treated Nets (ITN), and the use of Intermittent Preventive Treatment in pregnancy (IPTp) . EvidencOne key factor that occasioned the lack of universal utilization of malaria preventive interventions in the country is a poor understanding of the associated factors of the preventive interventions. Though, numerous studies have explored the correlates of different malaria preventive interventions in Nigeria and other countries \u201325. HoweOne, armed insurgency, such as the Boko Haram insurgency, destroys existing health facilities by reducing the numbers of healthcare personnel, the availability of essential drugs for malaria treatment, hinders access to appropriate care and makes the practice of preventive measures difficult \u201333. Two,The objective of the study was, therefore, to examine the prevalence and the associated individual and community factors of insecticide-treated nets in Northern Nigeria. The focus is on insecticide-treated nets because among the dominant preventive interventions in Nigeria, it is more widely accessible to Nigerian households, and freely distributed to households during malaria sensitization campaigns , 40. Tho. [The findings in the study will provide additional inputs for developing appropriate strategies to boost the use of insecticide-treated nets in Northern Nigeria. The study was guided by the question: what are the associated factors of the utilization of insecticide-treated nets in Northern Nigeria? The socio-ecological model developed by McLeroy et al. anchored. , 46.https://dhsprogram.com/pubs/pdf/MIS41.pdf. Overall, interviews were completed with 14,476 women aged 15\u201349 in 13,727 households. The individual and household datasets of the 2021 NMIS were merged in the study because some of the variables of interest were not available in the individual dataset. However, some women were excluded from the study. These are women from the southern region, women who do not have a mosquito bed net for sleeping, and women practicing traditional or other faiths, who were excluded due to their insignificant proportion in the population covered. The study thus analysed a weighted sample size of 6,873 women.The study adopted a cross-sectional design. The design entails analysing the 2021 Nigeria Malaria Indicator Survey (NMIS) data to describe the malaria-related characteristics of childbearing women in Northern Nigeria and to examine the possible associations between the characteristics and the use of insecticide-treated nets in the region. The survey was executed by the National Malaria Elimination Programme (NMEP) under the auspices of the Federal Ministry of Health (FMoH), and in collaboration with the National Population Commission (NPC) . The genThe outcome variable in the study is the utilization of insecticide-treated nets. The utilization was measured by asking women whether they slept under a mosquito bed net the night preceding the survey. This yielded a binary response, with \u2018yes\u2019 indicating that the respondent utilized the intervention, and \u2018no\u2019 indicating otherwise. Existing studies have applied this measure to operationalize the utilization of insecticide-treated nets , 48, 49.The explanatory variables were selected at the individual/household and community levels based on findings in existing studies that the utilization of preventive interventions is influenced by different factors operating at different levels of the social environment, particularly at the individual/household, and community levels \u201351. The The variables selected at the community level were the type of place of residence , geo-political zone of residence , the proportion of under-five children in the community who slept under mosquito bed nets , the proportion of women age 15\u201349 exposed to malaria media messages in the community , and community literacy level . These variables have also been identified as important correlates of the utilization of malaria preventive interventions , 50, 57.Statistical analyses were performed at different levels using Stata version 14 . At the Table Respondents from the north-west geo-political zone constitute more than half of the women (54.0%), while women from the north-central geo-political zone were the least sampled (18.8%). The majority of respondents reside in rural areas (72.9%). More than one-third of respondents live in communities with a high proportion of children under 5 sleeping under a mosquito net compared to those who reside in communities with either a low or moderate proportion of under 5 children who slept under a mosquito bed net. The proportions of low, medium, or high exposure to media messages about malaria were similar in the communities although the proportion residing in communities with moderate exposure was higher among the respondents (34.8%). The proportion of respondents who reside in communities with low literacy levels was higher among the sampled women (35.7%). Nearly half of the respondents live in households with two or fewer mosquito bed nets (47.3%). Likewise, more than two-fifths of the respondents live in households that possessed three to five mosquito bed nets. The households of the majority of respondents had three or fewer rooms for sleeping (67.6%).Table The association between the proportion of under-five children who slept under a bed net in the community and the use of insecticide-treated nets by childbearing women was positive, with a consistent rise in the level of use as the proportion of children who slept under a bed net in the community increased. In contrast, the proportion of reproductive-age women exposed to media messages about malaria reveals a mixed association with the use of insecticide-treated nets. Likewise, community literacy levels had a mixed association with the utilization of insecticide-treated nets. At the low and moderate literacy levels, a slight rise in the level of utilization was observed, but a dip occurred at the high literacy level. The geopolitical zone of residence had a positive association with the use of insecticide-treated nets, with a higher level of use observed in the northeast zone. A higher level of use of insecticide-treated nets was observed in the rural areas compared to the urban areas showing a significant positive association. A significant positive association was observed between the number of mosquito bed nets and their utilization, while the number of rooms used for sleeping was negatively associated with the use of insecticide-treated nets. All the variables showed a VIF value of less than ten and were selected for the multilevel modeling. However, religion, sex of the head of household, and proportion of women exposed to media messages about malaria were excluded having shown no statistical significance at the bivariate level.Table In Model 2, higher parity remained significantly associated with higher odds of the use of insecticide-treated nets, while a large household size remained significantly associated with lower odds of the use of insecticide-treated nets. Other individual/household characteristics revealed no statistical significance. Two community-level characteristics, namely, the proportion of under five children who slept under a mosquito bed net in the community and geopolitical zone of residence were significantly associated with the utilization of insecticide-treated nets. However, the proportion of variation in the use of insecticide-treated nets attributable to the community factors dropped compared to the proportion in Model 1 (ICC\u2009=\u20090.216).In the full model (Model 3), on one hand, two individual/household characteristics, namely, parity and household size, were significantly associated with the use of insecticide-treated nets. On the other hand, two community characteristics, namely, the proportion of under-five children who slept under a mosquito bed net in the community and the geopolitical zone of residence were significant correlates of the use of insecticide-treated nets. As parity was increasing, the odds of utilizing insecticide-treated nets also increased consistently. Childbearing women living in large-sized households were associated with lower odds of utilizing insecticide-treated nets . As the proportion of under-five children who slept under mosquito bed nets in the community increased, the odds of utilizing insecticide-treated nets by childbearing women consistently increased. The odds of utilizing insecticide-treated nets were higher in the northeast zone and northwest zone compared to the northcentral zone. Also, an increasing number of mosquito bed nets in households was associated with higher odds of their utilization. In contrast, increasing the number of rooms for sleeping in households was associated with lower odds of utilizing insecticide-treated nets.The study examined the prevalence and associated factors of the utilization of insecticide-treated nets in Northern Nigeria. The study found a utilization level lower than the observed average for the region in a recent Nigerian study . HoweverThe study further revealed that some individual/household and community characteristics are important correlates of the utilization of insecticide-treated nets. One, gender matters in the utilization of insecticide-treated nets. It is reasoned that since more females compared to males use malaria preventive interventions , women aThree, community contexts are source of variations in the level of use of insecticide-treated nets, though not in a substantial proportion. These community factors include the geo-political zone of residence and the proportion of under-five children in the community who slept under treated bed nets. The geopolitical zone of residence, particularly being residents in the states in the northeast and northwest zones was found to the drive utilization of insecticide-treated nets in line with findings in two recent studies , 51. ThiThe paper assessed the prevalence and correlates of the utilization of insecticide-treated nets in Northern Nigeria based on data extracted from a nationally representative survey. The study revealed that the utilization of insecticide-treated nets was not universal among childbearing women in the region and that some individual-level and community-level characteristics were associated with the utilization of insecticide-treated nets. Improving the level of utilization in the region requires targeting more individual characteristics of childbearing women, as well as embarking on more community engagements to amplify governments and non-government strategies to boost utilization of malaria preventive measures."} +{"text": "In Egypt, academic organizations, professional societies, and research groups develop clinical practice guidelines (CPGs) in order to improve patient quality care and safety. Although important improvements have been made over the past years, many of these consensus-based guideline documents still lack the transparency and methodological rigor of international standards and methodologies recommended by reference evidence-based healthcare and guideline organizations like the Guidelines International Network.In the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG), we have adopted one of the CPG formal adaptation methodological frameworks named the \u2018Adapted ADAPTE\u2019, relevant CPG resources , and involved key stakeholders including clinical and healthcare topic experts and guideline methodologists in producing 32 trustworthy national evidence-based CPGs and one protocol customized to the healthcare context and services provided for Egyptian children. An EPG online website was launched to make these CPGs available and accessible as CPG summaries for pediatricians and relevant healthcare providers.The lessons learned, enablers, challenges, and solutions relevant to Egyptian National Pediatric CPGs identified in this paper could be used to address and enrich the debate on pediatric high-quality CPGs, especially for countries of similar contexts and systems.The online version contains supplementary material available at 10.1186/s42269-023-01059-0. Clinical practice guidelines (CPGs) are statements that include recommendations for improving patient care. A systematic review of evidence and an assessment of the benefits and costs of alternative care options inform these statements (Institute of Medicine (US) Committee on Standards for Developing Trustworthy Clinical Practice Guidelines High-quality evidence-based CPGs are known to support the clinical decisions of relevant healthcare providers and to improve patient outcomes and adaptation (when there are existing and published one or more eligible CPGs) (and the former ADAPTE Collaboration) as \u201cthe systematic approach to the modification of a guideline(s) or recommendation(s) produced in one cultural and organizational setting for application in a different context. Adaptation may be used as an alternative to de novo guideline development existing guideline/s to suit the local context)\u201d ], CPG tools , or CPG standards . Yao et al. reportedWang et al. coined tTo date, there have been several institutional and national CPG adaptation initiatives in the Eastern Mediterranean Region. One of the early CPG formal adaptation methodological frameworks that were applied in the Arab Republic of Egypt was the ADAPTE and one of its modified versions: The \u2018Adapted ADAPTE\u2019 , 9 modules, and 24 steps. The \u2018Adapted ADAPTE\u2019 was proposed by the founding members of the Alexandria Center for Evidence-Based Clinical Practice Guidelines at Alexandria University, Egypt and it included the same overall framework of the original ADAPTE in addition to 3 modified tools, 3 new tools, and 4 alternative steps was established and conducted several strategic planning meetings and discussions and launched the first pediatric national CPG program with the Supreme Council of Egyptian University Hospitals marks the first national and collaborative initiative for the generation of Pediatric CPGs using an evidence-based methodology in Egypt.After the foundation of the EPG under the auspices of the Supreme Council of Egyptian University Hospitals and the Armed Forces College of Medicine, it added 5 EPG subcommittees for (i) strategic planning, (ii) CPG advisory (methodology), (iii) implementation, (iv) publication and research, and (v) quality control.The strategic plan for national pediatric evidence-based CPGs included: (i) identifying the national healthcare priorities in the field of pediatrics and child health; (ii) identifying a scientifically rigorous and evidence-based methodology for CPGs; and (iii) scope of function, roles, and responsibilities of the members of the EPG and the subspecialty CPG groups.The EPG decided to use the CPG adaptation methodology, specifically the \u2018Adapted ADAPTE\u2019 methodological framework. The Adapted ADAPTE CPG adaptation process is summarized in Fig.\u00a0The founding members reached out and recruited representative faculty staff from the Departments of Pediatrics of 14 Egyptian Universities and one National Research Centre, including, in alphabetical order, the faculties of medicine at the universities of Ain Shams, Al-Azhar, Alexandria, Assiut, Benha, Cairo, Helwan, Mansoura, Menoufia, Minia, October 6, Port Said, Suez Canal, and Zagazig, as well as the Ministry of Health with a clinical lead and several contributors from multiple universities in the same subspecialty (in contrast to the known term Guideline Development Group or GDG that is saved for groups that use the de-novo development methodology), and (2) The External Review Group (or ERG).The CPG adaptation project involved the collaboration of two main distinct and independent groups: (1) The Each GAG was divided into two subgroups: (i) The Clinical expert subgroup, which includes the Clinical lead of the GAG and its members nominated by the related EPG Pediatric subspecialty group with the EPG Chairman, and (ii) The CPG Methodology supervision subgroup that includes faculty staff and pediatricians with expertise as CPG Methodologists and working experience with the Adapted ADAPTE.Most members of the EPG CPGs\u2019 GAGs and ERGs are staff of Egyptian Universities, University Hospitals, National Research Centres, the Ministry of Health, or their clinical and methodological networks. They have contributed to the EPG CPG projects on a voluntary basis not related to or funded by any pharmaceutical company, industrial body, or research grants. Some members of the ERGs were international clinical or methodological experts. The declaration of the conflict of interests of all contributors was transparent.The recruitment process for EPG members was open to any interested child healthcare provider primarily pediatricians and others like clinical pharmacists, and nurses as relevant to the specific health topics representing university hospitals and different healthcare sectors and facilities in Egypt.The EPG has completed five waves of parallel CPG adaptation projects from 2018 to date that has produced 32 adapted national Evidence-Based CPGs for high-priority pediatric health topics in Egypt, in addition to a consensus-based national protocol for COVID-19 (including four versions so far) and other social media networks.Furthermore, as faculty teaching staff, chairpersons of pediatrics or child healthcare departments, senior consultants, or directors in their institutions, EPG members represent clinical and quality champions supporting CPG implementation. Detailed post-implementation findings for each CPG health topic will be reported individually.The EPG has future plans to evaluate the success of uptaking and implementing its CPGs in real pediatric practice and evaluate their accessibility to the relevant healthcare providers and target users through interventions like (i) Knowledge, Attitude, and Practices (KAP) surveys, (ii) audit and feedback, and (iii) Plan-Do-Check-Act (PDCA) Quality Improvement Cycles.Despite the fact that the COVID-19 pandemic posed challenges to education, research, and other projects and services, the EPG different GAG clinical and methodology members expressed great enthusiasm and resilience by shifting all of the face-to-face meetings and activities to online Zoom meetings and a set of WhatsApp groups for each GAG in addition to the main EPG group was recently established in 2018 as part of the Universal Health Insurance System in Egypt. GAHAR published seven handbooks of accreditation standards covering different healthcare services throughout which it recommended adherence to CPGs, protocols, and policies and procedures .Lack of financial support dedicated to developing, disseminating, and implementing National CPGs to cover costs like design and printing and article processing fees for CPGs and other potential implementation resources such as National CPGs\u2019 website or database maintenance and CPG mobile Apps.There is lack of a national agreement on the process of development, adaptation, official approval, Implementation, revision and update, and auditing of National Guidelines in Egypt.There is no national body or center assigned to develop, revise, evaluate, validate, and/or officially approve National Guidelines in Egypt similar to the examples of the National Evidence-Based Medicine Center of the Saudi Health Council in Saudi Arabia, the Ministry of Public Health in Qatar, the National Authority for Assessment and Accreditation in Healthcare in Tunisia, the National Institute for Health and Care Excellence (NICE) in the United Kingdom, and the National Health and Medical Research Council (NHMRC) in Australia , Curative Care Organization (CCO), Teaching hospitals and institutes organization (THIO), Health Insurance Organization (HIO), Ministry of Higher Education (MOHE) , and Ministry of Defense (MoD) and Ministry of Interior (MoI). The private sector has the Private medical insurance, Household out-of-pocket payments, and Non-Governmental Organizations. This pluralistic healthcare system poses great challenges to implementing National Guidelines in Egypt. Universal health insurance (UHI) is a new entity established to provide Universal Health Insurance services for all Egyptians and is expected to address some of these barriers Saleh .There is lack of integration and collaboration with relevant national initiatives like the Health Technology Assessment (HTA) Institutionalization by The Egyptian Authority for Unified Procurement, Medical Supply and the Management of Medical Technology (UPA) in collaboration with NICE International and the National Egyptian Network Pediatric Stroke and Hemiplegia Registry (NENPSHR), there is a lack of relevant national registries for other high-priority pediatric health topics that in turn disable our estimates for diagnostic and management difficulties in these topics with the CPG evidence-based recommendations as they fear that CPGs adherence may limit their clinical autonomy, flexibility and individualized approach and the International Network of Agencies for Health Technology Assessment (INAHTA)].Collaborate with similar national guidelines centers in the Eastern Mediterranean Region to build capacity and exchange experiences with consideration of the similarities and differences between the health systems.Integrate the EPG CPGs into the GAHAR Accreditation Standards that are related to child healthcare services and facilities.Integrate formal training, modules, and courses of evidence-based healthcare and CPG tools and skills into the curricula of undergraduate and postgraduate students of Health Colleges and Faculties like Medicine, Pharmacy, Nursing, etc. [a good example is the recently launched International Guideline Development Credentialing & Certification Program (or INGUIDE)] INGUIDE .Integrate and align relevant national initiatives to achieve the balance between clinical evidence through CPGs and economic evidence through HTAs (Mason et al. We are, on behalf of the EPG, proposing the following recommendations and solutions to address the aforementioned barriers to National Pediatric CPGs in Egypt and to open them for discussion in countries of similar contexts and systems:The lessons learned enablers, challenges, and solutions relevant to Egyptian National Pediatric CPGs identified in this paper could be used to address and enrich the debate on pediatric high-quality CPGs, especially for countries of similar contexts and systems.Additional file 1. Recognition and Honor List."} +{"text": "For many years, the central nervous system (CNS) was thought to be immune-privileged due to the presence of the blood-brain barrier (BBB) and the absence of lymphatic vasculature. However, recent studies have uncovered the intricate interactions between the CNS and the immune system. In particular, microglia\u2013resident immune cells in the brain\u2013share developmental origins and functions with monocytes in the immune system, playing crucial roles in monitoring and modulating neuronal activity produced by the choroid plexus in the brain can enter the cervical lymph nodes and cranial bone marrow via the dura lymphatic system inhibits inflammatory signaling pathways and promotes anti-inflammatory polarization of microglia in ischemic rats.To date, rehabilitation is a widely used and effective treatment for brain injury in the clinic. Rehabilitation programs include stimulation with electricity, magnetism, light, and heat on the CNS and peripheral nervous system (PNS), along with physical therapy, virtual reality, motion imagination, and so on. Although the neuroprotective mechanism of rehabilitation involves multiple targets and multiple factors, inflammatory regulation is its pivotal process. Transcranial-direct-current-stimulation (TDCS) can decrease microglial activation and reduce the release of pro-inflammatory cytokines in experimental stroke models , which can proliferate, migrate, and differentiate into neural cells, can take part in nerve repair and neural plasticity by replacing the injured neural cells (Liu et al., Overall, neuroimmune communication is correlated with the physiological functions of various tissues and organs and the internal environmental balance. Dysregulation of neuroimmune communication homeostasis is both the underlying pathological mechanism and the potential therapeutic target in brain injury. A thorough clarification of the cellular and molecular mechanisms of neuroimmune communication in brain injury is an essential and necessary endeavor in the search for new therapeutic targets for this type of disorder.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "Acute exacerbations of chronic bronchitis (AECB) are recurrent and potentially severe medical events for the 13 million people in the United States who have chronic bronchitis. Medical resource use associated with AECB can have a substantial economic impact on the patients, health care system, and society overall.To evaluate literature on the economic impact of AECB in terms of cost of illness, cost of treatments, and cost-effectiveness.A MEDLINE literature search was conducted for studies of chronic bronchitis and costs. Reference lists of identified articles were also retrieved for review.Eight published studies were identified: 2 cost-of-illness studies, 1 comparative cost study, and 5 cost-effectiveness studies. Important drivers of costs associated with AECB include hospitalization and choice of antibiotics. In mild to moderate AECB, patient adherence with therapy is essential to consider when selecting treatment. The antibiotic with the lowest acquisition cost has not been shown to be the most cost effective, as adherence and clinical outcomes, particularly re-hospitalization rates, differ.Further research in these areas is needed to guide clinical decision making and the conduct of disease management programs."} +{"text": "Dear Editor,A Caucasian woman, 54 years old, Fitzpatrick phototype II, complained of a painful lesion on the right malar region, with rapid growth and aggressive behavior, which had appeared three months before. The patient lived in a rural area and worked in agriculture, referring chronic sun exposure due to her working conditions. When questioned, she denied history of trauma at the site of the lesion, previous skin cancer, immunosuppression, and exposure to artificial radiation. Dermatological examination showed an infiltrated and painful erythematous plaque with exudation, crusts, ulceration, and telangiectasias in the malar region extending to the right nasal ala . Skin daThe immunohistochemical analysis showed positivity for cytokeratin 5/6 and p63; and was focally positive for BerEp4, EMA, and factor XIIIa; with negativity for adipophilin, androgen receptor and CEA , confirmCutaneous squamous cell carcinoma (SCC) is classified into many subtypes, with a wide range of clinical manifestations ranging from indolent growth to aggressive tumors with significant metastatic potential.Cutaneous clear-cell SCC is a rare neoplasia the etiology of which is still incompletely understood. This variant was described in 1980 by Kuo.SCC usually manifests itself on photo exposed areas of elderly Caucasian men with a history of chronic sun exposure and multiple skin neoplasms.Clear-cell SCC can be classified into three variants: keratinizing (type I), non-keratinizing with no connection to the epidermis (type II), and pleomorphic (type III).On histopathology, the atypical clear cells showed evident nuclear pleomorphism, squamous differentiation foci, and areas of acantholysis, with some dyskeratotic cells amidst pseudo glandular spaces.It is difficult to define the prognosis of this rare variant, as few cases were published in the literature up to 2022. Cohen et al. (2008) suggested that human papillomavirus (HPV) infection may be associated with tumor oncogenesis, but only two reported cases were associated with this virus.In conclusion, the present study describes the atypical case of a 54-year-old woman with a facial neoplasm compatible with clear cell SCC, histopathologically mimicking sebaceous carcinoma. Both dermatologists and dermatopathologists must be aware of the peculiarities of this SCC variant, which grew fast and was quite aggressive in the present report.None declared.Emily Neves Souza: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.Lucia Martins Diniz: Design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.Luana Amaral de Moura: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature.Alexandre Calegari Oliosi: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature.Marcela Sc\u00e1rdua Sabbagh de Azevedo: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature.M\u00e1rgya Neves Souza: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature.None declared."} +{"text": "Obsessive-compulsive and related disorders (OCRDs) constitute a group of psychiatric conditions characterized by obsessive thoughts and/or compulsive behaviors. In DSM-5, the section on OCRDs is narrowly defined, including obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder (HD), trichotillomania (TTM) or hair-pulling disorder, and skin-picking (excoriation) disorder (SPD) . The ICDWhile significant progress has been made in understanding these underrecognized disorders, there are still aspects not yet fully understood. This Research Topic in Frontiers in Psychiatry aimed to shed light on the current state of knowledge on OCRDs in general community and clinical samples of all ages. This Research Topic presents nine manuscripts, including a brief research report, a clinical trial, several original research papers, and a systematic review, from experts worldwide.Strappini et al. investigated the therapeutic alliance as a component of treatment in OCD. Their systematic review and meta-analysis provided evidence of an interactive effect between the therapeutic alliance and outcomes of cognitive behavior therapy (CBT) in patients with OCD. They recommended that future studies should focus on refinement of the temporal assessment of the alliance, in larger samples, and measurement of other interacting variables, to enrich the current understanding of therapeutic change factors that could benefit evidence-based treatment.Liao et al. provided evidence of satisfactory psychometric properties of the Family Accommodation Scale Self-rated version (FAS-SR) in a large group of patients with OCD and relatives, suggesting that this scale can assist in the evaluation and treatment of OCD.In addition to the therapeutic relationship, the relationship between OCD and family dynamics has also attracted increasing attention from researchers. The concept of family accommodation (FA) refers to family members' participation in patients' rituals and accommodating their compulsions to alleviate their anxiety. Addressing FA is an important part of the treatment plan. Hollmann et al. demonstrated the effectiveness of internet-based CBT in German children and adolescents with mild to moderate OCD.CBT including exposure exercises with response prevention (E/RP), is the established treatment of choice for OCD. However, there are many barriers to accessing CBT, including lack of availability, lack of experience of service providers, and financial and time constraints. Internet-based psychotherapy could help overcome some of these barriers and Wang et al. explored the moderating effect of executive functioning on the relationship between anxiety and compulsive checking in adults with OCD. The study suggested that anxiety symptoms play a negligible role in explaining compulsive checking in individuals with OCD with relatively strong visuospatial working memory ability, but a substantial role in explaining compulsive checking in individuals with relatively weak visuospatial working memory. These findings encourage further research regarding how cognitive vulnerability factors of OCD and emotional factors interact to induce or maintain different OCD symptoms, providing additional insights into the mechanisms underpinning OCD.Changing direction from investigations of treatment to the mechanisms underpinning OCD, Kang et al. used survey to investigate BDD and depression in male university students in Malaysia. The study found that a significant proportion exhibited symptoms of BDD and depression, with BDD concerns mainly related to dissatisfaction with their height, which significantly correlated with the severity of depressive symptoms. This study responds to the quest for more research on the epidemiology of mental disorders among male adolescents, and highlights the importance of better support services.Addressing the paucity of research on, and low treatment rates of, mental illnesses in men, Brennan et al. used a qualitative approach to explore the lived experiences of individuals with BDD (In press). Three themes were identified: being consumed by the disorder, the flawed self, and intolerance of uncertainty about appearance, and were discussed in relation to the cognitive-behavioral model.In another contribution to this Research Topic on OCRDs, Aquino and Lins investigated the association between problematic buying/shopping with the Big Five's personality factors, during the COVID-19 pandemic, using an online survey of Portuguese adults. Regression analysis revealed significant correlations between various instances of buying/shopping, such as impulsive buying, compulsive buying, and panic buying, and some of the Big Five traits, highlighting the potential for improved understanding of these traits to inform preventive measures and effective treatment approaches.Rocha et al. conducted a survey on the association between early maladaptive schemas (EMS) and compulsive and impulsive buying in young adults from Portugal. They found the overvigilance and inhibition schema was the main predictor of both impulsive and compulsive buying and that impaired limits was negatively associated with these tendencies. Coping mechanisms within this context were also explored.Both aforementioned studies contribute to the conceptualization and study of problematic buying/shopping tendencies in populations other than Western, Educated, Industrialized, Rich, and Democratic (WEIRD) samples.Di Ponzio et al. reported on the positive effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left DLPFC in Italian individuals with OCRDs, including SPD, TTM and HD. This study suggests that this rTMS protocol is a promising treatment option for OCRDs and highlight common circuits involved in these disorders.In conclusion, the manuscripts included under this Research Topic cover a diverse range of themes, from the mechanisms underlying OCRDs, to the quest for personalized treatment approaches across the lifespan, while also addressing the misconception that these disorders are merely bad habits. The authors emphasized the need to further elucidate the etiologies and lifespan trajectories of OCRDs, as well as the development of eHealth treatment approaches. Nonetheless, this initiative demonstrates the progress made through global efforts, employing rigorous methodological standards, which can enhance clinical practice in addressing the unmet needs of patients throughout their lifetime.CL: Writing\u2014original draft, Writing\u2014review and editing. KP: Writing\u2014review and editing. EG: Writing\u2014review and editing."} +{"text": "Axial spondyloarthritis (axSpA) is a subtype of SpA that mainly affects the sacroiliac joints and the spine. One of the hallmarks of axSpA is radiographic progression, which refers to the progressive structural damage seen on imaging tests. Radiographic progression is associated with increased disability, quality of life, and higher healthcare costs . The datKhmelinskii et al. reviewed the role of various imaging modalities in the diagnosis, classification, and monitoring of axSpA. They highlighted the advantages and limitations of X-rays, MRI scans, computed tomography (CT), and ultrasound, and discussed the use of various scoring systems, such as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), the Berlin MRI score. They concluded that a combination of imaging tests and clinical assessments is necessary for accurate and timely diagnosis and monitoring of axSpA, and that new imaging techniques and biomarkers are promising avenues for future research.The diagnosis of axSpA is based on a combination of clinical features, laboratory tests, and imaging findings. Imaging techniques play a crucial role in detecting and monitoring the spinal and sacroiliac joint inflammation and structural damage in axSpA. Kang et al. used group-based trajectory modelling and decision trees to identify the patterns and predictors of radiographic progression in patients with ankylosing spondylitis (AS). They classified the patients into four distinct trajectory groups based on the mSASSS scores over 10 years of follow-up: no progression, slow progression, moderate progression, and rapid progression. They found that male sex, older age, longer disease duration, elevated C-reactive protein (CRP), and higher baseline mSASSS scores were associated with a higher risk of radiographic progression. They also developed decision trees that showed the most important predictors of each trajectory group. This study provides valuable insights into the heterogeneity of radiographic progression in AS/r-axSpA and the potential for personalized risk prediction.Radiographic progression is a major concern in the management of axSpA, as it can lead to irreversible structural damage and functional impairment. Therefore, identifying the predictors of radiographic progression is an important research area. Lee et al. investigated the impact of pregnancy on radiographic progression in 36 women with r-axSpA using CT scans of the spine and sacroiliac joints before and after pregnancy. They found that pregnancy did not significantly affect radiographic progression, as measured by the mSASSS and New York criteria scores. They also observed a trend towards decreased inflammation scores during pregnancy, suggesting a potential beneficial effect of pregnancy on disease activity. However, this study has some limitations, such as the small sample size, the lack of a control group and the imaging technique (CT) adopted.AxSpA disease onset is frequently observed in childbearing age. Therefore, pregnancy can affect the course and outcome of axSpA. Nam et al. explored the impact of smoking status on radiographic progression in patients with AS/r-axSpA who received tumor necrosis factor inhibitors (TNFi) treatment. They found that current smokers had a higher risk of radiographic progression, as measured by the mSASSS scores, than former or never smokers. They also observed that current smokers had lower serum TNFi levels and higher CRP levels than non-smokers, indicating a possible mechanism for the detrimental effect of smoking on treatment response and radiographic progression. This study highlights the importance of smoking cessation in the management of axSpA.Smoking is a well-known risk factor for radiographic progression in axSpA . Unlike In conclusion, radiographic progression in axSpA is a complex and multifactorial process that affects the spine and sacroiliac joints and the articles in this topic show crucial role of imaging in the diagnosis and classification, the effect of smoking and pregnancy on radiographic progression and help to predict prognosis in patients with AS. Additionally, recent studies have identified several risk factors and predictors of radiographic progression, such as male sex, older age, longer disease duration, elevated CRP, and smoking. These findings have important implications for the personalized management of axSpA and the development of new therapeutic strategies. This topic also shows more research is required and future research may focus on the validation and implementation of imaging biomarkers and scoring systems, as well as the exploration of novel treatment targets and approaches.FP-S and NA drafted the manuscript. All authors reviewed and approved the editorial."} +{"text": "AlGhamdi The authors regret the omission of two of the authors, Sheta M. Sheta and Said M. El-Sheikh, from the original manuscript. The corrected author list is as shown above.The authors regret that the funding information was incorrectly shown in the acknowledgements section of the original manuscript. The corrected funding acknowledgement is as shown below:The authors extend their appreciation to the Deanship of Scientific Research at Northern Border University, Arar, KSA for funding this research work through the project number NBU-FFR-2023-0051.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "The World Health Organization has called on economic operators to \u201csubstitute, whenever possible, higher-alcohol products with no-alcohol and lower-alcohol products in their overall product portfolios, with the goal of decreasing the overall levels of alcohol consumption in populations and consumer groups, while avoiding the circumvention of existing regulations for alcoholic beverages and the targeting of new consumer groups with alcohol marketing, advertising and promotional activities\u201d (see ).As Anderson et al. discuss, lower-strength alcohol products can be split into two groups: (i) specifically produced no-alcohol products; (ii) existing products reformulated to contain less alcohol . Across When considering the public health impact of non-alcoholic products, one of the difficulties relating to monitoring and evaluation is the differing definitions across jurisdictions . To resoAs reviewed by Anderson et al. , and speFurther analyses of Spanish household data found that decreases in the ABV of existing beers and wines had a much greater impact in reducing purchases (in grams) of all alcohol than the relatively small increases in purchases of no-alcohol beers and wines . AnalyseWith respect to the health impact, it has been questioned whether people with severe alcohol problems safely switch to consuming no-alcohol products. On the one hand, as noted in the review by Anderson et al. , survey Rehm et al. undertook a modeling study to estimate the population-level health impact achieved by the current introduction of no- or low-alcohol beverages in Great Britain and Spain, and the impact of reducing the ABV of all alcohol products by a relative 10% amongst France, Germany, Italy, Poland, Spain, and United Kingdom . They foThrough addressing the product, reducing the ABV is only one of several innovative policy approaches. An alternative approach is to reduce serving sizes. The narrative review of Mantzari & Marteau found that reducing the size of servings, glasses, and bottles of wine could reduce wine consumption across populations .Nutt and colleagues proposed an even more novel approach: developing functional drinks that do not use alcohol yet mimic the positive, pro-social effects of alcohol without the associated harm .In conclusion, the introduction of no-alcohol products has health benefits for individual consumers, but very limited benefit at the population level due to very low levels of consumption; reformulation of existing products to contain less alcohol could, if realized across all products with a 10% relative reduction in ABV, have a substantial population-level impact, reducing the harm caused by alcohol. Alcohol producers should respond to the World Health Organization\u2019s call for substitution by reducing the alcoholic strength of all their products forthwith. Governments can promote substitution by increasing taxes on alcohol products, with harmonization of taxes per gram of alcohol and taxes rising per ABV of the product; were the tax rises much steeper at very low levels of ABV, this would also promote increased demand for and consumption of no-alcohol products (see )."} +{"text": "The globalization of the food market has created a pressing need for food producers to meet the ever-increasing demands of consumers while ensuring adherence to stringent food safety and quality standards . The comIn response to these challenges, the field of food analysis has witnessed remarkable advancements through the utilization of advanced spectroscopic techniques. These cutting-edge methods, including X-ray-based approaches, hyperspectral and multispectral imaging, NMR, Raman, IR, mass, UV, visible, and fluorescence spectroscopy, offer non-destructive, rapid, solvent-efficient, eco-friendly, and cost-effective alternatives to conventional methods . LeveragIt is with great pleasure that we present this Special Issue, which focuses on recent developments and applications of advanced spectroscopic techniques in food analysis, quality evaluation, safety assessment, and practical industrial implementations, with a specific emphasis on chemometric approaches. The collection of papers included in this Issue offers a valuable insight into the diverse range of research and applications in this field, shedding light on the potential of these techniques to revolutionize food analysis.The accepted papers cover a broad spectrum of topics within the scope of this Special Issue. The first paper presents a comprehensive review of the current applications of advancing spectroscopy techniques in food analysis, focusing on the data handling aspect with chemometric approaches . This reFritillaria thunbergia [Furthermore, one paper details an innovative application of laser-induced breakdown spectroscopy coupled with variable selection algorithms and chemometrics for the detection of heavy metals in unbergia . Anotherunbergia . Additiounbergia .In another study, the discrimination of Brazilian stingless bee honey based on its iron-based biogeographical origin is investigated, showcasing the applicability of discriminant analysis in ensuring the authenticity and traceability of food products . The quaAdditionally, the effect of moisture content on the analysis of quality attributes of red pepper powder is explored using a hyperspectral system, providing valuable insights into the impact of moisture on food analysis outcomes . MoreovePrunus genus by botanical origin and harvest year based on carbohydrates profiles is investigated, shedding light on the application of spectroscopic techniques for the authentication of botanical products [Salvia botanicals are explored using GC/Q-ToF and chemometrics, providing crucial insights into the identification and characterization of herbal products [Furthermore, the classification of products . The cheproducts .Lastly, the detection of pesticide residue levels in grapes is studied using hyperspectral imaging and machine learning, illustrating the potential of these techniques for ensuring food safety .In conclusion, this Special Issue brings together a collection of research papers that highlight the immense potential of advanced spectroscopic techniques in the field of food analysis and quality evaluation. By presenting a range of innovative applications, these studies demonstrate the power of these techniques to enhance food safety, authenticity, and overall quality. We hope that the papers in this Special Issue provide valuable insights, inspire further research, and encourage the adoption of advanced spectroscopic techniques in the food industry."} +{"text": "Nanomaterials proudly presents a Special Issue titled \u201cState-of-the-Art 2D and Carbon Nanomaterials in France\u201d, showcasing the groundbreaking research from some of the most eminent researchers in the field. The various publications cover a wide range of topics, including the synthesis, characterization, and applications of various carbon-based nanomaterials. These contributions shed light on the significant progress made in this area and collectively offer valuable insights into the current state and prospects of nanomaterial research in France.Nanotechnology has revolutionized various industries by enabling the manipulation and fabrication of materials at the nanoscale. In the realm of nanomaterials, 2D materials and carbon nanomaterials have emerged as frontrunners, promising a plethora of applications ranging from electronics to energy storage. France, with its rich scientific heritage, has been at the forefront of nanomaterials research, and the journal One of the key areas of focus in this issue concerns the synthesis of vertically aligned carbon nanotubes (VACNTs), wherein researchers in France have made noteworthy contributions and their insights have the potential to revolutionize the applications and production of VACNTs. By exploring various factors such as carbon source content , Fe/C raFurthermore, within the realm of carbon nanomaterials, this issue presents cutting-edge research exploring the world of curved polyaromatic hydrocarbons, known as carbon nanobelts. Employing laser-induced vaporization and ionization techniques, scientists have investigated collision impacts between species, leading to mass loss and the formation of new circular strained dehydrobenzoannulene species . These fAnother exciting contribution to this issue is the exploration of germanane, a two-dimensional material with stacks of atomically thin germanium sheets. The study focused on improving germanane\u2019s electrical transport properties to develop atomic-scale devices . The res2/graphene hetero-bilayer by varying the twist angle [2 monolayers, including the tunable WS2 spin-orbit splitting, offering new avenues for controlling the band dispersion of van der Waals materials. The insights gained from this research offer exciting opportunities for designing novel electronic devices and uncovering previously unexplored physical phenomena, holding immense potential for the electronics industry and future technological advancements.The potential of hetero-bilayer structures, where strain and spin-orbit coupling can be engineered, is also explored in this Special Issue, revealing exciting possibilities for tuning electronic band structures in van der Waals materials. Scientists have investigated the band structure of the WSst angle . Their wAdditionally, this issue includes research on the transfer process of monocrystalline graphene and its influence on the quality, morphology, and electrical properties of the transferred graphene . The con2 and KOH-based approaches, to enhance CO2 adsorption capacity [2 adsorption performance, showcasing the potential for efficient CO2 capture using activated graphene. This research highlights the significance of activation techniques in enhancing the surface and porosity of carbon nanomaterials, opening up potential carbon dioxide capture applications. Such advancements are critical in addressing environmental challenges and exploring sustainable energy solutions.Moreover, this Special Issue delves into the activation of graphene oxide, using COcapacity . These aIn addition, the exploration of hydrogen storage in nanoporous carbons holds promise for unlocking the potential of hydrogen-based energy systems. A review in this Special Issue explores the possibilities of nanoporous carbons for effective hydrogen storage by physisorption, highlights the current limitations, and proposes strategies to improve storage performance, including chemical modifications of carbon pore walls . PrelimiFinally, the complex structure and extraordinary properties of glass-like carbon (GLC), a vitreous material with exceptional properties that remain relatively unexplored, are discussed. By reviewing different models and a physical route involving pulsed laser deposition, the author outlines our understanding of GLC structure, topology, and geometry . The anaTo summarize, the contributions in this issue cover a wide range of topics, including the design of novel materials, the development of new synthesis methods, and the characterization of the properties of nanomaterials. French researchers have been at the forefront of advancing the understanding of carbon-based nanomaterials, such as carbon nanotubes and fullerenes, exploring their unique electronic, optical, and mechanical properties.One of the most exciting aspects of the research highlighted in this issue is its potential for real-world impact. For example, the development of 2D materials with tailored properties could lead to breakthroughs in electronics and photonics, while the use of carbon-based nanomaterials in energy storage devices could help to address the growing demand for renewable energy. Additionally, the biocompatibility of these materials makes them promising candidates for use in biomedical applications such as drug delivery and biosensing.Nanomaterials provides a comprehensive and up-to-date overview of the latest research in 2D and carbon-based nanomaterials in France. The contributions of French researchers in this field are significant, and their work is helping to advance our understanding of the unique properties and potential applications of these materials. As nanotechnology continues to evolve, it is clear that France will remain a key player in this exciting field. As we move forward, the collaboration between various stakeholders will be vital in translating these discoveries into practical solutions that benefit society and contribute to a more sustainable future.Overall, this Special Issue of We hope that this collection will provide a comprehensive overview of the current state-of-the-art of 2D and carbon nanomaterials research in France. We would like to express our gratitude to the authors for their valuable contributions to this Special Issue. We also thank the reviewers for their insightful comments and suggestions, which have greatly improved the quality of the papers. Finally, we hope that this Special Issue will inspire further research and collaboration in the field of nanomaterials in France and beyond."} +{"text": "Superconducting materials have been gradually applied in many areas including energy, transportation, medical imaging and communication. Among them, superconducting magnets that can generate a strong magnetic field above 10 Tesla with absolute advantages of higher quality, lower energy loss, and smaller volume, have become key to the performance improvement of cutting-edge science and large-scale engineering devices such as high-energy accelerators, thermonuclear fusion reactors, and magnetic resonance imaging devices and all-This special topic includes a review, an interview and two research papers, whose main purpose is to introduce the concept and connotation of \u2018mechanical perturbations induced quench\u2019, and the latest research progress, including studies of alleviating the brittleness of superconducting materials, and the influences of cracks on the thermomagnetic instability, which is often considered a reason for quench.The authors of the review article are Prof. You-He Zhou and Prof. Y. Iwasa, who are from Lanzhou University and Massachusetts Institute of Technology, respectively. They reviewed the research progress and challenges of fundamental mechanical problems in high-field superconducting magnets . In thiset al. [2Cu3O7-x (YBCO) superconductors, without reducing its superconducting properties, based on the customized 3D printing combined with a freeze-drying process. The second research paper in this special issue comes from Prof. Ze Jing of Northwestern Polytechnical University. Prof. Jing has been selected into the Young Elite Scientists Sponsorship Program of the China Association for Science and Technology, and won the first prize of the Jan Evetts SUST Award by the international journal Superconductor Science and Technology in 2020. Prof. Jing focuses on the effects of edge cracks on the thermomagnetic instability (TMI) of Type-II superconducting films and finds that the threshold field, the avalanche patterns, and the multifractal spectrum of the TMI process transit with the extension of the edge crack [The first research paper in this special issue comes from Lanzhou University. Zhang et al. have conIt can be seen from the above articles and interview that, on the one hand, SM is extremely important for the development of high-field superconducting magnets; on the other hand, the influence of mechanics to superconductivity, is not only part of the traditional understanding of superconductivity degradation, but also central to the new concept of \u2018mechanical perturbations induced quench\u2019. It is hoped that through the publication of this special issue of SM, electrical engineers can better understand the nature of \u2018mechanical perturbations induced quench\u2019, and continue making progress in developing high-field superconducting magnets."} +{"text": "Vitamin D performs a differentiating, metabolic and anti-inflammatory function, through genomic, non-genomic and mitochondrial mechanisms of action. In fact, vitamin D not only controls the transcription of thousands of genes and is involved in the modulation of calcium fluxes, but it also influences cellular metabolism and the maintenance of specific nuclear programs. Due to its broad spectrum of action, and because of the large number of target tissues, the deficiency of vitamin D and the molecular defects of its signaling pathway, such as VDR polymorphism or epigenetic silencing, can be involved in many pathologies.In this Special Issue, many scientists have contributed to elucidating the role of vitamin D in health and disease. Eight research articles and a compendium of nine reviews are published, covering different aspects of the activity of vitamin D and its defective signaling or low levels associated with many pathological conditions. Among diseases, the impact of vitamin D deficiency and supplementation in COVID-19 remains a hot topic, as revealed in the previous Special Issue \u201cThe role of vitamin D in human health and diseases\u201d and confirmed in this collection. Here, in addition to a systematic review discussing the evidence of beneficial effects of vitamin D supplementation in COVID-19 patients . SimilarThe effect of vitamin D in pregnancy was considered in two other studies of this collection. A systematic review examined the associations between maternal vitamin D levels and offspring neuropsychiatric and psychiatric outcomes, finding a positive association for attention-deficit/hyperactivity disorder and schizophrenia . MoreoveAmong the signaling pathways analyzed in this collection, the antioxidant and anti-inflammatory properties of vitamin D were largely investigated, and several studies revealed the central role of vitamin D in inflammatory diseases, such as COVID-19, diabetes, AKI, liver and kidney disease. The anti-inflammatory effects of vitamin D were explored in the adipose tissue of obese mice fed a high-fat diet , in T ceAmong the causes of variability in vitamin D signaling, single nucleotide polymorphisms (SNPs) are to be mentioned. Indeed, SNPs can influence the expression and/or functions of the VDR and of other genes in the vitamin D metabolic pathways, and may justify interindividual differences in responsiveness to the hormone. One study of this Special Issue explored five SNPs in the VDR gene in order to unravel the role of genetic polymorphisms on VDR expression in periodontal fibroblasts during simulated orthodontic compressive force . GeneticFinally, the effects of vitamin D supplementation were investigated in inflammatory diseases ,10 and iAs a whole, this Special Issue contains an interesting combination of research articles and reviews that present novel data on the effects of vitamin D in many pathologies, such as COVID-19 and diabetes, and in kidney, liver and cardiometabolic disease. The anti-inflammatory properties of vitamin D are the \u201cfil rouge\u201d in the heterogeneous spectrum of beneficial effects of the hormone described in this collection, which discusses current knowledge of the impact of vitamin D deficiency and supplementation in a variety of diseases."} +{"text": "Although nicotine and its pharmacological effects are central for sustaining tobacco product use, they may be insufficient to support product acceptance, as sensory stimuli attributable to flavors are particularly critical, reducing subjective measures of craving and withdrawal4. Therefore, in recent years, the tobacco industry has developed and introduced various cigarette technologies and design features, including new tobacco blends, additives, and, subsequently, new flavors. While the importance of flavors has been researched by the tobacco industry in the context of product development, the assessment of flavors for regulatory purposes with the use of sensory and chemical analyses is still under development \u2013 hence an emerging area for incoming tobacco control researchers5.The design and additives of tobacco products are significant factors that facilitate industry innovations that may undermine public health programs and contribute to tobacco use and addictionFurthermore, novel tobacco products that further perpetuate the complexity of understanding and effectively regulating products have emerged, and hence tobacco control research now covers a breadth of products. Like the breadth of COVID-19 variants encountered during the pandemic \u2013 each tobacco product has a different epidemiology and different \u2018high-risk groups\u2019, but all can be appropriately addressed with the application of specific surveillance and mitigation measures.6. The project proposes a series of integrated studies that were proposed to facilitate the training of researchers to examine tobacco product systems, their mechanisms and purpose, interactions between key design characteristics and their assessment, and monitoring in the population. The research training facilitated within EUREST-RISE will be coupled with training on communicating to key stakeholders, among others, policymakers, the media and the general public.In response to this new reality in tobacco control, the EUREST-RISE Project was launched with funding under the Marie Sk\u0142odowska-Curie Action for Staff ExchangesWith a consortium of academic and non-academic partner organizations, the EUREST-RISE project has three operational pillars, each of them directly linked to one of the vertical Work Packages (WPs).WP2 aims to facilitate the exchange of expertise on complex dataset analysis and interpretation at both the product and population level through the analysis of European Union Common Entry Gate (EU-CEG) product-level data and available European population-based secondary datasets.WP3 supports the exchange of expertise on the sensory and chemical analysis of tobacco, e-cigarettes and novel products, including training and research on chemical and toxicological assessment.WP4 supports training in advocacy, policy integration and communication on tobacco control with training in peer-to-peer, media, and stakeholder communication.The complex and multidisciplinary nature of tobacco product regulation involving public health, epidemiology, toxicology, chemistry, sensory science, and public policy, are constructs of training which have yet to be formulated into any formal academic training process in the EU. It is this gap that the EUREST-RISE project will cover through the creation of a cohort of researchers who will be trained as scholars on state-of-the-art aspects of European tobacco product regulatory science."} +{"text": "Science and technology have allowed human beings to live longer, more comfortably, and in relative safe life from natural weathering. In this scenario, non-communicable diseases linked to aging, sedentarism, and excess of energy consumption have become the major disorders to be contended with. Unfortunately, occasional movements against science have denied the benefit of historical conquests such as vaccination. Meanwhile, nutrition has a special appeal to the unscientifically minded; cyclically, a micronutrient emerges as a panacea able to guarantee health and protect against several chronic disorders. This thinking, similarly to the unfounded concern over vaccinations, tends to find basis in only observational studies with little other scientific backing. The last decade marked the turn of vitamin D. Previously considered a specialized molecule involved in the regulation of mineral metabolism, vitamin D is currently considered a pleiotropic hormone, as virtually all tissues and cells express vitamin D receptor - 3 . SuIn time of pandemic, researchers, physicians, and all chain of health employees are working hard to develop vaccine and drugs, as well as to assist patients harboring the SARS-CoV-2. Unexpectedly, they must also waste time alerting people to avoid false offers of therapy for prevention and treatment of COVID-19 that have no scientific basis and can have detrimental effects, including pharmacological dosage of vitamin D. In the present issue of the Archives of Endocrinology and Metabolism, Santos and cols. bring an appropriate view on the recommendation of vitamin D for those subjects showing vitamin D deficiency . More iFinally, I would like to give to the reader the consensual opinion from The International Osteoporosis Foundation (IOF), American Society for Bone and Mineral Research (ASBMR), American Association of Clinical Endocrinologists (AACE), Endocrine Society, European Calcified Tissue Society (ECTS), and National Osteoporosis Foundation (NOF) on usage of vitamin D in response to the current global pandemic, the COVID-19 . They aIn summary, safe exposition for few minutes (15-30 min) to sunshine naturally enables human beings to acquire the necessary amount of vitamin D, via auto sustainable synthesis of cholecalciferol. Alternatively, exogenous Vitamin D may safely bypass the thermal control of cholecalciferol synthesis within the skin when used in appropriate amounts. This target can securely be attained in most adults following the recommendation of IOM . The ra"} +{"text": "Cognitive Social Learning theory Bandura, tries toSelf-efficacy beliefs as a predictor of quality of life and burnout among university lecturers . The second analyzes How does teacher-perceived principal leadership affect teacher self-efficacy between different teaching experiences through collaboration in China .A total of 9 articles and 68 authors have contributed to the objective of showing recent models and evidence, derived from Albert Bandura's original theoretical model. Two papers, carried out by the participating researchers, analyze the effect of a key construct in Bandura: the Self-Efficacy. The first work is focused on the effect of Predictive model of the dropout intention of Chilean university students ; the second, entitled You and Me Versus the Rest of the World: The Effects of Affiliative Motivation and Ingroup Partner Status on Social Tuning .Other works have presented evidence regarding the effect of motivation in the teaching-learning process. The first refers to the The effect of individual and classroom moral disengagement on antisocial behaviors in Colombian adolescents shows this phenomenon.An article has addressed another essential aspect of his theory, referred to the moral impact of disengagement, as an explanatory mechanism of aggression and antisocial behavior. The work entitled Self-Regulated Learning, an essential construction derived from A. Bandura's theory. Shows the Short and Long-Term Effects on Academic Performance of a School-Based Training in Self-Regulation Learning .An experimental work is focused on internal and external regulation, applicable to different psychological contexts, in the paper entitled Advances on Self-Regulation Models: A New Research Agenda Through the SR vs ER Behavior Theory in Different Psychology Contexts . Complementarily, an initial validation study of the Assessment Scales of the Regulation/non-regulation/dyregulation construct is presented, in the work titled Self- vs. External-Regulation Behavior Scale TM in different psychological contexts: A validation study .Finally, two papers show a new, broader model of self-regulation, derived from the Theory of A. Bandura, presenting types of In conclusion, this Research Topic is also dedicated to the incredible person and psychologist Albert E. Bandura (1925-2021). Dr. Albert Bandura, was one of the most influential psychologists of all time. Bandura pioneered the field of social learning theory with his landmark Bobo doll experiment. He defined the construct of self-efficacy and proposed an agentic theory of human behavior that challenged the central tenants of behaviorism. Born in Alberta, Canada, in 1925, Bandura earned his undergraduate degree from the University of British Columbia in Vancouver and his graduate degree from the University of Iowa. He joined the faculty at Stanford University in 1953, where he served as the David Staff Jordan Professor of Social Science in Psychology. Bandura was elected APA president in 1973 and encouraged our organization to pursue matters of public interest. Bandura's significant contributions to the field of psychology were recognized in 1980 with APA's Distinguished Scientific Contribution Award and in 2004 with our Award for Outstanding Lifetime Contribution to Psychology. He also received the Gold Medal Award for Distinguished Lifetime Contribution to Psychological Science from APF and the Lifetime Career Award from the International Union of Psychological Science. In 2016, he was awarded the National Medal of Science by President Barack Obama.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "Staphylococcus aureus is an extracellular bacterium that causes surface to severe hematogenous infections with high infection rate and mortality. Thus, novel antibiotics are urgently required to treat these bacteria. Essential oils (EOs) showed the antibacterial activity and has become the basis of many applications, including alternative medicine, natural therapies, food preservation, raw and processed, and pharmaceuticals. Natural products with EOs can be make use of as raw materials in antibacterial substances.Subjects and Methods: In this study, the \u0251-pinene is a major compound of Pinus densiflora Sieb. et Zucc. (PSZ) EOs. The antibacterial activity of the essential oil extracted from PSZ against MRSA was investigated. The inhibitory effect of \u0251-pinene on MRSA growth, acid production, biofilm formation and expression of virulence factors were examined.Results: PSZ EO was analyzed by gas chromatography (GC) and GC coupled for mass spectrometry, which identified 58 constituents, accounting to 90.98% of the total EO. The most components in all the EOs is \u03b1-pinene (20.56%). At concentrations of higher than 0.25\u2005mg/mL (p<0.05), the \u0251-pinene was examined to inhibit the growth of MRSA. After using the safranin staining method, \u0251-pinene showed an inhibitory effect against biofilm formation. As well as the experimental results were similar to the scanning electron microscopy. At high concentrations with \u0251-pinene in a concentration dependent manner (of 1\u20138\u2005mg/mL) also showed a bactericidal effect by the confocal microscopy. According to the real-time polymerase chain reaction, mRNA expression of virulence factor genes, sea, agrA, mecA, and sarA, was observed. All the expression was observed at a concentration of 0.25\u2005mg/mL by \u0251-pinene.Conclusions: These results suggest that \u0251-pinene, a major compound of PSZ EOs, has the antibacterial activity against MRSA, antibiotic resistant bacteria.This paper was supported by Wonkwang University in 2019.aCunbo Wua Chongqing Mental Health Center, Gele Mountain, Shapingba district, Chongqing, China.Objective: To investigate whether modified electronconvulsive therapy (MECT) causes fever and its causes and feature.Methods: In accordance with the inclusion and exclusion criteria, Data analysis was conducted on 12 patients with mental disorders who were treated with modified electronconvulsive fever after treatment from February to May 2022 at chongqing Mental Health Center.Results: Fever is more common in adolescents after MECT treatment, 4 persons under the age of 20, accounting for 33.3%; 5 persons aged 20-29, accounting for 41.7%; mainly with moderate fever, 7 cases (58.3%), usually occurs in the second time of MECT (50%) and in that afternoon of the day after operation, 11 cases (91.6%). One case was fever after the third time, accounting for 10%; Two cases (20%) developed fever after the eighth MECT. 4 cases had normal blood routine after MECT. 8 cases (66.7%) had elevated WBC. 4 cases (33.3%) showed normal CRP during fever after MECT. CRP was elevated in 8 cases (66.7%). Among the patients with fever, there were 5 females (41.7%) and 7 males (58.3%). 9 cases (75%) of febrile patients were schizophrenic. 2 cases of affective disorder (16.7%); 1 case (8.3%).Conclusions: The fever caused by MECT should not be ignored and should be treated promptly. Relevant auxiliary examination should be improved to clarify the cause and further treatment. MECT treatment should be suspended if necessary.a, Bing Hua, Qinjing Lia, Linlin Liua, Zhenzhen Doua, Zhihui Zhaob, Liang Zhua, Tianming Chena, Lingyun Guoa, Gang LiuaXin Guoa Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, 100045, China, b Department of Heart Diseases, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, 100045, China.Background: Infective endocarditis (IE) is a rare and fatal disease in children, with Staphylococcus aureus (SA) as the leading cause in many regions of the world. Staphylococcus aureus infective endocarditis (SAIE) often presents sudden onset of sepsis and embolism, with multiple organs damage. SAIE with persistent bacteremia is a challenge in clinical practice. Some specific antibiotics such as daptomycin are available as an alternative when conventional treatment fail.Subjects and Methods: The research team retrospectively analyzed the medical records of 7 pediatric patients with infective endocarditis caused by Staphylococcus aureus admitted to Beijing Children\u2019s Hospital from February 1, 2018 to February 28, 2021. The etiology, symptoms and signs, laboratory results, treatment and prognosis were collected, and compared with 13 other cases. Blood culture and echocardiography were used to diagnose the disease, and the efficacy of different antibiotics was analyzed.Results: SAIE accounted for 35% (7/20) of all IE patients, with 7 cases ranging in age from 1 year 5 months to 13 years 8 months. 3 cases (42.9%) had methicillin- resistant Staphylococcus aureus (MRSA) and 4 cases (57.1%) were methicillin-sensitive Staphylococcus aureus (MSSA). A total of 4 cases (57.1%) had congenital heart disease. All patients (100%) had fever and 3 cases (42.9%) had major vessel embolic events. 4 cases (57.1%) had central nervous system complications and 4 cases left heart endocarditis. All patients initially received vancomycin-based treatment regimens. 2 cases (28.6%) with persistent bacteremia were changed to a 9\u2005mg/kg/dose of daptomycin when the conventional treatment failed to vancomycin therapy. The outcomes were good and no significant side effects occurred. Daptomycin in our study was first applied successfully for SAIE with persistent bacteremia in Chinese children.Conclusions: SA was the common major pathogen detected in IE. Appropriate antibiotic therapy needs to be adopted, and evaluation of persistent bacteremia and vascular embolic events is needed. The study also showed that vancomycin and linezolid are still the first-line choices for treatment of the disease, but daptomycin can also be an effective treatment option.The authors would like to thank Huiyu Liu\u2019s writing support from MSD, Qinjing Li and Tianming Chen\u2019s support during the conduction of this study.a, Lin Niub, Haijun Shana, Caihong Caoa, Yingying Zhanga, Yujin HouaXiaosu Jiea Child Rehabilitation Department, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, China, b Department of medical technology, Zhengzhou Railway Vocational and Technical College, Zhengzhou, China.Background: This study analyzed the effects of Jiao\u2019s scalp acupuncture combined with task-oriented training on gross motor function classification, gross motor function assessment and motor development of children with spastic cerebral palsy. Spastic cerebral palsy is the most common type of cerebral palsy with motor dysfunction among the main clinical manifestations. Even the severe patients can not walk for life. So exercise intervention is the focus of cerebral palsy treatment. This study aims to provide more effective treatment methods for pediatric spastic cerebral palsy.Subjects and Methods: Fifty children admitted to our hospital for spastic cerebral palsy from January 2020 to June 2021 were enrolled, and assigned to the control group (n=25) receiving task-oriented training, and the observation group (n=25) receiving Jiao\u2019s scalp acupuncture plus task-oriented training. Before and at 6 months after treatment, the gross motor function grade, gross motor function assessment score changes and the satisfaction of children\u2019s guardians with rehabilitation treatment were compared.Results: After the treatment, the total gross motor function score was higher in the observation group (P<0.05). The number of gross motor function in patients with decreased grade, the Peabody motor development score, the satisfaction and overall clinical efficacy of the children\u2019s guardians were higher in the observation group .Conclusions: Jiao\u2019s scalp needle was founded by Professor Jiao Shunfa in 1971. Based on the theory of cerebral scalp needle has been widely used in the clinical treatment of various encephalopathy in China due to its convenient acupoint selection and simple operation, and has achieved positive clinical effect in the treatment of spastic cerebral palsy in children. Jiao\u2019s scalp acupuncture combined with task-oriented training applied in spastic cerebral palsy children has obvious practical effect. They can reduce the disease of children and improve the level of gross motor function of children, improve the quality of life and self-reliance, self-care ability of children at the same time. It also can enhance parents\u2019 confidence in rehabilitation and improve parents\u2019 satisfaction with rehabilitation treatment. As a result, the effect is better than that of task-oriented training routine treatment.This work was supported by the Scientific research project of traditional Chinese medicine in Henan Province, Project: 2019ZY2056a, Yi FengaChenlin Wanga School of Art and Design, Beijing Forestry University, Beijing, China.Background: The incidence of Autism Spectrum Disorder (ASD) in children around the world is on the rise, and the development of mental health in autistic children due to physical defects can lead to cognitive, emotional, behavioral and other disorders. Since the etiology and biochemical abnormalities of ASD have not been fully elucidated, and there is no specific drug to treat ASD pathologically, ASD has increasingly become a worldwide problem facing human society. The importance of toys for the healthy development of children makes it possible to improve the above problems through toy training. The design of cognitive behavioral training toys for children with ASD has received a lot of attention. The INPD method is widely used in many fields, providing the possibility to solve the problem of designing cognitive behavioral training toys for children with ASD.Subjects and Methods: Based on the design method of INPD theory, the design strategy of ASD Children\u2019s cognitive behavioral health training toys is explored. This paper uses INPD, combined with AHP, to guide the toy design ideas for ASD children. Firstly, the design gaps is found from SET analysis method; then, a questionnaire survey is conducted on ASD children\u2019s families to clarify the needs of ASD children\u2019s families for cognitive behavioral health training toys and classify the needs to form a hierarchical diagram of user needs; finally, the nine-scale method of AHP hierarchical analysis is introduced to calculate the important priorities of different levels of needs. Finally, different requirements are sorted into design strategies in priority order.Results: The product concept is then translated into a design strategy. According to the priority order of needs, the design strategy of ASD children\u2019s cognitive behavior training toys should focus on logic and cooperation in content, establish toy IP and develop intelligent training toys. In addition to following the safety principle, the design principle should also pay attention to the simplicity and scalability of toys, so as to fully realize the purpose of training the physical functions of ASD children and letting them grow up healthily.Conclusions: The design method of combining INPD and AHP effectively solves the problem of prioritization of user needs in toy design, provides a new design idea for the design of cognitive behavioral health training toys for autistic children, and also provides a new method for other research on user needs.aJunwei Wanga Wuhan Sports University, Wuhan 430079, China.Background: With the rapid development of high quality in the education, the aim of this study was to Children sensory integration has become the focus of global education. It has important theoretical and practical significance to improve children\u2019s sensory integration through sports activities or training.Subjects and Methods: Take the development frontier and practice cases of children sports and sensory integration abroad as an opportunity, this paper uses comprehensive analysis methods, such as literature review and data statistics, to comb the meaning, application and design of children\u2019s sport and sensory integration. Meanwhile, this research will focus on the development history, current situation, function and role of sensory integration. Combining the special functions of sports and empirical cases, explain children\u2019s bad behaviors in the environment, life, and learning, and provide a scientific de mainly base sign path.Results: Sensory integration training is based on games to cultivate children\u2019s learning interest, self-consciousness, and teamwork capabilities. They Correct children\u2019s incorrect standing, sitting, walking, running, etc. through specific language environment, body movements and teaching aid guidance and behavior habits. Therefore, children sports is a brand-new training model tailored to the individual needs of children. Studies have found that the early childhood stage is a key stage for the development of the sensory nervous system. It is believed that the sensory system is a sub-component of the brain motor control system, which needs sports activities or training to stimulate the neural linkage, and the linkage is realized through the complementary relationship between static and dynamic components, On the child\u2019s brain growth and limbs and trunk have a healthy role in promoting.Conclusions: Sports activity or training can promote children\u2019s body, vestibular, tactile and other sensory systems to process, improve the flexibility and adaptability of children\u2019s body posture, joints, muscles, eyesight, hearing and other body parts during exercise, and have a positive impact on children\u2019s cognitive and mental health. The purpose is to solve children\u2019s behavioral cognition and mental strengthening training, so that the child\u2019s brain can smoothly integrate and process various sensory information and make correct decisions. Therefore, learning sports activities in childhood is an important functional attribute of promoting the healthy growth of children.Foundation Project: 2019 Scientific Research Program of Hubei Provincial Department of Education (Project number: B2019196); Wuhan Sports University Scientific Innovation team of young and middle-aged funding project.a,b, Haili Lib, Shi Guob, Guoping Wangb and Hairong LiubPenghui Xua Department of Management, Jiangsu University, Zhenjiang, Jiangsu 212013,China, b Anhui Key Laboratory of Philosophy and Social Sciences for Public Health Crisis Management in Colleges and Universities, Wannan Medical College, Wuhu 241002, China.Background: To investigate the impact mechanism of health input structure attributes on health development and its regional differences based on the perspective of human capital.Subjects and Methods: Using panel data from 31 Chinese provinces from 2011 to 2018 and using the systematic GMM estimation method, the public health output effects of the health expenditure structure and its regional differences were investigated.Results: Firstly, the empirical results showed that social health expenditure significantly increased public health output. There were regional differences: the eastern region showed the strongest effect in this regard, the central region had the second strongest, and the western region involved the weakest effect. However, government health and personal hygiene investment did not significantly increase public health output. Second, the number of doctors per thousand people had a significant impact on public health output, but there were significant regional differences: the eastern region had the strongest promotional effect, while the central and western regions were not significant. Third, there were significant regional differences in the impact of the number of beds per thousand people on health output, of which the western region was the most significant, followed by the central region, and the promotional effect in the eastern region is not significant. Fourth, the per capita GDP and environmental factors in the three major regions of eastern, middle, and western China had no significant impact on the health level, while there was a significant regional difference in the impact of per capita education level on the health level. The regional promotional effect was relatively high, while the central and western regions were not significant.Conclusions: The conclusions of this study have important policy implications. In order to further improve the health of residents and build a healthy China, we put forward the following policy recommendations: Strengthen the input of health resources in key areas is to ensure basic medical services, effectively ensure the equalization of basic medical services, and improve the accessibility and affordability of medical services; The government should increase support for social health in the central and western regions, implement a variety of tax incentives to promote the continuous growth of social health expenditure, and build a mechanism to maximize the efficiency of health resources.The authors thank all participants who made an effort in this study. This study was funded by the grants from the Ministry of Education of China (grant 20YJCZH193) and Anhui Provincial Department of Education (grant SK2017A0212).a, Xiaoyu Changa, Qinglan Liua, Kaiwen Zhaob, Songqiang Yic, Yingmei Yua, Sansan Shaoa, Zhenghua Huanga, Ruili Lid, Siming LiaHan Yana Key Laboratory for quality and safety control of poultry products, Ministry of Agriculture and Rural Affairs of the People\u2019s Republic of China, Institute for Quality & Safety and Standards of Agricultural Products Research, Jiangxi Academy of Agricultural Sciences, Nanlian Road 602, Nanchang 330200, China, b Nanchang Institute of Technology, Nanchang 330044, China, c Agricultural Technology Extension Center of Jiangxi Province, Nanchang 330046, China, d Yantai Academy of Agricultural Sciences, Yantai 265500, China.Background: Selenium is a necessary nutrient element in the human body. Because the human body cannot synthesize selenium, it needs to be supplemented from the outside. Moderate supplement of selenium can improve human immunity and resistance, and promote human health. At the same time, with the improvement of people\u2019s living standards, the development of healthy and safe functional selenium enriched eggs has attracted more and more attention. In this study, Dongxiang green-shell laying hens was taken as the experimental object, to investigate the effect of nine different kinds of selenium (Se) feeding methods to Dongxiang green-shell laying hens with different morphological characteristics (red and purple comb) on egg concentration, viscera antioxidant properties, and slaughter index. In order to provide a basis for the production of safe and healthy selenium enriched green shell eggs.Subjects and Methods: The experiment was carried out on two hundred and fifty two 30-week-old Dongxiang black feather laying hens and the red comb ones and purple crests ones equal share of the total number of the test. These hens were allocated to nine dietary treatments and each group was divided into four parallels with 7 hens per replicate and two of the replicates have red crests and the other have purple crests. respectively. The hens were free to eat and drink during the experiment. We controlled the winter feeding temperature between 16 and 18 \u00b0C and the lighting in hen house was 14h daily.Results: The result shows that the organic selenium group has higher portion of selenium in all indicators measured than inorganic selenium group significantly (P<0.1). Also the total selenium content is higher in high concentration group than in low ones under the stress of the same selenium source. Moreover, enrichment of selenium content in egg and breast was the most effective via application of dietary selenomethionine (0.6\u2005mg/kg) in purple crown group. Statistically, there is a significant difference (P\uff1c0.1) in the concentration of selenium deposition in eggs between purple and red cockles in the same selenium source group . And the difference in the color of chicken\u2019s crown had a significant effect on the selenium content deposited in the plasma and visceral of the selenomethionine treatment group (P<0.1).Conclusions: the selenium supplemental concentration was positively correlated with the anti-oxidant capacity in viscera and the effect was significant. In conclusion, adding 0.6\u2005mg/kg selenomethionine in the diet of purple crown laying hens has the best effect on selenium enrichment in eggs and tissues, and the detection indexes are better than those of red crown ones. This study provides a theoretical basis for the development of selenium-rich products.Study on selenium deposition mechanism and key technologies of Product development and utilization in green shell eggs (Item number: 20202BBFL63029); Study on technology system of nutritional evaluation of agricultural products (JXXTCXNLTS202103); Study and application of key technologies for high value fermentation of Selenium-rich rice (Item number: 20202BBFL63011).a,b, Weixiong Liaoa, Zhongyan Wenb, Yue Zhaoc, Yonghui Liub, Jincan ChenbGanbin Qiua Imaging department of Zhaoqing Medical College, Zhaoqing 526020, China, b Department of Radiology, The First People\u2019s Hospital of Zhaoqing, Zhaoqing 506040, China, c Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou 510000, China.Background: To compare the changes of brain low-frequency amplitude (ALFF) in patients with primary insomnia (PI) and healthy control group (HC) before and after the treatment of Shenmen combined with Neiguan point, and to explore the neural mechanism of brain function changes in patients with PI by electroacupuncture Shenmen combined with Neiguan point.Subjects and Methods: From November 2019 to May 2022, 23 PI patients were recruited in Zhaoqing First People\u2019s Hospital as the study group, and 26 healthy volunteers with age, sex and education level were recruited in society as the control group; All the subjects were scored with the clinical Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) before acupuncture, and all the subjects were scanned with resting MRI before acupuncture treatment; Then select Shenmen and Neiguan points of the two groups of subjects for electroacupuncture therapy. After \u201cDeqi\u201d, the electroacupuncture will continue to stimulate for 30 minutes. After another electroacupuncture treatment the next day, the resting MRI scan will be performed again. The low frequency amplitude (ALFF) analysis method was used to calculate the ALFF of brain regions between PI group and HC group before and after acupuncture, and the rest state in PI group before and after acupuncture.Results: There was no significant difference in gender and age between the two groups (p>0.05), but the PSQI score, HAMA score and HAMD score of patients in the study group were significantly higher than those in the control group (p<0.05). Before acupuncture treatment, the brain areas with increased ALFF values in PI group included the right cuneiform lobe, left inferior temporal gyrus, left amygdala, etc., while the brain areas with decreased ALFF values included the right parahippocampal gyrus, right anterior cuneiform lobe, left inferior parietal lobule, and left thalamus; After acupuncture treatment, the brain areas with increased ALFF values in PI group included the left posterior cingulate gyrus, bilateral anterior cuneiform lobe and right cuneiform lobe, and the brain areas with decreased ALFF values included the left amygdala, the right transverse temporal gyrus, and the right posterior central gyrus.Conclusions: The brain regions of default network, significant network and part of emotional cognitive network in patients with primary insomnia (PI) are damaged, which may be the microcosmic manifestation of daily behavior and cognitive abnormalities in PI population. The combination of electroacupuncture at Shenmen and Neiguan points can activate part of the damaged brain areas of PI population, so as to improve the mental state and sleep, which may provide a new auxiliary scheme for clinical treatment of PI population.This work was supported by the Science and Technology innovation of Zhaoqing City, Guangdong Province, China under Grant (No. 2019N008). This work was supported by Medical Scientific Research Foundation of Guangdong Province, China under Grant (No.B2020225).a, Tian Tiana, Shengzhi Tana, Tao Liua, Dong Wanga, Yuan Lia, Di Wua, Rong TanaKai Cuia Department of Spine Surgery, Strategic Support Force of Chinese PLA, Beijing, 100101, China.Background: To evaluate the safety and reliability of minimally invasive Dynesys implantation and discectomy (MIS-Dynesys) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant tube in single level lumbar degenerative diseases.Subjects and Methods: From January 2016 to December 2018, a retrospective analysis was carried out on 65 patients with single-segment lumbar degenerative diseases admitted to our hospital. Among them, 21 patients, 12 males and 9 females, with an average age of 64.57\u2009\u00b1\u20096.8 years, were treated in the MIS-Dynesys group, and 44 patients in the MIS-TLIF group, 19 cases in men and 25 cases in women, with an average age of 64.16\u2009\u00b1\u20095.71 years old. The general data, duration of surgery, bleeding volume, drainage, and oswestry disability index (ODI), JOA score (Japanese Orthopedic Association), and Visual Analogue Scale (VAS) for preoperative and postoperative and final follow-up were recorded to evaluate clinical efficacy. Before surgery, X-rays of lumbar orthovertebral lateral position and flexion and extension position, lumbar CT, lumbar spine MRI combined with clinical determination of the responsibility gap. 2 days after the operation, X-rays of the lumbar vertebrae in the lateral position and the flexile and extensive position were taken, and the LUM CT was re-determined to determine the internal fixation position and then moved to the ground. At the last follow-up, both patients were taken X-rays of the lumbar orthovertebral lateral position and flexion and extension motility position, the mobility of the surgical segment was measured, and the fusion group reviewed the CT to assess the fusion effect, and the data were collected for comparative study.Results: The follow-up time of the two groups of patients was 6-39 months. The results of the MIS-Dynesys group and the MIS-TLIF group were not statistically significant in terms of general data, and operation time, and bleeding volume (P>0.05), and the former had significantly lower drainage than the latter, and the difference was statistically significant (P<0.05). Preoperative ODI JOA lumbago and leg pain VAS scores in 2 groups were not statistically significant (P>0.05); ODI JOA and lumbago and leg pain VAS scores in 2 groups at the end of 3 months after surgery were significantly improved compared with those before surgery, and the differences were statistically significant (P<0.05); ODI JOA and lumbago and leg pain VAS scores were not statistically significant between the two groups at the end of 3 months after surgery(P>0.05).There was no statistical difference in the activity results of the preoperative target segment (P>0.05) between the two groups, and the postoperative follow-up, the former of which still maintained a certain degree of activity, and the latter was well fused, the mobility was 0, and the difference was statistically significant (P<0.05).Conclusions: For single level lumbar degenerative diseases, MIS-Dynesys can achieve similar result with the MIS-TLIF. The MIS-TLIF group had more drainage and fusion. The MIS-Dynesys group maintain a degree of motion.a, Fangliang Huanga, Tongping ShenaHuanqing Xua School of Medicine and Information Engineering, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China.Background: To cultivate new medical talents with high information literacy and healthy mental qualities, the teaching of basic computer courses in medical schools should be made more practical, specialized and useful. The goal of this paper is to study how the characteristics and advantages of the subject matter of basic computer courses in medical schools can be combined with mental health education and permeated in classroom teaching, in order to cultivate good motivation and a healthy personality for students and to establish a positive and active mental quality for later entry into the workplace.Subjects and Methods: This paper is to highlight the professional characteristics of medicine in the teaching of basic computer courses at Anhui University of Chinese Medicine, and to create a computer course with a \u201cmedical flavor\u201d. The course integrates computational thinking into the curriculum and further enhances students\u2019 understanding and absorption of knowledge by \u201cdissecting\u201d complex problems at different levels. In addition, the online and offline integration of the SPOC teaching model can fully motivate students to learn on their own. In the teaching of basic computer courses, the overall objective of quality education should be taken as the basis for establishing corresponding mental quality objectives. Through training, counselling, implication and infection, students\u2019 mental quality will be improved, their mental barriers will be solved, their mental health will be promoted and their healthy mental qualities will be cultivated.Results: After one cycle of reform practice, the teaching results of four Applied Psychology classes of different grades taught by the author were remarkable. A comparison of the course formative assessment results shows that the SPOC combined with the computational thinking development teaching model and integrate into mental health education has greatly stimulated students\u2019 interest in learning, with a significant increase in both pass and merit rates.Conclusions: Classroom practice shows the importance of integrating computational thinking and health education into the SPOC teaching model as a \u2018new treatment\u2019 to facilitate the development of pedagogical reform in the course.This study was supported by the Key Project of Scientific Research in Anhui Higher Education Institutions of China under Grant NO. KJ2021A0587 and NO. SK2020A0244, the Provincial Quality Engineering Project in Anhui Higher Education Institutions of China under Grant No.2020jyxm1029 and 2022jyxm857.a, Feng Shana, Yimeng Wangb, Ya Liua, Yao Liua, Yunfang ZhenaJun Wena Department of Orthopaedics, Children\u2019s Hospital of Soochow University, Suzhou, Jiangsu 215000, China, b Department of Orthopaedics, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.WJ and SF contributed equally to this study.Background: To explore the efficacy of interlocking intramedullary nail in the treatment of femoral shaft fractures in adolescents.Subjects and Methods: The clinical data of 10 adolescent femoral shaft fractures treated with interlocking intramedullary nailing in our hospital from January 2020 to December 2021 were retrospectively analyzed. Among the patients, 8 were male and 2 were female. Their ages ranged from 11.5 to 15.3 years . Their weight ranged from 50.2kg to 70.2\u2005kg . The procedure was fixed with a static interlocking intramedullary nail. Periodic follow-up examinations were performed to monitor the occurrence of complications and to record the time of union of the fracture. At the last follow-up, neck shaft angle (NSA), medial proximal tibial angle (MPFA), femoral head diameter (FHD), femoral neck diameter (FND), and articulotrochanteric distance (ATD) were measured on the X-ray. Functional recovery of the affected limb was assessed using Thoresen\u2019s criteria.Result: The mean follow-up time was 14.4 months (10-17 months). All fractures healed, and all incisions healed at the first stage. No infection or incision dehiscence occurred. The average fracture union time was 5.1 weeks (4-8 weeks). The average radiological union time of the fracture was 9.6 weeks (6-12 weeks). There was no nonunion of the fracture,no delayed union, no malunion, no broken nails, no re-fracture. A leg length discrepancy of 1.4cm was observed in one case. One patient had ectopic ossification above the greater trochanter. Pressure ulcers occurred at the ankle in one patient. The NSA, MPFA, FHD, FND, and ATD at the final follow-up were, respectively, for the affected side,which were insignificantly different from those for the healthy side (P>0.05). According to the Thoresen criteria, there were 8 (80%) excellent, 1 (10%) good, and 1 (10%) satisfactory results with an excellent to good rate of 90%.Conclusion: Interlocking intramedullary nailing is clinically effective in the treatment of femoral shaft fractures in adolescents, with excellent fracture union, few complications and no significant effects on proximal femur development in the short term.This work was supported by funds from National Natural Science Foundation of China (no. 82172520).a, Guoshuai Mab, Gandan Sic, Xiaoqiang Liud, Lixin CheneFenglan Guoa School of Physical Education, Xinjiang Normal University, China, b Xinjiang Institute of Engineering, China, c School of Physical Education, Changji University, China, d Urumqi NO.8 middle school, China, e Xingjiang Vocational Institute of Energy Technology, China.Background: In the era of \u201cInternet +\u201d, the application of blended teaching method has become an important starting point for the construction of first-class physical education courses in China, which is the direction of the curriculum reform of higher physical education and highlights its unique advantages in the application and development of physical education classroom teaching, namely, blended teaching can not only be applied to the theory and health knowledge classroom, but also can be combined with physical education technology teaching. And then provide services to promote students\u2019 health, health education and its physical and mental health.Subjects and Methods: This study takes blended teaching method of general track and field courses as the research theme, adopts the methods of literature review, questionnaire survey and on-the-spot investigation to carry out the application implementation of the online and offline blended teaching method for the students in Grade 2021 of physical education major, and explores the application effect of online and offline blended teaching practice of general track and field courses.Results: (1) Blended teaching of track and field general courses should include independent learning, cooperative learning, question answering, practice consolidation, summary and evaluation. (2) The application of mixed teaching of track and field general courses has different degrees of influence on the innovation of teaching and learning, the working efficiency of teachers, the improvement of students\u2019 technical skills and abilities, and the evaluation of teaching performance. (3) Combining mixed teaching of track and field general course with ideological and political practice of the course has a certain promoting effect and value on the mining, design and practical application of ideological and political elements of the course. (4) Through the combination of online and offline teaching and practice platform of track and field courses, the concept of physical and medical integration can be integrated into the sports training and rehabilitation education and learning of college students majoring in physical education, so that the sports health education of college students majoring in physical education can develop in a scientific wayConclusion: (1) Use the Chaoxing Learning platform to carry out blended teaching design and practice, expand students\u2019 multiple ways of learning in track and field, meet students\u2019 professional learning needs, and improve students\u2019 self-learning ability (2) By teaching theories and health knowledge about track and field events online, and learning skills online and offline, students can better master the health knowledge about track and field, fitness means and skills, cultivate students\u2019 professional quality of teachers, and enhance students\u2019 comprehensive ability of sustainable development. (3) The referee practice of track and field general training events and the ability training of demonstration and explanation are carried out in the way of cooperative group rotation, so as to stimulate students to give full play to their potential, integrate and expand the application of what they have learned, and cultivate the core quality of physical education teachers in primary and secondary schools. (4) Integrate ideological and political education into the online and offline teaching process, improve students\u2019 comprehensive ability and the effect of ideological and political education in the course, so that the core quality of students\u2019 future teacher career can be improved accordingly, which is in line with the talent training program. (5) The combination of online and offline teaching methods can organically combine skill practice with theoretical learning of sports health education, so as to promote the effectiveness and scientific development of track and field courses.This work was supported by the First-Class Undergraduate Course of Xinjiang Normal University in 2021 ----Hybrid Online and Offline First-Class Courses (Track and Field), the Social Science Fund of Autonomous Region, Project No.: 22CTY031.aJian Xua China Export & Credit Insurance Corporation, Beijing 100033, China.Background: To illustrate how RCEP offers positive psychological incentives and emotional regulation for the traders and investors, thus promoting trade and investment in East Asia, and to give some suggestions on how China export credit insurance could play an important role in serving China\u2019s opening up and supporting enterprises to develop markets in the contracting parties.Methods: This paper, from the psychological perspective, compares RCEP with the General Agreement on Tariffs and Trade (GATT), the General Agreement on Trade in Services (GATS), the Agreement on Trade-Related Investment Measures (TRIMs), the Trade Facilitation Agreement (TFA), Agreement on Safeguards(AS), the US-Canada-Mexico Agreement (USMCA), the EU-Canada Comprehensive Economic and Trade Agreement (CETA), and the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) to illustrate how RCEP offers psychological incentives and emotional regulation for the traders and investors, thus promoting trade and investment in east Asia. Besides, the paper preliminarily judges the opportunities and challenges of China export credit insurance to support China\u2019s enterprises in conducting trade and investment in the contracting parties, finally, it gives some suggestions on how China export credit insurance could play an important role in serving China\u2019s opening up and supporting enterprises to develop markets in the contracting parties.Results: The analysis of RCEP rules shows that RCEP will give positive psychological incentives and emotional regulation to traders and investors in East Asia, and then expand regional trade and investment in the region. At the same time, RCEP allows the parties to take relevant protective measures, which may reduce the psychological expectations of traders and investors, and thus may have negative effects on trade and investment in the region. Based on the above, from a practical point of view, China export credit insurance could strengthen the positive psychological incentive and emotional regulation of the agreement, stabilize the psychological expectation of China\u2019s traders and investors to develop market in East Asia.Conclusions: RCEP rules could give positive psychological incentives and emotional regulation to traders and investors in East Asia. At the same time, RCEP may have negative effects on trade and investment in the region. China export credit insurance, starting from the following 4 aspects, could strengthen the positive psychological incentive and emotional regulation of the agreement, stabilize the psychological expectation of China\u2019s traders and investors to develop market in east Asia: 1. A deep understanding that opportunities brought by RCEP are conducive to better integration of China export credit insurance into the China\u2019s development; 2. Take the bidding list of the contracting parties within RCEP as the starting point, and clarify the specific support direction from China export credit insurance for China\u2019s enterprises; 3. China export credit insurance shall provide timely support to promote China\u2019s enterprises to build a more mature supply chain layout of foreign trade industry among contracting countries within RCEP.a, Qiyan JiangbDawei Yanga Shandong Polytechnic, Jinan, Shandong, 250104, China, b Zaozhuang Transportation Service Center, Zaozhuang Shandong, 277800, China.Background: The purpose of this dissertation is to explore the impact of rural health human resource allocation on the mental health of rural residents. The increasingly prominent problem of health human resource allocation in rural areas affects the quality and coverage of medical services and has an important impact on the psychological health of rural residents.Subjects and Methods: Through collecting relevant literature and field research, this paper analyzes the main problems of rural health human resource allocation, including insufficient number of medical personnel, low level of medical technology, and uneven distribution of medical resources. These problems have led to difficulties in accessing medical services and mental health support for rural residents. This dissertation also explores the relationship between rural health human resource allocation and the mental health of rural residents.Results: An unreasonable allocation of health human resources can lead to rural residents\u2019 dissatisfaction and distrust of medical resources, which in turn affects their mental health status. The lack of professional mental health service personnel and psychological support mechanisms is also an important cause of mental health problems among rural residents. However, some positive practices and countermeasures have been proposed, including strengthening the training and introduction of health human resources, improving the mental health literacy of medical personnel, and establishing a sound mental health service network.Conclusions: Through an in-depth study of the impact of rural health human resource allocation on the mental health of rural residents, we can better understand the root causes of the problem and the mechanisms of influence, and make corresponding policy and practice recommendations. Improving rural health human resource allocation and providing better medical services and psychological support are important for promoting the mental health of rural residents. This study provides useful references for relevant departments and policy makers to better respond to the rural health human resource allocation problem and improve the mental health of rural residents.a, Jin Yana, Feiqin LibKaigang Yia School of Business Administration, Zhejiang Gongshang University, Zhejiang, 310018, China, b Zhejiang Gongshang University Hangzhou College of Commerce, Zhejiang, 311508, ChinaBackground: Credit is the key mental health factor to support the economic development of the platform, while demand-side users are the direct \u201cfact implementers\u201d of credit fraud on the network platform, but they are also easily overlooked subjects. Studying the formation mechanism of demand-side users\u2019 credit fraud from the perspective of consumer psychology can provide a new direction for the governance of credit fraud on the network platform. Based on the theory of planned behavior and fraud risk factors, this paper integrates and constructs a theoretical model of the mechanism of credit fraud of platform demand-side users through theoretical applicability analysis.Subjects and Methods: On the basis of theoretical deduction, seven hypotheses were constructed, and 312 valid questionnaires were collected by taking the demand-side users of online shopping platform as the empirical research object. On the basis of reliability and validity test, the structural equation model was used to statistically test the fitting degree and research hypotheses of the whole model, and then the nest model method was used for further verification.Results: (1) attitude of credit fraud, subjective norms of credit fraud, and control of perceived behavior of credit fraud have direct positive effects on the intention to commit credit fraud; (2) Perceived risk indirectly affects the intention to commit credit fraud through the control of perceived behavior of credit fraud; (3) Risk preference plays a moderating role in the influence of perceived risk on the control of perceived behavior of credit fraud.Conclusions: According to consumer psychology, credit fraud committed by platform demand-side users is influenced by personal morality and interests, government supervision and punishment, and important stakeholders in society, which provides a certain direction for innovative research on governance countermeasures. (1) At the regulatory level, the government and the platform main body should first pay more attention to the harmfulness of credit fraud of demand-side users of the platform, and speed up the formulation of special programs or special documents to deal with this problem; (2) At the technical level, we should, on the basis of the relatively mature technical discrimination against credit fraud of platform supplier users, draw lessons and innovate technical means to strengthen the transaction management of demand-side users, and use technology to empower supervision and warn fraud, so as to reduce the implementation space of fraud; (3) At the social level, it is necessary to carry out thematic series of publicity and reports in combination with the special actions of industry and commerce department, public security department and other departments aimed at the governance of online platform credit fraud.This paper was funded by the Youth Project of the National Philosophy and Social Sciences Foundation (19AGL009) and the Zhejiang Philosophy and Social Science Foundation (17NDJC218YB).a, Xiaoyu Changa, Qinglan Liua, Jiewei Liub, Ruili Lib, Kaiwen Zhaoc, Dawen Zhanga, Yingmei Yua, Huanhuan Wana, Biaojin Zhanga, Siming LiaHan Yana Key Laboratory for quality and safety control of poultry products, Ministry of Agriculture and Rural Affairs of the People\u2019s Republic of China, Institute for Quality & Safety and Standards of Agricultural Products Research, Jiangxi Academy of Agricultural Sciences, Nanlian Road 602, Nanchang 330200, China, b Institute of Animal Science, Yantai Academy of Agricultural Sciences, Yantai, Shandong 265500, China, c Nanchang Institute of Technology, Nanchang, Jiangxi 330044, China.H Yan and XY Chang contributed equally to this study.Background: The trace element selenium is not only one of the essential nutrients for the human body, but also an indispensable element for animal growth and development that is closely related to many important physiological functions of animals. At the same time, a lack of selenium lowers the body\u2019s immune function, which is a hallmark of depression. This experiment was designed to investigate the effects physiological functions of different selenium sources on slaughter performance, meat health and antioxidant activity of Dongxiang green-shell laying hens.Subjects and Methods: A total of 450 30-week-old healthy Dongxiang green-shelled laying hens with similar body weight were randomly divided into 9 groups. All the animals were fed the same basal diet. The control group was fed a non-supplemented diet. T1 and T2 were added sodium selenite (SS).T3 and T4 were enriched with selenium yeast (SY). T5 and T6 were fed with diet comprising Kappa-Selenocarrageenan (SK). And T7 and T8 were supplemented with selenomethionine (SM). And the concentrations of each type of selenium medium added above were 0.30\u2005mg/kg and 0.60\u2005mg/kg, respectively. The prefeeding period was 3 days, and the formal experiment lasted for 28 days.Results: 1) The carcass weight of T7 and T8 were increased significantly (P<0.05) compared with the control group. The rate of half breast meat was higher in T7 group higher than in other groups (P<0.05). The abdominal fat percentage in groups T1, T2 and T4 was higher than that in control group (P<0.05). 2) The ovarian index of Dongxiang green-shelled laying hens increased significantly (P<0.05) in T7 and T8 groups. The spleen index of T2 group was lower than that of control group (P<0.05). The liver index of Dongxiang green-shelled laying hens was not significantly affected by different levels of selenium sources in additive groups (P>0.05). 3) Chromaticity values of T1 and T3 were lower than those of the control group (P<0.05). PH value in T2 and T3 groups was higher than that in control group (P<0.05), while that in T6 group was lower than that in control group (P<0.05). A higher Se level was detected in all experimental groups (P<0.05). And selenium content increased with the increasing supplemental level, and T8 group had the highest selenium content, which was 0.191mg/kg. 4) The antioxidant values of liver and spleen in experimental groups were significantly higher than those in control group (P<0.05). Serum antioxidant values of experimental groups except T1 were significantly higher than those of control group (P<0.05).Conclusions: Different selenium source levels can regulate physiological and immune functions of Dongxiang green-shelled laying hens. Reasonable supplementation of organic selenium sources, especially selenium-rich yeast and selenium-methionine can improve slaughter performance, meat quality and antioxidant capacity of Dongxiang green-shelled laying hens.This work was supported by two key research and development projects of Jiangxi Province, their project numbers are 20202BBFL63029, JXXTCXNLTS202103 and 20202BBF63011.a, Yiwen CaoaYuan Wanga Institutes of Education, Dalian University, Dalian, Liaoning, China.Background: The big data era has changed society, including education, requiring teachers to possess data literacy skills. However, little research exists on primary school teachers\u2019 data literacy skills, particularly regarding gender psychological differences. This study aims to investigate potential gender psychological differences in data literacy to promote gender equity in developing these skills. Understanding gender psychological differences can enhance teachers\u2019 ability to use data to improve teaching decisions.Subjects and Methods: The study collects data on the completion process and results of assignments of pre-service elementary school teachers of different genders through an online teaching platform that assigns data analysis assignments in education and teaching fields. The study also uses a questionnaire to gain insight into the current gender psychological differences in data literacy of pre-service elementary and secondary school teachers in China. The questionnaire is divided into two parts, the first part is the basic information of the respondents, and the second part is a survey on the current situation of data literacy of pre-service elementary school teachers of different genders. The study conducts a big data analysis using descriptive statistics, t-tests, and regression analysis to analyze the data. Understanding gender psychological differences can enhance teachers\u2019 ability to use data to improve teaching decisions and promote gender equality.Results: This study analyzed the data literacy of pre-service elementary school teachers of different genders in terms of their completion of data analysis assignments, four dimensions of data literacy, and gender psychological differences. The results showed that male pre-service elementary school teachers have slightly higher data literacy than female pre-service elementary school teachers. The mean score of data literacy of male pre-service elementary school teachers was high, while the mean score of data literacy of female pre-service elementary school teachers was moderate. Male pre-service elementary school teachers had a significantly higher mean score than female pre-service elementary school teachers in the core skills dimension. The regression analysis showed that gender was a significant predictor of data literacy after controlling for age and educational level. The findings suggest the importance of addressing gender psychological differences in data literacy and providing targeted training programs to promote data literacy among female pre-service teachers.Conclusions: The study found significant gender psychological differences in specific aspects of data literacy among pre-service elementary school teachers in the context of big data. Despite similar overall levels of data literacy between male and female participants, targeted interventions are necessary to address these differences and improve the data literacy skills of all pre-service teachers. However, the study\u2019s limitations suggest the need for larger, more diverse samples and objective measures of data literacy in future research. Overall, the study contributes to our understanding of gender psychological differences in data literacy and highlights the importance of addressing these differences to effectively navigate the era of big data in education.aAihua Liua School of Preschool Education, Changsha Normal College, Changsha, Hunan, China.Background: To explore the influence of Chinese excellent traditional cultural knowledge and experience level on the development tendency of prosocial behavior of children aged 5-6 based on children\u2019s native mental health education.Subjects and Methods: 260 children from 8 classes of 3 kindergartens in XX Province of China were selected as subjects, including 2 in cities and 1 in township, aged 5-6 years, all of whom were native speakers of Chinese. After conducting the prosocial behavior development tendency evaluation on 260 people, 130 children randomly selected from the main test participated in the interview on the knowledge and experience level of Chinese excellent traditional culture and scored. 7 modules of \u201csocial adaptation\u201d of 5-6 years old in the Chinese version of the Guidelines for the Development of Children Aged 3-6 years old were used as the evaluation tool of prosocial behavior development tendency; Compile the knowledge and experience of Chinese excellent traditional culture and the main test questionnaire. Statistical analysis was conducted for the two types of results.Results: There is a statistical correlation between the level of knowing and experiencing Chinese excellent traditional culture and prosocial behavior development tendency; The difference of prosocial behavior development tendency between high level group and low level group was statistically significant; There is a statistically negative correlation between the level of knowledge and experience excellent Chinese traditional culture and the modules of \u201clike and adapt to group life\u201d and \u201cabide by basic rules of behavior\u201d, which lead to the risk of mental health education.Conclusion: There is a statistical correlation between the level of knowledge and experience excellent Chinese traditional culture and the development tendency of prosocial behavior of 5-6 year old children, and there is a statistical correlation with some high-level prosocial behavior modules; The unsuitable education mode of Chinese excellent traditional culture has educational risks, which have a negative impact on the mental health of preschool children.a, Chen Yea, Xiaoyi Hub, Yan JiangcYun Luoa School of Education, Zhaoqing University, Duanzhou District Zhaoqing, 526061, China, b Faculty of English Language and Culture, Guangdong University of Foreign Studies, 2 North Baiyun Street, Guangzhou, 510420, China, c Psychological Counseling Center, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai, 20444, China.Background: Since 2020, great social changes have occurred, and people\u2019s mental health have been affected due to the COVID-19 pandemic. The COVID-19 outbreak changed the lifestyle of college students significantly. One of the changes is in learning experience. The shift from traditional, offline, face-to-face teaching to online teaching often requires the use of smart devices. Studies have shown that incorrect or problematic smartphone use will lead to depressive symptoms. The model of recovery from depressive symptoms states that while facing malignant life events, individuals with depression will experience higher levels of hopelessness. Thus, people prefer to explain and attribute malignant life events in negatively and individual attribution will affect the level of academic burnout. This study explored the relationship between depressive symptoms and academic burnout among university students during the COVID-19 pandemic.Subjects and Methods: We conducted an online survey with 3,123 undergraduates from universities in Shanghai from March to April 2020. The study used the nine-item Patient Health Questionnaire, Maslach Burnout Inventory\u2013Student Survey, and Positive Psychological Capital Questionnaire. In this study, SPSS 26.0 was used to perform an independent sample t test for groups between students whose academic performance was affected by the pandemic and students whose academic performance was not affected, and the results demonstrated that it was statistically significant. Second, descriptive statistics and correlations for the two groups were analyzed for three dimensions. Third, AMOS 23.0 was used to construct the structural equation model and analyze it to test whether the mediation model was valid.Results: The results showed that depressive symptoms predicted academic burnout. Psychological capital played a mediating role between depressive symptoms and academic burnout. The higher the level of depressive symptoms, lower the level of psychological capital and higher the degree of academic burnout. Furthermore, the effects among students whose academic performance had been affected by the COVID-19 pandemic were significantly different from those whose academic performance had not been affected.Conclusions: These findings have potential implications for practical measures while facing a pandemic. Positive psychological capital is conducive for college students and for the establishment and maintenance of a stable mental health state during the COVID-19 pandemic. Furthermore, in this study, the effect of psychological capital on academic burnout manifests not only in its own characteristics but also from its opposite side: psychological inflexibility, and scholars have explained this mechanism. Thus, depressive symptoms are significant negatively predicted academic burnout through psychological capital and its four dimensions.aHanyang Lia School of Journalism and Communication, Minnan Normal University, Zhangzhou, 363000, ChinaBackground: Federico Fellini\u2019s film Amarcord, released in 1973, presents a vivid and surreal world that captures the essence of a small Italian provincial town in the 1930s. The film combines chaos, absurdity, and ordinary life to create a poetic and humorous narrative. Fellini\u2019s unique aesthetic style reconstructs the dreams, dignity, and poetry of ordinary people during that era. This article explores the carnival poetics theory proposed by Mikhail Bakhtin and its relevance to understanding the imagery in Amarcord.Subjects and Methods: The article applies Bakhtin\u2019s theory of carnival poetics to analyze the film\u2019s imagery. The theory describes carnival as a festival that breaks social norms, allowing for subversion and renewal. It emphasizes the universal, inclusive, festive, and dual nature of carnival laughter. The analysis focuses on the structure of Amarcord, the carnival-like atmosphere throughout the film, and its portrayal of universal laughter, festiveness, and duality.Results: The analysis reveals that Amarcord exhibits the key features of carnival poetics as defined by Bakhtin. The film\u2019s structure is a mosaic-like collection of stories that portray the town\u2019s life in a comical manner. Laughter permeates the film, representing a carnival-style banter that is universal and inclusive, embracing all aspects of life. The festive atmosphere in the film reflects a connection between the cycle of seasons and the cycle of human life, emphasizing rebirth and renewal. The duality in Amarcord is evident in its use of laughter to both reflect and criticize societal norms, ideologies, and institutions. This duality offers a thought-provoking perspective on the world, inviting viewers to challenge rigid and stagnant beliefs.Conclusions: Fellini\u2019s Amarcord effectively captures the spirit of carnival through its imagery and narrative. The film\u2019s carnival poetics, influenced by Bakhtin\u2019s theory, presents a world that is simultaneously ordinary and extraordinary. The universal laughter, festiveness, and duality depicted in the film challenge established hierarchies and ideologies, providing a profound reflection on human existence. Amarcord\u2019s exploration of the carnival spirit offers viewers an opportunity for introspection, renewal, and a deeper understanding of the complexities of life. By engaging with the film\u2019s carnival imagery, audiences can experience a psychotherapeutic effect that encourages critical thinking and reevaluation of societal norms. Ultimately, Amarcord stands as a timeless masterpiece that invites audiences to revisit its poetic images and contemplate the inherent truths of the human experience.a, Yi FengaHongsu Chena School of Art and Design, Beijing Forestry University, Beijing, China.Background: The increasing abundance of material goods and the rising health awareness of the whole population. Healthy living has become the new trend, and healthy eating is an important part of it. Healthy cooking not only reduces the loss of nutrients in food, but also prevents cancer and can effectively reduce the incidence of diseases such as high blood sugar and high blood cholesterol. Maintaining a healthy diet over time reduces the risk of obesity, cardiovascular disease, diabetes and other chronic diseases. Physical health has a positive effect on mental health. At the same time, healthy eating habits can improve the user\u2019s sense of pleasure and contribute to mental health. With the Chinese eating habit of three meals a day, rice cooker is an essential household appliance. Kansei engineering theory is widely used in many fields and provides new ideas for understanding the shape of the user\u2019s favourite smart rice cooker.Subjects and Methods: Based on the design method of Kansei engineering theory, the product appearance design strategy of intelligent rice cooker is studied. Establish a product sample space through market research, extract product design elements, collect perceptual image vocabulary, and then measure users\u2019 perceptual needs using semantic difference method. Key perceptual image words are obtained through factor analysis. Then perform partial correlation analysis on the results of the above methods to identify the corresponding relationship between factors and perceptual image space. Finally, obtain the corresponding relationship between the user\u2019s emotional needs and the design elements of the intelligent rice cooker.Results: Translate the mapping relationship between emotional needs and design elements into design strategies. The more exquisite the smart rice cooker looks outside, the easier it is to win the favor of users. Users choosing smart rice cookers can effectively improve their nutritional level and dietary health, ensure their physical and mental health can balance development, and achieve the goal of physical and mental health.Conclusions: This research mainly uses the research methods of Kansei engineering to guide the appearance design of smart rice cookers, effectively providing new design ideas for the design and development of smart rice cookers, which is conducive to improving consumers\u2019 satisfaction with the appearance of smart rice cookers.a, Lili Huanga, Xinmin Yanga, Di Wua, Yan LiaLixin Bua Chengde College of Applied Technology, Chengde, 067060, China.Background: The objective of the study is to establish an evaluation system that can mobilize teachers to devote themselves to education, thus cultivating a generation of the new era with overall development of moral qualities, intellectual ability, physical fitness, aesthetic appreciation, hard-working spirit, and healthy mentality. Guided by establishing scientific education objectives to ensure a correct development direction of education, the establishment of the new system starts from the perspective of guiding the psychological health of teachers and students, and shaping their positive qualities. Aimed at cultivating the positive power and qualities of teachers and students, developing their psychological potential, and promoting a full, vibrant, and happy life for them, the evaluation features \u201cimproving result, strengthening process, exploring added value, and improving comprehensiveness\u201d.Subjects and Methods: Firstly, based on modern information technology, the study aims to comprehensively showcase the positive psychological factors that lead teachers\u2019 professional growth and students to possess a scientific career, energetic emotions, optimistic personality, and other positive psychological factors. The experimental goals of the study are ensured by scientifically and accurately identifying the core elements that affect teachers\u2019 educational ability and students\u2019 physical and mental health, developing scientific and effective intervention strategies, increasing positive emotions among teachers and students, shaping optimistic personalities, and tapping into psychological potential, so as to maintain the best state of their lives and to achieve happiness in education. Secondly, strategies and design plans will be formulated in research and practice from the aspects of core goals, consensus on concepts, institutional construction, team building, practical promotion, expected results, and demonstration and promotion. A scientifically sound new evaluation model will be formed ultimately, which will guide the implementation of the fundamental task of cultivating morality and virtues, establish standards for improving students\u2019 physical and mental health education and guide the promotion of \u201c Educating Six Domains Simultaneously\u201d. This model will further lay a foundation for improving the quality control system, adding impetus to the modernization of governance in vocational colleges.Results: The \u201cFive Ones\u201d goals of the reform: to establish a system; to cultivate a new generation; to generate a batch of achievements; to foster virtue through education; to develop a new evaluation model that guides teachers and students to establish correct values and promote the development of physical and mental health.Conclusion: Guided by the overall development of moral qualities, intellectual ability, physical fitness, aesthetic appreciation, hard-working spirit and healthy mind, the new evaluation system targets at guiding teachers to establish the goal of \u201c cultivating morality and virtues \u201c and leading students to coordinated development of thought, body, mind, academic ability, and personality. The model will fully utilize information technology to extract core elements that affect teachers\u2019 professional development and students\u2019 physical and mental health. An internal evaluation system will be formulated through Directionality Principle in psychology, helping teachers and students better unleash their potential and creativity. The system highlights the distinct characteristics of vocational education as a type of education, which will promote the high-quality development of the college and play a leading and exemplary role in evaluation reform in corresponding regions.Research Project of Social Science Development in Hebei Province in 2022 (Project category: key project. Project number: 20220101003).a, Han YanbXiaoyan Chena School of Economics and Management, North China University of Technology, Beijing, China, b School of Management, Xiamen University, Fujian, China.Background: In the context of China\u2019s green development strategy system, corporate environmental governance and executives\u2019 management mode both face great challenges. How to achieve excellent business performance and environmental performance in the market competition raises many questions about executive psychological anxiety. Corporate executives show many unhealthy psychological problems and psychological anxiety, such as short-termism and utilitarianism, they are eager to pursue short-term corporate value and make decisions that harm the environment. It is urgent for enterprises and the whole society to find correct solutions to achieve personal development, sustainable economic and social development. For example, when corporate environmental violations occur, the government\u2019s environmental penalties and enforcement can timely ease such psychological anxiety problems of executives and improve their correct cognition of sustainable environmental governance, and enhance their positive attitude of other business management behaviors such as corporate tax payment.Subjects and Methods: This paper aims to explore the impact of government environmental penalties on corporate tax burden and executive psychological anxiety. This paper subdivides environmental penalties into two dimensions: environmental penalty frequency and environmental penalty intensity based on the breadth and depth of environmental penalties. Then I take Chinese listed firms in heavy pollution industries as research samples, and use OLS regression analysis to test the impact of environmental penalty frequency and environmental penalty intensity on corporate tax burden. Finally, I conducted field interviews with some executives to analyze the impact of environmental penalties and law enforcement on their psychological anxiety.Results: The study finds that both the frequency and intensity of government environmental penalties have a significant positive impact on corporate tax burden, indicating that the more environmental penalty frequency and the greater environmental penalty intensity, the higher level of corporate tax burden. Further analysis shows that the direct influence path of the above effect is the increase of corporate tax payment rate and corporate income tax burden, and the indirect influence path is the decrease of tax shield effect of corporate new bank loan. In addition, the interview study finds that executive psychological anxiety about short-termism and utilitarianism has been effectively alleviated after the government\u2019s environmental penalties.Conclusions: The results show that environmental law enforcement can help ease executive psychological anxiety problems in terms of corporate sustainable development, and enhance their positive attitude of business management behaviors such as environmental sustainability and tax payment. This study reminds executives to focus on long-termism rather than short-termism. In addition, this study has important practical significance and enlightenment for promoting the multi-party co-governance of environmental governance by the government, tax authorities and firms. I suggest that the government, tax authorities and firms should make joint efforts to create a good environmental governance system.This research was supported by Research Foundation Project of North China University of Technology (Grant No. 110051360002).a, Dandan Wangb, Yulan YubJun Luoa Guangdong University of Science and Technology, Dongguan, China, b Department of Psychology/ Research Center for Quality of Life and Applied Psychology, Guangdong Medical University, China.JL and DW contributed equally to this work.Background: Adverse childhood experiences (ACEs) are associated with pool mental health, whereas few studies paid attention to the potential buffers. This study aims to: (a) establish predictive relationships between ACEs and character strengths (CS); and (b) exam the joint contribution of ACEs and CS to predict depressive symptoms.Subjects and Methods: We used systematic sampling technic to get samples and performed a self-administered survey among students at a university in southern, China. We analyzed data through descriptive statistics, logistic regression model and mediating effect analysis.Results: Linear regression model in the present study showed that history of ACEs predicted lower relationship (p=0.049), enthusiasm (p=0.009), vitality (p=0.0002) domains of character strengths significantly, while vitality (p=1.23e-08) and justice (p=0.03) domains predicted lower depressive symptoms significantly. Vitality domain of character strengths was a full mediator in the relationship between ACEs and depressive symptoms among university students. Indirect effect was 0.25, 95%CI , and direct effect was 0.21, 95%CI , and total effect was 0.46, 95%CI . Proportion of mediation was 54%.Conclusions: Vitality domain of character strength mediated the effect of ACEs on depressive symptoms fully. The finding provided mechanism explanation and empirical evidence for future intervention direction among university students with ACEs. However, caveats regarding recall bias, social desirability bias, and lack of generalizability are also recommended in the interpretation of the study findings.This research was funded by Guangdong Provincial Philosophy and Social Science Planning Project (GD22XJY25) and Postgraduate Education Innovation Project of Guangdong Province (2022JGXM106).aZemei Shena School of Medicine, Chongqing Institute of Engineering, Chongqing, China.Background: The purpose of this paper is to explore the feasibility of cross-regional coordinated development and cooperation between private universities in the two cities under the drive of the Chengdu-Chongqing economic circle, and its influence on students\u2019 psychological health, and to sort out the problems of students\u2019 psychological health in this process.Subjects and Methods: Literature research method was used to study and analyze the present situation, theoretical basis, driving factors of cross-regional collaborative development of private universities in Chengdu-Chongqing Economic Circle, as well as the importance, convenience and substantive significance of factors influencing students\u2019 psychological health, main problems, and cross-regional development of professional education on the maintenance of students\u2019 psychological health, in the hope of helping private universities in Chengdu-Chongqing Economic Circle achieve cross-regional coordinated development, and also to alleviate students\u2019 psychological problems such as learning pressure and learning anxiety in the process of cross-regional development of professional education in private universities in both places, so as to maintain the psychological health of students in private universities in both places.Results: The study found that private universities are an important part of higher education in China. Under the drive of the Chengdu-Chongqing Economic Circle, a study on the development status of private universities in the Chengdu-Chongqing economic circle and the promotion of cross-regional coordinated development between private universities in the two cities can better promote the scale and cluster-based management of private universities in the Chengdu-Chongqing economic circle, improve the quality of education, and provide more comprehensive talent and intellectual support for the current construction of the Chengdu-Chongqing economic circle. Meanwhile, discussing the influence of the cross-regional development of professional education in private universities in the two places on the maintenance of students\u2019 psychological health can also provide some help for the training of talents in the two places and escort the smooth cross-regional coordinated development of private universities in Chengdu and Chongqing.Conclusions: Private universities in the Chengdu-Chongqing Economic Circle should strengthen cross-regional coordinated development, learn from each other\u2019s strengths, and progress together. Meanwhile, due to the challenges that students may face in the process of cross-regional coordinated development, such as poor resilience, fear of learning, high learning pressure, and anxiety, it is important to pay attention to and jointly maintain students\u2019 psychological health.Fund Project: \u201cResearch on Influencing Factors, Mode Construction and Realization Path of Cross-regional Coordinated Development of Private universities in Chengdu-Chongqing Economic Circle\u201d in Research and Planning Project of Humanities and Social Sciences of Chongqing Education Commission in 2022 (22SKGH502); The offline \u201cgolden course\u201d of Chongqing Institute of Technology\u2019s \u201cGolden Courses\u201d Construction Project in 2021\u2014Market Survey (KC20210323).aJie Baia Zi Jie Medical Beauty, Beijing 100006, China.Objective: This study aims to investigate the effect of lower eyelid blepharoplasty via transconjunctival route combined with nano fat transplantation in orbital rejuvenation.Methods: Retrospective analysis was conducted on 126 orbital rejuvenation surgery patients admitted in our hospital from August 2019 to August 2021, who were divided into combined surgery group and conventional surgery group according to the treatment approach. Patients in the combined surgery group received lower eyelid blepharoplasty via transconjunctival route combined with nano fat transplantation, including a total of 76 patients, and patients in the conventional surgery group received lower eyelid blepharoplasty via transconjunctival route, including a total of 50 patients. The recovery results of the two groups at 6 months after surgery were observed, and the tear trough deformity scale scores, patient satisfaction and postoperative complication rates of the two groups were compared.Results: The postoperative TTRS scores decreased in both groups, with more obvious decrease in the combined surgery group than in the conventional surgery group, showing significant difference between the two groups (P < 0.05). The surgical satisfaction rate was 96.05% in the combined surgery group and 80.00% in the conventional surgery group, showing statistically significant difference between the two groups (P < 0.05). The incidence of postoperative complications was 11.84% in the combined surgery group and 24.00% in the conventional surgery group, showing no statistically significant difference between the two groups (P > 0.05).Conclusion: Lower eyelid blepharoplasty via transconjunctival route combined with nano fat transplantation has good efficacy in orbital rejuvenation, with patients\u2019 symptoms significantly alleviated. The surgery has certain safety, and patients have high satisfaction with the postoperative results.a, Zhihui Yangb, Zhifei Songa, Xiaobo TaoaXihuang Laia Graduate School, North China University of Technology, Beijing, China, b Brunel London School, North China University of Technology, Beijing, China.Background: Improving postgraduates\u2019 mental health will be implemented as an important reference factor for the layout of degree authorization points. The integration between industry and education is an important way to guarantee postgraduates\u2019 mental health. Those joint training bases built on the mutual collaboration provide strong guarantees for graduates in shaping their mental health, cultivating the application ability of basic theory and expanding the field of vision of industry.Subjects and Methods: This paper proposes a strategy of multi-dimensional mutual encouragement and integration, multi-mode construction approaches, as well as multi-dimensional evaluation and guarantee system, which can better solve the problems of shortages of resources, lack of mutual trust in school enterprise cooperation, imperfect operation mechanism and system, which exist widely in local universities and have significant impact on postgraduates\u2019 mental health. In addition, combined with the operating experience of the joint training base for graduate students in relevant universities, an overall management scheme of the bases is given from the viewpoint of base creation, daily management and sustainable development of bases in order to provide practical implementation reference for the construction of bases among local universities.Results: The construction of the joint training base for graduate students of the school has achieved initial results. Up to now, the number of off-campus joint training bases for graduate students has grown from 8 at the beginning to 180 at present, and the production and education integration joint training base has truly achieved a win-win situation between school and enterprise, both of which improve postgraduates\u2019 mental health to a great extent.Conclusions: To improve postgraduates\u2019 mental health, universities should start from the three aspects of \u201cmulti-mode training base\u201d, \u201cmulti-faceted training guarantee\u201d and \u201cmulti-dimensional evaluation system\u201d to build a joint training base construction mode of \u201cmulti-dimensional mutual encouragement\u201d. With the overall goal of \u201cprofessional knowledge plus ability expansion\u201d, the school has established a graduate ability pool and provided ability reports for graduate students. \u201cMulti-mode training base\u201d, \u201cmulti-faceted training guarantee\u201d and \u201cmulti-dimensional evaluation system\u201d have formed a new model for the construction of joint training bases for graduate students in local universities, and the three influence and promote each other to achieve pluralism and unity, which can effectively mobilize the enthusiasm of enterprises and participate in the construction of practice bases, and improve postgraduates\u2019 mental health significantly.This article is a phased research result of the 2021 ideological and political work research topic of Beijing colleges and universities by the Education Work Committee of the Beijing Municipal Committee of the Communist Party of China and Beijing Higher Education Teaching Reform and innovation project, \u201cConstruction and Implementation of an Evaluation System for the Comprehensive Development of Postgraduates Oriented by Ability Cultivation\u201d (Project No.BJSZ2021ZC63).a, Yuan Songb, Tao Liub, Jiaxuan Shena, Xudong Lianga, Jing Qiaoa, Keyu Zhua, Shenghua LibTuanzhuang Zhanga Gansu University of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Lanzhou 730000, Gansu Province, China, b Gansu Hospital of Traditional Chinese Medicine, Hand Surgery, Lanzhou 730050, Gansu Province, China.Background: This study aims to investigate the effect of Xiaozhong Zhitong mixture on flap ischaemia-reperfusion (I/R) injury and its action mechanism.Methods: Sixty SPF SD rats were randomly divided into six groups (n=10 each): sham operation group, model control group, Xiaozhong Zhigang mixture group, p38MAPK inhibitor group, PPAR\u03b3 inhibitor group, and NF-\u03baB inhibitor group. Random flaps (8cm\u00d72cm) were constructed on the back of rats except those in sham operation group. After operation, the flaps were sutured in situ with 3-0 suture to establish the flap I/R injury model. At 7 days after surgery, the rats were observed morphologically and the levels of TNF\u03b1, IL-6 and intercellular adhesion molecule-1 (ICAM-1) were measured. Western blotting was used to detect the protein expression of p38 MAPK-PPAR\u03b3/NF-\u03baB pathway. The whole genome chip was used to screen the differentially expressed genes after treatment, and the expression patterns of the differentially expressed genes were analyzed by clustering, GO and KEGG. The differentially expressed genes and the biological processes and the most important signal transduction pathways in the process of Xiaozhongzhipain mixture in the treatment of flap ischemia reperfusion injury were screened. The highest and lowest temperatures of the flaps of rats were detected by infrared thermography, and the edema and leukocyte infiltration of the flaps were observed by hematoxylin-eosin staining.Results: On POD 7, the survival area of rats in the Xiaozhong Zhitong mixture group, p38 MAPK inhibitor group, and NF-\u03baB inhibitor group increased. The levels of TNF\u03b1, IL-6 and ICAM-1 were decreased by Xiaotumorzhidong mixture, p38 MAPK inhibitor and NF-\u03baB inhibitor. Xiaozhong Zhutong mixture can up-regulate the expression of PPAR\u03b3 and I\u03baB\u03b1, and down-regulate the expression of p38MAPK and NF-\u03baB. The whole genome microarray analysis showed that the attenuation of flap I/R injury by Xiaotumoranalgesic mixture was related to inflammatory response, immune system process regulation, cell proliferation, cell adhesion and neutrophil migration. Xiaotumorzhidong mixture can alleviate flap I/R injury in PPAR signaling pathway, MAPK signaling pathway and NF-\u03baB signaling pathway.Conclusions: The Xiaozhong Zhitong mixture may reduce I/R injury in rat flaps by modulating the p38 MAPK-PPAR\u03b3/NF-\u03baB pathway.This work was supported by a grant from the Regional Project of the National Natural Science Foundation of China (Grant No.81860863).a,b, Chunyan Daia,c,dChaoyan Denga Rattanakosin International College of Creative Entrepreneurship, Rajamangala University of Technology, Phuttamonthon, Nakhon Pathom 73170, Thailand, b School of Chemistry and Materials Engineering, Liupanshui Normal University, Liupanshui, Guizhou 553004, China, c School of Management Science and Engineering, Chongqing Technology and Business University, Chongqing 400067, China, d Development Information Management Engineering Technology Research Center in Chongqing, Chongqing 400067, China.Background: As the social progress and economic development have brought about an increasingly warming climate, countries have promised their carbon neutrality goals, and China has solemnly promised to the world that it will achieve carbon neutrality in 2060. For this reason, the relevant carbon emission accounting and scenario prediction are particularly important to provide the technical and theoretical basis for urging the low-carbon transformation of relevant industries. Under the current local policies of industrial revitalization and characteristic tourism development, it is of great significance to analyze and study the carbon emission intensity and residents\u2019 health under the vision of \u201ccarbon neutrality\u201d for Liupanshui as an old industrial city in the former third-line construction, the Coal Capital in the Regions South of the Yangtze River and the Cool Capital of China.Subjects and Methods: In this study, the energy consumption and production carbon emissions of four administrative regions including Zhongshan District, Shuicheng District, Liuzhi Special District, and Panzhou City, which constitute Liupanshui City, were calculated from 2011 to 2020. The carbon emissions increment model of Liupanshui City was constructed by the Logarithmic Mean Divisia Index (LMDI) method, and the impact of carbon emissions on residents\u2019 health in Liupanshui City was studied through qualitative analysis. On this basis, the spatial distribution model of carbon emissions in Liupanshui was constructed by using big data, energy consumption data and infrastructure spatial distribution data. The driving force and influencing factors of carbon emissions in Liupanshui were analyzed by using historical data of Liupanshui, and the internal mechanism of carbon emissions, socio-economic factors and spatial form indicators was explored.Results: The results show that in recent ten years, the overall trend of carbon emissions in Liupanshui is wavy, the trend of carbon emissions per capita is similar to the intensity of carbon emissions, and the intensity of carbon emissions shows a steady downward trend. The empirical analysis of carbon emission increment of energy consumption in Liupanshui shows that the carbon emission increment caused by economic scale effect first increases and then decreases, the carbon emission increment caused by regional structure effect changes little, the carbon emission increment caused by technological progress effect is sometimes positive and sometimes negative, and the carbon emission increment caused by energy consumption structure effect is similar to technological progress effect. Extreme weather caused by greenhouse gases indirectly harms people\u2019s physical and mental health, induces an increase in the incidence of cardiovascular and respiratory diseases, and accelerates the spread and spread of epidemic diseases. Based on people\u2019s recognition, local residents are actively making improvements towards a healthier lifestyle. In addition, the government is also strengthening the introduction of relevant low-carbon policies.Conclusions: The above research results will provide data support and decision-making suggestions for energy conservation and emission reduction, urban planning, and related scientific research, and policy suggestions on how to implement energy conservation and emission reduction planningas well as feasible solutions on how to achieve the goal of \u201ccarbon neutrality\u201d in Liupanshui in the future, a good environment for physical and mental health of Liupanshui residents.The authors gratefully acknowledge the financial support of Guizhou Social Sciences \u201cTheoretical Innovation Project\u201d special fund supported project (No. GZLCZB-2022-3-5-1); Philosophy and Social Science Project of Liupanshui City (No. lpsskllh-2022-76).a, Zhen RenaMingmin Hea Sichuan University Jinjiang College, Meishan 620860, China.Background: The purpose of this study was to investigate the effectiveness of two embodied learning approaches, finger-tracking, and observation-tracking, in Chinese character learning and to explore their relationship with learners\u2019 working memory and students\u2019 anxiety.Subjects and Methods: A total of 31 undergraduate students from non-native Chinese speaking universities, of whom 7 were male and 24 were female, participated in our study. The working memory capacity was measured using the Visual Patterns Test (VPT). The study materials included 36 kanji (12 kanji for each teaching style). We measured the effectiveness of learning through two rounds of tests: immediate post-test and delayed post-test. The effectiveness of finger tracking and observational finger tracking in Chinese language learning was investigated empirically by comparing the performance of the finger tracking group, the observational tracking group and the control group on the recognition and cue recall tasks in the post-test and the delayed post-test. As an indication of experienced anxiety during the learning phase and directly after each of the post-test phases participants were questioned on a 7-point anxiety scale.Results: We found that: 1) the observation tracking learning method could improve the performance on the delayed post-test during the learning of Chinese characters for beginners, resulting in better retention of learning effects and was effective only for learners with low working memory capacity; 2) the finger-tracking learning method had a negative impact on performance in Chinese character learning, especially for learners with low working memory capacity; 3) students in the observation tracking task report significant less anxiety compare to in the finger-tracking learning task and control learning task; students in the finger-tracking learning task report the higher anxiety than in other tasks.Conclusions: The results of this study suggest that when designing instruction for Chinese language learning, instructors should choose a reasonable teaching style. Observational tracking learning as a form of embodied learning helps Chinese language learning and reduces students\u2019 anxiety.The finger-tracking learning method had a negative impact on performance and increased students\u2019 learning anxiety, especially for learners with low working memory capacity.aShiyong Songa School of Political Science and Law, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong 250353, China.Background: The management and legal protection of trade secrets is the common goal of all countries. At the same time, however, the issue of trade secrets profoundly reflects the psychological game between obligees, obligors and infringers. In judicial practice, a large number of infringement cases are actually done maliciously by the infringer based on the unhealthy psychology of prying, which also causes psychological anxiety to the business secret manager that he may leak at any time. Metaverse, as a new concept, has produced great social influence in the economic field of various countries. Blockchain protection of trade secrets is considered to be the best mode in the meta-universe. The characteristics of decentralization and traceability of Blockchain technology can limit the infringer\u2019s unhealthy psychology of snooping, reduce the inner anxiety of trade secret managers, improve their psychological satisfaction and professional happiness, and promote the benign development of trade secret protection.Subjects and Methods: Taking Russia and India of the Shanghai Cooperation Organization for reference, through literature review and empirical analysis, this paper probes into various legal problems faced by countries with trade secret laws and countries without special trade secret protection laws in the two-way psychological game between trade secret owners (managers) and infringers who apply this law. Compared with China\u2019s anti-unfair competition law as the main mode of regulating trade secrets, Russia has a special trade secret protection law. India has not included trade secrets in its intellectual property protection system. India\u2019s trade secret protection mainly provides comprehensive protection through its criminal law, contract law and information technology law. In the face of different legal provisions, anyone will always choose his own behavior mode according to the higher and closer standards of his psychological happiness index. The purpose of this study is to explore the psychological obstacles faced by users at all nodes of Blockchain under the cosmic background , as well as various legal risks and coping strategies at this time.Results: Although the meta-universe has exerted great social influence in the economic fields of various countries, on the whole, the meta-universe is only a beautiful idea under the kidnapping of various kinds of capital, and it does not have the conditions for special legal regulation. Users of Metaverse can\u2019t completely move freely without Blockchain technology, which has caused their psychological limitations in behavior, which is reflected in the protection of trade secrets. They don\u2019t have a higher sense of happiness and satisfaction psychologically because of Blockchain technology, but they continue to need to guard against infringement at all times. At the same time, due to the transnational characteristics of users under the background of Blockchain technology and meta-universe, this psychological fear will be further amplified.Conclusions: Compared with the traditional environment, the meta-cosmic scene is more likely to cause more psychological obstacles to the trade secret owners, and generally has a distrust of new technologies, thus affecting their normal social communication ability. At present, the manipulation of the Metaverse by capital magnifies people\u2019s abnormal snooping psychology and unhealthy psychology of illegal possession of social public assets, which is extremely unfavorable to the protection of trade secrets.This work was supported by: Shandong Philosophy and Social Science Planning Project---Study on the Overall Risk of Blockchain Protecting Trade Secrets in Meta-Universe (Grant No.22CFXJ03); The major special project of regional and country studies of Shanghai Cooperation Organization of Qilu University of Technology (Shandong Academy of Sciences) (Grant No.2022-122).a, Wenjuan Yana, Dixia Qia, Hui Yaoa, Shuxian Lia, Juan Zhaoa, Nan Kanga, Rongyan Zhanga, Aiqin Xua, Fang Liua, Fang Liua, Juan Zhaoa, Yinghui Pana, Yongfang Fenga, Ningli Suna, Jing Xua, Shunda Liua, Wenjuan Zhanga, Guilian MaaYuxia Zhua Ningxia Hui Autonomous Region People\u2019s Hospital, Yinchuan City, Ningxia, 750002, ChinaBackground: To explore the effect of knowledge-belief-practice model on influencing factors of quality of life in elderly patients with acute myocardial infarction (AMI).Subjects and Methods: 124 elderly patients with AMI were randomly divided into control group and observation group with 62 cases in each group. The control group was given routine nursing through clinical pathway, while the observation group was given questionnaires by patients\u2019 general questionnaire and quality of life rating scale (WHOQOL-BREF) on the basis of the control group, and the results were analyzed by single factor and multivariate analysis.Results: In the observation group, sex, marital status, educational level, heart function at admission, hospitalization times and payment methods of medical expenses were the main factors affecting the quality of life of elderly AMI patients. Logistic regression analysis showed that resilience (CD-RISC), health belief (CHBMS), depression (SDS) and anxiety (SAS) were the influencing factors of comprehensive scores of elderly AMI patients. Taking the above influencing factors as the main problems of intervention research, the KAP model was applied to intervene, and the effects of the two groups before intervention and one week after intervention were compared. After one week of intervention, the scores of CD-RISC and CHBMS in the observation group were 76.89\u2009\u00b1\u20096.82 and 141.12\u2009\u00b1\u200922.28 respectively, which were higher than those in the control group (P < 0.05); SDS and SAS scores of patients in observation group were lower than those in control group (P < 0.05). After the intervention, the scores of knowledge, belief and behavior in the observation group were higher than those in the control group (P < 0.01).Conclusions: KAP model can effectively improve the resilience level, health belief and negative emotion of elderly AMI patients.This work was supported by Ningxia Hui Autonomous Region Science and Technology Benefiting the People Project (2022KJHM0020).a, Qianyu Zhuangb, Junyi Duanc, Jin Xuc, Zhanbiao Zhaoa, Ping ZhangaJianlei Wanga AECC Beijing Institute of Aeronautical Materials, Beijing, China, b National Innovation (Qingdao) High speed Train Material Research Institute Co. LTD, Qingdao, China, c School of Environmental Science and Safety Engineering, Tianjin University of Technology, Tianjin, China.Background: With the rapid development of the construction industry, the number of safety accidents is increasing. Safety psychology is a science that studies people\u2019s psychological state and its changes in production activities. It can point out the direction for how to mobilize the enthusiasm of construction workers to reduce the occurrence of safety accidents. Therefore, how to analyze the psychological problems of construction workers from the perspective of safety psychology, find out the main conflicts causing psychological problems and put forward safety strategies has become a new research task.Subjects and Methods: Based on safety psychology, this paper analyzes and points out the unsafe psychology and occupational health problems of construction workers in the construction industry, as well as the conflict relationship between individuals, families and enterprises (industries) environment, etc., and puts forward safety strategy suggestions for the application of safety psychology in the construction industry. It can achieve the purpose that construction workers have correct occupational health and safety psychology and reduce safety accidents, thus promoting the healthy development of individuals and enterprises.Results: Before the accident, the construction workers generally had fluky psychology, burnout psychology, rebellious psychology, paralysis psychology and conformity psychology, and the prominent occupational health and safety psychological problem was burnout psychology. There are many factors that cause unhealthy psychological problems, such as individuals themselves, families, and enterprises (industries). All parties should pay more attention to the psychology of construction workers, be good at self-regulation, build a harmonious family relationship, and improve the mechanism of enterprises (industries), starting from the maintenance of mental health and the implementation of safety strategies.Conclusions: With regard to the safety strategy of construction workers in the construction industry, it is necessary to explore the psychological activity rules and contradictions of construction workers under the guidance of the theory of safety psychology, so as to accurately predict the unsafe behaviors of construction workers, adjust and deal with unsafe psychology with scientific methods, prescribe the right medicine, and avoid unsafe psychological problems and safety accidents. The safety strategy based on safety psychology has very important theoretical and practical significance for reducing the frequency of safety accidents in construction.a, Lei Wanga,bRong Huanga School of Physical Education, Shaanxi University of Technology, Hanzhong, 723001, Shaanxi, China, b School of Computer Science and Engineering, Xi\u2019an University of Technology, Xi\u2019an, 710048, Shaanxi, ChinaBackground: The World Health Organization has recently recommended the amount of aerobic exercise for teenagers. However, the guidelines are more instructive than practical, and cannot be directly used as the individualized aerobic fitness program for college students. Under the background of \u201ccombination of sports and medicine\u201d, the principle of \u201csuiting the remedy to the case\u201d followed by medical rehabilitation work is also applicable to the sports fitness programs. Meanwhile the manner in which to apply machine learning to individualized aerobic exercise programs has attracted more and more attention. In this research it assumed that the relationship between human body data indicators and aerobic fitness program could be expressed by an artificial neural network.Subjects and Methods: The research aimed to verify the feasibility and effectiveness of constructing the functional relationship between college students\u2019 static body data and aerobic fitness programs based on artificial neural network, and realize the individualized aerobic fitness activities for college students with the assistance of smart bracelets and mobile phones. 60 normal college students were recruited from Shaanxi University of Science and Technology to measure their static body data, meanwhile the test for heart rate under the aerobic exercise with different intensity and duration was carried out by smart bracelet. Based on the target heart rate (THR), a 3-layer artificial neural network between the static body data of the experimental object and the aerobic fitness program was constructed.Results: We had 52 participants to complete the experiment on schedule. The 3-layer artificial neural network was constructed by Back Propagation Algorithm which was iterated 5 times, and the relationship between human body indicators and running program was represented by the artificial neural network with 17 parameters in hidden layer and 10 parameters in output layer. However, because of the neglect of the lifestyle and chronic diseases for participant, 2 of 20 college students who engaged in the final test got unexpected result.Conclusions: The college students could achieve THR in exercise according to motion speed and duration of running provided by the artificial neural network without fitness professional. Considering the effectiveness, convenience and popularity, the running was selected as the aerobic fitness event, but there were many other aerobic exercises we could use. The 3-layer artificial neural network could be further optimized through multi-dimensional information obtained from different channels and multi-objective analysis method, by which it could promote the applicable scope of the 3-layer artificial neural network. At the same time, with the rapid development of cloud computing, big data and 5G technology, more complicated, efficient and convenient intelligent exercise prescription system will be constructed.This work was supported by a project grant from the Western China project of National Natural Science Foundation of China (Grant No.21XTY012).a, Junfan XiaoaRui Tana College of Humanities & Social Sciences, Huazhong Agricultural University, Wuhan, China.Background: Patients\u2019 trust deficit in doctor-patient relationships in China has caught research attention in recent times. The risk of trust between doctors and patients makes patients often suffer from anxiety, hesitation and other Negative emotions, which leads to the failure of diagnosis and treatment. Therefore, it is of great practical significance to explore the basis of trust between doctors and patients.Subjects and Methods: This study presents a framework for the effects of patients\u2019 risk resistance regarding patient trust, having applied multivariate regression models to analyse the causes of the patient trust deficit, based on data from the China Family Panel Studies .Results: It was shown that in terms of economic resilience, more comprehensive medical insurance and higher income among patients represented their capability to resist the economic risks induced by medical care, and that their willingness to establish good patient trust was stronger. In terms of social resources, higher social status levels and more stable work statuses improved patients\u2019 capability to handle the risk of medical resources and gave them the confidence to receive good medical services, which positively influenced the establishment of patient trust. With respect to health literacy, sound physical health conditions improved patients\u2019 capability to handle life safety risks.Conclusions: The results show that the lack of patient risk tolerance is the deep-seated reason it is difficult to build patient trust, which is reflected in the fact that the level of patient trust decreases when patients\u2019 economic resilience, social resources, and health literacy are insufficient. Therefore the government should embed the improvement of patients\u2019 risk resistance into all aspects of development of the medical field, pay attention to the assessment of risks faced by patients, and promote the sustainable development of patients\u2019 risk resistance.This study was supported by the Fundamental Research Funds for the Central Universities (Grant numbers: 2662021JC007).a, Tian LiaXueyan Jina College of Arts, Gansu University of Political Science and Law, Lanzhou 730070, China.Background: The construction of the Mogao Caves was influenced by Indian cave temples and embodies the characteristics of traditional Chinese wooden architecture, representing a process of localization of cave architecture. The architectural structure and spatial form exhibit distinct historical and regional features under the influence of geological environment, excavation technology, and subjective psychological perception of cave space by social groups. Forced by the expectation of survival, the lower class people can extricate themselves from the suffering of reality by worshiping Buddha piously, while the grottoes provide people with a space for spiritual practice, chanting and worshiping. The solemn and sacred atmosphere in the space promotes the frescoes of good and evil causality, and the dignified colored sculptures can heal people\u2019s psychological and physiological health, build their values and even promote the renewal of personality changes, help improve their psychological resilience, reduce stress and anxiety, improve their psychological emotions, and place beautiful expectations on life. It has positive significance in mental health and psychological rehabilitation.Subject and Methods: The shape of the main chamber roof in Mogao Caves is mainly divided into flat top, even Ceiling, herringbone drape and truncated pyramidal ceiling top. The number of caves Pyramidal Ceiling top is the largest, it was found that its spatial volume and top slope value showed an increasing trend. It provides a broad field of vision and enhances fluidity, making it possible to create large-scale three-dimensional sculptures and murals. In addition, the transparent and spacious top of truncated pyramid ceiling of cave forms a perspective effect with algae wells that progressively recede from outside to inside at different levels, extending users\u2019 psychological space while reducing feelings of psychological oppression. This is conducive to creating a solemn, peaceful, profound and sacred heavenly world. Devout believers will be integrated with the cave space and consciously immersed in the quiet and harmonious space atmosphere, so that their body and mind can be relieved and their spiritual and emotional sustenance can be relaxed; So as to alleviate the psychological pressure, anxiety, helplessness and other negative emotions brought by real life, maintain psychological balance and ensure mental health.Results: Although ancient people lacked systematic scientific exploration and analysis in constructing caves, they established relatively mature systems for cave structure shapes, proportional scales and environmental psychological mapping through persistent practical exploration and accumulated experience. The Mogao Caves\u2019 architecture not only reflects the progress of construction technology but also shows the development of users\u2019 psychological needs. As experiencers and users of cave architecture, people\u2019s ideology will penetrate every aspect of cave construction. Quantitative factors, such as cave structure, shape, spatial scale, color pattern, etc., will also guide and sort out people\u2019s negative emotions, which is beneficial to mental health.Conclusions: This paper discusses the construction technology of the caves from the space layout, scale, psychological atmosphere and other aspects, and discusses many influencing factors in the caves construction, which provides reliable information for studying the structural characteristics of the caves and the psychological mapping of users to the caves in vision and even subconscious. It is helpful for us to know the outstanding wisdom of the ancients in underground engineering technology and architectural psychology. Find out the positive influence of cave architecture on people\u2019s mental health.In addition to the influence of geographical environment and rock structure, the change and development of the structure and scale ratio of cave architecture are also related to the rule of the regime at that time, the life of the common group and the functional needs of the caves. From the perspective of scientific exploration and using computer simulating test, four models were established based on the same conditions, and the deformation and principal stress of Mogao Caves were compared, and it is found that the stability of pyramidal ceiling > even roof > herringbone > flat roof. Although the excavation was limited by cutting equipment and technique at that time, the top structure of caves cleverly utilized the structure and characteristics of rock mass, and the sequence of excavation from top to bottom reduced the influence on the surrounding rock of caves. Under the condition of no supporting lining, the stability and self-supporting ability of surrounding rock were guaranteed, and the demands of culture spreading and exhibition were taken into account in different times, showing the wisdom and engineering experience of ancient Chinese craftsmen, which had certain guiding significance for underground engineering construction. 2021 Young Doctor Fund Project of Gansu Province (Project No.: 2021QB101).aJia-qing Wanga School of Economics and Management, Wuhan University of Engineering Science, Wuhan 430200, Hubei, China.Background: The essence of psychological anxiety is a kind of psychological sub-health, which is externally manifested as negative and anxious emotions of employees\u2019 work attitude and behavior. In enterprise management, there is a basis for psychological anxiety in addition to personal characteristics, it is also related to the job position, job responsibilities and the management style of superior leaders, especially related to the company\u2019s principle of mutual benefit. The principle of mutual benefit is the basic factor for the harmonious coexistence of the organization, leaders and employees, and it is also the pillar of the maintenance of the organizational system, the implementation of leadership activities and the development of work behavior. If the principle of mutual benefit is not well guaranteed, then psychological anxiety will lose its space for existence, and correspondingly, organizational operation, leadership behavior and work behavior can be smoothly implemented. The principle of interest and emotion is the core of psychological anxiety, and it is also the legal principle of relationship performance and production performance. Charismatic leaders can have a positive effect on employee performance by alleviating psychological anxiety as an intermediate variable. Based on the internal logic of charismatic leadership traits and psychological anxiety, the relationship between psychological anxiety and employee performance and the mechanism of charismatic leadership and employee psychological anxiety alleviation were analyzed.Subjects and Methods: The research goal of this paper is to explore the positive leading role of alleviating psychological anxiety on employee performance from the perspective of organizational operation. The article argues that a leadership style that is highly consistent with the behavior of alleviating psychological anxiety is needed, that is, leadership ability and leadership art that is appealing and attractive. At the same time, based on the internal analysis and examination of the characteristics of charismatic leadership style, it is found that this leadership style feature is compatible with psychological anxiety behavior, and can stimulate employees\u2019 work initiative and enthusiasm in the form of alleviating psychological anxiety, thereby improving employee relationship performance and effectively interacting with organizational performance. By using a variety of statistical analysis techniques such as content analysis, literature analysis, exploratory factor analysis, confirmatory factor analysis, structural equation model and regression analysis, the influence of charismatic leadership on employee performance was studied with psychological anxiety as the mediating variable.Results: Through theoretical analysis and empirical research, it is found that the personal charisma traits of leaders constitute the main dimension of charismatic leadership. From the perspective of leadership behavior practice, the dimension of charismatic leadership is specifically manifested in the following aspects, namely: common vision, caring for employees, paying attention to the environment, daring to take risks and innovation, and extraordinary behavior. Charismatic leadership can play a role in alleviating psychological anxiety because of the application of these five elements. Based on a shared vision, charismatic leaders are usually exemplary and benchmarking to reinforce the alignment of employees with their own tasks, and guide employees to make efforts to improve organizational performance. The impact of charismatic leadership on employee performance is manifested as: the role model of charismatic leadership can strengthen employees\u2019 engagement in work; The vision of charismatic leaders can effectively awaken employees\u2019 work motivation; The personality factors of charismatic leaders can better enhance employees\u2019 loyalty to the organization; Charismatic leaders care for their jobs and improve employee satisfaction.Conclusions: This paper proposes a path for charismatic leaders to improve employees\u2019 performance from the perspective of alleviating psychological anxiety: focusing on the consistency between charisma traits and alleviating employees\u2019 psychological anxiety; Organizational commitments and rules for alleviating psychological anxiety construction should be followed; Caring about job satisfaction in the dimension of employee psychological anxiety; Lead and inspire employee loyalty to the organization.aJunjun Chena Student Affairs Office, Shandong Polytechnic, Jinan, Shandong 250104, China.Background: In recent years, more and more foreign students have entered higher vocational colleges in China. Mental health education of foreign students in higher vocational colleges is facing great challenges.Subjects and Methods: The purpose of this paper is to explore the application of painting psychological analysis in the mental health education of Bangladeshi students in higher vocational colleges, and to explore a new way to promote the harmonious development of physical and mental health of foreign students in higher vocational colleges. A total of 50 Bangladeshi students in Shandong Polytechnic were enrolled in the study. This paper evaluates the reliability and validity through qualitative research.Results: Painting psychoanalysis, which is characterized by its variety, easy operation and freedom from time and space constraints, is mainly used as a means of communication to bring more vitality and enlightenment to the mental health education of college students. The physical and mental health of Bangladeshi students in vocational colleges were fully developed and achieved psychological growth. The classroom atmosphere is more active. The students\u2019 psychological stress was significantly reduced, and their self-identity significantly increased.Conclusions: The psychological analysis of painting is integrated into the mental health education activities of the foreign students in Bangladesh, which is very popular among the foreign students. Through communication, teachers, counselors, students generally agree that painting activity has achieved good results. From the practice, it is found that the psychological analysis of painting is helpful to overcome the negative influence of culture and language, and is suitable for Bangladeshi students to carry out mental health education.aYadong Wanga School of Education, Nanchang Institute of Science and Technology, Nanchang, Jiangxi, China.Background: To explore effective ways of cultivating critical thinking quality of English majors from the perspective of educational psychology, especially the willpower. For willpower plays an important role in the entire process of cultivation of critical thinking quality. Students who possess strong willpower can consciously control and adjust their actions according to the purpose, and can overcome various difficulties to achieve the purpose. Also a strong willpower will usually lead to a strong determination, which is a key factor to success. A strong willpower is also helpful in cultivating students\u2019 healthy psychological mindset and character building.Subjects and Methods: 1. The willpower and motivation method: First, purpose education. To educate the students about the purpose and necessity of cultivating critical thinking quality. Then, turn them into a strong motivation. Third, educate the students about the importance of a strong willpower.When meeting difficulties, encourage them to get over difficulties by their strong willpower. 2. The willpower cultivation method: Besides educating students about the theoretical side of willpower, the teacher also educate them about the practical side, i.e. how to obtain a strong willpower. The teacher adopts various ways to cultivate students\u2019 physical and psychological willpower. To cultivate students\u2019 physical willpower, the teacher requires students to make a very specific plan for physical exercise. For example, running a certain distance every day and stick to it strictly. To cultivate students\u2019 psychological willpower, the teacher requires students to memorize a certain number of English vocabulary every day and stick to it strictly. The teacher controls the process by checking the students\u2019 progress periodically and establish a certain reward mechanism. In this way, help students cultivate a strong willpower as well as a healthy psychological mindset. 3. Integration method: The elements of critical thinking are integrated into classroom teaching activities such as text teaching, writing teaching, reading teaching. Through text analysis, main idea summary and question answering, students\u2019 logical thinking ability is exercised and developed. Through critical writing practice, students\u2019 critical ability is trained and developed.Results: 1. Through teacher\u2019s education of the purpose, the students know the importance and necessity of cultivating critical thinking quality. Through teacher\u2019s willpower and motivation education, the students know the important role the willpower plays in the cultivation process. The students\u2019 learning enthusiasm is greatly aroused with a strong motivation. 2. The logic theory required in the cultivation process is usually abstract, dull and hard to understand. However, through teacher\u2019s willpower education and cultivation, the students\u2019 strong willpower is gradually obtained and further enhanced. Thus, it enables the students to get over various difficulties occurred during the cultivation process. Meanwhile, it also helps the students develop a healthy psychological mindset and a good character.Conclusions: English teaching integrated with cultivation of critical thinking of English majors from the perspective of educational psychology is feasible. For willpower plays an important and irreplaceable role in the cultivation of critical thinking quality and a healthy psychological mindset. In colleges that do not offer a separate course on critical thinking, this method is both realistic and useful.a, Huayu GuanbMingchi Zhua Beijing-Dublin International College at BJUT, Beijing 100124, China, b Finance Office, School of Emergency Technology and Management, North China Institute of Science and Technology, Langfang 065201, China.Background: From the perspective of psychological satisfaction, fintech can reduce the management costs of commercial banks, improve operational efficiency, meet customer psychological needs, and achieve psychological satisfaction, thereby enhancing their core competitiveness. The Internet can break through the limitations of time and space blockade, increase the customer range of commercial banks, improve their psychological satisfaction level, greatly reduce the service costs of commercial banks, and thus increase the psychological satisfaction and loyalty of commercial bank customers.Subjects and Methods: This article studies the impact mechanism and empirical analysis of financial technology on customer psychological satisfaction from the perspective of customer psychological satisfaction, combined with the characteristics of commercial banks, from both theoretical and empirical perspectives. Based on this, this article uses the \u201ctext mining\u201d method to construct the impact index of financial technology, using state-owned large commercial banks, joint-stock banks, and urban commercial banks as samples, and measures the customer psychological satisfaction index, empirically analyzing the impact mechanism of financial technology on customer psychological satisfaction.Results: This article analyzes the impact mechanism of financial technology development on customer psychological satisfaction, and benchmark test results show that the development of financial technology significantly improves the level of customer psychological satisfaction. After a series of robustness tests, the main conclusions of this paper remain unchanged. Mechanism analysis found that the improvement of income level, the development of entrepreneurial activities, and the narrowing of urban-rural income gap are important reasons for the impact of financial technology development on customer psychological satisfaction.Conclusions: Financial technology can improve customers\u2019 psychological satisfaction, increase their happiness index, and achieve psychological satisfaction. According to empirical research results, due to historical and management system reasons, large state-owned commercial banks seem to have a slight lag in responding to external environmental changes, and their impact on customer psychological satisfaction is relatively low. However, equity banks and urban commercial banks are significantly weaker in responding to the impact of financial technology. Therefore, commercial banks should base themselves on their own strength, seize opportunities in the external environment, and enhance psychological satisfaction. At the same time, the government should support the development of fintech, promote the standardization of fintech in China, formulate policies and regulations related to fintech, promote the sustainable and healthy development of the financial industry, and thus improve customer psychological satisfaction and happiness index to a greater extent.a, Fujun Rena, Xiaoling Rua, Hui Guoa, Xiuyou WangaShigan Yua Fuyang Normal University Fuyang, 236041, Anhui, China.Background: The era of emerging engineering has endowed college teachers with a new mission, and training high-quality professionals to meet the needs of emerging engineering has become a new goal. As the core course of computer-related majors, the traditional teaching mode of the course lags behind the requirements of the emerging engineering era, which leads to the lack of learning initiative, low academic performance, backward practical ability, and weak ideological and political consciousness of the students majoring in computer science, thus causing their concerns about their employability after graduation. It makes students worried about their future and causes serious psychological problems. Therefore, the teaching mode of this course needs to be reformed.Subjects and Methods: This paper analyzes the problems in the traditional teaching process, studies the pain points in teaching, faces the strategic requirements of the new engineering era, takes training high-quality talents as the goal, takes students as the center, and makes students busy, teachers strong, management strict and the effect practical. This paper proposes PBL (Problem-based Learning) and \u201cPreview, Bridge in, Discussion, Evaluation, Exercise, Designing\u201d six-step teaching model, Online and offline hybrid teaching ideas, flipped classroom teaching methods, progressive curriculum ideological and political teaching process, experiential learning and Outcome-based Education (OBE) concept combined teaching system and curriculum innovation evaluation system.Results: Through the investigation and statistical analysis of the teaching reform results, it can be found that the innovative teaching reform aiming at the principle of computer composition has enhanced students\u2019 learning initiative, improved their academic performance, increased their practical ability, enhanced their ideological and political awareness, and cultivated a large number of patriotic and high-quality talents required by the new engineering era. It can reduce students\u2019 worries about their future employability and alleviates students\u2019 psychological problems. Conclusions: The new teaching method proposed in this paper has been proved to be efficient in practice, which can improve students\u2019 comprehensive ability, make students full of confidence in the future and relieve psychological anxiety, and preliminarily meet the requirements of the emerging engineering era. The course presenter will continue to promote the reform of teaching mode according to the connotation of the requirements of the emerging engineering, and cultivate a larger team of high-quality professionals.The work was supported in part by Quality project of Anhui Province with Grant number 2018mooc061, 2020xsjxms182, 2020mooc386, 2020zdxsjg260, 2020jyxm1423, 2021sx117, 2021jyxm1121 and 2021jxtd215, in part by Talent research launch start-up project of Fuyang Normal University under grant 2019kyqd0018, in part by Anhui Province university key research project under grant KJ2018A0669 and 2022AH052820, in part by List of first-class undergraduate programs in Anhui Province under Grant 209 and in part by Ministry of Education industry-school cooperative education project under grant 220601363062820.a, Tao Fana,b, Jian Wanga, Yan ShenaHuan Wanga College of Architectural and Civil Engineering, Xinjiang University, Urumqi 830047, China, b College of Architecture and Urban Planning, Tongji University, Shanghai 200092, China.Background: Due to the impact of the Internet on traditional business, bazaars in Xinjiang, China, have developed slowly in recent years. In order to activate this traditional commercial form, the government has carried out a series of construction practices of large bazaars. Although the actual operation effect of many bazaars is ideal, the problem of many bazaars is that the degree of public mental health and happiness is not enough, so it is necessary to study the strategy of commercial promotion based on the degree of public mental health and happiness.Subjects and Methods: The research object of this paper is the most famous commercial complex in Xinjiang -- Xinjiang International Grand Bazaar. Firstly, the objective analysis of customer behavior of Xinjiang International Grand Bazaar on the spot investigation of public mental health and happiness, including: walking traffic space status analysis, walking square space status analysis, function and landscape analysis. Secondly, 743 on-site and online questionnaires were used to conduct subjective analysis and evaluation on the status quo of public mental health and happiness in Xinjiang International Grand Bazaar.Results: Based on the objective analysis and subjective evaluation of public mental health and happiness, it is concluded that Xinjiang International Grand Bazaar puts emphasis on the renovation and upgrading of public square public space, gives full play to the synergistic effect produced by the combination of public space and commercial space, and improves the public mental health and happiness. The space has a strong degree of openness and inclusiveness. However, there is still some room for improvement in the degree of public mental health and happiness: (1) The utilization rate of the square is not enough, the lack of public space to meet different mental health needs. (2) Single functional area to increase functional space to meet more mental health needs. (3) Accessibility is not ideal and happiness is reduced.Conclusions: And finally put forward the promotion of mental health and happiness degree strategy: \u2474 rich square space to meet a variety of mental health needs, to create a comfortable and pleasant rest space, interactive space to promote mental health communication. (2) Expansion and reconstruction of functional zoning, reasonable distribution in each area of the International Bazaar; (3) establishment of body traffic, formation of \u201cmultiple first floor\u201d mode, and use of air corridor to increase building connectivity. This paper studies the degree of public mental health and happiness in Bazaar, the design strategy proposed in this paper can further activate the vitality of the Bazaar, attract consumers to higher floors or underground Spaces, and contribute to a more benign interaction between the International Grand Bazaar and the city, so as to improve its actual operation effect. It provides theoretical reference for the reconstruction of Xinjiang International Grand Bazaar and similar building design in the future.This work was supported by the project grant from 2020 Xinjiang Natural Science Foundation Youth Fund \u201cResearch on the Design Strategy of Public Cultural Service Function Based on Synergy Theory: A Case Study of Xinjiang Commercial Complex\u201d (Grand No. 2020D01C059).a, Mengjie Denga, Hao Tiana, Wenjing HuangbYihua Lia School of Transportation & Logistics, Central South University of Forestry & Technology, Changsha 410004, Hunan, China, b School of Materials Science and Engineering, Central South University of Forestry & Technology, Changsha 410004, Hunan, China.Background: In order to effectively cope with urban public health crisis, improve the toughness of the public health system, improve the level of medical health, and ensure the safety of consumers\u2019 medication. This study focuses on the most pressing difficulties and problems that are of great concern to the people in the field of medical and health. It aims to achieve low cost, high efficiency and high safety distribution of pharmaceutical products by conducting research on the joint distribution mode of pharmaceutical cold chain logistics.Subjects and Methods: In this paper, we first compose the development of pharmaceutical cold chain logistics and its infrastructure construction in China in recent years. Secondly, we compare and analyze three mainstream distribution modes in pharmaceutical cold chain logistics industry. Then we summarize the social benefits of carrying out joint distribution of pharmaceutical cold chain logistics. Finally, we enumerate the technical advantages of blockchain.Results: The results show that the development of pharmaceutical cold chain logistics has a bright prospect, and the implementation of joint distribution in pharmaceutical cold chain logistics can improve resource utilization, reduce business risks, help environmental friendliness and promote healthy development of the industry. The technical advantages of blockchain such as decentralization, distributed storage, tamper-evident, traceability and smart contract provide great convenience for the development of joint distribution business.Conclusions: The blockchain-based information service platform for joint distribution of pharmaceutical cold chain logistics can play a role in reducing costs and increasing efficiency, promoting cooperation and facilitating supervision. In addition, the real-time reaches of logistics data can greatly reduce the medical safety incident caused by the quality of medical products deteriorate in transportation process. The establishment of this information service platform has enlightening significance for the information construction of the entire pharmaceutical logistics industry.Support for this study was jointly provided by General Project of Chinese National Social Science Foundation \u201cResearch on the Balanced Path of the Cold Chain Logistics Structure System of Agricultural Products in the Digital Village Background\u201d (22BGL173), Major project of the Hunan Social Science Review Committee \u201cResearch on the Implementation Countermeasures for Promoting the Equalization of Basic Public Services in Hunan Province by Medical Cold Chain Logistics Driven by Data\u201d (XSP22ZDA006) and General Project of Hunan Natural Science Foundation (2022JJ31015). The authors would also thank all the institutions and units for providing statistical data, information, and documents used in this study.a, Ke Yinb, Yumeng YangcYi Xiaoa College of Public Administration; Chongqing Technology and Business University; Chongqing 400067, China, b College of Geographical and Travel, Chongqing Normal University, Chongqing 400047, China, c College of Business Administration, Chongqing Technology and Business University, Chongqing 400067, China.Background: Poverty alleviation in 2020, farmers still face various types of livelihood risks. In the livelihood risk analysis, livelihood capital is the core of the analysis. Therefore, it is necessary and practical to study the impact of livelihood capital on the livelihood risk and mental health of farmers in poor mountainous areas in Southwest China, so as to provide empirical basis for the government to better formulate relevant policies and consolidate the results of poverty alleviation.Subjects and Methods: Based on this, this study takes the questionnaire of 321 poverty-stricken farmers in the southwest poor mountainous areas as the sample data, analyze the impact of farmers\u2019 livelihood capital on their livelihood risk and mental health.Results: The results show: (1) Livelihood risks of poverty-stricken farmers include natural risks, economic risks, welfare risks and social risks. (2) Economic risk is affected by financial capital and human capital, natural risk is affected by natural capital and material capital, and welfare risk is affected by social capital, financial capital and material capital. Social risk is affected by natural capital and financial capital. It can be seen that human capital and financial capital are the key factors affecting the livelihood risk of farmers.Conclusions: On the one hand, the local government should increase the investment in the human capital of rural households to promote the systematization, diversification and specialization of farmers\u2019 employment training. Secondly, we should increase investment in education, improve the capital stock of farmers\u2019 livelihood and guide their mental health development as a whole; On the other hand, the government should improve the land utilization rate and promote the marketization process of rural land transfer. At the same time, the government should increase its support for farmers\u2019 cooperative organizations, accelerate the construction of a modern rural financial system, develop a diversified rural credit support model, and increase the financial capital stock of farmers, so as to effectively improve the livelihood level of farmers.This study was funded by National Social Science General Project: Study on Livelihood Risk and Sustainable Guarantee of Poverty Alleviation Farmers in Poor Mountainous Areas (20BJY166).a, Yi Yua, Zhiwei Tanga, Bo Hub, Dr. Ali AbidcXiaoke Yina Hunan Biological And Electromechanical Polytechnic, Changsha, 410127, China, b Beiya Middle School of Changsha, Changsha, 410005, China, c Allied Hospital, Faisalabad, Punjab 54590, Pakistan.Objective: According to the latest statistics of the World Health Organization, mental health problems are one of the main causes of extreme events (such as suicide). Therefore, the psychological health of college students is an extremely important research topic. The research on college students\u2019 mental health is traditionally based on small-scale questionnaires, scales or experimental data. This paper creatively proposes a diversified information based teaching method that combines online open courses, intelligent teaching platforms and virtual simulation teaching resources, and uses big data technology and concepts to analyze a large range of samples.Methods: The online open courses and virtual simulation teaching resources were organically integrated to solve the problem that students were difficult to understand the real learning situation; Integrate virtual simulation teaching resources and intelligent teaching platform organically to solve the problem that teachers cannot fully understand students\u2019 learning effects; The smart teaching platform and online open courses will be organically integrated to solve the problem that managers are difficult to understand the teaching situation. From the aspects of university economic life, academic performance, comprehensive performance, mental health and school satisfaction, the development of special enrollment plan students in rural and poor areas will be discussed.Results: The online open courses, intelligent teaching platform and virtual simulation teaching resources were integrated organically and promoted as a whole, and teaching methods were innovated, teaching resources were enriched and teaching effectiveness was improved. A machine learning model has been established to predict postpartum depression and depression through social media data, and the accuracy of the latter can reach 70%. Research based on microblog text and Instagram photos has also proved that machine learning methods can be used to identify patients with early depression with high accuracy. Literature systematically analyzed Sina Weibo users based on multi task regression and incremental regression algorithms and used them to predict the five personality traits.Conclusion: It can not only make up for the shortcomings of traditional classroom in colleges and universities, fully mobilize students\u2019 enthusiasm for learning, but also evaluate students\u2019 learning effects and timely adjust teaching strategies, so as to promote the comprehensive application of information and intelligence in education. Inspired by the recent education big data and computational social economics methodology, this paper intends to explore the relationship between students\u2019 mental health problems, especially depression symptoms and students\u2019 social behavior by analyzing students\u2019 behavior data under uncontrolled conditions.Obtained the \u201cFourteenth Five Year Plan\u201d of Hunan Education Planning Science in 2022, and \u201cResearch on the Path of Multi information Integration Teaching Means in Higher Vocational Colleges\u201d (Project No.: XJK22CGD076).aDeng Xina Department of Law, School of Political Science and Law, Xinjiang Normal University, Guanjing Road No. 100, Shuimogou District, Urumqi, Xinjiang, China.Background: With the fierce competition in modern society, various psychological problems have become important factors that seriously affect people\u2019s health and life satisfaction. The National Health Conference held in 2016 and the Outline of the Healthy China 2030 Plan issued after the conference raised the issue of universal health to a national strategic level. The Guidelines on Implementing the Healthy China Action, issued on July 15, 2019, clearly states that mental health promotion actions should be carried out. Thus, it can be seen that guaranteeing the mental health of the whole people plays an important role in the strategy of \u201cHealthy China\u201d. The formation of the national mental health system requires the construction of the top-level mental health coordination mechanism under the guidance of the idea of ecological civilization, and the system innovation of realizing the national mental health from the perspective of legal protection. To build an ecological mental health model for the whole people, this paper discusses the role of ecological civilization thought as an important ideological guidance as well as its application in realizing the legalization of promoting the national mental health.Subjects and Methods: To this end, this paper combs out the internal correlation between the thought of ecological civilization and the legal system of national mental health from the aspects of theoretical basis, logical consistency and historical experience, and analyzes the internal mechanism of realizing the legalization of the national mental health from the aspects of ecological jurisprudence foundation and ecological psychological system construction. From the perspective of legalization, this paper discusses the value, implication and practical path of how to raise the mental health problem of the whole people to the level of legal rights under the guidance of ecological civilization.Results: Based on the above analysis, this paper proposes to construct the legal environment through inheriting the excellent ecological mental health culture and creating the legal atmosphere of ecological mental health; unify the individual value orientation and common consciousness orientation by constructing a mental health ecological legal education system formed by theoretical cognition and practice; and leads the construction of the mental health awareness system of the whole people by optimizing the mental health rule of law under the guidance of ecological civilization.Conclusions: To realize the legal path of the right to mental health of the whole people, it is necessary to establish a right protection system on the basis of clarifying the subject of rights and the relative subject of obligations, and clarifying the content of rights and obligations between subjects. By integrating ecological civilization thought and practice into the process of exploring the legalization of promoting the national mental health, it is possible to promote all nationalities to actively construct the legal coordination mechanism and the relief assistance mechanism of mental health, providing a reference for the theoretical research and practice on promoting the national mental health.This work was supported by the project of \u201cResearch and Reform of Undergraduate Education and Teaching in Colleges and Universities\u201d by the Department of Education of Xinjiang Autonomous Region in 2022, \u201cIn-depth exploration and Organic integration of ideological and political Elements in the Course of Environmental and Resource Protection Law\u201d. (Grant No. XJGXPTJG-202227).a, Hua Zhoub, Yingli Lib, Mengqi WangbYuhang Wanga Institute of physical culture, Harbin University, Harbin, Heilongjiang 150076, China, b School of Marxism Northeast Agricultural University, Harbin, Heilongjiang 150030, China.Background: As we all know, physical exercise helps to enhance physical fitness and promote physical health. However, the effects of different physical exercise programs on psychological anxiety and depression have not attracted sufficient attention from scholars. This paper adopts the method of exercise intervention to study the impact of different physical exercise programs on anxiety and depression symptoms in college students, providing a theoretical reference for solving the mental health problems of college students, and providing a scientific basis for the formulation of exercise prescription.Subjects and Methods: Using the whole group sampling method, 60 undergraduates of Northeast Agricultural University with anxiety and depression symptom were selected as subjects. The subjects were divided into basketball group, badminton group and aerobics group according to their interest. The three groups of subjects were given 16 weeks of physical exercise intervention training. And Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) were used for assessment before and after the intervention. SPSS 20.0 statistical software was used for statistical analysis of the obtained data. The data before and after the same exercise program was compared by independent sample t test, and the data before and after the experiment between different exercise programs was compared by single factor ANOVA.Results: The anxiety level of the basketball group, the anxiety and depression level of the badminton group and the depression level of the aerobics group were significantly different before and after the experiment . The anxiety level of the aerobics group was extremely significant, and the depression of the basketball group was extremely significant . After the intervention, it was also found that SAS scores between basketball group and aerobics group, basketball group and badminton group, badminton group and aerobics group were all statistically significant and SDS scores between basketball group and aerobics group, basketball group and badminton group, badminton group and aerobics group are all statistically significant as well .Conclusions: The three kinds of physical exercise program can all significantly alleviate the anxiety and depression symptoms of college students, among them, aerobics program has the most significant effects on anxiety symptoms of college students followed by badminton program and basketball program. And badminton program has the most obvious effect on reducing the symptoms of depression followed by badminton program and aerobics program. This study only considered the effects of physical exercise programs on anxiety and depression of college students. It did not put the mediating variables such as gender factor, physical quality, personal characteristics into consideration, which should be considered in the follow-up study.Supported by a project grant from GJB1423410; GJE1422083.a, Yi WangaJiangxin Hea School of Marxism, Xi\u2019an University of Science and Technology, Xi\u2019an 710600, China.Background: The public recognition of low carbon psychology and anxiety about the environment are not only the objective requirement of people\u2019s response to climate change, but also the realistic need of the transformation and optimization of agricultural industry. Although low carbon life is a new concept, it does raise the world sustainable development of the old problem, it reflects the human because of climate change and the future environment concerns and anxiety. With agricultural modernizing, a great demand for carbon emission reduction and sequestration in agriculture and rural areas.Subjects and Methods: By identifying and confirming the basis and main types of carbon sources and sinks, as well as searching literature and conducting research, we found in-depth understanding of the existing problems of carbon emission in the Yangtze River Economic Belt, and ensure that the path of carbon emission reduction and sequestration is reasonable and effective. In this way, it can enhance people\u2019s recognition of low carbon psychology and relieve people\u2019s anxiety caused by environmental change.Results: Through studying the path of carbon emission reduction and sequestration in agriculture and rural areas under the condition of low carbon psychological identity and environmental anxiety, some problems existed in the Yangtze River Economic Belt region. For example, in the implementation of carbon reduction and sequestration goals, first of all, we should adhere to the green development of agriculture at the same time; Secondly, we should ensure the safety of agricultural products. While ensuring food production, we should also pay attention to the safety of agricultural products, which is related to people\u2019s health. Finally, we should optimize and innovate the system and mechanism.Conclusions: In order to promote the smooth implementation of carbon reduction and sequestration in agriculture and rural areas under the condition of low carbon psychological identity and environmental anxiety, technological innovation can be promoted and utilized. Developing conservation-oriented agriculture; Optimize agricultural management; Enhancing public awareness and changing lifestyles; Afforestation and other ways to solve the problem of carbon emissions polluting the environment, through these effective and reasonable paths, further improve the environmental state that people rely on for survival, can improve the public\u2019s psychological identification of low-carbon lifestyle, but also can alleviate people\u2019s anxiety about carbon emissions polluting the environment.a, Yuncai NingaSongtao Wanga School of Management, China University of Mining & Technology, Beijing, 100083, China.Background: Inclusive green growth is an important symbol of high-quality economic growth, and emotional regulation is a representative of social equity. The purpose of this article is to explore the impact of the digital economy on inclusive green growth, including emotional regulation, and analyze the important role of emotional regulation in inclusive green growth.Subjects and Methods: From the perspective of emotional regulation, a system dynamics model including emotional regulation was constructed to study the impact of the digital economy on emotional regulation. The system dynamics model includes stocks, variables, constants, etc.Results: The system dynamics model simulation results show that the digital economy can form positive feedback on emotion regulation, and emotion regulation plays a positive role in inclusive green growth. It can be seen from this that emotion regulation can reduce the income gap and promote inclusive green growth. The impact mechanism of the digital economy on inclusive green growth is that it can positively regulate emotions, thereby reducing the wealth gap and promoting inclusive green growth.Conclusions: This article studies the impact mechanism and system operation rules of the digital economy on inclusive green growth from the perspective of emotional regulation, which can provide theoretical support for relevant policy recommendations in the later stage. Therefore, the following policy recommendations are proposed: promoting the development of the digital economy is conducive to public emotional regulation, thereby reducing the wealth gap and improving mental health. Emphasizing the positive mechanism of the digital economy on emotional regulation is beneficial for inclusive green growth and strengthening the application of the digital economy. And utilize the strong vitality of the digital economy to promote inclusive green growth in cities, thereby promoting economic growth, alleviating national psychological pressure, and improving mental health. In the process of developing the digital economy, we should focus on increasing investment in the information industry, encouraging the development of new startups, and strengthening the application of the digital economy to strengthen it.a,b, Jianmei Xua, Xingying LibFusheng Lianga Huangshan University, Huangshan, 245041 China, b East China Normal University, Shanghai, 200241, China.Background: This paper discusses the developmental characteristics of fundamental motor skills of children aged 3-6 in Anhui Province, providing a basis for the creation and implementation of physical activities and games for young children, a reference for the improvement of children\u2019s physical fitness, as well as for the integration of sports, education, and medicine.Subjects and Methods: A total of 240 young children aged 3\u20136 in Anhui Province were selected as the survey subjects for statistical analysis by using the measurement tool of TGMD-3.Results: The average total scoring rate of fundamental motor skills for 3-6 year-old children in Anhui Province is 48.7%. Specifically, the average total scoring rate for fundamental motor skills is 30.1% for 3-4 year-olds, 47.85% for 4-5 year-olds, and 67.58% for 5-6 year-olds. There is a significant difference (P<0.05) in the Horizontal jump (S5) between boys and girls aged 3-4 years and 5-6 years, but there is no significant difference (P>0.05) in all other items for all age groups. The three items of Run (S1), Skip (S4), and Underhand throw (S13) all show significant differences (P<0.05), while the other items and total scores do not show significant differences (P>0.05). There is a significant difference (P<0.05) between the underweight and overweight groups for 3-4 year-olds and the overweight and normal groups for 4-5 year-olds. There is a highly significant difference (P<0.01) in the obese group for 4-5 year-olds. The multiple correlation coefficients of the comprehensive influencing factors for each age group are R=0.820, R=0.688, and R=0.866, and the significance is P<0.05 for all.Conclusions: Boys between the ages of 3-6 perform better in both locomotor skills and manipulative skills compared to girls of the same age group. There are significant differences in the development of fundamental motor skills between adjacent age groups of 3-6 year-olds, and the scoring rate increases are more pronounced in the 4-6-year-old group, with several individual items showing a greater increase. There are some urban-rural differences in the development of fundamental motor skills in 3-6 year-old children, and BMI has a certain impact on their fundamental motor skills. The family\u2019s exercise atmosphere, crawling experience in infancy, and participation in sports interest classes are positively correlated with children\u2019s fundamental motor skills, with the main effect of the family\u2019s exercise atmosphere being the most significant.This research was supported by the Young Backbone Teachers\u2019 Domestic Visiting Program of Anhui Province Provincial Education Department (gxgnfx2019036); the College Students\u2019 Innovation and Entrepreneurship Program in Anhui Province Province (S202010024); the Key Research Project in Humanities and Social Sciences in Higher Education Institutions in Anhui Province Province (SK2021A0632); and the Teaching and Research Project of Huangshan University (2021JXYJ12).a, Dan Wanga, Qiurong WangaZhaochu Qiana Chongqing Business Vocational College, Shapingba, Chongqing, China.Objective: Investors\u2019 confidence in the market largely affects the trend of foreign trade enterprises and even foreign trade markets. Based on the perspective of investors\u2019 psychological anxiety, this research analyzes the development status and practical constraints of Chongqing\u2019s foreign trade, and puts forward countermeasures to achieve high-quality development of Chongqing\u2019s foreign trade, so as to comprehensively promote the high-quality development of foreign trade in ChongqingMethods: Based on the change of investors\u2019 psychology, this research makes a multi-dimensional exploration of development in Chongqing from the perspective of investors\u2019 psychological anxiety by means of market subject analysis, quantitative analysis and field research.Results: The overall momentum of foreign trade development in Chongqing is good, but there are still some unfavorable factors. In terms of the external environment, the high inflationary pressures around the world is sustaining; the European economy is suffering a double blow; the impact of the mutation of the novel corona virus is continuing; the Sino-US economic and trade frictions is constant and presenting a long-lasting trend; the foreign trade enterprises are suffering survival pressure; and the investors\u2019 psychological anxiety is obvious. In terms of the internal constraints, the survival pressure of foreign trade enterprises is increasing; the structure of foreign trade is still unbalanced; the new drivers of foreign trade are not yet mature; and the ability of investors to withstand pressure is limited.Conclusion: After clarifying the causes of investors\u2019 anxiety, this research combines the law of foreign trade development with the law of investors\u2019 psychology change according to the actual development of foreign trade in Chongqing, and puts forward that the healthy development of foreign trade in Chongqing needs to work together from four aspects: strengthening the rescue of foreign trade enterprises, ensuring the stability and smooth of foreign trade industrial chain and supply chain, expanding foreign trade diversification and developing new business forms of foreign trade.This research has received the kind care, guidance and help from Chongqing Municipal Commission of Commerce and relevant enterprises in Chongqing. The systematic, forward-looking and practical content of this research has been significantly improved.aZhang Xiaa School of Foreign Language Mianyang Teachers\u2019 College Mianyang, Sichuan, China.Background: This study is to investigate internal and external factors that influence on the effectiveness of relieving students\u2019 psychological anxiety under the web-based college English teaching management.Subjects and Methods: The author mainly used quantitative study methodology. Data was collected from 445 students of eight colleges/universities in Mianyang city. Also introduced the phenomenological study by in-depth interview technique to support the quantitative study. The key informants are six college teachers, two leaders and twelve students from eight colleges/universities in Mianyang city. The study instruments were questionnaires and in-depth interviews. The statistics in analyzing the data were percentage, mean, standard deviation, one-way ANONA, T-test, correlation analysis, and multiple regression analysis.Results: The results showed that the internal factors have much more influence than external factors on the effectiveness of relieving students\u2019 psychological anxiety under the web-based college English teaching management.Conclusions: Finally, it concludeed the special management would be like this: \u201cweb-based teaching in class and web-based autonomous learning after class\u201d: that is to take full advantages of internet and build a good platform for students\u2019 self-learning, personalized learning and collaborative learning, so as to improve effectiveness on relieving students\u2019 psychological anxiety under web-based college English teaching management.aRenlin Guoa Beijing Enterprise Safety and Environment Information Science Research Institute, Beijing 100048, China.Background: Psychological anxiety is an important factor that causes safety risks for employees. In order to evaluate the impact of psychological anxiety on safety culture, this article constructs an SEM model to study the quantitative impact of psychological anxiety on safety culture in high-risk industries.Subjects and Methods: Psychological anxiety is influenced by multiple factors. As an important method to measure the impact of one group of multiple factors on another group of multiple factors, this article uses structural equation modeling to study the impact of psychological anxiety on safety culture in high-risk industries based on the obvious factors of psychological anxiety and safety culture.Results: The conclusion indicates that psychological anxiety is an important factor affecting the level of safety culture in high-risk industries, and there is a negative correlation between the two. That is, the higher the psychological anxiety of employees in high-risk industries, the lower the level of enterprise safety culture. Therefore, enterprises in high-risk industries should strengthen the level of enterprise safety investment, try their best to eliminate employee psychological anxiety, thereby improving the level of safety culture, and adopt various methods to alleviate employee anxiety, Enable employees to work in a warm atmosphere, thereby creating a good level of safety culture in the enterprise.Conclusions: The conclusion indicates that psychological anxiety is an important factor affecting the safety culture level of high-risk industry enterprises. Therefore, high-risk industry enterprises should eliminate employee psychological anxiety and improve safety culture level in the following aspects: firstly, strengthen safety investment, cultivate a good corporate safety culture, and minimize employee psychological anxiety; Secondly, carry out various safety activities to reduce employees\u2019 psychological anxiety and create a warm working atmosphere; The third is to correctly view psychological anxiety and safety management level, and organically link the two together.This research was supported by the Langfang science and technology research and development project (project number: 2021029083).a,b, Rui Sunc, Yuan YuancKun Zhaoa Tan Siu Lin Business School, Quanzhou Normal University, Quanzhou 362021, China b National Academy of Econnomic Strategy, Chinese Academy of Social Sciences, Beijing 100028, China c School of Business Administration of Huaqiao University, Quanzhou 362021, China.Background: The article analyzes the impact of online trust of Chinese investment company TMT on investment decision propensity of entrepreneurial projects and investors\u2019 psychological health.Subjects and Methods: Firstly, the article defines the \u201ctrust\u201d in the individual behavior attribute as \u201csituation trust\u201d and \u201cquality trust\u201d as the conceptual basis, and defines the trust relationship between the investment enterprise TMT and the entrepreneur. Second, by conducting an inductive longitudinal cross-case analysis on three Internet startup platforms in China, this study summarizes the relationships of the acquisition of situational and quality trust by investment company TMTs with the investment decision-making for entrepreneurial projects made by these TMTs. Thirdly, a research proposition is then proposed for further verification, from which the influence mechanism of investors\u2019 psychological health under the condition of interacting situational trust and quality trust of TMTs are identified.Results: The article finds that TMT online trust have a positive impact on TMT investment decision-making and investors\u2019 psychological health. Online situational trust influences investment decision propensity through the heterogeneity of situational perception, while when TMT shows higher quality trust, it helps investors to take joint action on market, information, and cooperation, as well as to conduct experimental learning to generate investment value, and to improve online investment decision propensity and reduce psychological anxiety. The existence of transactional or value-based trust transfer between online situational trust and quality trust determines different types of relationships between the two trusting subjects and induces TMT to choose the investment strategy corresponding to them.Conclusions: The article has important implications for further deepening the research on TMT online decision propensity of entrepreneurial projects and investors\u2019 psychological health. First, the article fills a gap in the literature regarding the \u201cinternal mechanisms\u201d and \u201ctrust transfer\u201d of online trust processes in explaining investment decision propensity and investor mental health. Second, by revealing the mechanism of online trust transfer between TMT situational trust and quality trust based on transactional and value-based, the article provides new ideas for in-depth interpretation of investors\u2019 online investment decisions and reduction of psychological anxiety. Thirdly, TMT should fully consider its own trust type and trust level, carefully design online trust investment mechanism, and choose the investment psychological strategy that fits with the trust type and trust level. Consistent with the problems of established inductive case studies, the findings of this study have limited external generalizability, and future research could expand the sample through other methods to improve external validity.Supported by a project grant from \u201cCognitive neural mechanism of personalized recommendation users\u2019 privacy response\u201d (Grand No.21FGLB041) and \u201cResearch on the formation mechanism and evolution path of intrepreneurial capability of manufacturing enterprises in Fujian driven by digital innovation\u201d (Grand No.FJ2022B055).a,b, Shuqin TianbDongqiang Wanga School of Management Science and Real Estate, Chongqing University, Chongqing, 400045, China, b Chongqing University of Arts and Sciences, Chongqing, 402160, China.Background: At present, the rural areas become the leading position, key area and weak link of epidemic prevention and control along with people\u2019s mental health in China.Subjects and Methods: This study trys to construct modern governance system for epidemic prevention and control in rural areas and analyse their impact on people\u2019s mental health from the perspective of all aspects, the whole process and all elements. A total of four cases were collected and analyzed according to the database involved epidemic prevention and control in rural areas in China and their impact on people\u2019s mental health built by the text analysis, grounded theory and multi-case analysis.Results: The results show that four typical models of epidemic prevention and control in rural areas in China and their impact on people\u2019s mental health, including legal leading model, local mobilization model, general grid model, and technical service model, are summarized and and a multi-case comparative study is conducted from the aspects of governance orientation, governance way, and governance mechanism. No matter which mode, COVID-19 had an impact on people\u2019s mental health, mainly manifested as depression, anxiety, stress, loneliness, helplessness.Conclusions: From the perspective of holistic management, this paper puts forward some policy suggestions to further strengthen the work of epidemic prevention and control in rural areas and reduce their impact on people\u2019s mental health: functional integration to establish a centralized and efficient leadership and command system; benign interaction to improve the communication and coordination mechanism of effective connection between different departments; demand orientation to take a holistic management and diversification model according to local conditions; crossing borders to build and share the work digital information platform of epidemic prevention and control in rural areas.This paper was supported by the National Social Science Foundation Project \u201cResearch on the Effect Measurement and Path Optimization of Social Forces Participating in Rural Revitalization in Key Assistance Counties\u201d (No. 22ASH014).a, Can Chenb, Yusheng LongcYajun Gua Tongji Zhejiang College, Jiaxing 314051, Zhejiang Province, China, b Jiaxing Nanhu University, Jiaxing 314001, Zhejiang Province, China, c Beijing University ShenZhen Hospital, ShenZhen 518000, Guangdong Province, China.Background: Investment decisions should not only consider the investment-return itself, but also analyze the psychological state of the decision-making subject, especially the psychological stability of the decision-making entity. This is a destabilizing factor that is independent of technological drivers. An individual\u2019s psychological stability is subject to biological factors such as disease, psychological factors such as personality traits, sociological factors such as the family environment of origin, and other factors. The result of the decision-making entity\u2019s processing of the above information ultimately becomes the key to the investment decision.Subjects and Methods: 1. The factor analysis method and the comprehensive analysis method are used to obtain the main contents affecting the psychological stability of the decision-making subject. 2. The investment decision-making model is constructed. Based on the assumption that the state of technological progress and the efficiency of new technology adoption are uncertain, the Bellman equation for optimal investment is obtained, and the optimal investment time of the project operator is calculated. 3. Parameter analysis of the investment decision-making model. 4. Using association analysis, relying on the psychological stability analysis of decision-making subjects, the decision-making results under different preferences are obtained according to the risk preferences of decision-making subjects.Results: 1. Psychological stability is subject to a variety of factors, and has strong instability and randomness. 2. The speed of technological progress is positively correlated with the uncertainty of positive benefits brought about by the adoption of new technologies, the positive rate of change in the adoption efficiency of new technologies, and the opportunity value F(V) and investment threshold V* adopted by telecommunications operators, while the negative rate of change in the adoption efficiency of new technologies is negatively correlated with the opportunity value F(V) and investment threshold V* adopted by new technologies adopted by telecommunications operators.Conclusions: In the field of telecommunications, operators make decisions on investment in new technologies, which is not only determined by technology itself, but also by the psychological stability of decision-making subjects is more decisive for the implementation of decision-making behavior. In fact, the psychological stability or broad sense of decision-making subjects is mental health the key to the success or failure of decision-making. In order to avoid the uncontrollability of individual decisions, team decisions can more rationally complete new telecommunications investment decisions. Broadly, similar methods can be used to make other types of decisions.aHao Penga School of Foreign Languages, Wuhan Polytechnic University, Wuhan 430024, China.Background: Language is a tool for human beings to convey their feelings and ideas. Human beings use language not only to convey information, but also to express their inner feelings. Therefore, language is also a window into people\u2019s mental health. Through verbal communication, psychiatrists can diagnose patients with mental disorders; Using big language data, scientists can quantify the special experience of doctors and develop intelligent products for early diagnosis of mental disorders. Linguistic researchers not only need to reveal the information of mental health through language, but also need to explore the neural mechanisms related to it.Subjects and Methods: AI studies how to use computer to simulate the ability of human brain to recognize, understand, participate, reason, learn, think and solve problems, and AI can perceive the external environment, further think, learn, and output corresponding behavior. AI has been described as the use of algorithms and software to approximate human cognition when resolving complex data. All AI involved in this paper belongs to the field of computer science and will adopt a series of technologies and methods: machine learning, natural language processing, speech processing, robotics, and similar automated decision making, etc., for developing and implementing human-specific language cognitive processes and mental health monitoring therapies.Results: Language production involves brain networks that process auditory, somatosensory, and visual input, as well as language perception and production. Mental illness often results in abnormalities in these brain networks, so analyzing language patterns can help diagnose mental disorders. Deficiencies in verbal communication are evident in many severe mental disorders, particularly those involving psychomotor retardation, affective retardation, and poverty of speech content. Language is an effective method to detect the mental state of patients. Existing research using artificial intelligence techniques to analyze voice and language patterns has been highly accurate in screening for mental health problems. Some researchers have developed algorithms into artificial intelligence systems that evaluate speech samples and compare them with previous samples of the same patient to score their mental status. Research has found that AI model scoring can be as accurate as human clinicians.Conclusions: Thanks to the rapid development of machine learning, the accuracy of predicting mental disorders by analysing linguistic data is also increasing. Language is a window through which experienced psychiatrists can assess a patient\u2019s mental state. If artificial intelligence can quantify the doctor\u2019s special experience, it will greatly improve the objectivity and popularity of diagnosis. In addition to the flexibility and universality of the collection, language features as a tool for early screening of mental disorders have unique advantages. In addition, social platform language big data can also be used for monitoring users\u2019 psychological status, and the analysis results can provide objective basis for government departments\u2019 decision-making in mental health. Similarly, rapid advances in neuroscience and biological science have provided scientific tools for exploring the relationship between explicit language and Behavior and internal psychology and spirit. Although artificial intelligence and neuroscience have made initial achievements in exploring brain mechanisms and identifying mental disorders using language information, they are still far from practical clinical application. On the way of monitoring and protecting people\u2019s mental health through the window of language data, multidisciplinary linguistic research still has a long way to go.a, Wen Shia, Hongbo FuaYuezi Weia School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China.Background: For the higher mathematics curriculum, it is still a new subject to carry out curriculum ideological and political reform and integrate ideological and political elements into curriculum teaching. Higher emotional intelligence is conducive to the formation of sound personalities. Combining ideological and political education with curriculum reform and teaching practice has an important means and method to cultivate people\u2019s personality.Subjects and Methods: Starting from affairs around us and national events, we internalized ideological and political education into the classroom teaching of higher mathematics, and practiced and explored the actual links. Through the teaching of ideological and political cases with the characteristics of the epoch and infectious, it opens a channel for students to connect mathematics with the outside world, and establishes the sound mentality of students.Results: In this way, students\u2019 enthusiasm and initiative in learning mathematics are improved, knowledge updating and cross-integration are realized, and students get the ability to find and solve problems. Through ideological and political education, psychological education cultivates students\u2019 high-quality emotional intelligence and shapes sound personalities, so that college students can form a healthy psychology.Conclusions: Teaching with ideological and political materials can promote the establishment and perfection of students\u2019 mentality. By integrating ideological and political education with the study of mathematics, it not only educates students in ideology and morality, but also allows students to understand the method of mathematical modeling from the mathematical model, and understands the practicality of mathematics. We will train professionals who have a healthy personality, healthy psychology, ideal and faith, morality, correct value pursuit, ability and responsibility of The Times, and promote the construction of new engineering and new medical sciences.This work was supported by the Second Batch of Industry-University Collaborative Education Project of the Ministry of Education in 2019 (Project No. 201902120032); the Education Science Planning Project of Guangzhou in 2020 (Project No. 06-410-2113029); and the First-class Major Construction Project of Guangzhou Medical University (Project No.: 02-408-2304-11-010XM).aFengxiang Denga School of Marxism, Hunan City University, Yiyang, Hunan, 413000, China.Background: During the COVID-19, many universities used remote online teaching methods, and online examination became a research topic. College students have two distinct psychological attitudes towards courses during the pandemic. The first type is a relaxed mentality, believing that loose and remote exams will give them great opportunities, so there is no need to study hard. The second type is anxiety, where some students are worried that the exam format may not be suitable or that they may find it difficult to achieve good grades. Some students may believe that remote exams can lead to inconsistent exam situations for different students, thereby harming the fairness and justice of exams.Subjects and Methods: The first is the feasibility of online exams. The progress of technology and society has put forward new requirements for exams, and the popularization of computers and mobile phones has made online exams possible. The emergence of the epidemic and natural disasters has made online exams necessary. Online exams are not only an improvement in assessment methods, but also a beneficial practice of open and personalized assessment, which meets the basic requirements of course teaching. The second is how effective online exams can be in eliminating exam anxiety among college students. There are three research methods. The first is literature research. We have collected various international achievements on the psychological anxiety caused by online exams and solutions, and screened the correctness and universality of these views in order to obtain the best solution based on our research subjects. The second is to conduct empirical research through online exams, which includes three parts: pre exam preparation, exam implementation, and post exam summary and improvement. The third is a survey of candidate satisfaction.Results: In theory, our colleague Lin Xiaojin et al.\u2018s research has proven that online exams are feasible. Practitioner Yue Sun also believes that universities should give more consideration to the selection and construction of online platforms, and carefully arrange online teaching. In practice, we have conducted ten years of repeated practice and compared the results of the offline exam in 2018 with the online exam in 2020, demonstrating that the results of the online and offline exams are equivalent. Through public opinion surveys, it is believed that online exams are better than offline exams.Conclusions: Online and offline exams have equivalence, and are superior in terms of convenience and fairness compared to offline exams. College students are very satisfied with online exams, with 66.23% of students highly recognizing computer-based exams, 24.12% of students believing that computer-based exams can be used, and only 9.65% of students still cling to traditional offline exams. This indicates that online exams during the epidemic period based on student anxiety resolution are successful.This work has been supported by the Education Department of Hunan Province, China . Professor Tu Jianhua of the Principles Teaching and Research Section of the School of Marxism, Hunan City University, China, has made great contributions to this topic, and other colleagues of the teaching and research section have participated in the research of this topic.a,b, Yuan Yuana,b, Yuntao Liua,b, Shunjie Zhonga,b, Luotong Liua, Liang Liua,cZhiyong Taoa Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, No.25, Taiping Street, Luzhou City, Luzhou, 646000, China, b Neurosurgery Clinical Medical Research Center of Sichuan Province, Luzhou, China, c Neurosurgery Clinical Medical Research Center of Sichuan Province, Neurological Diseases and Brain Function Laboratory, Luzhou, China.Background: VP shunts provide an important means of treating hydrocephalus, and infection is one of the main complications after a shunt placement operation. Infection can cause intellectual damage and ventricle separation and even lead to patient death. According to the affected site, infections associated with VP shunts can be classified as wound infections, meningitis, peritonitis, and shunt infections. Shunt infection caused by gastrointestinal perforation is a rare complication after VP shunt placement. After gastrointestinal perforation, intestinal bacteria can enter the intracranial system through the shunt, leading to ventriculitis, meningitis and even infection of intracranial nerves and brain parenchyma. At present, the cause of gastrointestinal perforation after VP shunt placement is not clear. We report a case of the intestinal penetration of a traumatic hydrocephalus-associated VP shunt in which intracranial infection resulted.Subjects and Methods: A patient of admitted to the neurosurgery department from October 2011 in Affiliated Hospital of Southwest Medical University was enrolled in the study. A case report.Results: The patient was a 10-year-old male with car accident-related injuries resulting in a consciousness disorder that required hospitalization. The diagnosis at admission was diffuse axonal injury. During hospitalization, the results of a head CT showed that the patient had hydrocephalus, and the patient received a ventricular abdominal shunt. Postoperatively, the patient could open his eyes on his own and had a GCS score of 7 points; 4 months after surgery, the patient developed a high fever. A head CT examination suggested bilateral lateral ventricle posterior angle abnormal density fluid level on imaging, which supported a suspicion of intracranial infection. The patient\u2019s abdominal CT examination showed a drainage tube that visibly ended in the ascending colon. The child underwent laparoscopic exploration, and the abdominal end of the tube was found to have entered the intestine. The patient\u2019s drainage device was removed, and the patient underwent external drainage surgery. Postoperatively, anti-infection and antiepilepsy treatments were given. Two months after surgery, the patient died due to circulatory failure.Conclusions: Infection is one of the main complications after shunt placement; a shunt infection due to gastrointestinal perforation is a rare complication after VP; and neurosurgeons should pay close attention to the development of intracranial infection after VP shunt placement.Experimental study on the effect of TPO on apoptosis and inhibition of brain edema, Luzhou Science and Technology Bureau, No.2021-JYJ-63.a,b, Zehua Panb, Minhan XieaPeng Hana Xiamen Huaxia University, Xiamen 361024, China, b Japan and South Korea Creative Entrepreneurship Research Center, Liaoning University, Shenyang 110036, China, c Jiangxi Industry Polytechnic College, Nanchang 330099, China.Background: This paper aims to analyze the influence of perceptual elements in agricultural product packaging on the purchase intention and psychological sentiment behavior of consumers from consumer psychological perception.Subjects and Methods: This paper applied a combination of internet content analysis and the IPA model analysis to capture comment information on consumer about agricultural products packaging on the Internet and used the ROST CM6 software to perform high-frequency vocabulary, semantic network, and emotional perception analysis on internet content. This research summarized and encoded the agricultural product packaging elements that affect the purchase intention and emotional behavior of consumers. At the same time, this paper used the IPA analysis to construct the analysis model. It analyzed the influence of the satisfaction and attention of each perceived factor in the packaging of agricultural products on the purchase intention and psychological needs of consumers.Results: The results showed that perceptual factors such as packaging appearance, capacity space, and material significantly impact the purchase intention and emotional behavior changes of consumers. Meanwhile, the aspects of low consumer satisfaction, such as packaging pattern, durability, and bearing capacity, needed to be further optimized.Conclusions: This paper analyzed the influence of perceptual elements on the purchase intention and changes of psychological emotional behavior of consumers from the perspective of consumer psychological perception. It summarized the theoretical ideas of agricultural product packaging design in line with the perceived value and psychological emotional behavior of consumers and enriched the research content of agricultural product packaging.This work was supported by a project grant from education and research project of young and middle-aged teachers in Fujian Province in 2022, Grant number (JAS22213).a, Zhiyong Taoa, Yuan Yuana, Shunjie Zhonga, Liang LiuaYuntao Liua Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.Background: Intracranial teratomas, which represent 0.5% of all intracranial tumors and 2\u20134% of pediatric intracranial tumors, can be classified into mature, immature and malignant types depending on histological variation. Most intracranial germinomas occur in the midline. Teratomas are commonly found in the pineal gland and suprasellar region but rarely in the third ventricle. Rupture of mature teratomas is a rare event. To date, only four cases of intracranial teratoma rupture have been reported: a spontaneous teratoma rupture in a 16-year-old female and a teratoma rupture in a 45-year-old male, while the other two patients died during the fetal period. Intracranial teratoma rupture with hemorrhage, on the other hand, has never been reported. We were the first to report a case of spontaneous rupture and hemorrhage of pediatric teratoma and achieved a good outcome through surgical treatment.Subjects and Methods: This study reports a 9-year-old boy who was hospitalized due to symptoms such as lethargy accompanied by headache, nausea and vomiting. Cranial computed tomography (CT) revealed a mass with hemorrhage in the third ventricle. MRI revealed a mass in the third ventricle with hemorrhage and an intraventricular hematocele.To solve the symptoms caused by hydrocephalus and tumor hemorrhage, bilateral ventriculocentesis and drainage were performed and then tumorectomy was performed through a transcallosal approach. Postoperative pathology showed mature teratoma rupture with hemorrhage.Results: After the operation, the serum AFP decreased to normal, and \u03b2HCG was significantly reduced (32.78 mIU/ml). The patient had clear consciousness and little speech when discharged from the hospital. His right upper and lower limb muscle strength was grade 4, his left limb muscle strength was normal. Enhanced MRI reexamination revealed no residual tumor or recurrence 3 months after surgery. Currently, the patient is in good condition and can walk independently without signs of tumor recurrence.Conclusion: To the best of our knowledge, this is the first report of mature teratoma rupture with hemorrhage in the third ventricle. We performed serum \u03b2HCG tests on the pediatric patient before and after surgery and found that the preoperative blood \u03b2HCG was >1,000 mI/ml, while the postoperative \u03b2HCG declined significantly to 32.78 mIU/ml, thus proving the possible diagnostic value of \u03b2HCG for teratomas. We proposed a treatment scheme in which the symptoms of tumor apoplexy and hydrocephalus are relieved by ventricular drainage prior to performing tumor resection. With these procedures, the patient had a good outcome, without the presence of residual tumor or recurrence during follow-up.a, Jiuwang Yub, Zhiheng Dongc, Dusubilige Wend, Lidao Baob, Lan WudSachula Baoyina Beijing University of Chinese Medicine, Beijing, 010030, P. R. China, b Hohhot Hospital of Traditional Chinese Medicine and Mongolian Medicine, Hohhot, Inner Mongolia, 010030, P. R. China, c Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010059, P. R. China, d Mongolia Medical School, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010110, P. R. China.S Baoyin and JW Yu contribute equally to this work.Background: In this study, the protective mechnism of traditional Mongolian medicine Nagab-9 on acute lung injury model rats and its material base were discussed.Method: Acute lung injury model were developed using SPF SD male rats by bleomycin thorugh trachea injection (3.5\u2005mg/kg). Then, model rats randomly devided into Nagab-9 middle dose (126\u2005mg/kg), Nagab-9 high dose (252\u2005mg/kg) and dexamethasone groups, 12 rat each group. Rats of sham-operated group were given same amount of physiological saline. Drug was given for once a day and continued for 21 days. Lung pathological changes were observed by HE staining method. The level of serum TNF-a and IL-6 were detected by ELISA and qPCR. The differentially expressed genes comparing different groups were examined by transcriptional screening technique and validated by qPCR. Also, related signaling pathways were analyzed through KEGG and GO analysis. The active metabolic compounds of Nagab-9 were tested by UPLC-QE-MS/MS untargeted metabolic assay and the active molecules from Nagab-9 were observed. Furthermore, AutoDock Tools (1.5.6) was used to analyze the detected active molecule of Nagab-9 and its target. Finally, the level of NF-kB in lung tissue was tested by immunohistochemistry and the level of proteins Raf, p-Raf, MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, Nur77 was analyzed by western blot.Result: Nagab-9 effectively reduced the level of inflammatory factors TNF-a and IL-6 in serum of ALI rats. Transcriptomic analysis found the expression level of NR4A1, Raf, Mek, ERK and NF-kB genes were significantly regulated by Nagab-9. KEGG and GO analysis showed MAPK signaling pathway was significantly mediated, especially, NR4A1 was highly expressed in model. Serum pharmacology result showed 24 of Nagab-9 compounds. Among them, small molecule lidocaine showed coorelation with MEK/ERK and NF-kB pathway. Molecular docking result revealed that the the interacting score of lidocaine and Nur77 was -5.0. Lidocaine was also detected and quantified in blood sample. qPCR and western resluts indicated that Nagab-9 can significantly down-regulate NR4A1, Raf/Mek/ERK, NF-kB at protein level in the lung tissue of ALI rats.Conclusion: Nagab-9 can effectively relieve normal symptoms and lung pathalogical changes of ALI rats. The possible molecular mechanism is that the small molecule lidocaine from Nagab-9 inhibit the expression of NR41 and prevent Raf/Mek/ERK pathway, thereby prohibit Raf/Mek/ERK pathway and consequently decrease NF-kB inflammation and reaction.This research is funded by the following projects: Natural Science Foundation of China (No. 82160794 and 82160703); Natural Science Foundation of Inner Mongolia Autonomous Region (No. 2020MS08106); Project of Health Science and Technology in Inner Mongolia Autonomous Region (No. 202201238); Inner Mongolia Autonomous Region Chinese Medicine (Mongolian Medicine) Young and Middle-aged Leading Talents Cultivation Project; Grassland Yingcai in Inner Mongolia Autonomous Region; Qihuang Scholar.a, Fangfang Mab, Gongxing Wub, Huiyuan ZoubYanhong Lia School of Management, West Yunnan University of Applied Sciences, Dali, 671000, China, b School of Management Engineering and Electronic Commerce, Zhejiang Gongshang University, Hangzhou, 310018, China.Background: In recent years, the COVID-19 pandemic, the China-Us trade war and other events have caused an unprecedented impact on globalization. The profound adjustment and restructuring of the global industrial chain have had a profound impact on the supplier and customer relations and trade development of enterprises. At the present time of fluctuating global economic situation, how to build a solid trade relationship network and consolidate the psychological and emotion relationship network of both sides of the trade is worth in-depth discussion in a scientific and effective way. In the context of the digital economy, this study analyzes and discusses the mechanism of the supplier - customer relationship network affecting the high-quality trade development from the perspective of emotion regulation.Subjects and Methods: Using enterprise supplier - customer data to construct enterprise supplier - customer relationship network, calculate PageRank value to depict enterprise supplier - customer relationship strength, and use the data of China\u2019s A-share listed companies from 2010 to 2020 to carry out empirical research. The influence mechanism of supplier - customer relationship network on trade quality development under the adjustment of digitalization degree and marketization degree is analyzed. The methods proposed in this study can also be further developed theoretically from the perspective of emotional regulation. Through the construction of a network of psychological and emotional exchanges and win-win cooperation, it can provide strong support for a more solid and stable e-commerce trade, so as to promote the high-quality development of China\u2019s trade.Results: The results show that both the supplier and customer network relationship and its proportion have a positive and significant impact on the development of trade quality. Both the degree of digitalization and the degree of marketization have a positive interaction effect on the relationship between supplier - customer relationship network and trade quality development. Moreover, in the market environment with weak environmental uncertainty, the supplier - customer relationship network is more significant to the high-quality trade development, and the moderating effect of the degree of digitalization and the degree of marketization of enterprises is also stronger. Under a stable emotional regulation network, both sides of the trade can adjust their trade psychological health and maintain high-quality economic and trade development with positive behaviors and communication trends.Conclusions: Based on the calculation results and theoretical analysis of this study, we can deeply study the influence mechanism of supplier-customer relationship network to promoting high-quality trade development from the perspective of digital economy and emotion regulation, analyze the various characteristics of cross-border e-commerce in modern enterprise trade which are different from traditional trade, and analyze how to regulate supplier-customer emotional network relationship, maintain a positive attitude under the situation of good behavior, high-quality economic and trade development. At the end of the paper, some directional suggestions are given for further research.Supported by the Digital Trade and Silk Road E-commerce Engineering Research Center of Yunnan Provincial Education Department and Major scientific and technological support projects in Dali prefecture \u201cThe Application of Digital Trade and Cross-border E-commerce in Dali Prefecture\u201d.a, Ri Chena, Qihui MaaJiayi Wanga Cilin Hospital, Ningbo, Zhejiang Province, China.Objective: To explore the effect and safety of calcium polycarbophil combined with compound polyethylene glycol electrolyte powder on bowel preparation for colonoscopy.Methods: A total of 539 patients undergoing colonoscopy and treatment in Cixi Cilin Hospital, Ningbo, Zhejiang Province from January 2021 to July 2022 were randomly divided into three groups: A, B and C. Study group A (n=180) adopted calcium polycarbophil tablets within 48 hours before taking compound polyethylene glycol electrolyte powder in preparation for intestinal colonoscopy. Study group B (n=180) adopted calcium polycarbophil tablets within 72 hours before taking compound polyethylene glycol electrolyte powder in preparation for intestinal colonoscopy. Control group C (n=179) only took compound polyethylene glycol electrolyte powder for intestinal cleansing. The intestinal cleaning effect and antifoam effect of the three groups were evaluated by the Boston Bowel Preparation Scale (BBPS), and the adverse reactions during the bowel preparation of the three groups were observed.Results: The Boston scores were corrected by the Bonferroni method. The intestinal cleanliness and antifoam effect of the patients in study group A and study group B were significantly higher than those in control group C and there were significant differences (P<0.001). There were no significant differences in intestinal cleaning effect and antifoam effect of the patients between group A and group B which points the effects in the two groups were equivalent. No serious adverse reactions occurred in all three groups, and the incidence of adverse reactions was low without statistical difference between groups (P>0.05).Conclusion: The effect of taking calcium polycarbophil tablets combined with compound polyethylene glycol electrolyte powder for intestinal preparation 48 hours and 72 hours before colonoscopy are better than that of using compound polyethylene glycol electrolyte powder alone which are safe and acceptable with low incidence of adverse reactions and no serious adverse reactions.This work was supported by the under Grant [number CN2018010].a, Qian Lia, Yesong Chenga, Fei Pengb, Dingqiang HuangaWujun Zoua Department of otorhinolaryngology head and neck surgery, Chengdu Second People\u2019s Hospital, Chengdu 610000, China, b Department of Anesthesia, West China Hospital of Sichuan University, Chengdu 610000, China.Background: Tonsillectomy is one of the most frequent operations performed by otolaryngologists in children. Hence, it is essential to prevent postoperative complications in children undergoing tonsillectomy. A successful preoperative education might prevent postoperative complications. This study aimed to investigate the effect of preoperative education using a cartoon video for the prevention of postoperative complications in children scheduled for tonsillectomy.Subjects and Methods: A total of 154 patients scheduled for elective tonsillectomy met the inclusion and exclusion criteria and were randomly divided into the control (77 cases) and cartoon video (77 cases) groups. Patients\u2019 eline data were carefully recorded. The duration of operation, intraoperative blood loss, postoperative diet recovery time, VAS pain scores on the first, third and seventh day after surgery, tonsillar fossa infection, the incidence of postoperative bleeding, upper respiratory symptoms and digestive symptoms was evaluated.Results: Compared with the control group, the average visual assessment score (VAS) pain scores on days 1 and 3 after surgery were significantly decreased in the cartoon video group (P < 0.05). Moreover, the eating time was markedly reduced in the experimental group (P < 0.05). There was no significant difference in intraoperative blood loss, postoperative pain score (day 7), postoperative bleeding, tonsillar fossa infection, digestive symptoms and upper respiratory tract infections.Conclusions: For children scheduled for tonsillectomy, preoperative communication using the cartoon video can effectively improve postoperative recovery. The cartoon video can help children understand the contents of preoperative education more easily, deserving extensive promotion.aChen Chena School of Business Management, Hangzhou Polytechnic of Science and Technology, Hangzhou, China.Background: By investigating the employment quality of e-commerce employees and its impact on Subjective Happiness, this paper proposes countermeasures for improving employment quality that can improve the happiness of e-commerce employees, and provides opinions and suggestions for e-commerce employees, governments, universities and enterprises.Subjects and Methods: Taking e-commerce employees of small and medium-sized enterprises in Hangzhou, Ningbo, Wenzhou, Taizhou, Jinhua and Yiwu as the research objects, this paper adopts the subjective and objective evaluation indicators of employment quality and the data of 379 valid questionnaires collected from the survey to study the employment quality and its impact on Subjective Happiness. In the research process, questionnaire survey, field survey, interview and other methods are mainly adopted. The questionnaire designed was answered by Likert\u2019s 5-point scale. In the data processing process, SPSS software and Excel were mainly used to carry out statistical analysis. For example, univariate analysis , bivariate analysis , or multivariate correlation analysis is used.Results: (1) Among the four dimensions of employment quality, the average score of interpersonal relationship is the highest, followed by job adaptation and career development, and the score of work intensity is the lowest. (2) Most people think they can adapt to their current jobs, and as they grow older, they become more adaptable; (3) E-commerce employees work long hours and are under great pressure, but they are still looking forward to their work; (4) Most people pay more attention to whether their job has development prospects and whether doing this job has harm to their health. The happiness index of a job with prospects and good health is high; (5) They think their spare time is colorful, but they don\u2019t have enough time to spend with their families; (6) Career development, job adaptation and interpersonal relationship have a significant positive impact on job Subjective Happiness, and work intensity has a significant negative impact on job Subjective Happiness; Career development, job adaptation and interpersonal relationship have a significant positive impact on Life Subjective Happiness, while work intensity has a significant negative impact on Life Subjective Happiness.Conclusions: In order to improve the Subjective Happiness of e-commerce employees, it is suggested that the government level, enterprise level and individual level make joint efforts to create a fair and just competition environment for the e-commerce industry and promote the realization of higher quality employment of e-commerce employees, including the establishment of supervision mechanism and the improvement of social insurance mechanism. Pay attention to the career development of employees, improve the welfare and compensation system, give full play to the initiative of employees; Do a good job planning, according to interests and professional ability to choose positions and other countermeasures.a, Jun Denga, Zhihua Liaob, Si Chenc, Rongjun ZhaoaYuxiao Luoa Department of Foreign Languages, Zhongshan Institute, University of Electronic Science and Technology of China, Zhongshan, Guangdong, 528402, China, b Department of Humanities, Shanghai University of Finance and Economics, Shanghai, 200433, China, c Department of Nursing, Southwest Medical University, Luzhou, Sichuan, 646000, China.Background: Mobile learning has been regarded as an essential scheme to optimize the allocation of educational resources and to ensure the fairness of education. Scholars both domestically and internationally have conducted the extensive research on mobile learning by utilizing the UTAUT model and other related prior models, in order to glean insights and ideas for improving learners\u2019 emotional and behavioral experiences during the mobile learning process. However, compared with the general College English, the influencing factors of behavioral emotions in the mobile learning process of Medical English have rarely been included in the current massive amounts of studies.Methods: Based on the UTAUT model, a schematic model of the influencing factors was constructed, and a quantitative questionnaire was designed to profoundly explore the influencing factors of behavioral emotions in the mobile learning process among Medical English learners. The questionnaire scale includes participants\u2019 moderating factors, critical factors, and behavioral emotions, which involves 50 declarative sentences. The simple random sampling was applied to choose 180 participants from 360 learners in Medical English. The descriptive statistics, Pearson Chi-Square analysis, Pearson correlation analysis, and regression analysis have been employed to validate hypotheses.Results: There are no significant differences in participants\u2019 behavioral emotions including potential intentions and genuine attitudes to embark on the mobile learning behaviors with the aid of modern information technology when participants are grouped into male-science, male-liberal arts, female-science, and female-liberal arts. There is a positive significant correlation between participants\u2019 voluntary and four critical factors. There is also a positive significant correlation between participants\u2019 experience and four critical factors. Participants\u2019 moderating factors positively correlate with their behavioral emotions, including potential intentions and genuine attitudes. The univariate linear regression analysis shows that there is a linear regression relationship between participants\u2019 extent of facilitating condition and their behavioral emotions, between participants\u2019 extent of effort expectancy and their behavioral emotions, between participants\u2019 extent of social influence and their behavioral emotions, and between participants\u2019 extent of performance expectancy and their behavioral emotions.Conclusions: The results of this study imply that participants\u2019 psychological capital can not only help them identify the critical influencing factors, but also mobilize their own behavioral emotions including potential intentions and genuine attitudes, which may finally be transformed into the practical mobile learning behaviors. This research may not only provide some inspirations for administrators and teachers to improve behavioral emotions of learners in the mobile learning process, but also usher in some theoretical and practical implications for researchers who intend to conduct relative studies in the near future.Supported by projects\u2019 grant from Research on Influencing Factors of Learners\u2019 Stickiness in the First-Class Course from the Perspective of Social Cognition Theory (Grant No. GD22XJY18); Research on the Intervention Mechanism of College Students\u2019 Psychological Health Based on Self-Regulation (Grant No. 2021GXSZ117).a, Chuna Chena, Pan Chena, Xiaojun Jinb, Qingtian Menga, Xuchang ZhangcYanxia Qina Department of rehabilitation medicine, Second Affiliated Hospital of the Chinese University of Hong Kong, Shenzhen, 518172, China, b Imaging Department, Second Affiliated Hospital of the Chinese University of Hong Kong, Shenzhen, 518172, China, c Department of Geriatric Medicine, Second Affiliated Hospital of the Chinese University of Hong Kong, Shenzhen, 518172, China.Background: It is well known that swallowing is a more complex sensorimotor activity, which includes both the voluntary movement but also the non-voluntary movement. All of these movements require the brain stem, the cortex and the nerves around the brain stem to regulate. Stroke is an important cause of patients with swallowing disorders, in the process of clinical treatment of swallowing disorder patients after stroke, medical staff by taking transcranial direct current stimulation has achieved good experimental results, and transcranial direct current stimulation as a new type of non-invasive brain nerve stimulation technology, is increasingly applied to the clinical after stroke swallowing function rehabilitation. However, the injury mechanism after cerebral hemisphere stroke is yet clear. This article mainly analyzes by taking the stroke patients transcranial direct current stimulation can improve the specific function of swallowing, and contrast into the patients of side, side swallowing cortex transcranial direct current excitatory stimulation after specific curative effect difference, the application of blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) technology in before and after tDCS treatment brain structure and function of imaging data, analysis of tCS on the cortex, clear swallowing function rehabilitation and brain function activation mode, location is relationship.Subjects and Methods: By selecting 60 patients with swallowing disorders who came to our hospital from January 2021 to November 2022, and by using a random allocation of numbers. They were divided into three groups: affected side group, healthy side group and control group, for these three groups of patients are subjected to routine swallowing training, ice stimulation, and functional electrical stimulation therapy, for patients in the healthy group and patients in the affected group. On the basis of swallowing training, ice stimulation, and functional electrical stimulation therapy, give excitatory stimulation on the healthy side and excitatory stimulation on the affected side, respectively.Results: After treatment of the 60 patients, the SSA scores were significantly higher in all three groups than before treatment, Healthy side group> affected side group > control group; swallowing lithography (VFSS) examination: before treatment than after treatment, and healthy side group > affected side group > control group; cranial fMRI examination: blood oxygen level dependent method (BOLD-fMRI) examination showed bilateral anterior central gyrus, posterior central gyrus, cingulate gyrus, insula, prefrontal, cuneus swallowing activation area, respectively, more than and stronger than before treatment, and the healthy side group > affected side group > control group.Conclusions: In conclusion, after treatment, the patients in the healthy group were significantly higher than patients in the affected group and the control group, and the difference between the affected group and the control group was not statistically significant.This work was supported by the Shenzhen Longgang District Economic and Science and Technology Development Special Fund for Medical and Health Science and Technology Project (LGKCYLWS2020001764).a, Shuoyang ZhaobYanqiu Yanga Director of Hospital Infection-Control Department, Beijing Daxing District People\u2019s Hospital, Beijing 102600, China, b Beijing Jishuitan Hospital, Beijing 100096, China.Background: To evaluate the reliability of ultra-fast fluorescence bio-monitoring method in high pressure steam sterilization monitoring.Subjects and Methods: The software program SPSS 20.0 was used to conduct the statistical analysis. Continuous variables were expressed as mean \u00b1 standard deviation (SD). Discontinuous variables were expressed in percentage (%). P<0.05 was considered statistically significant. We compared two methods under three conditions: 134\u00b0C/70 S, 134\u00b0C/160 S and 134\u00b0C/250 S. The sterilization effect of pressure steam was monitored by these two methods, and the reliability of the ultra-fast fluorescent biological method was evaluated by comparing this with the results obtained through the conventional bio-monitoring method.Results: The one-hour ultra-fast fluorescence test result obtained by the biological reader was highly consistent with the result of the 48-hour incubation with ultra-fast bio-indicators, as well as the incubation result after seven days using the traditional biological monitoring method. It was found that there was no significant difference between these. Using the traditional biological monitoring methods, the cultivation needs a long time, which is not good to the turnover and effective use of surgical instruments. The purchase of more surgical instruments for turnover will need more money, which is generally not approved by the hospital. A better solution is speeding up the cleaning, disinfection and sterilization of surgical instruments. Biological monitoring is the gold standard for surgical instruments, especially those with implants or lumens, and sterilization is mainly a process of killing pathogenic microorganisms. Therefore, the parameters of accelerated biological monitoring were selected for verification, to ensure the safety of surgery and medical treatment while ensuring the speed. When the ultra-fast bio-indicator was self-cultured, 36 of these turned yellow at 48 hours, and 36 of these turned yellow at 168 hour. There was no increase in positive results, and the results detected within one hour were consistent with the final biological culture results. The color change results were identical with those of the traditional bio-monitoring sterilization indicator at the seven-day culture.Conclusions: The one-hour ultra-fast fluorescence bio-monitoring method is extremely accurate and reliable. This method can be widely used to improve the time-efficacy of biological monitoring. In conclusion, the results obtained by this kind of ultra-fast fluorescence biological monitoring method are both accurate and reliable, and can be used in the biological monitoring of high-pressure steam sterilization. This can fundamentally solve the limitation of the long monitoring of traditional biological indicators, realizing a seamless workflow process of cleaning, packaging, sterilization and distribution, and thereby improving the turnover rate and work efficiency of equipment.a, Pengfei LibShaoyu Donga School of Business Administration, Northeastern University, Shenyang, China, b School of Computer Science and Engineering, Northeastern University, Shenyang, China.Background: Chinese family firms have entered a peak period of inheritance, development, transformation, and upgrading; intergenerational succession is bound to affect family firms substantially. The smooth inheritance of a family firm is not only related to the longevity of the firm itself but also to the healthy and sustainable development of the national private economy. Therefore, seeking global-scale development opportunities has become essential for sustainable development for family firms. However, current studies mainly focus on the influence of family firms\u2019 internationalization based on the intergenerational succession scale. Moreover, psychological anxiety is another important factor that can impact family firm internationalization. Starting or expanding a business in a foreign market can be a daunting task, and psychological anxiety can make this process even more challenging. Few studies focus on family firm successors\u2019 psychological anxiety at different stages of succession, and few focus on the intrinsic logic and action mechanism of second-generation successors\u2019 impact on family firm internationalization. In this paper, we innovatively combined the concept in cognitive psychology to understand better the influence of intergenerational succession and psychological anxiety on family firm internationalization.Subjects and Methods: In this paper, we explored the internal mechanism of intergenerational succession that affects the degree of internationalization of family firms and further proposed a series of theoretical hypotheses based on the characteristics of China\u2019s trade policy environment and the actual situation of the intergenerational succession of family firms. This paper takes 1219 listed family businesses in China from 2010 to 2018 as a sample to study intergenerational succession\u2019s impact on the degree of internationalization.Results: By providing comprehensive empirical tests, we found a positive correlation between family firm intergenerational transfer and the degree of internationalization. Further tests, such as instrumental variables, Tobit regression, and robustness tests, show that: (1) intergenerational succession has a significant positive impact on the degree of family firm internationalization, and the results still hold after considering potential endogeneity issues and conducting a series of robustness tests.; (2) through analyzing of mediating effect test results, we find that increases in long-term borrowing and corporate social responsibility is an important means for intergenerational succession to enhance internationalization; (3) the heterogeneity analysis results reveal that family firms belonging to the high-tech industry can promote the degree of internationalization in the stage of intergenerational succession, and compared with the period of parent-child co-governance, \u201csecond-generation autonomy\u201d can promote the degree of internationalization because it eliminates the psychological anxiety of managers.Conclusion: Our study enriches the research in intergenerational succession on the degree of internationalization of family firms, and we also provide a reference for exploring family firm inheritance and maintaining long-term competitiveness by providing four aspects of suggestions.This work was supported by National Natural Science Foundation of China (No. 71873027); Humanities and Social Science Foundation of Ministry of Education of China (18YJA790063).aRenlin Guoa Beijing Enterprise Safety and Environment Information Science Research Institute, Beijing, China.Background: Psychological health is the foundation of safety culture. This article uses the DEA-tobit model to evaluate the safety culture of enterprises, and proposes policy recommendations to improve the level of psychological health.Subjects and Methods: Mental health is the focus and important aspect of safety culture construction. Based on clarifying the concept of mental health, this article reviews the literature on mental health and evaluates the efficiency of safety culture from the perspectives of industry and enterprises using the DEA-Tobit model. The level of mental health is calculated, and policy recommendations are proposed based on the research conclusions.Results: Research based on the measurement of mental health and safety culture shows that there is a positive correlation between mental health and safety culture levels in coal mines. The higher the level of mental health, the higher the level of safety management in coal mining enterprises. Therefore, coal mining enterprises must clarify the importance and necessity of mental health, in order to build a strong level of safety culture, reveal the relationship between safety culture and mental health, and have significant implications for improving the level of coal mine safety management. This will enable coal mines to increase safety investment, establish long-term mental health concepts, and comply with various safety production and investment regulations.Conclusions: The research conclusions of this article include improving the mental health level of coal mines, increasing safety investment, establishing a soft culture of coal mine safety, enabling employees to establish correct mental health concepts, accelerating enterprise modernization, improving safety management level, raising the entry threshold for frontline employees from the perspective of mental health, strengthening investment in safety training and education, improving and improving labor union organizations, and increasing investment in safety funds and scientific research funds, Effectively improving the level of mental health and safety culture.This research was supported by Shandong Social Science Planning and Research Project: Research on the comprehensive allocation level measurement and optimization strategy of urban innovation factors in Shandong Province under the digital economy (22DGLJ23).a, Changgan FangbWei Qina Youth League Committee of Wuzhou University, Wuzhou, Guangxi 543002, China, b Department of Scientific Research, Wuzhou University, Wuzhou, Guangxi 5430002, China.Background: With the continuous deepening of global modernity, traditional dance must undergo new adaptation and reproduction under the influence of modernity. Dancers have psychological problems such as stage fright, excessive excitement, and ineffective emotional expression in the process of traditional dance reproduction.Subjects and Methods: From the perspective of dance psychology, this study takes dancers in the reproduction process of the Zhuang traditional board shoe dance \u201crun for the sun\u201d as the research object, and uses qualitative research methods to conduct the research. By using the researcher as the research instrument, the non-scale methods such as personal in-depth interviews, focus group interviews, state observation, and psychoanalysis were employed to investigate the dancers\u2019 psychological phenomena as a whole in a natural context. The author collected and recorded data in various aspects, analyzed the data using inductive methods to form theories, gained an interpretive understanding of the dancers\u2019 movement behaviors and meaning constructions through interaction with the research objects.Results: Based on the choreographer\u2019s requirements of neatness, upper-air technical difficulty, and character portrayal for the dancers in the traditional dance reproduction, the psychological problems that the dancers encounter or exhibit in the traditional dance reproduction and the adverse effects on the dancers\u2019 physical and psychological health are analyzed. On this basis, by observing the dancer\u2019s psychological quality and character traits, it was analyzed that the dancer\u2019s psychological problems are caused by unsound psychological quality, which trigger unstable behaviors such as nervousness and stiff limbs. Based on the analysis of psychological problem images and causes, effective methods are proposed to overcome the psychological problems in the traditional dance reproduction, and finally the reproduction of traditional dance and the construction of dancers\u2019 psychological health are completed.Conclusions: The results show that psychological intervention based on dance psychology can achieve the effects of stabilizing self-emotions, improving self-confidence and enhancing cultural quality, which plays an important role in the cultivation of dancers\u2019 physical and psychological health.This work was supported by the 2019 Annual Stage Art Creation Founding Project of National Arts Foundation under Grant 2019-A-02-(079)-0211.a, Tiantian Wanga, Li Zhua, YanQiong Goua, Hui Tana, JinZhi MaaYuan Wena Yellow River Sanmenxia Hospital, Henan Province, Sanmenxia 472000, China.Background: Objective Analysis found that the young urethral orifice mass as the main manifestation, and misdiagnosed as vagina, clinical diagnosis and treatment of vegetation, in order to improve the understanding of the disease.Subjects and Methods: Reviewing a case admitted to Sanmenxia Hospital in Henan Province, the clinical and laboratory examination data from January 27, 2023 to February 2, 2023, reviewed relevant documents, analyzed the causes of the misdiagnosis and summarized the literature.Results: In this case, the child was misdiagnosed as the vaginal burden because the child could not cooperate with the examination, and the final intraoperative exploration was hysteroscopy after anesthesia, and after detailed examination, it was confirmed as the uroid mass, and the pathology was confirmed as condyloma at the urethral mouth after resection. The main reasons for delayed diagnosis and misdiagnosis include: lack of awareness of the disease. Failed to grasp the exclusion features of diagnosis, the medical history was not detailed, and the children could not cooperate with the physical examination. The incidence of vaginal and urethral mass was low. Young period, vaginal and urethral anatomical position, when long vegetation larger, mass root through simple physical examination is not easy to find, children fear and fear for detailed physical caused difficult.Conclusions: the conclusion of seemingly young vaginal oral redundant cases for clinical characteristics, because of the young vaginal, urethral opening distance close, difficult to identify, need to find the urethral opening anatomical location if failed to find obvious urethral entrance or children completely cannot cooperate, need to consider the urethral opening mass, and urethral opening mucosal valgus may be, need further examination under anesthesia. In order to avoid misdiagnosis and mistreatment. Condyloma acuminata is less rare, condyloma acuminata growing around the urethral opening is rarer, friction tissue edema, easy to misdiagnosed vaginal tumor and urethral opening mucosa valgus. Therefore, young girls to prevent such diseases pay attention to improve their own immunity and resistance, but also to prevent other ways of infection.a, Dawei LiuaQian Lia College of Public Management, Guizhou University of Finance and Economics, Guiyang 550025, China.Background: Whether the regional disparities in the development of higher education in China have changed since the implementation of the connotative development has received widespread attention from the society. However, few studies have focused on this issue based on statistical data. The regional disparities in higher education development have a direct impact on the difficulty and quality of students\u2019 college admission, which in turn can affect the psychological needs of students from different regions for entering their ideal universities and their anxiety towards college admission.Subjects and Methods: Using a panel data approach covering the period of 2013-2020, this study comparatively analyzed the regional disparities in higher education development in the Eastern, Central, Western, and Northeastern regions of China as well as across provinces. Furthermore, the study explored the possible impact of these disparities on students\u2019 anxiety about college admission.Results: From 2013 to 2020, the number of regular institutions of higher education per million people in China increased from 1.82 to 1.94. Notably, the densities of institutions of higher education in Beijing and Tianjin were much higher than in other provinces, at 4.20 and 4.04 institutions per million people, respectively. With regard to high-level educational resources, in 2020, the number of doctoral students in Beijing exceeded that of undergraduate students by 20%, while the number of master\u2019s students exceeded that of undergraduate students by 55%. Meanwhile, in some western provinces, the number of doctoral students was still less than 1% of the undergraduate student population. The proportion of GDP allocated to higher education increased from 1.33% in 2013 to 1.41% in 2020 on a national level.Conclusions: Since the implementation of the connotative development, the disparity in the scale of higher education among different regions in China has gradually narrowed. The distribution of high-level educational resources in the central and western regions lags significantly behind that in the eastern regions. The regional differences in high-level education have a direct impact on students\u2019 psychological expectations for college entrance, which in turn leads to varying degrees of college-going anxiety.This paper was supported by the Humanities and Social Sciences Project of the Ministry of Education of China (22XJA790005) and Research Initiation Projects for Introduced Talents of Guizhou University of Finance and Economics (2018YJ44).a,b; Yunru Sic; Jian XiaodNali Shena Business School, Southwest University of Political Science and Law, Chongqing 401120, China, b China Region Public Brand Research Center at Southwest University of Political Science and Law, Chongqing 401120, China, c School of Public Management, Chongqing University, Chongqing 400044, China, d School of Mathematics and Statistics, Chongqing University, Chongqing 401331, China.Background: In this paper, we study the incentive mechanism of customer knowledge sharing and revenue sharing designed by the manufacturer as the core firm in the supply chain based on emotional behavior in big data environment. The value of customer knowledge sharing and potential barriers were analyzed, then by designing an effective incentive mechanism to create a positive emotional climate that fosters customer knowledge sharing and ultimately leads to better cooperation benefits for both retailers and the manufacturer.Subjects and Methods: Considering retailers\u2019 emotional behaviors, a principle-agent theory method was used to build mathematical models to analyze behaviors of manufacturers and retailers. The organization emotional behavior theory about incentive was also used to analyze the original organizational psychological states and changes after executing incentive mechanism. And a numerical method was applied to describe change trends of the main factors for knowledge sharing between electronic retailers and manufacturers.Results: there is a positive correlation between a single e-retailer\u2019s effort level of customer knowledge sharing to maximize its expected revenue based on its emotional behavior in big data environment, and the proportion of revenue sharing and the number of e-retailers owned by the manufacturer. The optimal revenue sharing ratio obtained by e-retailers is negatively correlated with the manufacturer\u2019s customer knowledge innovation ability and the number of e-retailers owned by the manufacturer, but positively correlated with the e-retailers\u2019 customer knowledge sharing ability.Conclusions: Revenue sharing incentive is an effective mechanism based on organization emotional behavior. The number of manufacturer-owned e-retailers have a positive effect on e-retailers\u2019 efforts to improve customer knowledge sharing. The optimal revenue-sharing ratio was related with the effort elasticity coefficient the manufacturer and retailers, and emotional behaviors would affect their efforts in the process of knowledge sharing. The incentive mechanism for customer knowledge sharing has changed the organizational emotional behavior of retailers, affected the emotional behavior of manufacturers, would promote knowledge sharing between both parties, and ultimately improved cooperation performance. Therefore, in the knowledge sharing cooperation between retailers and manufacturers in big data context, analyzing the organizational emotional behavior before cooperation, designing incentive mechanisms to affect their emotional behaviors, motivating both parties to make efforts to share customer knowledge, which can promote cooperation benefits for both parties.This work supported by a project grant from National Social Science Fund of China (18BGL102).a, Runzhao Qib, Xue Baic, Ke HuangaWenjing Donga School of Architecture and Urban Planning, Chongqing Jiaotong University, Chongqing, China, b School of Architecture and Environmental Art, Sichuan Fine Arts Institute, China, c Institute of Architecture & Planning Design Co., Ltd., Chongqing University, Chongqing, China.Background: Public health is a public service that is related to the public health of a country or region, and the prevention of major infectious diseases is the top priority. Driven by the public health affairs of the global COVID-19 outbreak, people pay more and more attention to the indoor air quality in public places. Indoor air quality in public places plays a decisive role in public health, and is an important factor affecting the physical health, work efficiency and mental health of users. As a crowded place, creating good indoor air quality is the necessary guarantee to ensure the physical and mental health of teachers and students and improve the efficiency of teaching activities.Subjects and Methods: Taking public health as the guide, this paper combines many technical measures for the reconstruction of existing classrooms to form different reconstruction schemes, and uses numerical simulation method to compare and analyze the indoor air environment quality of a university classroom in Chongqing under different schemes. The article puts forward built-in thermal insulation, closing the gaps of doors and windows, and setting fresh air as the transformation measures. At the same time, taking into account the use conditions of opening and closing doors and windows, the paper selects five factors that affect the indoor air quality: temperature, humidity, CO2 concentration, O2 concentration, and PM2.5 concentration for comparative analysis.Results: The results show that the increase of thermal insulation layer has the greatest impact on the temperature in the classroom when the doors and windows have gaps; Fresh air has the best effect on reducing CO2 concentration in the classroom, followed by fully open doors and windows; After strengthening the treatment of door and window gaps, closing the doors and windows and ventilating fresh air have the best effect on the control of PM2.5 concentration in the classroom.Conclusions: The effect of continuous fresh air in reducing the concentration of indoor pollutants is better than that of natural ventilation. The internal thermal insulation setting can effectively ensure the indoor temperature. The research results can provide a basis for putting forward a reasonable classroom reconstruction plan, controlling the quality of indoor air environment, and providing a certain reference for creating a comfortable and healthy indoor thermal environment in public places and ensuring public health.a, Shanshan ZhouaXiaocheng Gua Department of Accounting, Anhui Business & Technology College, Hefei, Anhui, China.Background: To verify that Power Business Intelligence (Power BI) tool is more efficient than traditional Excel tool in processing financial data through typical financial cases, and can improve the efficiency of financial personnel data processing. At the same time, using questionnaire survey method, this paper explores the impact of Power BI on the mental health of financial workers in Chinese enterprises from a micro perspective, which is helpful to understand the relationship between the development of financial digitalization and individual behavior at the micro level. To find out the psychological needs of financial workers, and make timely intervention and adjustment, effectively resolve the contradiction, to ensure the efficient and orderly progress of financial work.Subjects and Methods: Excel and Power BI were used to solve financial problems in typical financial cases, and the complexity of the two calculation processes was compared and analyzed to show the high efficiency of Power BI tools in financial number processing. Through a questionnaire survey, we compared and analyzed the work and psychological impact of using Excel and using Power BI to solve financial problems, and discussed the impact of digitalization on financial practitioners from the perspective of psychology.Results: Power BI tools also provide financial workers with more efficient choices in data processing. Our study answers the question of whether the development of financial digitization affects individual psychological health, which has important theoretical and practical significance. In addition, based on China, a typical developing country, the research results have important practical significance for the development of financial digitization in developing countries.Conclusions: Financial digital transformation is an inevitable trend in the digital era. Power BI tool can improve the efficiency of financial workers\u2019 data processing and is an important tool in digital transformation. However, the process of digital transformation will also bring certain psychological pressure to financial workers, including digital overload and cognitive load, which requires timely intervention and adjustment. At the same time, under the background of digitalization, financial personnel need to constantly learn and update their skills, adapt to the changes and challenges of the digital environment, and improve their competitiveness. In order to better participate in the financial business in the digital era.This work was supported by the provincial Quality Engineering Teaching and Research Project of Anhui Province [grant number 2021JYXM0161]; the provincial Quality Engineering Teaching and Research Project of Anhui Province [2022JYXM152]; Anhui Province Teaching and Research Project [2021XJJY19]; Anhui Province Teaching and Research Project [2019XJJXTD01].a, Tieliang Guob, Qing LicJunjie Zhanga Academic Affairs Office, Wuzhou University, Guangxi 543002, China, b College of Electronics and Information Engineering, Wuzhou University, Guangxi 543002, China, c Psychological Counseling Center, Wuzhou University, Guangxi 543002, China.Background: Since the outbreak of new coronavirus pneumonia, it has attracted extensive international attention. In order to understand the impact of this public health emergency on the mental health of young people, The subjects of this survey are all young people aged 18-22..Subjects and Methods: Through the network questionnaire survey, a total of 4305 students were surveyed, including 1222 boys and 3083 girls. This study adopts the self-made general situation questionnaire and the norm of symptom checklist (SCL-90) as well as interviews for factors.Results:In the early and later stages of the epidemic, students\u2019 emotions changed. Most of the students had a good psychological state, while a small number of students had bad emotions such as nervousness, fear and irritability. College students, SCL-90 the difference in the detection rate of symptoms of each factor was not statistically significant. The trend of the factors of different gender students was different before and after the epidemic, and the factors of different levels at different levels, and different data were obtained after the variance.Conclusions: Through mental health testing of 18-22 year olds, comparative analysis of the gap between negative and positive effects, the differences in young people\u2019s personal health adjustment in the face of public health emergencies are studied from the aspects of health philosophy, health knowledge and healthy lifestyle, Explore low-cost paths that can alleviate the lack of medical resources, release the pressure of the medical system, and promote the sustainable development of public health. According to research, since the outbreak of the epidemic, young people with a calm mind have mostly adopted art related adjustment methods. Through promotion, the test was conducted again among young people, and the influencing factors of some young people\u2019s mental health decreased significantly. Therefore, it is suggested that such methods can be used for reference in the adjustment of public health after public health emergencies.The work was supported by the 2022 Guangxi Higher Education Undergraduate Teaching Reform Project (Grant No. 2022JGZ167), and the 2020 Guangxi Higher Education Undergraduate Teaching Reform Project (Grant No. 2020JGB369).a, Caixia WuaXiaobei Huanga School of Economics and Management, North China University of Technology, Beijing, 100144, China.Purpose: The purpose of this paper is to investigate whether investors who develop psychological anxiety will rely more on the management earnings forecast of Chinese listed firms during the coronavirus pandemic.Methods: Based on the quarterly earnings forecasts of all A-share listed companies in China from 2018 to 2021, this paper examines the market reactions of investors to management earnings forecasts before and after the coronavirus pandemic using difference-in-difference methods.Results: The results show that uncertainty due to the coronavirus pandemic can affect investors\u2019 psychological expectations of the future economic situation and induce psychological anxiety, which will trigger investors\u2019 vague aversion, the irrational sentiments lead to pessimistic judgment of investors on the future operation of listed companies, resulting in a significant decline in the market reaction to management earnings forecast during the pandemic. The quality of the management earnings forecast is further controlled in the regression model and the research conclusion remains unchanged, excluding the impacts of information quality on the research conclusion.Conclusions: The coronavirus pandemic has caused unprecedented uncertainty, which also triggers psychological anxiety of investors and affects investment decisions. In the pandemic, investors have demonstrated ambiguity aversions, and less trust in earnings forecasts of corporate management. The results are not driven by the changes in the quality of management earnings forecasts. This research helps the market learn more about the behavioral logic of corporate management and the influence of investors\u2019 decision-making during the pandemic, which can also provide evidence for regulators to further standardize the information disclosure of listed companies and improve the information environment of the Chinese capital market.The paper was supported by National Natural Science Foundation of China (71602004), the Social Science Foundation of Beijing (19GLC059).aQun Wanga University of Jinan, Jinan, Shandong 250022, China.Background: The excellent traditional culture of China is the inexhaustible motive force for the Chinese nation\u2019s endless and sustainable development. Integrating the excellent traditional culture of China into the mental health education in colleges and universities, stimulating the vitality and vitality of the excellent traditional culture of China, and highlighting the value of the times are not only important measures to improve the effectiveness of mental health education for college students, but also important measures to inherit the national spirit blood, absorb rich historical and cultural nourishment, and enhance the national cultural soft power and international discourse power, It is a realistic need to build a socialist cultural power with Chinese characteristics and comprehensively improve the cultural literacy of the people. Given that there are still many problems with the excellent traditional Chinese culture in college students\u2019 mental health education, we must strengthen efforts to promote the creative transformation and innovative development of the excellent traditional Chinese culture.Subjects and Methods: Mental health education in colleges and universities is related to the major issue of cultivating qualified builders and successors of socialism with Chinese characteristics for the new era. We must take scientific and effective measures, adhere to the principle of making the past serve the present, bring forth the new, treat them differently, inherit the useful and discard the useless, draw essence from the excellent traditional Chinese culture, and strive to use all the spiritual wealth created by the Chinese nation to educate people with culture.Results: Do a good job in the creative transformation and innovative development of Chinese excellent traditional culture in college mental health education, and build a harmonious campus culture by exploring the harmonious view of Chinese excellent traditional culture; Pay attention to the space concept of the excellent traditional Chinese culture and do a good job in its \u201cthree entry\u201d work; Develop the dynamic view of Chinese excellent traditional culture, innovate teaching methods, and pay attention to educational effectiveness; Highlight the characteristics of Chinese excellent traditional culture and enrich the carrier of Chinese excellent traditional culture education; Strengthen the people-oriented view of Chinese excellent traditional culture and improve the teaching level of teachers; Adhere to the concept of knowledge and action of Chinese excellent traditional culture, and build a \u201ctrinity\u201d education model of Chinese excellent traditional culture of school, society and family.Conclusions: The excellent traditional Chinese culture is both historical and contemporary; It is both national and global. We should more consciously and actively promote the adaptation of the excellent traditional Chinese culture to the contemporary society and the coordination with the modernization process, better promote the creative transformation and innovative development, and promote the mental health education of college students.This paper was supported by a project from the foundation \u201c Research on the Integration of Excellent Traditional Chinese Culture into the Education and Teaching of Ideological and Political Theory Course\u201d\u20142015 Shandong Provincial Social Science Planning Project (15cszj04).a, Tao Xiaob, Meihong ZhengcYinchou Zhoua Department of Foreign Languages and Literatures, Tsinghua University, Beijing 100084, China, b Institute of Industrial Development and Governance Innovation, Zhejiang Guangsha Vocational and Technical University of Construction, Jinhua, 322103, Zhejiang, China, c School of Social Sciences, Tsinghua University, Beijing 100084, China.Background: Current treatments of transcortical motor aphasia are based on the attribution of typical symptoms and brain regions. However, the large individual differences between patients and the uncertainty of stroke injury areas make it difficult to adapt to the dynamic changes of post-stroke aphasia recovery. In order to make the symptom analysis of transcortical motor aphasia more dynamic and better fit for patients, this study attempts to reexamine the specific symptom representations with the perspective of a holistic process from verbal intent to speech behavior.Subjects and Methods: Based on the neural basis of language processing as well as the results of the PDC model and P-chain model, we have proposed a three-module model consisting of linguistic expression, coordinated connectivity, and motor output \u2014\u2014after generating the expressive intention in part 1 and then projects the expressive intention and content to the motor control system in part 3 through the coordination of part 2 and the motor output of the language after integrating the articulatory organs, thus completing the complete language expression.Results: Language expression can be understood as a process from intention to behavior, in which \u201clanguage production\u201d at the beginning and \u201cmotor output\u201d at the end of the process are linked in a loop, while the aSPPO area is specific for speech-motor connectivity and there is overlap with brain areas damaged in patients with transcortical motor aphasia. Thus transcortical motor aphasia can be at least partially explained by the fact that disruptions in the coordinated connectivity pathway involving the aSPPO area may lead to the inability of individuals to produce effective language output even when the speech production and vocalization sites are functional.Conclusions: Based on brain plasticity and the fact that the aSPPO area is between the hand action area and the oral-facial action area, there may be practical value in two behavioral intervention treatment options for transcortical motor aphasia: assistance in functional overlap areas, which means after training individuals to conceptualize verbal content in the brain (without expressing it) while performing non-verbal actions such as licking their lips and smiling, the originally damaged coordination connectivity pathways involved in aSPPO can be reactivated to some extent; and compensation in adjacent areas, referring to individuals who perform right-handed hand action or facial action training will have significantly improved verbal motor output.a, Shizheng LibXiaoxue Zhanga School of Management Science and Engineering, Anhui University of Finance and Economics, Bengbu 233030, China, b School of Finance, Anhui University of Finance and Economics, Bengbu 233030, China.Background: Despite the multitude of studies exploring the causes of mental health problems among college students in China, the impact of academic performance on mental health has not been adequately investigated. Purpose: Analyzing the relationship between student self-evaluation comprehensive academic performance score, as well as their scores on 7 different sub-dimensions of academic performance, and the mental health status of college students.Subjects and Methods: A 41-item scale was developed to evaluate participants\u2019 academic performance. 10 items from the PSS-14 were used to measure the mental health status of participants. Descriptive statistics were initially employed to analyze the distribution and numerical characteristics of academic performance and perceived stress among the participants. Seven logistic regression models were constructed to investigate the predictive effect of different dimensions of academic performance on the mental health.Results: Online teaching prompted by the COVID-19 pandemic did not yield a significant impact on the mental health of the respondents. Gender did not emerge as a predictive factor for mental health status. Stress related to academic performance is not limited to students who struggle with their studies, as academic achievers may face higher risks. Academic performance scores obtained through the self-evaluation scale demonstrated better predictive power for mental health status than traditional GPA scores.Conclusions: The threshold for safeguarding the mental health of college students must be shifted to an earlier stage of education. It is imperative for China to pursue a gradual and sequenced approach to the implementation of mental health education in primary, secondary, and tertiary schools, with a focus on enhancing the professionalism and expertise of mental health education practitioners.This work is supported by Anhui University of Finance and Economics\u2019 Teaching Research Project (acjyzd2020004).a, Weiqing Zhaoa, Ye Liub, Yaozhou Wanga, Caiyun Xionga, Hao ZhouaLinyin Luoa Department of Pediatrics, Guizhou Provincial People\u2019s Hospital, Guiyang, 550002, China, b Department of Otolaryngology, Guizhou Provincial People\u2019s Hospital, Guiyang, 550002, China.LL and WZ contributed equally to this research.Background: This study examined changes in \u03b3-aminobutyric acid type A (GABAA) \u03b11 (GABAA\u03b11) and \u03b12 (GABAA\u03b12) receptor expression in autism model rodents and children with autism spectrum disorders (ASD) with the aim of providing insights about causes and treatment of autism.Subjects and Methods: Neuronal expression of GABAA\u03b11 and GABAA\u03b12 in the frontal cortex of control rats and gestational valproic acid (VPA)-induced ASD rats was measured by immunohistochemistry (IHC), western blot, and real-time quantitative PCR (RT-qPCR). Serum GABAA\u03b11 and GABAA\u03b12 expression in 37 autistic children and 32 healthy children were determined by enzyme-linked immunosorbent assay (ELISA).Results: Immunohistochemical staining showed that the VPA-induced ASD rats had significantly higher mean GABAA \u03b11 and GABAA\u03b12 expression than controls. Western blot detection showed that the relative grayscale values of GABAA\u03b11 and GABAA\u03b12 protein were slightly higher in the VPA group than in controls, although the differences were not statistically significant. The VPA group also had higher GABAA\u03b11 (P>0.05) and GABAA\u03b12 (P<0.05) mRNA expression in the frontal cortex compared to controls. Similar to the findings in rodent models, autistic children had higher serum GABAA\u03b11 and GABAA\u03b12 levels than controls.Conclusions: Abnormal expression of GABAA receptor subunits may contribute to autism pathogenesis.a,b, Xiaodan Bia,b, Xingqiang Huanga,b, Xu Tanga,b, Jinpeng Yanga,b, Tingting Zhaoa,bZhenrun Zhana Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, China, b Changzhi Medical College, Changzhi, Shanxi 046000, ChinaBackground: Atherosclerosis, an immunoinflammatory disease caused by lipids, is a significant factor in coronary heart disease and stroke. Researchers worldwide are working to develop more effective ways of diagnosing and treating it. This article introduces a machine-learning algorithm that screens biomarkers and performs pan-cancer analysis as a reference.Subjects and Methods: We first downloaded the GEO dataset containing information on atherosclerotic patients for differential gene screening and analyzed differential mRNAs using KEGG and GO enrichment analysis. Then, we combined WGCNA, protein interaction network analysis, and mechanistic learning algorithms to screen for core genes, perform basic experimental validation, and immuno-infiltration analysis. Finally, we used TCGA and GTEx databases for pan-carcinogenic analysis of differentially expressed genes.Results: After screening differentially expressed genes from the GSE28829 dataset, we performed WGCNA and obtained 122 key genes by combining module genes and differential expression genes. We used four machine learning algorithms to calculate the critical genes and obtain the junction of the results, which led us to identify four hub genes . Next, we built a diagnostic model and assessed its capabilities. The ROC curves of the four genes suggested their critical role in the development of atherosclerosis. We then performed gene correlation analysis, immune infiltration analysis, and RT-PCR verification of the four core genes and finally screened out TLR2 for pancarcinoma. Our analysis found that TLR2\u2019s expression in patients with various tumors differed from that in healthy individuals, and it was strongly associated with the prognosis of patients with diverse cancers.Conclusions: TLR2 may be a target for intervention in developing diseases such as atherosclerosis and tumors.This study was supported by the Shanxi Province Graduate Education Innovation Project (2022Y726/737), the Basic Research Program of Shanxi Province (202203021212010), and the Youth Start-up Fund of Heping Hospital affiliated to Changzhi Medical College (HPYJ202225).a, Zhong Lib, Weibai LiucYongcai Zhanga School of Law and Business, Shaoyang University, Shaoyang 422000, China, b School of Business Administration, Hunan University of Finance and Economics, Changsha 410205, China, c School of Economics and Management, Hunan University of Science and Technology, Yongzhou 425199, China.Background: Food satisfaction can solve the problem of hunger, alleviate social anxiety and improve people\u2019s mental health. Food is an important source of food, Food security is the most important ballast for economic development and social stability. Therefore, the social status of food is decisive and its yield and quality is particularly important. Food security lies not only in output growth, structural adjustment and optimization, but more importantly in further improvement of grain productivity and alleviate social anxiety.Methods: Fuzzy logic theory, super-efficiency DEA and Bootstrap DEA methods are used to measure the grain productivity of China from 1978 to 2018. Fuzzy logic adopts \u201cFuzzy ToolkitUoN\u201d to make a fuzzy logic control, with its implicit boundaries of the qualitative knowledge and experience, the aid of concept of subordinate degree function, fuzzy set and relation, the fuzzy logic can simulate the human brain implementation of rule-based reasoning, deal with the uncertainties created by logic deficiency of \u201claw of excluded middle. The super-efficiency DEA model includes several models such as CCR, BCC and SBM, which is to make the same type of unit evaluation based on the decision making unit of \u201cinput\u201d and \u201coutput\u201d data. Bootstrap-DEA method is to introduce Bootstrap into DEA model. Bootstrap sample data are constructed repeatedly through the method.Results: The above data indicate that the traditional DEA method has defects, and more accurate super efficiency DEA and Bootstrap-DEA are needed to calculate the efficiency. Show that the grain yield efficiency is closely related to national policies and social development. China\u2019s grain productivity is relatively stable on the whole, but the return to scale fluctuates greatly, and the return to scale even decreased for 13 consecutive years. Therefore, how to improve the production of food and its productivity in scientific ways to alleviate social anxiety. Since 2013, the comprehensive efficiency has been on a steady rise, and the efficiency value gradually increased from 0.8370 to 1. In addition, its technical efficiency has been stable with an efficiency of 1 for four consecutive years since 2015, indicating that technological progress has promoted the improvement of comprehensive efficiency. At the same time, the scale efficiency value is also above 0.9, and the comprehensive effect of technological progress and scale efficiency got a higher comprehensive efficiency value, improve people\u2019s mental health.Conclusions: To ensure the sustainable development and food security of China\u2019s grain industry and alleviate social anxiety, it is necessary to strictly observe the minimized reserve of cultivated land, strengthen the efforts for the protection of cultivated land, establish and improve policies and incentive mechanisms for the introduction of agricultural scientific and technological personnel, strengthen efforts to make grain more market-oriented, and promote the integrated development of the grain industry with the secondary and tertiary industries. The efficiency of food production will be improved and when society is active, improve people\u2019s mental health, maintain family and social security.Research and Planning Fund for Humanities and Social Sciences of the Ministry of Education of China (22YJA790038);Projects of Natural Science Foundation of Hunan Province, China ; Project of Education Department of Hunan Province, China .aMingzhou Wanga Shanghai Urban Construction Vocational College, Shanghai, 200438, China.Background: Cultural festivals and events refer to a series of cultural activities or events held in cities, which have strong local, cultural, concentrated, and interesting characteristics. They can meet the psychological needs of citizens, enhance their sense of happiness, help alleviate social anxiety, and promote social stability and harmony. By analyzing and summarizing the key factors that can successfully host world-renowned cultural festivals, this paper proposes innovative measures to host the Yangtze River Cultural Festival.Subjects and Methods: Using literature review and data collection methods, we selected world-renowned cultural festivals such as the London Mayor\u2019s Thames Riverside Festival, Seoul\u2019s \u201cHan River Celebration\u201d, and Dalian International Beach Cultural Festival as research objects to analyze the positive effects of cultural festivals on citizens and tourists, such as joy of participation, stress relief, relaxation, and psychological pleasure, and discussed creativity, brand The role of participants and other factors in cultural festival activities.Results: Currently, with the rapid development of society, the pace of life has significantly accelerated, and with the rapid growth of the economy, there are also tremendous negative emotions such as stress, anxiety, and depression, which pose a great threat to people\u2019s psychological and physical health. By participating in cultural festivals and experiencing lively and interesting activities, citizens can gain more opportunities for interpersonal communication, increase individual social interaction, resist negative emotional influences, eliminate depression and anxiety, and promote mental health. A successful cultural festival event must rely on the city\u2019s existing resource endowment, use innovative thinking for top-level design, pay special attention to setting up distinctive and interesting activities, mobilize the participation of diverse subjects, especially young people, and actively meet their daily entertainment and mental health needs. In addition, it is necessary to create a market-oriented, government assisted operating mechanism.Conclusions: As one of the cultural supply products in cities, cultural festivals and events have a positive impact on enriching citizens\u2019 daily cultural life and promoting their mental health. Research has shown that participating in cultural events can help people maintain good interpersonal relationships and self understanding, maintain a positive mental state, and effectively reduce the incidence of mental illness. Cities along the Yangtze River have rich resources to carry out Yangtze River cultural festivals. By learning from the successful experience of world-renowned cultural festivals and holding colorful Yangtze River cultural festivals, it is possible to explore a new path for urban cultural supply.a,b, Xiaodong Zhenga,c, Miao Wanga, Fan ZhangaYongping Lia Faculty of Humanities and Arts, Macau University of Science and Technology, Macau 999078, China, b Ningbo University of Finance and Economics, Ningbo, Zhejiang 315175, China, c School of Computer and Information Engineering, Nantong Institute of Technology, Nantong, Jiangsu 226002, China.Background: Under the background of consumption era, more and more tourist areas begin to create unique cultural symbols as an important basis for their market attraction and brand effect. However, in the past few years, influenced by COVID-19, people are generally anxious and have no strong desire to travel, which leads to a sharp drop in tourist flow in scenic spots, a continuous downturn in tourism consumption, and a huge impact on tourism. With the gradual disappearance of the epidemic, the global tourism industry has regained its confidence and gained great opportunities. How to accurately grasp and construct cultural symbols, so as to alleviate tourists\u2019 anxiety and enhance tourists\u2019 willingness to travel, has become an important proposition to be solved urgently in every tourist area.Subjects and Methods: Taking Putuo Mountain Tourist Area in Zhoushan City, Zhejiang Province as the research object, this paper discusses the relationship between cultural symbol cognition, tourism psychology and tourism willingness, aiming at clarifying the difficulties faced by Putuo Mountain Tourist Area, helping to establish and strengthen its unique cultural symbols, thus effectively improving the popularity and passenger flow of the tourist area. Firstly, based on the theory of symbolic interaction and symbolic consumption, the corresponding question hypothesis and questionnaire are put forward. Secondly, the questionnaire survey was carried out through the network platform, and the questionnaire results were processed and analyzed by SPSS software. Finally, the corresponding results are obtained by regression analysis to verify the hypothesis.Results: A total of 1000 questionnaires were distributed and 833 questionnaires were collected. After eliminating 172 invalid questionnaires, 661 valid questionnaires were obtained. Using SPSS software to process and analyze the questionnaire data, the results show that tourists\u2019 cognition of Putuo Mountain cultural symbol is positively correlated with their willingness to travel, and the degree of tourists\u2019 psychological anxiety is also positively correlated with their willingness to travel. In addition, the analysis results show that personal education level, personal age, personal income level, image perception of tourist destination and hardware facilities are also important factors affecting tourism willingness.Conclusions: Zhoushan is the main maritime gateway for China to open to the outside world, and it is the only place for Chinese and foreign ships to sail from south to north. There are unique mountain and sea landscapes and island fishing customs here, and tourism has become one of the local pillar industries. As an important scenic spot in Zhoushan, Putuo Mountain attracts a large number of tourists every year with its beautiful scenery and unique cultural heritage. In the future, Putuo Mountain must vigorously publicize its unique cultural symbols, enhance its cultural heritage and speed up the construction of tourism infrastructure to maintain its sustainable attraction as a tourist destination.This paper is supported by 2021 Nantong Science and Technology Plan Project (JCZ21074), 2020 Jiangsu University Philosophy and Social Science Research Project (2020SJA1612), Young and Middle-Aged Key Teachers Training (Scientific Research) Project of Nantong Institute of Technology (ZQNGGJS202120), Key Scientific Research Project of Zhejiang Provincial Department of Culture and Tourism (2021KYZ006), Key Project of Ningbo Education Science Planning (2021YZD019).a,b, Yongtian Wub, Zhiheng Chenc, Xuekai WeibJianping Liua College of Civil and Environmental Engineering, Hunan University of Science and Engineering, Yongzhou, Hunan, 425199, China, b Bama Hetai Longevity Industry Co., Ltd., Bama, Guangxi, 547500, China, c Department of Health Management, Xiangya Third Hospital, Central South University, Changsha, Hunan 425099, China.Background: The high incidence of hyperuricemia has become a major medical and social problem affecting the health of Chinese residents. The existing medical system has not yet explored the formation mechanism of hyperuricemia, resulting in little effect on the prevention and treatment of hyperuricemia.Subjects and Methods: From the perspective of nutritional medicine, the development and changes of nutrient intake and dietary preferences of Chinese residents in the past three decades have been analyzed in depth by using the time series analysis method, and the formation process and mechanism of hyperuricemia have been systematically studied by using the whole-cycle theory.Results: The research shows that excessive uric acid production and too little uric acid excretion are the two causes of high incidence of hyperuricemia. The excessive production of uric acid is caused by the preference for high-purine food, the structural nutrient intake imbalance caused by the overall insufficient intake, the excess intake of some nutrients and the uneven intake of nutrients of long-term nutrients, and the metabolic abnormalities of human related enzymes. Too little uric acid excretion is caused by the structural imbalance of long-term nutrient intake, which is the main cause of hyperuricemia.Conclusions: The basic mechanism of hyperuricemia is the excessive re-absorption of kidney caused by the long-term imbalance of nutrients intake, especially the insufficient intake of water nutrients. We can effectively prevent and treat hyperuricemia by controlling the intake of high-purine exogenous foods, balanced intake of daily nutrients, taking disease-based strategies, strengthening daily independent health management and other measures. The research provides a new theoretical perspective and specific implementation methods for the prevention and treatment of hyperuricemia in China, which has great theoretical value and practical significance.This work was supported by a project grant from Natural Science Foundation of Hunan Province (Grant No.2019JJ50915) and Hunan University of Science and Technology Applied Characteristic Discipline Construction Project (Grant No.18TSXK-001).a, Youyou Zhanga, Yuehan QiaoaHuansong Yanga Hangzhou Normal University, Hangzhou City, Zhejiang Province 310000, China.Background: According to the 2019 Chinese Women\u2019s Confidence Report, 40 percent of Chinese women underestimate themselves. In other words, two out of every five Chinese women are not confident. A survey of 2,000 women by a UK institute found that 42 percent of women never give themselves a good compliment and criticize themselves at least eight times a day. This paper takes the method of psychological mining and performance of the hero of character documentary as the research content, explores the influence and contribution of streaming media anchor, a new profession, on the development of female mental health, and strives to find out a set of methods of psychological mining and performance of documentary characters.Methods: Based on psychological principles such as threshold effect, seesaw law, congruence effect, external behavior and manner of characters reflecting internal psychology, and research methods, this paper explores the psychological mining methods of film and television character documentaries, and explores the positive influence of the rise of \u201ca female anchor who sells goods through live streaming\u201d on women\u2019s mental health according to specific character interviews and surveys. The research on the psychology of the protagonist in the character documentary of \u201ca female anchor who sells goods through live streaming\u201d can provide experience and reference for the creation of character documentary in the future, so as to better shape the character image in the documentary creation.Results: The research shows that: 1. In professional documentaries, the use of audio-visual language can excavate the psychological changes of characters to a certain extent. For example, the use of long lens and depth of field lens can capture and amplify the psychological and emotional changes of characters.2.the color tone of the picture, simultaneous sound processing and music sound can play a key role in the portrayal of the character image and character psychology.3. The rise of \u201ca female anchor who sells goods through live streaming\u201d has greatly enhanced women\u2019s self-confidence and has a positive impact on women\u2019s mental health.4. As women have found broader career paths, their social status and recognition have also increased along with their economic level, which has a significant effect on their mental health.Conclusions: With the development of the e-commerce industry, a large number of women have found their own value in the work, thus blooming the charm and brilliance of different age groups. Influencing and inspiring others while maximizing their own worth is part of the magic that careers confer on women. Through the psychological mining and mental health research of the heroine of \u201ca female anchor who sells goods through live streaming\u201d, the author hopes that in the future career development and career planning, there will be more emerging industries to help women realize their self-worth.This research was supported by Fund program: Zhejiang Province digital cultural and creative Industry Production and education integration engineering base project (Zhejiang development reform society [2020] No.319)a, Li LibHongqi Zhoua Xianda College of Economics and Humanities, Shanghai International Studies University, Shanghai 200000, China, b Hunan University of Technology, Zhuzhou, Hunan 412000, China.Background: This study focuses on the behavioral and psychological needs of users and advocates the use of universal design concepts to improve the design of open space facilities in country parks, so as to better reflect the \u201cpeople-oriented\u201d purpose of design and meet the needs of users for respect, comfort, equality and care. The research provides reference for the design of public space facilities.Subjects and Methods: Firstly, through literature research method, the basic theories related to the study were summarized. Secondly, through on-site investigation, the current status of recreational facilities was understood, and the needs of users\u2019 physiological and psychological fairness, respect, safety and other characteristics were understood. Finally, through investigation and analysis, strategies for the universal design of recreational facilities in the countryside park were proposed.Results: According to the characteristics of country parks, the physical and psychological needs of users, the design of country park recreation facilities should follow the principles of fairness, systemization, safety, comfort and aesthetics, and embody the \u201cpeople-oriented\u201d design purpose, so that urban recreation facilities can better meet the needs of everyone.Conclusions: Recreational facilities are an important part of the recreational space in the countryside park, and their design should fully respect users\u2019 behaviors and psychological needs. The design should aim to provide equal, safe, and comfortable universal functions for as many users as possible, effectively reducing conflicts between environmental facilities and individual characteristics. This approach can better embody social care and equity.a, Yan LuaYabing Shana The Third Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, China.Background: We aim to develop a preoperative nomogram to evaluate the risk of death within a year of the operation in patients with resectable hepatocellular carcinoma.Subjects and Methods: Retrospective study of 490 hepatocellular carcinoma patients who were treated with hepatectomy. Multiple logistic regression analysis was performed to identify factors associated with early death in these patients. A nomogram was constructed based on the independent risk factors, and predictive accuracy of nomogram was valued.Results: Tumor size, portal vein tumor thrombus, fibrinogen to albumin ratio and geriatric nutritional risk index were found to be independent predictors of death at 1 year after surgery in resectable hepatocellular carcinoma patients and were finally entered into the nomogram. The calibration curves for the possibility of one year mortality showed optimal agreement between nomogram prediction and actual observation. The concordance index and the area under curve of receiver-operating characteristic showed that the nomogram in current study was superior to the Barcelona Clinic Liver Cancer classi\ufb01cation, Child-Pugh score, and Okuda stage in predicting early death of hepatocellular carcinoma patients with sugery.Conclusions: Our nomogram got a better accuracy in predicting mortality within a year after operation in patients with hepatocellular carcinoma.The authors disclose the receipt of financial support for the research, authorship, and/or publication of this article from the Planned project of Zhejiang Administration of Traditional Chinese Medicine approved by Zhejiang Provincial Health Commission (2011ZB059).a, Wenhui Zhanga, Jin Xua, Yiwen QiaZhenfeng Xiaoa Tianjin University, Tianjin 300350, China.Background: Flannery O\u2019Connor is a representative writer of postmodernism in the American Southern literary genre. She lived at a time when the American South was in the midst of intense turmoil, with the rise of the feminist movement, the rapid expansion of the capitalist economy, increasing social conflicts, and serious distortions in human relationships and the inner spirit of man. With her own unique life experience and keen insight into the darkness of human nature, O\u2019Connor was deeply influenced by Jung and consciously used the psychological perspective in her creation to penetrate the hidden inner world of the characters and present their true spiritual state, shaping a group of characters who abandoned their faith and had deformed personalities. The externalized expression of individual thoughts and mental activities is a direct mapping of character. In modern society, the reason why human beings live in an orderly and harmonious society lies in the regulation of law and ethics, while in the American South at the early stage of development and even in the period of seclusion, the root of the stability of social relations lies in the internal control of individuals, i.e., self-control, and psychological health and personality perfection are the basic conditions for the existence of self-control. This paper analyzes the O\u2019Connor series of novels from a psychological perspective. The purpose of this article is to study the results of the influence of psychological and external factors on the development of individuals and society.Subjects and Methods: Psychological analysis is not only a method of literary criticism, but also a way and perspective to see the world. Based on Jung\u2019s personality theory, this paper takes five short stories of O\u2019Connor: A Good Man is Hard to Find, Good Country Man, Greenleaf, and To Save a Man is to Save Himself as the objects of textual research, aiming to analyze the characters in O\u2019Connor\u2019s novels from a psychological perspective through a close reading of the text, with the intention of studying the influence of psychological factors and external factors on personal development and even social. O\u2019Connor draws a rich and diverse portrait of a monstrous group of characters in his short stories. In the development of the characters\u2019 personalities, the external personality masks play a key role. Through the external personality masks, the distorted life caused by the unbalanced mask and shadow of the main character is analyzed, thus revealing the indifference and alienation between people in a sick society.Results: Jung\u2019s theory of analytical psychology explains the madness hidden in the depths of the collective unconscious and reveals the complexity and universality of human psychological contradictions. The purpose of this study is to examine the influence of psychological factors and external factors on individual development and even on society. From the outside to the inside, the potential implications are explored to reveal the rich connotation and great tension of the characters in O\u2019Connor\u2019s novel under Jung\u2019s archetypal theory. O\u2019Connor\u2019s unique artistic style, her use of dynamic language, the expression of the grotesque and death, gives the novel a different kind of aesthetic interest. At the same time, the alienated society and the radical changes of the times make us see the goodness, evil, beauty and ugliness of human nature through the archetypal characters, and understand the fate of the characters, while more than anything else, it arouses our concern for life, our desire for the sublime, and our persistent pursuit of faith.Conclusions: In human history, society is often in a state of constant change, and with it, the transformation of human psychology, in other words, the course of human psychological development is closely related to the continuous development of society. In other words, the course of human psychological development is closely related to the continuous development and change of society, which is a huge collective of individuals with different personalities and psychological states. The society is a huge collective of individuals with different personalities and psychological states, and being in the collective, the universal or majority will is regarded as the unified goal and premise of development in the society. The intersection of psychology and literature is adapted to the needs of the times. Understanding a work is not only limited to knowing people, but also based on understanding the psychology of the writer, in order to better enter into the main character of the work. O\u2019Connor was deeply influenced by Jung, and looking at O\u2019Connor from the perspective of Jungian analytical psychology undoubtedly opens a new door for us to know O\u2019Connor and her novels.This work is supported in part by the Tianjin Philosophy and Social Sciences Research Program Funding Project under Grant TJWW21-006.a, Zhenzhao Wanga, Jing SuaWei Liua School of Mathematics and Computer Science, Guangdong Ocean University, Zhanjiang, Guangdong, China.Background: As of September 17, 2022, the World Health Organization has reported 59147 laboratory confirmed cases of monkeypox virus and 489 possible cases, including 22 deaths. The rampant spread of the monkeypox virus poses a grave threat to the lives and well-being of people worldwide. In order to reduce the large-scale spread of monkeypox in the world and reduce the impact of monkeypox on the public health system and international trade economy, it is essential to timely warn monkeypox through artificial intelligence.Subjects and Methods: We integrate 131 days of monkeypox infection data into the Susceptible- Exposed-Infection-Removed (SEIR) model and the Long Short Term memory (LSTM) model to obtain the epidemic curve. We also propose a four-tier architecture system that can visualize data and predict epidemic situation. The system submits the predicted data to the module within the corresponding system to form a clear and concise visual page, which is displayed on the IOT device.Results: We compare the prediction performance of SEIR and LSTM models for monkeypox virus, and found that LSTM neural network performs well in the prediction of monkeypox epidemic. The LSTM model used by the ten countries most affected by the epidemic has good fitting results . We predict the United States, Spain, Brazil, France, the United Kingdom, Germany, Peru, Canada, Colombia and the Netherlands, the top 10 countries in the list of infections. The goodness of fit R2 of several countries exceeded 0.99 . According to the model, the threat of monkeypox virus will basically end in December 2022, while the United States will end early around November 19, 2022 (in the LSTM model).Conclusions: This paper proposes a monkeypox virus early warning and visualization system based on LSTM neural network. The results show that it is feasible to use LSTM neural network to predict monkeypox epidemic. The visualization system can assist decision makers to make decisions and minimize the harm of infectious diseases, which is worthy of our promotion.a, Jun RenbLiuliu Shenga Taizhou Vocational and Technical College, Zhejiang 318000, China, b Zhejiang Normal University, Zhejiang 321000, China.Background: With the development of the network society and the wide spread of negative cases, some regions have been labeled as \u201cstigmatized\u201d, and regional stigma has been constantly constructed, thus forming a negative stereotype of the region. Negative stereotypes not only affect people\u2019s mental health, but also lead to the formation of bad coping styles, thereby affecting their social functions. To explore whether regional stereotypes exist in North and South China and what characteristics they have at the explicit and implicit levels. Subjects were randomly selected from the southern population and the northern population, with the Qinling-Huaihe Line as the boundary.Methods: In the process of research, it is necessary to pay special attention to the mental health of the subjects. The existence of regional stereotype may induce the psychological stress and anxiety of the subjects, thus affecting their emotional and behavioral performance. Therefore, it is necessary to give full informed consent in advance, introduce the main content and purpose of the experiment to the subjects, and inform them that they have the right to refuse to participate in the experiment without any punishment, gain or loss. It is necessary to pay full attention to and protect the mental health of the subjects in the process of research to ensure the scientific and reliability of the experimental results. In the whole process of the study, free response method and trait corresponding behavior were used to collect questionnaires to verify the existence of regional stereotypes. Then explicit regional stereotypes were measured by behavior rating questionnaire and implicit regional stereotypes were measured by stereotype explanatory bias questionnaire.Results: The measurement, collection and analysis of regional stereotypes can help people understand their own psychological conditions, including emotions, thinking, behavior and other aspects, and identify the factors causing negative regional stereotypes, so as to take corresponding actions, measures and interventions to improve their mental health. Among the findings: (1) At the explicit level, the subjects had negative regional stereotypes. The main effect of gender on negative stereotypes was not significant, while the main effect of household registration was significant. The interaction between gender and household registration was not significant. Both Southern and Northern subjects showed in-group preference and out-group rejection. (2) At the implicit level, the subjects had negative regional stereotypes. The main effects of gender and household registration were not significant, and the interaction was also not significant. Both Southern and Northern subjects showed more attributions and external attributions for inconsistent situations, and fewer attributions and internal attributions for consistent situations. (3) Presenting a larger amount of counter-stereotype information can reduce negative stereotypes of the target group more effectively. The research results support the Thin Slice Model. Presenting moderately abnormal counter-stereotype information can reduce negative stereotypes of the target group more effectively than presenting extremely abnormal counter-stereotype information, which is inconsistent with the content of the Transformation Model. Presenting moderately abnormal and a larger amount of counter-stereotype information is most effective in reducing negative regional stereotypes.Conclusions: At the explicit and implicit levels, regional stereotypes exist in both the north and south groups in China, showing the characteristics of in-group preference and out-group rejection. Medium anomaly and large amount of counter-stereotype information can suppress negative regional stereotypes more effectively. In the future, while applying the research results to promote social harmony and stability, it is necessary to pay attention to and protect the mental health, and adopt reasonable means and methods to reduce the negative emotional experience of the subjects such as anxiety and pressure. For example, researchers can use psychological intervention methods to stimulate positive emotions, guide cognitive reconstruction, relieve stress and anxiety during the experiment to help subjects adjust their mental state and mental health, and promote their positive emotions and physical and mental health. In addition, the results show that the medium anomaly and large amount of counter-stereotype information can effectively suppress the negative regional stereotype. Therefore, in real life, relevant departments and individuals can adopt some scientific and rational means and measures to encourage diversification and promote exchanges and cooperation, present moderate abnormal and large amount of positive information, reduce the negative impact of regional stereotypes, and promote the harmonious and stable development of society. In conclusion, while promoting the application of research results, we need to pay full attention to and protect the mental health of the participants, promote social stability and people\u2019s happiness, and achieve the goal of healthy, harmonious and sustainable development.This work was supported by the [2022 Professional Development Project for Domestic Visiting Scholars and Teachers in Colleges and Universities] under Grant [number: FX2022130], and by the Taizhou Aien Kangze Health Management Co., Ltd under Grant [number: HX2022237].a, Lu Zhanga, Miaoyu WangaXingxiang Xinga Shaoxing Central Blood Station, Shaoxing City 312000, China.Background: To understand the blood safety situation in the Shaoxing area and propose effective measures to prevent and control transfusion-related infectious diseases.Subjects and Methods: A retrospective analysis was conducted on the results of 8 transfusion-related infectious disease markers from 214,474 voluntary blood donation samples collected between 2019 and 2022. Five of these markers were compared with results from 190,264 voluntary blood donation samples collected between 2006 and 2010. An empirical study was also conducted on the blood testing strategy for voluntary blood donation.Results: The overall rate of unqualified test results for the 8 markers was 1.25%, with the unqualified rates for ALT, HBsAg, Anti-HCV, Anti-HIV, Anti-TP, HBV-DNA, HCV-RNA, and HIV-RNA being 0.42%, 0.17%, 0.15%, 0.08%, 0.18%, 0.19%, 0.01%, and 0.01%, respectively. These rates were at a relatively good level and showed a significant decrease compared to the rates from 2006 to 2010. The analysis of population characteristics showed that the unqualified rates were relatively higher for males, young people, farmers and workers, those with low education levels, and first-time donors. A total of 83.38% of infection markers were detected as unqualified in all ELISA tests (including Anti-TP). The total detection rates of HBV, HCV, and HIV infection in ELISA testing after the first and second tests were completed were 39.24%, 59.61%, 85.94%, 100%, 39.89%, and 99.44%, respectively. The proportion of ELISA first test results that match the ELISA second test results was 21.32%. There were 16 cases of Anti-HIV positive, accounting for 94.12% of WB confirmed cases. All Anti-TP cases were screened by ELISA, and the detection rate of the first test was 41.42%. NAT could detect 65.85% of HBV-infected individuals (40.39% of which were supplemented by screening based on ELISA), 3.75% of HCV-infected individuals , and 100% of confirmed HIV-infected individuals . The proportion of NAT and ELISA results that are consistent was 16.53%Conclusions: ELISA is the basic means to ensure blood safety and can detect most transfusion-related infectious disease markers. NAT can detect hidden, \u201cwindow period\u201d infected individuals, etc., reducing missed diagnoses and is an important means of blood screening. Under the current context of mature and routine NAT, it is still necessary to continue with ELISA testing twice. Blood testing is an important step in preventing the transmission of transfusion-related infectious diseases, but the role of recruiting blood volunteers and pre-blood collection screening cannot be ignored.We would like to express our gratitude to Director Sang Liyong and Vice Director Fu Liqiang of the Shaoxing Central Blood Station, as well as Director Chen Jinkun of the Shaoxing Center for Disease Control and Prevention, for their significant assistance, guidance, and support in this study.a, Mingxiu Yanga, Xinbin Xiaa, Zhaojie Wanga, Jiale Lia, Zheming TianaYing Dua School of Humanities and Management, Hunan University of Chinese Medicine, 300 Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, China.Background: To calculate and analyze the treatment costs of malignant tumors in Hunan Province in 2021, to investigate the depression and anxiety of tumor patients, so as to clarify the influence of patients\u2019 disease economic burden on their psychological anxiety, and to provide data support for the formulation and improvement of policies by the health department.Subjects and Methods: Referring to the \u201c2021 Hunan Province Health Finance Annual Report\u201d and \u201c2021 Hunan Province Health Statistics Summary\u201d, based on the \u201cSystem of Health Account 2011\u201d, we calculated and analyzed the disease types, beneficiaries, institutional distribution and financing status of malignant tumors diseases. Then we investigated the status quo of depression and anxiety in patients with malignant tumor and analyzed its dynamic changes.Results: In 2021, the total cost of malignant tumor treatment in Hunan Province was 440,596,800 yuan. The top five were malignant tumors of digestive organs (40.10%), malignant tumors of respiratory and intrathoracic organs (17.62%), and malignant tumors of breast (12.24%), female genital organ malignant tumors (9.88%) and lip, oral cavity and pharynx malignant tumors (6.87%). The 35 to 79-year-old age group has higher treatment costs. The costs are concentrated in general hospitals. Funding sources mainly come from government financing and family health expenditure. Among them, family health expenditure accounts for a relatively high proportion. The main influencing factors of malignant tumor hospitalization expenses are gender, length of stay, age, drug proportion, institution level and medical institution type.Conclusions: The disease burden of malignant tumors is relatively serious, and it has a positive effect on patients\u2019 anxiety. The primary medical and health institutions lack health resources. Because the household health expenditure accounted for a relatively high proportion, the economic burden of patients with malignant tumor Further aggravated. As a result, the patients\u2019 psychological anxiety was promoted. This directly influenced the quality of life and life expectancy of patients. Therefore, hierarchical diagnosis and treatment should be promoted reasonably, key diseases and populations should be focused, medical security policies should be improved. These initiatives are expected to reduce the economic burden of disease in patients with malignant tumors and their families\u2019, reduce their psychological anxiety and improve their quality of life and life expectancy.a, Fu Jiangb, Yanyan LiuaKunxiu Lua Guangdong University of Science & Technology, Guangdong, 523083, China, b Guangdong Peizheng College, Guangdong, 510830, ChinaObjective: Under the background of the new era, the turnover rate of the new generation of employees is high, which brings some problems to the enterprise development. From the employee\u2019s point of view, the intention to leave must also have its own internal psychological factors based on the antecedent influences. In view of this, this study takes new employees who have worked for less than three years after 90 years as the investigation object, focuses on the inner evolution process of employees\u2019 psychological feelings based on emotion regulation theory, and examines the research on the influence path of new generation new employees\u2019 perceived overqualification on turnover intention.Methods: Based on the theory of emotion regulation, the structural equation model was used to analyze the questionnaire of 357 new employees.Results: Perceived overqualification had a positive effect on turnover intention, the adjustment effect of working years on perceived overqualification and turnover intention was not significant.Conclusion: This study explores the direct influence of perceived overqualification on turnover intention and the influence factors of boundary. From the results of the study, perceived overqualification is one of the sources of stress for new employees, which in turn leads to negative emotional attitudes such as intention to leave, so companies need to be concerned about the psychological perceptions of new generation employees. In addition, enterprises should pay more attention to employees who have left their jobs and understand the reasons for leaving so as to alleviate the talent shortage caused by employees leaving.This research received partial financial support from Planning Office of Philosophy and Social Sciences of Guangdong Province, China (Grant Number: GD21CGL07); Guangdong Education Department, China (Grant Number: 2021ZDJS113); and Guangdong University of Science & Technology, China (Grant Number: GKY-2022 KYZDW-6).a,bDaogang Hea School of Leisure Sports and Tourism, Beijing Sport University, Beijing, China, b Chengdu Aeronautic Polytechnic, Chengdu, China.Background: Ultimate Frisbee is a popular recreational sport that combines physical exercise and recreation, and is emerging as a lifestyle choice for young people. Previous studies have shown that participating in leisure-time physical activity is linked to improved mental well-being, but few studies have investigated the relationship between motivation and mental health. This study aimed to segment and analyze the motivations for participating in Ultimate Frisbee and explore their association with mental health.Methods: A mixed research approach was used, based on self-determination theory, to investigate the drivers of participation in Frisbee sports. This included the Physical Activity and Leisure Participation Motivation Scale, observational data from interviews, and field surveys of disc participants (N=207), as well as focus group interviews with 18 participants. Data were analyzed to identify motivations for disc sports participation and their relationship with mental health, using the basic psychological needs theory.Results: The study identified six dimensions of motivations for disc sports participation, including entertainment, appearance, physical condition, others\u2019 expectations, competition/ego, and social interaction. These dimensions were related to the need for autonomy, competence, and relatedness, represented by health, recreation, and socialization. All motivations for participation were related to mental health, in addition to physical condition. Qualitative analysis identified three motivational factors, including gender equality, trend following, and additional skill level, which were related to the six dimensions. Psychological need satisfaction was primarily related to changes in autonomy and competence, as well as physical activity and mental health.Conclusions: The study identified six distinct motivations for participating in disc sports, including recreation, appearance, physical conditioning, expectations from others, competition/ego, and social interaction. These dimensions were further elaborated upon, and three additional motivational factors - gender equality, following trends, and skill level - were also identified. Motivators related to mental health, such as social interaction, recreational motivation, appearance, and expectations of others, were confirmed as significant factors for participating in Frisbee. Releasing psychological stress through participation in Frisbee, thus promoting mental health and enhancing well-being, is also an important motivation for people to participate in Frisbee. The following trends and gender equality as motivational factors of disc participants can firmly explain the widespread phenomenon of disc sports. It also provides a new perspective for assessing disc sports and their participation motivation from a sociological perspective. The resulting framework provides a comprehensive understanding of the various motivations that drive individuals to participate in disc sports.This study was supported by a grant of the Youth Project of National Social Science Foundation of China (to Xi CHEN) (21CTY007) and Sichuan Province Philosophy and Social Science Key Research Base Tianfu International Sports Events Research Center (YJY2020010).a,b, Shuyue Zhanga, Qiuju WangcWeiwei Huanga Faculty of Education, Guangxi Normal University, Guilin 541004, China, b School of Education, Zhaoqing University, Zhaoqing 526061, China, c Normal College, Eastern Liaoning University, Dandong 118003, China.Background: The healthy physical and mental growth of children is a major concern for parents, and childcare services for children under the age of 3 are an important form of early childhood education in China. High-quality childcare services are a basic guarantee for the healthy physical and mental growth of children and an important way to reduce parents\u2019 parenting anxiety. Therefore, in response to the current situation that child care services in China fail to meet parents\u2019 psychological needs, this study explores how to improve and optimize the quality of child care services for children under 3 years old from the perspective of enhancing parents\u2019 satisfaction and reducing parents\u2019 parenting anxietySubjects and Methods: In this study, on the basis of in-depth understanding of parents\u2019 psychological needs and the factors affecting the parenting anxiety of parents through interviews, the author compiled the Survey Scale of Parents\u2019 Satisfaction with Childcare Service Quality for Children Under the Age of 3.The Survey Scale of Parents\u2019 Satisfaction with Childcare Service Quality for Children Under the Age of 3 was used to survey parents in a province in East China, and 516 valid questionnaires were collected, and the data were analyzed using the Kano-IPA integrated model.Results: The analysis results showed that in order to reduce parents\u2019 anxiety and increase their willingness to send their children to childcare institutions, childcare institutions need to improve the five areas parents are most concerned about: \u201cChildcare service institution could provide safety inspection reports for their decoration materials, facilities, equipment, toys, etc.,\u201d, \u201cService personal of the childcare institution has first aid knowledge\u201d, \u201cSpecific sleeping area in the childcare institution\u201d, \u201cIndependent and safe outdoor space for activities in the childcare institution\u201d, and \u201cThe childcare institution has sufficiently large indoor activity space for children\u201d.Conclusions: Whether the materials used in the hardware facilities of childcare institutions for children under the age of 3 are safe or not is an issue that parents are very concerned with, and it is a basic attribute that affects the satisfaction of parents. The rationality and adequacy of the space setting of childcare institutions for children under 3 years old are factors parents attach importance to, and they are very easy to be perceived and evaluated by parents due to obvious comparability. The qualifications of the staff of the childcare institution constitute a factor that ensures the quality of the service. Only by paying close attention to the psychological needs of parents and improving the quality of childcare services, can childcare institutions institutions improve the satisfaction of parents, reduce the anxiety of parents in raising children, improve the willingness of parents of child-bearing age to have children, and alleviate the problem of population aging.This study was supported by a research grant from the National Natural Science Foundation of China (32060197).aJia Zhenga Xi\u2019an Polytechnic University, Xi\u2019an, Shaanxi 710048 China.Background: The psychological health of individuals is of paramount importance in the university context, where there is a constant demand for innovation and inheritance of both traditional culture and modern developments. This study proposes an innovative model of instruction for art majors, with a focus on the living transmission of intangible cultural heritage (ICH) as its defining characteristic. The study underscores the positive interaction between psychological health education and the inheritance of ICH in arts courses.Subjects and Methods: Four paired models for the \u201cliving transmission\u201d of ICH - namely, \u201ctheoretical teaching\u201d, \u201cpractical teaching\u201d, \u201ctalent cultivation base construction\u201d, and \u201cInternet teaching\u201d- that incorporate diverse cultural elements, enrich students\u2019 innovative thinking abilities and enhance their confidence, thereby providing potential avenues for independent entrepreneurship were proposed.Results: The study finds that learning ICH skills enriches the content of talent cultivation, improves an individual\u2019s manual skills, and has a positive effect on concerning issues such as stress relief and anxiety emotions discharge in modern society.Conclusions: This study highlights the necessity of integrating \u201cliving transmission\u201d elements of ICH into theoretical teaching, practical teaching, talent cultivation base construction, and internet teaching, and establishes the innovative teaching model of the \u201cliving transmission\u201d of ICH in art teaching.aYang Lia School of Public Finance and Taxation, Central University of Finance and Economics, Beijing, China.Background: Cross-border investment is a strategic choice for enterprises to test their comprehensive capabilities, which requires comprehensive measurement of their own financial capabilities, management levels, mental health of enterprises managers, market sensitivity and technology absorption capabilities. Based on the data of enterprises with overseas connections among China\u2019s A-share non-financial listed companies from 2009 to 2019, this paper attempts to construct a theoretical framework of technological innovation effect and transmission mechanism of cross-border investment of Chinese enterprises.Subjects and Methods: Based on the theory analysis, this research uses econometric methods, using enterprise-level microdata for data analysis and model regression. Meanwhile, in the process of analyzing the innovation spillover effect of cross-border investment of enterprises, this research adopts the two-stage least squares method and introduces instrumental variables for endogenous problem analysis.Results: The results show that cross-border investment by Chinese enterprises has a positive effect on technological innovation, and the leap in technological innovation capability is the most significant through the reverse technology spillover mechanism, followed by the optimization effect of resource allocation, and the transmission effect of financing constraint mitigation is not significant. In the process of cross-border investment, entrepreneurs show their desire and demand for technological innovation, market sensitivity and personality and psychological needs determine the effectiveness of cross-border investment innovation.Conclusions: Based on the research conclusions, this paper further puts forward policy suggestions to optimize government support to guide more enterprises to promote technological innovation through cross-border investment.a, Qiuchen ZhengaZhiyue Zoua Guangzhou Xinhua University, Guangzhou 510520, China.Background: To investigate whether the T3 sandhi of Mandarin in adults with cochlear implantation has the same computational mechanism as in hearing adults.Subjects and Methods: 6 cochlear-implanted adults and 6 hearing adults were tested for mandarin T3 sandhi. After collecting the corpus, the analysis is carried out in two ways: first, three teachers of speech correction for the hearing impairment score all the corpus subjectively, and compare the correct rate of pitch shift; second, extract the fundamental frequency through the Praat and convert it into a semitone value, make a contrast curve and observe.Results: From the perspective of the correct rate of tone-shifting in the two groups, the correct rate of the three types of words in the experimental group was much lower than that in the control group, the correct rate of true words was higher than that of the other two types of words, and the correct rate of false words was the lowest. From the analysis of the comparison curve, it was found that the curve of some subjects in the experimental group was close to that of the control group, but the fluctuation was small, and it could still be regarded as a correct tone change. The curves of other subjects were flat or fluctuated greatly. When combined with non-T3, the tail tuning was up, which has the meaning of the original tuning. Therefore, it shows that adults with cochlear implants have mastered a certain T3 tuning mechanism.Conclusions: The T3 sandhi of adults with cochlear implantation is far behind that of hearing adults. If they want to master the T3 sandhi more proficiently, they should first change the phonetic environment, and control the low point of the fundamental frequency by listening to the correct pronunciation. Hearing equipment is upgraded to the best or adjusted to expand the range of hearing thresholds.This work was supported by a project grant from Guangzhou Xinhua University (Grant No. 2019KYQN17).a,bXing Hea China West Normal University, College of Management, Nanchong, Sichuan 637002, China, b Sichuan Research and Study Travel Development Research Center, Nanchong, Sichuan 637002, China.Background: Since the reform and opening up for 40 years, my country\u2019s tourism industry has experienced a development process from a rise, rapid to a comprehensive, and has gradually become the most dynamic industry in the national economic system.Subjects and Methods: According to the tourism research and residents\u2019 mental health level situation in the past 40 years of my country\u2019s reform and opening up, the development of my country\u2019s modern tourism industry is divided into four development stages: commercialization, marketization, industrialization and socialization, and summarizes eight major turning points in the development of my country\u2019s modern tourism industry. This study chooses worry, perceived control and desire to stimulate to represent emotion, cognition and motivation respectively, and constructs an impact model of psychological factors on tourism risk prevention behavior. Taking actual tourists as the research object, it uses questionnaire method to conduct empirical tests to verify the deep influence mechanism of emotional factors, cognitive factors, motivation factors and risk prevention behavior, as well as the condition boundary of this mechanism channel.Results: It also sorts out, compares and reviews related literatures with qualitative and quantitative research methods, which usefully supplements the theoretical and methodological results of modern tourism research in my country since the reform and opening up, and also conducts research on the shortcomings of modern tourism development in my country Reflection. The study found that the impact mechanism of psychological factors on tourists\u2019 risk perception and prevention behavior is very complex. Worry will not directly affect risk prevention behavior, but will significantly affect prevention behavior through perceived risk; Perceived control directly and indirectly affects risk prevention behavior through perceived risk; Stimulating desire will have a significant negative impact on risk prevention behavior. This mechanism path is regulated by tourism experience. Compared with the first tourists, the revisiters\u2019 concerns, perceived control and perceived risk have a greater impact on risk prevention behavior. Tourism experience also regulates the intermediary role of perceived risk, while the intermediary role of perceived risk of first-time tourists is not significant; The intermediary effect of perceived risk of revisiters is significant.Conclusions: Therefore, more attention should be paid to the impact of psychological factors such as emotion, cognition and motivation on tourists\u2019 tourism risk perception and prevention behavior, and more accurate risk management strategies should be adopted for newcomers and revisiters. At the same time, it is proposed that the combination of modern information technology and \u201ctourism+\u201d industrial research, in the face of unknown public safety incidents, strengthening international cooperation, and building a world tourism community with a shared future will be the development trend of modern tourism in my country.This paper is Supported by the 2022 project of Sichuan Social Science Planning (No.: SC22C026), the Sichuan Ethnic Mountain Economic Development Research Center Project (No.: SDJJ202224), the Sichuan Ethnic Mountain Economic Development Research Center Project (No.: YX22-38), the Sichuan Provincial Key Research Base for Humanities and Social Sciences of Colleges and Universities, the 2022 project of Sichuan Research Travel Development Research Center (No.: YX22-38) The 2022 Project of Sichuan Tourism Development Research Center, a key research base of social sciences in Sichuan Province (No. LY22-40), the Innovation Team for Studying Travel Theory and Practice of West China Normal University (No. SCXTD2022-6), the 2021 Doctoral Initiation Project of West China Normal University (No. 21E002).a,b, Panzhen Zhaoc,d, Long ShiaJun Chena Youjiang Medical University for Nationalities, Baise, China, b Philippine Christian University Center for International Education, Manila, Philippines,1004, c Faculty of Educational Studies, Universiti Putra Malaysia, Selangor, Malaysia, d College of Foreign Languages, Baise University, Baise, China.Background: The first consultation at the grass-roots level is the key link to promote the construction of hierarchical diagnosis and treatment system, which is conducive to promoting the sinking of public health resources and increasing the accessibility of residents\u2019 medical services. Research on residents\u2019 choice behavior and its influencing factors, which has important practical significance for establishing the first diagnosis system at the grass-roots level and guiding residents to form good medical habits.Subjects and Methods: Based on the data of household follow-up survey in China in 2018, based on Andersen\u2019s behavior model as the theoretical analysis framework, the article analyzed the influence of predisposition factors, energy-promoting factors and demand factors on the behavior of Chinese residents\u2019 choice of medical facilities by using the method of disorder and multi-classification Logistic regression.Results: The study found that the grass-roots medical institution is the place with the highest possibility for Chinese residents to go to hospital when they are ill. Meanwhile, due to the unbalanced distribution of medical resources in China, there is a certain degree of difference in the medical level of different levels of medical institutions. There are obvious differences in the behavior of Chinese residents in choosing medical institutions for medical treatment when they are ill. Still, more than one third of respondents prefer to go to general hospitals when they are ill. The study also found that (1) in terms of propensity factors, gender, job nature, education level, social frequency and satisfaction with medical conditions had a significant impact on residents\u2019 choice behavior of medical places; (2) in terms of energy promoting factors, personal income, medical insurance participation, etc. had a significant impact on residents\u2019 choice behaviors of medical places; (3) in terms of demand factors, Health self-assessment and chronic disease have significant influence on residents\u2019 choice behaviors of medical places.Conclusions: The improvement of the system of first diagnosis at the grass-roots level shall take into full consideration of the influencing factors of Chinese residents\u2019 choice of medical facilities, guide the residents to choose basic medical institutions for medical treatment through improving the incentive mechanism of basic medical insurance, and encourage residents to cultivate the reasonable habit of first-time diagnosis and two-way referral system. so as to promote the optimal allocation of medical resources.This study was supported by the Project of the Planning Project of Guangxi Province Philosophy and Social Science (2021CGL002), National Natural Science Foundation of China (72164036), National Natural Science Foundation of Guangxi Province (2019JJA180060).aHuizhen Xua Fair Friend Institute of Intelligent Manufacturing, Hangzhou Vocational& Technical College, Zhejiang, ChinaBackground: With the continuous development of the times and the deepening reform of university education, the engineering education model is also changing, which presents new challenges and opportunities for the cultivation of design talents. The transformation and upgrading of enterprises have intensified the challenges of design talent cultivation, and how to effectively carry out design education and cultivate innovative design talents with complex technical skills has put design teachers under increasing pressure. However, these pressures may lead to psychological problems such as anxiety and emotional disorders among teachers, which will affect students\u2019 learning outcomes and teachers\u2019 teaching reforms if not addressed effectively and timely. The purpose of this study is to explore the current situation of talent cultivation in design disciplines and the reform practice of design teaching from the perspective of psychological health.Methods: This study adopts a problem-oriented approach, introduces the concept of health psychology and TRIZ theory, and uses the cause-and-effect analysis method to conduct an in-depth analysis of the pain and difficulties in design teaching to find the deep-seated reasons for the difficulty in implementing teaching reform. Combining the deep-level reasons, the expectation model of physical-field is constructed, the design teaching reform strategy with psychological health as the starting point is proposed, and the design teaching reform scheme of creative ideas materialization is practically applied to solve the problems of difficult creative innovation, difficult implementation and difficult technical realization in design teaching, and the feasibility of its scheme is verified.Results: For design majors, a four-stage \u201cTRIZ+ Core Curriculum\u201d training system was designed, a \u201cTRIZ+ Design\u201d resource case platform of interest to students was created, a \u201cstudio-style\u201d teaching environment and an interdisciplinary teaching team were formed, and precise assessment and evaluation were designed. The five-step project-driven teaching method is implemented, including \u201cinitiation, teaching and learning, practice and enlightenment, evaluation, and expansion\u201d, which effectively solves the problems in design teaching, transforms virtual concepts into physical objects, enables students to understand design ideas more intuitively, and cultivates students\u2019 understanding of design. Students and teachers have achieved fruitful teaching results, and the satisfaction of enterprises has been improved, and the effect of teaching reform has been significantly improved.Conclusion: From the perspective of psychological health, the teaching reform strategy of creative ideas materialization can transform the pressure of teachers and students into motivation and relieve the psychological pressure of teachers and students in design disciplines. This teaching reform strategy can not only help teachers improve their teaching ability, but also help students enhance their innovation and engineering realization ability, and promote the rapid development of design education. Through the successful practice of this study, teachers and students will get a broader space to play and a more genuine sense of achievement.a, Fan Zhangb, Siti Rohaida Binti Mohamed ZainalcJiaqi Zhanga School of Management, Universiti Sains Malaysia (USM), GelugorPulau Penang, Malaysia, b School of Innovation and Entrepreneurship, Guangdong Polytechnic Normal University (GPNU), Guangzhou, China, c School of Management, Universiti Sains Malaysia (USM), GelugorPulau Penang, Malaysia.Background: Based on the perspective of competitive value architecture, this paper discusses the impact mechanism of strategy on organizational effectiveness of enterprises, and proposes corresponding application strategies.Subjects and Methods: In the increasingly competitive environment, enterprise employees are facing increasing psychological pressure. Enterprise employees are prone to problems such as low mood, physical and mental exhaustion, lack of work enthusiasm, decreased awareness of corporate culture, and lack of innovative spirit. Therefore, this puts forward higher requirements for enterprise human resource management. From the perspective of competitive value architecture, this article discusses strategic human resources, competitive value architecture theory, and strategic human resource management models. It analyzes the impact mechanisms of different strategic human resource management models, such as win-win cooperation, open innovation, control and coordination, and performance evaluation models, on enterprise organizational effectiveness, reveals the role of strategic human resource management in enterprise organizational effectiveness, and propose corresponding application strategies.Results: The impact carriers of strategic human resources on organizational effectiveness include organizational culture and organizational commitment. In order to protect and enhance the mental health of employees, it is very valuable to pay attention to the psychological empowerment of employees. Employee mental health is the key to improving organizational effectiveness. Among them, organizational commitment also affects employees\u2019 psychological empowerment, which in turn affects their level of loyalty to the organization. Employees feel empowered when they feel influential and meaningful within the organization. Therefore, psychological empowerment is of great significance to both employees and organizations, such as improving employee motivation and engagement, which in turn affects organizational performance. Building on the concept of psychological empowerment, this paper finds that, under the win-win cooperation model, a scientific, reasonable, fair and impartial performance contribution evaluation system is used to improve employee compensation satisfaction, enhance employee evaluation fairness, and generate a sense of belonging to the enterprise, thereby promoting the achievement of organizational efficiency goals. Under the open innovation model, both professional quality and innovative creativity affect organizational effectiveness through organizational culture and organizational commitment, stimulate enterprise innovation and creativity, promote enterprise development and innovation, promote the integration of internal and external resources, build resource synergy, and improve organizational efficiency. The control and coordination model enhances organizational effectiveness through a fair, just, and coordinated organizational culture and standardized and institutionalized organizational commitment. The performance evaluation model adopts a quantitative evaluation method to directly evaluate the contribution of strategic human resources to the organizational effectiveness of enterprises, providing a basis for optimizing the structure of strategic human resources and improving the quality of strategic human resources.Conclusions: This study found that, strategic human resource management mainly affects organizational effectiveness through organizational culture and organizational commitment. It is undeniable that there is often a positive correlation between employees\u2019 perceptions of psychological empowerment and mental health. The significant impact of organizational commitment on psychological empowerment of employees will further affect organizational effectiveness by affecting factors such as employee loyalty and enthusiasm.a, Landong Xub, Sixiang Taoa, Jingtang HeaHongzhao Wanga Department of Physical Education, Huainan Normal University, Huainan 232038, China, b School of Physical Education, Changchun Guanghua University, Changchun 130033, China.Background: Fitness and health (FH) testing in universities in China involved several health related components, such as BMI, vital capacity, flexibility, speed, aerobic endurance, power and muscle strength by National Fitness and Health Standards of Students (NFHSS). These components with specific reference values are considered markers of physical and mental health, and has been shown to be positively associated with cognition, weight status, and academic performance. Evaluation physical condition is a matter of concern of in public physical education (P.E) not only for conforming prevalence of FH conditions but also for implementing strategy of effective teaching. Monitoring physical fitness indicators is therefore considerable importance for social medicine, health education and health management, but it requires specialized equipment. Consequently, FH is rarely measured at the population level in public P.E teaching due to time, budget, complicated procedures and logistic limitations. A single-index of physical fitness components is a simple and cost-effective method to estimate FH status, which is an alternative to integrated testing system. Therefore, the purpose of the observational study was to examine the validity of pull-ups\u2019 cut-off score screening FH status among physically excellent male college students from Northeast, China.Subjects and Methods: The study was based on NFHSS, which was performed in 3 dimensional conducts consisting of morphology, function and fitness. A total of 5669 male college students aged 18-21 years were selected from Changchun Guanghua University. All participants\u2019 FH status were categorized into trichotomy groups as excellent, sound and no-pass by NFHSS. The difference of FH were analyzed by one-way ANOVA with components of the dependent variable and FH status as the factor. Regression analyses indicated whether the pull ups was able to predict the FH status of male college students among physically excellent and sound. Receiver operating characteristic (ROC) curve was applied to evaluate pull ups cut-off score indicating FT status and to discriminate the prediction ability of male college students among physically excellent and sound.Results: Mutually adjusted analysis showed a significant association between FH status and performance of pull ups in male college students who are physically excellent and sound. The cut- offs of pull-ups assessed by the ROC curve can discriminate the FH status between excellent and sound.Conclusions: Pull-ups was significantly associated with FH status and contributed to the excellent/sound model\u2019s prediction for FH status among physically excellent and sound students. Single index of pull-ups could be a useful prediction tool to identify and monitor variation in FH status of male college students between physically excellent and sound.This work was supported by a project grant from Scientific Research Foundation of Education Department of Anhui Province of China (Grant No.SK2021A0560).a, Lan DingaYuchang Houa School of Foreign Languages, Henan University, Kaifeng 475001, China.Background: Under the current situation of the \u201cdouble reduction\u201d policy in China, formative assessment in EFL (English as a foreign language) classroom is receiving increasing attention. According to Positive Psychology, emotions have direct influence during language learning process. For achieving satisfactory result of formative assessment, the present paper aims to investigate the EFL teacher\u2019s emotions in formative assessment and put forward practical strategies and skills to better use teacher\u2019s positive emotions and reduce their negative emotions, such as anxieties, gloominess and self-doubt.Subjects and Methods: To study the current level of emotions of EFL teachers towards formative assessment, questionnaires and interviews were administered randomly to 20 EFL teachers from 4 major junior high schools in China. To study the influence of EFL teacher\u2019s positive emotions on the effect of formative assessment, an 18-week positive psychology-based professional development program was conducted with a series of methods for result analysis including interviews, class observations, discussions and exams. To make the above-mentioned two studies reasonable, logical and scientific, all the experiments in the present paper were tightly grounded on the relevant theories and models to positive psychology.There are two limitations in the present study. First, the number of participants is not large. Second, the professional development program does not last long enough. Despite these limitations, this is a new study showing the emotion factor of EFL teachers during the formative assessment, a more emphasized kind of assessment under the \u201cdouble reduction\u201d policy newly and currently implemented in China.Results: Study 1 of the present paper found that the current level of classroom emotions of Chinese Junior School EFL teachers is not satisfactorily high. Data collected from Study 2 of the present paper showed that the professional development program was greatly beneficial. All the 20 participants have demonstrated an increased level of empathy toward students, which in turn brings motivation, enjoyment and confidence to themselves.Conclusions: Chinese teachers in junior high school have already noticed the importance of classroom emotions and teachers\u2019 positive emotions can make students ease in mind and actively engage in class tasks. Moreover, teachers\u2019 positive emotions can enhance their feedback that moves students forward. In general, teachers\u2019 positive emotions can act as instructional resources for building a closer and friendlier relationship with students and boost their teaching of English eventually.As we are trying to improve English teaching effectiveness and coming across more difficulties under the \u201cdouble reduction\u201d policy, it would probably be a reliable solution to shift from the summative assessment to the formative assessment, from the learner to the teacher, and from the teaching and learning of knowledge to the classroom emotions.This study was supported by the Teacher\u2019s Development Research Fund of Henan University (Grant No.: YB-JFZX-2022-19) and the Education Reform Project for Postgraduate Program of Henan University (Grant No.: SYLAL202201) and the Undergraduate-oriented Project of Henan University Research Laboratories (Grant No: 20221701024).aJialin Chenga Zhuhai College of Science and Technology, Zhuhai 519041, China.Background: In the post-pandemic era, life education for university students has become particularly necessary and important, as the COVID-19 pandemic has not only caused huge losses to people\u2019s lives and property, but also had a significant impact on the knowledge production mode and talent cultivation methods of higher education. In this context, life education for university students has acquired a richer connotation and significance.Subjects and Methods: It should cover three aspects: life consciousness education, survival ability education, and life value sublimation education. To achieve this, it is necessary to further broaden the concept of life education, enrich its content, innovate its methods, build its platforms, and ensure the effectiveness of the education process and its components.Results: The serious problems of narrow educational concepts, knowledge-based educational contents, fixed educational methods, limited educational levels, and closed educational platforms in life education for university students have seriously affected the formation of their life consciousness, the improvement of survival ability, and the sublimation of life values. Apparently, focusing on the physical and mental health and life development of university students, strengthening life education for university students in the post-epidemic era is not only a timely choice to adapt to the external environment of higher education but also an active choice to implement the fundamental task of moral education and talent cultivation.Conclusions: Strengthening life education for university students can help them establish a correct view of life and practice a positive outlook on life.a, Zehui JiangaMing Wanga Zhuhai College of Science and Technology, Zhuhai, Guangdong 519041, China.Background: With the change of times, the rapid development of economy and society, medical and health undertakings and sports industry is undergoing a period of rapid development; The decline of physical health has gradually become the main public health problem faced by human beings, and people\u2019s pursuit and need for health has become a rigid need. The Outline of the Healthy China 2030 Plan has been issued, and the combination of physical medicine has quickly become a new model of health intervention, emphasizing the need to add more means of physical fitness to modern medical treatment and rehabilitation.Subjects and Methods: By looking up literature related to the combination of physical medicine and its model, traditional national sports on CNKI platform, and looking up books about sports promoting health in the library, data were collected for the writing of this paper. At present, we advocate the organic combination of sports and medicine as well as the health intervention of non-medical means, and aim to establish the promoting mechanism of health education in schools with a focus on colleges and universities, and analyze the differences in the implementation of national traditional physical education courses under the concept of combination of physical medicine. From the school, physical education teachers, families and students four aspects try to analyze the relevant influencing factors, and put forward countermeasures.Results: The combination of physical medicine is a long-term method to enhance physical fitness and immunity. Based on the construction of \u201cfirst-class undergraduate courses\u201d, this paper starts from three aspects: general education courses, professional education courses and practical education courses, establishes the educational concept of \u201cintegration of physical and medical\u201d, optimizes the construction of the content system of \u201cintegration of physical and medical\u201d ethnic traditional sports courses, and cultivates ethnic traditional sports guidance talents to ensure public health. It can also build up cultural confidence in colleges and universities and promote the inheritance and development of traditional national sports.Conclusions: The \u201cGuangdong-Hong Kong-Macao Greater Bay Area\u201d strategy has been put forward and implemented, and the exchanges and coordination in the economy, science and technology, education, culture and quality life circle of the \u201c9\u2005+\u20052\u201d urban agglomeration are constantly expanding. Traditional ethnic sports, as an important way of cultural exchange, play an important role in promoting the coordinated development of sports and industries in the Guangdong-Hong Kong-Macao Greater Bay Area. By means of literature research, field research, SWOT analysis and other methods, this paper analyzes the strengths, weaknesses, opportunities and threats of the coordinated development of ethnic traditional sports in colleges and universities in the Guangdong-Hong Kong-Macao Greater Bay Area. It is suggested to promote the coordinated and integrated development of traditional ethnic sports in higher education institutions in the Greater Bay Area by implementing national strategies and policies, building exchange platforms for higher education institutions, cultivating academic exchange talents, building ethnic sports events, and combining sports and medicine.This work was supported by 2021 Annual Education Science Planning Project \u201cResearch on the inheritance and development of traditional ethnic sports culture in universities in the Guangdong-Hong Kong-Macao Greater Bay Area\u201d (Project No.: 2021GXJK080) and \u201cThree Levels\u201d talent Construction Project of Zhuhai College of Science and Technology.aJingjing Caoa School of Culture and Media, Xi\u2019an Eurasia University, Xi\u2019an, Shaanxi, China.Background: With the continuous development of emerging digital media technology and the continuous expansion of the application scenarios of digital media technology in daily life, building a digital country has become a global consensus, and promoting the digital village strategy has become an inherent requirement and inevitable choice for building the network powerful nation,digital China and smart society. However, according to the survey Investigation and Analysis Report on Digital Literacy in Rural China under the Background of Rural Revitalization Strategy released by the Center for Informatization Study of the Chinese Academy of Social Sciences, the digital literacy gap between urban and rural residents is 37.5%. The digital literacy score of rural residents is significantly lower than that of other professional groups. Rural residents\u2019 digital identity anxiety began to emerge.Subjects and Methods: The psychological identity of digital identity and digital literacy of rural residents has a direct impact on the digital village, rural revitalization and digital China construction. How to improve the digital literacy of rural residents in the strategic perspective of comprehensively promoting rural revitalization has become an urgent problem to be solved. Therefore, based on the existing research, the author discusses the value connotation, current situation, existing problems and reasons of rural residents\u2019 digital literacy, and then puts forward a practical and feasible way to improve rural residents\u2019 digital literacy.Results: The author puts forward four feasible suggestions according to the problems and reasons of rural residents\u2019 digital literacy: solve the rural residents\u2019 digital gap based on the problem of using digital products, solve the idle problem of digital products based on the use demand of rural residents, provide training on digital literacy and cultivate digital village culture, introduce digital technology cultivation projects and enhance the participation of rural residents.Conclusions: Rural residents\u2019 psychological anxiety about digital identity comes from the application of digital identity in individual virtual practice in the digital era. Improving the digital literacy of rural residents has a direct impact on alleviating this problem. Improving the digital literacy of rural residents is a long-term and arduous task, which requires a large amount of human, material and financial resources.This research is under the scientific research project \u201cResearch on the promotion path of digital literacy of rural residents in Shaanxi Province from the perspective of Rural Revitalization\u201d, which is supported by the Shaanxi Provincial Education Department (Grant No. 22JK0133), and the project of the 14th Five-Year Plan \u201cResearch on the Practice of Mixed Teaching Mode for News and Communication Courses in the Digital Era\u201d, which is supported by Shaanxi Academy of Educational Sciences.aWenqu Xua School of business Minnan Normal University, Zhangzhou, Fujian 363000, China.Background: The healthy personality of college students is a kind of self-consciousness gradually built up by college students in their life experience with their lifestyle and life style. It is a comprehensive embodiment and important symbol of people\u2019s world outlook, psychological quality and moral cultivation, and it is the psychological basis for college students to accurately grasp themselves, find a social position suitable for their own development, and obtain respect and goodwill from others. College students are the mainstay of the country\u2019s future development and the most valuable human resources of the country. The research on the shaping of college students\u2019 healthy personality and guiding college students to establish healthy and optimistic psychological quality have important practical enlightenment for cultivating college students to become talents with all-round development of morality, intelligence and physique and realizing the prosperity of the country.Subjects and Methods: The subjects of this study are college students in a university in Fujian. The scale used in this study was the Big Five Personality Inventory simplified version (NEO-FFI). The Big Five personality trait model divides personality into five dimensions, including neuroticism, extraversion, openness, agreeableness and conscientiousness, which are measured by five sub-tests of 12 questions per dimension, with a total of 60 questions. The simplified Big Five Personality Inventory (NEO-FFI) is a personality measurement tool for Chinese college students. Its \u03b1 reliability coefficient is 0.77 for neuroticism, 0.78 for extraversion, 0.63 for openness, 0.72 for agreeableness, and 0.74 for conscientiousness, which has good reliability and validity. Stratified sampling was used in the questionnaire survey, and 309 valid questionnaires were collected. In terms of statistical processing, SPSS22.0 Chinese version was used for statisticalanalysis of the survey data, mainly using specific statistical analysis methods such as descriptive statistics, independent sample T test and variance test.Results: Through the analysis of the NEO-FFI questionnaire, the research found that: first, there is no significant difference in personality traits between different genders and different grades; Second, the personality traits of different majors, whether they are student leaders, future planning types and self-promotion types have significant differences in a certain dimension. Specifically, in terms of professional categories, the neuroticism of liberal arts is significantly higher than that of science; The conscientiousness and extraversion of student cadres are significantly higher than that of non-student cadres, while neuroticism is significantly lower than that of non-student cadres. In terms of future planning type, the extroversion and conscientiousness of students with clear goals were significantly higher than those with uncertain goals. In terms of self-improvement types, conscientiousness and extraversion were significantly higher in students with ideas and practices than in students with no ideas and practices, while neuroticism was significantly lower than in students with no ideas and practices.Conclusions: College students in the new era are the hope and future of the country. The healthy personality of college students is related to the prosperity and prosperity of the country. It is suggested that the theory and method of human resource management should be integrated into the whole process of cultivating healthy personality of college students. Recruitment and configuration, training and development, performance management, salary welfare management and labor relations management six modules as the research basis, on college students\u2019 healthy personality training targeted Suggestions, so as to cultivate good social adaptation ability and stable sense of self, and good quality, independent thinking, good ability to life positive and optimistic attitude, emotion regulation and interpersonal harmony friendly health, etc Excellent college students with personality characteristics will provide qualified builders and successors for realizing the prosperity of the country.This work was supported by a project grant from2020 Fujian Young and Middle aged Teacher Education Research Project (JAT200333) and 2019 General Project of Fujian Research Center for Socialism with Chinese Characteristics (2019ZTD19).a,c, Yun Lib, Shanxian LiaXuejun Wanga College of Sports Economics and Management, Guangxi University of Finance and Economics, Nanning, Guangxi 530001, China, b School of Big Data and Artificial Intelligence, Guangxi University of Finance and Economics, Nanning, Guangxi 530001, China, c College of Education, Jose Rizal University, Manila, Philippines.Background: To speed up high-quality economic development and further give play to the sports industry\u2019s role in promoting green development, expanding domestic demand and cultivating new economic driving force cannot be separated from the support of local policies. The introduction of local policies will promote economic development, expand employment, and alleviate pressure through internal emotional regulation to generate positive emotions such as joy and happiness.Subjects and Methods: Taking the sports industry development of Guangxi as an example, the sports industry-related policies issued by 14 cities since 2018 were studied, focusing on the correlation between the policy issuance of each city and the development of the sports industry. By constructing the PMC-E quantitative policy evaluation system, the quality index of Six Aspects of Emotional Regulation local policies promoting the development of sports industry is quantified from a multi-dimensional perspective, and the quality index of local sports industry policy development is measured according to the weight, and the effect of various local policies promoting the development of sports industry is tested.Results: Nanning, Liuzhou and Guilin had strong local policies. Good effect on emotional regulation, Urban sports industry policy is reasonable. Other cities are in the acceptable range, the city sports industry policy is generally applicable.Conclusions: The average structure level of sports industry policies in Guangxi is reasonable, which promotes the release of vitality of sports market, Good emotional regulation, generating positive emotions. The PMC-E value of sports industry promoted by urban policies is consistent with the overall objective data, and the optimization suggestions are put forward for improving the local policies to promote the development of sports industry in Guangxi.This work was supported by the 2022 Guangxi Philosophy and Social Science Planning Project: Research on Artificial Intelligence Empowering High-Quality Sports Development in Guangxi (22FTY019); funded by the 2022 Guangxi First-class Discipline Applied Economics (Sports Economics and Management) Project.a,b, Zhibing Zoua, Shiqi Liua, Ruhai Feia, Wang Zhanga, Licheng Qina, Jiaxiang Fana, Guosong Wua, Liwei Zhenga, Nianmao LicWenxing Tana School of Sports and Health Science, Xiangsihu College of Guangxi Minzu University, Nanning, 530008, China, b Graduate School, University of Baguio, Baguio City 2600, Philippines, c School of Sports and Health Science, Guangxi Minzu University, Nanning, 530006, China.Background: From the perspective of mental health, the identification of their own identity is also an important evaluation index. Students\u2019 recognition of their major affects their choice of future career and attitude towards future work, which is professional cognition from the level of consciousness. The employment of college students directly reflects the quality of talent training in colleges and universities, which is related to the selection and training of high-quality talents. Based on the perspective of psychological identity, Combined with the background of targeted employment, this paper analyzes various practical problems that affect the training of social sports guidance and management professionals.Subjects and Methods: Subjects and Methods: Based on a common perspective of mental health and professional identity. This paper takes the major of social sports guidance and management as the research object, and adopts the research methods of literature review, interview and logical analysis.Results: The research shows that there are some problems in the training process of applied talents in social sports guidance and management: the absence of courses and teachers, the lack of social sports industry experience of teachers; The professional boundary is not clear, and the characteristics of applied professional skills training are not significant; The separation of specialty and occupation makes it difficult to cultivate and design applied talents. The disconnection between the profession and the society and the failure to train professional talents according to the needs of the society. The fundamental goal of talent training in colleges and universities is to cultivate healthy professional talents for the society, and the health here should be a comprehensive health state including mental health and moral health. Psychological identity is the basis of students\u2019 identification of professional learning, recognition from the internal recognition of the professional, is also the basis of learning motivation, and has a close relationship with their academic achievement. Application-oriented talents should be cultivated in an educational environment conducive to students\u2019 psychological identity, which can help students have a deeper understanding of their major. This paper puts forward the construction of application-oriented courses based on professional requirements to realize the effective diversion of talents; puts forward practical skills training-oriented by professional characteristics to link vocational qualification certificates; puts forward social need-oriented service-oriented teaching practice to accurately meet employment needs; puts forward the cultivation of core competitiveness oriented by targeted employment to improve the reform and innovation ways of talent provision mechanism.Conclusions: The major of social sports guidance and management is an application-oriented talent trained for social sports service and a professional talent characterized by practical maintenance group. Considering the students\u2019 mental health and professional cognition, the formation of their own professional identity is a prerequisite for the establishment of long-term career development planning. Professional identity directly affects the learning attitude, motivation and performance of students majoring in physical education, as well as their career development direction. Based on students\u2019 psychological identification with the major of social sports guidance and management, a four-in-one application-oriented talent training system of \u201ctheoretical knowledge-sports skills-teaching ability-comprehensive literacy\u201d is constructed, and the exploration and practical experience of \u201chigh-grade, targeted and advanced\u201d talent reform are summarized in combination with the background of targeted employment.This work was supported by 2022 key project of Guangxi Higher Education Undergraduate Teaching Reform Project [number 2022JGZ187]; 2023 Guangxi Young and Middle-aged Teachers Basic Research Ability Improvement Project [number 2023KY1668]; 2023 Annual Project of the \u201c14th Five-Year Plan\u201d of Guangxi Education Science [number 2023A122].a, Jinsan Qib, Hui Wangc, Zhixiang GaodHui Lia School of Foreign Languages, Zhejiang University, Hangzhou 310058, China, b School of Foreign Languages, Anyang Normal University, Anyang 455000, China, c College of Humanities, Ningbo University of Finance & Economics, Ningbo, 315175, China, d School of Foreign Languages, Institute of Disaster Prevention, Sanhe 065201, China.Background: Non-literal language is a typical pragmatic expression, and the comprehension and production of non-literal language involve advanced cognitive activities. Children with autism spectrum disorder (ASD), however, are pervasively impaired in processing non-literal language. Therefore, non-literal language comprehension and production ability can be important means to investigate pragmatic competence in autistic children. Recently, with the shift of language pathology to pragmatics, non-literal language processing in autistic children has become a research hotspot in clinical pragmatics worldwide. This paper intends to systematically formulate the comprehension and production characteristics, and the developmental patterns of non-literal language in autistic children, and then to provide worthwhile insights for future clinical language research and intervention.Subjects and Methods: According to the Convention on the Rights of the Child, this paper concerns autistic children under the age of 18. This review paper first retrieves empirical studies in irony/metaphor/idiom/proverb/pun/metonymy in autistic children from the Web of Science in the past two decades. And literature is further selected by refining the titles and abstracts, examining the comprehension and production of non-literal language in autistic children, and then expanding the search via literature-tracking. Finally, 34 empirical research papers are chosen.Results: This paper summarizes that research in non-literal language comprehension and production in autistic children roughly follows three pathways, that is, the characteristics of acquisition and development, the cortical activation patterns, and the influencing factors. To be exact, compared with their typically developing counterparts, not only are autistic children developmentally delayed in comprehending and producing non-literal language, significant differences exist among autistic children, but also they exhibit unique neural activation patterns. Moreover, performances in autistic children are constrained by their structural language competence, general cognitive mechanisms and deficient capacity of online semantic integration, and the complexity or diversity of the experimental tasks. Even so, autistic children do possess some capabilities to comprehend and produce non-literal language and even exhibit creativity to some extent.Conclusions: Three research threads sorted out by this paper presents a comprehensive picture of research in comprehension and production of non-literal language in autistic children. Overall, typically impaired and delayed in comprehending and producing non-literal language, autistic children demonstrate their unique developmental patterns and characteristics. Moreover, due to the complex nature of non-literal language, the nature of experimental tasks, and autistic children\u2019 cognitive abilities, their social environments, structural language capacities as well as pragmatic skills need to be coordinated. However, there exists a debate over the specific role these factors play. Heterogeneous participants and lack of standardized methodologies make the experimental results lack comparability and inclusiveness. Accordingly, several implications for future research and intervention are advocated such as the standardization of experimental research, the implementation of qualitative analysis, the setting of a specific target for individuals, etc.This study is supported by the key project of Social Science Foundation of China \u201cA Comparative Study on Multimodal Reference Strategies of Chinese Children with Autistic and Typical children\u201d (Project No: 17AYY009).aXiaomeng Lyua School of Economics and Management, Shenyang Institute of Technology, Shenyang, Liaoning, 113122, China.Background: With the development of mobile internet technology and the popularity of smart phones in the world, mobile apps has rapidly entered the daily life of people, which has a profound impact on people\u2019s thoughts, emotions and consumer behavior. It is generally believed that the cost of acquiring new customers is much higher than retaining existing customers. However, app users still have varying degrees of concern during the using process. More specifically, the level of psychological anxiety can to some extent affect users\u2019 use behavior and intention to continue using. This study aims to investigate the relationship between the degree of psychological anxiety of college students and the intention to continue using mobile travel Apps.Subjects and Methods: In order to achieve the purpose of the study, literature analysis method, questionnaire survey method and statistical analysis method were used in this research. In order to ensure the diversity of sample sources, different major groups of college students were selected from different universities in China. An online questionnaire platform \u201cQuestionnaire star\u201d has been used to distribute and collect questionnaires. Finally, 489 questionnaires were collected. Before data analysis, strict data filtering is performed to check whether there is invalid data or abnormal values. Questionnaires with incomplete and missing items and the questionnaire with the same answer on 5 consecutive questions were considered invalid, and 445 valid samples were obtained. After data collection, SPSS 22.0 and AMOS 22.0 were adopted as tools for data analysis. The data analysis of this study was conducted using structural equation modeling (SEM) technique and followed the two-step approach of for assessing the measurement and structural models respectively.Results: By referencing the results of significance analysis of path coefficients, the eight hypotheses proposed in the study were supported. These findings in this study are also consistent with those in Bhattacherjee\u2019s study, the five original hypotheses of ECM model are supported. And this study further supports that ECM has the ability to interpret users\u2019 continuance intention of mobile travel apps. Besides, the variable of perceived interactivity was also verified in the study to have an impact on satisfaction and continuance intention. The revised model can be used to guide research on post-acceptance behavior. Increased perceived usefulness, confirmation and perceived interactivity can reduce the degree of psychological anxiety of college students and improve users\u2019 satisfaction and continuance intention. The results extend the findings of ECM model to the context of mobile travel apps and the hypothesis testing indicate that the ECM model is applicable to and can be stretched to the study of travel apps continuance intention.Conclusions: Improved perceived interactivity can reduce psychological anxiety of college students and enhance consumers\u2019 intention to continue using. E-commerce platforms should attach importance to enhancing perceived interactivity.This work was supported by my thesis advisor Professor Youngkyu Kim from Keimyung University.a,b, Qinghua LicRong Xiea School of Architecture and Engineering, Suqian University, Suqian City 223800, China, b School of Fine Arts, Qiongtai Normal University, Haikou City 571100, China, c School of Arts and Communications, Suqian University, Suqian City 223800, China.Background: With the increasingly prominent problems of modern diseases, urban diseases and sub-health, the wellness industry, as an important supplement to modern medical and old-age care institutions, has been booming, and the wellness homestay is one of the important forms of business.Subjects and Methods: The development of the healing function is inseparable from the elaborate design and construction of its landscape space and atmosphere. The article introduced Herman. Schmitz\u2019s new phenomenological concept of body economics to study the psychological mechanism of the healing function of landscape space in wellness homestays. In that case, the carefully created landscape space and atmosphere can effectively adjust and intervene in the structural and dynamic characteristics of the occupant\u2019s body economics, so that the occupant\u2019s body economic structure and dynamic characteristics can maintain a good state of tension, and can achieve a smooth transition between narrow atmosphere and wide atmosphere.Results: In an ideal state, not only the indoor and outdoor environment and landscape space of wellness homestay are carefully designed, organic agriculture, fishery, gardening and traditional handicraft practices are carefully organized and carried out, but also the rich regional culture, traditional festival folk custom, lifestyle, as well as the rich ethnic culture play a vital role in the atmosphere of wellness homestay space.It also has an important impact on the health function of homestays.Conclusions: All these colorful original and present elements, through the effective adjustment and intervention of the economic structure and dynamic characteristics of the body in the process of the restoration and liberation of the subject personality of the residents, can help them to restore a good balance and tension state, complete the smooth transition between the restoration and liberation of the subject personality, and finally realize the healing function of the landscape space of the residential health.This paper is an in-depth study of the complex psychological mechanisms in this process.This work was supported by Philosophy and Social Science Planning Project in Hainan Province (HNSK(ZC)21-163).a,b, Yanhua Zhangc, Chengfan Dua, Shijun Xia,d, Xiaochun Penga,eQiong Wanga Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, China, b Department of Nursing, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, China, c Department of Physiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, China, d Shanghai Zhaxin traditional Chinese western medicine hospital, Jing\u2019an District Shanghai, 200435, China, e Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, China.QW and YZ contributed equally to this study.Background: The ideological and political education (IPE)as an integral part of higher education is faced with different challenges amid this modern era of globalization. Therefore, the integration of IPE into the whole subject teachings, the so-called curriculum ideological and political education (CIPE)is an effective way to solve this problem. This study is the first to properly introduce the concept and history of curriculum ideological and political education in China. Additionally, it also analyzes the evaluation of students\u2019 psychological state and the importance of mental health education for the implementation of the curriculum IPE.Subjects and Methods: For those purpose, a total of 211 research subjects from Yangtze university are investigated to report the students\u2019 motivation and behavior toward the ideological, political, and pathophysiology courses Furthermore, a questionnaire survey is used to explore the relationship between pathophysiology and ideological and political courses, and their satisfaction with the implementation of ideological, and political courses in pathophysiology and mental health education importance.Results: The results demonstrate that there are significant differences between educational background and the degree of interest in ideological and political courses, gender differences, and the feedback data on the learning of professional courses. Postgraduate students are more interested in the ideological and political courses, whereas the females report that it is difficult to study pathophysiology; In addition, the results of one-way ANOVA show that the implementation effect of IPE in the pathophysiology curriculum depends on the degree of interest in IPE and pathophysiology curriculum, the degree of considering the importance of professional courses, the professional harvest after learning pathophysiology, and the degree of understanding the relationship between IPE and CIPE. A total of 81.04% of the students believe that the teachers telling stories themselves is the most popular way to spread education in the process of CIPE. This reflects the importance of mental health education from the perspective of CIPE. Additionally, this study also implies that PBL and flipped classroom teaching modes are the popular modes of teaching for CIPE.Conclusions: This study is conducive to promoting the improvement and implementation of CIPE with mental health education in higher education courses; thereby, providing valuable insights for the educational decision-makers.This work was supported by a project grant from National innovation and entrepreneurship training program for College Students (grant no. 202010489017), Hubei Province Natural Science Foundation of China (grant no. 2017CFB786), the Scientific Research Project of Education Department of Yangtze university (grant no. JY2020134), the Curriculum Ideology and Politic Project of Graduate School of Yangtze University (grant no. YSZ202111), and Yangtze University 2022 Full-English Teaching Course Construction Project(grant no. 202215).aYongli Tana Department of English, Chengdu University of Technology, Chengdu, Sichuan 510059, China.Objective: To investigate the efficacy of aesthetic education in reading and writing through the spatial image description reading of a famous writer\u2019s novels, and to analyze the college students\u2019 aesthetic psychological needs when they are in face of anxiety.Methods: First, close-reading is used in the interpretation. Bai Xianyong\u2019s novels have their own narrative discourse aesthetic feeling. The artistic characteristics are mainly elegant, light and gentle, delicate and sensitive, and peeling off impurities. There is a sense of loneliness in the works, showing a unique aesthetic style. From his works to observe the presentation of aesthetic style, spatial image is an indispensable means of expression. Second, observation is used in the classroom teaching. During a semester, the author systematically observed, recorded and analyzed students\u2019 mood changes in reading Bai Xianyong\u2019s novels in order to obtain the relationship of aesthetic reading and relieving the students\u2019 reading and writing anxiety. The author tried to keep objective and maintain the natural exposure of the observed students, and the obtained results were relatively effective.Results: In the reading and writing, there were a comparatively focused time out of interference and the participation of the students was full. And through the close-reading and observation, the author found the students\u2019 anxiety was relieved when the teacher served them novels with beautiful descriptions, and their aesthetic psychological needs were largely satisfied. Since novels have integrated the author\u2019s observer perspective, creative expression and the aesthetic consciousness of the readers\u2019 imagination, aesthetic reading before writing is an effective way to overcome writing anxiety.Conclusions: I suggest that the aesthetic psychological needs are students\u2019 innate motive for reading and writing, so meeting the aesthetic psychological needs of students have potential to assist educators to become more reflective about their full development and to assist the students to relieve the anxiety and to articulate their own reading and writing schedule. In this paper\u2019s example, through the aesthetic interpretation of the three types of spatial images with the highest frequency in Bai Xianyong\u2019s novels, the residence living room, the midnight park and the ballroom and the bar, the students understand the space-time dislocation, identity pursuit and uncertain fate. The students were led to discuss the relationship of psychology and metaphor, and to explore the specific aesthetic space elements such as body perception, emotion and thought in the novels. After the aesthetic analysis of this novel, the students were more active about their own readings and writings.This research was supported by Chengdu University of Technology \u201cDouble First-Class\u201d Initiative Construction Philosophy and Social Sciences Key Construction Project (ZDJS202318).a, Zhifang HanbXiaobo Taoa Graduate School, North China University of Technology, Beijing, China, b School of Economics and Management, North China University of Technology, Beijing, China.Background: With the development of economy and society, the personal quality of employees has been generally improved. However, many employees feel more pressure on how to achieve the best results in the competition with rising tide. Some near-morbid competition phenomena have caused many unhealthy psychological problems, such as high psychological pressure and heavy depression tendency. It is urgent for enterprises and the whole society to find correct solutions to achieve personal development, sustainable economic and social development. Sustainable supply chain management seems to be a reasonable choice. It is a modern management mode that comprehensively considers and balances economic, social, and environmental benefits. As an important part of social benefits, mental health can be maintained in a reasonable range through sustainable supply chain management.Subjects and Methods: Through interviews with three companies, namely company A, company B and company C, which all belong to the manufacturing industry, this paper analyzes the interview results with View of Grounded Theory. The reason why the selected companies belong to the manufacturing industry is that the popularization of automation in the manufacturing industry has become the trend of the times, which makes employees face the major problem of how not to be eliminated in the performance appraisal. Generally speaking, it is difficult for employees to maintain a healthy psychological state under such circumstances, which makes the manufacturing industry a very suitable research object for this article. In the analysis of the interview results, this paper divided the experiment into three parts according to the grounded theory: open coding, spindle coding and selective coding.Results: Based on the grounded theory, this paper sorted out 108 open coding results, 24 spindle coding results and 6 selective coding results in the interview contents. This paper described and analyzed the spindle coding results and the selective coding results to ensure that the sources of the results are true and credible, and finally proposed possible research issues and research directions.Conclusions: Research and analysis based on grounded theory shows that sustainable supply chain management will effectively improve the psychological health of employees. This will require enterprises to consider and discuss multiple aspects when formulating sustainable supply chain management strategies, and develop more diversified sustainable supply chain management strategies, so as to achieve the improvement of multiple benign indicators and benefits, and ultimately help employees and society achieve healthy and sustainable development.aMingzhu Zhua Innovation and Entrepreneurship Development Center, Tianjin Sino-German University of Applied Sciences, Haihe Education Park, Tianjin 300350, China.Background: To realize the development of innovation and entrepreneurship education in Chinese application-oriented universities, the integration with professional education is an important way to cultivate the entrepreneurship of students and promote the higher quality employment of graduates. In recent years, outstanding achievements have been made in the theoretical research and practice of innovation and entrepreneurship education in Chinese universities. However, China\u2019s innovation and entrepreneurship education is still in the exploration stage, especially in the integration with professional education. The separation has a negative impact on students\u2019 innovation and entrepreneurship education. Moreover, it is unknown to what extent the impact on students\u2019 mental health. This paper tries to comprehensively analyze the current situation, problems and results of the integration of innovation and entrepreneurship education and professional education. The corresponding solutions are proposed to help students complete better innovation and entrepreneurship education and to play a positive role in students\u2019 mental health.Subjects and Methods: This paper adopts the case analysis method and the questionnaire survey method. Taking an application-oriented university as a case, this paper analyzes the status in the integration of this university to find the phenomena and problems in the practice of innovation and entrepreneurship education in universities. Students are the important subjects and direct beneficiaries of education. Students\u2019 subjective feelings and objective needs are both important factors influencing education. The actual impact on the mental health of the students is analyzed through the questionnaire survey of the students in this university.Results: The integration model of innovation and entrepreneurship education in application-oriented universities is proposed from the perspective of universities, government and enterprises based on the symbiosis theory. An application-oriented university is taken as a case to explore the mechanism of innovation and entrepreneurship education, and the successful experience in the integration of education and its impact on students\u2019 mental health. Finally, three suggestions are put forward for the effective integration of innovation and entrepreneurship education and professional education in Chinese application-oriented universities. This also can play a positive role in students\u2019 mental health.Conclusions: The development of innovation and entrepreneurship education in universities should be deeply integrated with professional education. The universities, government and enterprises, all three should participate in the whole development of innovation and entrepreneurship education. The integration of innovation and entrepreneurship education and professional education in application-oriented universities can cultivate students\u2019 entrepreneurship better, help students to complete employment better, and help students\u2019 to improve in mental health better.This work was funded by achievements of the key research project of Tianjin education (JYDY-20223006) and the scientific research project of Tianjin Sino-German University of Applied Sciences (zdkt2021-013).aXinyi Zhanga School of Marxism, China University of Political Science and Law, Beijing, China.Background: To investigate whether the psychopathic agents who have deficits in emotional processing and inhibitory control are really competent with moral concepts and can make genuine moral judgements as non-psychopathic agents do, and to defend a specific kind of ethical view based on the analysis of relevant results came from psychological and neuroscientific experiments.Subjects and Methods: A certain number of representative existing moral psychological experiments were discussed and analyzed with an eye to arguing for and against relevant competing views about moral concepts and judgements, i.e. the judgmentalist view and the motivationalist view. These experiments including roughly three types, among which the first type is the experiments that using the moral/conventional distinction to test whether psychopaths have the ability to distinguish between moral transgressions and conventional transgressions, the second type is the experiments that using moral dilemmas such as the trolley problem constructed by philosophers to test whether psychopaths can properly distinguish personal harms from impersonal harms. Two phenomena could be observed from these empirical tests, i.e. firstly, psychopaths and non-psychopaths make different judgements with regard to personal aggressions; secondly, both psychopaths and non-psychopaths show the capacity to distinguish personal aggressions from impersonal aggressions. Since the judgmentalist view and some sophisticated version of motivationalist view could accommodate the two phenomena equally well, a third type of psychological experiments was appealed to, i.e. the neuroscientific experiments that using brain imaging techniques such as functional magnetic resonance imaging (fMRI) to reveal patterns of activation in cognitively-relevant areas and emotionally-relevant areas when psychological and non- psychological subjects are presented with moral dilemmas and make moral judgements as well as judgements about how to act. The data from fMRI scans were then used to support the judgmentalist and emotionist hypothesis about moral judgements.Results: The brain imaging experiments showed that, with regard to judgements about the moral properties of relevant actions and judgements about degrees of severity of moral violations, there was some kind of symmetry in psychopaths\u2019 mental mechanisms as well as in non-psychopaths\u2019 when they make moral evaluations. Non-psychopaths\u2019 judgments about moral properties and judgments about severity are both associated with emotion-related brain regions, while both types of judgments of psychopaths are connected to cognition-related brain regions. These two types of judgements are not actually generated by different mental mechanisms and processes.Conclusions: Although there is no significant difference between psychopaths and non-psychopaths in various moral judgment results, psychopaths lack the ability to make genuine moral judgments. This gives us a good reason to support the judgmentalist and emotionist view.The work on this paper was supported by the Humanities and Social Science Foundation of Ministry of Education of China (Grant No. 22YJC720022).a,bHaixia Baia Tourism and Economic Management Department, Lijiang Teachers College, Lijiang 674199, China, b School of Business, Yunnan University of Finance & Economics, Kunming 650221, China.Background: Huge Crisis always brings unprecedented impact to the tourism industry, leading the theme of resilience which aims for recovery become a hot topic in tourism research. However, the tourists\u2019 psychological resilience has been largely ignored, the mechanism of how tourists give play to their psychological resilience when facing the destination crisis is still ambiguity, and the impact on tourism industry is also unclear, forming a huge research gap. By exploring tourists\u2019 psychological resilience, this paper aims to enrich the literature on tourism resilience theoretically, and in practice, explores the enlightenment of tourism recovery under the crisis context from the perspective of demand.Subjects and Methods: Based on SOR theory and Maslow\u2019s Needs theory, this paper adopts the longitudinal research method to collect data to track the diachronic changes of the COVID-19 pandemic situation from January 2020 to December 2022 in Lijiang, a small tourist city in southwest China that is popular with domestic and foreign tourists. The Focus group discussion (FGD) method is used to summarize the stages of tourists\u2019 psychological changes, analyze the important role played by technology forces in this process, and predict the trend of digital transformation in the tourism industry.Results: In the early stage of the pandemic, due to the risk perception of external policies and internal loss aversion, tourists show travel fear or travel avoidance behavior out of the motivation of seeking safety. In this stage, they think highly of digital based countermeasures to ensure health and safety. In the middle stage, the depressed tourism demand seeks to release. On the one hand, tourists flow to local tourism markets such as travel around, suburban tourism, rural tourism and micro vacation, increasing the stable closed-loop circulation capacity of the local market. On the other hand, they pursue new forms of digital tourism, which can relieve the suffering of \u201clovesickness\u201d for tourism to some extent. In the later stage, the pandemic situation tends to ease, some tourists show a tendency of compensatory tourism and start taking \u201can instant trip\u201d mode, while more tourists remain cautious and planning long distance travel. At this stage, tourism psychology shows a strong preference for social needs and shows dependence on digital technology.Conclusions: Amid the crisis, tourists follow the psychological mechanism model of \u201cEnvironment-perception- motivation -behavior\u201d, showing the evolution and change law of three stages, namely, early period-travel fear, middle period-demand depression, late period-differentiation and transformation. Besides, digital technology plays an important role in each stage. From the perspective of tourists\u2019 psychology, this paper reveals that after the crisis, the recovery of tourism industry needs a process of gradual adaptation and restart. This research also gives some advice on the research agenda of tourists\u2019 psychological resilience in the future.This work was supported by a project grant from The National Social Science Fund of China (Grant No.22BGL151).a, Shizhen BaiaShiying Wanga School of Management, Harbin University of Commerce, Harbin 150028, China.Background: In recent years, as COVID-19, Ebola, monkeypox and other infectious diseases continue to spread around the world, public health emergencies have become another important factor affecting people\u2019s work and life. Public health emergencies are unexpected, unpredictable and irresistible, and they will cause devastating consequences and damage people\u2019s body, mind, spirit and other aspects. When people face these stressful events, once they cannot solve or deal with them, serious psychological imbalance will occur, which is called crisis. Acute psychological disturbance may occur during a crisis. The main reason for this is that people are afraid of the uncertainty and opacity of the event itself. Therefore, this paper uses the infectious disease model to establish the prediction model of public health emergencies. Through the model, the development trend of the events, mortality and other indicators are effectively predicted, so as to alleviate people\u2019s panic.Subjects and Methods: In this paper, a prediction model of public health emergencies based on SEIHD was established by improving the traditional infectious disease model and using three indicators, namely viral infection rate, virus incubation period and recovery rate. The SEIR model was improved and the parameters were modified to simulate the external intervention measures to predict the development trend of the epidemic.Results: In this paper, the law of epidemic transmission in Hubei Province was taken as an example to predict the number of confirmed cases and the number of deaths in two stages. The cumulative number of confirmed cases in Wuhan from January 11, 2020 to February 18, 2020, predicted by the prediction model, and the real data during this period was fitted. The two curves were compared, showing good fitting. The data of the COVID-19 epidemic in Hubei Province from January 11, 2020 to February 18, 2020 were input into the model as the basic data to predict the death toll during this period. The data were fitted to the real data respectively. At the same time, it was assumed that quarantine measures were taken ten days in advance to predict the death toll. The same method was used to predict the number of confirmed cases and deaths from February 18, 2020 to April 14, 2020, and the results were correct.Conclusions: The prediction results are basically consistent with the real data, which confirms the validity of this prediction method. The research proves that early detection, early prevention and control of public health emergencies can control their development trend, curb their widespread spread, and reduce the harmful impact on social life and economy. At the same time, it can alleviate people\u2019s panic about the epidemic to a certain extent. So as to avoid the acute psychological disturbance caused by insufficient cognition of public health emergencies.This work is supported by Humanities and Social Science Project of Ministry of Education (18YJCZH175); the National Grant Natural Science Foundation of Heilongjiang Province (YQ2019G004); University Nursing Program for Yong Scholars with Creative Talents in Heilongjiang Province (UNPYSCT-2020081).a, Yuanxin ZhangbXueqing Kanga School of Economics, Sichuan University, Chengdu 610065, China, b Chengdu Institution of New Economic Development, Chengdu 610042, China.Background: New-type urbanization is not only the urbanization of population, but also the citizenization of agricultural transfer population and realize social psychology integration in aspects of lifestyle, cultural types, psychological resources and corresponding social structure. The psychological health level of the agricultural transfer population is a key component of promoting social integration of agricultural transfer population into cities, which can improve new-type urbanization. Compared with the expanding capital demand of these related projects, it is far from enough to rely on fiscal revenue, therefore optimizing investment and financing mechanism for urbanization and strengthening financial support for new urbanization is urgent.Subject and Method: This study aims to analyze the agricultural transfer population\u2019s demand of social integration to improve their psychological health level and conduct to optimize the allocation of supporting financial resources in process of new-type urbanization. By analyzing the financial support mechanism of agricultural transfer populations\u2019 social integration from the perspective of environmental psychology, we establish a new financial support path design containing general path as well as specific path, tested by structural equation model based on panel data 31 provinces of mainland China from 2008 to 2017.Result: The results show that the effect of financial support for agricultural transfer population\u2019s social integration to China\u2019s new-type urbanization is more significant than fiscal revenue support, and the supporting function is realized through general path and specific path respectively to ensure migrant people\u2019s equal access to infrastructure and public services to help them to form place connection to gain social integration, which is beneficial for the agricultural transfer population to obtain a sense of happiness from urban life, thereby improving their psychological health status.Conclusion: This study recommends that the enterprises engaged in agricultural transfer population employment and governments need to pay attention to their psychological health status and enhance related infrastructure and equalization of social security to help them achieve social integration. Meanwhile, it is indispensable to build a diversified financial support system in paths of entity economy development, infrastructure construction, employment, education, housing, social security to form place connection from physical environment dimension and solve the recent financial support system\u2019s problem of unitary structure, insufficient innovation and scale, which will enhance agricultural transfer population\u2019s security sense of social security and local trust through place connection to raise their psychological health level to realize social integration.This paper is supported by the National Social Science Fund of China (grant number 14BJY055).a, Tae-Won KangbJing Chia Department of Global Entrepreneurship, Kunsan National University Gunsan 54150, Republic of Korea, b Department of Supply Chain and Logistics, College of Social Sciences, Kunsan National University, Gunsan 54150, Republic of Korea.Background: To explore the promotional strategies for university library reading and summarize the experience gained in the course of disseminating Chinese traditional culture in the context of national reading, based on user psychological needs and relying on college student volunteers.Subjects and Methods: In 2009, the Library of SDNU analyzed user needs, refined its collection advantages, and took the dissemination of traditional Chinese culture as a starting point to bring college student volunteers into the role of reading promoters, gained support from the university as well as the social forces, uniformly planed marketing development and focused on the impact assessment. In this article, the specific case of the SDNU Library Reading Promotion Project \u201cPromoting Volunteerism and Reading to the N-th Power\u201d was analyzed, and the origin, goals, products, evaluation and main processes of project were introduced.Results: The reading marketing project \u201cPromoting Volunteerism and Reading to the N-th Power\u201d was planned and organized by the Library of SDNU from 2009. The inspiration for the project derived from the classic book A Single Spark Can Start A Prairie Fire by Mao Zedong, the great leader of China. Since the launch of the project, the Library of SDNU has been awarded the national-level \u201cDemonstration Base for National Reading\u201d (at the team level); the university student volunteers in the library have won three gold awards in the three major categories of university student reading promotion nationwide ; the cooperation between the Library of SDNU and public welfare organizations and social enterprises has become increasingly close (at the marketing level); the satisfaction survey of readers among the faculty and students at SDNU Library has ranked first for consecutive years, and the number of social readers following their new media platform for marketing projects has been increasing year by year . The volunteer reading promotion project for college students in the Library of SDNU has been reported by many media outlets such as Renmin.com, Dazhong.com, Fenghuang.com, Qilu Evening News, and Life Daily, and has aroused strong social repercussions . The \u201cPromoting Volunteerism and Reading to the N-th Power\u201d reading marketing project of SDNU Library is gradually realizing the potential of starting a prairie fire with a single spark, taking university libraries as the front line.Conclusions: This project, based on users\u2019 psychological needs, leveraging college student volunteers to promote traditional Chinese culture in university libraries, is a positive manifestation of the views and attitudes of the International Federation of Library Associations and Institutions (IFLA) strategic plan. The project is conducive to the internationalization and branding development of Chinese library reading marketing projects and the establishment of a marketing system for the global dissemination of traditional Chinese culture through university library systems. The design and implementation of the project\u2019s working methods have a close social, school, and personal background. The Library of SDNU has actively responded to the National Reading initiative by cultivating excellent reading promotion projects that can be used for reference and easy to replicate, spreading the permanent charm of Chinese culture and the style of the times, which is conducive to enhancing the reading happiness of people at all levels of society, including entrepreneurs, students, farmers, and other groups; and by cultivating excellent reading promoters, giving full play to the advantages of peer partners, and achieving positive self-development through mutual assistance and cooperation, which is conducive to the unification of the \u201cself-value\u201d and \u201csocial value\u201d of the personality of the Chinese youth generation.aLancang Wanga Beijing University of Chemical Technology, Beijing 100029, China.Background: According to a survey of 126000 college students in China, it was found that 20.23% of college students have psychological disorders, 11.7% of college students have different degrees of psychological diseases, and 75% have experienced psychological crisis. Will quality is an important part of athletes\u2019 competitive ability, a necessary guarantee for their excellent performance, and also the embodiment of sports spirit and sports culture, especially for college athletes at the growing stage. At the same time, mental health is of great significance for college athletes to resist mental diseases, improve learning efficiency, complete training tasks, and improve interpersonal communication and quality of life.Subjects and Methods: This paper uses the methods of literature, experiment and mathematical statistics to study the CUBA players of several universities in Chaoyang District of Beijing. The experiment was divided into two groups. The experimental group added outward bound training to the training plan, while the control group carried out according to the original training plan. Before and after the experiment, the professional psychological scale was used to measure and record the various indicators of the subjects for analysis and research.Results: Through theoretical analysis and experimental research, outward bound training plays a positive role in the cultivation of CUBA athletes\u2019 mental health. The experimental research shows that the addition of outward bound training in the training has a positive effect on the cultivation and improvement of the will quality of college students\u2019 athletes. Although this improvement is unbalanced, there is no significant difference in the three aspects of hardiness, tenacity and goal clarity from the statistical point of view, but it is very obvious in the three aspects of decisiveness, self-control and self-confidence (P<0.05).Conclusions: It is suggested to pay more attention to and cultivate the mental health level of college athletes. It is suggested that university sports teams should selectively integrate part of outward-bound training into the training of sports teams according to their own conditions, so as to improve the mental health level and willpower quality of athletes. And gradually establish and improve the curriculum system in line with the training of various projects of the university based on their own needs.a, Ling Miaob, Yanjie WangcXiaoxi Suna The CPC Henan Provincial Party Committee Party School, Zhengzhou, Henan 451464, China, b The CPC Henan Provincial Party Committee Party School, Zhengzhou, Henan 451464, China, c College of Humanities and Development Studies, China Agricultural University, Beijing 100089, China.Background: This article analyzes the development of franchising in China, its growing role in the Chinese economy, and how its development differs from that of developed economies. And the article attempts to analyze from three dimensions: system, culture, and practitioners\u2019 mental health. The results show that these three dimensions will have a significant impact on franchising in China, and it is necessary to focus on these three aspects when formulating policies and implementing them in the future. In particular, the psychological health of practitioners is closely related to the future sustainable development of franchising operations to a certain extent. Therefore, it is necessary to conduct necessary intervention and guidance on the psychological health of practitioners to ensure that they can maintain a good psychological state to carry out their daily work. Franchising in China has shown great advantages and taken a crucial role in the rapid growth of the Chinese economy. While few scholars have explained the unique practices of franchising in the Chinese context. Franchising has become a significant business model in China after reform and opening up as in Western countries.Subjects and Methods: This article is organized as follows. First provide a brief review of the franchising around the world and then discuss the trends of franchising development in China. With a comparison of law and regulation, economy, and culture, the institutional and cultural differences in China are analysed. After that, this article summarize the unique characteristics of franchising in China and discuss how franchising works differently in China. Finally, the authors identify special issues and shed new light on the existing franchising literature in the emerging business environment.Results: Present the growth of franchising in China as a business model relative to the West. The cultural and institutional characteristics compared with the West make franchising in China different. Successful franchises in China have less reliance on contracts and more on trust and personal ties between franchisor and franchisee.Conclusions: In general, franchising will become increasingly accepted and encouraged because the arrival of franchises contributes to the growth of the economy in China. Since the first pilot franchise regulations were adopted in the late 1990s, domestic franchises have taken off with the growing purchasing power gained by Chinese consumers. In addition, universal cultural trends allow many international franchises to enter China. As in Western economies, both international and domestic franchise chains have become a significant business model in China and have grown substantially over the past twenty years. Although this competitive business model has received a surge of scholarly interests, research in this area has sought to provide a franchising model from the Western perspective. The public\u2019s understanding of franchising in China is low. This research focuses on the differences in franchising in China. Franchising in China has developed specific characteristics compared with the West, which is by driven institutional and cultural differences, as well as China\u2019s level of development. Built on trust, a franchisor-franchisee relationship has the requisite guanxi for business success in China. The implications can be applied to some Asia countries with similar cultural backgrounds. Future studies are encouraged to compare the development of franchising in emerging business landscapes, which accounts for most of the world\u2019s population and over half of the world\u2019s natural resources.Soft Science Project: Challenges and Countermeasures for the Digital Transformation of Traditional Industries in Henan Province under the \u201cDouble Carbon\u201d Goal (232400410201).a, Min ZhangaXiang Lia School of Education, Huaibei Normal University, Huaibei 235000, Anhui, China.Background: The emotion of gratitude reflects the level of individual mental health by affecting moral judgment. This study aims to investigate the impact of gratitude on college students\u2019 moral judgment ability.Subjects and Methods: In experiment 1, the psychological experimental programming software E-prime was used to compile moral word judgment task for pre-post test. Experiment 2 adopted a 2\u2009\u00d7\u20092\u00d72 experiment design between subjects, which revealed the influence mechanism of gratitude on college students\u2019 moral judgment by examining three variables: gender, gratitude degree and whether one word is moral word or not.Results: It was found that: (1) the short film used in the study could effectively induce the subjects\u2019 gratitude ; (2) College students displayed significant gender difference in moral word judgment task ; (3) College students\u2019 gratitude degree exerted significantly different impact on moral word judgment task ; (4) College students\u2019 gender and gratitude degree exerted significant interaction effect on moral word judgment task . Conclusions: Gratitude has a significant impact on college students\u2019 moral judgment. High gratitude individuals have more active cognitive processing, resulting in greatly improved quality in thinking and decision-making. Also, such individuals have higher moral judgment level, showing greater positivity than low gratitude individuals in moral judgment.The paper was supported by Study on Mental Health Promotion Model for Special Education Teachers Based on Mental Resilience (Project No.: 23500024).a, Lin Kuanga, Tingyu Xua, Wei Lua, Jialing ShiaYangfan Wua Hunan University of Chinese Medicine, Changsha, Hunan, ChinaBackground: Genital herpes (GH) is a common sexually transmitted disease mainly caused by herpes simplex virus type 2 (HSV-2), which lurks innerve roots and causes recurrent disease. Currently, there is no cure for GH, but nucleoside antiviral drug can inhibit viral replication,and acyclovir is one of the drugs commonly used in clinic to improve its symptoms.Subjects and Methods: The effect of acyclovir on HSV-2 infected human neuroblastoma cells (SH-SY5Y) was studied by label-free quantitative proteomics in order to explore the action mechanism of acyclovir on HSV-2 virus lurking in neurons. In this study, we treated SH-SY5Y cells infected with HSV-2 virus with acyclovir drug-containing serum. After modeling, extracted cell proteins, detected protein expression differences using label-free quantitative proteomics, and analyzed the GO functional enrichment, domain enrichment and transcription factor annotation of these differential proteins.Results: The results showed that 1011 proteins were involved in the intervention of acyclovir against HSV-2 virus lurking in neurons, of which 513 were up-regulated and 498 were down-regulated. These proteins were mainly concentrated in biological processes, cell composition and molecular function. The results of GO functional enrichment analysis, domain enrichment analysis and transcription factor analysis of differential proteins showed that, the potential targets of acyclovir are mainly concentrated in the nucleus and mitochondria, acyclovir mainly acted on mitochondrial carrier domain, ATPase conserved sites and annexin sites, and acyclovir mainly interfered with HMG-box, zf-C2H2, CSD, Homeobox and other transcription factors to inhibit the replication of HSV-2 virus.Conclusions: Acyclovir interferes with the replication of HSV-2 virus in cells by affecting the catabolic process of nuclear transcription mRNA, mitochondrial respiratory function and ATPase activity.This study was supported by grants from Project supported by the National Natural Science Foundation of China (Grant No.82174391); Chinese Medicine Scientific Research Foundation of Hunan (Grant No.2021058).aYulan Zhoua Academy of Fine Arts, Sichuan Minzu College, Kangding, Sichuan 626001, China.Background: Tibetan embroidery of Relieving anxiety and improving mental health is facing the inheritance crisis such as the fault of the inheritance population, the increase of Tibetan embroidery substitutes and the decrease of public acceptance. Promoting the industrialization development of Tibetan embroidery skills with the integration of culture and tourism; drive the personalized development of Tibetan embroidery skills with innovative ideas; drive the intensive development of Tibetan embroidery skills with capable craftsmen; promote the socialized development of Tibetan embroidery skills with targeted poverty alleviation.Subjects and Methods: Conduct empirical research in Tibet-related areas.Results: How Tibetan embroidery can help poverty alleviation and rural revitalization under the consciousness of building a Chinese national community.Conclusions: Carefully summarize and promote the experience of poverty alleviation, and continue to consolidate the stable employment of the helpers; fully implement the revitalization of Tibetan embroidery, focusing on strengthening the integrated development of Tibetan embroidery tourism; focus on building the development of the whole industry chain of Tibetan embroidery, and promote the revitalization of Tibetan embroidery industry to empower rural areas; adhere to innovation to lead the living inheritance of Tibetan embroidery and expand the market consumption space of Tibetan embroidery products; guide college students with relevant ambitions to tap the cultural and creative resources of Tibetan embroidery, highlight the advantages of manual creation, and finally realize that college students can promote employment through entrepreneurship and alleviate the pressure of social employment. Tibetan embroidery plays an increasingly important role and shoulders the mission and responsibility from poverty alleviation to rural revitalization. The internal logical mechanism between the two requires Tibetan embroidery to take the initiative to take advantage of the development of the rural revitalization strategy. It is necessary to strengthen the inheritance education of Tibetan embroidery, enhance the consciousness and self-confidence consciousness of the inheritance subjectivity, reshape the self-respect and self-confidence of its own historical and cultural characteristics, cultivate the endogenous motivation of rural revitalization, and awaken the road consciousness and road self-confidence of Tibetan compatriots to conspire with their own national characteristics. We should also adhere to innovative development, live inheritance, fully tap the profound cultural heritage and unique capitalization transformation advantages of Tibetan embroidery, enhance the potential industrial development ability of Tibetan embroidery in various forms, and promote the integration of Tibetan embroidery into modern life on the basis of maintaining the national style and local characteristics of the original process.This work was supported by 2021-2023 Sichuan Higher Education Talent Training Quality and Teaching Reform Project: Theoretical and Practical Research on Teaching Reform of Building the Chinese National Community Consciousness Education in Universities in Ethnic Areas (JG2021-1417); National Ethnic Affairs Commission\u2019s Teaching Reform Project \u201cResearch on Building Chinese National Community Consciousness into the Ideological and Political Curriculum Construction of Ganzi Universities\u201d (ZL21064);Sichuan Minzu College 2021-2023 Higher Education Talents Training Quality and Teaching Reform Project \u2018 Research and Practice of Diversified and Innovative Talents Training of Tibetan Folk Crafts\u2019 (JG202111).a, Feng Luob, Zhe WangbWei Shanga School of Management, Chengdu University of Information Technology, No.24 Block 1, Xuefu Road, Chengdu, China, b School of Economics and Management, Sichuan Tourism University, No.459, Hongling Road, Chengdu, ChinaBackground: As a new form of team joint, cross-platform service emerges at the moment and gets good feedback from the market. In recent years, performance appraisal as an environmental cue has been widely concerned by the academic community. However, the impact of performance appraisal on cross-platform services is unknown, especially given the psychological awareness and stress of employees, which is undoubtedly an urgent issue for enterprises to understand.Subjects and Methods: Based on the two-factor theory, this paper explores the influence of performance appraisal on cross-platform service preference and its internal mechanism, and explores the moderating effects of different types of performance appraisal in this process. Through 4 experiments, experiment 1 is a field experiment between single factor groups, experiment 2 is a laboratory experiment between single factor groups, experiment 3 is an online questionnaire between single factor groups, experiment 4 is a 2\u2009\u00d7\u20092 field experiment, the research method of combining field experiment and laboratory experiment is adopted, and the research design supported by actual service evaluation and questionnaire measurement is adopted. The variance analysis and bootstrap method were used to examine the internal mechanism of performance appraisal\u2019s preference for cross-platform services through psychological stress and anxiety.Results: The results show that experiment 1 verifies that compared with non-performance appraisal state, employees in performance appraisal state show lower preference for cross-platform services. In experiment 2, other competitive explanation mechanisms were excluded and it was again verified that, compared with non-performance appraisal state, employees were less likely to prefer cross-platform services in appraisal. Experiment 3 verifies that the two-factor theory plays a psychological mediating role in the relationship between performance appraisal and cross-platform service preference, and clarifies the internal two-factor psychological cognition mechanism of this relationship. In experiment 4, the experimental situation was changed, that is, the performance appraisal level was divided into assessment and non-assessment, and the assessment type was divided into individual assessment group and class assessment group, which verified the rationality of the two-factor theory as the internal mechanism of performance appraisal for cross-platform service preference. At the same time, it is found that the performance appraisal type has a moderating effect on the influence of performance appraisal on cross-platform service preference and the mediating effect of the two-factor theory.Conclusions: The research results theoretically expand the relevant theoretical research on job assessment, employee psychology, service support and manufacturer association. At the same time, in practice, it not only provides feasible suggestions for the work arrangement and psychological pressure relief of employees in manufacturing enterprises, but also provides valuable suggestions for service providers to carry out manufacturer association and cross-platform service recommendation. Therefore, this paper has important theoretical contribution and practical significance.a,b,c, Nan Kanga,b,c, Wenjuan Yana,b,cYuxia Zhua People\u2019s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia 750001, China, b Ningxia Eye Hospital, Yinchuan, Ningxia 750001, China, c The First Affiliated Hospital of Northwest University for Nationalities, Yinchuan, Ningxia 750001, China.Background: To investigate the effect of Child-Pugh grading standard in the surgical treatment of liver cirrhosis with gallstones in elderly patients.Subjects and Methods: This retrospective analysis selected 68 elderly patients of liver cirrhosis with gallstones treated in Ningnan Hospital from February 2021 to February 2022. According to Child-Pugh grading criteria and the individual liver reserve function, all patients were divided into three grades, grade A, B and C. Then, patients were classified into different groups according to varies surgical methods. 33 patients were in the first group which following laparoscopic cholecystectomy (named LC), 28 patients were in the second group which following traditional laparotomy for cholecystectomy (named OC), while 7 cases were in third group for mixed ways (named LC + OC). All the patients were confirmed by CT and MR. The effectiveness results of 68 elderly patients with cirrhosis complicated with gallstones after different surgical treatment were analyzed.Results: Child-Pugh grading on a scale of 5 to 7 is the safest range for the three types of surgery. When the score is higher than 10, it implicates a great risk, and surgical treatment should be carefully selected according to the patient\u2019s condition in these cases. The 33 patients in LC group recovered quickly and were discharged from hospital on the 5th day after surgery. Among the 28 patients in the OC group, the condition recovery was slower than that in the LC group, and 4 patients had mild complications and extended hospitalization for 3 days. Among the 7 patients in LC+OC group, due to their serious condition, 1 patient had complications during the recovery period and was hospitalized for 5 days longer. Another 1 patient\u2019s condition deteriorated and died 2 days after surgery in LC+OC group. The study also conducted a followed up process, 67 patients were discharged and followed up, 11 of which were re-hospitalized.Conclusions: Child-Pugh grading criteria can help doctors effectively evaluate the liver reserve function of patients, and has a guiding effect on the rehabilitation of elderly patients with liver cirrhosis complicated with gallstone after surgical treatment. Our research finds that Child-Pugh grading can reduce the risk of surgery, shorten the length of hospitalization, reduce the re-hospitalization rate, prevent complications and improve the quality of life of the patients.This work was supported by a project grant from Major R & D Plan Project of Ningxia Hui Autonomous Region (Grant No. 2017 BY 036)a, Yiru YangaDeyu Chena School of Accounting, Guangzhou College of Commerce, Guangzhou 511363, China.Background: With the rapid upgrading of the industrial structure in the Pearl River Delta (PRD), the competition in the manufacturing market is becoming more and more fierce? It not only causes the psychological anxiety of the managers and employees of the enterprises in the Pearl River Delta, but also directly affects the economic benefits of the enterprises and their sustainable development in the future. At present, an important obstacle to the construction of a harmonious socialist society is the pressure and psychological anxiety of employees. The manufacturing industry in the Pearl River Delta region is developed with a large number of employees. Due to the employees\u2019 educational background, skills and income being in a weak position, they bear more pressure and psychological anxiety than other organizations, reduce corporate profits, while bringing serious family and social problems to society.Subjects and Methods: This paper discusses the current situation and causes of cost management of manufacturing enterprises in the Pearl River Delta, taking kub pen company as an example, this paper analyzes the psychological anxiety of enterprise cost managers in the Pearl River Delta by means of activity-based costing (ABC), which includes the lack of cost awareness, the lack of cost management, the lack of material management and the lack of basic work.Results: The various problems in cost management of manufacturing industry in the Pearl River Delta (PRD) have resulted in the decline of the profits of manufacturing enterprises. The manufacturing enterprise has no core competitive power, and the low-cost comparative advantage is losing, the crisis is not only the production crisis, but the survival crisis, which also causes the enterprise manager\u2019s psychological pressure to be extremely big, even part of the enterprise management because can not stand the pressure to choose to jump off the building to end life. To solve these problems, we must make a reasonable response strategy to enhance the sustained competitiveness in the whole market economy.Conclusions: According to the psychological anxiety of enterprise cost managers in the Pearl River Delta, the author puts forward some countermeasures: strengthening the management of activity-based costing, establishing the management mechanism of responsibility cost, improving the quality of basic data; Develop preventive measures and strict cost accounting. By establishing a scientific and effective cost management system, the manufacturing enterprises in the Pearl River Delta can alleviate the psychological anxiety of the managers and employees, and improve the economic benefits of the manufacturing industry, thus enhance the competitiveness of enterprises in the Pearl River Delta in the regional market.a, Lili Zhoub, Xin XucKaige Zhoua New Economic Reseach Institute, Ningbo University of Finance&Economics, Ningbo, Zhejiang 315175, China, b Nanchang Institute of Technology, Nanchang 330511, China, c Library of Huaiyin Normal University, Huai\u2019an, Jiangsu, 223001, China.Background: Emergency medical supplies are a necessary material guarantee for dealing with public health emergencies. Good emergency medical supplies inventory management is an important part of emergency medical management mechanism, which will provide strong support for effective response to public health emergencies.Subjects and Methods: Supply chain management of emergency medical supplies has become an important factor to reduce sudden disasters and emergency medical accidents. The optimization of medical supplies inventory can improve the level of emergency medical treatment, control the spread of infectious diseases and reduce the losses caused by infectious diseases. Medical big data shows that the formulation of emergency medical supplies inventory strategy is affected by demand, price and other factors. This paper proposes and analyzes the dynamics of a supply chain system under inventory and price factors with the feature of piecewise linearity. This switched linear model composed of four subsystems extends the classic inventory models under inventory. Based on properties of switched model, some analytical stability results are derived, and the global dynamic behavior is theoretically examined. Simulation experiments are designed to show the stability results and observe other nonlinear phenomena. It is illustrated that the inventory-dependent demand function and the forecasting inventory rate combine to bring about the stability result or arise more complicated nonlinear dynamics, such as chaotic and periodic fluctuations of inventory and order.Results: These results are suitable for understand the dynamic complexities of supply chain system and present the direction for choosing the decision parameters to improve overall performance. Some illustrative examples demonstrate the effectiveness of the obtained scheme.Conclusions: Efficient inventory management based on medical big data can flexibly respond to the rapidly changing demand of medical supplies in an emergency epidemic, so as to improve the accuracy and timeliness of medical assistance, promote the early control of the emergency, shorten the spread time of the emergency, and reduce the harm caused by the emergency to the society. It has positive significance for the rapid elimination of major emergency after the outbreak, and is worthy of promotion.This work was supported by a project grant from the 2021 Annual Project of \u201cthe Chinese Society for Technical and Vocational Education\u201d & \u201cNew-Era TVET Institute of China\u201d, Historical Mission and responsibility of vocational education in the construction of Healthy China (Grant No.SZ21A003).a, Yuanhui CuiaGuangwei Zhanga School of Information Science and Engineering, Dalian Polytechnic University, Dalian, Liaoning 116034, China.Background: To explore methods of body fat measurement and improve the accuracy of body fat measurement. It is of great significance for body shape management, monitoring human health, and preventing diseases such as hypertension and hyperglycemia.Subjects and Methods: An impedance measurement system was designed based on a human body impedance measurement model. Sixty college students were randomly selected to measure their body fat ratio, body impedance, height, weight, age, and gender to form 60 sets of data sets. Use MATLAB software to build an extremum learning body fat prediction model based on tent mapping and particle swarm optimization (TPSO-ELM). The traditional extremum learning machine (ELM) model and standard particle swarm optimization extremum learning machine (PSO-ELM) model were set as control experimental groups. Then select 50 sets of data from 60 sets of data as the training dataset, and the remaining 10 sets of data as the test dataset.Results: Observe the extremum learning body fat prediction model based on tent mapping and particle swarm optimization and the broken line chart of the body fat prediction results of the control group. The predicted results of the extremum learning body fat prediction model based on tent mapping and particle swarm optimization have the best fit with the true value curve. Calculate the absolute error of the extremum learning body fat prediction model based on tent mapping and particle swarm optimization and the control group. Then calculate the average of the absolute errors of 10 sets of data. The average absolute error of the predicted value of the extremum learning body fat prediction model based on tent mapping and particle swarm optimization was 0.0085, compared to 0.22 and 0.023 in the control group. Therefore, the body fat prediction algorithm of extreme learning machine based on particle swarm algorithm of tent mapping proposed in this paper improves the accuracy of body fat measurement.Conclusions: This paper proposes an extremum learning body fat prediction model based on tent mapping and particle swarm optimization. Human impedance, height, age, weight, and gender were used as input parameters for the body fat prediction model. The simulation experiment proves that the new body fat prediction model proposed in this paper improves the accuracy and efficiency of body fat prediction. Body mass index (BMI) is currently the standard recommended by the World Health Organization (WHO) to evaluate body fat and lean. The experimental data were validated according to the obesity and obesity standards established by the World Health Organization, and the results showed good consistency. The fitness prediction algorithm proposed in this paper improves the accuracy of body fat prediction to a new level. The predicted body fat by this method is more useful in monitoring human health and effectively preventing diseases.aGuangli Longa School of Physics and Telecommunication Engineering, Shaanxi University of Tecnology, Hanzhong City 723001, China.Background: The purpose of health management is to prevent and control the occurrence and development of diseases, to reduce the medical cost and to improve the quality of life, and health risk factors associated with their lifestyle, through health information collection, health testing, health assessment, personalized monitoring management programs, health interventions and other means to continue to improve the process and methods. The problem of food safety is a key issue concerning human health, the most important part of which is the detection of food spoilage, spoilage and deterioration of food, regardless of sensory or physical and chemical properties, it is very important to detect the level of food spoilage quickly and accurately.Subjects and Methods: In view of the current problems is people\u2019s concern about the relationship between food and human health, as well as the harmful effects of rotten food on the human body, etc., a kind of food spoilage detection circuit based on health management is designed, The circuit is based on STC12C5A60S2 microcontroller using resistance detection network and moisture sensors to collect data,DHT11 temperature sensor is used to measure the temperature, test results are displayed by the LCD12864 and broadcast by the voice broadcast module SYN6288, and several kinds of normal food standard values are stored in the microprocessor, kinds of food is replaced by pressing button.Results: The experiment proved that the circuit can realized the normal measurement of food. Measurement time, food resistance and moisture as well as the current room temperature can be displayed on the display, the test results whether the food consumed can be broadcasted.Conclusions: Health management is the use of information and medical technology, a complete, thorough and personalized service procedures are built on health care, medical science, its aim is to help healthy people and sub-healthy people to establish an orderly and healthy life style, reduce risk state and keep away from disease by maintaining and promoting health, through the arrangement of medical services, as soon as possible to restore health. In this paper, the mechanism of food spoilage was studied. The resistance and moisture content of food were detected by using water detection circuit and resistance detection network, and compared with the standard value of fresh food, to judge the extent of spoilage of food spoilage, to make food edible or not. Spoilage and deterioration of food can cause poisoning or potential harm to the human body. People with mild poisoning often have symptoms of acute gastroenteritis, such as vomiting, diarrhea or abdominal pain, fever, etc., severe poisoning in the respiratory, nervous, circulatory and other system symptoms, a slight delay may appear life-threatening. Therefore, food spoilage and deterioration has a great impact on human health, detection of food spoilage and deterioration of human health management is of great significance.This work was supported by Ministry of Education industry-university Cooperation Project (project number: 220604307070644), and this paper is supported by the college-level first-class specialty Communication Engineering Construction Project of in Shaanxi University of Technology.a, Xinmeng KebSha Lia Department of Foreign Language, Zhengzhou University of Science and Technology, Zhengzhou, Henan 450064, China, b Office of Academic Affairs, Zhengzhou Railway Vocational and Technical College, Zhengzhou, Henan 450064, China.Objective: In recent years, in college oral English teaching, it has been found that more and more students are feeling anxious and afraid of opening their mouth to speak English, which hinders the improvement of their oral communicative ability. This is not in line with the policy of cultivating application-oriented talents. Therefore, this paper aims to analyze the reasons that lead to students\u2019 anxiety in oral English class and then proposes strategies that could help to adjust students\u2019 anxiety. It is hoped that teachers could get some suggestions to ease students\u2019 anxiety and help them maintain a healthy mentality in oral English learning, which is conducive to cultivate students\u2019 communicative ability to meet the standards of application-oriented talents cultivation.Method: This paper mainly adopts qualitative analysis based on the analysis of previous literature. In order to effectively solve the problem of students\u2019 anxiety in oral English learning, this paper first makes a brief summary of anxiety from psychological perspective, and then analyzes in depth the important impact of anxiety on college students\u2019 oral English learning. Then, the main subjective and objective factors influencing the degree of students\u2019 anxiety are analyzed. Based on the problems found in previous section, effective strategies to ease students\u2019 anxiety are put forward.Results: It is pointed out in this paper that anxiety has an negative influence on students\u2019 oral English learning. Then the subjective and objective factors contributing to anxiety are analyzed. The subjective factors are ideal level, learning motivation and learning ability while the objective factors are teachers\u2019 teaching ability and region differences. At last, strategies to help students reduce anxiety in oral English learning are proposed. The main strategies are building a good classroom atmosphere for oral English teaching, organizing group activities appropriately, timely guiding students to correct oral mistakes, scientifically designing classroom questioning, enriching language and culture input.Conclusions: Based on the analysis of the negative impact of anxiety on oral English learning and its major influencing factors from both the subjective and objective perspective, the strategies proposed in this paper are aimed to help students adjust their anxiety, overcome the psychological stress during the learning process so as to fundamentally promote students\u2019 oral English learning efficiency and effect, exercise and develop their oral expression and English application skills, which can ensure the effect and quality of oral English teaching to truly meet the needs for oral English professionals for the development of the society in the context of globalization.a, Weirong Wanga, Wen Qiaoa, Xinyi LiaTing Zhanga Department of Public Policy and Management, Northwestern Polytechnical University, Xi\u2019an, Shaanxi 710072, China.Background: The provincial comprehensive medical reform is an important pilot policy to improve the efficiency of China\u2019s basic medical and health services. It is of great theoretical and practical significance to systematically explore the impact of policy implementation on optimizing resource allocation and improving the service efficiency of primary medical and health institutions.Subjects and Methods: Based on this, we first adopted the super-efficient DEA model to evaluate the medical service efficiency in primary healthcare institutions in China from 2010 to 2019, then analyzed the effect and the influencing factors of policy implementation in the first pilot areas through the synthetic control method.Results: 1. the service efficiency of primary healthcare institutions in China ranges from 1.061 to 1.01, the average values of the efficiency in the eastern, central and western regions were 1.259, 0.835 and 0.962 in that order. The eastern region shows an inverted \u201cN\u201d shape, the central region shows a \u201cU\u201d-shaped cycle, and the western region has shown a fluctuating downward trend. 2. In the pilot area, the gap between Jiangsu and synthetic Jiangsu is widening after the implementation of the policy, it shows that the provincial healthcare reform pilot policy effect in Jiangsu is obvious. The probability of the ineffectiveness of that policy is less than 10%. The placebo test was not effective in the pilot areas other than Jiangsu.Conclusions: 1. The service efficiency of grass-roots medical and health institutions in China presents an Eastern > Western > Central trend. The service efficiency shows a decline in different degrees, with a large gap between provinces. 2. Only Jiangsu province has an apparent positive policy effect among the first batch of pilot regions. After the policy implementation, the changing trends of the Anhui, Fujian and Qinghai provinces cannot reflect the effect of the policy. To improve the efficiency of medical and health institutions in China, this paper puts forward some suggestions in terms of strengthening the structural investment of medical resources in the central and western regions and promoting the implementation of a graded diagnosis and treatment system.This work was supported by a project grant from General Project of National Social Science Fundation (Grant No.20BJY076).a,b, Yufei Qiua, Sitong Jia, Jianwu Chenb, Lu Yuc, Shengnan Oud, Xiaoya XiedMingwei Xua Department of Safety Engineering, School of Safety Engineering,Beijing Institute of Petrochemical Technology, Beijing 102617, China, b China Academy of Safety Science and Technology Beijing 100083, China, c Department of Safety Engineering, School of Traffic and Transportation Engineering, Dalian Jiaotong University Dalian 116021, China, d School of Civil and Resource Engineering, University of Science and Technology Beijing 100083, China.Background: In modern workplaces, noise pollution has been identified as a significant risk factor that poses a threat to the safety productivity and workers\u2019 occupational health. However, the impact of sound level and frequency on workers\u2019 attention and behavior in confined spaces is not fully understood. Therefore, this study aimed to investigate the effects of sound level and frequency on attention concentration ability, reaction time, and discrimination time in a confined space environment.Subjects and Methods: A human experiment was conducted with 13 participants. The experiment design included three sound levels and three frequency levels . Participants were exposed to different sound levels and frequencies in a confined space to investigate the impact of sound level and frequency on their attention concentration ability, reaction time, and discrimination time.Results: The study results showed that sound level and frequency had different mechanisms of influence on attention. Sound level had a more significant impact on workers\u2019 attention concentrating ability, indicating that the greater the sound level, the less attention was paid to safety. On the other hand, frequency primarily affected attention concentration level, with intermediate frequency noise significantly reducing the attention concentration level. When the sound level was 70 dB or the frequency was 1000 Hz, the simple reaction time and discrimination time increased significantly, and the concentration ability was the weakest. When the sound level was 60 dB or the frequency was 100 Hz, the attention level of the subjects was the lowest.Conclusions: This study\u2019s findings demonstrate that noise pollution in confined spaces can have detrimental effects on workers\u2019 attention concentration, reaction time, and discrimination time. Sound level and frequency were found to have different impacts on attention, with sound level being more significant in reducing attention concentration ability. These findings highlight the need to control noise pollution in confined spaces and to consider both sound level and frequency when developing noise control strategies to enhance occupational safety and efficiency. Therefore, appropriate noise control measures must be implemented to minimize the risk of noise exposure and protect workers\u2019 health and well-being.This work was supported by a project grant from Beijing Municipal Commission of Education (Grant No. KM202310017002) and National Natural Science Foundation of China (Grant No. 5230041812).a, Farzaneh Haratyana, Fei JiangbQingzhao Lia School of Foreign Languages, Suzhou University, Suzhou, Anhui, 234000, China, b School of Information Engineering, Suzhou University, Suzhou, Anhui, 234000, China.Background: Emotional regulation refers to a psychological process in which individuals change the intensity, quality, and duration of emotions through self-regulation in an environment that stimulates emotions. Emotional regulation is closely related to nonverbal communication, as nonverbal communication is often the main way to express emotions. In nonverbal communication, individuals can convey their emotional state by adjusting their own facial expressions, gestures, and sounds, while also interpreting others\u2019 nonverbal signals to obtain information and infer others\u2019 emotional state. Both verbal and nonverbal communications are involved in the teaching and learning activities. Verbal behavior is the main channel through which teachers impart knowledge to students, while nonverbal behavior is the main channel through which teachers convey their emotions, simplify teaching instructions, activate the student\u2019s learning interest and enhance teaching effectiveness.Subjects and Methods: This paper reviewed the findings of twenty recently related research inside and outside Chinese contexts and discussed how they converged or diverged in their achieved results about this concept of nonverbal communication in pre covid and post covid era. This paper also included the way it has been defined, practiced, and evaluated considering various variables that interact and affect nonverbal communication.Results: The changes in emotional regulation and nonverbal communication pre covid and post covid are mainly reflected in the attitudes of positive expression, negative emotions and moderate expression. There are close links between the nonverbal signals and the emotional expressions, and the intention of the sender of the information can be revealed frequently from non-verbal cues. Both students and teachers can benefit from practicing nonverbal communication skills.Conclusions: The changes in emotional regulation in nonverbal communication before and after the epidemic reflect people\u2019s psychological state and coping strategies in the epidemic environment. In nonverbal communication, people can communicate and obtain information by adjusting their emotions, and they can also infer the emotional state of others by interpreting their nonverbal signals. This paper maintains how students\u2019 attention, initiative and participation beside other psychological mechanisms in education can be influenced and how to focus on emotional regulation and nonverbal communication strategies to promote both students and teachers\u2019 emotional health. Effective non-verbal communication skills have a positive effect on both teaching and learning. This paper is beneficial to teacher trainers to enhance the effectiveness of college English teaching.This work was supported by a project grant from Anhui Provincial Department of Education, (Grant No. 2020jyxm2196) and a project grant from Anhui University Humanities and Social Sciences Research Project (Grant No. SK2021A0714).a, Xiao Tanb, Siyang Yub, Xilong QubZhecong Wanga Software Academy, Changsha Commerce & Tourism College, Changsha, Hunan 410116, China, b School of Information Technology & Management, Hunan University of Finance and Economics, Changsha, Hunan 410205, China.Background: Environmental monitoring plays a crucial role in medical facilities, impacting patient outcomes and staff safety. Manual monitoring methods are time-consuming and prone to errors. However, with advancements in sensor technology, ZigBee communication protocols, and mobile devices, intelligent environmental monitoring systems offer efficient and accurate real-time monitoring. In hospitals, monitoring temperature, humidity, air quality, and other environmental factors is essential for maintaining a sterile and safe environment for both patients and healthcare providers. Traditional manual detection and recording methods are labor-intensive and error prone. Intelligent environmental monitoring systems, on the other hand, offer several benefits that can enhance the quality of care in medical facilities.Subjects and Methods: Wireless communication between sensing devices, using ZigBee technology, and a central monitoring system allows easy deployment and scalability. Sensing devices placed throughout the hospital monitor critical areas such as operating rooms, patient rooms, and laboratories. The data collected from these sensors transmits quickly to the central monitoring system, alerting healthcare providers if there are any deviations from the desired environmental conditions. The integration of mobile devices such as smartphones or tablets enables remote access to the monitoring system, facilitating real-time monitoring of different areas of the hospital. Healthcare providers can monitor environmental conditions, even when they are not physically present in the hospital, ensuring timely intervention if required.Results: Moreover, intelligent environmental monitoring systems have expanded beyond temperature and humidity control. They can also monitor gas levels, radiation, and dust particles to ensure a safe environment for patients and healthcare providers. Additionally, they can monitor power consumption, contributing to energy-efficient management in medical facilities. Considering the complex environment of hospital storage, we attach the monitoring system to a mobile tool (such as a mobile car), which can make the detection method of the entire system more flexible, with a wider detection radius, and enable the system to be used for temperature and humidity monitoring in these diverse environments.Conclusions: When ZigBee technology, sensing technology, and mobile devices are combined to form a temperature and humidity monitoring system, it has the advantages of low cost, rapid installation, and high availability compared to common solutions in the industry. As technology continues to advance, further research and development in environmental monitoring systems will lead to more effective applications in modern medical treatment.This research was supported by Scientific Research Key Project of Hunan Education Department[21A0592], Education Reform Project of Hunan Province[HNJG-2021-1378], Hunan Natural Science Foundation Project (2023)[Research on Resource Scheduling Strategy for Energy Efficiency Optimization in Mobile Cloud Computing].aQiang Zhoua School of Finance and Economics Management, Sichuan University of Arts and Sciences, Dazhou, 635002, China.Background: In the implementation process of the rural revitalization strategy in the Sichuan Shaanxi Revolutionary Old Area, due to the relative uncertainty of policy responses from multiple parties, this article takes the alleviation of psychological anxiety in the process of changing the livelihood of farmers in the revolutionary old area during the government governance process as one of the research subjects. In analyzing the effectiveness of the rural revitalization strategy with the participation of social capital, the strategic evolution game between the government, social capital, and farmers is taken as the research goal, Defining farmers in old areas as units that examine the effectiveness of social capital and government policies is in line with the implementation units and fields of the current rural revitalization strategy. Reflect the stability, continuity, and balance of interests of all parties in the long-term dynamic strategy process.Subjects and Methods: Evolutionary game theory was used to study the dynamic process of governance, select a mechanism with dynamic incentive factors, and combine the social capital participation in the process of rural revitalization with the measures taken by villagers to alleviate life anxiety and psychological counseling in the process of rural revitalization, reflecting the relative stability and long-term nature of the government decision-making process and the process of people\u2019s livelihood.Result: As the government actively promotes rural revitalization and the development of red tourism resources in revolutionary old areas, and improves the effectiveness of incentive subsidies, the probability of social capital and farmers choosing cooperation strategies in the short term increases. However, due to the long-term existence of subsidies, incentive subsidy policies can only stimulate cooperation between the two in a short period of time. In addition, with the increase in subsidy amounts, the convergence speed actively promoted by the government due to incentive subsidy expenditures has also slowed down. Similarly, numerical simulations can simulate the impact of punishment costs on the level of psychological anxiety during changes in social capital, farmer behavior, and livelihood status. Overall, in regulating non cooperative behavior between social capital and farmers, the increase in punishment costs is more effective than incentives, and all three are more sensitive to incentive returns. Thus, in the process of promoting rural revitalization policies, the anxiety state of farmers\u2019 livelihood changes caused by policy promotion has been effectively improved.Conclusion: The stability of the evolutionary game model established at the governance level of rural revitalization strategy will directly have a significant impact on the implementation of rural revitalization policies. And it plays a certain helping role in improving the livelihood status of regional farmers and alleviating psychological anxiety. Therefore, this article has certain theoretical innovation significance and practical value. The countermeasures derived from the tripartite evolutionary game model have certain guiding significance for policy and theoretical decision-making departments.a, Zitong Suna, Xiwen Xua, Ling Sub, Yuting Lia, Xiuran Wanga, Wei HuaMei Yanga College of Life Sciences, Jilin Agricultural University, Changchun, Jilin 130118, China, b Engineering Research Center of Edible and Medicinal Fungi Ministry of Education, Jilin Agricultural University, Changchun, Jilin 130118, ChinaObjective: enzymatic hydrolysis peptide of antler plate is an ossified substance formed in the spring of the second year after deer antler is cut off or sawed. Modern pharmacological research shows that anlter plate has many pharmacological activities. Protein and peptides account for about 40% of the total components of antler plate. They are rich in amino acids, including essential amino acids. According to the content and types of amino acids, it is speculated that the bioactive protein or polypeptide contained in the enzymatic hydrolysis peptide of antler plate of sika deer-red deer hybrid deer has immune activity. The active peptide is a protein peptide segment with biological function after protein is hydrolyzed by protease. The peptide segment not only has certain biological activity, but also retains its original biological activity.Patients and Methods: In this study, the enzymatic hydrolysis peptide of antler plate of sika deer-red deer hybrid was used as raw material. The enzymatic hydrolysis peptide of enzymatic hydrolysis peptide of antler plate was obtained by enzymatic hydrolysis technology, and the immune activity of the enzymatic hydrolysis peptide was evaluated by its influence on the immune function of mice. Firstly, the total protein was extracted from the enzymatic hydrolysis peptide of antler plate of sika deer-red deer hybrid deer by alkali extraction and acid precipitation, and the effects of several common proteases on the total proteolytic efficiency and immune activity of enzymatic hydrolysis peptide of antler plate were investigated, so as to obtain the enzymatic hydrolysis peptides with the best immune activity. The gastric administration doses of enzymatic hydrolysis peptides of mice in each group were 100\u2005mg/kg in low dose, 200\u2005mg/kg in medium dose and 400\u2005mg/kg in high dose respectively for 14 days. Then cyclophosphamide was used to induce mice to establish immunosuppressed mouse model. Finally, the changes of body weight, immune organ index, proliferation ability of mouse spleen lymphocytes and phagocytic activity of peritoneal macrophages were detected, and the changes of cytokine and immunoglobulin expression levels in serum were detected by ELISA sandwich method.Results: The Results showed that the proliferation ability of RAW264.7 macrophages treated with trypsin was the best, so trypsin was selected to hydrolyze the total protein of anlter plate. The enzymatic hydrolysis conditions were as follows: temperature 40\u2103, time 3h, E/S 3%, pH 7 and enzyme dosage 3000\u2005U/g. The immune activity experiment showed that compared with the model group, the experimental group could significantly increase the weight of mice, improve the index of immune organs, enhance the proliferation of spleen lymphocytes and the phagocytosis of peritoneal macrophages, and also improve the expression levels of serum cytokines and immunoglobulins .Conclusions: enzymatic hydrolysis peptide of antler plate has obvious immunoregulation effect on immunosuppressed mice, and effectively improves the suppressed humoral immune function of mice.This study was supported by Jilin Science and Technology Development Plan Project (Nos.20200404024YY), and Special Fund Project for Provincial Industrial Innovation in Jilin Province (Nos. 2018C048-4).a, Guoxia Hub, Shuling HecSuitai Suna College of Art of Guangxi Minzu Normal University, Chongzuo, Guangxi 532200, China, b College of Marxism of Guangxi Minzu Normal University, Chongzuo, Guangxi 532200, China, c Institute of Applied Technology of Honghe University, Honghe, Yunan 661199, China.Purpose: College students\u2019 mental health, aesthetic taste and aesthetic ability have been deeply concerned by all social strata in recent years. Therefore, the ultimate purpose of this study is to explore the necessity of carrying out aesthetic education in universities to alleviate college students\u2019 mental health problems and cultivate aesthetic values.Methods: By means of questionnaire survey and interview, the necessity of aesthetic education in alleviating the mental health problems and cultivating aesthetic values of college students of different majors, grades, genders and sources were investigated and analyzed.Results: The mental health index of male students and female students before and after aesthetic education from freshman to senior year were significantly different. The mental health indexes after aesthetic education were 97%, 94%, 90% and 86%, respectively, and the decline trend was slow. Science, engineering and sports students mostly considered beauty to be natural beauty, while music and art students, on the other hand, considered beauty to be exotic dresses or a fashion trend. The proportion of freshmen who considered beauty is natural beauty was the highest 85%, the proportion of junior college students who think beauty is fashion trend and exotic clothes is the same as that of sophomore college students, accounting for 56%. The proportion of male students and female students in the fourth grade of university who thought beauty as natural beauty was 32%, 31% respectively. The proportion of freshmen who considered beauty is natural beauty is the highest at 42%, the proportion of urban sophomores who prefer fashion trends is the highest at 44%, the proportion of urban juniors who think beauty is fashion trends is the highest at 48%, and the proportion of urban seniors who think beauty is physical beauty is the highest at 32%. Among parents of college students from different walks of life, 70.84% of the parents of farmers and 50.58% of the parents of workers think that college education is the main front and effective way to cultivate college students\u2019 aesthetic education. Teachers of different subjects in colleges and universities think that the average values of aesthetic education in colleges and universities are respectively 55.4%, 26.0%, 12.3% and 6.4%. Students of different grades participate in different activities in different numbers, types and ways. According to the average number of college students taking part in different practice channels, the number of students taking part in summer three trips to the countryside accounted for 18% at most, and the number of students visiting red bases accounted for 13.5% at least.Conclusion: It is necessary to carry out aesthetic education in colleges and universities to alleviate college students\u2019 psychological health and cultivate aesthetic values.This is the Class B Project of Undergraduate Teaching Reform Project of Guangxi Higher Education in 2021 \u201cThe Construction and Teaching Research of Red Resources in Left and right river area Region into the Courses of Art Major in Local Colleges and Universities\u201d (Project No.: 2021JGB378); 2022 School-level Curriculum Ideological and Political Teaching Team of Guangxi Normal University for Nationalities \u201cInheriting Classics: Ideological and Political Teaching Team of Chinese Painting Course\u201d (Project No.: KCSZJXTD202204); 2022 School-level Curriculum Ideological and Political Demonstration Course of Guangxi Normal University for Nationalities \u201cCreation of Chinese Landscape Painting\u201d (Project No.: KCSZSFKC202207) Phased results. The completion of this thesis is inseparable from the valuable suggestions and suggestions put forward by your colleagues. Thank you again for giving me a lot of encouragement and help. Recall the whole writing process of the thesis, although it is not easy, but let me get rid of impetuous, a lot of gains.a, Lili TangaAihui Jina Zhuhai College of Science and Technology, Zhuhai 519041, China.Background: Chinese culture, since ancient times, has been instrumental in nurturing the refinement, cognitive skills, and ethical virtues necessary for building and maintaining a healthy society, thus serving as the \u201cidentity card\u201d and spiritual glue of the nation. With the advancement and progress of society, propelled by modern science and technology, and the ongoing process of economic globalization, new cultural elements have emerged. These include network culture, information culture, competition culture, and leisure culture, which are increasingly diverse and prominent. In the current cultural milieu, university students not only engage in knowledge acquisition but are also exposed to a diverse range of cultures that affect their values, which may give rise to various psychological and cognitive issues. The psychological and value-oriented issues among university students caused by cultural problems have prompted widespread attention.Subjects and Methods: Private universities, as an essential constituent of universities, share a responsibility for imparting the core socialist values, promoting the excellent traditions of Chinese culture, guiding students\u2019 healthy psychological development and assume significant influence on education.Results: Exploring the convergence between ideological and political education and Liberal Arts Education in the context of contemporary healthy psychological culture can establish students\u2019 accurate worldview, life philosophy, and values, which can help in enhancing their overall psychological well-being.Conclusions: The significance of cultural psychology in achieving cultural inheritance, resisting the invasion of decadent culture, and establishing student beliefs is instrumental, especially in the context of cultural integration. Therefore, in the education and teaching of private universities, schools must prioritize a healthy psychological and cultural perspective and pay attention to the role of cultural psychology in the integration of Liberal Arts Education and ideological and political theory courses. This will enable schools to exploit their specific educational advantages, which will foster better development and progress of students in private universities.Supported by the 2020 research project of the \u201cThirteenth Five-Year Plan\u201d for Guangdong Province\u2019s Education Science / Office of the Leading Group for Guangdong Education Science Planning: \u201cIn-depth Research on the Integrated Development of Liberal Arts Education and Ideological and Political Education in Private Universities from the Perspective of Cultural Power\u201d. (Project No.: 2020JKDY056).aFuhong Guoa City Institute, Dalian University of Technology, Dalian 116600, China.Background: Consumer psychological anxiety is a negative emotion that occurs when there is a BTM cost in the P2P leasing market, resulting in a decrease in total consumer surplus. When perceived threats or risks of the elasticity suppliers and renters exceed their personal control, it leads to negative emotions such as unease, tension, and distress, resulting in psychological anxiety for both elasticity suppliers and renters. This is manifested as the concern for the new elasticity suppliers whether they should continue to rent out their unused products and the concern of renters whether they should rent products in the P2P leasing market. Although theoretically elastic suppliers can rent out their unused assets for free in the P2P rental market, in practice, there is at least some cost associated with providing a rentable product. The rise of the \u201csharing economy\u201d has been driven by a significant reduction in these costs, and the P2P rental market has brought an increase in consumer surplus and social welfare. However, in the long run, the cost of entering the market, or the BTM cost, has reduced the total consumer surplus in the P2P rental market. This paper analyzes the mechanism through which BTM costs affect consumer surplus in the P2P rental market and finds that they reduce the total consumer surplus, leading to a decrease in profits for elastic suppliers and renters, and causing them psychological anxiety about whether to exit the P2P rental market. Based on this, the paper proposes recommendations for reducing consumer anxiety and promoting the operation and development of the P2P rental market.Subjects and Methods: Firstly, this paper reviews the literature on P2P rental market, BTM costs and consumer psychological anxiety. Secondly, this paper compares short-term consumer surplus between the existence and absence of BTM costs in P2P rental market and draws conclusions. Thirdly, when BTM costs exist, this paper compares long-term and short-term consumer surplus in P2P rental market and draws relevant conclusions. The last part is the conclusion and inspiration of this paper.Results: This paper concludes through the comparative analysis of short-term and long-term consumer surplus in P2P rental market with and without BTM costs: BTM costs reduce total consumer surplus in P2P rental market and cause psychological anxiety for elastic suppliers and renters. Short-term consumer surplus is higher than long-term consumer surplus, and even when long-term consumer surplus reaches the lowest point, psychological anxiety for elastic suppliers and renters reaches its highest point, which leads to their unwillingness to participate in P2P rental market.Conclusions: Based on the analysis results, P2P rental platforms should reduce BTM costs, as much as possible in the long term. This can increase the income of elastic suppliers and renters, thereby reducing the psychological anxiety of both parties and lower psychological anxiety for elastic suppliers and attract more elastic suppliers who can offer more idle products in P2P rental market. There are two main ways to reduce BTM costs: one is for P2P rental platforms to find renters and achieve the best match between elastic suppliers and renters, while monitoring the entire process of product rental use, protecting the rights and interests of elastic suppliers, and reducing their psychological anxiety. The other is to achieve economies of scale and scope in P2P rental market, which can reduce unit cost for elastic suppliers and rental price for renters, and lower their psychological anxiety, thus increasing the willingness of elastic suppliers and renters to participate in P2P rental market.This work was supported by a project grant from the Funding Project for Teaching and Research of Liaoning Provincial Department of Education. (Grant No. LJKR0679) and Project funded by the Liaoning Provincial Social Science Fund (Grant No. L18BJY014).a, Jingyun Yub, Zhaoru Zhoub, Haotian Wangb, Shuo Hana, Hao Suna, Zhipeng Zhaoa, Pengda SunaSitong Zhoua Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China, b The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, China.SZ and JY contributed equally to this work.Background: Increasing incidence of colon cancer, the role of Scutellaria barbata polysaccharides (SBP) in tumors has drawn widespread attention. In order to further investigate its mechanism of action in the treatment of colon cancer, this paper try to use network pharmacology approaches to predict its possible mechanism of action.Methods: The literature was reviewed to understand the active components of SBP; the Swisstarget database was used to obtain the potential targets of the active components of SBP; the GeneCards and DisGeNET databases were used to screen the disease-related targets of colon cancer, set the relevant parameters and summarize the disease targets, and finally the intersection of the potential targets of SBP and the disease targets was taken to plot the Venn. The STRING database was used to construct the target protein interaction (PPI) network to obtain the core target proteins; gene ontology (GO) analysis and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment analysis were performed on the potential genes, and the key signaling pathways of SBP in colon cancer were obtained by using the DAVID6. 8 online tool.Results: The results showed 12 monosaccharide components were obtained from some magazines and journals, such as Rhamnose, Fucose, Arabinose, Xylose and Mannose etal. The Swisstarget database records 23 potential targets of Scutellaria barbata polysaccharides (SBP), and there are 1391 colon cancer disease targets, which were summarized from two databases, GeneCards and DisGeNET. There were 8 intersecting targets of Scutellaria barbata polysaccharides and colon cancer, namely VEGFA, HSP90AA1, LGALS3, FGF2, CDK1, HPSE, LGALS4, and FOLH1. Enrichment analysis showed that MAPK signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway were the main affected pathways. We predict that the process of colon carcinogenesis may be regulated by acting on intersectional targets as well as signaling pathways to alleviate disease symptoms.Conclusions: Scutellaria barbata polysaccharides is a kind of polysaccharide formed by the compound of many monosaccharides. It can exert the mechanism of action for the treatment of colon cancer through multiple components with multiple targets and pathways.This work was supported by project grants from Natural Science Foundation of Jilin Province (Grant No.20200201014JC) and Finance Department Health Special Project of Jilin Province (Grant No. 3D5204921429).a, Zhiyao LiaXutao Zhenga China University of Mining and Technology (Beijing), Beijing 100083, China.Background: To investigate the dissemination effects and audience attitudes towards various types of epidemic prevention slogans, with the aim of better safeguarding the positive emotions of the public during public health emergencies.Subjects and Methods: In this study, the linguistic styles of epidemic prevention slogans were divided into serious, friendly, rude and other categories, and 831 epidemic prevention slogans were quantitatively analyzed. At the same time, 55 people were interviewed to study the influence of different linguistic styles of slogans on the attitudes of the audience. In particular, this paper focuses on the impact of rude slogans on the mood of the audience.Results: The study found that there were significant differences in linguistic styles among epidemic prevention slogans released in urban and rural areas, as well as those released by different regions or publishers. Even in the early stages of the pandemic, rude slogans were not the majority among epidemic prevention slogans. The center region has a larger percentage of crude slogans as compared to other areas. Villages have a larger percentage of crude slogans than towns do. The township (subdistrict office), public organizations, and village (neighborhood) committees are more likely to print rude and friendly slogans as compared to other levels of public management organizations. The severity of the pandemic, the publisher\u2019s understanding of the target audience, the publisher\u2019s role in epidemic prevention, and legal awareness were all factors that affected the content of the slogans. Different audience attitudes were observed towards various linguistic styles of the slogans. Slogans that can bring positive feelings to the audience are more likely to be observed by the audience. Serious and friendly slogans were more likely to receive positive evaluations and compliance. Although rude slogans could elicit some degree of compliance, they were not easily accepted by the audience and may even prompt negative emotions such as resistance, dissatisfaction, anger, fear, and other adverse responses. The reasons why rude style slogans are followed by some people may be related to the potential punishment of the publisher, the authority of public management organizations and the warning effect of such slogans.Conclusion: In terms of the dissemination effects of epidemic prevention slogans, public managers and researchers should not only focus on whether the public is complying with the epidemic prevention policies and following the requirements of the slogans, but also pay attention to the impact of epidemic prevention slogans on public emotions and psychology. During public health emergencies, public managers must pay close attention to emotional management, respect the emotions of audience, protect citizen privacy, and use more friendly slogans rather than crude ones.a, Wenjing DuanaXia Taoa Wuhan Institute of Technology, School of Marxism, Wuhan 430200, China.Background: The youth of today are the backbone of social development and the leaders of the progress of the times. In the context of the new era, the key to achieving comprehensive rural revitalization lies in education, and the key to education development lies in teachers, especially young teachers. Through research and studies, it is found that the phenomenon of rural young teachers\u2019 attrition is obvious, and teachers\u2019 mental health problems are prominent, especially young teachers in rural areas with lower economic development levels have relatively high psychological anxiety index. Therefore, it is urgent to provide high-quality education services in rural areas, strive to build an excellent teaching force, further narrow the gap between urban and rural education, alleviate teachers\u2019 psychological anxiety, and stabilize the development of rural basic education.Subjects and Methods: For rural schools in province H with different levels of economic development, 16 rural young teachers who joined in 2015 and had leaving experiences were selected through a targeted sampling method, and the texts of the interviewees were coded and analyzed using the rooted theory research method, and after open coding, spindle coding, and selective coding, a theoretical model was constructed for the influencing factors of rural young teachers\u2019 attrition and their psychological anxiety.Results: Through the analysis of the rooted theory research method, the four highest dimensional categories were finally summarized and concluded that the factors affecting rural young teachers\u2019 attrition and their psychological anxiety are mainly school factors, parental factors, social factors, and personal factors, and specific contents were collated in each factor, containing a total of 14 aspects.Conclusions: Based on the current situation of rural young teachers\u2019 attrition and their psychological anxiety, this study endeavors to improve teachers\u2019 psychological quality, enhance their sense of belonging and happiness at work, and devote themselves to education with full motivation from the perspective of paying attention to teachers\u2019 psychological health. Based on this, reducing rural young teachers\u2019 attrition rate and alleviating teachers\u2019 psychological anxiety are mainly based on improving school infrastructure, focusing on joint home-school education, accelerating rural economic development, and meeting career development needs, which have practical implications for the development of rural basic education.This research was supported by the open fund project of Hubei Teacher Education Research Center, a key research base of humanities and social sciences in Hubei universities in 2022, entitled \u201cResearch on the Influencing of Rural Teacher Loss and Psychological Anxiety: an Empirical Study based on Province H\u201d (Project No. jsjy202203).a, Naikao WangbLinwen Xiaoa School of Economics and Management, Nanning Normal University, Nanning, Guangxi 530001, China, b School of Journalism and Communication, Nanning Normal University, Nanning, Guangxi 530001, ChinaBackground: In traditional China, the gap between urban and rural areas is large, so is the psychological distance between urban and rural areas. There is a two-way stereotype between urban people and rural people. In the process of rapid urban-rural integration, they need to break the psychological barrier quickly. If this problem is not solved well, the social group will appear psychological sub-health state.Subjects and Methods: In recent years, China\u2019s urban-rural integration has accelerated. However, neither urban nor rural people showed any of these collective mental health problems. In order to find out how to adjust urban and rural psychological contradictions in the process of accelerated integration, the research group selected Gangwei Town, Longhai District, Zhangzhou City, Fujian Province, China, as the research object, and conducted research using the grounded theory research method.Results: The results show that: (1) In the process of urban-rural integration, the melting speed of urban-rural cultural and psychological boundary is greater than that of urban-rural material space boundary. (2) Short video plays an important role in psychological adjustment during the process of psychological boundary ablation. (3) In the creation, dissemination and consumption of short videos, urban people and rural people participate in the process of cultural production, forming a psychological adjustment mechanism of cultural communism and cultural sharing. (4) Under this psychological adjustment mechanism, the cultural boundary between urban and rural people is eliminated, and the psychological gap is crossed, and no mental health problems caused by the rapid integration of urban and rural areas appear.Conclusions: Short videos satisfy the psychological needs of mutual lookout between urban and rural areas, and content creators actively promote the cultural communization and sharing mechanism between urban and rural areas, avoiding the group mental health problems caused by the rapid integration of urban and rural areas. The Chinese government should pay full attention to the psychological adjustment role of short video and other new media in the process of urban-rural integration, guide people\u2019s new understanding, new attitude and new behavior of the new urban-rural relationship through new media, and then actively promote the rural revitalization and urban-rural development. This study is a case study, and this mechanism may be more complicated, which needs further discussion.This work was supported by a project grant from The 14th Five-Year Plan Education Project of Fujian Province, China \u201cResearch on the Training Mechanism of College Students\u2019 Short Video Content Entrepreneurial Talents\u201d(Grant No.FJKBK21-135).a,d, Yan Duana, Rubing Xiaa,d, Jinwei Lvc, Peng Zhanga, Zhizhong Shena,d, Yong Lua, Mingku Jue, Haoran Tenga, Yang HuangbHao Wua College of Humanities and Social Development, Nanjing Agricultural University, Jiangsu, Nanjing 210095, China, b School of Cultural Heritage and Information Management, Shanghai University, Shanghai 200444, China, c Institute of History, Jiangsu Academy of Social Sciences, Jiangsu, Nanjing 210004, China, d College of Agricultural Civilization, Grand Canal Cultural Belt Construction Research Institute, Jiangsu, Nanjing 210004 China, e School of History and Culture, Henan Normal University, Henan, Xinxiang, 453007, China.Background: The dietetic culture heritage of the Jiangsu section of the Grand Canal has a very important impact on people\u2019s physical and mental health. Diet is based on agriculture. In terms of traditional Chinese social form, China has always been an agricultural society. Agriculture is the main production sector of society, providing food services to the people, and the vast majority of social material wealth is provided by agriculture. Based on this natural ecological environment, the regional dietetic culture of the people in the Jiangsu section of the Grand Canal has been integrated into the cultural mechanisms of different cities in Jiangsu, with unique cultural symbolic significance and emotional memory. The resulting customs and habits show the local people\u2019s understanding of the nature of food. Along the Grand Canal, people\u2019s preferences for food taste, food material types and even cooking skills express the residents\u2019 preferences for food mental health, and the resulting ideological, emotional and economic factors, which are the living inheritors of the sustainable development of dietetic culture\u2019s dietetic culture heritage.Subjects and Methods: This paper takes the operation, service and management concepts of the inheritors of dietetic culture heritage as the research entry point, systematically combs the dietetic culture related heritage in the Intangible Cultural Heritage List of Jiangsu Province, combs the number of national level projects, interviews the inheritors of dietetic culture heritage, investigates their attitude towards the future development of dietetic culture heritage, and analyzes their psychological and external reasons for this attitude. At the same time, it combed the dietetic culture inheritance bases related to Grand Canal in Jiangsu Province, discussed the relationship between base construction and inheritance protection, and the resulting impact on the mental health of residents along the Grand Canal.Results: Through the above investigation and analysis, the development of dietetic culture heritage of Grand Canal in Jiangsu has a positive impact on the mental health of surrounding residents. We will find that a specific diet structure will produce a specific diet psychological structure, while the dietetic culture heritage of Grand Canal in Jiangsu has a long history, healthy diet, strong cultural genes, relatively perfect diet hygiene conditions and other characteristics. It is no longer just a simple satisfaction of appetite, but increasingly displays aesthetic psychological characteristics. At the same time, the dietetic culture heritage of Grand Canal in Jiangsu still has four problems: lack of strategic thinking and specific development goals, lack of talent training mechanism, imperfect support system, and unclear inheritance and protection standards. Although the existence of these problems does not have a great impact on the mental health of residents, in the long run, these problems will lead to negative effects on the dietetic culture heritage of Grand Canal in Jiangsu. In order to prevent these negative problems, this paper puts forward some suggestions, such as formulating comprehensive strategic goals, strengthening the psychological health intervention of inheritors, improving food hygiene policy support, highlighting the development of key dietetic culture heritage, strengthening academic support of universities, so that the dietetic culture heritage of Grand Canal in Jiangsu can develop healthily and orderly, and continue to adhere to the principle of the unity of truth and innovation in the process of inheritance, And incorporate the concepts of food tradition, food hygiene, and food innovation.Conclusions: The formation of dietetic culture heritage in the Jiangsu section of the Grand Canal is closely related to the mental health of residents along the Grand Canal. What to eat is not only a phenomenon, but also a psychological behavior of people, which is inseparable from the psychological factors behind it. Therefore, we adhere to the principle that the dietetic culture heritage of Grand Canal in Jiangsu should be global, national, scientific and historic. Only in this way can the dietetic culture heritage of Grand Canal in Jiangsu maintain its vitality in the new historical period, thus having a positive impact on the residents along the Grand Canal in its development process.This work was supported by a project grant from Grand Canal Cultural Belt Construction Research Institute (Jiangsu) think tank special research project \u201cResearch on Agricultural civilization resources and its Exploitation and utilization in Grand Canal\u201d (DYH19ZXA1). Nanjing Agricultural University Central University operating funds project \u201cInvestigation and research on the Diet Cultural Heritage in the Grand Canal coastal area of Jiangsu Province\u201d (SKYC2020008). Key project of Sichuan Cuisine Development Research Center, Philosophy and Social Science Key Research Base of Sichuan Education Department \u201dStudy on Conservation of Jiangsu Traditional Diet Cultural Heritage Resources\u201d(CC18W01)a, Ziyang ZhouaJianhua Zhua School of Economics and Finance, Zhanjiang University of Science and Technology, Zhanjiang, Guangdong 524094, China.Background: to summarize the effects of psychological anxiety under the intensity of environmental regulation on foreign direct investment FDI and the technological complexity of Chinese exports, and to analyze the regularity of such effects, in order to improve the technical complexity of China\u2019s export products, we can alleviate the psychological anxiety caused by environmental regulation, improve the psychological expectation of FDI, optimize the psychological account and investment portfolio.Subjects and Methods: Based on Chinese provincial panel data from 2010 to 2019, the GMM model was used to examine the relationship between export technology complexity, foreign direct investment anxiety and environmental regulation intensity, the degree of psychological anxiety was quantified by the size of the foreign direct investment, and the panel threshold model was used to examine the relationship between the export technological complexity and the foreign direct investment under different environmental regulatory intensities, and the foreign direct investment characteristics of export technological complexity and the variation of psychological anxiety under different environmental regulatory intensities.Results: (1)environmental regulation had a significant positive effect on the psychological anxiety of FDI. Different environmental control intensity will lead to \u201cPollution halo\u201d and \u201cPollution shelter\u201d, but it will not change the psychological goal and investment direction of FDI. (2) there is a U-shaped relationship between environmental regulation and the increasing complexity of export technology. The increased complexity of exporting technology depends on the sum of the \u201cCost-offsetting\u201d and \u201cInnovation-offsetting\u201d effects, as well as the degree of psychological anxiety of the foreign direct investment. (3)the psychological anxiety of the foreign direct investment has a significant effect on the increase of export technological complexity. With the increase of environmental regulation, the complexity of FDI and export technology shows the \u201cN\u201d-type double threshold characteristics affected by investment psychological anxiety. (4) while foreign direct investment are affected by the psychological anxieties arising from the strengthening of environmental regulations, and the complexity of exporting technologies is indirectly affected through the effective interaction of environmental regulations, the intensity of environmental regulations must be moderate, can only play a catalytic role in a certain range.Conclusions: under the background of strengthening environmental supervision, the psychological anxiety of FDI will increase, and it will affect the technological complexity of export products, moreover, there is a significant positive effect between the intensity of environmental regulation, the degree of psychological anxiety of FDI and the technological complexity of export products, it is necessary to stabilize investment expectations for FDI, to control foreign direct investment anxiety and to increase the technological complexity of Chinese exports.The authors acknowledge support from Major Program of National Social Science Foundation of China [19XMZ089].a,b, Yi Wangc, Youyang Youd, Yufei Hed, Yangyu Oud, Qiuyue ZoudDonghua Zhanga School of Economics, Yunnan University of Finance and Economics, Kunming 650221, China, b School of Economics and Management, Dali University, Dali, 671003, China, c School of Logistics and Management Engineering, Yunnan University of Finance and Economics, Kunming 650221, China, d International Business School, Yunnan University of Finance and Economics, Kunming 650221, China.Background: As an important part of our life, happiness has become an important indicator to measure a person\u2019s quality of life, which helps to enhance personal and physical health, increase social stability, and promote personal and social development. People with high levels of well-being tend to be more able to experience positive emotions, such as optimism, self-confidence, satisfaction, happiness, etc., and are also more likely to cope with negative emotions and stress in life. Mental health can improve the quality of life and happiness of individuals, promote physical health, and also contribute to social stability and development. Among the many factors that affect residents\u2019 sense of well-being and happiness index, the impact of urban innovation level cannot be ignored. As a key path to improve the city\u2019s happiness index and residents\u2019 sense of well-being, technological progress has become a hot spot in academic research.Subjects and Methods: This paper takes the Yangtze River Delta urban agglomeration as the research object, and explores the innovation efficiency of the Yangtze River Delta urban agglomeration and its influencing factors by constructing a three-stage DEA model and a K-means cluster analysis model. The advantages of using the three-stage DEA model to measure the innovation efficiency of the Yangtze River Delta urban agglomeration lie in the following aspects: First, the weights of input variables and output variables are generated by mathematical models through data, and do not need to be set in advance, which reduces the error of subjective weight setting; The second and third stages of DEA eliminate the influence of environmental variables and random noise in the second stage, making the results more accurate. K-means clustering further expands the research of this paper.Results: The research found that: (1) After excluding environmental factors and random factors, the innovation efficiency of cities in the Yangtze River Delta urban agglomeration has been significantly improved; (2) Urban innovation efficiency is affected by the level of economic development, the degree of advanced industrial structure, government support, and the intensity of innovative human capital. (3) The innovation efficiency level of the Yangtze River Delta urban agglomeration can be roughly divided into innovation lagging type, innovation development type and innovation leading type.Conclusions: This study has important guiding significance for improving the innovation efficiency of urban agglomerations and enhancing the mental health and happiness of residents.a, Songyan ZhangaYijie Tanga School of Economics and Management, Zhejiang University of Science and Technology, Hangzhou, Zhejiang 310000, China.Background: Healthy mental state needs to be based on good material conditions. The economic level and material conditions in rural areas are lower than those in urban areas, which may lead to adverse development of rural household mental health. As one of the important factors to promote regional economic development, financial model can affect the mental health of farmers by changing material conditions. Therefore, the innovation and development level of financial model deserve high attention. At present, there are some financial problems such as brain drain, low financing demand, few mortgage loans, poor infrastructure, imperfect credit investigation system and diversified demand in the process of rural revitalization in Zhejiang Province. In rural areas with low economic level, there are some mental health problems such as spiritual poverty, lack of confidence, lack of motivation for poverty alleviation and incorrect concept of development. This paper aims to study the operation mechanism of innovative financial model in rural areas of Zhejiang Province and its impact on farmers\u2019 mental health, and put forward relevant suggestions for promoting rural revitalization, sustainable development of agricultural health and cultivation of farmers\u2019 mental health in Zhejiang Province.Subjects and Methods: The innovative financial model in rural areas of Zhejiang Province is selected as the research object. First, look up and read a large number of case materials, and have an in-depth understanding of the rural revitalization strategy, the concept of financial model, the situation of rural revitalization in Zhejiang Province and the mental health status of rural households. Second, the paper investigates the innovative financial models generated in the process of rural revitalization in Zhejiang Province and makes a preliminary analysis. Third, select influential and representative innovation models such as \u201cinsurance + futures\u201d model, supply chain finance model, \u201cclean energy + green building\u201d model as the main research object. This paper analyzes how different financial models support rural revitalization and affect the mental health status of farmers, and obtains the operating mechanism, key content and main impact from actual cases.Results: The three innovative financial models have a good effect on the development of financial level in rural areas, effectively solve the financial problems and farmers\u2019 mental health problems in rural areas of Zhejiang Province, and significantly improve the economic level, material conditions and farmers\u2019 mental health degree in rural areas.Conclusions: \u201cInsurance + futures\u201d mode can affect the psychology of farmers and promote the development of their mental health by improving their material conditions. Supply chain finance model plays a significant role in solving the psychological poverty problem of farmers. The model of \u201cclean energy + green building\u201d can promote farmers to shape the concept of sustainable development and form healthy psychology.This research was supported by a project grant from National College Student Innovation and Entrepreneurship Training Program.a,b, Qing ZhangcWenjun Zhanga School of Marxism, Chongqing Technology and Business University, Chongqing, China, b People\u2019s Government of Oitak Town, Aketao County, Xinjiang, China, c Primary School of Xinli Town, Zhongxian County,Chongqing, China.Background: This paper aims to investigate the current situation and influencing factors of Chinese college students\u2019 psychological Sense of Gain in the process of Ideological and Theoretical Courses, so as to provide reference for the implementation of curriculum teaching reform for China and other countries.Subjects and Methods: This paper uses the \u201csurvey method\u201d to conduct the relevant research, and uses SPSS software to sort out the questionnaire data, and adopted descriptive statistics and correlation analysis to carry out empirical analysis of the status quo and influencing factors of the Sense of Gain of more than 800 Chinese college students.Results: From the investigation, the psychological Sense of Gain of Chinese college students from Ideological and Theoretical Courses is between \u201caverage\u201d and \u201crelatively strong\u201d, which is not strong enough. From the viewpoint of the factors influencing students\u2019 learning psychology in the Ideological and Theoretical Courses, the \u201cSense of Gain\u201d is mainly influenced by the learning psychological stress and learning participation, and the teaching objectives, contents and methods, teachers\u2019 emotional care and affinity also has a relatively influence. Moreover, the students\u2019 learning environment also has some influence on learning psychology in Ideological and Theoretical Courses.Conclusions: In view of the current situation of college students\u2019 psychological Sense of Gain in Ideological and Theoretical Courses and the existence of these influencing factors. First of all, Ideological and Theoretical Courses teachers and other course teachers need to increase the teaching affinity between teachers and students in the Ideological and Theoretical Courses, close the psychological distance between teaching and students, ease students\u2019 negative emotion. Second, teachers need consider the learning psychology needs of college students when formulating the objectives, content and methods, reduce students\u2019 psychological stress of learning. Third, teachers need give college students enough emotional care in the course to create a heart warming study environment, so that to inspire college students\u2019 produce positive learning motivation, so as to stabilize their will to learn. Those methods could promote the \u201cemotional resonance\u201d and \u201cpsychological integration\u201d between teachers and students, making college students feel the positive emotional and psychological impact in course. Moreover, it isn\u2019t only helps college student continuously increase the knowledge in the learning process,but also achieves the purpose of further enhancing college students\u2019 psychological Sense of Gain in Ideological and Theoretical Courses.a,b, Haijian HucChang Yua School of Music, Guangdong Polytechnic Normal University, Guangzhou 510665, Guangdong, China, b School of Education, City University of Macau, Macau 999078, China, c School of Marxism, Guangdong Polytechnic of Science and Technology, Zhuhai 510640, Guangdong, China.Background: Dance education in China has experienced new development since the turn of the century, and the evaluation of the effectiveness of dance teaching in colleges and universities has expanded after the \u201cOverall Plan for Deepening Educational Evaluation Reform in the New Era\u201d was issued by the State Council. During the process of teaching dance, it is essential to effectively understand students\u2019 psychological response to dance and the positive psychological effects of learning dance. It is important to cultivate self-awareness, self-control, self-efficacy, and adaptive thinking in students, which will help them handle challenges and stress in learning, achieve higher quality learning outcomes, and increase satisfaction with their dance education. Such psychological qualities are also integral to the development of a student\u2019s dance performance, and can greatly enhance the effectiveness of dance teaching.Subjects and Methods: Based on the theory of the 21st Century 5C Key Competencies Model and the maturity scale of domestic classroom teaching effectiveness, starting in2020 this study adapted and verified the 5C key competencies and dance teaching effectiveness scale specifically for college dance majors. Descriptive, correlation, and regression analyses were used to analyze 634 valid questionnaires from Guangdong universities and explore the correlation between 5C key competencies and the effectiveness of dance teaching in universities. Thus, this study explores the path from the 5C key competencies to dance psychology to ensure the teaching effectiveness of \u201cHeart-Dance in Harmony.\u201dResults: The results of data analysis showed a significant correlation between the 5C key competencies and the effectiveness of dance teaching in colleges; the 5C key competencies had predictive power for the effectiveness of college dance teaching.Conclusions: Dance education has a positive impact on reducing students\u2019 stress and negative emotions from multiple aspects. In dance teaching, students can cultivate their understanding and appreciation of culture, which helps them feel a sense of self-identity and belonging in dance while enhancing their cultural confidence. Improving critical thinking skills can reduce loneliness and self-doubt, enabling students to face challenges and stress more confidently. Developing innovative skills can enhance students\u2019 dance thinking ability and creative ability, increase self-efficacy and belief. In collective teaching and training, effective communication and cooperation can build stronger and healthier interpersonal relationships, fostering students\u2019 cooperation spirit, trust, sharing, and sense of responsibility. the 5C key competencies are bestowed upon educational and psychological research, enabling students to deal with stress, alleviate pressure, and promote their mental and physical health more effectively. This study aimed to explore the effectiveness of university dance education in light of the 5C key competencies. It adhered to the principles of combining scientificity and practicality in education, focusing on positive psychological effects. In this modern age, university educators must encourage the physical and mental development of their students in line with the 5C standards while also possessing the 5C key competencies themselves. Through focused efforts, they can enhance the reach, depth, and orientation of dance instruction within university classrooms. A key aspect of this endeavor is the exploration of individual potential and strengths. This involves honing the creativity, communication, cooperation, critical thinking, and cultural awareness of students to aid in their attainment of success and personal fulfillment.This work was supported by a project grant from 2022 Annual Project of the \u201c14th Five-Year Plan\u201d for the Development of Philosophy and Social Sciences in Guangzhou; \u201cResearch on developing Guangzhou as a model city for educational reform and development in the Guangdong-Hong Kong-Macao Greater Bay Area: from the perspective of aesthetic education empowering a humanistic Bay Area development\u201d (Project grant No.2022GZGJ289).a, Qiong WangaAizhong Wanga College of Tourism, Chongqing University of Arts and Sciences, Chongqing 402160, China.Background: Under the background of all-for-one tourism, the integration of fruit tourism is becoming an important driving force for the development of rural tourism. This paper studies the consumer psychological needs and consumption behavior of rural tourism consumers in Wulong District, Chongqing municipality, analyzes the problems existing in the integrated development model of fruit tourism in Wulong District and the integrated development of fruit tourism in the whole district, and puts forward targeted countermeasures to provide a basis for policy formulation and long-term planning of the government and rural tourism enterprises.Subjects and Methods: Based on the theory of consumer behavior, this paper takes consumer behavior and consumer psychology research as the breakthrough, adopts the methods of stratified sampling and random sampling, divides the tourist population into existing consumers and potential consumers, selects several typical rural tourism scenic spots, important fruit production areas, leisure picking intensive areas as the research area, and investigates the demographic characteristics of tourists, the characteristics of tourists\u2019 consumption behavior, the psychological characteristics of tourists, and the development status, mode and problems of fruit tourism. A total of 1,000 questionnaires were distributed, and 988 were recovered, with a recovery rate of 98.8%, of which 926 were valid. After the survey, the data were statistically analyzed using SPSS20.0 software.Results: Relaxation, leisure and entertainment, psychological anxiety, melancholy getting rid of, emotional regulation, nostalgia, perception and show-off, personality traits, etc. have become the main motivations for people to choose fruit tourism. Among them, relaxation, leisure and entertainment are the traditional influencing factors of rural tourism development, and the importance of nostalgia, personality traits and psychological anxiety in the integration of fruit tourism is becoming more and more prominent. The survey results of tourist satisfaction show that there is a serious phenomenon of psychological homogenization and inferiority among tourists caused by the lack of fruit tourism products and projects is serious, and the lag of public service facilities, the lack of human resources, and the lack of integration mechanism aggravate tourists\u2019 sense of disappointment and psychological identity. According to the psychological characteristics and behavioral habits of tourism consumers, the integrated development model of fruit tourism in Wulong District is divided into government intervention type, collective loose type and peasant household freedom type.Conclusions: Under the background of all-for-one tourism, the consumer factors of the integrated development of fruit tourism in Wulong District should not only consider the consumption needs of traditional tourists such as relaxation and leisure, but also pay attention to psychological motivations such as psychological anxiety, depression and desolation, emotional regulation, nostalgia, personality traits and perception of show-off. Relevant parties can regulate and control by studying the actual needs of tourism consumers, tapping regional advantages and characteristics, optimizing public infrastructure construction, and building an innovative mechanism for the linkage development of fruit tourism.This work was supported by the Humanities and Social Sciences Project of the Ministry of Education\u201c Research on the Global Development Mode and Realization Mechanism of Non-Optimal Tourism District in Wuling Mountain Area under the Strategy of Rural Revitalization\u201d (19YJC630161)a, Lu Zhanga, Qichao Maoa, Miaoyu WangaXingxiang Xinga Shaoxing Central Blood Station, Shaoxing City 312000, China.Background: To understand and evaluate the detection efficacy of different testing strategies for transfusion-transmissible infections markers in blood donations, to choose appropriate testing strategies, and to effectively prevent transfusion-transmitted infections.Subjects and Methods: The detection results of transfusion-transmissible infections markers in 214,474 blood donation samples collected between 2019 and 2022 were retrospectively analyzed and compared using three testing strategies based on relevant specifications.Results: The total nonconformity rate of blood tests under testing strategy A was 1.25%, and the nonconformity rates of ALT, HBsAg, Anti-HCV, Anti-HIV, Anti-TP, HBV-DNA, HCV-RNA, and HIV-RNA were 0.42%, 0.17%, 0.15%, 0.08%, 0.18%, 0.19%, 0.01%, and 0.01%, respectively, indicating a relatively low level of nonconformity. Among 17 confirmed HIV-infected donors, NAT detected 1 case first. The consistency rates of positive results for HBV, HCV, and HIV infection-related markers were 16.53%, 27.09%, and 20.43% under testing strategies A, B, and C, respectively. The total nonconformity rates of HBV, HCV, and HIV infection-related markers were 0.52%, 0.40%, and 0.39%, respectively, with statistically significant differences in nonconformity rates between HBV and HIV infection-related markers. Compared with testing strategy A, the relative detection rates of HBV, HCV, and HIV infection-related markers were 77.69% and 76.06% under testing strategies B and C, respectively. Testing strategy B detected 247 fewer cases compared to strategy A, with 246 fewer cases of HBV infection, no difference in HCV infection, and 1 fewer case of HIV infection. On the other hand, testing strategy C detected 265 fewer cases compared to strategy A, with 113 fewer cases of HBV infection, 46 fewer cases of HCV infection, and 106 fewer cases of HIV infection.Conclusions: Testing strategies with more comprehensive detection items ensure a higher level of blood safety. Multiple testing methods with different types of markers are necessary in practice. Testing strategies with fewer detection items need to be cautiously applied. NAT is essential for blood screening, and the combination of multiple testing methods can improve detection rates.We would like to express our gratitude to Mr. Sang Liyong, Director of Shaoxing Central Blood Station, and Mr. Fu Liqiang, Deputy Director, for their valuable guidance, help, and support during this study.aZhiying Liua Jiang Su Urban and Construction Vocational College, Changzhou city, Jiangsu Province 213000, China.Background: According to the research report of China Academy of Fiscal Science on the labor cost of China labor market, in the first half of 2018-2021, the average monthly wage of sample enterprises increased from 4,182 yuan to 5,367 yuan, with an average increase of 9.44%, especially in the first half of 2021, the average monthly wage increased by 12.63%. Enterprises are facing the pressure of rising costs, and job seekers are facing a state of job anxiety, how to solve the adverse effects and provide a positive signal for job seekers is the focus of this paper. Under the difficulty of rising labor costs, enterprises have psychological anxiety; job seekers face the increasing problems of rising living and housing costs. If the psychological anxiety problem is not paid attention to, and cannot be alleviated, it will develop into anxiety disorders, which may lead to changes in people\u2019s body, and cause social problems.The accurate distribution and analysis of labor cost realize reasonable control and provides a feasible path for enterprises.Subjects and Methods: This paper studies the multi-level analysis of labor cost difference in standard cost method; In the paper the comparative analysis and case analysis are used. In the article a manufacturing company is chosen as a typical case.Results: The labor cost problem needs the joint efforts of internal and external parties, such as external policy support, but it is also very important for enterprises to adopt appropriate cost methods. At present, there are two systems for the treatment of labor costs, which are the actual cost allocation method based on working hours and the standard cost method based on standards. Both methods have their shortcomings.Conclusion: The key to the traditional standard based accounting and distribution method lies in the determination of standard working hours and wage rate standards. Besides the strong subjectivity in the formulation of standards, the reference factors are single and the labor level and the nature of jobs are not considered, which is also a major problem. The multi-level analysis of standard cost method proposed in this paper ensures the stability and systematic of cost indicators. This method can explain the causes of differences in detail and provide data support for later cost control and provide positive signal and relief the mental pressure relative to labor.a, Qinhai MaaYing Zhaoa School of Business Administration, Northeastern University, Shenyang 110819, China.Background: This research aims to investigate the impact of brand logo change on consumers\u2019 emotion regulation by exploring the effects of logo design characteristic changes. Enterprises often modify their logos to maintain their brand image, which requires continuous planning and adaptation to consumers\u2019 emotion regulation. Therefore, brands aim to keep up with the times and maintain a positive image by redesigning their logos in ways that satisfy consumers\u2019 emotional needs. Such needs include familiarity for loyal customers, meaning similarity with the old logo for the target audience, and the ability to evoke positive affect and good surprise. Consumers\u2019 emotional needs are critical for brand logo changes to be effective, as they influence how consumers respond to and engage with logos.Subjects and Methods: Our research involves conducting empirical experiments to investigate the relationship between logo design characteristics and consumer responses. Firstly, we identified eight distinct logo design characteristics. Secondly, we identified four different types of consumer responses to logo changes. Thirdly, we identified four underlying design dimensions of logo changes, which are natural, harmonious, elaborate, and integral, and four response dimensions. Finally, we conducted an empirical analysis of 100 logos to identify those that meet three different strategic objectives.Results: Our empirical research has led us to propose design guidelines for logo changes that take into account consumers\u2019 emotion regulation. Our analysis revealed that for minor logo changes in a mature market, the change should be medium in terms of naturalness and elaboration, low in terms of harmony, and high in terms of integrity. Conversely, major logo changes in a mature market should involve a high level of natural change transitioning to medium, a positive and substantial change in harmony, a low to medium level of elaboration, and a negative and low change in integrity. For logo changes in a young market, the guidelines suggest a low to medium level of natural change, a positive and substantial change in harmony, a low to medium level of elaboration, and a negative and low change in integrity.Conclusions: Our findings indicate that any change in brand logos can have a significant impact on consumers, highlighting the importance of catering to their emotion regulation. The design guidelines for logo changes provide marketing managers with a reliable theoretical basis for minimizing or avoiding potentially negative effects, such as reduced market competitiveness, increased costs, or the risk of losing brand assets. Our research contributes to the design guidelines of brand logo change in several ways. First, it offers a new perspective on the relationship between a series of design characteristics of brand logos and their impact on consumers\u2019 response, which is closely linked to their emotion regulation. Second, it proposes design guidelines for logo changes with respect to three different strategic objectives. Third, we provide purely illustrative recommendations for different types of logo changes, taking into account the impact on consumers\u2019 emotion regulation.a, Hongmei Lib, Lizhang DongbYifan Wanga School of Education, Baoshan University, Yunnan 678000, China, b School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China.Background: Since the start of the epidemic, people across the country have experienced a \u201clockdown period\u201d in early 2020, when all places are closed down and travel restricted, and a \u201cplateau period\u201d when the epidemic is relatively stable after the epidemic is brought under control and the lockdown is lifted. The plateau period is a period of continuous response, reflection and adjustment to the epidemic situation. It is of great value and significance to explore the mental health status of college students during the plateau period, which can provide a new direction of thinking for the subsequent mental health education of college students. Depression is a condition to be concerned about; Psychological capital is an effective mediating variable of the psychological stress response of college students under the epidemic. For the mental health education of colleges and universities, it is helpful to reduce the impact of the major epidemic on the mental health of college students, promote the self-growth of college students, and promote the scientific psychological education model of colleges and universities. The impact of major epidemic on the psychological capital of Chinese college students has both advantages and disadvantages Positive environment and support resources such as effective prevention and control of the government, concerted efforts of the people and family companionship are conducive to the growth of optimism and hope factors of psychological capital. At the same time, the major epidemic has a negative impact on the self-efficacy and psychological resilience of college students with little stress experience, weak personality foundation, high psychological pressure and little social support. In order to explore the influence of college students\u2019 risk perception level on their depressive state and the protective role of psychological capital in the stable period of the epidemic, this study investigated freshmen and seniors of Baoshan University in Yunnan Province.Subjects and Methods: Totally 5138 college students were surveyed using the COVID-19 Risk Perception Scale (PRCPS), Depression Angst Stress Scale (DASS-21) and Compound PsyCap Scale (CPC-12)Results: (1) Risk perception positively predicts depression; (2) Hope, efficacy and optimism in psychological capital can negatively predict depression; (3) The efficacy dimension of psychological capital moderates the relationship between risk perception and depressive state, that is, the predictive power of risk perception on depressive state decreases with the increase of efficacy.Conclusion: High risk perception tends to lead to depression in college students, while psychological capital can reduce the occurrence of depression, and the efficacy dimension of psychological capital plays a protective role in the relationship between risk perception and depression.a, Aihong WangaDan Longa School of Design and Art, Jingdezhen Ceramic University, Jingdezhen 333000, China.Background: \u201cIt is one of the important varieties of glaze decoration of traditional Chinese ceramics, and is an artistic expression with ceramics as the carrier. The development of pastel has a certain transitional period. This paper studies the beauty of ceramic pastel decoration in the three Qing dynasties from the perspective of \u201cpsychological needs\u201d and explores the role of its \u201cunique\u201d painting language in psychological healing. The purpose of this study is to examine the psychological development of the human psyche and the psychological role of aesthetics.Subjects and Methods: Using Maslow\u2019s Theory of Needs as a theoretical guide and a combination of qualitative and quantitative and comparative research methods, the study aims to analyze the role and healing of the \u201caesthetic expression\u201d of the painting language of pastel decoration in the Qing and Third Dynasties on mental health.Results: The analysis focuses on the meaning of the lines, composition and craftsmanship in relation to psychological needs and psychological health, and the interrelationship between the \u201cartistic characteristics\u201d and \u201cpsychological needs\u201d of Qing Dynasty pastels. The analysis shows that the Qing Dynasty pastel decorations were effective in relieving people\u2019s stress and anxiety at the level of \u201cpractical needs\u201d, in healing people\u2019s aesthetic psychology at the level of \u201caesthetic needs\u201d, and in relieving people\u2019s negative emotions at the level of \u201cvalue needs\u201d.Conclusions: From this, it is concluded that the pastel decoration of the Qing Dynasty has a unique aesthetic of art, both psychological regulation and compensatory dynamic function, but also can make the artistic literacy and artistic inculcation of people to facilitate the maintenance of psychological health, art from life and above life, so that art into real life, so that people maintain a positive and healthy psychological needs of the development of the situation is particularly necessary.This research was supported by the project.a, Xiaoshu Lib, Ruhaizin Sulaimana, Khairul Manami Kamarudina, Rosalam Che MeaKang Jia Faculty of Design and Architecture, Universiti Putra Malaysia, Serdang, 43400, Malaysia, b School of art & design, Zhengzhou University of Aeronautics, Zhengzhou, 450046, China.Objective: Maintaining a healthy lifestyle plays a vital role in personal health and social development. However, in reality, many people have various problems maintaining healthy behaviors and are unable to maintain a healthy lifestyle. Most of the existing healthy lifestyle-related products on the market are designed based on the principle of persuasion, and intervene in behavior through various persuasive strategies, so as to achieve the purpose of changing behavior. In order to provide designers and researchers with more effective design solutions in product design in the future, this study systematically analyzes and gives an objective assessment of the persuasive principles and strategies used in product persuasive design.Methods: Through the method of systematic literature review, search the persuasion technology and application of persuasion strategies in healthy life and the Fogg behavior model (FBM) from the two search engines of Scopus and Connected Paper, then strictly follow the PRISMA flow chart to provide relevant screening and evaluation according to the requirements of eligibility, inclusion or exclusion of articles, 23 eligible articles were finally selected for systematic analysis.Results: This study found that the Fogg Behavior Model and persuasive strategy used in the existing products can effectively promote the formation of healthy behavior and improve people\u2019s healthy lifestyle. In addition, the effectiveness of persuasive technology will also be affected by a variety of other factors, such as the influencing factors of target behavior, social environment, intervention stage of persuasive strategy, intervention duration, etc. In order to improve the effectiveness of products, these factors should be considered by researchers and designers.Conclusions: The systematic literature review provides an important theoretical basis for designers and researchers in the process of product design related to healthy lifestyle through the study of persuasive principles, persuasive strategies and Fogg Behavior Model. This study emphasizes the importance of persuasive technology and design in the process of healthy lifestyle intervention and summarizes the advantages of persuasive design from four aspects: orientation, friendliness, interactivity and ethics.a, Haiju Liub, Chunsheng LiaXiaolei Rena Urology Department, Affiliated Hospital of Chifeng University, Institute of Urology, Chifeng University 024000 Chifeng, China, b Cancer Screening Department, Chifeng Cancer Hospital, 024000 Chifeng, China.XR and HL contributed equally to this study.Background: To evaluate the safety and efficacy of 980\u2005nm diode laser enucleation for treatment of non-Muscle-invasive bladder cancer.Subjects and Methods: The data of the patients with non\u2013muscle-invasive bladder cancer treated by either 980\u2005nm diode laser enucleation (n=56) or conventional transurethral resection of bladder tumor (n=52) were analyzed retrospectively. The preoperative characteristics and intraoperative complications were compared in the 2 groups.Results: No significant differences in the sex, age, mean tumor number, mean tumor max. size, tumor multiplicity, tumor location, tumor stage, and recurrence risk of the 2 groups were observed. All patients accepted the successful 980\u2005nm diode laser enucleation or TURBT, respectively. No obturator nerve reflex and bladder perforation occurred during surgery in the 980\u2005nm diode laser group. However, 11 patients in the conventional transurethral resection of bladder tumor group encountered obturator nerve reflex, and 2 of them encountered bladder perforation. There were no significant differences between the 2 groups in transfusion rate. Patients in the 980\u2005nm diode laser group had shorter the mean duration time of the operation, duration postoperative continuous bladder irrigation time, and catheterization time than that in the conventional transurethral resection of bladder tumor group. There was no significant difference in the overall 1-year recurrence rate between the 2 groups during the follow-up periods. Also, no statistical difference was found when the comparison was made among every risk subgroups between the two groups.Conclusions: 980\u2005nm diode laser enucleation for treatment of non\u2013muscle-invasive bladder cancer demonstrates an advantage over conventional transurethral resection of bladder tumor in reducing intraoperative complications, shortening the mean duration time of the operation, shorting the time of duration of postoperative continuous bladder irrigation, and shorting the time of catheterization.This research was supported by Inner Mongolia Autonomous Region Higher Education Science Research Project: NJZY21140.a,Tong ZhaobGuirong Hea Department of China International Language and Culture College, Krirk University, Bangkok10220, Thailand, b Department of Culture Industry, College of Humanities and Social Sciences, Kwangwoon University, Seoul, 01897, Republic of Korea.Background: With the acceleration of the process of globalization, more and more people have a strong interest in learning Chinese language and culture. In international Chinese education, Chinese calligraphy, as a unique cultural and artistic form, has profound historical origin and cultural connotation, and has become an effective way and means to attract foreigners to learn Chinese. However, in the actual teaching process, due to the different cultural background and learning style, different psychological pressure, psychological anxiety and other bad emotions that are not conducive to physical and mental health will be produced in the learning process. How to effectively teach Chinese calligraphy in the cross-cultural background has become an urgent problem to be solved. In order to improve the effect of Chinese calligraphy education, promote the common development of international Chinese education and mental health education. Based on the mental health perspective, this paper studies the development of the communication mode of Chinese calligraphy education for international Chinese education.Subjects and Methods: Based on this, in order to improve the effect of integrating mental health education into Chinese calligraphy education in international Chinese education, and promote the integrated development of international Chinese education and mental health education. This paper first discusses the basic situation of international Chinese education; then it analyzes the basic connotation of Chinese calligraphy education. Then, from the perspective of psychology, this paper discusses and analyzes the psychological health factors of the communication mode of Chinese calligraphy education. Finally, based on the investigation of the audience of international Chinese education, this paper analyzes the specific mode of the future development of Chinese calligraphy education in China.Results: This paper mainly adopts the form of questionnaire survey to study Chinese calligraphy education under international Chinese education. The results show that the highest proportion of male study time is less than one year, accounting for about 35%. While the highest proportion of female study time is 3-4 years, accounting for about 23%. With the growth of age, the study time of participants under the age of 20 was less than one year, accounting for about 77% of the total; the study duration of 20-30 year-old participants is less than one year, accounting for about 48%; the study duration of participants over 30 years old is the highest of 2-3 years, accounting for about 36%. At the same time, the most popular way of learning is an online course, which accounts for about 40% of women. The largest number of Chinese calligraphy communication carriers that participants are interested in is painting, which accounts for about 34% of participants aged 20-30.Conclusions: This research not only provides a reference for improving the effectiveness of Chinese calligraphy education, but also makes an objective contribution to the future sustainable development of international Chinese education.This work was supported by a project grant from the Connotations and Values of Local Calligraphy Heritage in Zhongshan City, which used Xiaolan Town in Zhongshan City as an example. (Grant No.202357).a, Qinhai MaaYing Zhaoa School of Business Administration, Northeastern University, Shenyang 110819, China.Background: In the digital age, online reviews have become a crucial factor in shaping consumer purchase decisions. As such, understanding the factors that influence the credibility of online reviews is essential for businesses that seek to attract and retain customers. Previous research has identified several factors that affect online review credibility, such as review valence, length, and source credibility. However, little is known about how the psychological needs of consumers may impact their perceptions of review credibility. This study aims to investigate the influence of psychological needs, such as the need for social validation and the need for self-enhancement, on consumers\u2019 perceptions of online review credibility.Subjects and Methods: A survey was conducted with 500 participants who had recently made an online purchase. Participants were asked to rate the credibility of a fictitious online review, which varied in terms of review valence, length, and source credibility. Participants also completed a questionnaire that measured their psychological needs, such as the need for social validation and the need for self-enhancement. Structural equation modeling was used to analyze the data and determine the extent to which psychological needs influenced consumers\u2019 perceptions of online review credibility.Results: The results of the study indicate that psychological needs play a significant role in consumers\u2019 perceptions of online review credibility. Specifically, the need for social validation was found to positively influence consumers\u2019 perceptions of review credibility, while the need for self-enhancement was found to negatively influence consumers\u2019 perceptions of review credibility. Furthermore, the results suggest that the influence of psychological needs on review credibility may vary depending on the source credibility of the review.Conclusions: This study provides important insights into the factors that influence consumers\u2019 perceptions of online review credibility. The findings suggest that businesses can enhance the credibility of their online reviews by appealing to consumers\u2019 psychological needs for social validation, while avoiding tactics that may trigger consumers\u2019 need for self-enhancement. By understanding the psychological needs that underlie consumers\u2019 perceptions of online review credibility, businesses can better tailor their review management strategies to attract and retain customers.a, Li LibXianli Gaoa School of Foreign Languages, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China, b School of Foreign Studies, Guangzhou University, Guangzhou, Guangdong 510006, ChinaBackground: With the development of positive psychology, well-being, as a healthy psychological mechanism, has become an important factor to explain employees\u2019 behavioral attitudes and improve their job performance, which gradually enriches the relevant researches on teachers\u2019 subjective well-being. Predicting job performance based on subjective well-being has always been a major concern in the field of organizational behavior. In view of this, based on the perspective of positive management, the purpose of this study was to explore the internal mechanism of the impact of tertiary teachers\u2019 subjective well-being on job performance in the context of innovation and entrepreneurship by introducing organizational identity as a moderating variable.Subjects and Methods: Two hundred and sixty-seven Chinese tertiary teachers of foreign languages in innovation and entrepreneurship education from 10 universities were chosen through random sampling. Questionnaires were employed to measure job performance, subjective well-being and organizational identity in this study, and the data was analyzed by the descriptive statistics, correlation and regression analyses to examine the internal mechanism of the impact of tertiary teachers\u2019 subjective well-being on job performance in the context of innovation and entrepreneurship by introducing organizational identity as a moderating variable.Results: The findings obtained from the study are as follows: (a) Subjective well-being and organizational identity were important factors affecting job performance of tertiary teachers of foreign languages, (b) Subjective well-being of tertiary teachers of foreign languages had a significant positive impact on job performance and organizational identity, (c) Organizational identity had a significant positive impact on job performance of tertiary teachers of foreign languages. Conclusions: The moderating mechanism between teachers\u2019 subjective well-being and job performance is also a problem worthy of in-depth study. The propulsive relationship of organizational identity on subjective well-being and job performance showed that Chinese tertiary teachers of foreign languages could improve subjective well-being and job performance through organizational identity. Therefore, urging Chinese tertiary teachers of foreign languages to identify with institutions of higher learning and motivating teachers\u2019 enthusiasm for innovation and entrepreneurship education was one of the effective ways to improve teachers\u2019 job performance.th Five Year Plan of National Education Sciences grants (No. 2020GXJK468); The 2st Batch of Industry-University Cooperative Education Projects in 2022 by the Ministry of Education of China grants (NO. 220802193315018); Higher Education Special Funds (2021) of Department of Education of Guangdong Province.This work was supported by Guangdong Provincial Undergraduate Teaching Reform and Quality Engineering Construction Project grants (No. GDJG2021295); Planning Subject for the 13a, Yanrui Jiab, Xiaoyan XinbYu Wanga School of Management, Guangdong University of Science & Technology, Dongguan, Guangdong 523083, China, b School of Business Administration, Jimei University, Xiamen, Fujian 361021, China.Background: With the rise and development of e-commerce, the speed and scope of IWOM have spread more rapidly and extensively than traditional word-of-mouth. IWOM affected consumers\u2019 shopping mood and decision-making behavior. The quality of IWOM is increasingly becoming a primary consideration in consumer shopping choices.Subjects and Methods: The influencing factors of IWOM quality were analyzed from four dimensions such as IWOM recipients, channels, merchants and IWOM itself. The influencing factors of consumers mainly included consumers\u2019 gender, personality, mood and the type of products they bought. The influencing factors analyzed from the communication channels were the type and authority of websites. From the merchants\u2019 perspective, their influencing factors were the merchants\u2019 reputation, after-sales service, payment methods and measures such as cashback to consumers in order to get good reviews, as well as the merchants\u2019 handling of poor reviews given by consumers. The influencing factors of IWOM itself were mainly the directionality and the level of detail of IWOM. The questionnaire was designed according to the above four dimensions, and the proposed hypotheses were argued one by one through the empirical analysis method of questionnaire survey.Results: The study found that the stronger the trust tendency in consumers\u2019 mood, the higher the credibility of IWOM. Consumers\u2019 gender has no effect on IWOM quality. Consumers are more influenced by IWOM quality for highly involved products. Website authority, merchants\u2019 credibility and guarantee measures positively affect IWOM quality. Merchants\u2019 means of misleading implementation negatively affect IWOM quality. The higher the level of detail of IWOM, the higher its IWOM quality. The type of online platform and the positive or negative nature of IWOM itself do not have significant effects on IWOM quality.Conclusions: Based on the research results, certain reference suggestions are made for enterprises or businesses, consumers, governments, and communication channels. Enterprises should encourage and guide consumers to publish more detailed IWOM as much as possible. They should focus on and influence consumer mood and try to target their marketing to consumers with lower expertise and higher trust tendency. Consumers, as publishers or disseminators of IWOM information, should adhere to the principle of truthfulness and truthfulness, and publish true and effective IWOM. The government can formulate relevant legal norms and take measures to punish merchants to reduce false IWOM and enhance the objective accuracy of IWOM. Websites, as the main communication channels, should avoid the spread of false IWOM on websites by strengthening supervision.a, Xinzhe Zhaib, Yi Wub, Jianli HanaRui Yanga General Surgery Department, Shanxi Bethune Hospital, Shanxi, Taiyuan 030032, China, b Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Shanxi, Taiyuan, 030032, China.Background: Metabolic diseases caused by obesity are diverse, and many large population studies have reported a direct correlation between obesity and the occurrence of various diseases, which can affect the function of multiple endocrine organs including thyroid function. The relationship and mechanism between Hashimoto\u2019s thyroiditis (HT) and type 2 diabetes mellitus (DM) as two common obesity-related complications remain yet unclear.Subjects and Methods: The National Center for Biotechnology Information (NCBI) database was searched for GEO datasets (https://www.ncbi.nlm.nih.gov/geo), and datasets GSE18470 and GSE138198 were selected for data analysis. After analyzing the differentially expressed genes between the groups, the results were submitted to the DIANA TOOLS website and the MirPath tool was used for pathway enrichment analysis. The KEGG pathway enrichment results were selected as the data for further analysis, and key genes were identified.Results: Compared with simple obesity, there are more associated genes in obese patients with type 2 diabetes (DM) and HT, suggesting that type 2 DM may increase the chance of obese patients developing HT. The TGF-beta signaling pathway and Proteoglycans in cancer pathways contained the most genes, with 10 genes each. The TGF-beta signaling pathway (p=1.776067e-06) ranked higher than the Proteoglycans in cancer pathway (p=8.47584e-05), suggesting that the TGF-beta signaling pathway may be the key pathway for obese patients with type 2 DM to develop HT.Conclusions: This study not only found that there are more associated genes in obese patients with type 2 DM and HT, but also suggested that the TGF-beta signaling pathway is the key bridge for the occurrence of these two conditions. The 10 associated genes in the TGF-beta signaling pathway identified in this study can be the focus of future research. Identifying the possible mechanisms leading to the occurrence of HT in obese patients with type 2 DM can provide feasible treatment options for subsequent HT treatment.This study was funded by Shanxi Province \u201c136 Revitalization Medical Project Construction Funds\u201d (2021YZ05).a, Weiwei Fana, Qingqing MaaYanrui Jiaa School of Business Administration, Jimei University, Xiamen, Fujian 361021, China.Background: With the rapid development of Internet technology, a wide variety of digital information technologies have gradually integrated into people\u2019s lives and effected consumers\u2019 usage willingness and mood. Consumers have begun to expect payment methods to become more secure, convenient, and intelligent. Then various payment methods based on human biometric for identity verification have gradually emerged.Subjects and Methods: This study combined initial trust theory and perceived risk theory to investigate the effects of a total of five factors such as structural assurance, trust propensity, company reputation, initial trust, and perceived risk on consumers\u2019 psychological willingness and mood to use face swipe payment. Structural assurance is the guarantee of consumers\u2019 environmental security when using face payment. Trust propensity is the degree of consumers\u2019 personal tendency to believe in something new. Company reputation refers to the reputation of the backend company of face payment. Initial trust is the degree of consumers\u2019 trust in face payment in the beginning. Perceived risk refers to consumers\u2019 psychological expectation of unknown negative effects brought by using face payment. With the above five factors as independent variables and consumers\u2019 willingness and mood as dependent variables, the research model was constructed and the hypotheses were verified by using questionnaires and SPSS data analysis.Results: Structural assurance, trust propensity, company reputation, and initial trust significantly and positively affect consumers\u2019 willingness and mood to use face payment. Perceived risk significantly and negatively influenced consumers\u2019 willingness and mood to use. The details are as follows specifically. Higher structural assurance enhances consumers\u2019 initial trust in face payment and thus consumers\u2019 willingness to use it. The characteristic of being more likely to believe in something new positively drives consumers\u2019 initial trust in face payment. The good reputation of the company makes consumers more willing to use the company\u2019s face payment technology. The higher the initial trust, the stronger consumers\u2019 willingness to use face payment. The higher the perceived risk level of face payment, the lower the willingness to use.Conclusions: Valuable reference suggestions were proposed for enterprises to influence consumers\u2019 willingness and mood to use face swipe payment. They need to develop consumer-related protection mechanisms and establish comprehensive information security to maximize the safety of consumers\u2019 personal information and property. Enterprises should pay attention to maintaining their good reputation. Providing consumers with high-quality products and good services is the basis for enterprises to establish good reputation. They should emphasize the advantages of payment technology to attract consumers. When promoting face payment, enterprises should emphasize its convenient and safe functional advantages. They need to strictly comply with the laws and regulations related to face payment and protect consumers\u2019 rights and interests, which is the way to long-term development of enterprises.aLingling Tonga School of Social Service and Development, Zhengzhou Normal University, Zhengzhou, Henan, 450000, China.Background: Chinese entrepreneurs are known as the world\u2019s most hardworking, indomitable and persistent qualities. They not only have the ability to withstand tremendous pressure and deal with complex practices, but also able to keep a balance between their career, family and self-growth. In fact, many Chinese entrepreneurs have serious psychological and health problems due to their work stress and psychological anxiety.Subjects and Methods: From January 2022 to February 2023, 100 entrepreneurs and executives from different fields and industries were selected in Beijing, Shenzhen, Hubei, Xi \u2018an, Zhengzhou and other places for case interviews, observation, visits and questionnaires.Results: In recent years, with the integration of the world economy, the embedding of the Internet economy and the vigorous development of the digital economy, the pace is getting faster and faster, which makes the work pressure and physical and mental health condition of Chinese entrepreneurs cannot be ignored. Many entrepreneurs have physical health problems due to the work pressure and psychological anxiety cannot be well alleviated, such as sleep disorder, fatty liver, chronic gastritis, migraine, alcohol paralysis, low performance, depression, Job burnout, etc.Conclusions: This paper analyzes the influencing factors of entrepreneur\u2019s stress on individual psychological anxiety and establishes a structural model of the influence of entrepreneur\u2019s stress on emotion. Based on the empirical research data, this paper proposes the adjustment strategies and means of entrepreneur\u2019s job stress.Key words: Chinese entrepreneur; psychological anxiety; work pressure; affective disorder; health indicators1.This paper is one of the key research results of the undergraduate Teaching Engineering and Teaching Reform Research project of Zhengzhou Normal University, Research on the Cultivation Model and Standard Evaluation of Undergraduate Excellent Teachers \u201cResearch on the Impact of University Financial Assistance on the Development of Poor Students and Its Influencing Factors\u201d .aWenju Hana College of Foreign Languages and Literature, Northwest Normal University, Lanzhou, China.Background: This paper studies Martin Amis\u2019s masterpiece Money: a Suicide Note, aims to reveal the socioeconomic and psychological impact of mass media\u2019s consumption of body, such as the psychological anxiety.Subjects and Methods: This paper studies the novel from the perspective of media ecology, Baudrillard\u2019s social theories on the consumer society, body in the consumer culture, psychological anxiety and etc.Results: By focusing on the under-examined correlation between mass media, body consumption and anxiety in Amis\u2019s Money, this paper finds out that unlike orality and typography which produce abstract image of body in the mind of different people, the visual media such as TV produce concrete standards of body images, which highlight the importance of appearance, wiping out the uniqueness in people\u2019s appearance. By presenting a vast amount of visual images of the body through make-up, plastic surgery, lights, dressing and etc, the visual media construct ideal and standard images of male and female body, which foreground forever youth, beauty and health that are in fact impossible, and body image is associated with masculinity, femininity, self-discipline and social status, arousing people\u2019s consciousness of their body and anxiety, creating their desire of consumption to maintain their body, thus the mass media reach the goal of promoting consumerism and selling the goods. In order to meet or approximate the criteria of beauty set by visual media, people take various instrumental means to build their body. In this process, they accept the capital and power\u2019s discipline of their body willingly.Conclusions: In conclusion, this paper argues that the male and female body is commodified by mass media, causing great anxiety. In Amis\u2019s Money, under the discipline of media culture, John Self, the protagonist, is preoccupied with his appearance and full of anxiety. Self is so willing to do everything to preserve his body that he would rather quit reading because it hurts his body, which causes anti-intellectualism. And the male characters model after the film stars in their body image and even undergo plastic surgery. So in the age of visual media and high technology, body is oppressed and damaged to a deeper degree. The female characters in Money such as Selina, Caduta self-monitor their body to meet the standards of beauty set by the mass media. Therefore, mass media strengthen the commodification of male and female body, which reduces the value of female to sex and consumption. Instead of being liberated, the human body is still oppressed by aesthetic violence in the contemporary consumer society.This work was supported by the [Northwest Normal University] under Grant [number 2916]a, Chuanping Leib, Qingda Lia, Junling Mac, Li JiadHong Changa School of Marxism, Zhongkai University of Agriculture and Engineering, GuangZhou, Guangdong 510550, China, b School of Marxism, Sun Yat-sen University, GuangZhou, Guangdong 510275, China, c School of Humanities and Management, Guangdong Medical University, Dongguan, Guangdong 523808, China. dHC and CL contributed equally to this study.Background: Human enhancement technology can help people solve better social, economic, and medical problems and improve the social and medical environment. Human enhancement technology aim to improve human productivity through retinal implants, cochlear implants, and other audio-visual enhancement technologies, brain enhancement technologies such as drugs, brain implants, and brain-computer interfaces, and physical enhancement technologies such as exoskeletons and quality of life, thus promoting the progress of society.Subjects and Methods: This study aims to explore the research hotspots and cutting-edge trends of human enhancement technologies in the past 20 years. This study collected literature on human enhancement technologies from the Web of Science database. This study used bibliometric and visual analysis methods to conduct the study. The main paths of knowledge evolution of human enhancement technologies were mapped using CiteSpace visualization software. One of the main ways to perform word contribution analysis is to extract keywords, abstracts, and other relevant information from the dataset and draw a visual knowledge map to determine the relationships between topics in the disciplines represented in the dataset. The literature and the degree of deviation from the current knowledge structure are studied according to the structural transformation model in the citation network.Results: In the last 20 years of human enhancement research, this study identified 159 highly productive scholars and ten collaborative teams with large research sizes. Cluster analysis revealed that the Research was focused on \u201ccognitive enhancement,\u201d \u201cethical enhancement,\u201d \u201cemotional enhancement,\u201d and \u201cdisease and technology enhancement ethics\u201d. There are three shifts in the research themes and directions of human augmentation research, from disease treatment research to general human augmentation research; from medical examination of human cognitive augmentation to ethics of moral and emotional augmentation research; and from human drug augmentation research to biotechnological augmentation research under convergence technology. The frontier literature on human enhancement technology research involves multiple disciplines such as medicine, neuroscience, molecular biology, psychology, ethics, and sociology, and future Research is bound to focus on the convergence and innovation of multiple technologies, multiple topics, and multiple fields.Conclusions: The results of this paper can provide necessary references for researchers engaged in human genetic engineering, drugs, biomedical technology and other aspects of human enhancement technologies, and provide necessary guidance for future research directions.This work was supported by a project grant from \u201cHuman Enhancement Technology Risk Research: Causes, Models and Protocols\u201d, Ministry of Education, Humanities and Social Sciences Research Youth Project (Grant No. 22YJCZH012); \u201cA Philosophical Hermeneutic Study on Emerging Human Enhancement Technologies\u201d, Guangdong Philosophy and Social Sciences Planning Project (Grant No. GD20CZX01); Teaching reform Project of Guangdong Medical University \u201cResearch on Humanistic Quality Training Path of Medical Students in the Vision of Collaborative Education\u201d (Grant No.1JG21083); Guangdong Provincial University characteristic innovation project \u201cConstruction of Humanistic Medicine from the Perspective of Life Culture\u201d (Grant No.2021WTSCX034).a, Qin Zhoua, Wenchao GaobCui Shana College of Civil Engineering, Putian University, Putian, Fujian 351131, China, b CNNC Huachen Construction Engineering Co., Ltd, Putian, Fujian 351100, China.Background: With the rapid rise of China\u2019s social economy from 1998 to 2022, university teachers constantly face dual challenges from society and profession. Their mental health is constantly affected, especially female teachers in Chinese universities. This paper which analyzes the research results on the mental health of female teachers in universities from 1998 to 2022, reveals the development law of the research, summarizes and analyzes the research contents.Subjects and Methods: On the platform of China National Knowledge Network (CNKI), a total of 93 valid literatures were obtained, through the advanced search of the two subject words \u201cfemale teachers in universities\u201d and \u201cmental health\u201d. CiteSpace software is used to cluster analysis for the sample literature. It mainly contains the cluster analysis of literature authors, research institutions and keywords.Results: (1) From the annual trend of research results, the research development trend in the field of mental health of female teachers in universities can be roughly divided into three periods. First, the initial exploration period, paying attention to mental health investigation. Second, the rapid growth period, focusing on the psychological characteristics and influencing factors of female teachers in universities. Finally, the slow growth period, caring on the analysis of coping strategies in mental health problems and the improvement of career happiness. Moreover, the number of published papers peaked in 2008. (2) From the perspective of literature sources, key authors and research institutions, the research results in the field of mental health of female teachers in universities have been published in a wide range of journals, especially in mental health, education and teaching, higher education research field. (3) From the perspective of research contents, hotspots, frontiers and trends, the research contents in the field of mental health of female teachers in universities include the investigation of mental health status, influencing factors of mental health, and strategies for improving mental health. (4) Research hotspots focused on the female teachers in universities mental health status, and strategies to improve mental health problems. (5) Research frontiers can be roughly divided into three research periods.Conclusions: (1) From 2014 to now, the research popularity in the field of mental health of female teachers in universities has declined, and the quantity and quality of research results in this field have great room for improvement. (2) In the future, new technologies and methods, such as simulation prediction model and big data, can be introduced into the research methods in oder to improve the practicability and innovation of the research results in this field. (3) China\u2019s first-tier cities have more developed economies, and more students, higher school standards, and greater pressure on teachers\u2019 life and career. Therefore, the future research area can be further focused on China\u2019s first-tier cities. (4) At present, most researchers and research institutions have a lot of room for future cooperation. The further expansion of cooperative relations is conducive to the overall development of China\u2019s higher education.This work was supported by a project grant from Education and Research Project for Young and Middle-aged Teachers of Fujian Province (Grant No.JAS21249); Education Science Planning Project of Fujian Province (Grant No.FJJKC2020-029); University-level Education Reform Project of Putian University (Grant No. JG2022068).a, Xiaofeng LuobLimin Zhanga Sichuan University Jinjiang College, Pengshan, Sichuan, 620860, China b Sichuan Police College, Luzhou, Sichuan, 646000, China.Background: At the beginning of 2020, the COVID-19 began to sweep across China from Hubei, and the public health safety of Huanggang in Hubei was the first to bear the brunt. Huanggang was known as Huangzhou in ancient China. In 1079 AD, Su Shi, who was selected by the French newspaper Le Monde as one of the \u201cheroes of the millennium\u201d who influenced the world, was demoted to Huangzhou due to the Wutai poetry case. When the plague broke out, he announced the anti epidemic prescription \u201cSheng San Zi Fang\u201d to the public, and countless people survived!Subjects and Methods: During his demotion, Su Shi encountered plagues many times. Due to his rich epidemic prevention experience and effective public health management measures, he repeatedly saved people from distress. In terms of Su Shi\u2019s anti epidemic practice, effective public health management measures are as follows: During the initial stage of the epidemic, go deep into the epidemic area, truthfully report to the superior, and bought time for the government\u2019s timely rescue; Pay attention to drinking water hygiene and prevent accidents before they occur; During the epidemic, he actively promoted the use of prescription drugs to treat the epidemic, while donating funds to establish the \u201cAnle Fang\u201d equivalent to the prototype of a modern square cabin hospital to carry out isolation and self rescue, And integrate civil forces to assist in combating the epidemic; After the epidemic, it is recommended that the government exempt taxes and provide relief to restore people\u2019s livelihood. He also requires that officials who fail to perform their duties in the prevention and control of the epidemic be held accountable, and rectify the official atmosphere to ensure the normal operation of state power in the future.Results: In the early stages of the epidemic, due to the implementation of timely and effective public health prevention measures, the source of infection of the epidemic was quickly cut off; During the epidemic, Public health management measures are timely and effective, fully mobilizing the forces of all sectors of society, saving countless people, and minimizing the harm of the epidemic; After the epidemic ended, economic remedial measures were taken to appease the people\u2019s livelihood, and the lives of the people and government functions gradually returned to normal operation.Conclusion: Su Shi\u2019s series of anti epidemic practices from prevention to treatment are also scientific and reasonable, and still have important reference significance for the prevention and treatment of contemporary epidemic situations; As a great scholar, he also had a profound understanding of traditional Chinese medicine; Whether selflessly donating anti epidemic prescriptions, compiling medical books, or generously donating money to build a shelter hospital to fight the epidemic, these fully reflect his people-oriented, benevolent and pragmatic medical feelings.aXinxia Fanga Department of Music, Yancheng Teachers University, Yancheng, 224007, China.Background: China\u2019s National Mental Health Development Report (2021-2022) shows that the primary factors affecting depression and anxiety levels are age and income, and among which young people are the high-risk groups. According to the report and some relevant statistics, young people are faced with many troubles and challenges such as academic pressure, employment pressure, economic pressure, emotional pressure and so on. Mastering the ability to adjust emotions or words and deeds such as self-regulating depression, dissatisfaction and irritability, and learning to maintain an optimistic and peaceful attitude is a necessary quality to relieve psychological anxiety. What\u2019s more, traditional Chinese culture contains rich and profound psychological values, among which the representative works, such as Jung\u2019s theory of analytical psychology, are greatly inspired by traditional Chinese culture. The Chinese government attaches great importance to the inheritance of traditional Chinese opera, and has issued relevant policies such as \u201cOpinions on the Implementation of traditional Chinese Opera on Entering the Campus\u201d, \u201cOpinions on Comprehensively Strengthening and Improving School aesthetic education in the New Era\u201d, \u201cCompulsory Education Curriculum Plan and Curriculum Standards (2022 Edition Curriculum Standard)\u201d and so on to further encourage the inheritance and development of traditional Chinese opera, which promotes the mental health development of students to a large extent. In the era of new media, it should be remembered that only through continuous innovation can the inheritance methods and means of traditional Chinese opera achieve more remarkable results.Subjects and Methods: Relying on its advantages of low cost, immediacy, fast interaction, etc., the new media has become an important communication platform for traditional Chinese opera. Taking TikTok and Bilibili as an example, the author uses a combination of quantitative analysis and qualitative research to carry out research, and then analyzes the characteristics and trends of people\u2019s cognition, aesthetics and other aspects of traditional Chinese opera, so as to put forward targeted plans for primary and secondary school students to improve their cultural spiritual literacy, enhance the sense of national cultural identity and strengthen their mental health.Results: According to some relevant surveys, there are still insufficiency in netizens\u2019 awareness of traditional Chinese opera inheritance and knowledge reserve. In order to promote the physical and mental health of the general public through the dissemination of traditional Chinese opera, it is really necessary to cultivate their appreciation ability of traditional Chinese opera from an early age, strengthen the promotion of aesthetic education infiltration practice activities on primary and medium-sized campuses, and realize the whole process of aesthetic education for the whole people.Conclusions: The peaceful, harmonious, tenacious and optimistic aesthetic characteristics embodied in the traditional Chinese opera will not only have a positive guidance to the audience\u2019s psychology, but also strengthen their sense of national cultural identity and enhance their national cohesion. Additionally, while inheriting traditional Chinese culture, we should realize that the personality development and mental health of students and always bear in mind that the cultivation of aesthetic consciousness should be cultivated from an early age. What counts most is that, rich and colorful traditional Chinese opera aesthetic education activities should be designed according to the psychological characteristics and learning ability of students of different ages.aShuhan Hua School of Visual Communication, Lu Xun Academy of Fine Arts, Liaoning Province, China.Background: Art therapy is a separate discipline born in Europe in the 1930s and 1940s from the fusion of art and psychology as a form of creative expression for therapeutic purposes. The art therapy process consists primarily of the creation of art as therapy itself, and the resulting interaction between the practitioner and the subject. Art therapy has been widely used in Europe and the United States and has been shown to have a positive effect on a person\u2019s mental health and to alleviate many mental illnesses through art therapy, while art therapy is still in its infancy in theory and practice in China.Subjects and Methods: This paper first discusses the relationship between art creation and mental health, and then goes through the applications of art therapy in life, medicine and society respectively, pointing out through case studies that art creation can release psychological stress, relieve pain, alleviate illness and make a prominent contribution to mental health, followed by a brief overview of the current state of development of art therapy in China.Results: Artistic creation in psychological healing is not only an expression of one\u2019s emotions, but also a clear contribution to physical and mental health.Conclusions: Art therapy is an art of communication methods that has made an outstanding contribution not only to the psychological meaning of visual symbolism, to the relationship between creativity and health, but also to alternative therapeutic approaches. In the future this discipline will play an even greater role in building the field of mental health and has even greater potential to be explored. It has a role to play in human understanding of the self, healing and healthy living that cannot be ignored.a, Luxia LinaYanrui Jiaa School of Business Administration, Jimei University, Xiamen, Fujian 361021, China.Background: With the rapid development of Internet and information technology, a number of \u201cnet celebrities\u201d with distinctive features and economic benefits have emerged on social media platforms. Through social media platforms, net celebrities conveyed information about corporate brands or products to consumers, which improved their visibility and profoundly affected people\u2019s online consumption intention and mood. It is an emerging trend for companies to rely on social media platforms to influence consumers\u2019 shopping behavior through the Netflix model.Subjects and Methods: This paper firstly explained the theoretical foundation of social media and the current situation of Netflix, and analyzed the influencing factors of consumers\u2019 online purchase intention and mood, then deduced the influencing factors of consumers\u2019 purchase behavior under the Netflix model. Secondly, through the empirical study of quantitative analysis, the model of the influence of Netflix communication on consumers\u2019 purchase intention was constructed, with consumers\u2019 purchase intention as the dependent variable and with the product factor, the Netflix factor and the perception factor as independent variables. Finally, relevant conclusions were drawn by using questionnaires, SPSS data correlation analysis and regression analysis.Results: The factors that positively influence consumers\u2019 purchase intention and mood under Netflix social communication include product quality, users\u2019 product evaluation, interactive attitude of Netflix, multi-channel publicity of Netflix, and consumers\u2019 perceived value of the product. The specific descriptions are as follows. The higher the product quality, the better the consumer\u2019s shopping experience. The better the user\u2019s product evaluation, the stronger the consumer\u2019s purchase intention. The good interactive attitude can meet the consumer\u2019s demand. The multi-channel publicity both reduces the cost and expands the effect of Netflix. The higher the consumer\u2019s perceived value of the product, the stronger the consumer\u2019s purchase intention. In contrast, product information and perceived risk have no positive influence on consumers\u2019 purchase intention, i.e., specific and accurate product information does not have a significant positive influence on consumers\u2019 purchase intention, and consumers\u2019 perceived risk of the product has no significant negative influence on purchase intention.Conclusions: Marketing suggestions for enterprises to effect consumers\u2019 purchase intention and mood are presented. Firstly, enterprises can use differentiated Netflix groups to improve consumers\u2019 perceived value of their products. Secondly, focus on interactive marketing. Net celebrities should publish content according to consumers\u2019 interests, share their own real feelings of using the products, and actively interact with consumers on platforms such as video, live streaming or social. Thirdly, improve product quality. Companies can enhance consumer participation, so that consumers can participate in the process of designing and improving products. Finally, establish channel advantages. Enterprises should choose the right social media platform for cooperation according to their own product and industry characteristics to establish their long-term channel advantages.aFeng Yanga College of Chinese Language and Culture, Zhejiang Yuexiu University, Shaoxing, Zhejiang 312000, China.Background: This paper combines respiratory and acoustic signals from a physiological and acoustic perspective to write a program that divides the prosodic hierarchy based on the magnitude of respiratory reset amplitude, explores the corresponding relationship between the respiratory reset amplitude and the prosodic hierarchy, also explores the respiratory physiological mechanisms of acoustic features such as pauses, pitch dips, and amplitude dips in speech flow. To provide methods for speech rehabilitation training, improve patients\u2019 speech naturalness and fluency, enhance the effect of speech rehabilitation training. It provides a new method and thought for speech rehabilitation.Subjects and Methods: In this paper, the acoustic analysis method is used to record the voice and respiratory signals of 80 short passages read by four announcers. Write a Matlab program to analyze the four signals. Firstly, automatically mark the various respiratory reset positions of the chest and abdomen respiratory signals, calculate parameters such as respiratory reset amplitude, inhalation and exhalation duration, and then divide the prosodic hierarchy based on the magnitude of respiratory reset amplitude, mark the boundaries of prosodic units, and finally output parameters such as the duration, fundamental frequency, and amplitude of each prosodic unit.Results: The results show that there is a corresponding relationship between the repositioning amplitude of respiration and the prosodic boundary in discourse reading. (1) In discourse reading, the amplitude of respiratory reset can be divided into three levels. The first level respiratory reset corresponds to paragraph or complex sentence boundaries, the second level respiratory reset corresponds to clause boundaries, and the third level respiratory reset corresponds to prosodic phrase boundaries. (2) The pause coincides with the inspiratory segment, and the reason for the pause is to inhale for pronunciation, while the phonetic segment coincides with the expiratory segment. (3) Along with the pitch dip, the amplitude dip occurs simultaneously within a breathing cycle. The dip is caused by the continuous exhalation of air flow from the lungs during the exhalation pronunciation stage, resulting in a decrease in air pressure. The focus stress is mainly manifested as an increase in pitch. Phonological fluency is related to respiratory reassignment, which can be used for phonological rehabilitation training.Conclusions: The physiological reason for the pause is the completion of inspiratory movement, and the downward pitch and amplitude decline are caused by the attenuation of the airflow pressure in the expiratory segment of the lungs. In the process of language rehabilitation training, patients should master the correct breath control method, and adopt different sizes of breath resets according to the pause position of the discourse, so as to improve the effect of language rehabilitation training and the naturalness of the pronunciation of reading training.This work was supported by Major Projects of National Social Science Foundation \u2018Research on the contact and integration of Chinese languages\u2019 (Grant No.22&ZD213).a, Huiqiong HubBin Liua Jingzhou Central Hospital, Jingzhou 434020, China, b Hubei College of Chinese Medicine, Jingzhou 434020, China.Background: To provide reference for the diagnosis and treatment of influenza A (H3N2) in clinic and to reduce the mortality in patients with influenza A (H3N2) through the study on the level change of serum amyloid A (SAA), interleukin-6 (IL-6) and hypersensitive-C-reactive protein (hs-CRP) in patients with influenza A (H3N2).Subjects and Methods: 177 patients who had the clinical manifestations of influenza and were positive for H3N2 subtype influenza virus in the nucleic acid testing of the nasopharyngeal swab or sputum samples in Jingzhou Central Hospital from January 1, 2022 to December 30, 2022 were selected as the influenza A (H3N2) group. Another 169 subjects who underwent health examinations during the same period were selected as the healthy control group. The venous blood samples were collected in the influenza A (H3N2) group and healthy control group to detect the levels of SAA, IL-6, and hs-CRP in peripheral blood. The levels of the SAA, IL-6, and hs-CRP in the influenza A (H3N2) group and healthy control group were analyzed, and area under the curve (AUC), cutoff value, sensitivity, specificity, and Yoden index of single detection of SAA, IL-6, and hs-CRP and joined detection (SAA + IL-6+ hs-CRP) were compared to analyze the diagnostic value of single detection and joint detection on the diagnosis and treatment of influenza A (H3N2).Results: The levels of SAA, IL-6 and hs-CRP in influenza A (H3N2) group were 46.49\u2009\u00b1\u200929.08\u2005mg/L, 22.03\u2009\u00b1\u200911.59 pg/mL and 14.88\u2009\u00b1\u20097.80\u2005mg/L, respectively, significantly higher than those in healthy control group. The differences of SAA, IL-6 and hs-CRP between the two groups were statistically significant in test . The area under the curve (AUC), cutoff value, sensitivity, specificity and Yoden index of single detection of SAA, IL-6 and hs-CRP in influenza A (H3N2) group showed that the cutoff value of the serum SAA was 12.40\u2005mg/L with AUC, sensitivity, specificity, and Yoden index of 0.952, 0.819 and 0.988, respectively, significantly higher than that of IL-6 and hs-CRP; the AUC, sensitivity, and Yoden index of the joint detection (SAA + IL-6+ hs-CRP) were 0.964, 0.938, and 0.820, respectively, higher than those in the single detections; however, the specificity of the joint detection (SAA + IL-6+ hs-CRP) in influenza A (H3N2) group was 0.882, lower than that in the single detection.Conclusions: Markedly increased level of serum SAA can be found in patients with influenza A (H3N2). The joint detection of of SAA, IL-6 and hs-CRP is helpful for the diagnosis and evaluation of conditions of patients with influenza A (H3N2), which can be used as the reference for the diagnosis and treatment of influenza A (H3N2) in clinic with significant clinic value.a, Longhui ZhoubLiqiu Lina College of Physical Education and Health, Guangdong Vocational College of Science and Technology, 519090, Zhuhai, Guangdong, China, b Physical Education, Guangdong Jiangmen China Medicine College, Jiangmen 529000, Guangdong, China.Background: To briefly discuss related strategies of integrating sports psychology into physical education teaching in colleges and universities, so as to provide experience reference and help for practitioners in related industries, and promote the development of sports literacy of students in colleges and universities. This paper discusses the significance of integrating physical education into sports psychology health education in colleges and universities, and puts forward relevant countermeasures accordingly, in order to provide reference for physical education teachers in colleges and universities.Subjects and Methods: Questionnaire survey, logical analysis, expert interview and empirical research were used to explore the significance of integrating physical education into sports psychology health education in colleges and universities, and corresponding countermeasures were put forward.Results: In the physical education teaching practice of colleges and universities, it is necessary to infiltrate and integrate the related content of sports psychology, so as to continuously enhance the mental health quality in the teaching process and achieve excellent results in sports training. Constantly improve the ability of thinking control and self-regulation control of college students, to improve the physical psychology of college students to lay the foundation. In order to realize the cultivation of mental health quality of young people in colleges and universities in sports, the organization and development of sports should be guided by the law of physical and mental development of young people and the law of physical education teaching, take positive emotion, experience success, democratic autonomy and individual guidance as the basic principles, and take the organic, moderate and flexible penetration in the process, content and method of sports as the main strategy, so as to be practical. Training design and effective classroom management as process control to construct the physical sports youth mental health quality training path.Conclusions: By analyzing the correlation between the discipline orientation of sports psychology and the connotation of sports core literacy, the promoting effect of sports psychology research content on sports core literacy, and how to cultivate sports core literacy in sports psychology teaching, this paper tries to clarify the role of sports psychology curriculum in promoting students\u2019 sports core literacy, so as to better cultivate students\u2019 knowledge of sports psychology. Ability to solve problems related to sports practice.a, Manyi Chenb, Junling Maa, Cheng Yuc, Chuanping LeidLi Jiaa School of Humanities and Management, Guangdong Medical University, Dongguan, Guangdong 523808, China, b Nanling Corridor Country Revitalization Research Institute, Xiangnan University, Chenzhou 423000, China, c School of Medicine, Sun Yat-sen University, Shenzhen 518107, China, d School of Marxism, Sun Yat-sen University, GuangZhou, Guangdong 510275, China.LJ and MC contributed equally to this study.Background: The frequent occurrence of doctor-patient conflicts and medical disputes in the process of healthcare system reform has made medical humanities research a critical issue in public and scientific research. Despite the increasing number of studies on medical humanities, there is a lack of comprehensive and systematic combing based on bibliometrics.Subjects and Methods: This study uses author collaboration, institutional collaboration, keyword co-occurrence, cluster analysis, Structural Variation Analysis, bipartite graph overlay, and country and keyword bimodal mapping construction based on medical humanities-related research literature data from 1974-2022 in the Web of Science database to comprehensively and systematically sort out medical humanities.Results: The study found that the authors in the field of medical humanities research have been working on the following topics: scientific cooperation, research hotspots, and frontiers, knowledge base evolution trends, and prediction of potential, influential literature. It was found that author co-location and institutional cooperation in medical humanities research are relatively close, forming a complex cooperative network. Institutional research is more active in countries such as the United States, Canada, and the United Kingdom. The knowledge base and significant fields in medical humanities research show diversified development, and the intersection of subject areas is becoming stronger. Hot research issues represented by medical humanities education, medical humanities care, doctor-patient communication, and medical ethics have been formed. Moreover, 11 pieces of potentially influential literature have been mined.Conclusions: This study uses bibliometrics to systematically sort out the development trend, research hotspot and potentially influential literature in the field of medical humanities research since 1974, so as to provides relevant theoretical references and references for research in medical humanities and even medical humanities education.This work was supported by a project grant from National Social Science Fundation: Research on China\u2019s Experience and Global Sharing in Building a Human Health Community (Grant No. 20&ZD122); Teaching reform Project of Guangdong Medical University \u201cResearch on Humanistic Quality Training Path of Medical Students in the Vision of Collaborative Education\u201d (Grant No.1JG21083); Guangdong Provincial University characteristic innovation project \u201cConstruction of Humanistic Medicine from the Perspective of Life Culture\u201d (Grant No.2021WTSCX034).a, Deling Yanga, Feng Fenga, Jianhua Yangb, Xijun Huanga, Shiqi ChenaXiao Zhanga Guangzhou Academy of Fine Arts, Guangzhou, China, b Qingdao University of Science and Technology, Qingdao, China.Background: To explore the main technical applications for increasing the effectiveness of smart museum exhibitions in providing psychologically therapeutic services for visitors in the aftermath of the COVID-19 pandemic, with the goal of investigating the development of museum services for psychological treatment of visitors.Subjects and Methods: From the perspectives of art therapy and cognitive psychology theory, this paper provides a literature review of relevant papers and monographs on social psychological therapy in smart museums. Focusing on museums\u2019 psychological therapeutic services, the analysis examines trends in the development of smart museum exhibition technologies for visitors\u2019 psychological therapeutic services.Results: The psychological problems caused by the pandemic are similar to those of post-traumatic stress disorder (PTSD), making museums an ideal platform for artistic experiences and psychological healing. First, museums provide visitors with an experience environment that reflects a beautiful society and life, helping them to recover from negative emotions and addressing issues related to intrusive memory affecting psychological health. Second, museums offer creative exhibition activities to enhance social communication, helping visitors overcome fear and anxiety, while cultivating confidence and hope for a better future, addressing psychological health problems related to excessive pessimism leading to a loss of willpower. Third, museums provide an enjoyable experience that helps to heal the soul, addressing psychological health problems related to social anxiety.Conclusions: Firstly, smart museums can provide more open and inclusive services to the public by integrating online and offline exhibitions through the use of virtual reality and mobile communication technologies. By breaking down social barriers and alleviating post-pandemic social anxiety, smart museums can attract visitors to return to the museum environment. Secondly, by closely integrating artificial intelligence, the Internet of Things and collection resources in the planning of museum exhibitions, smart museums can create distinctive features that provide more targeted healing solutions for diverse groups of people with various psychological disorders. Thirdly, smart museums can explore scientific methods for treating psychological problems through exhibitions by leveraging big data, cloud computing and collaborating with relevant institutions, thereby making the focus on visitors\u2019 psychological health an important service content of museums. This study aims to contribute new technological applications to the development and construction of enhancing visitors\u2019 psychological health in museum exhibitions.This research partially funded by Ministry of Education of China under the Humanities and Social Sciences with the project \u201cResearch on the normal form of personalized interpretation of smart museum exhibition\u201d (project number 21YJA760093). The research is partially supported under and the 2021 Guangdong province graduate education innovation plan with the project \u201cGuangdong joint postgraduate training demonstration base\u201d (project number: 6040121010). Thanks should go to Ministry of Culture and Tourism of China under the Art Research Key Project Support Plan of 2022 Social Science Fund with the project \u201cComparative Study of Chinese, Japanese and Hollywood Animation Film Aesthetic and Cross-Cultural Communication Strategy\u201d (project number 22AC003). Special thanks to Guangzhou Academy of Fine Arts for the support of project on Film and Television Special Effects (project number: 6040321054), Science and Technology Art Experimental Class (project number: 6040321002), Research on the Teaching Method of Cultivating Graduate Students\u2019 Cross Media Art Creation Practice (project number: 6040122012LHKY), Research on the Design Method of Digital Exhibition in Smart Museums Based on Technology and Art (project number: 23XSC32).a, JinQi SongaXuan Songa Central South University of Forestry and Technology of Business, Changsha 410000, Hunan, China.Background: Based on the sustainable livelihood analysis framework, this paper conducts in-depth research on the impact of livelihood capital and mental health on the differentiation of farmers in mountainous areas. This is important as industrial differentiation provides a reference for promoting multi-channel income generation for farmers and achieving rural revitalization in mountainous areas.Subjects and Methods: A comparative analysis and multivalue selection model were used to explore the occupational differentiation of 180 farmers in mountainous areas of Hunan Province under different influencing factors.Results: The research results indicate that social capital differentiates pure and non-agricultural farmers into part-time farmers. Rich natural capital can attract farmers to differentiate into pure farmers or part-time farmer enterprises. Moreover, increased financial capital will help part-time farmers focus on agricultural production and encourage non-agricultural operators to engage in agricultural operations. The impact of physical capital will transform farmers into pure or non-agricultural full-time farmers. However, farmers with work experience are likelier to choose part-time agricultural forms. Providing agricultural technology training to farmers can help them immerse themselves in agricultural production by improving their production and management abilities. Additionally, mental health positively impacts the differentiation of pure farmers into part-time farmers and the livelihood capital differentiating the farmers depending on the proximity to the central market.Conclusions: The following suggestions are proposed. Increase psychological health training, develop farmers\u2019 enthusiasm, implement \u201cendogenous\u201d and \u201cexogenous\u201d industrial assistance, and ensure employment. Additionally, attention should be paid to optimizing and combining various livelihood capital and increasing immigrant livelihoods\u2019 sustainable endogenous driving force. Moreover, increase opportunities for immigrants to engage in non-agricultural businesses and encourage the development of ethnic minority characteristic tourism industries and online operation of \u201ccharacteristic products\u201d. While increasing support for non-agricultural skill training, it is necessary to assist the psychological health construction of migrant workers\u2019 families mainly engaged in agricultural production. Land asset transfer and appreciation work for contracted land for relocation, mountainous forest land, and homestead land are also important. Finally, restoring social networks, cultural protection, and development for ethnic minority immigrants should be considered.a, Li Zhonga, Qinghong Houa, Yunning TanbChangping Yina School of Accounting, Chongqing University of Technology, Chongqing, China, b School of Accounting, Chongqing Technology and Business University, Chongqing, China.Background: \u201cMitigating and adapting to global warming and reducing carbon dioxide emissions\u201d has become the political consensus of all countries in the world, and is also a common challenge for the world. Greenhouse gas emissions, such as carbon dioxide, not only affect political, economic and cultural development, but also have a significant negative impact on the psychological health and happiness of the general public. In order to reduce carbon emissions, the countries of the world have signed and introduced the Kyoto Protocol, the Paris Agreement, the Glasgow Climate Convention and other international conventions. In September 2020, China proposed at the 75th session of the United Nations General Assembly that \u201cChina should strive to reach peak carbon dioxide emissions by 2030 and achieve carbon neutrality by 2060\u201d .Subjects and Methods: On February 28, 2022, the United Nations Intergovernmental Panel on Climate Change (IPCC) issued a bulletin stating that greenhouse gas emissions such as carbon dioxide can lead to a series of psychological health problems. In order to better reduce carbon emissions, this paper constructs a carbon audit index system under the carbon peaking and carbon neutrality target based on the hierarchical analysis method with the perspective of the audit and the carbon peaking and carbon neutrality target as the guide.Results: This paper constructs a carbon audit index system based on the main line of \u201ccarbon emission policy formulation and implementation \u2192 carbon emission reduction governance investment \u2192 carbon emission project management \u2192 carbon emission governance output \u2192 carbon emission management effect\u201d, in an attempt to comprehensively, systematically and scientifically evaluate and authenticate the carbon reduction and emission reduction behaviors of each region and unit, and suppress the negative impact of carbon emission on people\u2019s psychological health.Conclusions: Carbon emission is a global issue, closely related to human economic and social development and physical and psychological health. As the \u201cinspector\u201d of policy implementation and the main national governance system, we should give full play to the role of audit in promoting the \u201cdouble carbon\u201d work, strengthen the audit supervision of carbon emission policies, projects, funds and benefits, and help achieve the national carbon peaking and carbon neutrality goals.This work was supported by a project grant from China Postdoctoral Science Foundation (Grant No. 2020M683255), and the National Social Science Fund Item (No. 22BJY033), and the Humanities and Social Sciences Project of the Ministry of Education (No. 19YJC630205).a, Deling Yanga, Feng Fenga, Jianhua Yangb, Shiqi Chena, Xijun HuangaXiao Zhanga Guangzhou Academy of Fine Arts, Guangzhou, Guangdong Province, People\u2019s Republic of China, b Qingdao University of Science and Technology, Qingdao, Shandong Province, People\u2019s Republic of China.Background: Contemporary social work and life stress bring about psychological issues such as depression and anxiety. However, due to limited medical resources, it is necessary to explore the use of art healing as a means to provide psychological therapy services to the general public.Subjects and Methods: This study explores the application of traditional immersive garden exhibition art healing as a method of psychological therapy through natural scenery and humanistic art therapy for the general public. Specific research includes the ways in which exhibitions soothe the emotions of the general public, the use of immersive experiential innovative art healing in exhibitions, and the integration of individuals undergoing art healing into society through exhibitions. Through the analysis of psychological therapy cases and qualitative analysis, taking the \u201cThree Mountains and Five Gardens Exhibition\u201d as an example, the application of art healing in exhibitions for psychological therapy is analyzed and studied from the aspects of communicating audience emotions, allowing audiences to immerse themselves in the art field, and creating a panoramic discourse space for artistic symbols to project new emotions from the audience.Results: First, the \u201cThree Mountains and Five Gardens Exhibition\u201d constructs artistic discourse and achieves emotional resonance and psychological comfort for the audience. Second, virtual reality immersive exhibitions encourage audience participation and artistic experience, achieving emotional healing. Third, the exhibition integrates artistic symbols, recreates cultural symbol representations through various media, and forms a panoramic discourse space constituted by artistic symbols, projecting the audience\u2019s emotions into a new cultural imaginary space for psychological healing.Conclusions: First, art healing fulfills the social responsibility of exhibition updates, reflects the exhibition\u2019s deeper care for the public, and extends the psychological therapy services of traditional immersive garden exhibitions. Second, exhibitions innovate the psychological therapy methods of art healing. Through the panoramic discourse space created by the exhibition\u2019s artistic symbols, the audience can project new emotions and achieve physical and mental healing. Third, the healed audience can better express their thoughts and release emotions through exhibitions to enhance communication. Therefore, the exhibition of innovative art therapy can serve the mental health of the public in a new way.This research partially funded by Ministry of Education of China under the Humanities and Social Sciences with the project \u201cResearch on the normal form of personalized interpretation of smart museum exhibition\u201d (project number 21YJA760093). The research is partially supported under and the 2021 Guangdong province graduate education innovation plan with the project \u201cGuangdong joint postgraduate training demonstration base\u201d (project number: 6040121010). Thanks should go to Ministry of Culture and Tourism of China under the Art Research Key Project Support Plan of 2022 Social Science Fund with the project \u201cComparative Study of Chinese, Japanese and Hollywood Animation Film Aesthetic and Cross-Cultural Communication Strategy\u201d (project number 22AC003). Special thanks to Guangzhou Academy of Fine Arts for the support of project on Film and Television Special Effects (project number: 6040321054), Science and Technology Art Experimental Class (project number: 6040321002), Research on the Teaching Method of Cultivating Graduate Students\u2019 Cross Media Art Creation Practice (project number: 6040122012LHKY), Research on the Design Method of Digital Exhibition in Smart Museums Based on Technology and Art (project number: 23XSC32).a, Menghua Liub, Qian Dua, Xianglei ZhucLongchao Xua Department of Social policy & Social work, School of Humanities, Taiwan National Chi Nan University, Taiwan, China, b Graduate School, University of Perpetual Help System DALTA, Las Pi\u00f1as City, Philippines, c Department of Health Sociology, School of Humanities and Management, Guangdong Medical University, Dongguan, China.LX and ML contributed equally to this study.Background: In recent years, the widespread use of smart devices for the elderly has also triggered more and more attention to how the elderly use smart devices and the importance of smart devices for the health management of the elderly. To this end, this study will investigate the relationship between the use of smart devices and the health management of the elderly to provide a scientific reference basis for optimizing the use of smart devices and implementing health management in the elderly.Subjects and Methods: This paper mainly uses the ordered Probit model to study the effects of smart device use on physical health and mental health of older adults. This paper examines the effects of attitudes, subjective norms, and perceived behavioral control on the physical and mental health of older adults based on planned behavior theory using CGSS 2017 data on older adults aged 60 years and older as a research sample, and analyzes the effects of educational attainment on the relationship between them.Results: It was found that more positive attitudes towards smart device use were associated with higher levels of physical and mental health. However, the moderating effect of educational attainment on the relationship between smart device use and physical and mental health was not significant. In addition, this paper makes the following recommendations: (1) communities increase education and training on the application of smart device for older adults. (2) Family as the smallest unit of support system, with intergenerational interaction to promote digital feedback, can effectively drive the digital integration of older adults.Conclusions: This study found that in China, older adults have more positive attitudes toward smart device use. Moreover, the more positive the attitude toward smart device use, the higher the level of physical and mental health. However, the moderating effect of education level on the relationship between smart device use and physical and mental health was not significant, but the regression coefficient was negative. This paper to provide more practically meaningful guidance and suggestions for the use of smart devices in the elderly, and to provide better support and assistance for health management and smart device use in the elderly.This article is the research output of the introduced talent scientific research launch fund project of Guangdong Medical University--\u201cApplication and improvement research of innovative technology of social work service for the Elderly\u201d.a,b, Yongtian Wub, Peitao Yangc, Xuekai WeibJianping Liua College of Civil and Environmental Engineering, Hunan University of Science and Engineering, Yongzhou, Hunan 425199, China, b Bama Hetai Longevity Industry Co., Ltd., Bama, Guangxi 547500, China, c College of Economics, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.Background: The psychological recognition level of rural residents is the basis and prerequisite for choosing and promoting innovative development of rural industries. However, for a long time, the relatively weak foundation of rural industrial development, insufficient competitive advantages in industries, and relatively low output return rates have led to deep doubts among rural residents about whether they can promote innovative development of rural industries. It is urgent to alleviate the psychological anxiety of rural residents in both theoretical and psychological aspects, this has important theoretical and practical significance in promoting innovation and sustainable development of rural industries, achieving coordinated development between urban and rural areas and regions. However, there has been no research exploring the correlation and impact of rural industrial development and residents\u2019 psychological interaction from the perspective of psychological health and symbiosis theory.Subjects and Methods: Using the research method of symbiosis theory, an in-depth analysis and summary of the common anxiety problems in villagers\u2019 psychology were conducted from the perspective of mental health management. A comprehensive and systematic study in Some aspects of the construction and improvement of villagers\u2019 psychological health, improvement of psychological cognition level, composition of rural industrial symbiosis system, symbiotic connection mechanism, symbiotic interface, symbiotic mode, symbiotic ecosystem and other aspects has been researched on the interactive mechanism between the psychological logic and motivation of villagers\u2019 psychological anxiety and the innovative development of rural industries.Results: The research results indicate that villagers\u2019 psychological anxiety is the fundamental obstacle that restricts the innovative development of rural industries. The level of villagers\u2019 psychological health is the fundamental prerequisite for determining and influencing the innovative development of rural industries. Insufficient or biased psychological cognition of villagers is the primary obstacle that hinders the development of rural industries, and the lag in development awareness and thinking is the internal reason that hinders the development of rural industries, The insufficient level and depth of integration are the main practical problems faced by the development of rural industries, and the weak linkage mechanism is the fundamental reason that restricts the development of rural industries.Conclusions: There is an urgent need to build a sustainable development path for rural industries in some aspects of alleviating villagers\u2019 psychological anxiety, improving their mental health level, improving their psychological cognition level, strengthening the concept of innovative symbiotic development, constructing a connecting carrier platform, constructing efficient symbiotic mode, smoothing symbiotic interfaces, creating a positive symbiotic environment, constructing symbiotic connection mechanism, and strengthening co-effectiveness, in order to create a symbiotic ecosystem for innovative development of rural industries, To provide theoretical and practical references for promoting the sustainable development of rural industries.This work was supported by a project grant from Natural Science Foundation of Hunan Province(Grant No.2019JJ40545) and Hunan University of Science and Technology Applied Characteristic Discipline Construction Project(Grant No.18TSXK-001).a, Shanshan Niua, Yijian WangaChunyi Caoa Zhejiang Institute of Economics and Trade, Zhejiang Province, Hangzhou, China.Background: To achieve rural revitalization more quickly and effectively, it is necessary to enhance the quality of the vast peasantry, as farmers are an important human resource for rural revitalization. However, there are still issues such as low mental health level of farmers and long-term neglect of farmers\u2019 psychological problems. Therefore, it is imperative to conduct research on improving the mental health level of farmers in the context of rural revitalization.Methods: Based on Maslow\u2019s Hierarchy of Needs theory, research and analyses of farmers\u2019 actual needs can be conducted. With the support of metaverse technologies, artificial intelligence and virtual reality technologies, an all-in-one agricultural assistance platform can be built to provide innovative digital content applications for farmers\u2019 production, sales, and livelihood.Results: Based on the agricultural assistance platform, 3D virtual sports interaction with fun elements can be utilized to address the issues of inadequate sports facilities and farmers\u2019 weak awareness of fitness, thereby improving farmers\u2019 physical fitness and meeting their physiological needs. Through online and offline e-commerce skills training and the agricultural assistance platform, the problem of farmers lacking e-commerce skills and sales channels can be solved, thus fulfilling farmers\u2019 safety needs. By leveraging metaverse technologies to allow users to understand the original production process of products, communication between farmers and consumers can be promoted, satisfying farmers\u2019 social needs. Through big data and AI technologies, brand planning and design for agricultural products can be carried out, thus meeting farmers\u2019 self-actualization needs and promoting the holistic development of rural residents\u2019 physical and mental health.Conclusions: As a research hotspot in the digital economy, the integration and development of metaverse with the agricultural field holds great potential. Particularly, the innovative approach of incorporating metaverse into farmers\u2019 mental health in this article is noteworthy. Improving the overall mental well-being of rural areas is crucial for ensuring sustainable development in rural areas, and there is still a long way to go.a, Weifeng Xieb, Guo Fengb, Pengpeng Yub, Xianhui DuanaYanhua Zhoua College of Urban Construction, Jiangxi University of Technology, Nanchang 330098, China, b Department of Material Science and Engineering, Jingdezhen Ceramic Institute, Jingdezhen 333000, China.YZ and WX contribute equally to this work.Background: The rapid development of phosphor application materials and technology provides a very important platform and means for the research and development of medical detection, and the key to effective control and treatment of diseases is that accurate detection can be carried out at an early stage, so the development of new, stable, simple preparation conditions, practical value of red phosphor is a very meaningful work. Near-infrared light has important applications in security monitoring, biomedicine, plant lighting, spectral detection and other fields. Traditional near infrared light source cannot meet people\u2019s demand for fast and convenient use of near infrared equipment. Near-infrared phosphor conversion LED can make up for the deficiency of the traditional near-infrared light source, and it is the most promising new near-infrared light source to replace the traditional near-infrared light source.Subjects and Methods: Red phosphor has excellent optical properties, can emit red fluorescence, has the advantages of high stability and high efficiency, and can be used for biomedical detection. NaLa4(SiO4)3F: Eu3+ red phosphor was prepared by solid-phase method, and the influence of preparative process parameters on performance was systematically studied.Results: The study found that: the minimum temperature for the synthesis of NaLa4(SiO4)3F phase by solid-phase method was 750\u2103, the minimum temperature for the preparation of NaLa4(SiO4)3F pure phase was 850\u2103, and the optimal heat treatment temperature is 950\u2103. The optimal dosage of sodium fluoride (multiple of relative stoichiometric ratio) x = 1.3. The use of heat treatment and heterogeneous methods to strengthen the conversion of fluorescent materials in disease and biomedical detection has great significance and considerable application prospects. It is believed that the thermal stability regulation and design of phosphor will become an important research hotspot of phosphor research, will be widely concerned by researchers, and will become a kind of very potential phosphor matrix materials.Conclusions: The phosphor particles prepared by the solid phase method are spherical-shaped, with clear edges and surfaces, narrow particle size distribution, and are suitable for LED packaging. NaLa4(SiO4)3F: Eu3+ red phosphor will become an important tool to assist related medical testing, and is also widely used in portable and real-time related testing, providing important support and guarantee for medical testing.This work was supported by the Higher Education Teaching Reform Project of Jiangxi Provinc China (JXJG-22-24-5), the National Natural Science Foundation of China , Jiangxi Provincial Natural Science Foundation , Open fund project of the Key Laboratory of Inorganic Coating Materials, Chinese Academy of Science (ICM-202001), the Projects of Jiangxi Provincial Department of Science and Technology (20202BABL214013), the Science Foundation of Jiangxi Provincial Department of Education .aShaoyun Yanga Business Administration School, Zhuhai Technology Colleg, Zhuhai City 516000, China.Background: In recent years, with the acceleration of urbanization and economic development, the sense of happiness and belonging brought by cities has not been satisfactory. Cities gather population and various resources, but at the same time, the oppression and decadence caused by living issues such as wages, childbirth, education, transportation, and prices are becoming increasingly severe. Citizens\u2019 impression of the city has changed from a warm home to ubiquitous work pressure. This phenomenon constantly reminds us that there have been social and psychological problems in China\u2019s urbanization process. A series of popular communication trends such as \u201cfleeing Beijing, Shanghai, and Guangzhou\u201d have shown us that the main body of urban image shaping should be understanding the happiness of life, reflecting more on the psychological health and spiritual satisfaction of citizens. Nowadays, people have created increasingly diverse forms of communication through the communication platforms provided by modern technology, and their recognition of regional culture is becoming increasingly strong. The increasing pressure and anxiety in urban life are psychological issues in the development of Chinese cities, but these issues also provide soil for the construction and development of urban culture and image.Subjects and Methods: Urban image refers to various perceptual factors presented by a city in the public\u2019s mind, which can be the influence of various aspects such as architecture, culture, history, environment, cultural activities, etc., as well as people\u2019s understanding and interpretation of the symbols and meanings generated by these factors.Audience psychology refers to the thinking, emotions, and behavioral reactions that occur during the process of receiving and processing information. In communication activities, understanding the characteristics and changing trends of audience psychology can effectively formulate communication strategies and creativity, thereby improving communication effectiveness.Literature research and data analysis methods are used in this article. In the current era of information explosion, all kinds of communication media are using different communication strategies to attract the attention of the audience. In fact, they are trying to break through the audience\u2019s psychological system: make appropriate information according to the criteria of the audience\u2019s psychological selection, so that the information transmitted can enter the audience\u2019s psychological system faster and better through the psychological selection of the audience. Therefore, the psychological selection process of the audience has become the \u201cinvisible axis\u201d of various media production content today.Understanding the psychological characteristics of the audience is the foundation for developing effective communication strategies. Communicators need to deeply understand the characteristics and needs of the audience, design and optimize communication content and methods based on the audience\u2019s psychology, in order to maximize the effectiveness of communication.Results: The attractiveness of a city\u2019s image to its audience is not only an external manifestation of its comprehensive strength, but also a symbol of its soft power. People come with \u201cdreams\u201d and strive for their dreams in the city. However, when the development of the city encounters bottlenecks or lags behind, people\u2019s dreams will also be shattered, leading to a series of social psychological effects such as weakened individual psychological feedback and increased social exclusion. When regional economic development lags behind, people tend to focus more on material interests rather than emotional needs, but at the same time, the motivation to participate in social or economic activities decreases, entering a vicious cycle. Due to the motivating effect of urban image internally and the attractive effect externally, the dissemination of urban image will expand the space for urban development: the combination of the creativity of foreign residents and new spaces provides vitality for urban development, while also providing a path to realize dreams and spiritual support for citizens. Urban popularity is an important indicator of urban development. Through urban image promotion, more people can understand the city, generate interest and favoritism towards the city, and attract more people to travel, study, work, and live in the city.Conclusion: In recent years, with the acceleration of urbanization and economic development, the sense of happiness and belonging brought by cities has not been satisfactory. Cities gather population and various resources, but at the same time, the oppression and decadence caused by living issues such as wages, childbirth, education, transportation, and prices are becoming increasingly severe. Citizens\u2019 impression of the city has changed from a warm home to ubiquitous work pressure. This phenomenon constantly reminds us that there have been social and psychological problems in China\u2019s urbanization process. A series of popular communication trends such as \u201cfleeing Beijing, Shanghai, and Guangzhou\u201d have shown us that the main body of urban image shaping should be understanding the happiness of life, reflecting more on the psychological health and spiritual satisfaction of citizens. Nowadays, people have created increasingly diverse forms of communication through the communication platforms provided by modern technology, and their recognition of regional culture is becoming increasingly strong. The increasing pressure and anxiety in urban life are psychological issues in the development of Chinese cities, but these issues also provide soil for the construction and development of urban culture and image.a, Yuxing Shanga, Qiaoyi Lva, Yangjing Zhaoa, Hui Wanga, Weili Caib, Hui Zhangc,Yanling Zhud, Xiuting Liangd, Qixiang Shaoa,bZhanghui Lia Reproductive Sciences Institute, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, P. R. China, b Institute of Medical Genetics and Reproductive Immunity, School of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Huai\u2019an 223002, Jiangsu, P. R. China, c Department of Clinical Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, P. R. China, d Department of Gynaecology and Obstetrics, The Xuzhou Hospital Affiliated to Jiangsu University, Xuzhou 221005, Jiangsu, P. R. China.Background: Ovarian cancer (OC) is one of the three malignant tumors with the highest mortality rate in the female reproductive system. Owing to the special anatomic location and the lack of typical clinical symptoms, the early onset is insidious. Due to drug resistance and easy recurrence, the 5-year survival rate of ovarian cancer remains has not improved significantly in the past thirty years, and mortality rate is also at a very high level, despite the great progress in chemotherapy, surgery and immune therapy. However, the mechanism of oncogenesis, progression, recurrence, and drug resistance of ovarian cancer have not been fully elucidated. Recently, it has been reported that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play pivotal roles in ovarian cancer initiation, progression, drug resistance and recurrence. Whereas, the regulatory role and its mechanisms of m6A modification on lncRNAs in ovarian cancer are still unclear. Therefore, it is important to elucidate the regulatory role of m6A modification of lncRNAs and its effects on the development and prognosis of ovarian cancer.Subjects and Methods: We comprehensively evaluated the m6A modification patterns of 29 m6A modification-related genes in 374 samples from the TCGA ovarian cancer database, constructed an independent prognostic model based on m6A modification-related lncRNAs. ROC analysis was performed to verify the reliability of the prognostic model based on the age, stage and type of the patients. The data of the patients were divided into high-risk group and low risk group. TMB analysis, GO and KEGG pathway analysis of immune cells, immune infiltrate analysis and drug sensitivity analysis were performed in the prognostic model. QRT-PCR was used to detect the expression levels of 5 m6A modified lncRNAs in ovarian cancer tissues, and the changes of immune checkpoints in peripheral blood of ovarian cancer patients were analysed by flow cytometry.Results: The prognosis model that we constructed was reliable, through the prognosis model, we found that the prognostic characteristics of patients with ovarian cancer are related to the prognostic model, Naive B cell was necessary and played an important role in ovarian cancer, TIGIT had high value in immune checkpoint analysis in prognostic models, and Pazopanib might be a targeted medicine for ovarian cancer. In tumor tissues and peripheral blood of patients, we further verified that FOXP4-AS1 played a m6A dependent role in ovarian cancer and TIGIT was abnormally elevated in the tumor microenvironment of patients with ovarian cancer.Conclusions: The results demonstrated that m6A modification-related lncRNAs participated in malignant progression, recurrence, and drug resistance of ovarian cancer by regulating the tumor immune microenvironment. FOXP4-AS1 may will serve as a potential biomarker for ovarian cancer.This work was supported by the National Natural Science Foundation of China (82071738). Institutional Review Board Statement: The study was conducted in accordance with the guidelines of the Declaration of Helsinki, and was approved by the Ethics Committee of the Affiliated Hospital of Jiangsu University (KY2022K0913) and the Ethics Committee of Xuzhou Hospital Affiliated of Jiangsu University (2019-02-010-K01), respectively.a, Wei Cuia, Lisheng ChenaWenlong Zhoua Shandong Youth University of Political Science, Shandong, China.Background: With the development and progress of the economy and society, accounting work is playing an increasingly important role. Accounting psychological barriers can easily lead to unethical accounting behavior. How to provide psychological adjustment is currently the focus of accounting work. This article explores the relationship between accounting psychological barriers and unethical accounting behavior from the perspective of accounting psychology, focusing on the specific manifestations of accounting psychology and unethical accounting behavior, as well as feasible suggestions for psychological adjustment of the psychological barriers that may arise. This article provides theoretical support and practical guidance for the psychological adjustment of unethical accounting behavior, and summarizes its application experience.Subjects and Methods: This research will primarily use normative analysis, supplemented by qualitative analysis, logic, and other methods. The main focus of this paper is to explore the relationship and influence between accounting psychological barriers, accounting misconduct, and psychological adjustment from the perspective of accounting psychology. Due to the difficulty of obtaining relevant research samples and data from public sources in both behavioral accounting research and accounting psychology research, this paper conducts a review of relevant literature and develops a survey questionnaire. Through theoretical analysis of the generation and change of psychological barriers in accounting subjects, as well as the relationship with accounting misconduct, this paper provides explanations and rationalization suggestions for the psychological adjustment of accounting psychological barriers.Results: This paper expounds on the historical development and current situation of accounting, analyzes the content, composition, and influencing factors of accounting psychology, explains the reasons and influencing factors of accounting psychological barriers and accounting misconduct. The relationship between accounting misconduct and accounting psychological barriers is discussed, and the process of accounting misconduct is emphasized. By referencing literature, questionnaire surveys, and other materials, this paper reveals the internal relationship between the subjective and objective environment and personal characteristics of accounting practitioners and the factors that contribute to the occurrence of psychological barriers and accounting misconduct. Finally, from the perspective of how to adjust psychological barriers, suggestions are made to standardize accounting behavior.Conclusions: The psychological barriers of accounting subjects engaged in accounting work are the key factors that lead to accounting misconduct. The two are closely related and influence each other. The psychological barriers of accounting subjects are the main reasons that affect the occurrence of accounting misconduct, while accounting misconduct is the manifestation of accounting psychological barriers. By studying the relationship between accounting psychological barriers and accounting misconduct, exploring the reasons for the emergence of accounting psychological barriers, and implementing reasonable and effective psychological adjustment measures, can we fundamentally find methods and strategies to standardize accounting behavior.Shandong Province Education Science \u201cthe thirteenth Five-Year Plan\u201d project: research on the construction of \u201cbig accounting\u201d professional practice teaching system in the era of digital intelligence (project number: 2020YB005).a, Hongyu Lana, Xinyu Laoa, Guangning Luob, Xiaolan MaaLeyi Shaoa School of Education Science, Nanning Normal University, Nanning, China, b Nanning School for the Special Education, Nanning, China.Background: Early childhood experience has a profound impact on an individual\u2019s lifelong development, and the quality of development is influenced by many factors of biological and social environment, among which the traumatic experience of children in early childhood is closely related to their later psychological problems and anxiety disorders, traumatic experiences mainly include physical abuse, physical neglect, emotional abuse, emotional neglect, sexual abuse, etc. Social anxiety disorder will directly affect social skills, which is not conducive to the development of individuals\u2019 social functions and the construction of good interpersonal relationships. Compared with normal students, Hearing-impaired students tend to perceive certain prejudice and hostility, so they have a strong defensive psychology and often exaggerate such prejudice. This hostility and distrust towards others can have a negative impact on the establishment of their interpersonal relationships, thus making them prone to anxiety when communicating with others. So they are more prone to emotional problems such as social avoidance and social anxiety. Emotional regulation self-efficacy, as a kind of self-efficacy with emotional regulation characteristics, actually refers to a sense of confidence formed by individuals based on their subjective evaluation of their own emotional regulation ability, which is a key factor to reduce social anxiety in adolescents. Under the dynamic effect of emotional regulation self-efficacy, individuals can take effective emotional regulation strategies and properly deal with emotional events, especially negative emotional events. Therefore, it is of great significance to explore the mechanism of emotional regulation self-efficacy between childhood maltreatment and social anxiety.Subjects and Methods: To investigate the influence mechanism of childhood maltreatment on social anxiety of hearing-impaired students, 135 hearing-impaired students were investigated by the Childhood Maltreatment Questionnaire (CTQ-SF), the Emotional Regulation Self-efficacy Scale (SR-ESE), and the Social Interaction Anxiety Scale (SIAS).Results: The results indicated that: (1) childhood maltreatment significantly positively predicted social anxiety; (2) childhood maltreatment and emotional regulation self-efficacy showed a significant negative correlation, and there was a significant positive correlation between emotional regulation self-efficacy and social anxiety; (3) emotional regulation self-efficacy played a mediating role between childhood maltreatment and social anxiety.Conclusions: It suggested that childhood maltreatment may have a long-term negative influence on hearing-impaired students\u2019 social anxiety, which is partially mediated through emotional regulation self-efficacy.This study is the phased research achievement of 2023 Guangxi Education Science \u201c14th Five-Year Plan\u201d Topic: Mental Health Status and Service System Construction of Sound healthy siblings in Families with Special Children, Project No.: 2023B145.a, Yuanyuan Maa,b, Zhiqiang Baoc, Narenchaoketua, Huan Wangd, Hua Lia, Huhemurena, Shui Linga, Siqina, Naqina, Yingsong Chena,dGuizhia Inner Mongolia Medical University Inner Mongolia, Hohhot 010010, China, b Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, Hohhot 010010, China, c Inner Mongolia Hospital of International Mongolian Medicine, Inner Mongolia, Hohhot 010065, China, d Inner Mongolia Minzu University, Tongliao 028000, China.Guizhi and YY Ma contributed equally to this study.Background: This research aims to examine the molecular mechanism of Mongolian medicine Nuan Gong Qi Wei Pill (NGQW) in treating diabetic kidney disease (DKD) based on network pharmacology and molecular docking and analyze the molecular regulatory mechanisms of its major active ingredients docking with the significant targets of DKD.Subjects and Methods: The active ingredients and their targets of NGQW were acquired from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopedia of Traditional Chinese Medicine (ETCM), and a high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB). DKD-related targets were founded by searching four databases: DisGeNET, Gene Cards Human Gene Database (GeneCards), Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The STRING database was used to construct a protein-protein interaction (PPI) network to search for major targets. Additionally, enrichment analysis involving main biological processes and pathways was carried out using the Database for Annotation, Visualization, and Discovery (DAVID) and Metascape databases. Cytoscape software was used to construct and analyze networks. AutoDock Vina and PyMOL were used to validate molecular docking between significant active ingredients and major key targets.Results: Collectively, 174 NGQW active ingredients, 492 potential targets, and 4227 DKD targets were screened. After the intersection procedure, 295 potential targets of NGQW for DKD were obtained. In addition, quercetin, beta-sitosterol, oleic acid, isoliquiritigenin, and apigenin were the possible key active ingredients of NGQW, Signal transducer and activator of transcription 3 (STAT3), Nuclear factor NF-kappa-B p65 subunit (RELA), Mitogen-activated protein kinase 1 (MAPK1), Heat shock protein 90 alpha family class A member 1 (HSP90AA1), and AKT Serine/Threonine Kinase 1 (AKT1) were important targets in the PPI network. The PI3K/AKT signaling pathway, the lipid and atherosclerosis signaling pathway, the AGE-RAGE signaling pathway in diabetic complications, and the MAPK signaling pathway were all involved in the enrichment analyses along with biological processes including the cellular response to oxidative stress, hormones, and nitrogen compounds. Furthermore, this study highlighted a good binding activity between key active ingredients and key targets.Conclusions: NGQW has the potential to treat DKD through multiple pathways, targets, and compounds. The main active ingredients in this medicine, such as quercetin, isoliquiritigenin, beta-sitosterol, oleic acid, and apigenin interfere with multiple signaling pathways including cellular response to nitrogen compounds, hormones, and oxidative stress by regulating crucial targets such as STAT3, RELA, HSP90AA1, MAPK1, and AKT1.This work was supported by a project grant from the word-class discipline\u201c construction project of Traditional Chinese Medicine (Mongolian medicine) of Inner Mongolia Medical University, (Grant No.myxylxk2022017).a, Chao FanbXiaobo Taoa School of Economics and Management, North China University of Technology, Beijing 100144, China, b School of Business, Central University of Finance and Economics, Beijing 100098, China.Background: With the continuous advancement of technology and the ongoing innovation of business models, companies are facing an increasingly competitive business environment. In this context, successful development of new products has become one of the key strategies for companies to cope with competition. In reality, practices led by companies and inviting customers to participate in new product development are becoming quite common, and as a result, many forms of customer involvement have emerged. However, the issue of how to effectively improve the satisfaction and mental health of customers, and encourage them more proactive and engaged in the company\u2019s new product development process, has received little attention. Mental health refers to a person\u2019s overall psychological well-being, including their emotional, cognitive, and social functioning. It encompasses how an individual thinks, feels, and behaves, as well as their ability to cope with life\u2019s challenges and adapt to changes. The promotion and preservation of mental health contributes to individuals\u2019 overall quality of life, productivity, and social integration, and it reduces the burden of mental illness on individuals, families, and society. Therefore, favorable levels of mental health among customers are conducive to enhancing their efficiency in participating in new product development.This requires companies to choose more appropriate forms of customer involvement in the new product development process, so as to not only improve customers satisfaction and mental health, but also further enhance company performance and put new product development on a healthier and more sustainable track. Based on this, the study will conduct a systematic exploration of how different forms of customer involvement affect new product development performance.Subjects and Methods: This study conducted a questionnaire survey on 287 high-tech companies with independent R&D departments in five provinces and cities including Beijing, Tianjin, Shandong, Shanghai, and Jiangsu. Finally, a set of 267 valid questionnaires was obtained. These questionnaires were mainly distributed across industries such as electronic information technology, biotechnology and new pharmaceutical technology, and aerospace technology.Results: Based on the regression analysis, the results suggested that customer involvement had a significant positive impact on new product development performance. Furthermore, the study revealed that the stronger the incremental innovation capability, the stronger the impact of customer involvement as an information source on new product development performance, while the impact of customer involvement as innovators was weaker. In comparison, the stronger the radical innovation capability, the stronger the impact of customer involvement as innovators on new product development performance, and the weaker the impact of customer involvement as an information source. However, the interaction effect of incremental or radical innovation capability and customer involvement as co-developers was not significant.Conclusions: When a company possess strong incremental innovation capability, customer involvement as an information source is more advantageous for enhancing new product development performance. Conversely, when companies possess strong radical innovation capability, customer involvement as innovators is more conducive to enhancing new product development performance. During this process, the mental health of customers plays a crucial role. The participants\u2019 good mental health level triggered by appropriate customer involvement strategies not only strengthens their ability to cope with stress, challenges, and maintain positive interpersonal relationships at work, but also further enhances their initiative and work efficiency in participating in new product development. Therefore, improving the mental health of participants is of significant importance in enhancing the performance of new product development. The study enriches the understanding of the mechanisms through which customer involvement influences new product development performance and offers empirical evidence for companies with diverse innovation capabilities to determine suitable customer involvement strategies for new product development.a, Lijun Wangb,c,d, Yuepeng Sune, Hyoung-Kil KangfJinggang Lia Sports Department, Jilin International Studies University, Changchun 130000, Jilin, China, b College of Physical Education and Health, Yulin Normal University, Yulin 537000, Guangxi, China, c International College, Krirk University, Bangkok 10220, Thailand, d Wuchang University of Technology, Wuhan 43000, Hubei, China, e Sports Department, Dalian Maritime University, Dalian, Liaoning 116026, China, f Graduate School of Education , Kyungnam University, Changwon, Republic of Korea.Background: This study aims to investigate the impact of Adversity Quotient Theory on the exercise persistence of Chinese college students and to develop an Exercise Adversity Coping Scale to explore the relationship between exercise adversity coping ability and student anxiety alleviation.Subjects and Methods: The present study aimed to develop an Exercise Adversity Coping Scale based on the Adversity Quotient Theory. The scale includes three dimensions and twelve items, and has been shown to have good reliability and validity. In addition, the study sought to validate the effect of the Adversity Quotient Theory on exercise persistence and the alleviation of student anxiety, through exercise behavior surveys and student interviews.Results: Based on data collected from interviews and questionnaires, typical exercise adversities were identified using NVivo12 software. Next, Exploratory Factor Analysis (EFA) was conducted on a sample of 345 Chinese college students to evaluate the psychometric properties of 54 items and develop a 15-item Exercise Adversity Coping Scale with three dimensions: Exercise Adversity Responsibility, Exercise Adversity Control, and Exercise Adversity Influence. This scale explained 63.54% of the cumulative variance, and its internal consistency reliability and split-half reliability were found to be 0.909 and 0.874, respectively. Additionally, Confirmatory Factor Analysis (CFA) was conducted on another sample of 300 college students, and the remaining 12 items were validated. According to the results of exercise behavior surveys, college students who consistently exercised had an average score of 3.63 on the exercise adversity coping ability scale. Moreover, interviews conducted with students who had high exercise adversity coping abilities revealed that they considered physical exercise to be an effective means of relieving stress, which is supported by related literature.Conclusions: The Exercise Adversity Coping Scale developed in this study has demonstrated acceptable reliability and validity. Moreover, the findings suggest that developing exercise adversity coping ability can enhance exercise persistence, which in turn may help alleviate student anxiety.a, Xiang WangbYan Jianga Psychological Counseling Center, Shanghai University, Shanghai, 20444, China, b Department of Nursing, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China.Background: The lifestyles and mental health of numerous college students were affected by the outbreak of the novel coronavirus disease. However, no study has examined the impact of subjective evaluations of exposure to the pressure on mental health. The current study was conducted and examined the relationship between problematic mobile social media usage and depressive symptoms, and the moderating effect of perception of the novel coronavirus disease.Subjects and Methods: A cross-sectional online questionnaire study of 3123 Chinese college students in the Shanghai was conducted in March and April 2020. Problematic mobile social media usage was assessed by the Problematic Mobile Social Media Usage Assessment Questionnaire and depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). 2056 students reported that they were affected by COVID-19, and 1067 students formed the \u201cunaffected group.\u201d Structural equation modeling (SEM) in Mplus 8.0 was used to examine whether the hypothesized relationship between problematic social network usage and depressive symptoms was affected by whether the respondents reported being affected by COVID-19.Results: The effect of problematic mobile social media usage on depressive symptoms was significant. The level of problematic mobile social media usage and depressive symptoms in the affected group was significantly higher than that in the unaffected group. The interaction between problematic mobile social media usage and perceived influence of COVID-19 was statistically significant. The effect of problematic mobile social media usage on depressive symptoms was moderated by perceived COVID-19 influence. Specifically, compared with students who were unaffected by the novel coronavirus disease, those affected showed more severe depressive symptoms.Conclusions: The findings suggest independent and interactive effects of problematic mobile social media usage. The results highlighted the underlying mechanisms in the relationship between problematic social media usage and depression. These findings provide practical insights into the development and implementation of psychological interventions when facing pressure.a, Qiuxiang Bib, Zhouyin Zhangc, Luote DaidAnzhong Huanga School of Economics and Management, Nanchang Institute of Science and Technology, Nanchang, 330108, China, b School of Management, Guangzhou Xinhua University, Dongguan, 523133, China, c School of Accounting and Finance, Anhui Xinhua University, Hefei, 230088, China, d School of Digital Economy and Trade, Wenzhou polytechnic, Wenzhou City, 325035, China.Background: Based on the hypothesis of the positive relationship between poverty and its vulnerability and residents\u2019 mental health, this paper aims to test whether the digital divide affects the efficiency of poverty alleviation in inclusive finance, so as to affect people\u2019s mental health.Subjects and Methods: Poverty is the main acoustic factor of people\u2019s mental health. Whether inclusive finance can improve poverty and finance to alleviate people\u2019s mental health has been debated in academic circles. Based on econometric analysis, this paper holds that the digital divide has a downward effect on the poverty alleviation effect of general finance, which in turn affects people\u2019s mental health.With the development of digital technology, digital inclusive finance is becoming the mainstream. However, the digital divide significantly affects the inclusiveness of financial development.Based on the measurement of China\u2019s digital financial inclusion and digital divide, this paper studies the moderating effect of digital divide\u2019s financial inclusion.Results: The test results show that family health, labor, the dependency ratio, per capita income levels, and the influence of the level of cash deposits are significantly negative, family average age for the action of increasing poverty vulnerability, and the influence of family size is may be due to the large family, more than in the case of more than three generations would cohabit stroke young family in pension spending is higher, This burden increases the vulnerability of households to poverty. The development of digital inclusive finance weakens the poverty vulnerability of households on the whole. The existence of digital divide does negatively affect the poverty alleviation effect of digital inclusive finance.Conclusions: The development of digital financial inclusion has a significant negative effect on the vulnerability to poverty and the digital divide significantly weakens the mitigation effect of digital financial inclusion on poverty vulnerability. Through poverty and poverty fragility, the digital divide has a negative impact on residents\u2019 mental health. The digital divide has a huge impact on families\u2019 mental health by affecting financial inclusion. The digital divide has a huge impact on families\u2019 mental health by affecting financial inclusion. So addressing the digital divide can not only improve financial inclusion, but also address the mental health pressures that families face. There is a significant negative correlation between the digital divide and the mental health of the poor resident. Therefore, addressing the digital divide can improve mental health of the poor resident.This study was supported by the 13th Five-Year plan research project of philosophy and social sciences of Guangdong province (GD17YGL03); the Project of Philosophy and Social Sciences Research in Jiangsu Universities (2019SJA1932); the Youth Fund Project of Humanities and Social Sciences Research of Ministry of Education (21YJC790086); the key project of Humanities and Social Sciences (SK2021A0776) and the Anhui Philosophy and Social Science planning Project (AHSKY2020D53).aChunlu Gaoa Chongqing Aerospace Polytechnic College, Chongqing, China.Background: With the improvement of people\u2019s living standards, contemporary individuals are constantly pursuing higher levels of experiential satisfaction in their daily lives. Travel demand, to a large extent, is inspired by the diverse and colorful cultural heritage found throughout different destinations, providing opportunities to experience and explore the diversity and uniqueness of culture. Intangible cultural heritage embodies the civilization of human society and represents the diversity of global cultures. Introducing intangible cultural heritage-related courses to students majoring in tourism management at vocational colleges is beneficial for enhancing their sense of pride in traditional Chinese culture, cultivating their interest in further learning and researching intangible cultural heritage, and encouraging them to find their life goals and build self-confidence, thereby promoting their mental health development.Subjects and Methods: The paper analyzed the impact of integrating intangible cultural heritage into tourism management education on enhancing students\u2019 self-efficacy, promoting cultural identity, and fostering respect and dedication. Further, it explored specific intangible cultural heritage elements that can be integrated into the teaching process, and proposed targeted strategies for incorporating these elements into the curriculum.Results: The findings indicate that integrating intangible cultural heritage into tourism management education allows students to gain knowledge and insights about intangible cultural heritage and its inheritors. Incorporating intangible cultural heritage into the growth process of cultivating personal character, developing professional skills, and fostering ethical values can produce positive emotions and fulfill students\u2019 psychological needs, mitigating the negative impact of emotions such as depression, low self-esteem, and sensitivity. This integration produces a significant positive effect on students\u2019 mental health and contributes greatly to their growth and development in the future.Conclusions: Based on the findings, it is recommended that the teaching curriculum of tourism management should be developed based on real-world contexts, with a focus on the theme of \u201cprotection and inheritance of intangible cultural heritage\u201d. It is crucial to recognize the significant role that tourism plays in safeguarding intangible cultural heritage and to undertake education reform and practical exploration to promote the simultaneous development of intangible cultural heritage preservation and tourism management education towards a \u201cwin-win\u201d outcome.This work was supported by the General Project of Higher Education Science Research of Chongqing Higher Education Institute from 2019 to 2020 \u201cResearch on Teaching Reform of \u20181+X\u2019 Certification System in Vocational Tourism Management Program\u201d under Grant number CQCJ19B142.a, Xinyu Laoa, Yexiao Lianga, Xia Chena, Rongchao Gonga, Liting LiuaLeyi Shaoa School of Education Science, Nanning Normal University, Nanning 530299, ChinaBackground: As direct participants in the education and rehabilitation of children with special needs, the anxiety of parents of children with special needs affects the rehabilitation process of children with special needs to a certain extent. In this study, we investigated the anxiety of parents of children with special needs and assessed the relevant factors affecting parents\u2019 anxiety levels.Subjects and Methods: In this study, a questionnaire was administered to 176 parents of children with special needs using the Self-Assessment Scale for Anxiety (SAS) and the results were statistically analysed using SPSS 20.0 software to investigate the anxiety status of parents of children with special needs, including basic personal information of the parents, basic information of the children, educational status of the children, monthly household income and educational status. At the same time, in order to ensure the completeness and richness of the information required for the study, a foundation was laid for the subsequent data collation and analysis. The researcher also conducted interviews with the parents of special children.Results: This study investigates the anxiety of parents of children with special needs and analyses the relevant factors that influence the level of parental anxiety, which consists of basic information about the family and the basic situation of the child. The anxiety index of parents of special children was shown to be (56.16\u2009\u00b1\u200912.55) points, which are at a mild level of anxiety. Among these factors, parental gender, age, type of family of the special child, parental status of the special child, occupation, education, monthly household income, number of children, gender of the child, type of disability of the child, degree of disability of the child, pattern of rehabilitation expenditure, special school and family placement had no effect on the anxiety level of the parents of the special child. The total anxiety score of parents of exceptional children was positively correlated with parental status, occupation, degree of impairment and the institution attended, and negatively correlated with the placement of the child in a regular kindergarten.Conclusions: By establishing a sound education system for children with special needs and increasing employment opportunities for parents of children with special needs, as well as conducting regular parent training and parent group support activities, these measures can effectively reduce the psychological pressure on parents of children with special needs.This study is the phased research achievement of 2023 Guangxi Education Science \u201c14th Five-Year Plan\u201d Topic: Mental Health Status and Service System Construction of Sound healthy siblings in Families with Special Children, Project No.: 2023B145.a, Kai Lia, Haonan Zhenga, Zhihu DingaWangwang Zenga Information Center, The First People\u2019s Hospital of Yunnan Province, Kunming 650032, China.WZ and KL contributed equally to this study.Background: With the continuous development of information technology and the continuous improvement of people\u2019s living standards, more and more people have put forward higher requirements for physical and mental health. While information technology has promoted the rapid development of hospitals, it has also produced a large number of redundant data. Patients have put forward higher requirements for the construction of hospital informatization. This paper will improve the quality of hospital data through a series of data governance measures, Improve the clinical business processes of hospitals to ensure their efficient operation. Through various national assessments such as interconnectivity ratings, three-level public hospital performance evaluations, and electronic medical record ratings, we aim to meet patients\u2019 requirements for hospital informatization construction to the greatest extent possible, enhance people\u2019s sense of medical service happiness, and ultimately promote the high-quality development of modern hospitals.Subjects and Methods: A special team for data governance was set up, a series of data governance rules and regulations were formulated, and software tools of the multi-party data governance platform were introduced. The team members regularly investigated the psychological needs of patients during diagnosis and treatment, and obtained specific opinions of patients on the hospital\u2019s diagnosis and treatment process and information system. Then, the diagnosis and treatment process was optimized, and the information system was transformed to meet the psychological needs of patients to the greatest extent, and improve the happiness of patients during the medical treatment process.Result: The outpatient volume and operational data of discharged patients in the hospital have significantly improved. The outpatient volume of the hospital has increased significantly for five consecutive years, and the average waiting time of patients has decreased for five consecutive years. In the questionnaire survey, it was found that the satisfaction of patients who came to the hospital for medical treatment has been greatly improved, their psychological needs have been met, and their sense of happiness has significantly improved. The hospital has made two consecutive breakthroughs in the performance evaluation ranking of tertiary public hospitals, and ranks first in the province through the interconnection of Class IV and Class AConclusion: Through data governance, various data indicators of the hospital have been significantly improved, and the hospital has developed at a high speed. Every year, the hospital can provide more patients with better quality diagnosis and treatment services. When patients come to the hospital for treatment, they always have a relaxed and happy diagnosis and treatment experience. While diagnosing and treating patients\u2019 physiological diseases, the psychological needs of patients have also been more satisfied, and the happiness of patients in the area has been greatly improved.This work was supported by a project grant from Yunnan Provincial Basic Research Program (Grant No.202201AY070001-258).a, Hanteng Liaob, Shaohe ZhangcHui Liua Business School, Nanfang College GuangZhou, Guangzhou 510970, China, b Higher Education Impact Assessment Center, Nanfang College GuangZhou, Guangzhou 510970, China, c School of Economics, Guangzhou College of Commerce, Guangzhou 511363, China.Background: To realize the practical theoretical innovation of industrial Internet combining modern service industry and advanced manufacturing industry, it is necessary to integrate the existing mainstream theories of sustainable transformation and update the meaningful case studies. Satisfying consumers\u2019 psychological needs and emotional behavior is key to promoting consumer upgrading under the new development pattern of \u201cdual circulation\u201d. The innovative practice theory of industrial Internet can provide more personalized, convenient, and efficient products and services, enabling consumers to enjoy pleasure and satisfaction in the purchasing process. This further enhances consumer loyalty and reputation for brands, bringing greater commercial value to businesses.Subjects and Methods: This paper uses theoretical analysis and case study methods. Based on the practical achievements of Rookie Network, this study firstly analyzes the development process of Rookie Network, as a logistics link under the digital economy, from the earliest information platform to intelligent logistics system with the mainstream theory of Industry 4.0 \u201cCyber-Physical System\u201d (CPS). As the mainstream multi-perspective sustainable transformation \u201csocial-technical system\u201d theory of sustainable transition, CPS is used to demonstrate and analyze the transition process of rookie network from the earliest odd-job economic platform to the \u201clow-carbon\u201d social-technical system that provides consumers with high-level emotional value and upgrades consumer experience.Results: The construction of intelligent logistics based on consumer psychological needs of intelligent logistics construction from C-end consumers and consumption scenarios must include the overall theoretical view of Industry 4.0 CP Logistics and multi-perspective sustainable transformation \u201csocial-technological system\u201d. Only in this way can logistics companies meet consumers\u2019 increasingly high demands on logistics. Help them to get logistics information quickly and accurately. Enjoy convenient and efficient logistics services, and improve the sense of experience and service quality in the logistics process. Get a sense of pleasure and satisfaction over good logistics services.Conclusions: It can ensure that the digitalization and digital transformation capabilities at the consumer side can be extended to the working side of commerce and industry, and drive the industrial transformation and upgrading path of advanced manufacturing industry with the deep integration of digital capacity building. Thus, enterprises can better understand consumer needs and launch products and services that meet their psychological needs and emotional behavior more accurately, and sustain development.This work was supported by two projects grant one from Nanfang College, Guangzhou A study on the influence of hog futures on hogs and the industry chain price of hogs (Grant No. 2021XK25), the other from The reform of digital teaching mode of Internet finance based on project management, a general project funded by the 14th Five Year Plan of China Association of Higher Education - A case study of Theory and Practice of Internet Finance (Grant No.21SZYB29).aJie Lia MBA Center, Shanghai University, Shanghai, 200444 China.Background: To alleviate the problems of extensive production, insufficient investment in cold chain, high transportation loss, and asymmetric information in China\u2019s agricultural product supply chain, regulate the management of the agricultural product supply chain, meet consumers\u2019 psychological needs for high-quality agricultural products, and guide suppliers to optimize the agricultural product supply chain mode based on consumers\u2019 attitudes, emotions, and hobbies.Subjects and Methods: Based on consumers\u2019 psychological needs for tea product quality, this paper took the agricultural standardization policies issued by 16 provinces in China as the basis and applied the panel data from 31 provinces between 2000 and 2020. Multiple-period difference-in-difference (DID) method was used to study the growth effect of the agricultural standardization work plan on the tea industry in China.Results: The results showed that the promotion of agricultural standardization work and the support of relevant policies can promote the growth of local tea production and also have a promoting effect on the growth of local tea value. Furthermore, it can effectively meet the psychological needs of consumers for high-quality tea, and influence consumers\u2019 purchasing motivation and behavior.Conclusion: Agricultural standardization has a positive impact on the yield and output value of agricultural products, is an important guarantee for promoting the development of the agricultural industry, and is also an important prerequisite for the standardization construction of the agricultural supply chain. It is recommended that China accelerate the research on the standardization of agricultural product supply chain, and take specific measures such as \u201ccontinuously strengthening the standardization of agricultural product supply chain, developing universal agricultural product supply chain standards; strengthening the construction of organizational guarantee measures to ensure the implementation of agricultural product standardization plans; strengthening the construction of logistics infrastructure to enhance the responsiveness of agricultural product inventory and distribution\u201d. This provides new ideas, new methods, and new channels for China to carry out agricultural product standardization construction, meeting consumers\u2019 psychological needs for agricultural products\u2019 freshness. Additionally, this has important theoretical and practical implications for the quality upgrading of agricultural product circulation.a, Kexiang Chenga, Xiaolin TanaCunbo Wua Chongqing Mental Health Center, Gele Mountain, Shapingba District, Chongqing,400036, China.Background: Autism comorbidities of mental retardation and epilepsy with cisterna magnum occipitalis in children are rare, Early recognition by clinicians is difficult, which led it easy to be neglect and difficult to thrapy that affect the children\u2019s mental health and physical health and increased the burden on the familySubjects and Methods: A child with autism comorbidities of mental retarded development and epilepsy with cistercius macroccipitalis was promptly treated with oxazepine for antiepilepsy from Chonging mental health center, he was emotional unstable, irritable, impulsive wounding, accompanied by obvious mental symptoms and anxiety, repeated toilet visits, could not speak human language, could not take care of his own life. We used Risperidone oral liquid for antipsychosis, Quetiapine combined with Ziprasidone injection for mood stabilization, completed relevant auxiliary examination, supplemented by rehabilitation training such as psychotherapy, behavior modification, hypnotherapy, biofeedback therapy to promote the rehabilitation of the child.Results: The child became emotional stability, not irritable, impulsive, hurtful and anxious feelings any more, mental symptoms gradually disappeared, could cooperate with simple educational training, although discharged automatically.Conclusions: Autism comorbidities with severe mental retardation and epilepsy are rare and difficult for clinicians to treat due to communication difficulties. Autism and mental retardation mainly rely on education training and psychotherapy, while epilepsy and primary disease caused by mood disorders, clinical psychiatry mainly medicated to solve. The patient is accompanied by large cisterna, whether it is the cause of the disease or coincidence, and whether it is used as the auxiliary basis for diagnosis, needs a large number of clinical samples and data to study. For such patients, it is also necessary to be cautious in drug use. Due to the retarded neurological development, the drug sensitivity is reduced and the drug tolerance is easy, so the choice of drugs should be more careful. Early identification, timely antiepileptic treatment and appropriate drug sedation therapy are very necessary for clinicians to pay attention to Comorbidities of mental retardation and epilepsy in children.aWeiwei Liua Basic Teaching Department Shandong Huayu University of Technology, Dezhou, Shandong, 253000, China.Background: From the perspective of mental health, this paper uses cognitive psychology, personality psychology and Nida\u2019s functional equivalence theory to further explore the translation strategies of English film and television drama language, so that film and television art can better play the role of film and television art in people\u2019s mental health and personality. The positive role of shaping clarifies the linkage relationship between the translation of film and television texts in promoting people\u2019s mental health and all-round development, in order to provide reference for the development of film and television style translation.Subjects and Methods: In order to promote the healthy development of people\u2019s mental health, this paper discusses the principles, methods and strategies of film and television translation on the basis of analyzing and summarizing the characteristics of film and television stylistic language - colloquial, easy to understand, cross-cultural and immediacy. According to the different contexts, semantics, and discourse conditions of specific translation examples, the principles and effects of the application of translation, free translation, abbreviated translation, and compilation strategies are emphasized.Results: In the process of translating film and television scripts, the translator must face the audience and give more consideration to the audience\u2019s objective needs, aesthetic taste and acceptance level, so as to finally achieve harmony and unity between the audience\u2019s expectations and the original intention of the translation, and improve the expression and integration of individual emotions. Control ability, promote the formation of human personality and the overall development of mental health. At the same time, we must strive to:1. Make good use of cognitive psychology theories and laws of cognitive psychology to complete the understanding and expression of the original text, actively mobilize the translator\u2019s psychological activities in the translation process, and improve the quality of translation.2. Make good use of the positive influence of personality factors in the translation process of film and television style, determine the translation objects and expressions, maintain the original style, and improve the translation quality.Conclusions: The translation of film and television style should not only pay attention to the expression of artistic techniques and stylistic characteristics, but also be people-oriented. It is absolutely necessary to promote people\u2019s mental health. Carrying out the translation strategy research of film and television style from the perspective of mental health can not only make the translator\u2019s personality tendency and film and television text realize two-way adaptation, but also make the correlation between the translator\u2019s cognitive activity law. The people-oriented concept has been deeply integrated, and the translator\u2019s emotional activity rules have been fully reflected in the translation examples, which has opened up a new path worth trying for the translation of film and television genres.This article is the phased research result of the 2019 scientific research platform research project of Shandong Huayu University of Technology - Applied Translation Research Center (No. 09) and College English Curriculum Construction.aChin-niang Chana School of Art, Minnan Normal University, Zhangzhou, Fujian, China.Background: As a product of artistic development, traditional Chinese opera is associated with human emotions through the process of visual and spiritual experience, thereby having a profound impact on human mental health. Through in-depth analysis of how traditional Chinese opera art affects emotions through visual experience, this study explains the close relationship between traditional Chinese opera art and mental health from a micro perspective, using the way that traditional Chinese opera art affects mental health.Subjects and Methods: This study examines the relationship between art and mental health in art therapy, using art based techniques such as traditional Chinese opera music as evidence based interventions for mental health issues such as anxiety and depression. More and more evidence suggests that art can be used in non-therapeutic environments to promote mental health, such as performing arts to understand the core subject areas of a school or to maintain a sense of mental health. In other words, practicing art can be used to establish the ability to manage a person\u2019s mental and emotional health.Results: The research results show that art affects mental health, and the healing effect of art works needs to be carried out to the extent that the audience can understand. If opera has a psychological relief and healing effect on the audience, then the art works or performers of this opera are effective for these audiences. The direction of this study is to focus on the artistic works themselves, as well as the psychological world and healing function of opera performances, in terms of art and mental health.Conclusions: The impact of traditional Chinese opera art on mental health is mainly produced through aesthetic experience. In the process of creating traditional Chinese opera art, individuals tend to pay attention to the expression of their physical and emotional tendencies in the actual inner experience of the artistic work; In the process of appreciating traditional Chinese opera art, individuals experience emotional flow and emotional release through re-experiencing the emotions expressed in artistic and technical works. The integration of artistic experience and artistic techniques can enable an individual to gain respect for their own feelings, thereby achieving the release and sublimation of the surrounding environment within. Show the artistic style characteristics of Gezi Opera and its healthy body and mind.a,b, Jie Fuc, Chi ZhangaTuo Shia Beijing Police College Department of Public Security Management, Beijing 102202, China, b Institute of Scientific and Technical Information of China, Beijing 100038, China, c Beijing Miyun District Administration Bureau, Beijing 100050, China.Background: With the increasing application of artificial intelligence (AI) in the field of public security and law enforcement, its integration into the practice of law enforcement is no longer a one-dimensional technical innovation, but a multidimensional empowerment that includes promoting the formation of multi-subject collaborative governance models, forcing upgrades of supporting institutional frameworks for public security, and driving the technological transformation of law enforcement methods. While AI has effectively improved law enforcement efficiency, it has also brought risks such as discrimination, privacy infringement, and deprivation of rights, causing psychological anxiety about technology.Subjects and Methods: This study discusses the negative effects of law enforcement caused by technology defects. It is supported by the theoretical framework of comprehensive public security and law enforcement, and integrates methods such as situational analysis and systematic deconstruction. The study systematically analyzes the types of psychological anxiety risks caused by AI technology integration into law enforcement, and investigates the inducements and impacts of psychological anxiety from the multidimensional perspectives of structural imbalances of the law enforcement subject, ineffective governance systems, and technological alienation.Results: From the perspective of the relationship structure of governance subjects, the monopoly of AI technology resources undermines the original intention of promoting the participation of multiple subjects in governance, and can even cause risks such as social disorder and psychological imbalance caused by the feeling of injustice among subjects. It becomes a huge obstacle to the modernization of governance capacity, deviating from the governance goal of \u201cjoint construction, joint governance, and sharing\u201d. From the perspective of the role of governance subjects, it causes further polarization and even group isolation and confrontation among social subjects, and algorithm-driven social polarization and even group isolation and confrontation causes more serious psychological disorder. From the perspective of technological alienation, over-reliance on data algorithms and the risk of uncontrolled application bring insurmountable psychological anxiety to subjects.Conclusions: The study results show that the main ways to effectively alleviate the psychological anxiety of subjects at the technical level include: the government\u2019s comprehensive coordination of the structural relationship among multiple subjects under the embedding of AI, promoting the formation of a multi-subject collaborative governance pattern, following up and improving warning decision-making, information resource sharing, and public security and crime prevention and control systems, and accelerating the construction of an \u201cAI governance system\u201d.This work was supported by a project grant from National Social Science Foundation Youth Program (Grant No.21CSH05).a, Shi Zhengb, Feng HuaWeichao Chenga School of Economics and Management, West Anhui University, Luan 237012, China, b School of Business, Sichuan University Jinjiang College, Meishan 620860, China.Background: The collapse of stock price will quickly evaporate the wealth of shareholders, greatly increasing their anxiety. Anxiety can have a dual impact on people\u2019s physical and mental well-being, Anxiety can bring complex and unpleasant emotions such as tension, unease, worry, annoyance, Insomnia and dreaminess to people, thereby affecting family harmony and happy life. Due to the late development of China\u2019s capital market, there is room for improvement in China\u2019s market regulatory mechanism and legal system, and the stock price crash risk are higher risk.Subjects and Methods: This paper using the Shapley-Shubik power index, which is based on cooperative game theory, and investigates the impact of major shareholders\u2019 shareholding structure on the psychological anxiety of shareholders, based on the perspective of stock price crash risk. stock price crash risk by examining a sample of A-share listed companies in China from 2003 to 2018. This study uses regression methods such as least squares to empirically test the research hypotheses proposed in this paper.Results: The study finds that: (1) Cash flow rights significantly reduce stock price crash risk, alleviated the anxiety of shareholders. The separation of cash flow rights and control rights significantly increases such risk, increased the anxiety of shareholders. While the control rights have no significant effect on the stock price crash risk; (2) More supportive behaviors and fewer hollowing-out ones play a partially intermediary role in the suppression of stock price crash risk by the cash flow rights, whereas fewer supervisory and more hollowing-out behaviors play a partially intermediary role in the crash effect of separation degree of control and cash flow rights.(3) The more powerful a firm\u2019s management and the weaker its external supervision, the more significant the role of the cash flow rights in suppressing stock price crash risk, and the more conspicuous the crash effect of separation degree of control and cash flow rights.Conclusions: Cash flow rights significantly alleviate the anxiety of shareholders, while the separation of cash flow rights and control rights significantly increases the anxiety of shareholders. The findings of this paper could provide useful theoretical and practical guidance for optimizing firms\u2019 shareholding structure, suppressing the risk of share price collapse, improving the quality of listed companies, promoting the stability of capital markets, and alleviating the anxiety of shareholders.This research was funded by West Anhui University Talent Introduction School Research Start-up Fund Project (No. 00701092302) and Youth foundation of SCUJJ (No. QNJJ-2022-A07).a, Yun YangbLing Miaoa The CPC Henan Provincial Party Committee Party School, Zhengzhou 451464, China, b School of Economics and Management, Zhongyuan University of Technology, Zhengzhou 450007, China.Background: As one of the most important social relationships in market economy, the labor-capital relationship is \u201cthe axis of rotation around all modern social systems\u201d (Engels). Nowadays, this relationships under China\u2019s \u201cnational integration model\u201d has basically completed the market-oriented transformation, but the labor-capital dilemma has become increasingly severe. According to the Chinese Law Blue Book, labor-capital incidents have accounted for 36.5% of China\u2019s mass incidents, which become major threats to China\u2019s economic and social construction, possible solutions thereby are needed. And in the current era where emotional health is becoming increasingly important, using emotional behavior as a research entry point can more intuitively reflect internal mechanisms and problems.Subjects and Methods: Based on the statistical data from 2000 to 2015, this paper concludes that (i) the number of mass labor disputes is proportional negative correlated to the labor compensation, while (ii) the number of mass labor disputes is proportional positive correlated to the capital property income with the cointegration theory and the generalized impulse response function. This paper studies the endogenous relationship between the loss of labor property rights, the decline of labor compensation proportion and the \u201coutside institutional struggle\u201d under property rights theory. Combined with data validation, it verifies the relationship between emotional behavior and large-scale industrial events, and verifies that emotional behavior can have an impact on industrial events.Results: We propose to (i) increase the proportion of labor compensation at the initial distribution stage as the reform direction; (ii) improve the \u201cthree rights of labor and capital\u201d; (iii) establish a long-term mechanism for wage growth; and (iv) develop the redistribution and adjustment mechanism of compensation to solve the problems mentioned above. And attention should be paid to the prevention and guidance of negative emotions and unhealthy behaviors caused by negative emotions.Conclusions: The decline in the proportion of labor compensation does not necessarily lead to mass labor incidents, but in a long run, labor compensation and capital property income have a causal relationship with mass labor disputes. That is, the continuous decline in the proportion of labor compensation makes workers fall into a psychology of disadvantage and their \u201cdeprivation feeling\u201d become solidified. An accidental event may lead to the mass labor-capital incidents. Furthermore, the consequence of the generalized impulse response function indicates that the number of mass labor disputes is negative correlated to labor compensation, while positive correlated to capital property income, which presents a crowding effect on labor compensation. Obviously, the long-term crowding effect of the labor compensation and the continuous decline of the labor compensation ratio have become the inherent reasons for mass labor and capital incidents. The prevention and guidance of emotions and behaviors can effectively solve the current practical problems in enterprises or society. Therefore, the prevention of negative emotions and the guidance of unhealthy behaviors caused by negative emotions are urgent.The period research results of the National Social Science Fund General Project \u201cResearch on the Fire-retardant Mechanism and Governance of Massive Labor Incidents Network\u201d (No. 18BGL237).a,b, Boping TianaJinyang Liua School of Mathematics, Harbin Institute of Technology, Harbin 150006, China, b School of Statistics, Chengdu University of Information Technology, Chengdu 610103, China.Objective: It is common knowledge that in the history of the world\u2019s medical development, various infectious diseases have been the most dangerous and deadly diseases for human health. Considering that the virus has not been fully explored and the scale of contagion is becoming more and more widespread, there is an urgent need for timely prediction of the spread of infectious diseases. With the continuous development of artificial intelligence in recent years, deep learning techniques have been used to predict infectious diseases in addition to traditional prediction methods. Therefore, proposing prediction models with better performance based on depth techniques is the main objective of this study.Methods: Long short-term memory (LSTM) and convolutional neural networks (CNN) are deep learning models, both of which perform well in predicting time-series data. Based on summarizing previous studies, the LSTM based on scaled dot-product attention and the CNN combined with feature-wise linear modulation (FiLM) were proposed. These methods improve the ability to capture key information about infectious diseases, which in turn improves the predictive performance of the model. To evaluate the fitting performance of those models, LOSS, RMSE, Pearson coefficient, and R2 of models were calculated in this study.Results: The fitting results of Scaled Dot-product Attention-LSTM and CNN-FiLM on time series data of infectious diseases from four countries were obtained based on Python. In conjunction with the calculated results of the evaluation metrics for model fitting, it can be seen that the two methods proposed in this study, based on Scaled Dot-product Attention-LSTM and CNN-FiLM, are suitable for the effective prediction of infectious disease time series, and both methods have improved to some extent in terms of model fit. Compared with Japan and Armenia, the two improved methods were relatively better fits for the epidemic data from China and India.Conclusions: To ensure effective prediction of infectious diseases, it is necessary to actively explore the establishment of excellent methods and models, strengthen the ability of models to be applied to different data, and minimize the error rate in prediction. Scaled Dot-product Attention-LSTM and CNN-FiLM can be easily adapted to many different temporal data analysis tasks, which greatly increases the scalability of time series prediction models. This study makes some attempts at the prediction methods and models of infectious diseases, and the research results may play a certain role in the effective response to similar infectious diseases that may occur in the future.This work was supported by a project grant from the Natural Science Foundation of China(NSFC) (No.91646106).a, Zhihui Yangb, Jing Caoc, Zhi FangdXihuang Laia Graduate School, North China University of Technology, Beijing 100144, China, b Brunel London School, North China University of Technology, Beijing 100144, China, c School of Electrical and Control Engineering, North China University of Technology, Beijing 100144, China, d School of Humanity and Law, North China University of Technology, Beijing 100144, China.Background: As the fresh troops in national innovative talents cultivation, postgraduate education shoulders the important mission of building China into a world leader in science and technology. However, the increasingly complex international environment and fierce competition of employment prospects make postgraduates bear great pressure. Some students even have mental problems. In order to alleviate the anxiety of the postgraduates nowadays, we put forward the goal of all-round development of talent cultivation on the basis of mental health with the corresponding assessment indicator system, trying to cultivate the sound personality and comprehensive quality of graduate students from the macro level of management and the micro level of personal development.Subjects and Methods: Firstly, through the method of literature survey, this paper analyzes in detail the practical dilemma and implementation bottleneck of mental health education based on physical, aesthetic and labor development at the graduate level. Then it combined with the management characteristics of our school, as well as the mental education, to establish a cultivation framework for the all-round development of graduate students. Secondly, according to the requirements of the comprehensive development in moral, intellectual, physical, aesthetic and labor aspects, and the demand of innovative-applied talents, we designed a relatively systematic questionnaire about postgraduate learning experience and mental health status, and carried out long-term data survey of our graduate students. On this basis, we further optimized the process of talent cultivation by putting forward the implementation strategy of \u201cmoral and intellectual education as the foundation, mental health education as the connection, practice as the way, team as the body part and multiple educations working together\u201d.Results: Under the influence of the reform of the postgraduates\u2019 comprehensive development mechanism of our university, the self-assessment survey of postgraduates\u2019 learning experience and mental health in recent two years shows that their degree of satisfaction with the work of multi-education integration carried out by our university is on the rise. We have successfully diverted students\u2019 attention and relieved their psychological problems caused by employment pressure, academic pressure, classmate relationship and emotion factors through conducting physical, aesthetic and labor education. And we have gradually shaped students\u2019 healthy psychology and sound personality as well as guide their all-round development in the process of education.Conclusions: The mental health of graduate students has been paid more and more attention, and universities are focusing on solving students\u2019 mental problems. We promote the organic integration of five educations with mental education, continue to improve the assessment system of graduate talent cultivation and optimize the implementation approach, urge the graduate management department to enhance the working methods through the way of assessment, and guide the graduate students to form good research habits and healthy mental state, to further improve the quality and effectiveness of graduate education. It is believed that the implementation strategies will provide a strong support and guarantee for cultivating high-level talents with excellent professional quality, noble character and mental health.This work was supported by the ideological and political work research project of Beijing universities (support project): Construction and implementation of the comprehensive development of postgraduates oriented by ability cultivation (Grant No. BJSZ2021ZC63), the Beijing higher education association project : Exploration and research on the quality evaluation of graduate practice in the new era (Grant No. MS2022291).aXuemin Zhua School of Foreign Languages, Sichuan University Jinjiang College, Pengshan, Sichuan 620860, China.Background: L2 motivation research has already attracted much attention in L2 field and this paper mainly focuses on the explorations of possible causes of low motivation in English learning in colleges of China and L2 motivational strategies in English Teaching of Chinese Context. Under the condition of maintaining and improving students\u2019 mental health, the investigation of the demotivation in EFL classrooms also takes psychological factors into consideration, which would probably help Chinese students ease academic stress and relieve anxiety in EFL classrooms, with the purpose of building students\u2019 confidence in L2 learning. Motivational problem also could be part of the contributions to promoting more effective language learning and teaching.Subjects and Methods: On the basis of related literature review, a qualitative research method is adopted in this study and therefore observation is chosen to be employed as the major method in the research. Meanwhile a case study is conducted among the college students. The discussing objects are mainly confined to the non-English majors who are studying in some colleges of the southwest city of China, in order to make the topic more clearly defined and elaborated.Results: Motivation to learn a foreign language depends on how much the individuals would like to learn L2 and how much satisfaction they would gain during the process of learning. In observational studies, the target learners have low motivation in EFL classrooms and the demotivating factors involves a series of problems, among which negative attitudes towards language learning have detrimental influence on the success of acquiring L2. Negative attitudes towards EFL classrooms may be caused by some psychological factors, including classroom anxiety and academic stress. Teaching methods, classroom atmosphere, teacher-and-student relationship and facilities problem are also taken into account.Conclusion: Negative attitudes are common and unavoidable in the discussed context, however, there is a more general recognition that suitable strategies may offer good chances to convert negative attitudes towards L2 learning into positive ones and even promotes the enjoyable process of language learning in some interesting ways. Moreover, this paper examines the teachers\u2019 role of setting up rapport with students in the motivational perspective and how it works as a spur to make L2 learners more confident and engaging in English learning. It also illustrates how important it is to create a pleasant and supportive environment for L2 learners to ease the pressure and anxiety in the process of language learning.a, Chunting DiaobRuiyue Zhua Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430061, China, b School of Medical Humanities, Hubei University of Chinese Medicine, Wuhan, Hubei 430070, China.Background: Alzheimer\u2019s disease has become one of the epidemic diseases in contemporary human society. In recent years, the number of elderly people in China has increased year by year, and the aging process has obviously accelerated. Among them, people with Alzheimer\u2019s disease in China have occupied a large proportion of the population. Alzheimer\u2019s disease, as an elderly disease that will lead to serious consequences and extensive effects, should attract people\u2019s extensive attention. Emotional therapy of Traditional Chinese Medicine is a kind of therapy based on the theory of Traditional Chinese Medicine, which is simple to operate and rarely has side effects. This paper discusses the effect of emotional therapy of Traditional Chinese Medicine on improving Alzheimer\u2019 s disease, and provide the application path.Subjects and Methods: Research subjects are elderly patients with Alzheimer\u2019s disease, generally considered to be 45 years old and above. Patients receive treatment from the emotional theory of Traditional Chinese Medicine, mainly including transforming emotions, meeting demand, dispelling doubts, diverting attention, hinting to switch ideas. This paper uses the method of literature review to sort out and analyze the literature related to emotional therapy of Traditional Chinese Medicine and Alzheimer\u2019s disease in recent 20 years.Results: The theory of emotion of Traditional Chinese Medicine emphasizes that the human body can help repulse the influence of negative emotions by mobilizing the positive emotions of the whole body, restore the body to a peaceful state, and balance the function of viscera thereby relieving or treating various diseases. Depending on the patient\u2019s condition, different Traditional Chinese Medicine emotional therapies can be selected. When the patient is emotional, transforming emotions therapy can be selected. When the patient has requirements, meeting demand therapy can be selected. In addition, the patient can also be enlightened by dispelling doubts therapy firstly. If the effect is unsatisfactory, hinting to switch ideas therapy can be continued. Based on the above, Traditional Chinese Medicine treatment mainly based on psychotherapy can effectively improve the symptoms of Alzheimer\u2019s disease.Conclusions: Traditional Chinese Medicine emotional therapy can effectively regulate the abnormal emotions of patients, help patients to release themselves, obey their wishes, and promote physical and mental health. It has a positive effect on improving the symptoms of patients, and is worthy of comprehensive promotion.This work was supported by a project grant from the Hubei Provincial Department of Education\u2019s Philosophy and Social Science Fund Project in 2020 (Grant No.20Q075).a, Nur Syuhada binti Mat Sina, Afeez Nawfal bin Mohd Isaa, DuoBao ChenbQi Chena Sultan Idris Education University, 35900, Tanjong Malim, Perak, Malaysia, b Anhui University of Science and Technology, 232001, Huainan, Anhui, China.Background: The development of new media has brought significant changes in the way people communicate and engage with the world. However, elderly people may struggle to keep up with the fast-paced technological advancements due to changes in their cognitive and physical capabilities. The prolonged exposure to new media may have adverse effects on senior mental health, such as depression, anxiety, and loneliness. Moreover, seniors\u2019 decreased ability to concentrate and process information may lead to difficulty in navigating complex digital interfaces, resulting in low adoption rates. It is crucial to consider the changing behavior and mental health of elderly individuals when designing digital technology to ensure inclusivity and accessibility for all age groups.Subjects and Methods: In this research, by analyzing the consumption demand and usage status of new media among elderly people, as well as the factors affecting their sense of happiness in life. we propose measures to optimize the new media platform, establish a comprehensive system for the elderly to enhance their living quality and mental health.Results: By analyzing a quantity of files, the elderly prefer simplicity and may become more conservative in their thinking. They still require social interaction, particularly spiritual support from loved ones. A user-friendly media application could help bridge the digital divide for them. In this research, conducting several points to elaborate key direction for improving the elderly\u2019s living experience and mental health.Conclusions: The proposed measures not only aim to improve the usability and accessibility of new media platforms for seniors but also promote their digital literacy, social engagement, and overall well-being. Through technology training classes and user-friendly interfaces, seniors can enhance their digital skills and feel more confident and connected while using new media. Additionally, optimizing new media platforms to meet the specific needs of the elderly, such as larger fonts, simpler navigation, and audio instructions, can significantly improve their user experience. Ultimately, promoting the adoption of new media among seniors can bring substantial benefits, including improved mental health, social connectedness, and quality of life.a, Yuewu Zhenga, Rumeng Tiana, Lei Pengb, Mushan LiaYing Zhanga School of Emergency Management, Henan Polytechnic University, Jiaozuo 454003, China, b School of Energy Science and Engineering, Henan Polytechnic University, Jiaozuo 454003, China.Background: In recent years, frequent occurrence of public health emergencies posed a serious threat to social public security. After the occurrence of public health emergencies, people concern about their own health and the unstable situation, along with media and public opinion out of control, emotion focused coping and irrational behavior happen frequently. As the important factor of responding to public health emergencies, public risk perception has important practical value. Therefore, studying the influencing factors of public risk perception under public health emergencies can help the government guide to respond to public health emergencies, so the public\u2019s risk perception ability will improve, and minimize the serious consequences of public health emergencies.Subjects and Methods: First of all, based on the PSR (Press-State-Response) model this article identifies and analyzes the influencing factors of public risk perception. It is concluded that the inherent risk of public health emergencies, the actual progress of the event, the government response, and the media communication as influencing factors and the degree of reaction of the public\u2019s own response behavior as dependent variable to interpret public risk perception level. Secondly, integrating previous research achievements, a theoretical model is constructed based on the research hypothesis of influencing factors of public risk perception under public health emergencies. Thirdly, data are obtained through questionnaire survey, and empirical analysis is conducted using structural equation models. Finally, this article proposes countermeasures and suggestions for scientifically optimizing the level of public risk perception.Results: The inherent risk of events and media communication have a positive impact on public risk perception; The actual progress of events and government response have a negative impact on public risk perception.Conclusions: Improving the public\u2019s risk perception ability, optimizing existing emergency management policies, strengthening the government\u2019s risk communication ability, and improving the media\u2019s risk information dissemination can improve the public\u2019s risk perception ability, and provide a decision-making basis for guiding the public to respond scientifically to public health emergencies.This study was supported by the General Project of Humanities and Social Sciences Research in Henan Universities (2021-ZDJH-0139), the Key Science Research Project in Universities of Henan (21A630015), Ph.D. Fund of Henan Polytechnic University (B2017-62), China Engineering Science and Technology Development Strategy Henan Research Institute Strategic Consulting Research Project (2023 HENZDB 05) and the Teaching Reform Research Project of Henan Polytechnic University \u201cExploration and Practice of Safety System Engineering Teaching Reform in the Perspective of New Engineering\u201d.aMingyue Suna Nanchang Institute of Technology, Nanchang, 330000,China.Background: In the film Wrath of Silence, due to illegal mining and urbanization, the dual contradiction between urban and rural areas becomes increasingly prominent, forming a completely different social landscape between rural and urban areas. Under the influence of psychological pressure, people living here adopt different ways of making a living, forming a distinct pyramid shaped social structure. In the psychological context, the \u201csilence\u201d of the lower class is a passive and ineffective struggle, while the \u201csilence\u201d of mining owners from the emerging upper class and lawyers from the middle elite class is an active choice. The film intuitively displays the negative psychology of anxiety, inferiority, depression, mania, cowardice, suspicion, greed, indifference, etc. among the pyramid class population. The dual dilemma of physical and psychological forces people belonging to different classes to implement a breakthrough in reality.Subjects and Methods: By talking about the film semiotics analysis, this paper deconstructs the structure of the story hidden in the text and the expression method of the text from the perspective of story, narrative time, narrative space and expression techniques. The details considered from a psychological perspective are as follows. First, through the dual tone of the film\u2019s realism and surrealism (magic) coexistence, we examine how the film establishes the style and tone of the entire film. Secondly, it deconstructs the pyramid shaped social structure through the gaze perspective in Freud\u2019s psychoanalysis. This tower shaped display image symbol is in line with the contemporary Chinese landscape of class opposition and interest conflicts. The collapsed and imbalanced hierarchical structure makes the tragedy presented in the film more profound and powerful. Third, by reconstructing the time sequence of the film, the deeper meaning of metaphors in each image symbol is deciphered. The film examines the different desires pursued by people of different classes.Results: Different from other crime suspense genre narrative films, to find the child is the starting point of the film, but not around the crime committed or crack crime to narrate. Instead, from the Gestalt film theory of mind, a large number of plots are left blank. Through a large number of symbols and plot blank, the audience can think and feel who is the real villain. The film seems to be looking for children, but in reality, it is the pursuit of different desires by people from different social classes.Conclusions: This study focuses on the imbalance of urban-rural development through the film Wrath of Silence, and explores the reality of the physical and mental plight of people in China\u2019s classes, especially in the rural areas, exploring the social symptoms of the upper class\u2019s loss of attitude, the middle class\u2019s loss of morality, the bottom class\u2019s loss of speech, and the earthly disorder. And the complexity and diversity of mental health issues will also lead to diverse discussions on the desires, difficulties, and psychology of different social classes in rural China. Furthermore, it brings positive psychological thinking to the audience, in order to alleviate negative psychology such as anxiety, stress, and suspicion.a; Zhongyan LinbKexin Jianga The Bartlett School of Environment, Energy and Resources, University College London, London, WC1H 0NN, UK, bSchool of International Digital Economy, Minjiang University, Fuzhou, China.Background: A person spends most of their time indoors. The quality of the indoor environment (IEQ) has a direct impact on people\u2019s comfort and health. In this circumstance, IEQ becomes the professional\u2019s main concern. For many years, offices have been one of the main topics of research. A variety of aspects that affect office occupants\u2019 health, wellbeing, and comfort have been researched and listed by many researchers, including indoor air quality, thermal comfort, and biophilic design.Subjects and Methods: This study focuses on the comfort, health, and wellbeing of office workers. Using Alker et al.\u2018s structure of office design to produce the literature review structure, the study first develops the overall picture of office design variables with health, welfare, and comfort. Then, a variety of studies are succinctly analyzed and organized to demonstrate the most recent findings in the area. Then, biophilic design as the main focal point in this study is analyzed. With the help of the biophilic design framework, a literature analysis is conducted to summarize the most recent research and offer recommendations for workplaces to improve the health, wellbeing and comfort status of employees.Results: There is information available on every aspect of workplace design, along with their recommendations. The table of research demonstrates the validity of the framework by Alker et al. and the relationships between various elements and the comfort, wellbeing, and health of occupants. The research on biophilic design then presents an ongoing process in the field and the significance of having the biophilic design in workplaces based on the framework for biophilic design. Some of the recommendations, meanwhile, have flimsy supporting data, necessitating more investigation. There is a need to do additional quantitative research on the relationships between biophilic components and health as a result of the limited research approaches in this study and existing research gaps.Conclusions: Based on the findings, stakeholders should take the office design structure into consideration to enhance the working environment. The compiled biophilic design recommendations can help design teams and building owners further optimize their workplaces for the comfort, health, and welfare of their employees. Additionally, a larger variety of constructed surroundings should emphasize the value of biophilic design in order to enhance the relationship between humans and nature.This work was supported by project grants from The National Key R&D program, the Intergovernmental International Science, Technology and Innovation Cooperation Project (EU Horizon Project-No.2017YFE0118800); Central Financial support for Local Science and Technology Development Special (No.2018L3007); Foreign cooperation project of Fujian Provincial Science and Technology Plan (NO.2020I0040).aHua Wanga School of Marxism, Xi\u2019an International Studies University, Xi\u2019an 710119, China.Background: Starting from the value of traditional Chinese health preservation and self-cultivation culture, analyze the main manifestations of current college students\u2019 psychological anxiety, and interpret the positive role and broad value of traditional Chinese health preservation and self-cultivation culture in alleviating college students\u2019 psychological anxiety.Subjects and Methods: The article mainly analyzes and summarizes the combined methods and practical significance of alleviating college students\u2019 psychological anxiety based on traditional Chinese health preservation and self-cultivation cultural concepts and practical practices. In the process of research, the methods of literature research and induction were mainly used. The article summarized and organized the content and characteristics of traditional Chinese self-cultivation culture, as well as the manifestations of college students\u2019 psychological anxiety, including relevant concepts and practices in traditional Chinese culture, as well as the methods to solve college students\u2019 psychological anxiety summarized through practical implementation and exploration.Results: Based on the analysis of the connotation of traditional Chinese health and self-cultivation culture and the main manifestations of college students\u2019 psychological anxiety, this article explores the role of traditional Chinese health and self-cultivation culture in positively alleviating college students\u2019 psychological anxiety, the specific implementation methods, and its broader practical and world significance in the future. This provides new ideas for the management of psychological anxiety among college students, and also provides a model for applying Chinese health preservation and self-cultivation culture to a wider range in the future.Conclusions: The concepts of calmness, harmony, and self consistency contained in traditional Chinese health and self-cultivation culture, as well as traditional practice methods such as traditional Chinese medicine and Tai Chi, have a very significant effect on positively relieving the psychological anxiety of college students. From a broader perspective, China\u2019s traditional health and self-cultivation culture has more practical and extensive value in relieving psychological anxiety for a wider population in the future.a, Lintao FubJingtong Zhaoa Department of Electronic Commerce and Law, Beijing University of Posts and Telecommunications, Beijing City 100000, China, b Department of Software engineering, Beijing University of Posts and Telecommunications, Beijing City 100000, China.Background: This paper aims to study the intellectual property protection platform for intangible cultural heritage digital works based on blockchain technology. With the development of digital technology, intangible cultural heritage (ICH) works face the challenge of intellectual property protection in digital dissemination. This study constructs a new type of intellectual property protection platform by utilizing the decentralized, transparent, and tamper resistant characteristics of blockchain. The platform adopts smart contract technology to ensure the confirmation, authorization, and supervision of intellectual property rights, and ensures the traceability and tamper resistance of works through the distributed storage and timestamp functions of blockchain. At the same time, the platform also provides a convenient authorization management and copyright trading mechanism, providing a fair, transparent, and efficient intellectual property protection solution for artists and rights holders. Through empirical research and case analysis, this paper verifies the feasibility and effectiveness of a blockchain based intellectual property protection platform for intangible cultural heritage digital works. This platform can not only promote the inheritance and protection of intangible cultural heritage works, but also promote the healthy development of digital art market. In order to protect the copyright of intangible cultural heritage works, assist in the standardized collection, digital protection and dissemination of intangible cultural heritage. In terms of mental health, intangible cultural heritage has a unique therapeutic and soothing effect. Participating in the inheritance and practical activities of intangible cultural heritage can help individuals reduce stress, alleviate anxiety, and promote emotional balance and self adjustment. The aesthetic experience and artistic creation of intangible cultural heritage can also stimulate people\u2019s creativity and imagination, enhance individual self-esteem and self-confidence. In addition, intangible cultural heritage activities can promote social interaction and group cohesion, provide social support and emotional security, and help prevent and respond to mental health issues.Subjects and Methods: This article proposes a blockchain based intellectual property protection platform for intangible cultural heritage digital works to address the copyright issues encountered in the current digitization process of intangible cultural heritage works. Provide a more humane and easy to understand operation process on the platform, better fit the psychological needs of non-genetic heirs.Results: By integrating blockchain technology into the intangible cultural heritage creation and exchange platform, blockchain stores the information of intangible cultural heritage creators and works. Blockchain, as a decentralized, reliable, and secure storage technology, can provide copyright protection for digital works, as well as new ideas and methods for digitizing intangible cultural heritage and IP construction. At the same time, at the level of mental health, the use of blockchain increases the security of data, so that creators can store data more securely, so as to form a platform with a credible degree that meets the psychological expectations of the authors.Conclusions: Taking the IP digitization process of the intangible cultural heritage of Buyi people \u201cMaple fragrans Dyeing\u201d in Daihua Town, Changshun County, Guizhou Province as an example. Non-genetic heirs have a good experience on the platform, which is in line with psychological expectations. This case verifies the effectiveness of using blockchain to confirm the rights of digital works of intangible cultural heritage and further implement the copyright transformation mode.a, Yunying Shib, Fangmei LiangaYingli Guoa School of Teacher Education, Hechi University, Hechi 546300, China, b School of Big Data and Computer, Hechi University, Hechi 546300, China.Background: In schools, issues related to mental health among students have been a significant concern for several years. Before the outbreak, statistical sources indicated a significant and increasing rate of depressive disorders, suicidal behavior, and various other issues in educational institutions among students. This includes issues such as the possibility of being depressed and worst committing suicide. Thus, this qualitative study aimed to explore the Hechi University students\u2019 lived experiences with online learning during the COVID-19 pandemic. Specifically, this analyzes college students\u2019 mental health and it is influencing factors during online learning. Based on the findings recommendations were proposed and the implications were presented.Subjects and Methods: This research utilized a qualitative method of research, particularly descriptive phenomenology. The participants of the study were ten (10) students studying using the online learning platforms, they were selected using convenient sampling. The criteria for the participants\u2019 selection were students from all levels, male or female, and those using the online learning modality. Thus, they are the most suitable participants of this study as they can best give their responses and testimonials based on what they have experienced while using the new learning platform. The data gathering for this study commenced from November to December 2022. The researcher conducted in-depth one-on-one interviews in gathering the data.Results: The overall results suggested that most students expressed a wide variety of unfavorable emotions they believed they had encountered throughout the course of the global outbreak. Throughout the lockdown, several pupils expressed feelings including \u201cfrustration,\u201d \u201cconstriction,\u201d \u201canxiety,\u201d and/or \u201cdepression.\u201d After then, a few of them discussed why these feelings affected their day-to-day performance, often in significant ways. Thus, it was revealed that distance learning can be strongly demanding for the mental health of the students. Thus, assistance for student\u2019s mental health is needed during online classes since virtual learning exacerbates pupils\u2019 anxiousness throughout a disease outbreak.Conclusions: Online education was deemed to have a severe effect on the student\u2019s mental health. It was recommended that the results of this study shall be presented to the Ministry of education to provide information, plan activities, and strategies, and create innovations to provide sufficient intrinsic and extrinsic motivation to excel and improve their academic achievement and attain quality and relevant education during the pandemic.This work is supported by Guangxi Natural Science Foundation Project and Research Basic Ability Improvement Project for Young and Middle-aged Teachers of Guangxi Universities .a,b,c, Peiyun Guoa, Linbo ZhuaJing Zhaoa Institute of Human Geography, School of Tourism, Xi\u2019an International Studies University, Xi\u2019an 710128, China, bShaanxi Tourism Research Institute, Xi\u2019an International Studies University, Xi\u2019an 710128, China, c Research Center for Tourism Cooperation and People-to-people Exchange among SCO Nations, Xi\u2019an International Studies University, Xi\u2019an 710128, China.Background: Growing volume of research suggests mental health benefits of natural environments. Psychological needs and motivations of tourists of different age groups and how to promote mental health of tourists remain relatively unexplored. This research was aimed to examine association between rural tourism and mental health among tourists of different age groups.Subjects and Methods: Analyzing psychological needs and features of tourists of different ages, this study constructed a table to summarize. In addition, this research analyzed the existing resources of rural tourism in Shaanxi, China, and explored how to use these resources to meet the different psychological needs of tourists, relieve their psychological anxiety, and promote their mental health.Results: Rural tourism can promote the mental health of tourists of different ages. Adolescents face a variety of pressures, such as difficulties of interpersonal communication, heavy academic burden, excessive expectations of parents and so on, which can trigger psychological anxiety of varying degrees. Middle-aged people bear the pressure from emotion, home, work, and physical health, in the face of high-intensity work tasks in the workplace, at the same time, bear the responsibility to take care of the elderly and children in the family, is the most anxious stage of life. Unlike adolescents and middle-aged people, loneliness may cause anxiety for elderly people, especially empty-nesters who live alone. Different types of rural tourism can meet different psychological needs. Wildlife tourism can meet psychological needs of seeking novelty and knowledge of tourists. Living in the countryside with beautiful scenery, tourists can experience the natural, simple and sincere lifestyle and cultural expression of the countryside, and meet the nostalgia psychological needs. Forest tourism can enable tourists to appreciate natural scenery, enjoy quiet time, relax in fresh air, relieve the pressure of life, and promote mental health of tourists.Conclusions: People of different ages groups in modern society are under great pressure and prone to psychological anxiety. The natural environment, wild animals and homestays in rural areas can meet the psychological needs of tourists from different angles, so that tourists can obtain happiness and satisfaction, produce a positive tourism experiences, and promote the mental health of tourists.This research was supported by the Innovation Capability Support Program of Shaanxi (Program No.2022KRM038), Shaanxi Higher Education Teaching Reform Research Project (No.21BY092), Research and Practice Project on Comprehensive Reform of Postgraduate Education of Xi\u2019an International Studies University (No. 22XWYJGA08). The authors also wish to thank the editor and the reviewer for their valuable comments.aJuanmiao Shia Department of Social Work, Zhejiang University of Finance Economics Dongfang College, Jiaxing 314000, China.Background: With the development of the infant care service industry, all sectors of society gradually focus on how to create a friendly environment for infants and children. Especially the concept of \u201cchild-friendly community\u201d advocated in recent years, all sectors of society gradually focus on how to create a friendly environment for infants and children. The independent infant care service model cannot fundamentally solve the parenting pressure of young families and solve the problem of gradually decreasing child ratio. An appropriate service model is urgently needed to relieve the physical and mental pressure of infant families, promoting the healthy growth of infants and their family members. This study combined with the social organization in the process of service integration community resources to assist the practice of infant family nursery demand experience, put forward the appropriate infant nursery service intervention path-integrated service mode.Subjects and Methods: Selecting \u201cz\u201d social organization as research object, this paper expounds how \u201cz\u201d social organization integrates resources of community health service centers, voluntary service organizations and other community social organizations to provide physical, psychological and social services for infants in the community, so as to promote the healthy growth of infants and young children.Results: In this study, social organizations provide services for infants relying on child-friendly community platforms, and an integrated service model suitable for infant care needs is proposed. The integrated infants nursery care model mainly takes baby-friendly service projects as samples, integrates the resource advantages of women\u2019s federations, grass-roots civil affairs departments, medical and health organizations and medical volunteers, provides social support for infants in the community, and creates a child-friendly community atmosphere of \u201csystem-friendly, environment-friendly and service-friendly\u201d, responding to the needs of infants and families and promoting the healthy growth of infants.Conclusions: According to the practical experience of social organizations using the integrated service mode to provide services for infants in the community, it is concluded that the integrated service mode has realized the needs of infants in the community to a certain extent, and according to the practical experience of the integrated service mode, it clarifies the roles and tasks of each resource subject in the infant care and nursing. The integrated service model of infant service plays an important role in the healthy development of infant\u2019s physical, psychological and social ability.This work was supported by a project grant from the 2021 Philosophy and Social Science Planning project of Zhejiang Province \u201cResearch on the Improvement of Children\u2019s Psychosocial Ability from the Perspective of Community Governance- -Taking the Children\u2019s Friendly (Grant No.21NDQN301YB), 2023 Zhejiang Province Civil Policy Theory Research Project \u201cResearch on the Path of Social Organizations Participating in Children Friendly Services from the Perspective of Community Governance\u201d (Project No.: ZMKT202388) and the key topics of Zhejiang University of Finance Economics Dongfang College \u201cResearch on the Construction of Early Development Service System of 0-3 Year Old Children in Zhejiang Province\u201d(Grant No.2020dfy001).a, Faridah binti SahariaYarui Huoa Faculty of Applied and Creative Arts, Universiti Malaysia Sarawak, Sarawak, Malaysia.Background: The trouser production industry is in the transformation and upgrading of the attack period. Intelligent manufacturing is an important strategic direction for the transformation and upgrading of China\u2019s manufacturing industry, the emotional behavior of employees affects the organizational efficiency of the trouser production line, and the study of organizational efficiency is the core of automated production in the face of the new pattern of industry development, the trouser production line managers fully consider the emotional behavior of employees, the introduction of automated equipment to help improve the organizational efficiency of the production line It is imperative to do so.Subjects and Methods: This paper explores the factors influencing the introduction of an automated hanging system in trouser production lines in four dimensions: employee emotional behavior, i.e., intention to use, user satisfaction, and system quality and organizational efficiency, and constructs a theoretical model of organizational efficiency of an automated transfer hanging system. This study was conducted with 268 front-line employees in a Chinese trouser manufacturing company and analyzed by structural equation modeling (SEM).Results: The results showed that (i) system quality had a significant positive effect on employees\u2019 emotional behavior, i.e., intention to use and user satisfaction; (ii) user satisfaction had a significant positive effect on intention to use. (iii) Employee\u2019s emotional behavior, i.e., intention to use and user satisfaction, positively affects organizational efficiency.Conclusions: This study addresses the results of the study, fully considers the direct and positive impact of employees\u2019 emotional behavior on the organizational efficiency of the automatic hanging system, and puts forward practical and feasible guiding suggestions for trouser manufacturing enterprises to introduce automated equipment and enhance their automation and intelligent development capabilities based on meeting employees\u2019 emotional needs.a,b, Deying Lina, Zhaomin Sanga, Xin Zhanga, Jinhua Wua, Luxiang HouaXiaolan Huanga Department of Psychology, Third Affiliated Hospital of Guizhou Medical University, Duyun 558000, Guizhou China, b School of Nursing, Guizhou Medical University, Guiyang 550000, Guizhou, China.Background: To study the positive effect of cognitive therapy in rehabilitation treatment and nursing of depression in adolescents in the southern ethnic regions of Guizhou.Subjects and Methods: 1. The study subjects were adolescents with depression who were officially admitted to our hospital for rehabilitation treatment in the southern ethnic regions of Guizhou from July 2020 to May 2022. 2. They were randomly divided into a clinical pathology research experimental group and a clinical pathology control group (referred to as the control group). The control group was given symptomatic conventional drug treatment and routine nursing measures for psychiatric and psychological departments; while the experimental group was given cognitive therapy intervention on the basis of the conventional rehabilitation treatment and nursing measures of the control group. The Hamilton Depression Scale (HAMD) scores of the two groups of depressed patients before and after the intervention were compared. 3. Firstly, analyze and study the gender, age, education level, ethnicity, living environment, and other factors of the control group and experimental group of adolescent depression. 4. Use SPSS 21.0 statistical software for statistical analysis and data processing. The basic data is presented as mean \u00b1 standard deviation. Single-factor ANOVA test and post-hoc multiple comparisons (LSD method) are used for statistical analysis of the experimental and control groups.Results: The research results show that: 1. Adolescent depression is mainly concentrated in female Bouyei ethnic middle school students in rural areas. This is mainly due to the lack of care from parents for their female children while working outside the home. This should be highly valued by the school, society, and family, and proper care and frustration education should be given to left-behind children to enhance the life confidence and ability to withstand pressure of female students.2. After rehabilitation treatment intervention, the HAMD scores of the experimental group were significantly reduced compared to those of the control group. The clinical comprehensive evaluation index was significantly better in the experimental group compared to the control group, and the difference had important clinical statistical guidance significance (P<0.05).Conclusion: In the rehabilitation treatment and nursing of depression in adolescents in the southern ethnic regions of Guizhou, cognitive therapy can be effectively applied to improve the degree of depression and enhance the ability of emotional self-control. It is worth promoting in the clinical rehabilitation treatment and nursing of depression in adolescents.This research was supported by:1. 2020 Special Scientific Research Project of Nursing Discipline of Guizhou Medical University (Project No. YJ20070);2. 2023 Science and Technology Fund Project of Guizhou Provincial Health Commission (Project No. gzwkj2023-146).a, Wenlu WeibZhichao Songa School of Economics and Management, North China University of Technology, Beijing 100000, China, b School of Communication, Weifang University, Weifang 261000, China.Background: With the development and maturity of social media power, the influence of social media on the communication effect of agricultural brands is becoming increasingly apparent. Relevant practitioners feel more pressure on how to meet the psychological needs in the competition of the new industry. Some pathological competition also affects the psychological health of practitioners, such as disorderly competition and industry anxiety. The industry and society need to find answers to the problems based on development to meet individual psychological needs, solve industry pathologies, and sustainable development of agricultural brands. Research on the mechanism of agricultural products\u2019 brand communication in the social media environment will be one of the solutions. It is a generalization and summary of communication methods and effects, and a universal and replicable communication mechanism is refined based on communication practice, which can also meet psychological needs, solve anxiety problems and protect psychological health.Subjects and Methods: This article uses grounded theory and coding analysis through theoretical studies, policies, news, activity reports, and in-depth interviews on the communication of agricultural brands on various social media platforms. Through the coding analysis, the research finds the causes of industry anxiety, the conditions to meet psychological needs, and the solution ideas of pathological competition, and the article constructs a model of the influence mechanism of social media on the communication of agricultural brands.Results: Based on grounded theory, this paper sorted out 58 open codes, 26 spindle codes, and six selective codes in interviews and data screening. This paper describes and analyzes the selective codes, and the extensive data ensures the rigor and credibility of the result sources. Finally, it proposes a mechanism for agricultural brand communication that satisfies psychological needs and alleviates industry anxiety.Conclusions: Research and analysis based on grounded theory show that the influence mechanism of social media on agricultural brand communication will effectively meet psychological needs, relieve industry anxiety and improve mental health. This requires government authorities, industry associations or enterprises, and brand users to think and discuss various aspects when formulating communication strategies and developing more three-dimensional communication strategies to realize the benefits of transformation of agricultural brand communication and ultimately help the industry and practitioners to grow healthily and sustainably.aZhitao Xiaoa Department of General Education, Guangzhou Huali College, Guangzhou 511325, China.Background: With the progress of society and the development of medical technology, people need to integrate a large amount of medical resources, allocate medical tasks reasonably, and achieve higher efficiency and less wastage in completing tasks. This article presents a principle submatrix algorithm for the assignment problem where the number of medical tasks exceeds the number of people.Subjects and Methods: Firstly, we present the theory of same solution transformation for n persons and kn tasks assignment problems, followed by a principle submatrix algorithm for this type of problem. Then, we transform the medical assignment problem with more tasks than the number of people into a n persons and kn tasks assignment problem with the same solution, and finally use the principle submatrix method to find the optimal assignment of the problem. The characteristic of this principle submatrix algorithm is that it does not need to consider the overall assignment matrix of the assignment problem, only needs to perform operations locally on the assignment matrix, starting from the first order principle submatrix, and finding the optimal assignment of the problem step by step in a regular manner.Results: For medical assignment problems with more tasks than the number of people, we do not need to transform it into a balanced assignment problem where the number of tasks equals the number of people, this assignment problem is first transformed into an n persons and kn tasks assignment problem with the same solution, and then the principle submatrix algorithm is used to obtain the optimal allocation of the original medical assignment problem. The principle submatrix algorithm for this medical assignment problems with more tasks than the number of people proposed in this article is more regular and operable compared to the commonly used Hungarian method for solving assignment problems.Conclusions: The principle submatrix method proposed in this article is a polynomial algorithm with a computational complexity of. The algorithm starts from a row minimum group of the principle submatrix of the first order of the assignment problem, finds the row minimum groups of the principle submatrix of each order step by step, and finally obtains an optimal assignment of the original medical assignment problem. Through this method, it is convenient to find the optimal assignment of medical tasks that exceed the number of people, and efficiently complete the reasonable assignment of medical resources.aHua Ouyanga Guangxi University of Finance and Economics, Nanning, Guangxi 530003, China.Background: The 21st century is the ocean century, the ocean is rich in resources, social and economic development is an important support. Guangxi is located in the Southwest China, with an area of about 40,000 square kilometers in the Gulf of Tonkin Sea, and has huge potential for marine economic development. But at present, the development of Guangxi\u2019s marine economy has encountered a bottleneck. Especially in the digital transformation of the marine economy, the development of digital economy and intelligentization has also brought about the problems of machine dependence, loss of skills, infatuation with the network, separation from reality and spiritual loss, so that people\u2019s mental health has been affected.Subjects and Methods: By analyzing the background and current situation of Guangxi Marine Economy Digital Transformation, this paper probes into the painful and difficult problems in the process of Guangxi Marine Economy Digital Transformation. In particular, the paper deeply analyzes the mental health problems brought by the digital transformation of marine economy, and puts forward feasible solutions.Results: Through the research, the paper finds that although the progress of Guangxi\u2019s marine economy digitization is steady and good, it still faces many problems and challenges, mainly as follows: the marine economy digitization process lags behind, the marine digital economy enterprises lack vitality, the marine digital talents are seriously lacking. The digital development of marine medicine is absent, and the digital transformation affects people\u2019s mental health.Conclusions: We should break the shackles of the traditional economic model on the development of marine industry, and promote the digital development of Guangxi Marine Economy, and finally realize the transformation from \u201cDigital ocean\u201d to \u201cSmart Ocean\u201d. First, to build a strong digital marine area and a modern digital marine economy; second, to accelerate digital innovation and promote a high degree of integration between the digital economy and the marine industry; and third, to formulate preferential policies, fourth, to construct the system of marine medicine to alleviate the mental illness brought by digitalization. We should actively carry out psychological intervention, find out problems as early as possible and try to adapt to the development process of digital economy, so as to fully enjoy the changing modern civilization.This work was supported by The 2018 National Social Science Foundation Project (Grant No.18BJL049), Guangxi First-class Discipline Applied Economics Construction Project Fund (Grant No.2022YBD06) and the 2022 Annual scientific research project of land-Sea Economic Integration Collaborative Innovation Center (Grant No.2022YB10).a, Bingquan Luoa, Huayu Zhaob, Jun Chua, Zihao Lia, Jiwen Zhanga, Wenrui ZhangaYue Rena Capital University of Physical Education and Sports, Beijing 100191, China, b Northeastern University at Qinhuangdao, Qinhuangdao 066004,China.Background: Multi-information sensing technology has gained prominence in various industries, including sports. Long jump, an ancient sport, requires a deep understanding of muscle contraction methods and characteristics during each stage. Previous studies have primarily focused on movement patterns and joint muscle activity, without exploring the anatomical function of muscles and joints or the role of individual joint muscle groups in exercise techniques. By incorporating multi-information fusion technology in long jump research, this study aims to investigate the muscle-specific capabilities of long jumpers and contribute to the medical and health aspects of sports performance.Subjects and Methods: Utilizing multi-source information fusion technology, this study examined the biomechanical attributes of muscle-specific capabilities during the take-off phase of long jumpers, aiming to effectively identify changes in muscle vitality of the take-off leg. The research employed the widely-accepted multi-source information fusion technology to explore the specific conditions of long-jumpers\u2019 leg muscles during the take-off action, which accurately reflects the athletes\u2019 physical condition and has potential implications for injury prevention, athlete health, and performance enhancement.Results: The findings demonstrate that the hip joint of the take-off leg generates greater hip extensor torque during the long jump take-off action, highlighting the importance of active contraction ability of the knee flexor group for successful take-off and avoidance of damage to the posterior femoral muscle group. The range of pressure center change lies between 51.26% and 74.35%, suggesting valuable applications in actual training for improving athletes\u2019 well-being, overall health, and performance in the long jump. Additionally, these results can contribute to the development of personalized training and rehabilitation programs that minimize the risk of overuse injuries and muscle imbalances, ultimately promoting better overall health and longevity in athletes\u2019 careers.Conclusions: This study provides valuable insights into the muscle-specific abilities of long jumpers during the take-off phase using multi-source information fusion technology, which has significant implications for medical and health-related aspects of sports performance. The results emphasize the importance of hip extensor torque and knee flexor group contraction in injury prevention and optimal performance, with potential applications for enhancing training regimens, promoting athlete health, and prolonging careers. Furthermore, the knowledge of these biomechanical characteristics can assist in the early detection and intervention in cases of suboptimal performance, thereby allowing timely adjustments to training or rehabilitation programs and ensuring the athletes\u2019 well-being.a, Yubiao Lib, Wenqi GongbYouxi Yana Department of International Applied Technology, Yibin University, Yibin, Sichuan 644000, China, b Department of Resources and Environment, Wuhan University of Technology, Wuhan, Hubei 430070, China.Background: Minqin settlement system located in the downstream of Shiyang River Basin is surrounded by Tengger Desert in the northeast and surrounded by Badain Jaran Desert in the northwest, with strong ecological sensitivity. At the end of the last century, with the increase of settlement population, excessive reclamation and wood-cutting activities resulted in lack of ecological barrier of settlement system and deterioration of human settlement environment, and the residents were in deep anxiety. In order to solve people\u2019s psychological anxiety and repair the residential environment of settlement system, the state and local governments have successively launched the key governance projects of Shiyang River Basin after 2000, and completed the treatment in 2015 and carried out the acceptance of the treatment results smoothly.Subjects and Methods: In order to objectively analyze the restoration effect of key governance on the ecological environment of the settlement system and regulate the anxiety of residents in Shiyang River Basin, the TM remote sensing images of Minqin County in 1980, 2000 and 2015 are taken as the main data sources, and the landscape pattern of Minqin County Settlement System is interpreted through image fusion, geometric correction, image enhancement, data registration and sampling verification by referring to the geospatial data cloud of Chinese Academy of Sciences.Results: In 1980, 2000 and 2015, the area of settlement patches continued to increase, the patch area of cultivated land first increased and then decreased, the patch area of grassland decreased first and then increased, the patch area of forest land was flattened first and then increased, the patch area of water area first decreased and then increased, and the area of desert patches decreased in turn, and the key governance effect did not appear, and the adjustment effect of residents\u2019 anxiety was unsatisfactory.Conclusions: The reason is that the key governance measures of Shiyang River Basin are improper, and the water conveyance mode in the settlement is still artificial lined channels, and the natural water transportation mode of Daxi River and Dadong River is abandoned. The east and west ecological barriers of settlement system cannot be restored naturally due to water shortage, and the residents are still anxious about ecological problems.This work was supported by Yibin University \u201cSailing\u201d plan project (2020QH02), General Project of Ministry of Education Foundation on Humanities and Social Sciences in 2021 (21XJA630008) and the fourth round key discipline of Yibin University \u201cResources and Environment\u201d.a,b, Boping Tiana, Guangqiang TengaJinyang Liua School of Mathematics, Harbin Institute of Technology, Harbin 150006, China, b School of Statistics, Chengdu University of Information Technology, Chengdu 610103, China.Objective: Infectious diseases are often fierce, dangerous, widely spread, and have a huge social impact. Countries have developed different prevention and control strategies according to the epidemiological status, disposal capacity, and social characteristics of their infectious diseases. Few quantitative studies have been conducted to compare and analyze the intervention effects of infectious disease epidemics in multiple countries. This study aims to use scientific models and methods to evaluate the effect of infectious disease intervention in different countries, sum up experience and lessons, and provide some suggestions for minimizing or effectively controlling infectious diseases that may occur in the future.Methods: This study used the classical epidemiological SIR model and calculates its basic regeneration number to compare the effectiveness of infectious disease epidemic control in four countries: China, America, Italy, and India. By solving the SIR model with a system of differential equations, the infectious disease epidemic curves can be fitted relatively accurately based on available data. It is only necessary to estimate the model parameters to predict the spread of infectious diseases, and then evaluate the intervention effect of infectious diseases.Results: In this study, the epidemic trends of infectious disease in four countries, China, America, Italy, and India, under natural conditions and government control, were obtained by simulation and the basic regeneration numbers were calculated. The study shows that the spread of the epidemic was effectively interrupted earlier in China under control, while the epidemic control was not more effective in America, Italy, and India.Conclusions: As transportation levels increase and the number of mobile populations grows, prevention of infectious diseases is no longer simply a matter of prevention in a particular region or country, but has expanded to a global level. In this study, the SIR model was used to compare and analyze the prevention and control effects of infectious disease outbreaks in four countries. The findings of the study deepen the understanding of infectious diseases and their intervention measures to a certain extent, which plays a role in the common and effective response to similar outbreaks of major infectious disease epidemics in the future. China\u2019s infectious disease intervention measures and related experiences are worthy of active reference by countries around the world.This work was supported by a project grant from the Natural Science Foundation of China(NSFC) (No.91646106).a, Ji GuoaTian Lia College of Arts, Gansu University of Political Science and Law, Lanzhou 730070, China.Background: Art therapy, also known as art psychotherapy, is an important intervention method for treating psychological issues. It spans multiple disciplines, including art, psychology, and medicine, and has gained increasing attention as society continues to develop. Painting therapy is one of the methods of expressive art therapy, which allows painters to use nonverbal tools through the creative process of painting to guide chaotic psychological states and feelings into a clear and orderly state. It can present the suppressed emotions and conflicts within the subconscious and obtain relief and satisfaction during the painting process, thus achieving diagnostic and therapeutic effects.Subjects and Methods: A certain number of college students with psychological issues were selected, and interviews, questionnaires, and analysis were conducted to summarize their psychological problems. Different treatment strategies were employed based on the specific psychological issues of the college students. There are various forms of painting therapy strategies, including free painting, theme painting , gestalt painting , and so on.Results: Painting therapy is a service-oriented profession that presents individual development, abilities, personality, interests, concerns, and conflicts through the use of painting media or materials, artistic imagery, creative artistic activities, and patient feedback on the work. Art therapy is generally suitable for individual psychotherapy. Through art therapy, various tense emotions and pressures can be released during the creative process, inherent experiences can be clarified, thoughts can be concretized, and certain psychological needs can be conveyed. Art creation opens a pathway to the subconscious, facilitating the expression, reflection, integration of individual development, abilities, interests, personality, thoughts, and inner emotional states, making it more accessible to the public.Conclusion: Through painting therapy, the suppressed emotions and conflicts in the patient\u2019s subconscious are presented. At the same time, during the process of painting therapy, the patient releases negative energy in their mind, emotions, and thoughts, decompresses, releases emotions, adjusts emotions and attitudes, repairs spiritual wounds, fills gaps in their inner world, and obtains a sense of satisfaction, achievement, and confidence, thereby achieving good diagnostic and therapeutic effects. Art therapy has vast prospects, but due to various objective factors and the low attention given to this therapy in China, there is limited research, insufficient studies, and a lack of prominent case studies, making it difficult to conduct specific and effective art therapy. This article mainly explains the implementation, directions, and unique significance of art therapy, aiming to provide a detailed introduction to the entire process of art therapy, its advantages, and development prospects.This study was supported by the 2021 Young Doctor Fund Project of Gansu Province (Project No.: 2021QB101).a, Borhannudin Bin Abdullahb, Hazizi Bin Abu SaadcChenxi Lua Faculty of Educational Studies, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia, b Faculty of Educational Studies, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia, c Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.Background: Intelligent somatosensory interactive exercises are the primary focus of this study because of their potential to improve motor skills and effect and on the psychological status in autistic children.Subjects and Methods: The present issues of hand movement training for children with autism, as well as the impact of somatosensory games on psychological status as well as on rehabilitation training for autism, are explored via the use of case studies. Somatosensory activities for teaching kids with autism how to use their hands effectively were studied. The impact of various variables on users\u2019 immersion is investigated via data collecting, classification, and analysis. Functions, programme flow, main features, and implementation effects of the somatosensory game are displayed, and an introduction to the development platform and key technologies used in the design and development of the somatosensory game module are provided.Results: Modelling, character management, task flow management, collision detection, an interactive interface, and natural interaction techniques including gesture and voice interaction are all presented as part of the somatosensory interaction system\u2019s development process. This research paper defines autism and describes its symptoms and features in youngsters. It lays the groundwork for future study by discussing the viability of using somatosensory games in the hand movement training of autistic children and by providing an in-depth analysis of the development status and use of somatosensory games. It also clarifies the product\u2019s intended direction and design content for somatosensory interactive training products based on the defined study material.Conclusion: Somatosensory games have been demonstrated to be useful in the improving the psychological status and rehabilitation of autistic youngsters. Children with autism showed improvements in their visual responses, anxiety responses, verbal communication, and interpersonal relationships after participating in a healthcare intervention based on intelligent interactive gesture technology.a, Yuanyuan DaiaHeshuang Yea Physical Education Institute, University of the Chizhou, Chizhou, Anhui 247100, China.Background: With the rapid development of society, college students often face various pressures, such as study, employment, love and so on. These pressures will seriously affect the mental health of college students. Only strong mental toughness can help them overcome difficulties and promote the good development of mental health.The purpose of this study is to explore the characteristics of mental toughness of college students majoring in physical education and non-physical education, and to provide ideas for further enhancing the mental health level of students of different majors.Methods: The psychological toughness of 788 students of different majors in Chizhou University was investigated by using the Adolescent Mental Toughness Scale and questionnaire survey. Among them, 340 students (217 boys and 123 girls) majored in physical education and 448 students (177 boys and 271 girls) majored in non-physical education. The collected scales and questionnaires were classified, and the data were recorded into Excel for statistics and SPSS 25.0 for independent sample T-test.Results: (1) The total score of the respondents\u2019 mental toughness was 81.02\u2009\u00b1\u200915.16. Among the dimensions of mental toughness, family support was the highest, followed by interpersonal assistance, goal focus and emotional control, and goal focus was the lowest. (2) For physical education major and non-physical education major, there were significant differences in goal focus, emotional control, family support and interpersonal assistance (P<0.01), and there were significant differences in total score of mental toughness and positive cognition (P<0.05); (3) There were significant differences in total score of mental toughness, emotional control, family support and interpersonal assistance between male physical education major and non-physical education major (P<0.01), and there were significant differences in goal concentration (P<0.05). (4) There were significant differences in goal focus, emotion control, positive cognition and interpersonal assistance between females majoring in sports and females not majoring in sports (P<0.01). (5) Male and female physical education major: The total score of mental toughness and each dimension had no statistical significance (P>0.01).Conclusion: (1) Family support had a significant impact on the psychological resilience of the respondents; (2) The overall mental toughness of physical education major is significantly better than that of non-physical education major; (3) In terms of total score of mental toughness, emotional control, family support and interpersonal assistance, male physical education major are better than female physical education major. In terms of goal focus and positive cognition, male physical education major are weaker than female physical education major. Tips: (1) When improving the mental toughness of college students, it is necessary to unite with their families. Through the joint intervention of family and school, the mental toughness of college students can be effectively promoted; (2) Physical exercise can effectively promote the level of mental toughness. Schools should strengthen physical education and create a strong physical exercise atmosphere. (3) In the work of mental health education, we should pay attention to gender differences and pay attention to teaching students according to their aptitude.This work was supported by 3 project grant from Key Humanities Project of Chizhou University(Grant No.CZ2021RWZ18); Key Research Project of Philosophy and Social Sciences in Higher Education Institutions of Anhui Province(Grant No.2022AH051811); Key Teaching Research Project of Chizhou University (Grant No.2021XJYXM03).a,b,c,d, Hao Tiana,b,c,d, Qin Maa,b,c,d, Lunzhi Yanga,b,c,d, Xue Zhoua,b,c,d, Ting Xiaoa,b,c,d, Ling Taoa,b,c,d, Linjing Wua,b,c,dYing Chena School of Pharmacy, Key Laboratory of Optimal, Utilizaiton of Natural Medicine Resources, Guizhou Medical University, Guiyang 550025, Guizhou, China, b State Key Lab of Functions and Applications of Medicinal Plants, Guiyang 550025, Guizhou, China, c Key Laboratory of Natural Medicine Pharmacology and Drug Evaluation of General Colleges and Universities in Guizhou Province, Guiyang 550025, Guizhou, China, d Guizhou Provincial Efficient Utilization Engineering Center of Featured Natural Medicine Resource, Guiyang 550025, Guizhou, China.YC and HT contributed equally to this work.Background: Rheumatoid arthritis is a type of inflammatory arthritis characterized by joint inflammation, swelling, pain and potential damage. Western medicine primarily focuses on controlling inflammation and regulating immune function in the treatment of RA, with commonly used clinical drugs including non-steroidal anti-inflammatory drugs, glucocorticoids, antirheumatic drugs and biological agents. However, prolonged use of these medications may lead to liver and kidney dysfunction as well as gastrointestinal complications. Polygonatum exhibits characteristics of \u201cmulticomponent, multitarget, and multipathway\u201d which provide potential advantages in the treatment of rheumatoid arthritis (RA). Network pharmacology integrates network biology with various pharmacological approaches based on existing databases. By investigating multiple targets, a \u201ccomponent-target-disease\u201d network can be constructed, providing a novel approach to explore the mechanism and synergistic effects of Polygonatum in treating rheumatoid arthritis.Subjects and Methods: This study aims to investigate the mechanism of rheumatoid arthritis treatment using network pharmacology and molecular docking techniques. Through literature mining and database retrieval, the compound components of Polygonatum were obtained, the potential targets of the compounds were predicted using the TCMSP database, and the related targets of rheumatoid arthritis were obtained through GeneCards, OMIM and other databases, and the intersection targets of Polygonatum for the treatment of rheumatoid arthritis were obtained. Based on the STRING database, Cytoscape software was used to construct the interaction network of the common target protein of Polygonatum and Rheumatoid Arthritis, and the key targets were selected for molecular docking with the chemical components of Polygonatum to verify and analyze the interaction between them.Results: The final screening results revealed the identification of 12 active components, 65 potential targets, and 4797 potential targets for rheumatoid arthritis. Additionally, a total of 48 common targets were identified. GO and KEGG enrichment analysis led to the discovery of 343 signal pathways related to the main components found in Polygonum japonicum. The core components \u03b2-sitosterol and baicalein exhibited strong binding affinity with key targets VEGFA and RELA.Conclusions: Through the application of TCM network pharmacology, this study revealed that Polygonatum may play a multi-component, multi-target and multi-pathway therapeutic effect on rheumatoid arthritis by regulating cell apoptosis and cholesterol-like hormone receptors, participating in cancer pathways and other mechanisms, which may provide a reference for the screening of clinical efficacy evaluation indicators for the treatment of rheumatoid arthritis.The research was supported by Guizhou Provincial Basic Research Program and Guizhou Provincial Key Technology R&D Program (No. [2020]4Y104).aChong Hea Department of Economics, Zhejiang University, Hangzhou 310030, China.Background: Study the incentives of the country for reporting emerging infectious disease outbreak, in order to reduce public panic and herd behavior during public health events.Subjects and Methods: This paper expands the existing single signal game on the motivation of national reporting epidemic to the infinite signal game. In the model, the main benefit of reporting infectious disease outbreak is to reduce casualties, while the main loss is the decrease in income caused by trade and travel disruptions. The model incorporates the loss of mental health of the population due to panic in an epidemic and the losses caused by disrupting social order due to herd behavior such as rushing to buy household goods. In addition, the model takes into account the accuracy of medical detection of infectious disease outbreak as a way to distinguish the behavior of the country under different parameters.Results: The country is more willing to truthfully report the diagnostic test of the disease outbreak in the infinite game than in a one-shot game in order to win the trust of the public and reduce social psychological panic. When trade and travel disruption intensifies, the country will tend to adopt an \u2018oscillating\u2019 strategy: conceals or adopts a mixed action when the volume of trade and travel is above the threshold, but truthfully reports the diagnostic test when the volume is below the threshold. The rapid growth of trade and travel may inhibit the willingness of the country to truthfully report the detection information and increases the risk of disease transmission.Conclusions: When making decisions, the government should not only consider economic losses, but also consider the psychological health issues among the public caused by the epidemic and lack of information, which helps the government truthfully report infectious disease outbreak. It is not better for the partner to impose trade and travel disruption as harshly as possible. The increase in assistance from international organizations such as WHO can help the country to report truthfully, but blindly improving the detection accuracy may only lead to the waste of funds. What\u2019s more, a financial mechanism led by the World Bank should be set up to compensate national and local governments for economic losses associated with outbreaks, especially in areas with the greatest lack of health resources.a, Dongyi Huangb, Wu LiucKaiwen Lia Wenshan University, Yunnan Wenshan 633099, China, b School of Sports Science, Guangzhou College of Applied Science and Technology, Guangzhou 511370, China, c Yunnan Vocational College of Mechanical and Electrical Technology, Yunnan Kunming 650203, China.Background: With the rapid development of China\u2019s economy, more and more college students are in the state of sub-health, among the types of exercise used in the clinical management of sub-health, some are related to the ancient Chinese traditions as Baduanjin. Despite the growing interest of the scientific community in Baduanjin, which has the theoretical basis of traditional Chinese medicine, its research is still in its infancy. It is noteworthy that, to the best of our knowledge, there are no studies that verified the influence of Baduanjin on sub-healthy college students. Therefore, the main objective of the present study was to investigate the effects of the Baduanjin, a traditional Chinese Qigong, on the physical and mental health of sub-healthy college students.Subjects and Methods: Explore the intervention effect of Baduanjin exercise on sub-health college students. The average age . Methods Comparative analysis method was used. Practicing baduanjin for 18 weeks, after the experiment, the improvement of physical, mental and fatigue sub-health was assessed by \u201cPersonal Health Status Questionnaire\u201d. HK6000, G100, JGW-B and FCS-10000 were used to evaluate the physical forward bend, grip strength, Reaction time, and vital capacity.Results: The 220 students were randomly allocated to the control or experimental group. Physical and mental health, fatigue status, and physical fitness were assessed in both groups before and after the experimental protocol. Compared with the control group, the physical subhealth and mental subhealth of the experimental group were significantly improved (P<0.05). The fatigue state of the experimental group was significantly relieved (P<0.05). Baduan jin intervention significantly improved sitting forward flexion ability and lung volume (P<0.05).Conclusion: It is proved that baduanjin has significant therapeutic effect on sub-health of college students. It provides a new way for researchers and coaches to conduct research and intervention from the perspective of traditional medicine.Thanks to Professor Gu Yongkun, Professor Liu Wu and coach Lu Tianxue for their support to the sub-health intervention students.aChin-niang Chana School of Art, Minnan Normal University, Zhangzhou, Fuijian, China.Background: Music therapy is different from conventional instrumental music, as it has the ability to evoke every possible emotion. A melodious voice can heal a person, and music therapy is a constantly evolving concept that can promote healing. Mainly, it is a therapeutic method that utilizes the natural emotional enhancement characteristics of music. In addition, it can also help people improve their mental health and overall happiness.Subjects and Methods: Music therapy includes developing music, writing songs, singing, dancing, listening to and discussing music. Especially, this form of treatment may be helpful for people with depression and anxiety. In addition, it may help improve the quality of life for people with physical health issues. The music of playing the yangqin can make us soar to unimaginable heights, comfort us in sadness or loneliness, help us release our anger or frustration in a way that does not harm anyone, make our bodies move, and bring peace and tranquility to our hearts.Results: Music therapy is an expressive art therapy that uses music to improve and maintain an individual\u2019s physical, psychological, and social well-being. In addition, it also involves a wide range of activities, such as listening to music, singing, and playing musical instruments. Music can also improve our health and happiness. Music heals, allowing wonderful music to improve our physical and mental well-being. After experiencing the baptism of hundreds of years of Chinese culture, the yangqin has achieved outstanding development in its performance form. In addition to solo performances, the yangqin is widely involved in various forms of performance such as traditional Chinese opera, Quyi accompaniment, ensemble, large, medium, and small ensemble, and has become an important component of Chinese ethnic instruments. A large number of literature references and field research are combined to obtain the original data, and the results can be obtained only after analysis and research.Conclusion: The increasing evidence of music therapy suggests that music therapy is not just a great way to boost energy, but can improve medical outcomes and quality of life in various ways. Surprised by the magic of music and its benefits in treating mental illnesses. Not only that, music therapy can also cure some symptoms of physical problems. Of course, there are some types of music to enhance emotions and relieve stress. The yangqin has been continuously absorbed, integrated, transformed, and developed in the process of historical transformation, and its development requires the improvement of the content of the work. In the creation and performance of traditional and modern works, it is necessary to strive for innovation through change and progress through development, making contributions to enriching and improving the art of yangqin.a,b, Bo Sua,bLingshan Lia School of Management, Hubei University of Chinese Traditional Medicine, Wuhan, Hubei 430070, China, b Research Center for the Development of Traditional Chinese Medicine, Key Research Institute of Humanities and Social Sciences of Hubei Province, Wuhan, Hubei 430070, China.Background: With the great contribution of the traditional Chinese medicine (TCM), China has made significant breakthroughs in combating the epidemic. Moreover, China has released many relevant policies to support the development of the traditional Chinese medicine industry. For the public, more and more people are paying attention to personal health management. The development of the traditional Chinese medicine industry will further promote the health of the entire population.Subjects and Methods: In order to further understand the degree of the development of Chinese medicine industry in China, this paper selects 62 listed companies in the traditional Chinese medicine (TCM) industry to research their growth in the future with their financial data in 2022. With reference to listed company performance evaluation index system, we constructed a index system of 12 indicators from 4 aspects using factor analysis for empirical analysis. These four indicators are profitability, debt paying ability, operational ability, and growth ability. These four abilities can comprehensively measure the overall situation of a company.Results: According to the empirical results, it can be found that among the 62 listed TCM companies, 32 companies got a growth score of more than 1, accounting for 51.61%, indicating that these companies had a good development prospect. However, only 3 listed TCM companies scored more than 1 in all indicators, which suggests that there is still a lot of development space for other companies to explore. The top ten companies all have well-known products and operate well.Conclusions: The TCM company needs to develop its own characteristics to enhance its growth potential. The TCM companies also need comprehensive development to be more competitive. The development of a company needs to meet the public\u2019s health needs in order to have greater development space. The development of the traditional Chinese medicine industry plays an important role in disease prevention and can better assist people in health management.a; Qiushuang DuanaXuecheng Wanga School of Economics and Management, North China University of Technology, Beijing, China.Background: Investor\u2019s mental health has a great impact on their investment behavior. Anxiety, autism and personality disorders may cause investors to loss their judgment, rely more on the herd effect, and make irrational investment behaviors. Frequent trading triggered by rumors and hot spots causes investors to ignore the value of stocks and lead to investment failure. The existing research shows that the digital transformation strategy has little impact on the profit of R&D-dependent industries as pharmaceutical and health industries. Will the hype about the concept of the digital economy lead to investors exhibiting irrational behaviour? Will listed companies in the pharmaceutical industry use the digital economy to push up their stock prices? This paper will examine the above issues.Subjects and Methods: This paper have tested whether there is an irrationality investment behavior caused by unhealthy psychology with individual fixed panel regression models of 299 A-share listed companies in China\u2019s pharmaceutical industry from 2010 to 2020.This paper uses abnormal trading volume to represent unassertive investment due to blindness, pressure and other negative psychology, uses the FGLS estimation method to estimate the parameters of the model, and use the two-step correction method for the coefficient correction of AR(1) and the PSCE method for the heteroskedasticity-robust covariance correction to produce more reliable regression results. We also performed robustness tests to avoid regression bias. All methods are based on theoretical deduction and empirical analysis of investment psychology.Results: The hypothesis that unhealthy investment psychology attracted by investment hot-spots encourages blind investment is well tested. There is a herd effect attracted by the digital transformation strategy of pharmaceutical companies. Investors trade frequently and drive up the stock price severely than normal. On average, an increase of 1 unit in the frequency of digital economy related vocabulary (per thousand words) in the annual reports will increase stock trading volume by 1000 million in a whole year. This result is significant at the 1% level. This result proves that overinvestment due to psychological problems exists. The robustness test also shows that the stock price will be raised by about 23.89%.The results can be used to explain the collective psychological problems in investment, such as excessive profit pressure, choice anxiety, and excessive comparison.Conclusions: Under the influence of herd mentality, investors will indeed make irrational investment behaviors. This unhealthy psychology is transmitted between groups, causing distortions in the value of the stock market. It can be seen that investors have high hopes for the digital transformation of pharmaceutical companies. But poor knowledge and overstress drive people to ignore risks. Before the digital economy strategy takes effect, investors should overcome anxiety and maintain a healthy mind. Pharmaceutical companies should increase corporate profits and promote the lasting development of the industry. The mechanism of individual psychological problems on market failure is the subject of further research.This research was supported by Beijing Social Science Foundation (Grant No.22JCC077) and Beijing Urban Governance Research Base of North China University of Technology.a, Dongmei Lia, Changqing FengaHongyan Shena Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China.Background: In recent years, with the increasing incidence of tic disorder in children, the author observed children suffering from tic disorder accounted for nearly one fifth of the chronic disease patients in the pediatric outpatient department of our hospital. Ranking the second after spleen and stomach disease, tic disorder has witnessed a decreasing trend in its onset age. Due to the complex etiology of tic disorder, there is no specific treatment method at present.Subjects and Methods: To explore the etiology and pathogenesis and provide favorable methods about prevention and treatment of tic disorder in children according to the theory of \u201coccurrence due to adding causative factors\u201d.In the process of the clinical research on tic disorder, we consulted, collected and sorted out a lot of literatures, including classical TCM ancient books and medical journals, etc., combined with clinical data, and systematically analyzed the diagnosis and treatment of tic disorder. We collected and referred to huge amounts of information in TCM books and periodicals, in order to further clarify the pathogenesis of tic disorder, and to identity the focus of treatment and prevention for tic disorder. In this paper, the pathogenesis of tic disorders in traditional Chinese medicine is clarified from all aspects. This study is based on the theory of \u201coccurrence due to adding causative factors\u201d, which clarify the pathogenesis of tic disorder from the inside to the outside, from the point to the surface, from multiple perspectives, including the children\u2019s constitution, body endowment and traditional Chinese medicine Yin and Yang, the five elements, and the visceral state.Results: The etiology and pathogenesis of tic disorder in children are similar to the theory of \u201coccurrence due to adding causative factors\u201d in Canon, which is the most classical TCM ancient book. The pathogenesis of tic disorder in children can be explored from the theory of \u201coccurrence due to adding causative factors \u201c, so as to guide the treatment for children with tic disorders.Conclusions: The treatment based on the theory of \u201coccurrence due to adding causative factors\u201d for children with tic disorder can better guide clinical treatment and differentiation of syndromes, so as to achieve \u201ccuring the disease to seek the root\u201d, guide the clinical children to \u201cprevent diseases before occurrence\u201d, and thus has certain clinical practical value.This paper was supported by the basic research project of the education department of Liaoning province (2100221274).a, Huiling Lua, Xiaopan Dia, Yan Lia, Bo Chena, Danyang Lia, Long Zhanga, Yuping Zhanga, Hui YaoaWei Duana Department of Medical, People\u2019s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia 750001, China.Background: To investigate the efficacy of 4S lying position lung rehabilitation exercise, in hospital-family integrated lung rehabilitation nursing of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) patients,and to summarize the application experience.Subjects and Methods: A total of 99 AECOPD patients who were hospitalized from March 2019 to June 2020 in People\u2019s Hospital of Ningxia Hui Autonomous Region were enrolled in the study. According to the inclusion criteria, Patients were randomly divided into observation group (49 cases) and control group (50 cases). The observation group had 34 males and 15 females, ranging in age from 63 to 84 years, with an average of (72.19\u2009\u00b1\u20097.89) years; the control group had 33 males and 17 females, ranging in age from 66 to 83 years, with an average of (73.70\u2009\u00b1\u20095.32) years. There was no statistically significant difference in gender and constitutional indext (P>0.05).Both groups received the same drug treatment. The observation group received 4S lying position lung rehabilitation exercise, while the control group received routine lung rehabilitation program. mMRC scores, 6MWT, CAT scores and compliance of family lung rehabilitation were compared between the two groups before and after intervention for 12weeks.Results: Comparison of the compliance of family lung rehabilitation between the observation group and the control group after 12 weeks of intervention was improved, but the improvement degree in the observation group was significantly higher than that in the control group(P < 0.05), with statistical significance. 12 weeks after intervention, the scores of mMRC, 6MWT and CAT in both groups were improved. The improvement of the observation group was significantly higher than that of the control group (P<0.05), with statistical significance.Conclusions: 4S lying position rehabilitation exercise is safe, effective and simple.It can relieved patient\u2019s dyspnea symptoms,promote exercise ability and quality of life, which has positive significance for patients\u2019 self-care ability, maximum social function and is thus worthy to promote hospital-family integrated lung rehabilitation nursing mode for AECOPD patients.This work was supported by a project grant from Ningxia Hui Autonomous Region Health System Scientific Research Project (Grant No.2022-NWKY-006).a, Junfang Zhub, Huifang Chenc,d, Haichao Huangb, Bo Lib, Yan Lid, Jianhua Yie, Bing Liuf, Hua Caod, Li YaogYang Niea School of Pharmaceutical Engineering, Guangdong Food & Drug Vocational College, Guangzhou 510520, China, b Experimental Training Center, Guangdong Food & Drug Vocational College, Guangzhou 510520, China, c College of Chemistry & Pharmacy, Guangxi Normal University, Guilin, 541004, China, d Guangdong Lingnan Institute of Technology, Guangzhou 510663, China, e Department of Orthopedics, East Hospital of the First Affiliated Hospital of Sun Yat sen University, Guangzhou,510700, China, f School of Health, Guangzhou Huaxia Vocational College, Guangzhou 510935, China, g School of Food Science and Biology, Guangdong Polytechnic of Science and Trade, Guangzhou, 510430, China.Y Nie and HF Chen contribute equally to this work.Background: This project aims preferred clebopride bioadhesive sustained-release tablets of the prescription and preparation processes, and to study the effects of Clebopride (CBP) bioadhensive sustained-release tablets on experimental gastric ulcer and gastrointestinal motility disorder.Subjects and Methods: Release tablets release as an indicator, the use of orthogonal design to optimize select clebopride prescription bioadhesive sustained release tablets. Gastric ulcer rat model was induced by ethanol and aspirin, and then divided into model group , common tablet (CBP tablet 0.072\u2005mg/kg) and sustained-release tablet high-dose and low-dose groups ; normal rats were included in normal control group ; they were given relevant medicine intragastrically, twice a day for sustained-release tablet, three times a day for other. Ulcer area were observed 2 and 4 days after medication to calculate healing rate of ulcer (n=6). Gastrointestinal motility disorder mice model was induced by atropine, and then divided into model group , common tablet group (CBP tablet 0.1\u2005mg/kg) and sustained-release tablet high-dose, medium-dose and low-dose groups ; normal mice were included in normal control group ; they were given relevant medicine intragastrically, once a day, for consecutive 3 days. The rate of gastric emptying and small intestinal propulsion were detected (n=6).Results: The optimized formulation consisting of hydroxypropyl methyl cellulose (HPMC 5.5g/100 tablets) and carbomer (CP 2.2g/100 tablets) bioadhesive and skeletal material, lactose as diluent (1.2g/100 film), starch as a filler and a disintegrant (2.0g/100 tablets), optimized in line with a sustained-release tablets prescription kinetic process, release meet the design requirements. Simultaneously with clebopride ordinary tablets measured and compared to the rat gastrointestinal tract adhesion. Compared with normal control group, ulcer area of rats increased in model group; compared with model group, that of rats decreased in common tablet group and sustained-release tablet high-dose, low-dose groups, with statistical significance (P< 0.01); healing rates of gastric ulcer were 32.35%-48.24% 2 days after medication, and those were above 70% 4 days after medication. Compared with normal control group, the rate of gastric emptying and small intestinal propulsion in mice decreased in model group; compared with model group, those of mice increased in common tablet group and sustained-release tablet high-dose, medium-dose, low-dose groups. The effects of sustained-release tablet high-dose and medium-dose groups were better than that of common tablet group; those difference had statistical significance (P< 0.01 or P< 0.05).Conclusions: This study obtained clebopride bioadhesive sustained-release tablets have good slow-release effect, reasonable preparation process is simple, and significant adhesion performance to meet clinical needs, CBP bioadhensive sustained-release tablets have improvement effects against gastric ulcer of rats and gastrointestinal motility disorder of mice, CBP bioadhensive sustained-release tablet has good development prospects.This work was supported by the key project grant of Natural Science Foundation of Guangxi Province in 2022: mitochondrial autophagy inhibits aBelta deposition and tau phosphorylation to improve cognitive function of AD model animals (Grant No.2022GXNSFAA035447).This thesis is also supported by the following project funds: 1) 2019 Guangdong Medical and Health Education Steering Committee Project: Deep Research on the Teaching Reform of Biopharmaceutical Technology Course under the Background of \u201cSchool enterprise Cooperation\u201d (Project No. 2019LX025); 2)the project of Guangdong Provincial Health and Health Commission on the development, pharmacokinetics and pharmacodynamics of coagulation factor XIII microsphere long-acting injection (No. A2021203) In 2021; 3)Evaluation on the Introduction, Tissue Culture, Rapid Propagation and Planting Effect of Genuine Rhizoma Bletillariae of Guangdong Provincial Bureau of Traditional Chinese Medicine (No. 20191242) in 2020."} +{"text": "ASD are heterogeneous pathological conditions characterized by difficulties in establishing social contacts and the manifestation of repetitive behavior. An atypical trajectory of brain maturation, impaired neurogenesis, synaptogenesis, and an imbalance in the excitatory and inhibitory systems of the CNS form the morphofunctional basis of the ASD.To understand the functioning of this complexly organized system in time and space, a three-dimensional model is needed. The closest in vitro model of the human brain from early embryonic stages to aging is brain organoids. Human brain organoids are self-organizing three-dimensional cell aggregates derived from pluripotent stem cells (hiPSCs)Organelles generalize neurogenesis, gliogenesis, synaptogenesis, cell migration and cell differentiation, gyrification of the cerebral cortex, and reflect the connections of brain regions.The use of telencephalon organelles in the RAS model revealed a deficit in neuronal migration, acceleration and disruption of cell cycle synchronization, aberrant cell proliferation, abundant synaptogenesis, temporary deviations in the development of the cortex, increased branching of neurons, unbalanced inhibitory differentiation of neurons, high activity of ion channels is a consequence of a violation of FOXG1 activity. Organelles generalize neurogenesis, gliogenesis, synaptogenesis, cell migration and cell differentiation, gyrification of the cerebral cortex, and reflect the connections of brain regions.The use of telencephalon organelles in the RAS model revealed a deficit in neuronal migration, acceleration and disruption of cell cycle synchronization, aberrant cell proliferation, abundant synaptogenesis, temporary deviations in the development of the cortex, increased branching of neurons, unbalanced inhibitory differentiation of neurons, high activity of ion channels is a consequence of a violation of FOXG1 activity .hiPSCs can provide insight into the cellular mechanisms underlying ASD as a neuropsychiatric disorder, providing access to the development of platforms for in vitro drug screening and individualized patient therapy.None Declared"} +{"text": "In this Special Issue, six articles using the Japan National Health and Nutrition Survey (NHNS) were published. Among the six articles, two examined the time trends ,2, two uIn Japan, the prevalence of hypertension has decreased with the improvement of medical treatment and decreased dietary salt intake. In panel data analysis, the trends in hypertension prevalence, treatment, and control were investigated by life expectancy at the prefectural level . It was Using the Joinpoint Regression Program, trends in food group intake were evaluated by physical size in young Japanese women in NHNS 2001\u20132019 data [In the super-aged society of Japan, it is expected that reducing dietary salt intake prevents cardiovascular disease and hence curbs growing healthcare expenditures. The effect of achieving global and national targets of salt reduction on cardiovascular events and national healthcare expenditures was estimated . CompareJapan experienced a decrease in cardiovascular mortality concurrently with a reduction in salt intake of the population since the 1950s. The impact of salt intake reduction on the long-term trends in cardiovascular mortality was estimated . CompareThe association between sources of free sugars and weight status among children and adolescents was examined in a cross-sectional study using the 2016 NHNS . It was In the NHNS, efforts are made to raise participation rates to ensure representativeness. Local government personnel in charge of NHNS were invited to discuss the measures to improve participation rates. The following measures were identified: standardization of survey methods, skills of survey staff, survey organization, venue setting, accessing target households, time of the survey, responses during the survey, confirming meal contents reported in the dietary intake survey, rewards/incentives, possible rewards, feedback on survey results, and practices during the COVID-19 pandemic . These rThese findings will help readers understand the current situation of health and nutrition of the Japanese population."} +{"text": "The World Health Organization\u2019s strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs.We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform.The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities.Seven European countries were selected, covering Europe\u2019s geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence\u2013based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors.This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space. Worldwide socioeconomic improvements have prolonged and will further prolong life expectancy, progressively shifting the structure of population pyramids toward aging populations . TherefoeHealth must be The European Horizon 2020 project GATEKEEPER is a European multicentric large-scale pilot on smart living environments . In lineThe GATEKEEPER project differs from most eHealth-related projects because of its broader scope. GATEKEEPER aims toward implementing a platform serving broad populations of aging citizens with heterogeneous needs, rather than disease-specific eHealth systems or settings targeting well-defined subgroups of citizens with homogeneous characteristics. Therefore, the definition of the most appropriate group of settings where the platform should be tested represents a challenge on its own. This paper describes the rationale for the selection of the group of settings used to test the GATEKEEPER platform, and presents the different implementation sites and reference use cases (RUCs), to provide an overview of the clinical and scientific meaningfulness of this platform.Testing a platform capable of accommodating any number and type of eHealth solutions for broad study populations of older citizens with diverse needs requires being systematic. To do so, we adopted a double stratification pyramid reflecting at the same time the overall health of the target study population for a given intervention as well as the intensity of the proposed intervention . The firOnce the GATEKEEPER double stratification pyramid was established, the next step involved the selection of deployment sites and the identification of relevant RUCs to be implemented. Two considerations were taken into account for the selection of implementation sites. First, it was important to test the system in as many different countries as possible, especially given the differences in regulations, health care systems\u2019 characteristics, and study population needs. In this regard, we plotted candidate countries by latitude and nominal Gross Domestic Product per capita (US dollar) from the International Monetary Fund\u2019s 2021 World Economic Outlook Database , to ensuSeven European countries were selected by trying to cover the geographical (north-south and east-west) and socioeconomic (spectrum of gross domestic product) heterogeneity of Europe: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom . Within Foremost, RUCs should act as demonstrators of the clinical and scientific value of the GATEKEEPER platform. All of the Project\u2019s RUCs were built upon existing expertise and resources matured in previous projects, such as ACTIVAGE . The cenThe main purpose of RUC1 is the promotion of healthy lifestyles among healthy older people to prevent or delay the onset and worsening of controlled common chronic diseases, such as obesity or hypertension. RUC1 will be based on timely interventions provided by artificial intelligence\u2013based digital coaches through natural language processing techniques, patient-generated longitudinal multidimensional data analyses, structured conversations, consultation, and education. Big data analytics techniques will be exploited to address risk stratification and early detection, based on lifestyle analysis, including pattern recognition for the improvement of public health surveillance ,18 and fChronic obstructive pulmonary disease has a huge burden worldwide, accounting for 3.3 million deaths and 74.4 million disability-adjusted life-years (DALYs) in 2019 . RUC2 prDiabetes mellitus (DM) is the leading cause of blindness, end-stage renal failure, nontraumatic limb amputations, and cardiovascular morbidity and mortality and has an immense burden worldwide . RUC3 aiParkinson disease (PD) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system . It is aHeart failure (HF) is a common disease, being the second leading cause of global DALYs loss in 2019 . RUC5 prStroke is a common disease, being the third leading cause of global DALYs loss in 2019 . RUC6 wiRUC7 targets chronic older patients with variable complexity according to GATEKEEPER\u2019s risk stratification pyramid. The EIP on AHA blueprint \u201cpersonas\u201d can provide good examples of potential participant profiles . RUC7 prHypertension or high blood pressure (HBP), is a serious medical condition with an estimated worldwide prevalence of 31% of adults (1.4 billion) that significantly increases the risk of heart, brain, kidney, and other diseases . RUC8 prAs of January 2023, more than 650 million COVID-19 cases and 6.7 million deaths have been confirmed globally . The onsThe establishment of the implementation sites and RUCs is the basis for the definition and execution of large-scale implementation studies. It is key to conceive the different studies individually, with their own target study population, interventions, and evaluation, but also collectively, as a federation of studies aiming to not only test the effectiveness of a given eHealth intervention but also assess the overall performance of a platform hosting the different interventions in a federated way. The promotion of common validated tools measuring activation, adherence, compliance, and outcomes is highly recommended, but it is even more important to consider a common evaluation framework. In this regard, the European Commission promotes the use of indicators for socioeconomic impact assessment by means of the Monitoring and Assessment Framework for the European Innovation Partnership on Active and Healthy Aging , which iThis paper describes how the GATEKEEPER consortium tackled the challenge of implementing and testing a platform serving broad study populations of aging citizens with heterogeneous needs, rather than disease-specific eHealth systems or solutions focusing on well-defined subgroups of citizens with homogeneous characteristics. Accordingly, we presented the rationale for the identification and definition of the most appropriate group of settings for the platform to be tested, including (1) the adoption of a double stratification pyramid reflecting at the same time the overall health of the target study population for a given intervention as well as the intensity of the proposed interventions, (2) the identification of a set of principles guiding the selection of implementation countries and sites, and (3) the elaboration of some guidelines for the selection of RUCs so they can be scientifically sound and clinically relevant while covering the whole spectrum of citizen complexities and intervention intensities. Finally, this has been completed with a description of the chosen implementation sites and RUCs, specific aims, and clinical relevance and scientific interest in the GATEKEEPER project.In recent years, the European Commission has shifted its scope in relation to eHealth implementation. After years of encouraging eHealth projects tackling a given disease in closed-controlled settings, the focus is moving toward fostering integrated programs and, later on, whole structures capable of sustaining multiple such programs while promoting big data approaches with a secured data flow. Projects, such as CONNECARE ,38 and AThe creation of a European Data Space (EDS) is one oIn conclusion, the approach presented in this paper is leading the current trends and the view of the European Commission, and it provides a methodology for setting up the required large-scale pilots, each with its specific features, that will eventually sustain the creation and development of the EDS. Moreover, this blueprint could be expanded to contexts and constraints outside Europe, as demonstrated by the inclusion of Asian implementation sites in GATEKEEPER."} +{"text": "Dear Editor,A 14-year-old female patient with a history of Down syndrome referred the appearance of lesions disseminated throughout the body that started at the age of seven. On dermatological examination, she had phototype IV skin, with erythematous plaques arranged in an annular fashion, superimposed by pustules at the periphery, located mainly on the trunk, skinfold regions, limbs and scalp, sparing the face and mucous membranes, associated with pruritus . For dia2, the patient showed complete resolution of the skin condition, maintaining lesion remission after phototherapy discontinuation, while maintaining dapsone use. There were only residual hyperchromic macules throughout the body (She then underwent phototherapy with narrow band-UVB (NB-UVB), associated with dapsone 100\u202fmg/day, which was already being used. After 36 sessions of NB-UVB twice a week, at a total cumulative dose of 10.7\u202fmJ/cmthe body .Fig. 3 and the most resistant to conventional therapies when compared to the intraepidermal neutrophilic type. In a histopathological analysis of 116 patients diagnosed with IgA pemphigus, in addition to intercellular IgA deposition, all patients had an inflammatory infiltrate in the dermis, consisting predominantly of neutrophils.The patient in the present case underwent treatment with dapsone for five years, at an optimized dose, without improvement. Therapy with NB-UVB was based on reports in the literature of its use as a therapeutic option for other chronic and immune-mediated dermatoses, being effective and safe for the treatment of children. The use of phototherapy reduces systemic therapies such as corticosteroids, and the pediatric age group presents mild, localized, and tolerable side effects.Phototherapy with NB-UVB decreases T-cell activation, the production of pro-inflammatory cytokines, and the number of antigen-presenting cells in the skin. In addition, this therapy increases the number of Treg cells that secrete suppressor cytokines, which contributes to a reduction in the inflammatory response in the dermis, a probable mechanism of action in the treatment of IgA pemphigus.There is no consensus in the literature regarding the treatment of IgA pemphigus. This study shows the use of phototherapy as a therapeutic option in the reduction of systemic therapies in extensive cutaneous dermatoses in the pediatric age group. Further studies are required to determine the mechanism of action and duration of treatment with NR-UVB to allow long-term disease control.None declared.Lilian Lemos Costa: Approval of the final version of the manuscript; drafting and editing of the manuscript; design and planning of the study; collection, analysis and interpretation of data; critical review of the literature; critical review of the manuscript.Roberta Buense Bedrikow: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Carolina Gon\u00e7alves Contin Proen\u00e7a: Approval of the final version of the manuscript; design and planning of the study; intellectual participation in the propaedeutic and/or therapeutic conduct of studied cases; critical review of the manuscript.Rute Facchini Lellis: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; critical review of the manuscript.None declared."} +{"text": "RSC Advances article due to significant portions of text overlap with a number of sources throughout the article, in particular ref. 13 and 14 of the original article and ref. The Royal Society of Chemistry hereby wholly retracts this The authors were informed about the retraction of this article but did not respond.RSC AdvancesSigned: Laura Fisher, Executive Editor, Date: 22nd August 2023"} +{"text": "Musical performance activities are the culmination of arduous work and dedication. Musical interpretation is, at its core, an act of openness and vulnerability, which makes stage anxiety a relevant issue in the musical community. Music Performance Anxiety (MPA) is a complex and multifaceted phenomenon, manifesting in different ways and affecting musicians to varying degrees, across all educational levels and musical genres and energetic arousal . The authors concluded that their findings point to the usefulness of stage training to become accustomed to realistic public self-exposure.Chang-Arana et al. investigated the effects of pianists' trait MPA, situational stress , and familiarity with the piece on listeners' perception and understanding of musical expressiveness. Their preliminary analyses with a group of 30 listeners showed that perceived expressiveness was significantly affected by pianists' trait MPA and familiarity with the piece, whereas interpersonal accuracy of musical expressiveness was significantly affected by situational stress. These findings were independent of listeners' musical background.Herman and Clark reviewed the literature to identify possible reasons for the limited efficacy of current approaches to managing MPA. They synthesize and discuss a broad array of key concepts. They note that MPA is predominantly seen as a negative construct with undesirable symptoms and, accordingly, most interventions aim at managing MPA by ameliorating symptoms. They conclude that depathologizing MPA could open new perspectives and have significant practical and theoretical implications.Starting from the observation that the prevalence of MPA has remained largely unchanged over the last 40 years, Irie et al. analyzed the content of reports by 38 student musicians and semi-structured interviews with eight musicians to find that the experience of mental MPA symptoms started as soon as musicians begin to prepare for public performance, the experience of physiological MPA symptoms peaked shortly before public performance, and the experience of behavioral MPA symptoms peaked during public performance. To deal with these different symptoms, musicians reported to use specific strategies such as positive self-talk, concentration, and deep breathing.Kenny, the creator of this instrument, examines the research that has used the K-MPAI and touches on a number of important related topics and constructs such as cross-cultural validation, theoretical and clinical conceptualizations of MPA, depression, low self-esteem, somatization, performance quality, and the idiosyncratic nature of MPA in each musician.The Kenny Music Performance Anxiety Inventory (K-MPAI) is one of the most widely used questionnaires to assess MPA. In her review article, Kirsner et al. take a lifespan perspective on MPA by investigating the potential impact of caregiver experiences and patterns of dysfunctional cognitive schemas during childhood and adolescence on the manifestation and severity of MPA in adulthood. Combining data from a survey with 100 musicians and from interviews with eight musicians, these authors show that high-anxious and low-anxious musicians differed in numerous childhood experiences with their parents and in the development of cognitive schemas related to the themes of failure, catastrophizing, and incompetence/dependence.Lubert et al. investigated the effects of a 10-week psychological chocking intervention comprising acclimatization training, goal setting, imagery, self-talk, and relaxation techniques in six musicians, two dancers and one actress. Their mixed-methods analysis revealed reduction in performance anxiety and fear of negative evaluation, and improved self-efficacy and performance quality.Choking under pressure refers to performing worse than expected despite high skills and motivation to perform well. In their study, Mazzarolo et al. explored the strategies that music educators use to help manage their students' MPA and teacher and student perceptions of teachers' role in MPA management. The nine articles included in the review indicate that the most common strategies are simulated performance, positive outlook, preparation, and breathing. Most of these strategies are not specifically employed by the educators to influence MPA; rather, they are part of their regular teaching practice. Most students would like to receive support both from their teachers and experts.In their PRISMA-based systematic review article, Moral-Bofill et al. investigated the effects of a 12-week electronic intervention program called Self-Regulation Skills for Performing Musicians on flow experience , MPA and social skills. Compared to a control group, the experimental group reported a significant improvement in flow experience (mainly in sense of control and loss of self-consciousness) and MPA from pre- to post-intervention.Passarotto et al. investigated the relationship between MPA, practice behaviors (practice time and number of repetitions), and performance quality by monitoring 30 healthy pianists practicing a short musical excerpt. State anxiety correlated positively with practice time and number of repetitions, which the authors interpreted as supporting the hypothesis that more anxious musicians are at higher risk of developing playing-related injuries as a result of overuse and repetitive strain. Pianists who improved their playing were also less anxious in the latter part of the experiment.Rosset et al. conducted a comprehensive health-related survey among 205 university first-year music students at the beginning of their first semester and 62 students at the end of their second semester. On average, mental health was good at the start of the first year but decreased at the end of the second semester. The article highlights differences between performance majors and music education majors in health-related knowledge and coping abilities and between instrument types in practice time and bodily pain. Moreover, students attending courses on musicians' health improved their knowledge about health risks.Sokoli et al. found that students' age, gender, and instrument were significant predictors of their pre-performance affective, cognitive, and somatic experience. The study further found that worsening in performance quality from practice to public performance was reported by almost half of the students and best predicted by pre-performance anxious feelings and breathing-related complaints. The authors suggested that the assessment of MPA could be refined by better taking into account instrument specific performance-related bodily complaints.In a sample of 186 university-level classical music students, Spahn et al. assessed dispositional MPA and state MPA during a concert among 67 young amateur musicians of a brass choir. In line with previous classifications, the authors identified three types of MPA with about 75% of the musicians being assigned to the positive type characterized by low levels of MPA symptoms and high levels of self-efficacy and positive functional coping. The article also provided an analysis of the degree of correlation between dispositional MPA and state MPA.Yao and Li investigated to what extent the Individual Zone of Optimal Functioning model can help predict performance quality using the three anxiety dimensions somatic anxiety, cognitive anxiety, and self-confidence among 30 college-level piano-major students. The study highlighted the strengths and limitations of this model, the idiosyncratic nature of the relationship between self-perceived anxiety and expert-rated performance quality, as well as important directions for future research in this area.In conclusion, the articles of this Research Topic greatly contribute to the advancement of our understanding of MPA and its role and implications for musicians' wellbeing, health, and career. They also show avenues and opportunities for further developments, demonstrating that MPA remains a highly relevant topic for research and practice in performance science.PG: Writing \u2013 original draft. OC: Writing \u2013 review & editing. KH: Writing \u2013 review & editing. MY: Writing \u2013 review & editing."} +{"text": "Durability and sustainability are important objectives within the development of cement and concrete composites , and havThis Special Issue, \u201cDurability and Sustainability of Cement and Concrete Composites\u201d aims to collate a set of papers presenting recent advances in the field of durability and sustainability of cement and concrete composites, including design, processing, performance, curing and maintenance, and on-site applications of cement and concrete composites. In total, we received 19 submissions, and 12 of them were published. Researchers from China, the United Kingdom, Japan, and France chose to share their recent research findings via this particular issue.Solid wastes , as alternative cementitious binders, help to reduce carbon footprint and improve the sustainability of cement and concrete composites. Ground-granulated blast-furnace slag (GGBS) is a kind of high-activity waste slag formed via the quenching and granulation of silicate and alumino-silicate as the main components in blast-furnace smelting pig iron. Feng et al. prepared2 and forming more compact hydration products. Furthermore, Yan et al. [In order to improve the negative effects of alternative cementitious binder on the early mechanical properties of cement-based materials, Wang et al. used poln et al. used natIn addition, low reactive or inert solid waste can also be used as an alternative aggregate. Recycled tyre shreds and crumbs were used by Maddalena to repla2 curing, and investigated its influence on the corrosion resistance of cement concrete. It was found that the freeze/thaw resistance and corrosion resistance of inner steel bars were improved by the application of CO2-cured sludge ceramsite. It was also found by Xu et al. [The major characteristic and advantage of sustainable development is the more efficient use of energy and the greater recycling of materials, achieved by conserving and reducing waste. Therefore, improving the durability of concrete can contribute to the sustainable development of concrete. It was reported in that theu et al. that theu et al. investigFurthermore, during its service life, the shrinkage and high-temperature resistance of concrete are also important factors affecting its durability. Yang et al. comparedThe findings presented in this editorial contribute to recent progress in the durability and sustainability of cement and concrete composites. Durability and sustainability will always be the focus of cement concrete research. Therefore, low carbon emissions and long service life should be the key objectives of the future development of the concrete industry."} +{"text": "Human trafficking is the third most lucrative form of trafficking in the world (following drugs and counterfeit goods). Multiple outbreaks of unrest between October 2016 and August 2017 in the Rakhine State of Myanmar triggered ~745,000 influxes of Rohingyas crossing into Bangladesh through the border boundaries at Teknaf and Ukhiya sub-districts of Cox's Bazar. In this regard, the media confirmed that over a thousand Rohingya people, particularly women and girls, were victims of human trafficking. This research aims to explore the underlying causes of human trafficking (HT) during emergency responses and seeks to understand how the knowledge and capacity of the refugee, local administration, and law enforcement agencies in Bangladesh can be improved in promoting counter-trafficking (CT) and safe migration processes. In order to achieve the objectives, this study reviews acts, rules, policies, and action plans of the Government of Bangladesh on the HT, CT, and safe migration processes. Then, a case study has been applied to present the ongoing CT and safe migration programs of an NGO called Young Power in Social Action (YPSA), which received funding and technical support from the International Organization of Migration (IOM) for this purpose. This study also evaluates the effectiveness of the program through conducting key informant interviews (KIIs) and focus group discussions (FGDs) with the beneficiary and non-beneficiary participants including refugees, law-enforcing agencies (LEAs), and NGOs in Teknaf and Ukhyia. Thus, this study identifies program-level strengths and weaknesses in relation to the CT and safe migration process and provides key directions on how they can be improved. It concludes that non-state actors have a significant role in preventing HT and promoting CT and safe migration for Rohingyas in Bangladesh. The Rohingya people have been experiencing massive state-driven discrimination, torture, and a sense of statelessness due to the deprivation of their basic needs and human rights in Rakhine State, Myanmar, since 1978 . Due to The forcibly displaced Rohingya Muslim population who crossed the borders of Myanmar to Bangladesh traveled a laborious path by foot or boat for safety and were forced to leave everything behind. In fact, many of their houses were burnt down to ashes in the Rakhine state. Due to geographical location and the scarcity of economic activities where they took refuge, there has been evidence of HT for years . A numbeTo place the literature review, research methods, results, and conclusions into context, we have considered definitions used by the United Nations. According to Article 3, paragraph (a) of the protocol to prevent, suppress, and punish trafficking in persons recognized by the United Nations, \u201chuman trafficking\u201d is defined asthe recruitment, transportation, transfer, harboring, or receipt of persons, by means of threat or the use of force or other forms of coercion; of abduction, of fraud, of deception, of the abuse of power or of a position of vulnerability, or of the giving or receiving of payments or benefits to achieve the consent of a person having control over another person, for the purpose of exploitation\u201d [ interventions including creating community awareness and mobilization; capacity-building within the community, its leaders, and law enforcement agencies (LEAs); and facilitating linkage and networking between VoTs and service providing entities were required , 9. OverSince the recent Rohingya influx in August 2017, donor agencies have been operating in the camps to provide protection, education, health, nutrition, food security, water, shelter, sanitation, and hygiene as well as to coordinate logistics for the sites. National and international NGOs have been working on HT in the Rohingya camp areas. Among them, YPSA, which is a leading, voluntary not-for-profit, and non-political organization, has been working on HT in Cox's Bazar since 1990. Donors contributed USD 2.59 billion between 25 August 2017 and 25 August 2021 to the Rohingya people . Notwithkey leader engagements' (KLEs) liaising with NGOs and LEA to combat human trafficking.If the planned activities are implemented, HT can be reduced to a great extent. YPSA in support of the IOM and other agencies is working to prevent HT and promote CT and safe migration processes for the Rohingya and host communities. Of these initiatives, a project entitled \u201cinitiatives to prevent human trafficking in emergency response\u201d has been launched, aiming to increase the knowledge of refugees and host communities on CT, and safe migration capacity-building with the community leaders through \u2018This research aims to evaluate the effectiveness of the program through conducting interviews and focus group discussions (FGDs) with the beneficiary and non-beneficiary participants from school teachers, journalists, the Rohingya community, local administration, and LEA to combat human trafficking in one of the world's largest refugee camps and its adjacent areas.Leda MS, Leda A, Leda-B, Leda C, and Leda D for this purpose. In addition, the evaluation team conducted dedicated meetings and conversations with project staff on different aspects of project management and interventions. Finally, an evaluation of the effectiveness of the program is provided which was a result of conducting KIIs and FGDs with both beneficiary and non-beneficiary participants from teachers, journalists, Rohingya refugees, local administration, and LEAs in Teknaf, and Ukhyia sub-districts.In the second phase, the study conducted a cross-sectional study interviewing both beneficiaries and non-beneficiaries with a pre-tested questionnaire that consists of both qualitative and quantitative questions. The questionnaire was pre-tested on 10 beneficiaries comprising five members from each group. The respondent's comments were considered while developing the main evaluation questionnaire. Targeted sampling was used to collect data from Rohingya and non-Rohingya communities between September and October 2019. Prior to conducting interviews, the participants were briefed on ethical protocols, the research purpose, and possible outcomes. Next, after being informed of the earlier, they could decide to either proceed and participate in the interviews or turn down the invitation. For this study, ethical clearance was sought and approved by the University of Chittagong's Ethics Committee for the Department of Geography (Protocol number: CUNI-13/0022). No personal identifiers were collected. The participants were coded by beneficiaries and non-beneficiaries with their professional identities remaining anonymous. Thus, the study maintained ethical standards, specifically in accordance with the Declaration of Helsinki\u2014ethical principles for research involving human subjects.Majhis (Majhis are community leaders of the Rohingyas).In this study, experimental research was designed in order to understand the knowledge gap between the beneficiary and non-beneficiary groups after project implementation. The data were collected using information from the questionnaire which assessed knowledge and awareness differences about HT, CT, rules and regulations, and the safe migration process. The participants included school teachers, journalists, Rohingya households, and Before conducting interviews, a checklist was prepared for the beneficiary participants who would be invited for interviews and FGDs. A total number of 48 interviews were conducted with the beneficiary and non-beneficiary groups to understand the difference in knowledge between the groups during the mid-term evaluation of the project. The interviews were conducted with school teachers and journalists.Majhis because of their strong influence on the Rohingya community. Of the four FGDs conducted, two each were conducted with beneficiary Majhi and non-beneficiary Majhi, respectively. The time and location of FGDs were pre-arranged in consultation with the participating Majhis. Eight Majhis who were cooperative and enthusiastic attended each FGD session. Majhis who participated in the FGDs are male subjects who represent muscular dominancy in the group. Finally, observation (overt and covert) has been used to document eyewitnesses and to understand the ongoing project interventions by project staff. This field visit also helps to understand the camp entry and exit gates, connectivity to adjacent roads and host communities, and overall environment . The weightage analysis method was used for exploring the quantitative finding of the study. Cronbach's alpha statistics were used to check the reliability of the weightage analysis performed. Cronbach's alpha reliability coefficient normally ranges between 0 and 1. The closer the coefficient is to 1.0, the greater the internal consistency of the items (variables) in the scale. Cronbach's alpha coefficient increases either as the number of items (variables) increases, or as the average inter-item correlations increase . After the completed Cronbach's alpha statistic to test reliability, the test found excellent condition (0.9) out of the five levels very confident to (1) very low confident . The tese levels .The results of the study are presented in two sections. First, we present the results of a review of the evaluation of the humanitarian initiatives led by YPSA. Especifically, we reviewed project activities such as intervention reports, quarterly progress reports, and training manuals. Second, the paper presents the research findings from the evaluation with the beneficiary and non-beneficiary stakeholders.Leda (specific name of the camp), and two locations in two administrative areas, particularly the Ukhia and Teknaf sub-district. Over 463,515 individuals live across 21 areas. The project's staff have attempted to implement different trafficking prevention activities for targeted beneficiaries. These programs directly addressed four different activities, namely courtyard meetings, drama/cultural events on CT, meetings with Majhi, and CT messages on Radio Naf such as early marriage and polygamy which are considered as the pull factors to HT. Finally, they explained how to deliver referral pathways and how services were made available for victims. The trainers who have expertise in HT have facilitated these programs at camp areas in the presence of YPSA's executive members.The project staff arranged the orientation program about CT issues and referral mechanisms with In the past, YPSA was partnered with the IOM on a project entitled \u201cInitiatives to Prevent Human Trafficking in Emergency Response (PHTER)\u201d to increase the knowledge of refugees and host communities on trafficking and safe migration, and capacity-building of community leaders, NGOs and LEA to combat HT. The participants in the capacity-building program receive training on the causes and consequences of HT, how to work together for the prevention of HT, the identification of the victims, and the referral mechanisms to learn about the key laws such as The Prevention and Suppression of Human Trafficking Act 2012 . In thisThe project team has prepared the module on developing awareness and capacity-building of Rohingya, Majhi, camp focal point person, and host community in selected camps areas. First, the module focused on the concept, causes and consequences, and prevention of HT. It also highlights the safe migration process. Then, it referred to a different awareness and prevention-related initiatives, particularly courtyard meetings, introducing District Manpower Office (DEMO), HT-related reference mechanisms, and provision of laws and policies. Finally, it developed and implemented referral modules to prevent HT and promote CT and safe migration.The quarterly reports are prepared to monitor and evaluate project activities and deliverables. Each activity was completed on time, except the activity on the orientation of the HT Act and referral services with law enforcement agencies. It was noted that a number of factors including prolonged rainy season and associated flash flooding, late approval from the office of the Refugee Relief and Repatriation Commissioner (RRRC), and staff dropouts interrupted the program's activities.Majhis and host communities on CT issues and referral mechanisms. They organized a \u201cWorkshop for Media Professionals/Journalists on Human Trafficking Act & Preventing TIP\u201d at the Mushroom Center, Bus Terminal, and Cox's Bazar Sadr. Moreover, the project staff observed \u201cWorld Day Against Trafficking-in-Persons\u201d and organized four street dramas to create awareness about anti-human trafficking in the Rohingya and host community. Furthermore, the project launched an awareness program on HT through community Radio Naf 99.2 FM which is a popular media in the project intervention area. Therefore, after the first quarter, project staff developed and maintained effective communication channels with targeted stakeholders.The quarterly progress report has evidenced that the project staff have successfully developed awareness of HT- and CT-related modules and arranged 216 courtyards meeting out of a total of 770 meetings with the Rohingya and host community. Some of the courtyard meetings were interrupted due to bad weather conditions. A session titled \u201cOrientation on Safe Migration Related issues for potential and out-going migrants\u201d was facilitated for the host community at DEMO, Cox's Bazar. The project organized five meetings with The findings suggest that school teachers and journalists who received orientation have higher levels of awareness and knowledge about the HT act and other acts, as well as referral services and safe migration, than non-beneficiary/non-beneficiaries. They have gained knowledge or ideas about the Prevention and Suppression of Human Trafficking Act 2012. In contrast, the non-beneficiary participants were very unaware of the act. All participants in KIIs have an understanding of the first chapter of the Prevention and Suppression of Human Trafficking Act 2012. The beneficiary group could mention ways to provide referral services for HT. The majority of participants were confident in explaining the HT act and referral services in both camp areas and host communities. On contrary, non-beneficiary participants were less confident in explaining about HT act and referral services in both camp areas and host communities. The beneficiary participants could identify nine types of acts and rules related to HT: (1) Bangladesh Constitution ; (2) Prevention and Suppression of Human Trafficking Act 2012; (3) Women and child prevention and suppression SAARC convention 2012; (4) Child Act 1974; (5) Bangladesh Labor Act 2006; (6) Women policy 2011; (7) Child right policy 2011; (8) Immigration rules 1982; and (9) Bangladesh Passport Act 1973.All beneficiary participants knew about the Bangladesh Constitution Articles, 34 and 38 on trafficking issues, Prevention and Suppression of Human Trafficking Act 2012, Child Act 1974, Women policy 2011, and Child right policy 2011. The majority of non-beneficiary participants personally knew about Bangladesh Constitution , Child Act 1974, and the Women policy 2011. Beneficiary participants suggested that they benefitted and received different training activities organized by YPSA on the human trafficking act and referral services. By attending orientation sessions and training, the participants have a clear idea about trafficking processes and traffickers, knowledge about anti-human trafficking tribunals and the trial of offenses, the human trafficking Act and rules, and how and where victims get security and legal support. The findings from KIIs have identified two major weaknesses: (1) training session on HT and CT is short; (2) there were not adequate local district and sub-district levels civil administrators, LEA and lawyers in the process.In response to causes of HT, most of the beneficiary participants identified nine reasons that include (1) financial insolvency; (2) expectation of a good job; (3) greed for money; (4) unemployment; (5) lack of awareness; (6) uncertain future; (7) violence; (8) lack of job; and (9) lack of appropriate housing. There are two types of factors, push and pull, which are responsible for human trafficking. During our opinion survey, beneficiary participants mentioned that 11 types of push factors responsible for the irregular migration include: (1) improved life expectation; (2) unemployment; (3) family feud; (4) a high number of forced marriages; (5) more earning offer; (6) border crossing opportunity; (7) early marriage; (8) physical, mental and sexual harassment; (9) helpless and dowry; (10) experiencing conflict situation; and (11) uncertain life and violence. Of these factors, unemployment, more earning offer, improved life expectation, and border crossing opportunity were the most prevalent push factors for HT among Rohingya communities.Beneficiary participants identified that six types of traffickers are involved in their regular migration processes. This includes relatives, neighbors, friends, influencing local leaders, employers/persons who help them to get employment, and unknown persons. The non-beneficiary participants said that five types of traffickers are responsible for illegal migration such as relatives, neighbors, friends, employer/person helping them to get employment, and unknown person, respectively. However, both beneficiary and non-beneficiary groups opined that most people are trafficked by strangers. In response to knowledge about victims of trafficking, both beneficiary and non-beneficiary Rohingya communities have clear ideas about who are the potential victims of HT. The potential victims include children, adolescents, males, females, widows, isolated persons, homeless persons, unemployed persons, and orphans.By attending CT and safe migration-related orientations such as courtyard meetings, day observation, Radio Naf, and street drama, beneficiary participants have a better understanding of counter-trafficking and safe migration than non-beneficiary participants do. The beneficiary Rohingya communities confirm that they are aware of six types of incidences involved with HT such as threat, force, kidnapping, exploitation, taking disadvantaged situations, and offering money. The participants heard about the incidence of threats, force, and kidnapping in the areas. They also reported that the victims were psychologically stigmatized and experienced different types of consequences such as personal , health , bad reputation, isolation or compel to leave overseas, social and economic losses.The beneficiary host community participants could identify a series of steps for safe migration that were introduced in training and courtyard meetings. These include having a passport, Bureau of Manpower Employment and Training (BMET) registration, registered recruitment agency, paying money with receipt, legal job agreement, visa, and its verification processes, BMET release letter and smartcard, and opening a bank account, respectively. In contrast, non-beneficiary participants opined that having a passport, visa, and its verification processes and BMET registration are the main steps for safe migration. Beneficiary participants suggested that courtyard meetings, street drama, day observation, and awareness of HT through Radio Naf are the most effective ways for reducing human trafficking and promoting CT in these areas. In response to queries relating to referral services for victims in the camp, the beneficiary participants mentioned three types of referral services: (1) referring to the relevant organization/entities for counseling and basic support; (2) referring to the relevant organization and entities for legal help and; (3) proper maintenance for the referral system.Chitttagonian language, the Rohingya communities suggest to use their own Rohingya language in Radio Naf; and (6) excessive people in each meeting.This evaluation has attempted to identify the weakness of CT and safe migration-related project items and delivery mechanisms. The participants identified six major weaknesses that include: (1) the number of meetings is less; (2) the duration of meetings was short; (3) the presence of women is less; (4) long time gap between two meetings; (5) instead of using Majhis from both beneficiary and non-beneficiary suggested that eight types of victims are trafficked, due to irregular migration in these areas. These victims are children, adolescents, males, females, widows, isolated, homeless persons, unemployed persons, and orphans. More recently both children and women have been trafficked by strangers or unknown persons and friends in these areas. By attending CT and safe migration-related awareness training, meetings, street drama, and listening to Radio Naf programs, the beneficiary Majhis could more confidently explain the legal procedure on CT and referral services for victims of trafficking. They also could confidently explain more about the push and pull factors of trafficking, potential type of traffickers, the most vulnerable victims, and safe migration procedures.Beneficiaries from both Rohingya and host communities became aware of HT and CT because they enhanced their understanding from different types of awareness programs such as courtyard meetings, street drama, day observation, and programs on HT through Radio Naf. Quantitative analysis suggests that the beneficiary participants from school teachers and journalists had a better understanding of HT, CT, and safe migration than the remaining three groups . This maThe weighted analysis suggests that the mean score of Majhi is low (2.0) among the four non-beneficiary groups . The aveThe quantitative evaluation of the HT and CT intervention activities undertaken by the YPSA suggests four types of activities including orientations on safe migration with potential migrants, day observation, street dramas on CT, and awareness on CT through Radio Naf are found useful. The other four types of activities, courtyard meetings, orientation sessions with Majhis, orientations on the human trafficking act and referral services, and capacity-building workshops for journalists are useful. The participants show positive gestures to attend the activities in the future and also provide specific suggestions for each type of activity .By conducting a narrative review of the literature, Lugova et al. reportedCounter-trafficking interventions gained phenomenal popularity since the adoption of the UN Trafficking Protocol 2000 which prompted the undertaking of a variety of efforts from the UN agencies, national governments, International Non-Governmental Organizations (INGOs), and NGOs . The actMajhi are to be empowered considering their influence and trust in the communities. It will require increasing the surveillance of LEA with modern equipment at each entry and exit gate. Sufficient food for the Rohingya people must be ensured because food insecurity is the main push factor to fall victim to traffickers. Partnership development with community, community-based organizations (CBOs), NGOs, and local administration, especially police for the CT process will be of great help.The key project intervention activities, courtyard meetings, orientations on safe migration with potential migrants, day observation, and street dramas on CT were attended by the beneficiary participants. This study identifies several key loopholes that need to be treated and improved. Interventions are required for future project deliveries. First, with regard to awareness generation activities, the beneficiary participants support ongoing courtyard meetings, orientation sessions, and street dramas that need to occur more frequently in a better place with appropriate facilities. Although women participated in each event, their equal participation should be ensured by the implementing organizations. Education and training activities launched by the other organizations at the camp may include HT awareness and the CT process. Awareness activities should be delivered in the local dialect especially when targeted participants are Rohingya communities. Because local administration and law enforcement authorities play a crucial role in the CT process, their inclusion should be one that will enhance the community's confidence in such types of interventions. Local community leaders and The Government of Bangladesh and Bangladeshi communities showed great humanity by hosting over 900,000 stateless Rohingyas which is appreciated by international communities. It was a significant challenge given the limited time to organize all the required food, clothing, shelter, and arrange for health opportunities for the large influx of Rohingyas. Due to limited basic needs and untight security options, there was evidence of HT of Rohingya refugees. Several international agencies, particularly the IOM, in partnerships with NGOs were active since August 2017 providing support to the local government and Rohingya community to promote CT activities. The activities implemented by the YPSA in the camp and adjacent host community demonstrated their effectiveness in creating awareness about HT, promoting CT, and safe migration in the area. The findings of this research and recommendations may be useful to enhance CT and safe migration in the refugee and non-refugee setting in Bangladesh and beyond. The study mainly evaluates HT-related activities implemented at the field level and the effectiveness of their deliveries. Thus, comments cannot be made on the actual outcome of the project activities. Therefore, more studies need to be conducted to evaluate the impact of the CT programs that were implemented following a rapid and large influx of Rohingya refugees in Bangladesh.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Institutional Review Board (or Ethics Committee) of the Department of Geography and Environmental Studies at the University of Chittagong, Bangladesh for studies involving humans. Written informed consent was obtained from the individual participant for the publication of any potentially identifiable images or data included in this article. The patients/participants provided their written informed consent to participate in this study.Conceptualization and writing\u2014review and editing: EA, MAR, and JB. Methodology and formal analysis: EA and MHM. Validation: EA, MKI, and MAR. Investigation: EA, MHM, and JB. Resources and supervision: EA and MAR. Data curation and visualization: EA and MKI. Writing\u2014original draft preparation: EA and MHM. Project administration: EA."} +{"text": "Musculoskeletal (MSK) disorders are among the top five contributors to disability-adjusted life years (DALYs) worldwide . These dSeveral articles in this Special Issue delve into the diagnostic accuracy of radiological measurements in different musculoskeletal conditions. Tagliafico et al. investigated the reliability of the Myeloma Spine and Bone Damage Score (MSBDS) in assessing myeloma-related spine and bone damage using whole-body computed tomography (WBCT) . This muThis Special Issue also explores the application of novel techniques to skeletal radiology. New sequences are expanding diagnostic capabilities, and AI-based techniques are revolutionizing the field via enhancing image interpretation and improving image acquisition protocols. Despite being introduced some time ago, the utilization of relatively new MRI sequences like DWI in skeletal radiology has been limited due to their susceptibility to artifacts and inhomogeneity . HoweverIn addition to diagnostic accuracy and advancements in skeletal radiology, this Special Issue features studies focusing on specific clinical applications. The diagnosis of systemic disorders, characterized by their wide-ranging impact on different organs, significantly relies on the field of skeletal radiology. Due to the non-specific nature of their clinical presentations and the presence of overlapping features, familiarity with the radiologic findings of these disorders is crucial. Radiologic and dermatologic presentations of systemic disorders, the visualization of dialysis-related amyloid arthropathy via 18F-FDG PET-CT scans, and radiographic findings of inflammatory arthritis and mimics in the hands are the topics of the studies focusing on systemic disorders in this issue ,14,15. TThis Special Issue on skeletal radiology encompasses a comprehensive array of articles that contribute to the advancement of this dynamic field. From studies on diagnostic accuracy to emerging applications and clinical reviews, the included articles show the progress and potential of skeletal radiology in improving patient care. The field of skeletal radiology offers promising prospects. Ongoing discussions focus on leveraging emerging technologies to enhance diagnostic capabilities and treatment planning. However, challenges persist, such as the need for standardized protocols, the addressal of data quality and privacy concerns, and the optimization of the integration of artificial intelligence. Further research is required to explore the potential of novel imaging techniques, including advanced MRI sequences and functional imaging modalities, in providing valuable insights into skeletal pathologies. The corresponding evolving technology and imaging techniques have the potential to revolutionize the practice of skeletal radiology, enabling more accurate diagnoses, personalized treatment approaches, and improved patient outcomes."} +{"text": "This significant milestone provided an opportunity to reflect on two decades of scientific advancements in the field of neurotrauma. Renowned speakers and participants from around the world gathered in the captivating city of Krakow, Poland, from May 12th to May 13th, 2023 . The Congress employed a hybrid model to increase accessibility to information, extending its reach beyond geographical borders. This model enabled a large audience to explore the complexities of neurotraumatology with greater depth. The event was attended by over 250 participants from diverse nations, including Romania, Poland, Egypt, Azerbaijan, Uzbekistan, and Mexico.The th, 2023 and brouEuropean Federation of Neurorehabilitation Societies (EFNR), World Federation for Neurorehabilitation (WFNR), the Foundation of the Society for the Study of Neuroprotection and Neuroplasticity (SSNN), European Academy of Neurology (EAN), European Society of Clinical Neuropharmacology (ESCNP), and the Foundation for the Study of Nanoneurosciences and Neuroregeneration. These collaborations enable the AMN to stay at the forefront of neurotraumatology research, teaching, and practical applications.The AMN actively strives for the advancement of neurotraumatology through various engagements, bringing upfront international scientific congresses to facilitate, encourage, and enhance knowledge and expertise exchange through comprehensive collaboration activities among experts. The Academy for Multidisciplinary Neurotraumatology makes the best use of its communication pillar that, over the decades, has developed into an acknowledged network of national and international associations, societies, and organizations involved in neurotraumatology. Furthermore, it is worth mentioning that the AMN is committed to delivering excellence in education by fostering cooperation with scientific academies, associations, societies, research institutions, and companies dedicated to neurotraumatology. The Academy boasts a global membership of over 600 individuals and maintains partnerships with prominent organizations such as the A teaching course on cognitive assessment after neurotrauma marked the beginning of the congress. The course was conducted by Prof. Nicole von Steinb\u00fcchel (Germany), the past President of the Academy for Multidisciplinary Neurotraumatology (AMN), who discussed the most relevant scientific scales in the domain of post-neurotrauma cognitive assessment.The welcome address of the 20th AMN Congress was expressed by Prof. Dr. Dafin Muresanu , Prof. Volker H\u00f6mberg (AMN Chairman of the Scientific Committee & WFNR President) and the president of the AMN, Prof. Johannes Vester.The first day of Congress was built upon a four-session structure, each session focusing on different aspects of neurotrauma. The Presidential Session covered topics related to neurological rehabilitation, recent advancements in clinical research on traumatic brain injury (TBI), non-interventional comparative effectiveness in TBI, and the impact of sociodemographic, premorbid, and injury-related factors on post-traumatic stress, anxiety, and depression following TBI. Complementary to the first session, the AMN Presidential Panel entitled \u201cThe pitfalls of neurotrauma basic and clinical research\", chaired by Michael Chopp (USA) and Dafin Muresanu (Romania), explored both the challenges and advancements of neurotrauma dynamics, with an emphasis on the value of multidisciplinary perspectives as a tool for broadening the field of neurotraumatology. The second session was focused on blood-brain barrier monitoring during acute ischemic stroke, the role of neurotrophic factors, the influence of endothelial cell-derived exosomes, and the effect of concussive head injury on Alzheimer's disease pathology. The third session marked a shift from the effects of neurotrauma to prehospital care for severe TBI patients and the use of multimodal approaches in ICU-based TBI treatment.The closing fourth session of the day centered around diffuse axonal injury (DAI), endoscopic surgery for acute subdural hematoma, and surgical interventions for TBI. As such, expertise was illustrated on the duration of coma after DAI, the occurrence of persisting motor weakness, and time of recovery for patients with DAI as opposed to focal injuries; regarding research on acute subdural hematoma (ASDH), radiologic and clinical data were presented, converging to the conclusion that endoscopic subdural hematoma removal is, under certain conditions, an effective and safe surgical technique. Further on, going beyond the need for guidelines in neurotrauma, the time factor was highlighted as a central focus in neurosurgery, with \u201cTime is Brain\u201d surpassing all technological developments. Esteemed speakers present at the event included Johannes Vester (Germany), Dafin Muresanu (Romania), Volker H\u00f6mberg (Germany), Nicole von Steinb\u00fcchel (Germany), S\u0142awomir Michalak (Poland), Michael Chopp (USA), Hari Shanker Sharma (Sweden), Helmut Trimmel (Austria), Klaudyna Kojder (Poland), Wojciech Dabrowski (Poland), Pieter Vos (The Netherlands), Se-Hyuk Kim (Korea), and Christian Matula (Austria), Razvan Chereches (Romania), Karin Diserens (Switzerland), Peter Lackner (Austria), Jongmin Lee (South Korea), Johannes Leitgeb (Austria), Marcin Michalak (Poland), Polona Pozeg (Switzerland), Katrin Rauen (Switzerland), and Andreas Winkler (Austria).The Patient Registry - Short Essential Neurotrauma (PRESENT) is an innovative initiative designed to provide comprehensive and multidisciplinary data regarding traumatic brain injury management and facilitate healthcare delivery across different countries. The registry also encourages long-term follow-up of patients. Marcin Michalak (Poland) presented the experience with the first 50 Polish patients included in the PRESENT registry, emphasizing its practical application. Furthermore, Peter Lackner (Austria) underlined the importance of neurotrauma registries in obtaining accurate assessments to further enhance patient care, and Razvan Chereches (Romania) discussed the piloting of a TBI registry in Moldova, Armenia, and Georgia. Following the presentations, the speakers shared interactive discussions with the audience. Session 5 of the event delved into post-TBI neurological assessments, highlighted the global burden of post-TBI depression, and emphasized the role of interdisciplinary neurotrauma management.The second day of the congress commenced with a round table entitled \u201cReal-World Evidence in TBI \u2013 Why Registries Matter\u201d, a dynamic session that highlighted the significance of real-world data in TBI and the vital role of registries in neurotrauma management, pinpointing the latest developments and implementation stages at various country levels. A stimulating discussion was brought forward by \"The AMN Vision - Panel on How to Develop Multidisciplinary Teams in Clinical Routine. The NTSC Vienna concept\" that pinpointed to the innovative Neurotrauma Treatment Simulation Center (NTSC) Program. The NTSC Program had its second edition on April 16-21, 2023 in Vienna, Austria, showcasing a novel approach to neurotrauma education and training. An innovative method in the field of neurotrauma, the program brings together specialists from various backgrounds, such as neurology, neurosurgery, trauma care, and anesthesiology, for a five-day training program in different medical locations. The panel, chaired by participants from the first NTSC edition, respectively Agata Andrzejewska (Poland) and Bassem Boulos (Egypt), featured the Austrian faculty members of the NTSC program, namely Christian Matula, Peter Lackner, Andreas Winkler, Johannes Leitgeb, and Helmut Trimmel. The special panel explored the concept of experiential learning and multidisciplinary teamwork promoted by the NTSC while placing under the loop the objectives of the program and the real-world impact it has on diagnosis, treatment, patient care, and follow-up.The last session of the day focused on motor recovery after neurotrauma, psychiatric neurorehabilitation, and multimodal neuroimaging of covert consciousness. Once again, experience and knowledge were shared regarding specific challenges in neurorehabilitation, i.e., high incidence and prevalence of TBI, notable and permanent degree of disability, and multimorbidity in the elderly. With the concept of neuronal plasticity as the core scientific basis for neurorehabilitation, therapeutic interventions, such as Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) are of top importance for restructuring neural networks.www.brain-amn.org and on YouTube.The AMN conducted an insightful interview with the AMN President Johannes Vester, addressing key messages for the Congress participants and AMN members and future developments and projects of the Academy for Multidisciplinary Neurotraumatology. Further on, the AMN Interview Series that conth edition of the AMN Congress , between 7-8 June . The eve"} +{"text": "Frontiers in Cell and Developmental Biology and reverse transcription\u2013polymerase chain reaction and/or immunohistochemical (IHC) analysis; ii) availability of histopathology, imaging, and clinical information; iii) exclusion of the possibility of bone metastasis and the triple sign and pseudo-cystic sign (via magnetic resonance imaging), those results had relatively low sensitivity precise diagnosis, ii) adequate clinical information, and iii) exclusion of metastasis. Such reviews would enable clarification of the real clinicopathological characteristics of the disease and, in turn, lead to meaningful prospective studies for standardization of therapy."} +{"text": "Dear Editor,Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic metabolic condition characterized by aberrant calcification with the fragmentation of elastic fibers in the dermis, retina and tunica intima of arteries.A 33-year-old woman with a history of systemic lupus erythematosus was referred because an ocular fundus examination revealed angioid streaks associated with decreased foveolar brightness and diffuse pigmentary changes called \u201cpeau d\u2019orange\u201d . PhysicaThe prevalence of PXE varies between 1/25,000 and 1/100,000, with female predominance. It is caused by a mutation in the ABCC6 gene, located on chromosome 16, which encodes a transmembrane transport protein MRP6.Although cutaneous findings usually represent the first clinical sign, they are typically subtle and not evident until the second or third decade.The first visible changes on funduscopy are pigment irregularities with a \u201cpeau d\u2019orange\u201d appearance that typically precedes angioid streaks by one to eight years. Angioid streaks originate from the optic disc and radiate outwards as brownish-grey irregular lines, histopathological findings show breaks of the calcified and thickened Bruch\u2019s membrane. The latter predisposes to secondary choroidal neovascularization with the consequent risk of hemorrhage and blindness in the later stages of the disease.Manifestations of vascular involvement include loss of peripheral pulses, claudication, hypertension, myocardial infarction and ischaemic or hemorrhagic strokes. These findings reflect the mineralization of the middle and intimal layers of small and medium-caliber arteries.3We present this case given the unusual clinical presentation and highlight the importance of cutaneous alterations in the diagnostic confirmation of this entity.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Catalina Jahr: Approval of the final version of the manuscript; composition of the manuscript; collection, analysis, and interpretation of data; participation in the design of the study; critical review of the literature; critical review of the manuscript.Valentina Vera: Approval of the final version of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.Roberto Bustos: Approval of the final version of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.Jos\u00e9 Contreras: Approval of the final version of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.None declared."} +{"text": "However, simple assessment and reporting of rates of contact with mental healthcare potentially overestimate the full expected health benefits of services. Therefore, in addition to monitor the coverage rate achieved by the services, the evaluation of the effectiveness of the care provided (effective coverage) is also of relevant importance.The evaluation of healthcare pathways must be considered of fundamental importance. The quality of care provided to patients with severe mental disorders (SMD) does not correspond to the standards set by the recommendations. Therefore, measures such as the real coverage rate of psychiatric patients\u2019 needs . 45,761 newly taken-in-care cases of depression, schizophrenia, bipolar, and personality disorder were included. A variant of the self-controlled case series method was used to estimate the incidence rate ratio (IRR) for the relationship between exposure and relapse episodes .Figure) during periods covered by (i) psychotherapy for patients with depression and bipolar disorder ; (ii) psychosocial interventions for those with depression , schizophrenia and bipolar disorder , (iii) pharmacotherapy for those with schizophrenia , and bipolar disorder . Coverage with generic mental healthcare, in the absence of psychosocial/psychotherapeutic interventions, did not affect the risk of relapse.11,500 relapses occurred. Relapse risk was reduced (Image:effective coverage, showing that real-world data can represent a useful resource to monitor mental healthcare paths and to assess the effectiveness of a mental health system.Psychosocial interventions, psychotherapies and specific pharmacotherapies can be considered particularly effective in treating patients with bipolar, depressive, and schizophrenic disorders. This study ascertained the gap between utilization of mental healthcare and None Declared"} +{"text": "Seafood is consumed all around the world. It is considered a high-quality food and an excellent source of vitamins, minerals, proteins, essential amino acids, and fatty acids \u20133. SeafoContamination of coastal areas and oceans, originating from human activities, disturbs marine ecosystems, thus causing seafood to be also a potential source of pollutants such as microplastics, pesticides, synthetic musks, persistent organic pollutants, metals, and pharmaceuticals \u20136. ThereLi et al. combined molecular biology and metabolomics techniques to thoroughly investigate the molecular mechanisms by which different plant proteins affect the proliferation and degradation of muscle proteins of yellow catfish. The authors found soybean meal, peanut meal, cottonseed meal, sesame meal and corn gluten meal regulated the biosynthesis and degradation of muscle protein by affecting the content of vitamin B6, proline, glutamic acid, and phenylalanine (tyrosine) in muscle. The plant proteins improved the flesh quality and texture, despite significantly reducing the growth performance. The authors observed that inhibition of myocyte proliferation-related genes in cottonseed, sesame and corn gluten groups might additionally be regulated by the increase of glutamic acid and the decrease of tyrosine contents . The work provides a needed theoretical basis for further understanding the mechanism of plant proteins regulating flesh quality.Fish is highly consumed around the world, representing 17% of the total animal protein consumed by humans in the feeds of aquaculture crayfish. Crustaceans have long been considered a delicacy. The demand for crustaceans, on the one hand, has been increasing worldwide, which can lead to overexploitation of wild species. On the other hand, the aquaculture farming of these species is costly due to the substantial amount of fishmeal required in the feeds . Insects are high in protein and fat, and an alternative of low environmental footprint. The investigation of Alvanou et al. found that 98 days fishmeal replacements of 50 and 100% in juvenile diets increased crayfish survival but negatively affected its growth performance and feed utilization. The inclusion of the fly larvae in the diet also altered the fatty acid levels and profiles of crayfish. The study shed some light on contradictory results available in the literature for other species.Still related to alternative protein sources, Quaresma et al. studied the protein quality of dried salted cod fish, the 3rd highest consumed fish in the European Union. Due to high demand and capture, Atlantic cod is considered a vulnerable species by the International Union for the Conservation of Nature. In comparison, Pacific cod is captured in lower amounts. Considering this, Quaresma et al. evaluated and classified the nutritional quality in relation to the cod species and harvesting areas (Norway and Iceland Exclusive Economic Zones) using an essential amino acid index. They found the amino acid profiles and the index produced full accurate discrimination of the cod species. Discrimination of the location was above 85%. Furthermore, Norwegian cod protein was classified as of high quality, while that of Iceland cod was of useful quality protein. The same five limiting amino acids were found in both species.On another relevant topic and with a different approach, Gao et al. approached seafood from the innovative perspective of marine bioactive peptides. They studied the potential of peptides from tilapia skin for the treatment of ulcerative colitis, which is a main type of Inflammatory Bowel Disease. Tilapia peptides display anti-inflammatory, antioxidant, antihypertensive, and immunomodulatory properties amongst others . The mechanistic investigation points out a role of such bioactive peptides in the protection against external stimuli, which passes through enhancing the barrier function of the colon epithelium, reducing the release of inflammatory cytokines, and suppressing apoptosis.By contrast, t others . The autIn sum, the contributing articles address either the benefits of seafood consumption, potential health usages, or alternatives to improve seafood safety and quality. These bring new information on relevant aspects of the topic, opening questions and challenges for future research related to alternative protein sources, the nutrient sensing signaling pathways, quality evaluation and species discrimination based on essential and non-essential amino acid profiles, and the role of fish bioactive peptides in health and disease.SS and MM wrote the original draft of the article. LG and VD reviewed and edited the article. All authors contributed to the article and approved the submitted version."} +{"text": "With increasing health awareness, food safety and quality have been a growing demand globally. Food safety and quality depend upon many factors, including microbes in food production, processing, preservation, and storage. On the one hand, microbes such as bacteria, molds, and yeasts have a long history of application in food production, such as in the production of wine, beer, bread, and dairy products. On the other hand, the growth of microorganisms and contamination by microorganisms lead to food spoilage or even foodborne illness, threatening the development of the food industry.Microorganisms play a crucial role in the production, preservation, and improvement of food. By transforming the chemical constituents of raw materials of plant/animal sources, functional microorganisms, particularly bacteria and yeast, can improve the sensory quality of food, enhance the bioactivity of nutrients, produce antioxidant and antimicrobial compounds, and promote food safety.Liu, Cao et al. utilized a mixture of yeast and Lactobacillus rhamnosus YL-1 as a starter in the fermentation process of salami sausage, which could effectively decrease the degree of lipid oxidation and result in changes in flavor profiles. The combination of Lactobacillus fermentum YZU-06, Staphylococcus saprophyticus CGMCC 3475, and leucine has also been applied in the production of fermented sausage, which improves not only the diversity of flavor compounds but also the overall quality of sausages . Liao et al. compared the quality and the main metabolic changes of instant dark teas fermented by different fungi, such as Aspergillus cristatus, Aspergillus niger, and Aspergillus tubingensis, revealing that the chemical constituents of instant dark teas were affected by the fungi. Tao et al. reviewed the utilization of microbiome in the fermentation process, which could remove the unpleasant beany flavors and enhance the aroma profile of plant-based meat analogs. Probiotics make a great contribution to gut health by improving digestion and enhancing nutrient absorption. Zhu Y. et al. demonstrated that feeding patterns can affect gut microbiota and the metabolites of Tibetan pigs, which further led to changes in meat quality.The physicochemical properties and the volatile flavor compounds of food are closely related to the nature of microorganisms, especially in fermented food. Yu et al. found that the temperature of beef aging could affect the microbial community, physiochemical attributes, and flavor profiles of beef. Liu A. et al. observed significant differences between the bacterial community of vinegar from the same day with different fermentation depths, but no apparent difference appeared in the fungal community. In addition, the function of microbiota and volatile flavor compounds were affected by the microbial community at different depths. By comparing the physicochemical properties and microbial community compositions of Jinhua fat ham and lean ham, Zhang et al. explored the potential mechanism of characteristic microorganisms affecting the formation of flavor in lean dry-cured hams.The process of fermentation is influenced by several factors such as temperature, time, pH, oxygen levels, and microbial starter cultures. Food quality can be monitored through the regulation of fermentation conditions. Liu C. et al.; Guo et al.; Fulano et al.). Unscientific storage of food can cause an infestation of harmful microorganisms. For example, various fungal strains have been found in the production and preservation of dark tea, leading to the proliferation of fungi toxins. Xu et al. reviewed the contamination levels of common mycotoxin species, the main microbial sources of mycotoxin, and the possible ways to cause mycotoxin contamination in dark tea, providing a foundation for the prevention of harmful fungi.Spoilage and pathogenic microorganisms are considered one of the main factors threatening food quality and safety (Chen et al. found that the microbiota, mainly Lactobacillus, inhibited the formation of biogenic amines during the traditional fermentation of Scomber japonicus. To extend the shelf life of food, packaging materials have been explored to protect food from chemical and microbiological changes. Schmid et al. investigated the contaminating bacterial growth and survival in different fiber-based food packaging materials and evaluated the role of pH as an intrinsic antimicrobial factor. Furthermore, some active substances have been found to have inhibitory effects on the growth and toxicity production of microorganisms. Some Aspergillus niger produce ochratoxin A, which has harmful effects on human health, whereas tea polyphenols and epigallocatechin gallate were found to inhibit the growth of Aspergillus niger and ochratoxin synthesis, according to Zhao et al.'s study. Based on Propidium Monoazide combined with real-time PCR, Liu, Huang et al. developed a new method for fast detection of the antibacterial and bacteriostatic activity of disinfectants.To avoid illness and prevent food from spoiling, various technologies of food preservation have been developed to control the growth of microorganisms. Some microorganisms produce antimicrobial compounds and organic acids that inhibit the growth of spoilage-causing bacteria. In conclusion, this Research Topic explored the beneficial and harmful effects of microorganisms on food quality and safety, highlighting the correlation between microbial community and volatile compounds. The reasonable application of beneficial microorganisms and the regulation of harmful microbial infestation are essential to achieve the desired properties, leading to reliable food products and ensuring food quality, safety, and consistency.YW, CZ, and FG collected literatures, organized information, and wrote the first draft of the article. JC provided writing ideas and checked and revised the first draft. All authors contributed to the article and approved the submitted version."} +{"text": "Dear Editor,Extramammary paget\u2019s disease (EMPD) has been associated with other several malignancies.in situ EMPD of the scrotal region .%.2, 6, 7It has been frequently reported that EMPD is associated with various malignant tumors.Kiltos et al.In our case, lymphadenopathies extending from the right external iliac artery were considered as manifestations of metastases of invasive EMPD. However, the subsequent distant metastases were likely malignant lymphoma. The rapidly enlarging abdominal subcutaneous tissue, maxillary sinus, and skull bone were suggestive of malignant lymphomas.In our case, immunostaining for MYC and BCL-2 showed positive findings. MYC/BCL-2 co-expression without underlying rearrangements is a new adverse prognostic indicator, termed double\u2010expressor lymphoma.Invasive EPMD also metastasizes to the lymphatics and may be difficult to be distinguished from malignant lymphoma, as observed in our case. The diagnosis of high-grade B-cell malignant lymphoma was established for the first time based on a resected metastatic skin lesion specimen. This pathological condition significantly affects the treatment, prognosis, and systemic condition of patients.We believe that patients with invasive EMPD require follow-up, considering the possibility of the development of malignant tumors that can influence the prognosis, in addition to genitourinary and colorectal cancers.None declared.Misato Ueda: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Makoto Omori: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; effective participation in research orientation; intellectual participation in therapeutic conduct of studied cases; critical review of the manuscript.Ayumi Sakai: Approval of the final version of the manuscript; design and planning of the study; intellectual participation in therapeutic conduct of studied cases; critical review of the manuscript.None declared."} +{"text": "This paper highlights the mutual influences and the relationships between the variables of type II diabetes, the type of psychiatric conditions, the administered treatment schemes, the imaging examinations and the impact on the functioning and quality of life of the patients.Analysis of the influences between diabetes and psychiatric disorders, studying the relationships between the variables of type 2 diabetes, the type of psychiatric disorders, treatmentregimens, imaging examinations and the impact on the functioning and quality of life of patients.Psychiatric interview, Hamilton, Reisberg and Rosenberg scales, laboratory analysysPatients with pre-existing diabetes, psychiatric disorders led to deterioration of its evolution, documented by HbA1c values, treatment schedule, frequency of diabetic emergencies; the increased frequency of psychotic phenomena is directly proportional to the number of diabetic emergencies; patients with uncontrolled, long-term diabetes have higher scores on HAM-D and Reisberg scales, while patients with controlled diabetes have higher scores on the self-esteem and quality of life scales; in patients with taste or odor disorders, cortical atrophy may be seen on CT examination, elevated HbA1c levels and the presence of polyneuropathy; alcohol consumption, smoking, high cholesterol levels, determine the advancement of diabetic complications, and these in turn correlate with higher scores on the HAM-D scales, Reisberg; patients who show large variations in blood glucose in the first days after hospitalization are those who exhibit irritability, irritability, nervousness and heteroaggression at the time of hospitalization;65% patients with depressive disorders, 10% - with organic personality disorder, 25% - with affective disorders and 30% associated with cognitive impairment. The duration of diabetes mellitus, glycosylated hemoglobin levels and the presence of diabetic complications is directly related to the HAM-D and Reisberg scores; and inversely proportional to quality of life scores and self-esteem.None Declared"} +{"text": "Immediately after Russia commenced aggression against Ukraine, the Polish Psychiatric Association publicly called for humanitarian support for Ukraine and initiated meetings with representatives of Psychiatric Societies operating in Ukraine in order to identify current needs in the war-stricken areas and coordinateaid.The PPA allocated its financial resources to humanitarian aid and, through the EPA, appealed for condemnation of military operations as well as support for Ukraine by individual NPAs.According to the UHNR data over 4 million displaced people, refugees, came to Poland so far and some of them benefited from such help.The Polish Psychiatric Association supports the initiatives of non-governmental organizations supporting refugees and monitors and responds to the needs reported by the Ukrainian side on an ongoing basis. At present, the PPA activities focus on the following priorities:1. Need-adapted-help: Provision of customized aid - not only medications but also power generators, technical equipment. And so, the PPA shipped to Ukraine some basic equipment, sleeping mats, bedding, mattresses, backpacks, cleaning products, personal hygiene products, as well as tools for renovation and construction.2. Awareness - highlighting the consequences of Russia\u2019s aggression on people with mental disorders in Ukraine and its impact on the entire population . Inviting and lobbying for dissemination of personal reports of Ukrainian health care workers and patients at international conventions, forums, events3. Empowerment of personnel - strengthening competences required in provision of assistance in war-related disorders, training, projects of activities both across Poland and Ukraine4. Supporting and responding to the needs reported by local psychiatric assistance centers facilitating and strengthening the competence of personnel in helping refugeesNone Declared"} +{"text": "The BRAIN Foundation hosted Synchrony 2022, a translational medicine conference focused on research into treatments for individuals with neurodevelopmental disorders (NDD), including those with autism spectrum disorders (ASD). One of the four roundtables focusing on some of the most difficult and unsolved problems in ASD focused on advancing the understanding and treatment of epilepsy and seizures in individuals with ASD. This is because epilepsy and seizures in ASD are more severe and difficult to treat as compared to those in typically developing individuals.Dr. Richard E. Frye, MD, Ph.D., President of the Autism Discovery and Treatment Foundation, chaired a roundtable with experts in epilepsy and ASD treatments. The selected experts gave presentations focusing on important topics . HoweverDr. Samuel Pleasure, MD, Ph.D., Professor of Neurology at the University of California, San Francisco, provided an overview of the role of autoimmunity in epilepsy. This included the specific characteristics of autoimmune epilepsy, specific autoantibodies involved in it, its syndromes, scoring systems used to assist in its diagnosis, and high-throughput techniques used for the discovery of novel autoantibodies that might drive it.Manuel F. Casanova, MD, Professor of Biomedical Sciences at the University of South Carolina, reviewed studies on ASD that indicated a high prevalence of brain malformations. Differences in cortical thickness, surface area, and cortical folding in neuroimaging studies indicate a disruption of normal brain development. Higher resolution studies using postmortem techniques evidence disturbances of both cell division and migration. A prominent commonality between human and animal models of ASD is the reduction in the number of parvalbumin interneurons. In ASD, the loss of these fast-spiking interneurons offers a neuropathological mechanism common to both seizures and executive dysfunction.Richard G. Boles, MD, Director of the NeuroGenomics Program at NeurAbilities and Chief Medical and Scientific Officer of NeuroNeeds, provided an overview of both genetic causes and contributors of epilepsy with a specific focus on ASD. He reviewed the large studies that outlined the genetic causes of epilepsy, specific cases of ASD in which novel de novo presumably causal variants were identified after extensive re-analysis of raw whole genome sequencing data, and inherited non-causal disease variants that may have provided a significant contribution to the underlying pathophysiological disease processes. Most significantly, Dr. Boles discussed various treatment approaches that could be implemented and improve outcomes in patients based on their identified genetic variation. He presented specific cases in which dramatic improvements in function and outcome resulted from the implementation of genetically guided treatments.Jeffrey Lewine, CEO of the Center for Advanced Diagnostics, Evaluation, and Therapeutics, discussed both clinical seizures and subclinical epileptiform activity in his presentation. Dr. Lewine demonstrated the significant advantage of using magnetoencephalography (MEG) for detecting subclinical discharges because of its increased sensitivity over standard and extended encephalography. Dr. Lewine demonstrated how MEG reveals patterns that correspond with clinical characteristics, such as language impairment and neurodevelopmental regression, and are predictive of the response to steroid treatment.John Gaitanis, Chief of Child Neurology at Hasbro Children\u2019s Hospital, Brown University, discussed several topics. Dr. Gaitanis introduced the novel hypothesis that individuals with ASD, neurodevelopmental regression, epilepsy, and aggressive behavior are linked. Dr. Gaitanis then went on to discuss the history of cannabis use in the treatment of epilepsy, demonstrating that it had originally been utilized to control the disorder in ancient China in 2838 BC by Shen Nung, the \u201cred emperor\u201d. Dr. Gaitanis went on to describe the important active components in cannabis and their mechanism of action on the brain. Dr. Gaitanis reviewed the preclinical and clinical studies supporting the use of cannabis in the treatment of epilepsy, including its marked efficacy for treating Dravet\u2019s syndrome and Lennox\u2013Gastaut syndrome.1, B9, E, and D; biotin; magnesium; manganese; selenium; calcium; and carnitine, and posited that a targeted multivitamin/mineral/micronutrient could be a safe and effective adjunctive treatment to other more traditional anti-epileptic drugs in order to improve seizure control in individuals with ASD.James Adams, Director of the Autism Program at Arizona State University, discussed dietary and nutritional changes in children with ASD and epilepsy and the implications of these changes on treatment. Dr. Adams reviewed the evidence for the use of the ketogenic diet and the modified Atkins diet for the treatment of epilepsy. Dr. Adams discussed the importance of key nutrients in pathways important for controlling seizures, including vitamins BLastly, Dr. Richard E. Frye discussed the specific metabolic disorders that are commonly associated with ASD and epilepsy, particularly cerebral folate deficiency, mitochondrial disorders, and redox abnormalities, including potential treatment approaches that have the potential to improve the disorder.Better defining the characteristics, etiology, diagnosis, and treatment of epilepsy in ASD, particularly in how they differ from epilepsy in those without ASD;Considering whether one unprovoked seizure should indicate initiation of anti-epileptic treatment given the high risk of its recurrence in individuals with ASD;Defining the difference between individuals with ASD who have early-onset and late-onset epilepsy;Defining the association between epilepsy and behavioral exacerbations;Defining the influence of common comorbid conditions on epilepsy, especially with the possibility of leveraging treatment of these comorbid abnormalities to improve treatment of epilepsy in ASD;Defining medical care models for improving seizure control in those with ASD.The discussion throughout the roundtable session converged on several important points that parents, clinicians, and scientists agreed should gain more attention: In an effort to move forward, many of the panelists agreed to work together to develop several review papers outlining current knowledge, defining knowledge gaps, and providing recommendations based on the available data. The ultimate goal of the group will be to develop a guideline that will be useful for clinicians in improving the care of children with ASD and epilepsy."} +{"text": "Depending on the specific neuronal subtype, human axons extend over distances that range from a few microns to over a meter in length. Accordingly, axons contain proportions of the neuronal cytoplasm that far surpass that of the somato-dendritic domain by thousands of orders of magnitude. Remarkably, nearly all cellular components contained in axons must be actively transported from their main site of synthesis at the neuronal soma. This daunting cellular process, collectively referred to as ) Black, , is furt) Black, . The larunique complements of membrane-bounded organelles (MBOs), cytoskeletal and soluble protein components. For example, the rapid propagation of action potentials in myelinated neurons depends on acute voltage-sensitive portions of the axonal plasma membrane at the AIS and nodes of Ranvier. This is achieved by the local insertion of vesicles containing specific subsets of voltage-gated sodium and potassium channels at the AIS axolemma, as well as the insertion of vesicles containing a different subset of channels to the nodes of Ranvier's axolemma , nodes of Ranvier, and presynaptic terminals are primary examples of discrete axonal subcompartments sustaining neuronal connectivity. Their specialized functions require a continuous, highly localized supply and turnover of phosphorylation represents the most widespread and better-documented mechanism. By extension, research addressing the roles of kinases and phosphatases in the axonal compartment is essential for a complete understanding of neuronal function.The correct functionality of specialized axonal subcompartments requires the coordination of diverse cellular processes including AT, assembled and localized remodeling of the cytoskeleton, spatial restriction of signaling pathways, and recycling of old materials and defective MBOs, among many others. From various mechanisms that regulate proteins involved in the execution of these cellular processes, Baculis et al. suggests a potential mechanism linking neuronal activity to ERK1/2 kinases and levels of potassium Kv7.3 channels inserted at the AIS to collectively modulate neuron-wide responses, including transduction of signals to the distant neuronal nuclei and the control of protein synthesis (Berth et al. discusses published work on the roles played by several protein kinases on specific molecular events supporting macroautophagy, a cellular process involving sequestration, packaging, and delivery of old and defective cellular components to lysosomes for degradation (Two manuscripts discuss both hypothesized and established roles of specific protein kinases in the regulation of cellular processes sustaining axonal health. ynthesis . In addiradation .Consistent with a critical role of kinases and phosphatases on axonal function, a large body of genetic and experimental evidence has linked alterations in their activities to axonal pathology, an early pathological signature common to most neurodegenerative disorders. Specifically, work from various experimental systems revealed that specific neuropathogenic proteins promote abnormal activation of selected axonal kinases and phosphatases, alterations in AT, and axonopathy (Brady and Morfini, Waller and Collins focuses on SARM1, an enzyme that acts as a sensor of metabolic stress and a critical component of pathways leading to axonal degeneration. These authors discuss findings supporting bi-directional regulation of axonal SARM1 and JNK kinases, as well as SARM1's ability to inhibit regeneration of injured axons through activation of the MAPK kinase ASK1 and its downstream effector kinase p38 (Baltissen et al. reports that a soluble fragment derived from proteolytic cleavage of the Alzheimer's disease-related protein APP ameliorates neuropathological features in a mouse model of a human tauopathy. Interestingly, this beneficial effect was associated with the inhibition of the kinase GSK3, which is aberrantly activated in this model and has been shown to inhibit anterograde AT (Morfini et al., Richards and Jaesnich hypothesizes a potential mechanism underlying axonal pathology and neurological complications associated with SARS-CoV-2 infection. This hypothesis is based on independent lines of experimental evidence showing that SARS-CoV-2 promotes the secretion of glial cytokines known to activate the kinases p38 and CK2, and reports show that active forms of these kinases inhibit AT by directly phosphorylating motor proteins (Morfini et al., A mini-review by nase p38 . In addiThe focus of this Research Topic is unique because it specifically features research on kinases, phosphatases, and phosphorylation-dephosphorylation-based mechanisms relevant to axonal function and pathology. Considering the rapid advance of methodologies for the study of kinases and phosphatases (White and Wolf-Yadlin, GM wrote the original draft. Both authors made substantial, direct, and intellectual contributions to the work. Both authors approved the final version of this Editorial for publication."} +{"text": "The accumulated experience, both with typical and atypical children, led to the desire for an easier integration into the collective.Detecting and encouraging the skills of the atypical child, with the help of combined arts techniques and environmental stimulation, supports their\u2019s integration into the comunity.Beneficiaries-Centered Art therapy, with the aim of identifying and developing outstanding skills, trough environmental manipulation and combined arts techniquesThe environmental manipulation method is used in the art therapy session trough artistic installations and colorful fabrics. Trough chromatics and textures are generated different contexts and atmospheres sense, through which the atypical child comes to accept and discover that environment. Through the manipulation of artistic installations, gross motor skills are also required, having to produce large movements with the whole body, in order to shape the elements in the environment.Costume making as a transitional phase in the adaptation of the beneficiary to the previously created environment independently or together with the art therapist, consists in harmonizing the beneficiary with the environment. These stages are achieved through mixed techniques of artistic work, painting, decorating, modeling, collage, weaving and binding techniques.By practicing these methods during the art therapy sessions, the beneficiaries increased their self-esteem through the achievements they had and discovered and improved their outstanding skills: fine and gross motor skills, color sense, visual thinking, hand-eye coordination; improved and developed both verbal and non-verbal communication between beneficiary - art therapist and beneficiary - beneficiary, in the case of group sessionsImage:Image 2:Image 3:The role of the artist/Art-therapist can be to identify and encourage the creative potential of the beneficiaries by making both individual and team artworks; to support social integration through art and to value the outstanding skills of the beneficiaries.None Declared"} +{"text": "Dear Editor,A one-year-old boy had erythematous-violaceous macules on the left lower limb and trunk since birth , associaThe investigation showed a normocephalic child, cervicothoracic scoliosis, posteriorly rotated ears, straight palpebral fissures, enlarged nasal base, retrognathia, flattened nasal philtrum, high palate, downturned oral commissures, and a palpable mass in the right epigastric region. He also had hemihypertrophy of limbs, enlarged hands and toes , and increased feet volume (left foot larger than the right one) with syndactyly between the second and the third and between the fourth and the fifth toes on the right. Vascular malformations were observed in the left lower limb, dorsum, thorax and genital region, besides linear epidermal nevus on the thorax. He had adequate neuropsychomotor development, without ocular alterations. The genetic analysis disclosed a male karyotype , with no qualitative or structural alterations.aProteus syndromebMaffucci SyndromecKlippel-Trenaunay-Weber syndromedMilroy DiseaseNamed in 1983 by Wiedmann et al.,The clinical manifestations are variable, with cases ranging from focal changes (isolated macrodactyly),The diagnosis of Proteus syndrome is based on clinical criteria, making it necessary to differentiate from other hamartoses, such as Klippel-Trenaunay-Weber and Maffucci syndromes .2Table 1Treatment is individualized and multidisciplinary, requiring a psychological and psychomotor evaluation when orthopedic and vascular surgical approaches are indicated. Oral inhibitors of the mTOR pathway (sirolimus 0.1\u202fmg/kg/d) have been reported to be effective in preventing the growth of connective tissue hamartomas.This child was followed by the dermatology, pediatrics, psychology, vascular surgery and orthopedics teams for 12 years. At the age of ten, he experienced a worsening of the gigantism of the lower limbs, leading to difficulty in walking and weight loss. The multidisciplinary team decided for a transtibial amputation of the right lower limb and a transfemoral amputation of the left lower limb.None declared.B\u00e1rbara Elias do Carmo Barbosa: Drafting of the manuscript; effective participation in research orientation; effective participation in propaedeutics; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.Melissa Almeida Corr\u00eaa Alfredo: Drafting of the manuscript; effective participation in research orientation; effective participation in propaedeutics; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.Luciana Patr\u00edcia Fernandes Abbade: Drafting of the manuscript; effective participation in research orientation; effective participation in propaedeutics; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.H\u00e9lio Amante Miot: Drafting of the manuscript; effective participation in research orientation; effective participation in propaedeutics; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.None declared."} +{"text": "Berry fruits contain a wide range of nutrients such as fiber, vitamins, minerals, and bioactive compounds such as (poly)phenols. Emerging scientific evidence supports their health-promoting potential against oxidative stress, inflammation, vascular dysfunction, and numerous metabolic dysregulations. However, most of the evidence derives from in vitro and animal models, while observations from human studies deserve further investigation. The Special Issue \u201cBerries and Human Health: Mechanisms and Evidence\u201d was open for submission of original research manuscripts focused on (i) dietary intervention studies exploring the role of berries and their (poly)phenols in the protection and promotion of human health; (ii) cell culture and animal studies devoted to evaluating the molecular mechanisms underpinning the modulation of metabolic and functional activities; (iii) systematic reviews and/or meta-analyses investigating the impact of berries in the modulation of risk factors and health outcome.This Special Issue features six contributions: two original articles ,2 and foRubus chamaemorus L.) attenuated the development of metabolic inflammation in a high-fat diet mouse model of obesity. Results showed that 6- and 12-week supplementation with cloudberry prevented the rise in the systemic inflammation marker serum amyloid A and the hepatic inflammation/injury marker alanine aminotransferase, as well as the increase in the expression of many inflammation-related genes in the liver and adipose tissue.The two articles focused on the anti-inflammatory effect of two different berries in animal models ,2. In deKim and coworkers evaluateThe four reviews collected in the Special Issue cover different topics. The review by De Amicis and colleagues focuses The remaining three reviews focus on the effects of berries on markers of cardio-metabolic health. Vendrame et al. providedFinally, the review by Venturi and coworkers summarizTaken together, results from the papers included in this Special Issue provide further evidence about the potential beneficial effects of berries on markers of human health, mostly related to cardiometabolic health and cognitive function. However, due to the heterogeneity of results found within studies, further evidence is needed to better elucidate the valuable role of the inclusion of berry fruits in the diet and the mechanisms that underpin such potential health effects."} +{"text": "The Inaugural Monash International Health Science and Technology Conference (MONASH INITIATE), with the theme \u201cInspiring Innovation via Multidisciplinary Collaboration,\u201d held in the School of Pharmacy of the Monash University Malaysia on 16th\u201317th June, 2021. The conference attracted over 100 local and international attendees with participation from Malaysian and foreign universities, research institutions and industry partners.The Research Topic aims to gather selected pharmacology-focused contributions to, The Research Topic compiles five high-quality review articles contributed by scientists in the field. The Research Topic of these publications revolve around cancer therapy, the traditional uses of medicinal plants, and the molecular mechanisms of phytochemicals in anticancer applications. These articles provide comprehensive overviews of the current research and knowledge in drug delivery and natural products-based drug discovery areas.Miatmoko et al., outlines the delivery of Ursolic acid by nano particles, namely, liposomes, nanospheres and polymeric micelles in cancer therapy. The authors highlighted that nanoparticles in particular are effective in improving relative survival rate; reducing tumor resistance, and improving tumor tissue histopathology. They are safe to be used preclinically and clinically, and it is worth noting that the use of liposome delivery of ursolic acid is in a phase 1 clinical trial.A scoping review article by Arbain et al., discussed the distribution, traditional uses, phytochemicals and biological activities of 96 species of Alocasia. The genus is distributed across Asia, Southeast Asia and Australia. Phytochemicals from the genus of the plants can be categorized into lignan, saponin, alkaloids, and phenolic compounds. Despite demonstrating numerous biological activities, including antidiabetic, antinoceptive, antiinflammation effects, the author highlighted the compound alocasgenoside B from A. cucullata tuber was potently cytotoxic to the cancer cells in-vitro.The systematic review article by Khuayjarernpanishk et al., outlined the anticancer activities of Polygonum odoratum Lour. The review highlighted eight anticancer studies from the phytochemicals of Polygonum odoratum including Flavanoids, tannins, and saponins. A range of cancer cell lines was screened and their anticancer activity reported against oral, lung, breast, colon, liver, T lymphoblast, lymphoma, and leukemia cells. The mechanistic study was reported, and included the inhibition of Akt expression, phosphorylated Akt, mTOR, and phosphorylated mTOR. The authors also identified the gaps and limitations in the current research that warrants future study, including the discovery and identification of different classes of phytochemicals as well as informed in-vivo studies.A systematic review by Yang et al., focuses on the mechanism of action of Scutellaria barbata on hepatocellular carcinoma. A rather systematic multi-step investigation biodiscovery approach was utilized in this study. Initially, the active components of Scutellaria barbata were identified using a database of traditional Chinese medicine compounds. Then, the potential targets of these active components were predicted using network pharmacology tools. Following that, the hepatocellular carcinoma related genes were collected from various databases, and the overlapping targets between Scutellaria barbata and hepatocellular carcinoma related genes were identified. Further analysis was conducted to explore the potential biological functions and pathways involved in the interactions between Scutellaria barbata and hepatocellular carcinoma. Eventually, the effect of Scutellaria barbata, a widely used medicinal herb in traditional Chinese medicine, was found to exert modulation of various signaling pathways, such as the PI3K/AKT, MAPK, and NF-\u03baB pathways in hepatocellular carcinoma.Meanwhile, Liang et al., reviews current literature on the anticancer applications of phytochemicals in gastric cancer. It summarizes the effects of different phytochemicals, such as flavonoids, phenolic compounds, alkaloids, and terpenoids, on gastric cancer cells in laboratory settings and animal models. Various mechanism of actions associated with the anticancer effect were detailed, including inhibiting cancer cell proliferation, inducing apoptosis (programmed cell death) in cancer cells, suppressing angiogenesis (formation of new blood vessels that supply tumors), inhibiting metastasis (spread of cancer to other parts of the body), and modulating signaling pathways involved in cancer development and progression. The article articulates the potential synergistic effects of combining different phytochemicals or combining phytochemicals with conventional chemotherapy or radiotherapy in the treatment of gastric cancer. It also emphasized a discussion on safety and bioavailability of phytochemicals, and their potential use as adjuvants to conventional therapies in gastric cancer patients.Finally, These publications provide valuable insights into the current research on cancer therapy which exploit the traditional uses of medicinal plants, nanoparticles, and the potential integration of network pharmacology methodology in identifying bioactive(s) and the elucidation of their molecular mechanism actions in cancer treatment. These publications contribute to the understanding of these fields and may serve as references for further research and development of novel cancer therapies. The editorial team would like to express gratitude to the review editors, reviewers, and authors for their contribution to this Research Topic. The editorial team is looking forward to having interested researchers participate in the forthcoming Monash INITIATE 2023 on 25th\u201326th October 2023 at Monash University Malaysia."} +{"text": "Glioma is a rapidly growing and aggressive primary malignant tumor of the central nervous system that can diffusely invade the brain tissue around, and the prognosis of patients is not significantly improved by traditional treatments. One of the most general posttranslational modifications of proteins is glycosylation, and the abnormal distribution of this modification in gliomas may shed light on how it affects biological behaviors of glioma cells, including proliferation, migration, and invasion, which may be produced by regulating protein function, cell\u2014matrix and cell\u2012cell interactions, and affecting receptor downstream pathways. In this paper, from the perspective of regulating protein glycosylation changes and abnormal expression of glycosylation-related proteins (such as glycosyltransferases in gliomas), we summarize how glycosylation may play a crucial role in the discovery of novel biomarkers and new targeted treatment options for gliomas. Overall, the mechanistic basis of abnormal glycosylation affecting glioma progression remains to be more widely and deeply explored, which not only helps to inspire researchers to further explore related diagnostic and prognostic markers but also provides ideas for discovering effective treatment strategies and improving glioma patient survival and prognosis. Glioma is among the most frequently occurring primary brain tumors and accounts for \u223c80% of primary malignancies in the central nervous system (CNS) . NumerouAlthough studies regarding the impact of DNA mutations on tumor progression provide genetic insights into cancer biology, the crucial role of epigenetic alterations in the development and treatment response of gliomas has recently attracted much attention \u20136. ProteIn the following work, we first describe the current understanding of glycosylation modifications, including N-linked glycosylation and O-linked glycosylation, sialylation, and fucosylation, and their implications for the progression of neoplastic diseases. Apart from summarizing the emerging evidence for glycosylation in glioma, we talk about how aberrant glycosylation mechanism is correlated with the proliferation and migration of glioma. Considering glycosylation alterations and the aberrant expression of glycosylation-associated enzymes in glioma, potential biomarkers and therapeutic targets are finally discussed. This review aims to yield a profound understanding of how abnormal glycosylation conduces to the proliferation, invasion and metastasis of glioma and to inspire novel strategies utilizing these changes in the advancement of biomarkers and targeted therapy.At present, many kinds of glycosylation process have been identified in mammalian species. In this paper, N-linked and O-linked glycosylation are mainly discussed according to the classification of linkage relationships between oligosaccharides. In addition, sialylation and fucosylation can be added to both and are also included. These glycosylation patterns are closely associated with glioma progression.N-linked glycosylation is one of the most general synergistic/posttranslational modification in eukaryotes; that is, oligosaccharides attach to nascent proteins by forming N-glycosyl bonds between monosaccharides and asparagine residues of the consensus sequence Asn-X-Ser/Thr/Cys, which has a profound impact on protein folding, oligomerization, quality control, and physiological function , 12.2. (ii) Under the replacement of Alg1, Alg2 and Alg11 mannosyltransferases (MTases), . I. I96]. Ima cells .Glycosylation is also the research direction of glioma treatment strategy because it can promote the drug delivery process, affect the interaction in targeted therapy and improve the stability of targeted drug delivery during the treatment. For example, human bone marrow mesenchymal stem cells (BM-hMSCs) have unique characteristics, including the ability to migrate or home and transplant into GBM, and have been investigated for therapeutic delivery in GBM, while their entry into tissues is largely dependent on glycosylation of glycan-glycans and glycan-protein adhesions between cells and the endothelium. It has been demonstrated that glycan composition differs between tissues causing homing of BM-hMSCs and tissues hindering BM-hMSCs in preclinical glioma stem cell xenograft (GSCX) models of GBM . In anotMultiomics analyses, such as TCGA and the Repository for Molecular Brain Tumor Data Repository (REMBRANDT), have revealed many cancer-related potential molecular targets, and the application of these successful personalized medicine approaching in other cancers is often unsatisfactory in gliomas . For exaThe application of glycosylation in glioma treatment strategies is discussed from the perspectives of glycosylation inhibitors, expression changes in glycosylation-related enzymes, promotion of drug delivery and targeted therapy, and potential molecular targets. In view of the link between abnormal glycosylation and the malignant behavior of glioma, the current research on glycosylation-related strategies is multifaceted and not limited to the four categories above. For example, Wen et al. tried to disrupt the interaction between neuron glial antigen 2 (NG2) chondroitin sulfate proteoglycan and galectin-3 to reduce glioma cell invasiveness, while N-linked glycosylation of NG2/D3 (D3 domain of NG2 core protein) was crucial in the interaction between the two . StudiesOverall, this article focuses on the evidence for aberrant glycosylation in glioma and its impact on tumor progression, related biomarkers and targeted therapeutic strategies. First, we summarized the research evidence that confirmed abnormal glycosylation in glioma cells and extracellular matrix based on the classification and specific process of glycosylation. Then, we investigated the specific mechanism of abnormal glycosylation affecting glioma progression from the perspectives of regulating protein function, affecting cell\u2012cell interactions, and triggering receptor downstream pathways. Its effects include promoting glioma cell proliferation, migration, and invasion, thereby enhancing the malignant characteristics of glioma. Finally, we discuss the utility of aberrant glycosylation in biomarkers and targeted therapies. In terms of markers, from the occurrence of altered protein glycosylation and abnormal expression of glycation-related proteins in gliomas, some proteins are expected to give some enlightenment for the advancement of novel diagnostic or prognostic biomarkers. In terms of treatment, this article discusses glycosylation inhibitors, regulation of glycosylation-related enzyme expression, promotion of drug delivery and targeting, and other targeted strategies and related targets. Although the current research on glycosylation and gliomas has involved many aspects and multiple angles, this topic needs to be more deeply explored compared with similar studies on other malignancies. For example, it is also necessary to enhance our thinking and understanding of (i) specific pathways downstream of receptors triggered by abnormal glycosylation; (ii) the link between glycosylation and glioma immunosuppression and evasion; (iii) how to apply the conjecture of glycosylation-related treatment strategies mentioned above to clinical practice; and (iv) how to break through tumor heterogeneity, signaling pathway redundancy and the blood\u2012brain barrier and strengthen the thinking and understanding of glycosylation-related glioma treatment and prognosis. With the development of data science, the existing glycosylation databases such as OGT-PIN and NetNGlyc can help the prediction of O-linked glycosylation and N-linked glycosylation modification sites respectively , 165. So"} +{"text": "The intention of this Special Issue is to highlight the peculiarities of low-intensity/low-concentration exposures for organisms and to examine the molecular mechanisms of the organismal responses.Low-intensity exposures are the most unexplored field of modern molecular toxicology. A lack of knowledge on the mechanisms of low-intensive factors causes problems in (1) the prediction of biological effects, (2) overcoming negative consequences, and (3) the application of positive results. Therefore, the analysis of low impacts is topical from both fundamental and applied standpoints, particularly important for ecology, biology, and medicine.Studies of the biological effects of low-dose exposures have been conducted since the 1960s ,3. ModerStudies of biological responses to various bioactive compounds and the radiation of different types under the conditions of low-intensity exposures were encouraged in this Special Issue. A chemical and biochemical basis for these responses was of interest. The results presented contribute to understanding the molecular mechanism of \u201chormetic\u201d responses to low concentrations of bioactive compounds and low-intensity radioactivity. One of the findings of this Special Issue is that the time of low-intensity exposure is a critical parameter in hormetic responses, along with the dose and type of active compounds . SimilarThe biomedical aspect of low-intensity exposure is the most evident in the papers published in the Special Issue. For example, antimicrobial, anti-inflammatory, and tissue-stimulating effects of cold argon atmospheric plasma (CAAP) accelerate its use in various fields of medicine. Ermakov and coworkers investigThe work of Hanson and coworkers focuses Kovel and SushThe advantages of bacterial bioluminescent bioassays were applied while studying the bioactivity of iron oxide nanoparticles and diffUnder the conditions of model oxidative stress, the bacterial bioassay revealed prooxidant activity, with a corresponding decay in the content of reactive oxygen species . The resThe review by Kolesnik and coauthors focused As an outline, the current Special Issue combined successfully research works which elucidated the molecular mechanisms of organismal low-dose/low-intensity responses to different physico-chemical factors, such as cold argon atmospheric plasma, low-dose radiation, and nanomaterials of different structures."} +{"text": "Neurometabolic imaging is the study and measurement of neurometabolic activity in the brain using various imaging methods. It is an important field of neuroimaging that has been widely employed in clinical research. Emission computed tomography and fMRI are among the methods used. Because of the benefits of non-invasive, non-radiation, and reproducible scanning, fMRI remains the primary imaging tool for the investigation of neurometabolism. This Research Topic contains a collection of papers on the application of neurometabolism-related fMRI methods to clinical disorders, intending to summarize research accomplishments in the field of neurometabolic imaging and probable future paths of development.Wu et al. used 1H-MRS (proton magnetic resonance spectroscopy) technology in conjunction with the Mescher-Garwood point resolved spectroscopy sequence to detect metabolite levels in the brain of MRI-negative temporal lobe epilepsy (TLE) patients and discovered \u03b3-Aminobutyric acid to be a potential biomarker for lateralization and monitoring the frequency of epileptic seizures in TLE patients in this Research Topic. However, MRS has long had drawbacks such as low spatial resolution and signal-to-noise ratio, as well as limited resolution of overlapping peaks, whereas chemical exchange saturation transfer imaging, a newer noninvasive method for characterization and quantification of intracerebral metabolites, has high sensitivity and spatial resolution. Zheng H. et al. discovered that the GluCEST technique was able to identify brain biochemical changes after acute carbon monoxide poisoning earlier than conventional MRI, and that the CEST technique might be able to compensate for the shortcomings of MRS to some extent. Lin et al. used 1H-MRS combined with the GluCEST technique to evaluate the condition and prognosis of patients with acute bilirubin encephalopathy, and discovered that the combination of the two could monitor metabolite levels in the patients' brains and assess the severity of the disease. In a multimodal magnetic resonance study of patients with bipolar disorder and depression, Kong et al. combined 1H-MRS, GluCEST, and diffusion kurtosis imaging techniques and discovered that the combination of multiple techniques helped to differentiate between these two disorders. Multimodal magnetic resonance methods will remain appealing and beneficial in the future as one of the avenues of advancement in neurometabolic imaging research.Magnetic resonance spectroscopy is a well-established method for quantifying metabolite concentrations in the brain. ex (proton exchange rate) MRI technique. DTI-ALPS is a new technique capable of quantitatively measuring the function of the lymphoid system proposed by Taoka et al. (On the other hand, the invention and refining of novel neurometabolic imaging methods are equally important research avenues. By investigating whether CEST-based ka et al. , and whia et al. , for exaIn conclusion, this Research Topic article enumerates the use of various types of neurometabolic imaging technologies in clinical research, emphasizes that the cross-use of different technologies and the advancement of new technology development can help to broaden the research space and improve the credibility of experiments, and enumerates the prospects for the use of corresponding technologies in various types of diseases. It serves as a resource for understanding the advancement of neurometabolic imaging techniques and directing future research.WZ: Data curation, Project administration, Writing\u2014original draft, Writing\u2014review and editing. ZD: Project administration, Writing\u2014review and editing. RW: Conceptualization, Project administration, Supervision, Writing\u2014review and editing. HS: Project administration, Writing\u2014review and editing."} +{"text": "Novel Therapeutic Approaches to Treat Neuroinflammation in the CNS as a Research Topic for Frontiers in Pharmacology. The topic is focused on neuroinflammation as a marker of multiple pathological conditions. Studies on the mechanisms associated with CNS-centered inflammation provide us with the knowledge to design safer and more effective therapeutics for treating various diseases.We are excited to present Hou et al. on the in vivo effect of Chinese Dodder seed, a medicinal plant, on the gut-neuroinflammation axis. The study uses a chronic unpredictable stress-induced depression model in mice to assess the effect of plant-derived compounds on multiple markers of inflammation, including proinflammatory cytokines, inflammatory proteins, and microglia activation. The observed anti-inflammatory effects were correlated with the changes in the gut microbiota of treated animals. Finally, Hou et al. stated the importance of the combination effects of chlorogenic acid and hypercin, the main constituents of this plant extract, on the in vivo outcomes.Our issue begins with an original research paper by Zhang et al. report the effect of levetiracetam, an antiepileptic drug, on the cognitive function of diabetic rats. Using the streptozotocin-induced diabetes model, the authors observed dose-dependent enhancement of cognitive function and hippocampus morphology of treated rats, as well as inhibition in microglia activation and CNS inflammation levels. This novel work is the first to report the ability of FDA-approved levetiracetam to prevent microglia polarization and induce mitochondrial M2 transformation as part of the cognitive impairment treatment strategy.The interplay between metabolic diseases and immune responses, immunometabolic responses, is a significant factor that defines clinical representation and treatment outcomes for multiple disorders, including diabetes and obesity. Further, microglia activation in animals has been linked with neuronal injury and cognitive impairment, possibly explaining higher risks of cognitive dysfunction in patients with diabetes. Lullau et al. have shown that multifaceted actions of this polypharmacological CNS agent result in a rapid and potent reduction of depression symptoms, increased stress resilience, and reversal of stress-induced dysfunctions.In the comprehensive review by a Norway team of scientists, the potential role of ketamine in the treatment of resistant cases of depression disorders has been assessed from multiple aspects, including neuroinflammation, neurotoxicity, and neurodegeneration. Archie et al. looking at the bases of postnatal neuroinflammation associated with prenatal e-sig exposure. The data conclusively show high levels of oxidative stress and mitochondrial dysfunction in pups of CD1 mice exposed to the e-cig vapor with 2.4% nicotine. In addition, higher levels of neuronal injury markers were observed in the postnatal brain, linking this publication to the previous work by this research team on the deterioration of motor, learning, and memory function in e-cig-exposed animals. These data warrant extensive studies on the effect of vaping in pregnant women on the levels and longitude of neuronal injury in neonates.Our issue is concluded with the original research article by Novel Therapeutic Approaches to Treat Neuroinflammation in the CNS\u201d provides recent advances in the deconvoluting mechanisms involved in this pathological process and identifying effective therapeutic strategies for the corresponding treatments. We acknowledge the contributions of all authors to make this research volume possible.Taken together, the issue of this Research Topic: \u201c"} +{"text": "Editorial on the Research TopicEducation and learning for digital healthEducation and Learning for Digital Health sparks novel thinking and insights into how and why health professionals learn to use emerging technologies. The Research Topic builds on established educational practices and associated works of literature on e-learning, blended learning, immersive virtual reality, digital simulations, and virtual patients. See for example the Frontiers Research Topic, Advancing Teaching and Learning in Health Sciences Across Healthcare Professionals. Many robust educational resources and tools for digital health have been developed, including Health Education England's e-learning for health (https://www.e-lfh.org.uk/). The COVID-19 pandemic impelled further innovation in health professionals\u2019 online learning as education providers worked tirelessly to avoid disruption to learning, as captured in the Frontiers Research Topic, Impact of COVID-19 on Healthcare Professions Education.At a time of rapid digital innovation, the Research Topic, 17 world-leading clinicians, researchers, and educators from Australia, Canada, the United States, and the Republic of Ireland, together with the expertise of article editors and peer reviewers from Finland, Netherlands, Ireland, Australia, the United Kingdom, United States, and Canada, advance the scientific paradigm of the discipline in four specific areas:\u2022Health professionals learning to adapt and use virtual care (VC)\u2022Digital professionalism in the use of smartphone technologies\u2022Preparing medical students to use artificial intelligence (AI) and machine learning (ML)\u2022Safe use of virtual reality (VR) technologies in professional educationIt is significant that the international collaborations, studies, and articles on this Research Topic were all produced during the pandemic. In effect, this context ignited digital health by necessity in order to maintain clinical care during social distancing and infection control protocols, while safeguarding human rights and preserving the ethics of healthcare.The articles in this Research Topic, which have been produced by Virtual Care and COVID-19: A Survey Study of Adoption, Satisfaction, and Continuing Education Preferences of Healthcare Providers in Newfoundland and Labrador, Canada, provides insights into healthcare providers\u2019 experiences during the unfolding pandemic. It demonstrates that not all VC methods were perceived to deliver the same quality of care that would be expected in traditional face-to-face clinical encounters, but there can be other advantages for maintaining virtual proximity to patients whilst minimising the risk of infection transfer. As a result, the authors recommend healthcare provider organisations ensure VC is backed up with Continuing Professional Development (CPD), guidelines, and resources including patient educational support.For example, in the first article, authors Vernon Curran, Ann Hollett, and Emily Peddle explain how the use of virtual care, such as virtual examinations, clinical assessments, and remote patient monitoring, expanded during COVID-19 to enable continued access to healthcare. Their survey study, Smartphone Technology for Clinical Communication in the COVID-19 Era: A Commentary on the Concerning Trends in Data Compliance. They argue that smartphone technologies afforded clinicians and patients many observed advantages during COVID-19, yet the long-term use of such devices needs to be compliant with protecting patient data security and privacy. Solutions offered include healthcare institutional guidelines, supportive digital professionalism training, and education opportunities.The second article focuses on the legal and ethical dimensions of smartphone technology. From the Republic of Ireland, Bernadette John, Christine McCreary, and Anthony Roberts authored The Desire of Medical Students to Integrate Artificial Intelligence Into Medical Education: An Opinion Article. They draw on their wealth of experience in precision medicine, drug discovery, diagnostics, and hospital administration to argue that the advancement of AI and machine learning algorithms are reshaping the way physicians and healthcare providers approach the practice of medicine. They call for medical schools across the world to take up their essential educational role to ensure that changes to healthcare are for the better and that future physicians will be more competent, inventive, and compassionate in the medicine of tomorrow.The authors of the third article in this Research Topic suggest that changes to support future healthcare should begin in medical schools. From the United States, authors Timothy Frommeyer, Reid Fursmidt, Michael Gilbert, and Ean Bett elaborate on Innovation During a Pandemic: Developing a Guideline for Infection Prevention and Control to Support Education Through Virtual Reality. Their article focuses on virtual reality as an educational technology with the ability to deliver flexible and immersive education. Their attention to safe infection control practices of VR head-worn display systems is ensuring safer transfer between clinicians.The fourth article considers how, alongside changes in curricula content, advanced technologies are changing the modes of education delivery to provide digitally enhanced learning experiences. From Australia, authors Nathan Moore, Kathy Dempsey, Peter Hockey, Susan Jain, Philip Poronnik, Ramon Shaban, and Naseem Ahmadpour explain their work on The insights from these articles show that education and learning for digital health need to address a growing range of patient rights, professional practice, and governance issues. The issues extend from the level of individual practitioner's use of technologies protecting patient confidentiality; to institutional policies, data licencing, copyright agreements, and intellectual property rights; to whole health system design and regulation of digital health technologies; as well as raising public awareness and trust in such advances .The Good Side of Technology: How We Can Harness the Positive Potential of Digital Technology to Maximize Well-being. The design and use of advanced technologies in healthcare are increasingly looking beyond hybrid and \u201chuman in the loop\u201d models towards the symbiosis of human-AI intelligent caring in healthcare design, resourcing, evaluation, and improvement (Looking to the future, it is through the combination of education and learning in humans and machines that new knowledge will gain the greatest power to maximise well-being, as explored in the related Frontiers Research Topic, rovement . This nerovement reinforcrovement . The iderovement takes thThe present innovative digital health landscape creates an opportunity to rapidly advance human-AI intelligent caring through enhanced educational curricula and transformative learning experiences ("} +{"text": "The worldwide spread of the COVID-19 pandemic affected all major sectors, including higher education. The measures to contain this deadly disease led to the closure of universities across the globe, introducing several changes in students\u2019 academic and social experience. During the last two years, self-isolation together with the difficulties linked to online teaching and learning, have amplified psychological burden and mental health vulnerability of students.We aimed to explore in depth students\u2019 feelings and perspectives regarding the impact of the COVID-19 on their mental health and to compare these data among students from Italy and the UK.Data were resulting from the qualitative arm of \u201cthe CAMPUS study\u201d, a large ongoing project to longitudinally assess the mental health of university students enrolled at the University of Milano-Bicocca and the University of Surrey . We conducted in-depth interviews through the Microsoft Teams online platform between September 2021 and April 2022, and thematically analysed the transcripts.A total of 33 students (15 for Unimib and 18 for UoS), with a wide range of sociodemographic characteristics, were interviewed. Four themes were identified: i) impact of COVID-19 on students\u2019 mental health; ii) causes of poor mental health; iii) most vulnerable subgroups; vi) coping strategies.Anxiety symptoms, social anxiety, and stress were frequently reported as negative effects of the pandemic, while the main sources of poor mental health were identified in loneliness, exceeding time online, unhealthy management of space and time, bad organization/communication with university, low motivation and uncertainty about the future. Freshers, international or off-campus students, as well as both extremely extroverted and introverted subjects, represented the most vulnerable populations, because of their extensive exposure to loneliness. Among coping strategies, the opportunity to take time for yourself, family support, and mental health support were common in the sample.Some differences were found comparing students from Italy and the UK. While at Unimib the impact of COVID-19 on mental health was mainly described in relation to academic worries and the inadequate organization of the university system, UoS students, familiar to the conviviality of campus life, explained these effects as a result of the drastic loss of social connectedness.The current study highlights the key role of mental health support for university students, mainly during crisis times, and calls for measures to improve communication between students and the educational institution, as well as to encourage social connectedness.None Declared"} +{"text": "Editorial on the Research TopicEfficacy, safety and biomarkers of novel therapeutics and regimens in the peri-operative setting of bone and soft tissue sarcomaRecent strides in the field of oncology have witnessed new advances and hope for patients with bone and soft tissue sarcomas. This research topic explores the evolving landscape of novel therapeutics and regimens in the peri-operative setting, highlighting their efficacy, safety, and the role of biomarkers in guiding treatment decisions for treating these rare diseases.The paradigm shift from amputation to limb salvage surgery seen 3 decades ago reflects the emergence of peri-operative chemotherapy and the understanding of tumor biology of sarcoma by sarcoma surgeons and tremendously impacts the treatment regimens of sarcoma . SimilarLi et al.), the early experience of implementing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies , the safety and risk factors of chest wall malignant tumor as well as the clinicopathological features of giant cell hemangioblastoma . These results have greatly improved our therapeutic armamentarium against bone and soft tissue sarcoma in the peri-operative stage.In this research topic, four exciting studies are focusing on various aspects of biomarkers and multimodal therapies for bone and soft tissue sarcoma, including a machine learning algorithm to predict the metastasis of osteosarcoma (While these studies provide novel insights to the landscape of sarcoma management, further research encompassing genetic alterations, gene expression patterns, and immune signatures is needed to be incorporated into the treatment regimens and the selection of appropriate therapies at the molecular level. Advancements in genomic sequencing, transcriptomics, and proteomics have facilitated the identification of potential biomarkers, paving the way for the development of such personalized treatment approaches. For example, preoperative therapies, including neoadjuvant chemo-radiation and otheWhile progress in sarcoma research fuels optimism, challenges remain on the path toward widespread implementation of these innovations. Combining targeted therapies into the peri-operative setting poses a threat of increasing post-surgery complications . AdditioIn conclusion, recent advancements in the efficacy, safety, and biomarkers of novel therapeutics and treatment regimens have infused the peri-operative management of bone and soft tissue sarcomas. The journey toward personalized medicine, guided by the intricate interplay of oncology practice and translational research, offers new avenues for improved patient outcomes. Continued collaboration among clinicians, researchers, and industry stakeholders is essential to surmount these challenges."} +{"text": "In May 2022, an unprecedented global outbreak of mpox emerged,Therefore, the Director-General of WHO concurred that the outbreak remained a Public Health Emergency of International Concern. WHO advised Member States to strengthen key areas of readiness and response to stop the outbreak, and to strive towards mpox elimination or control based on specific epidemiological contexts.First, as countries monitor the outbreak and develop elimination and control plans, surveillance must be sustained and strengthened. As the number of reported mpox cases continues to decline globally, all Member States should sustain national surveillance for suspected cases and continue to report confirmed and probable cases and deaths.,Second, integrate mpox surveillance, detection, prevention and care into primary care and sexual health services. Among mpox cases with known human immunodeficiency virus (HIV) status, approximately half are living with HIV, and advanced infection is an important risk factor for severe complications and death related to mpox.Third, enhance global commitment and cooperation to facilitate equitable access to diagnostics, vaccines and therapeutics. The mpox outbreak has again highlighted global inequities as vulnerable populations, ethnic minorities and persons living in low-income countries continue to face barriers to care.Fourth, strengthen and support capacity in resource-constrained settings, including for One Health approaches and for research at the animal-human interface, where zoonotic spillover is known or suspected to occur. Understanding of animal reservoirs and transmission to humans remains limited. Identifying factors that contribute to amplification of outbreaks or extended chains of transmission is also critical. Improving multisectoral collaboration to address socioeconomic and behavioural risk factors will support research to characterize animal-to-human and human-to-human transmission in different contexts.Fifth, implement a strategic and coordinated research agenda to ensure ongoing evidence generation. Strategic areas of focus include: investigating the origins of monkeypox virus; characterizing epidemiology and dynamics of viral transmission including for the global outbreak of clade IIb.B.1, which has never been found in animals;To achieve these goals, WHO will propose a global strategy for mpox elimination and control and approaches to support countries in all regions to develop their own integrated plans. This dual approach will help countries set clear targets for stopping human-to-human transmission; maintain high-quality indicator-based surveillance and event-based monitoring; support broader efforts towards epidemic and pandemic preparedness; and ensure adaptation of public health and communication strategies for specific contexts and groups at risk, particularly where mixed modes of transmission are observed.We have the tools to end this outbreak and ensure elimination of human-to-human transmission and ongoing control of mpox. To do this, the global health community must come together and invest in the key areas highlighted."} +{"text": "The COVID-19 pandemic has heavily influenced the teaching and practical training required for students enrolled in health sciences courses globally both at undergraduate, graduate and postgraduate levels. This public health threat has impacted not only the formation of physicians, dentists, pharmacists, nurses and midwives but of all healthcare professionals, mainly due to the cancellation of clinical clerkships and the transition of on-site to online education . HoweverEuropean Journal of Investigation in Health, Psychology and Education. Thus, it is beyond doubt that a Special Issue dedicated to the COVID-19 pandemic was warranted in the Health Sciences before, during and after the COVID-19 Pandemic, we explored relevant topics regarding the impact of the SARS-CoV-2 pandemic on education, as well as highlighted the results of research endeavors that thrived during this period of isolation. Following a thorough external peer-review, five papers were accepted for publication in this Special Issue: two original articles, one brief report and two systematic reviews .Herein, in the Special Issue In their cross-sectional study, Rogowska and Meres assessed the crosstalk established between job and life satisfaction and emotional intelligence. Their investigation enrolled over 300 subjects, consisting mainly of primary and secondary school teachers and pinpointed that emotional intelligence predicts both life and job satisfaction. In addition, they demonstrated that job satisfaction predicts life satisfaction, concluding that job satisfaction emerges as a mediator in the crosstalk of emotional intelligence and life satisfaction .Nash evaluated the potential role of doodling in the evaluation of burnout in healthcare researchers who experienced anxiety and/or depression related to their workplace activities. The investigator compared in-person pre-pandemic versus online meetings during the COVID-19 pandemic and pointed out that individuals who partook in these mindfulness activities were more likely to feel relaxed when doodling during in-person meetings, possibly because there was more interaction between participants during physical meetings .Tanoubi et al. explored the benefits of simulation-based education in the training of dental surgeons in procedural sedation and the management of related complications by means of theoretical and practical applications. A total of 16 Canadian dentists with expertise in oral and maxillofacial surgery were trained in anesthesia techniques and crisis resource management using simulation-based clinical scenarios. The authors argue for a need for sedation training for dental surgeons engaging in oromaxillofacial interventions .As the COVID-19 pandemic has mostly impacted the production of original research, researchers worldwide have focused on the production of narrative or systematic reviews, as well as meta-analyses, two of which have been published in this Special Issue.In their systematic review, Tsagkaris et al. investigated the applications of infrared radiation techniques in the management of musculoskeletal conditions: knee osteoarthritis, fibromyalgia, chronic low back pain, chronic myofascial syndrome, sacroiliitis and Gulf War Illness. Based on their findings, infrared radiation has been successfully applied in the therapeutic approach of knee osteoarthritis, fibromyalgia and chronic myofascial syndrome .In addition, Moysidis et al. explored the interplay between polycystic ovary syndrome and atrial fibrillation based on the data derived from electrocardiographic and echocardiographic studies. Their findings reflect that polycystic ovary syndrome is characterized by abnormal atrial conduction, as the meta-analysis point out that there is a prolonged maximum P-wave duration, an increased P-wave dispersion, increased echocardiographic measurements of atrial electromechanical delay, as well as altered electromechanical coupling parameters in the aforementioned endocrine disorder .In conclusion, the present Special Issue provides an overview of several aspects of the impact of the COVID-19 pandemic on health sciences, and also allows for the publication of several high-quality papers."} +{"text": "In many respects, the continent of Africa is undergoing multiple transitions of which the nutrition transition is the most prominent\u2014from a public health perspective. Popkin et al. define nWhile the papers included in this Research Topic do not cover the current COVID-19 pandemic, the Russia-Ukraine war, and other global crises such as climate change, the impact of these crises on the food environments, food availability, food prices, food affordability, and food security is real , 5. The However, our current understanding of the dynamics of the rapidly transitioning African food environments is limited. While hunger and food insecurity still persist, other forms of malnutrition such as obesity and related NCDs have emerged. Toward addressing malnutrition in all its forms, improving food environments in Africa is an urgent priority. Data-driven approaches, fit-for-local policies and actions and responding to all forms of malnutrition are needed. Fit-for-local purpose data can give insights into which policies may be more effective in combating the multiple forms of malnutrition in Africa. This Research Topic on African Food Environments aimed to solicit practice-impacting and policy-influencing evidence from researchers and practitioners working on the African food environments. It comprises a collection of nine papers from six African countries\u2014eight empiric studies, and a review.Mahopo et al.) and examined the nexus between food security indicators and anthropometric health. The authors identified opportunities for improving the food environments of a rural South African setting through the implementation of government policies that target street vendors. The authors recommended that, government in partnership with non-state actors deliver such interventions as training and microfinance to improve the business skills of street food vendors while promoting food safety and nutritious foods. Harper et al. estimated the prevalence of double burden of malnutrition in select South African households, and showed that about 70.2% of all stunted children lived with an overweight or obese adult.Two studies from South Africa characterized the operations of the street food enterprises . Only about 10% of the School Meal Programs identified overweight/obesity prevention as an objective. As Africa becomes increasingly urbanized, with transitioning dietary practices that favor processed foods, high in salt, high in sugar, high in unhealthy fat foods with limited consumption of fruits and vegetables but from the 2019 Global Survey of School Meal Programs, bles but , policy The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.ALaa: conceptualization and writing of first draft. KB, FZ, GA, and ALar: reviewing and editing of first and final drafts. All authors contributed to the article and approved the submitted version."} +{"text": "From the first appearance of Red Bull (RB) on the market in 1987 for the developing brain of adolescents and the medical and socio-legal standpoints on this EDs association.Petribu et al. analyzed several studies reporting that the acute or chronic AMED consumption, enhanced the alcohol intake and his motivational value, dose-dependently stimulated locomotion, and deteriorated movements capability. AMED intake time-dependently reduced anxiety, and a wide variety of effects on memory have been reported. The acute administration of AMED did not modify alcohol metabolism, but after its chronic assumption, blood alcohol concentrations were higher or lower than those of the alcohol-only group depending on the paradigm used. A comparable range of effects has been described about metabolic dysfunction. AMED intake produced an increase of pro-inflammatory cytokines, created oxidative stress and lipid peroxidation, but also in this case the results obtained depend on the protocol used. Briefly, AMED produces different outcomes depending on the amount of alcohol and EDs and the age, sex, and line of animals used.Sefen et al. addressed this issue and reported that the stimulatory properties of caffeine reduce the sedative effects of alcohol, making individuals more inclined to consume higher amount of alcohol -as they do not perceive the feeling of drunkness- and promoting risk-taking behavior. The increase of AMED drinking can be explained through activation on adenosine A2A receptors, which reduces alcohol intake , adenosine modulates immature synapses (Jeong et al., final cortical maturation (Serdar et al., Purines are involved in the refinement of several processes during the development of the brain, in particular in its growing architecture (Rodrigues et al., Sefen et al. on the regulation of AMED around the world can help the scientific community and influence public opinion and regulatory agencies to reflect on the need to regulate the sale and the consumption of EDs and AMED. In this regard, we foresee that the articles presented in this Research Topic provide a view of current preclinical and clinical studies in the field and allow new insights into the effects of AMED consumption on human health.Finally, the original report by VB wrote the article. EA, LD, MC, and JS critically revised and approved the final version of the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "Acute coronary syndrome (ACS) and venous thromboembolism (VTE) are costly conditions, largely due to the high initial cost of treatment, patient nonadherence to prescribed antiplatelet therapy, avoidable rehospitalization in patients with ACS, and high rate of recurrence and long-term complications in patients with VTE.To discuss the economic impact of ACS and VTE; factors that contribute to preventable morbidity, mortality, and costs associated with these conditions; and strategies that managed care pharmacists can use to improve clinician knowledge of evidence-based treatment guidelines and patient adherence to the treatment plan, thereby improving clinical and economic outcomes.Premature discontinuation of antiplatelet therapy increases the risk of death and rehospitalization in patients with ACS. Factors associated with premature discontinuation include advanced age, lack of education, unmarried status, pre-existing cardiovascular disease, high cost of health care, failure to receive discharge instructions, and lack of referral for cardiac rehabilitation. Managed care plan benefit design should provide for the effective treatment of ACS and VTE by identifying the optimal type and duration of anticoagulant and antiplatelet therapy. In patients with VTE, the use of low-molecular-weight heparin (LMWH) in outpatients is as safe and effective and less costly than standard intravenous unfractionated heparin on an inpatient basis. Long-term LMWH treatment for acute deep vein thrombosis is safe and effective, and it is preferred over warfarin for patients with cancer. Managed care pharmacists can improve the quality of care for patients with ACS and VTE by using a variety of strategies to improve clinician knowledge of evidence-based treatment guidelines and patient adherence to the treatment plan.Efforts by managed care pharmacists to improve the quality of care for patients with ACS and VTE can improve patient outcomes and reduce health care utilization and costs."} +{"text": "Decades of research and scholarship2\u20134 have shown that race is fundamentally not biological. A substantial body of evidence clarifies that race is a sociopolitical, not biological construct.5 Nevertheless, the harmful, unscientific practices of racial biological essentialism persist, which helps explain why the misuse of race in clinical decision-making, research, and education remains pervasive.The practices of contemporary clinical decision-making and care rely heavily on racial biological essentialism, which is a set of ideas originating in modern science that describes populations as comprising distinct subpopulations with unique sets of essential, heritable characteristics and propensities purportedly due to their biology.6 This work has taken many forms, including the de-implementation of race-based algorithms used as clinical decision-making tools. In 2020, the Ways and Means Committee in the U.S. House of Representatives asked professional societies across medical disciplines to rethink their use of race-based clinical algorithms. The Committee sent a \u201cRequest for Information\u201d (RFI) to medical professional societies endorsing the elimination of race-based clinical algorithms. The study findings and RFI responses were captured in a 2021 report and captured responses from the professional societies as well as recommendations to improve clinical decision-making.7 The Agency for Healthcare Research and Quality (AHRQ) is also taking on this issue. At the time of this publication, AHRQ is undertaking a systematic review to provide Congress and the public responses to key questions on the impact of race-based clinical algorithms on health outcomes, and what can be done to address and/or mitigate racial bias on the development, validation, etc., of clinical algorithms.8For many years, medical trainees, health equity scholars, and public health physicians have explained how race consciousness , which is the understanding of race as a sociopolitical construct, provides a more useful understanding for medicine and public health than racial biological essentialism does.9 The American College of Obstetrics and Gynecology no longer endorses a vaginal birth after caesarean calculator that uses race.10 Most recently, the American Thoracic Society issued updated recommendations in spirometry testing and the race-neutral reference equation for all patients, irrespective of race.11Since 2021, several professional societies have updated their positions on the inclusion of race in clinical algorithms within their respective specialties. The National Kidney Foundation and the American Society of Nephrology officially endorsed an estimated glomerular filtration rate (e-GFR) calculator without a race variable.12 Many social and clinical factors contribute to this stark inequity, including the misuse of race to modify the e-GFR score, which is used in the diagnosis and treatment of chronic kidney disease (CKD). Race and other social factors have been linked to the e-GFR and other statistics, which has been associated with disproportionate suffering due to (CKD) and its sequalae among Black populations .13As research continues to elucidate the harms and any benefits from including race in clinical algorithms, the urgency to address race-based algorithms is only intensifying. For instance, 35% of Americans suffering from renal failure are Black, while only representing 13% of the population.14 To meet the urgency of this moment, the NYC Department of Health and Mental Hygiene launched the Coalition to End Racism in Clinical Algorithms (CERCA). This coalition is a citywide initiative consisting of both safety-net hospitals and academic medical centers representing all five boroughs of NYC. Participation in CERCA requires that each coalition member commit to de-implement at least one race-based algorithm. Members are also required to furnish work, evaluation, and patient engagement plans regarding their de-implementation of race-based algorithms.16Health equity experts agree to the implementation of nonrace-based clinical algorithms that cannot be subjected to the over 10-year timeframe typical for medical research and its adoption into practice.16In the summer of 2023, the NYC Department of Health and Mental Hygiene hosted the first annual New York City Anti-racism in Medical Education Symposium in partnership with the Josiah Macy Jr. Foundation, the American Academy of Medical Colleges, and the Fund for Public Health NYC. This symposium aimed to identify key stakeholders involved in anti-racism and curriculum development at NYC medical schools and understand the depth and breadth of anti-racism praxis incorporated into their educational programming.Health Equity hopes to contribute to this growing body of knowledge regarding the de-implementation efforts needed to holistically address and eradicate race essentialism from practice and education. Specifically, this issue highlights scholarship in the following areas:Historical origins of race adjustment in medicine, clinical decision-making tools, and artificial intelligence tools in medicine;Current activities, successes, and challenges around removal of race from clinical decision-making tools at the institution- and system-level and its impact on patient outcomes;City, state, and federal policies and policy analysis supporting removal of race adjustment from clinical decision-making tools; andPrograms, interventions, and policies intended to interrupt or end algorithmic racial discrimination in medicine and health care.This special issue of We hope this publication captures the latest work in addressing race-based medicine and facilitate the adaptation and implementation of initiatives to correct and mitigate the harmful effects of racial discrimination in health care. As we chart the next steps of this movement\u2014which include equitable transplantation access, federal changes in Medicaid and Medicare policy on use of race-based algorithms, biases in artificial intelligence, application of public health critical race praxis (PHCRP) in research, to name a few emerging areas\u2014remaining abreast of current and needed work will be essential to realizing a more equitable, just, and healthy society.disciplinary self-critique, this special issue documents the continued misuse of race in clinical algorithms. It also offers constructive alternatives that can be implemented immediately.18According to PHCRP, which is a health equity offshoot of Critical Race Theory, the first step toward advancing health equity is to acknowledge how the conventions of our field help reinforce inequities however well-intentioned our efforts may be. The use of arbitrary race corrections in clinical algorithms relies on and reifies racial biological determinism. It undermines the ability of clinicians to uphold their commitment to beneficence, nonmaleficence, and justice in the provision of care. Failure to uphold them harms minoritized patients and communities through, for instance, delayed or missed diagnoses and the exacerbation of racialized stigmata. A substantial body of scholarship and research now exists to promote more equitable clinical decision-making and care. Consistent with the PHCRP principle of"} +{"text": "Saccharomyces, thanks to careful dissection of metabolic properties regulon after the ancestral whole genome duplication (WGD) in yeasts. This WGD results from an ancestral hybridization between two divergent non-WGD clades mapping in the progeny of crosses between two wine starter strains, one of which had an admixed genome with flor strains, the authors identify genetic factors of adaptive divergence between the flor yeast and the wine yeast and show also that introgressions from flor strains promoted the metabolic variability observed. Finally, the article by Krogerus et al. use synthetic tetraploid hybrids between Saccharomyces cerevisiae and Saccharomyces eubayanus to generate genetic diversity in the F2 progeny through meiotic segregation. They show that some of these derived strains show fermentation capacities similar to commercial lager strains and found that higher ploidy was generally associated with faster fermentation. This study highlights the potential of synthetic hybrid formation, followed by selection on the progeny, to generate new strains of industrial relevance.Due to their unique ability to adapt to new niches, hybrids are common among human-altered environments, including industrial settings. The two remaining articles of this Research Topic focus on Altogether, the six contributions to this Research Topic provide important new insights on diverse aspects related to fungal hybrids and underscore the potential of genomic approaches to study them.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.TG acknowledges support from the Spanish Ministry of Science and Innovation for grant PID2021-126067NB-I00, cofounded by European Regional Development Fund (ERDF); from the Catalan Research Agency (AGAUR) SGR423; from the European Union\u2019s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742); from the \u201cLa Caixa\u201d foundation (Grant LCF/PR/HR21/00737), and from the Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061- ISCIII-SGEFI/ERDF). CTH acknowledges support by the Great Lakes Bioenergy Research Center, U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research under Award Number DE-SC0018409; the National Science Foundation under Grant Nos. DEB-1442148 and DEB-2110403; and the USDA National Institute of Food and Agriculture (Hatch Project 1020204). CTH is an H. I. Romnes Faculty Fellow, supported by the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Precision health refers to personalized healthcare that combines genetic and genomic sequence, protein, metabolite, and microbiome information (collectively known as \u201comics\u201d information) with lifestyle, social, economic, cultural, and environmental influences to help individuals achieve optimal health and well-being ,2. The gThe need to provide precision healthcare to hereditary breast and ovarian cancer (HBOC) and Lynch Syndrome (LS) patients and their families has long been recognized and has been supported with efforts at national and international levels ,6,7. TheCancers, titled \u201cPrecision Healthcare and Interventions in Hereditary Breast and Ovarian Cancer and Lynch Syndrome\u201d, four reviews and three original research articles highlight recent trends, updates, and progress in caring for HBOC and LS individuals and families. The papers cover precision healthcare from prevention and early detection, treatment of disease, and psychosocial care of individuals carrying HBOC- and LS-associated variants and their biological relatives.In this Special Issue of BRCA1 and BRCA2 founder pathogenic variants within the Portuguese population. Their conclusions have implications for the development of genetic testing panels, the cost-effectiveness of cascade testing among biological relatives, and the accuracy of risk prediction models that are commonly used in clinical practice to aid medical decision making in prevention, early detection, and cancer surveillance.Vicente and colleagues review evidence supporting the prevalence of Two reviews by Gambini and colleagues and by Cassar and colleagues focus on the molecular mechanisms of carcinogenesis in LS and in ovarian cancer, respectively, and provide insights into opportunities for future therapeutic interventions. Gambini and colleagues present recent guidelines regarding early detection in LS patients. Regarding primary prevention, the authors focus on the comparative advantages of chemoprevention with aspirin, other non-steroidal anti-inflammatory drugs, and progestins over risk-reducing surgery, and highlight concerns over limited or conflicting evidence regarding some of the chemoprevention agents. Cassar and colleagues focus on the role of regulatory T cells in the development of ovarian cancer and review the role of these cells in pathophysiological mechanisms regulating the tumor microenvironment, angiogenesis, metastasis, drug resistance, and tumor immunity. Both reviews by Gambini and colleagues and by Cassar and colleagues emphasize the possibilities of immunotherapies that harness frameshift peptide effector T-cell responses, immunocheckpoint inhibitors, epigenetic drugs, and combinations of immunotherapies with regulatory T-cell-targeting drugs as promising new therapeutic pathways.Bernsetin-Molho and colleagues review recommendations for managing individuals with HBOC, focusing especially on those who have not developed cancer, and for whom primary cancer prevention and early detection are of pivotal importance. The authors reviewed 15 guidelines published by governmental and professional bodies in the US, Europe, and Australia, and other countries around the world. They point out inconsistencies, including conflicting or limited evidence in areas of modifiable risk factors, such as the age of first live birth, the use of oral contraception, and the use of tamoxifen for chemoprevention. For early detection, they point out the lack of consensus regarding the optimal surveillance and risk management of younger (<30 years old) and older (>60 years old) individuals with HBOC-associated pathogenic variants, and the conflicting or limited evidence regarding the value of biomarkers such as CA-125 and screening for pancreatic cancer. Finally, they review evidence regarding effects of in vitro fertilization and pre-implantation genetic testing diagnosis, and suggest that consistent evidence shows that there is no association between in vitro fertilization and the risk of breast and ovarian cancer.BRCA1 or/and BRCA2 variant. Their study included findings of a survey with n = 505 participants and in-depth interviews with a subsample of n = 40 participants. The study focused on childbearing practices before and after knowing one\u2019s BRCA status and on decision-making processes and self-conceptualization. The study found that most women of reproductive age who already had children opted not to have more children, while younger women who did not have children were likely to have children after risk-reducing surgery. Regardless of their childbearing practices, many participants felt significantly vulnerable and stigmatized, especially if they had already developed cancer. The sense of vulnerability did not diminish over time because the focus shifted from oneself to one\u2019s family. The study sheds light on a relatively unexplored topic and identifies unmet needs of these women for ongoing care and support.Hesse-Biber and colleagues focused on the psychosocial management of women with HBOC and conducted a mixed-methods study with women carrying a pathogenic n = 1933 participants from n = 518 family units harboring HBOC-associated variants. The study found that, although genetic literacy was higher among participants who had counselling, some risk factors were poorly understood, especially among those that had genetic counseling more than 5 years ago, had fewer years of formal education, and did not have a pronounced family history of cancer. Sarki and colleagues provided strong evidence for the potential impact of cascade testing as a precision public health intervention, as their study found that, from 304 individuals with HBOC- or LS-associated variants and 115 of their relatives, on average 10 biological relatives per participant were potentially eligible for cascade genetic testing. However, only two out of three individuals with a pathogenic variant wanted to invite their relatives to the cohort, and about 50% indicated a preference for family-mediated communication of testing results, possibly with the assistance of digital technology. Both studies emphasize the importance of the family environment as a means to facilitate better management of HBOC and LS and the implementation of cascade testing as a precision public health intervention.Finally, the studies of Pedrazzani and colleagues and Sarki and colleagues focus on family-mediated communication of genetic testing results and the impact on cascade testing of biological relatives. Pedrazzani and colleagues examined genetic literacy and the flow of information from carriers of pathogenic variants who had genetic counseling to their biological relatives who did not have counseling. The study combined data from three studies conducted in the U.S. and in Switzerland over 10 years with a pooled sample of In conclusion, technological advances and the growing application of precision healthcare and precision public health interventions have increased our knowledge of HBOC and LS and offer pathways for novel and personalized therapeutic opportunities. Personalized therapeutic opportunities will be most advantageous for individuals diagnosed with cancers associated with high morbidity and mortality, such as ovarian, pancreatic, and bile duct cancers. However, the translation of this knowledge into concrete and consistent prevention and early detection guidelines is lagging behind, due, to limited evidence from large epidemiological studies with comprehensive assessments of genetic and genomic, socioeconomic, cultural, and health behavioral data. There is even less evidence regarding the translation of this knowledge into the equitable psychosocial care of these individuals and families. This Special Issue helped identify areas where more evidence, from high-quality studies, is needed."} +{"text": "Affective science is a broad and burgeoning field, and the National Institutes of Health (NIH) support research on a similarly broad range of topics. Across NIH, funding is available for basic, translational, and intervention research, including research in non-human animals, healthy populations, and those with or at risk for disease. Multiple NIH Institutes and Centers have specific programs devoted to topics within the affective science umbrella. Here, we introduce the funding priorities of these six: the National Cancer Institute (NCI), National Center for Complementary and Integrative Health (NCCIH), National Institute of Mental Health (NIMH), National Institute on Aging (NIA), National Institute on Drug Abuse (NIDA), and National Institute on Minority Health and Health Disparities (NIMHD). We then discuss overlapping themes and offer a perspective on promising research directions. The experience, expression, and regulation of emotions influence many facets of health and well-being. Affective states and affective regulation can mediate and moderate behavioral and physiological processes, thereby impacting health outcomes. Social disconnection and loneliness increase the odds of all-cause mortality by more than 25% and have been labeled an epidemic by the United States Surgeon General . NCCIH seeks to fund research incorporating transdisciplinary approaches in the basic social, behavioral, psychological, and biological sciences to understand the factors that influence EWB, as well as clinical research on the use of mind\u2013body interventions to enhance EWB and whole person health. NCCIH\u2019s EWB High-Priority Networks include efforts to (1) explore the relationship between economic burden of illness and EWB; (2) study the modifiable elements of EWB across biological, behavioral, and experiential levels; and (3) deepen our understanding of how best to measure EWB and mechanisms through which mind\u2013body interventions promote and maintain EWB. The EWB Networks recently published a provisional conceptualization of EWB, accompanied by commentaries from various well-being research stakeholders, including NIH health services for youth and have the capacity to reach large and, importantly, diverse populations of children at different developmental time periods. NCCIH supports projects to test the efficacy or effectiveness of mind\u2013body interventions that can be delivered in a school-based setting or with students to promote MEB health and prevent MEB disorders among youth.NIMH\u2019s mission is to transform the understanding and treatment of mental illnesses, and research on the mechanisms underlying mood, affect, and their disruptions in mental illnesses is an integral part of NIMH\u2019s basic and translational research portfolios. Basic neuroscience priorities include investigations of neurobiological mechanisms underlying affect, resilience, and vulnerability to stress in humans and animals. NIMH supports research on mood and anxiety disorders in humans, including diagnostic and transdiagnostic studies of the developmental trajectories, etiology, progression, risk factors, assessment, treatment, and prevention of mental illness associated with dysregulated mood and affect. A transdiagnostic framework within NIMH\u2019s Research Domain Criteria (RDoC) initiative supports studies in affect-relevant domains of functioning, including arousal and regulatory systems, negative valence (threat and loss), positive valence (reward), and social processes. NIMH also aims to enhance support of research on affective processes and disorders that engages underrepresented study populations to understand mechanisms that contribute to mental health disparities.Examples of affective science research areas of interest to NIMH include (1) understanding how distributed brain circuits dynamically represent multi-dimensional social-emotional information. (2) Understanding the neurobiological mechanisms underlying stress mediated changes in social-affective and cognitive processes research.normative developmental trajectories of aging. Topics of particular interest include (1) impacts of early-life adversity on later life outcomes; (2) individual- and context-based variations in affective processing in mid- and late-life; (3) neural mechanisms underlying emotional changes with age; (4) social isolation and loneliness; and (5) impacts of optimism, purpose in life, compassion, and generativity on health and well-being across the lifecourse. In the context of AD/ADRD, NIA seeks to identify predictive psychological, behavioral, and biological markers for changes in emotional expression and regulation that may presage cognitive decline. We also support the development of strategies to detect, prevent, and treat affective and behavioral dysregulation in people living with dementia, including effects on caregiver health and well-being.NIA seeks to elucidate the core biopsychosocial processes underlying changes in affective functions, the interactions between affective and cognitive processes, and the complex profiles of emotional adaptation and compensation across NIA encourages basic and translational affective science research in humans and/or appropriate animal models. NIA strongly encourages the application of psychometrically sound behavioral assessment approaches, and use of digital technology to measure affective, motivational, and social responses across time in \u201creal-world\u201d contexts. NIA provides expansive support for longitudinal studies and cross-cohort comparisons. All NIA research is expected to make use of the NIA Health Disparities Research Framework . NIDA\u2019s interest in supporting research on affective neuroscience relates particularly to factors that influence risk for and protection from development of SUD, as well as relapse and recovery. Priorities include 1) expanding from studies of specific circuits or unidimensional constructs to the full constellation of affective and behavioral dysfunction observed in SUD; (2) multi-level and multidimensional approaches to conceptualizing SUD \u2014 considering individual , social that cannot be fully modeled in non-humans and challenges with aligning human neurobehavioral development with that of model species, we encourage investigators to consider modeling analogous social factors , and considering homologies (and limits thereof) across humans and model species with respect to the neuroaffective system of interest.Given the complexities surrounding SUD, we encourage longitudinal research designs, the use of large datasets Table , and NIDThe mission of the National Institute on Minority Health and Health Disparities (NIMHD) is to improve minority health and reduce health disparities through research including integrative biological and behavioral science, as well as community health, population sciences, clinical and health services research, and research on health systems and workforce development. Critically, research supported by NIMHD must include a focus on one or more of the following NIH-designated populations that experience health disparities in the United States: African Americans, Latinos/Hispanics, American Indians and Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, less privileged socioeconomic groups, underserved rural populations, and sexual and gender minorities.The NIMHD Research Framework developmental sensitive periods, and on systemic capacities for change. For this reason, NIH institutes prioritize studies incorporating developmental trajectories and recommend the use of longitudinal designs and datasets. We also note that temporal scales vary enormously: molecular events unfold in nanoseconds; an individual\u2019s developmental trajectory can take days, months, or years; affective and social experiences can influence health trans-generationally. NIH institutes recognize the challenges associated with incorporating the temporal dimension, and we encourage investigators in the affective sciences to embrace these challenges.All the NIH Institutes in this commentary support basic, translational, intervention, and clinical affective science research. NIH recognizes that affect is embedded with many aspects of life and health, and an NIH-wide goal is to better understand the roles and mechanisms by which emotional experiences impact health and well-being. We especially encourage multi-level investigations of stress, emotion regulation and buffering, resilience, reward systems, positive emotions and emotional well-being, and social and interpersonal factors and their impact during development and across the lifespan."} +{"text": "Chemical vapor deposition synthesis of graphene on polycrystalline copper substrates from methane is a promising technique for industrial production and application. However, the quality of grown graphene can be improved by using single-crystal copper (111). In this paper, we propose to synthesize graphene on epitaxial single-crystal Cu film deposited and recrystallized on a basal-plane sapphire substrate. The effect of film thickness, temperature, and time of annealing on the size of copper grains and their orientation is demonstrated. Under optimized conditions, the copper grains with the (111) orientation and a record size of several millimeters are obtained, and the single-crystal graphene is grown over their entire area. The high quality of synthesized graphene has been confirmed by Raman spectroscopy, scanning electron microscopy, and the sheet resistance measurements by the four point probe method. To obtain single-layer graphene of a large area and high quality by chemical vapor deposition (CVD), in addition to the synthesis process itself, the surface on which the nucleation of the carbon film begins is important. One of the most efficient ways to grow an ideal graphene monolayer is to use a smooth single-crystal bulk copper ,2,3. How2 and Ar gas atmosphere direction, which is optimal for graphene synthesis, during the usual stage of substrate annealing in a hydrogen atmosphere to remove natural oxide from its surface before graphene growth. In this case, high-quality single-crystal graphene is synthesized over the entire surface of recrystallized copper film. The quality of graphene has been approved by Raman spectroscopy, scanning electron microscopy, and the sheet resistance measurements using the four point probe method. The obtained result demonstrates the high potential of graphene CVD synthesis on thin copper films for industrial production and application. Of particular interest, in our opinion, is the possibility of using such a sandwich (sapphire/copper film/graphene) for the BB-LIFT of graphene patterns on an arbitrary substrate."} +{"text": "The ocean is a vast carbon sink and mediates global carbon cycling, essential for mitigating climate change. The deep-sea pelagic and sub-seafloor environments represent the largest microbial habitats on Earth and are key sites for organic matter remineralization and storage in the biosphere. Moreover, diverse unique and extreme habitats, e.g., seamounts, trenches, cold seeps, and hydrothermal vents exist in the deep sea, developing special and active microbial communities and metabolic processes that significantly impact global carbon cycling. It is therefore important to understand the diversity, activity and metabolism of deep-sea microorganisms, particularly their mechanisms for utilization and transformation of organic matter, and the environmental factors affecting these processes. The main aim of this Research Topic is to collect recent work focusing on the diversity and metabolic activities of microorganisms in different deep-sea habitats, in order to understand the microorganisms that drive carbon cycling in the deep ocean.Bradley et al. investigated patterns in the distribution of microbial cells, organic carbon, and the amounts of power used by microorganisms in global sediments. They found that trends in cell abundance, particulate organic carbon storage and degradation, and microbial power utilization are mainly structured by depositional settings and redox conditions, rather than sediment depth and age. Sediments deposited on continental shelves and margins are predominantly anoxic and contain active microbial cells that decline in power utilization in deeper and older settings. Conversely, microorganisms in abyssal sediments use consistently low amounts of power across large gradients in sediment depth and age. Overall, the study demonstrated broad global-scale connections between depositional settings and activity of deep biosphere microorganisms.Marine sediments harbor diverse physicochemical properties that regulate the assemblages of microorganisms. However, it is unclear how variations in sediment physicochemical properties impact microorganisms on a global scale. Zhang et al. compared the composition and functions of the microbial communities in sediments from deep-sea seamounts, trenches and cold seeps in the Pacific Ocean, via amplicon sequencing and metagenomic analysis. They demonstrated that the microbes in deep-sea sediments were diverse and were functionally different from each other in the seamount, trench, and cold seep ecosystems. These results help improve the understanding of the composition, diversity and function of microbial communities in deep-sea environments.Webster et al. characterized the microbial diversity, geochemistry and methanogenic activities of prokaryotic communities in seven Gulf of C\u00e1diz mud volcanoes. They concluded marked differences between the microbial biogeochemistry of mud volcano sediments and deep-sea control sediments. They found that methanogenic activities from methyl compounds, especially methylamine, within the top two meters of sediment were much higher than with the substrates H2/CO2 or acetate. The potential archaea responsible for the methanogenic metabolisms were explored and sediment enrichments were dominated by Methanococcoides methanogens.Deep-sea seeps are extreme environments with high hydrostatic pressure, yet the seep systems have a great impact on global carbon cycling through discharge of methane and petroleum hydrocarbons. Lyu et al. investigated the potential and activities of deep-sea microorganisms for alkane degradation in the sediments of cold seep areas. They enriched five oil-degrading consortia from sediments collected from the Haima cold seep areas of the South China Sea, and further isolated seven efficient alkane-degrading bacteria belonging to Acinetobacter, Alcanivorax, Kangiella, Limimaricola, Marinobacter, Flavobacterium, and Paracoccus. The degradation rates of these bacteria were the highest in alkanes with medium chains. This study provides insights into the community structures, and oil-degrading activity of the bacterial inhabitants in the Haima cold seep areas, South China Sea, and offers bacterial resources for cultivation of candidates with oil bioremediation application potential.RL wrote the draft. YW and GW revised and provided essential comments on the article. All authors have proofread and approved it for publication."} +{"text": "Long-term production practice proves that good liquor comes out of the old cellar, and the aged pit mud is very important to the quality of Luzhou-flavor liquor. X-ray diffraction, Fourier transform ion cyclotron resonance mass spectrometry, and infrared spectroscopy were used to investigate the composition characteristics of iron-bearing minerals and dissolved organic matter (DOM) in 2-year, 40-year, and 100-year pit mud and yellow soil of Luzhou Laojiao distillery. The results showed that the contents of total iron and crystalline iron minerals decreased significantly, while the ratio of Fe(II)/Fe(III) and the content of amorphous iron (hydr)oxides increased significantly with increasing cellar age. DOM richness, unsaturation, and aromaticity, as well as lignin/phenolics, polyphenols, and polycyclic aromatics ratios, were enhanced in pit mud. The results of the principal component analysis indicate that changes in the morphology and content of iron-bearing minerals in pit mud were significantly correlated with the changes in DOM molecular components, which is mainly attributed to the different affinities of amorphous iron (hydr)oxides and crystalline iron minerals for the DOM components. The study is important for understanding the evolution pattern of iron-bearing minerals and DOM and their interactions during the aging of pit mud and provides a new way to further understand the influence of aged pit mud on Luzhou-flavor liquor production. Chinese liquor is one of the oldest distilled spirits in the world, of which strong-flavor baijiu (SFB), also known as Luzhou-flavor liquor, is the best-selling in China, accounting for over 70% of total consumption in the Chinese baijiu market ,2. SFB pclostridium . T. T26]. TDOM compounds can also be further divided into different molecular types based on their element composition B 26]. T. T26]. TDOM is widespread in terrestrial ecosystems and plays a critical role in the evolution of soil biogeochemical processes and structure . The larPCA was used to evaluate the correlation between iron (hydr)oxides and DOM compounds . The difo has a larger specific surface area and more binding sites compared to Fec, resulting in a stronger adsorption capacity to preferentially bind to CDPA, VPDP, and HULP [c and positively correlated with Feo are more susceptible to bonding with iron (hydr)oxides to form Fe-OM complexes ,43. In aand HULP ,45. Thuswith Feo . In addio to Fec . Thus, t pit mud .Correlation analysis of NOSC values, O/C ratios, and Fe(II)/Fe(III) can also further explain the relationship between DOM and iron (hydr)oxides. The NOSC value and O/C ratios can represent the oxidation state of DOM molecules . The conc and CHONP molecules oxides are more dominant in aged pit mud. The richness, unsaturation, and aromaticity of DOM increased significantly during the aging of pit mud. DOM from aged pit mud contained more lignin/phenolics, polyphenols, and polycyclic aromatics. Furthermore, there is a significant correlation between the changes in the morphology and content of iron-bearing minerals in pit mud and the chemical characterization of the DOM molecules. Therefore, the use of microbial fermentation and other biotechnological methods to reduce the iron content of local yellow soil may help to promote the aging of new pit mud.In summary, the contents of total iron and crystalline iron minerals decreased significantly with the increase in cellar age, and the ratio of Fe(II)/Fe(III) and the content of amorphous iron (hydr)oxides increased significantly. In connection with this, the richness, unsaturation, and aromaticity of DOM and the ratio of lignin/phenolics, polyphenols, and polycyclic aromatics in pit mud were increased. The research showed that molecular diversity and chemical properties of DOM compounds were closely correlated with the content and morphological changes of iron (hydr)oxides during the aging process of pit mud, and the interaction between DOM and iron (hydr)oxides changes the inorganic and organic components in pit mud, which further changes the physicochemical properties of pit mud and affects the aging of pit mud. The changes in the content and composition of iron-bearing minerals and DOM are important potential factors affecting the aging of pit mud, which not only provides a new idea to improve the aging of pit mud by using biotechnology but also helps to understand the process and mechanism of aging of pit mud from the perspective of mineral and DOM composition."} +{"text": "Sustainable Stress Management: Aquatic plants vs. Terrestrial plants (IGW-SSMAT) which was jointly organized at the Friedrich Schiller University of Jena, Germany from 25 to 27 July 2022 by Prof. Dr. Ralf Oelm\u00fcller, Friedrich Schiller University of Jena, Germany as the German coordinator and Dr. K. Sowjanya Sree, Central University of Kerala, India as the Indian Coordinator. The workshop constituted researchers working in this field from both India and Germany and brought together these experts in the field of sustainable stress management for scientific discussions, brainstorming and networking.The Indo-German Science and Technology Centre (IGSTC) funded an Indo-German Workshop on Climate change and the rapid growth of the human population are major global challenges. Evolving sustainable strategies to counter their effects will be the tasks for the future. We need to produce more food, which includes higher crop yields per area, with plants that are better adapted to the upcoming threats, while nature and climate need to be protected simultaneously . Besides crop production for food and feed, the growing human population and modern technology require plant biomass also for energy production, in the chemical and pharmaceutical industries, in housing and in the textile industry. Further to the promotion of our knowledge on resistance mechanisms in utilized crop species, higher crop yields and biomass production require novel approaches such as the use of new non-conventional crop species and the exploration of new agriculturally suitable areas. Finally, the scientific achievements obtained with conventional crop plants must be tested and eventually transferred to newly introduced crop species, if possible, or new strategies need to be developed for new crop species and new agricultural systems.Sustainable Stress Management: Aquatic plants vs. Terrestrial plants (IGW-SSMAT) was organized at the Friedrich Schiller University of Jena, Germany from 25 to 27 July 2022. This workshop was funded by the Indo-German Science and Technology Centre (IGSTC) with Prof. Dr. Ralf Oelm\u00fcller, Friedrich Schiller University of Jena, Germany, as the German coordinator and Chair of the workshop and Dr. K. Sowjanya Sree, Central University of Kerala, India, as the Indian Coordinator and Co-chair of the workshop. The scientific organization of the workshop was supported by Dr. Klaus J. Appenroth, Friedrich Schiller University of Jena, Germany. Interestingly, the workshop was held in a seminar room of the Department of Indo-German Studies, University of Jena, Germany, which was an apt location for the exchange of scientific ideas between the researchers of the two countries , whereas strategies that allow the faster propagation of the plant population under different environmental conditions might be more important for aquatic plants.Wolffia arrhiza and Wolffia globosa) for human nutrition under the law of novel food cyt changes and phytohormones like jasmonates. Moreover, volatile-mediated plant\u2013plant communication play an important role in the biotic stress response improved the productivity of tomato crops both qualitatively and quantitatively. Prime-Verdant-applied plants performed well also under stress conditions . Furthermore, vegetable crop plants can become heavily infected by different plant viruses which results in damage to the crops. It is difficult to mitigate RNA and DNA viral diseases in vegetable crops. Piriformospora indica-colonized tomato plants developed increased resistance to Tomato yellow leaf curl virus, and the colonization of fruit plants like banana and papaya with P. indica effectively reduced the disease symptoms induced by RNA viruses like Banana bract mosaic virus and Papaya ring spot virus, respectively. Additionally, vegetable crops in association with P. indica developed more resistance against RNA virus , and DNA virus (Tomato leaf curl virus and Bhindi yellow vein mosaic virus) infections. Thus, P. indica colonization protects plants also against viral diseases . To understand the molecular basis of this P. indica-induced resistance, colonized and uncolonized crops after viral infections should be analysed with the molecular and biochemical tools available in the consortium.Autotrophs are constantly challenged by abiotic as well as biotic stressors. Insect pests of plants are one of the major biotic stressors. Plants have evolved several strategies to protect themselves from insect infestation. However, the signal transduction pathways induced early on that connect the process of wounding as a result of insect herbivory to the plant defence responses are yet to be well comprehended. Perceived by specific chemicals (herbivore-associated molecular patterns or damage-associated molecular patterns), plants respond with local and systemic signalling processes including [CaGermany; ,25). PlaLemna root re-growth test -tolerance capacity. The application of such management approaches is important, especially in the scenario where the ability of these plants to produce high amounts of biomass at a fast pace and the increasing practical applicability of this biomass in a circular economy are transforming duckweeds into a sustainable cropping system. The anatomical and molecular basis for the fast growth rate of these tiny aquatic plants was also revealed , i.e., by increasing salinity, a lack of nutrients or their exposure to heavy metals . EvidentGermany; ). The ma, India; ,28,29). , India; ). Flower, India; ). In angGermany; ). In a sGermany; . This unKnowledge flow between the researchers from both India and Germany on sustainable stress management in terrestrial and aquatic plants has helped to widen the understanding of the mechanism of stress management in general and also allowed inputs and learning into each field in order to work towards developing sustainable aquatic and terrestrial cropping systems that can deal with stress in a more efficient manner. The development of well-organized sustainable agriculture systems, which will enable us to create innovative technologies that can be integrated into circular economy, is the future. Our efforts to understand the stress-management strategies in both terrestrial plants and aquatic plants facilitated a holistic understanding of the requirements and strategies for building sustainable cropping systems."} +{"text": "In the past few decades, the rapid development and decreasing costs of sequencing technologies dramatically changed the landscape of epidemiological studies and surveillance of infectious diseases. Subsequently, pathogen genomic studies have become the forefront tool for investigating emerging infectious disease epidemics and supporting decision-making processes related to the mobilization of intervention resources. Since the introduction of next-generation sequencing (NGS), which expanded the capacity for whole genome sequencing (WGS), and the revolutionary growth of computational resources, viral or bacterial complete genomes can now be sequenced and characterized within a few days or even hours. Therefore, high-throughput sequencing technologies resulted in the exponential growth of genomic databases, unveiling novel insights into the biology, pathophysiology, and molecular epidemiology of infectious disease pathogens. Such significant developments in genome sequence technologies also resulted in important advances in the field of phylogenetic analysis. Modern analytical methods in phylogenetics improved the tracking and understanding of pathogen transmission and evolution of human and animal diseases. Thus, phylogenetic analysis of big genomic databases can be used to clarify key questions related to infectious disease epidemiology, such as the initial detection and characterization of outbreaks, accurate tracing of transmission chains between hosts, and dispersal among and within geographical regions. The threat of emerging and re-emerging infectious diseases continues to be a challenge to global public and animal health, in which sequencing is not just a critical tool in surveillance but also has a major role in a pandemic or outbreak response. The main objective of this Research Topic is to explore the current status and future perspectives of sequencing technologies in the control and prevention of infectious diseases, including the elucidation of diagnosis, molecular evolution, and epidemiology of infectious disease pathogens.Kariithi et al., Kim H.-J. et al., and Abbas et al. demonstrated multiple approaches in utilizing sequencing and phylogenetic analysis resources for improving genomic surveillance of avian infectious bronchitis virus in poultry by characterization of phylogenetic relationships, detection of critical recombination events, assessing vaccination effectiveness, and identifying evolutionary origins of endemic and emerging strains. Furthermore, Kim S.-W. et al. were able to confirm that avian reoviruses circulating in poultry flocks were originating from wild birds using straightforward traditional molecular characterization tools, similar to what Goraichuk et al., did with the Newcastle disease virus. However, Baek et al. went a step further by implementing Bayesian phylodynamic analysis to shed deeper insights into the evolutionary epidemiology of H5N8 avian influenza viruses. They demonstrated that wild birds were the ancestral host for multiple introductions of H5N8 viruses into poultry, but domesticated ducks more important in virus circulation and transmission among poultry flocks.NGS has become a primary diagnostic and characterization tool for genomic surveillance of pathogens that threaten biosecurity and food safety. Hyeon, Tseren-Ochir, et al., Gallardo et al., and Kim G. et al. Furthermore, the combination of WGS and phylodynamic analytical approaches was used by Pamornchainavakul et al. to unveil novel findings on how the rapid recombination events among porcine reproductive and respiratory syndrome virus 2 strains can accelerate their genetic mutations leading to the emergence of more virulent strains. Similarly, Wei et al. were able to identify evolutionary characteristics and geographical origins of the lumpy skin disease virus in cattle, using multiple gene segments of a strain isolated from an outbreak in China in 2009. Rossi et al. extended their genomic analytical pipeline by integrating ecological niche models to quantify the role of environmental and demographic risk factors in shaping the evolutionary epidemiology of Mycobacterium bovis in Cameroon, which is considered a novel and critical step in improving genomic surveillance of infectious diseases.African swine fever continues to be the most important devastating pathogen to swine populations, causing unprecedented annual economic loss on a global scale. NGS and WGS also continue to be the most essential tools for providing critical genetic, epidemiologic, therapeutic, and vaccine development resources for African swine fever intervention efforts, as illustrated by Chung et al. and Hyeon, Helal, et al. used NGS and WGS approaches to deeply characterize the genetic features of West Nile virus and lyssaviruses from wild animals in selected regions in the United States in order to shed important insights about their origins and transmission dynamics. Additionally, it is important to include genomic surveillance of pathogens in exotic pet animals, such as reptiles, to monitor evolutionary characteristics that may result in the emergence of novel pathogens, as demonstrated by Varga-Kugler et al..Genomic surveillance of infectious diseases in wildlife is the foundational pillar of implementing the One Health concept globally. Indeed, the rapid emergence and spread of West Nile and Rabies viruses from wild animal origins played an important role in building the foundation of the One Health concept, which necessitates integrating disease surveillance of humans, wildlife, and domestic animals. In this Research Topic, Lorente-Leal et al. revised the performance and agreement of four commonly used pipelines for WGS data analysis of M. bovis, the causative agent of bovine tuberculosis, Butt et al. highlighted the feasibility and utility of long-read random sequencing approaches to identify pathogens in clinical samples, and Cho et al. developed a novel tiling amplicon PCR method for feasible and rapid sequencing of complete genomes in clinical samples.Continuous development and revision of NGS and WGS pipelines are critical for ensuring the sustainable generation and accumulation of sound and reliable genetic data. In this Research Topic, Our Research Topic reinforces the importance of sequencing technologies in changing the landscape of infectious disease surveillance in animals and humans, with the aim of highlighting NGS and WGS approaches that continue to become more feasible and accessible globally. This Research Topic highlights the versatility of techniques for bench science and sequence analysis in its application to many problems in infectious diseases of veterinary importance. In this Research Topic alone, investigations on 13 infectious diseases of poultry, swine, bovine, and wildlife were presented. Furthermore, the authors of these investigations span 23 countries and five continents, highlighting the accessibility of NGS techniques and its continued lowering of costs. In this Research Topic, we aspire to further motivate physicians, veterinarians, epidemiologists, microbiologists, diagnosticians, and other scientists from related fields to make sequencing technologies the gold standard for the diagnosis and surveillance of infectious disease pathogens in order to improve their current and future intervention efforts.All authors were involved in the writing of this editorial and editing contributions to this Research Topic."} +{"text": "The South African Noise Induced Hearing Loss (NIHL) Regulations, mandates employers to conduct a noise risk assessment, which records specific variables for determining the status of exposure and the need for implementation of control measures.The study evaluated company noise risk assessment practices for alignment with legal requirements and specific risk assessment guidelines.Convenience sampling was used to select the four manufacturing and utilities companies that participated in the study. The participating companies submitted latest noise risk assessment records for evaluation through the READ approach.The noise risk assessment records of three of the four companies omitted the recording of factors such as the reasonable deterioration in or failure of control measures, adequate control and formalisation of hearing conservation programmes (HCPs). When evaluated against the South African National Standard 31000 Risk Assessment guidelines, the risk assessment processes of the respective companies were lacking in addressing aspects related to establishing communication and consultation, evaluation, adapting, continually improving, leadership and commitment, and integration.The recorded information on the noise risk assessment reports from the four participating companies were incomplete, negatively affecting subsequent HCP management processes and decision-making. Future studies should investigate other aspects such as the implementation status of recommended noise controls as well as their effectiveness as recorded in the noise risk assessment records.This study provided firsthand insights of company noise risk assessment practices, specifically identifying functional and technical areas requiring improvement to enhance current efforts directed towards the minimisation of NIHL within HCPs. The study highlighted that the current practices on recording noise risk assessment information remain incomplete, adversely diminishing the impact of the assessment as an important decision-making tool. The identified technical issues specifically, when addressed, will increase trust on the decisions derived from noise risk assessments. Occupational health programmes, including hearing conservation programmes (HCPs), offer employers a risk management tool for managing and minimising the impacts of exposure Khattab, and are A risk assessment is vital within the overall risk management process and includes aspects such as communication and consultation, context establishment, risk analysis, risk evaluation, risk treatment, monitoring and review 31000.The participating companies were conveniently selected, informed by a risk-based criteria of confirmed historic NIHL incidence, determined through the evaluation of sustainability reports. The final selected companies were identified and selected using a longitudinal study of 20 manufacturing and utilities companies, the method of which has been previously reported by Rikhotso et al. ; 2022a. The submitted noise risk assessment records were evaluated based on a criteria derived from the NIHL Regulations approach Faculty Committee on Research Ethics-Science: FCRE 2020/10/015 (FCPS 02) (SCI). The primary investigator (O.R.) signed disclosure agreements with the participating companies, as applicable.The confirmation and availability of the noise risk assessment records from the four companies were in response to employer obligations for securing legal compliance and to satisfy internal voluntary requirements. The reporting format of the submitted records diverged between full Microsoft Word, PDF, Microsoft Excel spreadsheets and checklists. The type and format of the noise risk assessment record affects the thoroughness and quality of information contained in such documents.Employers from Companies A, B and C delegated the duty of conducting noise risk assessments to occupational hygiene professionals who had varying Southern African Institute for Occupational Hygiene (SAIOH) certification levels ranging from occupational hygiene assistants, occupational hygiene technologist to occupational hygienists . These oThe NIHL Regulations prescribe that the assessment be conducted with involvement and participation of various stakeholders. Stakeholders with recorded involvement and participation in the respective company assessments includedn = 2, 18%) facilities recorded the noise sources. None of the companies recorded the reasonable deterioration in or failure of control measures. Furthermore, only two of 11 at Company A, two of six at Company C, and none for Companies B and C recorded the factors for determining the adequate control of exposure status. At Company D, none of the noise risk assessment variables outlined by the NIHL Regulations were recorded, a limitation of the use of a checklist as a risk assessment tool.The recorded information in the noise risk assessment records varied between the respective participating companies for Company A, whereas none was recorded for Companies C and D. Noise zone demarcation, an administrative control, was recorded in 6 of 11 and 2 of 6 at Company A and Company B, respectively. Furthermore, only 3 of 11 facilities at Company A recorded historic noise reduction efforts undertaken by the respective facilities, whereas none of Companies B, C and D recorded the same information, as applicable. None of Company D noise risk assessment records recorded the variables specified in SANS 10083 code of practice.In addition to the NIHL Regulations-prescribed variables to be recorded in noise risk assessments, the SANS 10083 code of practice also recommends the recording of additional information in the assessment. The recording of the HCP implementation status was 3 of 11 (The noise risk assessment frameworks of all participating companies did not demonstrate tangible evidence of conformance to the SANS 31000 clauses regarding leadership and commitment, integration, establishing communication and consultation, evaluation, adaptation and continual improvement, in general. This is expected against a national gap without a prescribed and adopted standard for conducting risk assessments by regulated industry.Once completed, the risk assessment should be reviewed, and the effectiveness of implemented control measures be continuously monitored. Companies A, B and C omitted At the time of writing, there remained limited publicly available scientific literature on the subject matter and studies of a similar study design to enable result comparisons.The reviewed records attest that participating companies were conducting noise risk assessments for regulatory compliance purposes HSE, , and forRisk assessors are expected to have thorough understanding and in-depth technical knowledge of a process being assessed to achieve meaningful results (Center for Chemical Process Safety, The multidisciplinary team required for conducting a noise risk assessment should cThe noise risk assessment determines and records sources of hazards, exposure levels where available, routes of exposure, exposure duration and frequency, and identification of the most exposed job categories (South Africa, Fragmentation in the risk assessment process, which can be avoided by adopting guidelines such as the SANS 31000, has implications that impact the decision-making process of deciding on implementing required control measures. The risk assessment processes of the participating companies in this study were misaligned with certain selected clauses of SANS 31000 (South African National Standard, Following the completion of the entire risk assessment process, practical steps to manage identified health risks should be taken, followed by an evaluation to assess the effectiveness of the effected measures, instruction and training HSE, , a practNoise risk assessments were a confirmed practice at the participating companies and were conducted by employer-delegated professionals inclusive of occupational hygienists, occupational health nurse or practitioner as well as a risk officer. Stakeholder involvement and participation during noise risk assessments was recorded extensively at Companies B and C, an indicator of internal communication and consultation in the risk management processes. Legally, health and safety representative and health and safety committee involvement and participation in noise risk assessment is an enforceable legal requirement which was absent in some facilities. Factors such as mention of any reasonable deterioration in or failure of control measures, adequate control and formalisation of HCP, recorded as part of risk assessment variables in the records were generally omitted in the noise risk assessments, adjudging the process as incomplete. The recording of information relating to these factors affects the risk analysis phase. The enrolled risk assessment records were also adjudged as being improperly aligned, in general, to the risk assessment guidelines specified in the SANS 31000 relating to elements such as establishing communication and consultation, evaluation, adapting, continually improving, leadership and commitment, and integration. Additionally, the review and monitoring of the assessed noise risk assessment aspects remained non-existent across all participating companies. Conclusively, the noise risk assessment processes at the four participating companies had technical shortcomings, which influences subsequent HCP management process. In general, an improvement in the noise risk assessment processes among the participating companies is recommended, in order to minimise the pervasive NIHL.Future studies should investigate the implementation stages and status of recommended noise controls and their effectiveness as outlined in noise risk assessment records. Furthermore, future studies should also investigate the roles of both the health and safety representatives, and health and safety committees in following up on recommended or proposed corrective actions for noise control."} +{"text": "With climate change becoming a global concern, a low-carbon economy has become an inevitable trend. Carbon neutrality is considered an important step in curbing global greenhouse gas emissions and reducing carbon footprints. However, a low-carbon economy is not only about environmental protection but also closely related to human health. Against this background, a special topic on low-carbon economy and health in the context of carbon neutrality is proposed, aiming to promote the emergence of a series of emerging research and the sustainable development of low-carbon economy and human health. The articles included under this topic have been researched from different perspectives, introducing new research perspectives, methods, and techniques for the further development of the topic, which will have a positive impact on promoting the in-depth research and development of the topic.Zhu et al. concluded that the NSGA-II algorithm performs well in the doctor-patient bilateral matching problem, but the matching accuracy needs to be further improved. In terms of the pharmaceutical supply chain, Fu and Zhao considered the risk of pharmaceutical supply chain disruption under two modes of centralized and decentralized decision-making and constructed a combined contract model to effectively coordinate the pharmaceutical supply chain under supply disruption crises, but further research is needed in the area of stable coordination of pharmaceutical supply chain with multi-levels and multi-objects. In terms of public health expenditures, Omri et al. concluded from their study that public and private health expenditure is effective in mitigating environmental degradation on health status in Saudi Arabia, especially public health expenditure. In terms of regional green development, Wang W et al. constructed a rating model for the high-quality development of China's Yangtze River Delta Green Integration Demonstration Zone, and proposed methods and approaches to measure the construction milestones of high-quality development, which provides a reference for the evaluation study of high-quality development in other city clusters. The model suitability can be further improved by combining the actual data of city clusters in future studies. In terms of government guidance, Xu et al. observed in their study that the characteristics of local government information sources have a significant positive effect on consumers' willingness to purchase low-carbon agricultural products, which can effectively promote the development of low-carbon agriculture. However, the study lacks quantitative research on the degree of contribution of regional brand low-carbon agricultural products to the development of low-carbon agriculture. Hu et al. offer suggestions for establishing and managing a low-carbon technology innovation system, along with insights into theoretical research on public health and high-quality development in China. Wang Q et al. examine the impact mechanism of environmental education on environmental quality in the context of low-carbon economy. Wu et al. analyze the optimal use of urban resources based on public health. Bai et al. utilize unit root tests, co-integration tests, and regression analysis to empirically investigate the associations between carbon emissions and GDP in the industry, construction, and transportation sectors. Zheng et al. provide significant practical contributions to sustainable development and the promotion of responsible population growth.The topic of low-carbon economy and health in the context of carbon neutrality has been studied multidimensionally in the articles included in this topic. In terms of the doctor-patient relationship, To sum up, for the special topic of low-carbon economy and health in the context of carbon neutrality, researchers have carried out relevant research in the areas of healthcare resource allocation, public health resources, urban green and low-carbon development, and the process of low carbonization of sub-fields. The further deepening of this topic expands the research field, provides subdivided research directions, relevant theoretical foundations, research methodological references, data support, and case analyses, and plays a positive role in promoting subsequent in-depth research. In more in-depth research in the future, the following can be further explored: the evaluation system of healthcare resource allocation and the construction of a low-carbon supply chain, the supply and allocation of public health resources in less developed regions, the quantitative assessment method of the impact of low-carbon economic policies and measures on health, and the process of decarbonization in the fields of agriculture, industry, and urban construction, as well as synergistic effects among different fields.YZ: Writing\u2014original draft. ZL: Writing\u2014review and editing. CH: Writing\u2014review and editing."} +{"text": "Editorial on the Research TopicHighlights in quality of life 2021/22www.pubmed.gov, the growth immediately becomes apparent, with 2,038 papers published in 1992, 7,391 in 2002, but a staggering 40,740 in 2022 alone.Quality of life (QoL) has long been a part of medical research, attracting a steadily increasing amount of attention from scholars around the world. However, recent years have seen an unprecedented rise in research about the topic. Once the terms [(patient-reported outcomes) or ] are entered into the search strategy at Patient-Reported Outcome Measures (PROs) are used to assess QoL. A PRO has been defined as any report about patient health status which comes directly from the patient, without being interpreted by a physician or anyone else . PROs arProtocol for the Cultural Translation and Adaptation of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project Endometriosis Participant Questionnaire (EPHect) presents the process in detail. Content and face validity of WERF EPHect EPQ-M were performed. The cross-cultural translation and adaptation of the questionnaire was carried out using the recommended guidelines and COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN standards) (The paper andards) . The proandards) .International databases are becoming increasingly important, especially in the context of collecting data to conduct analyses on large groups of subjects in many conditions, e.g., in endometriosis, as presented in the paper. Research data registries contain shared datasets and facilitate collaborative research between various international centers. Surgical databases which collect information about the outcomes of the procedure and complications are of great importance.Community-Engaged Approaches to Cervical Cancer Prevention and Control in Sub-Saharan Africa: A Scoping Review, deals with the issues of cervical cancer prevention. Organized screening has decreased cervical cancer incidence in the developed countries. However, at the same time, cervical cancer remains to be the leading cause of cancer-related mortality among African women. The paper is a narrative review describing community-engaged approaches to cervical cancer prevention and control methods in Sub-Saharan Africa (SSA). The Covidence systematic review software was used and nine articles were selected for the final analysis. The objectives of the review were as follows: to describe community engagement activities in cervical cancer prevention and control in SSA, to identify the aspects of cervical cancer research which used community engagement, and to describe the best practices for community engagement in achieving the goal of cervical cancer prevention and control. The study presented a Community-Based Participatory Research (CBPR) framework and analyzed the research, in accordance with its eight principles.The following article, Cervical cancer is a global public health problem, with a particularly high burden in many low- and middle-income countries. The proven effectiveness of interventions such as vaccination against the most oncogenic human papillomavirus (HPV) types, and screening, particularly with HPV-based methods, makes cervical cancer a largely preventable disease . SubstanMis et al., is released under the auspices of the World Endometriosis Research Foundation. The organization aims to be a global charity facilitating research into endometriosis to improve knowledge and treatment. In turn, the authors of the narrative review highlight the role of tribal leaders, religious leaders, and community health workers in increasing knowledge about cervical cancer and screening. They highlight strategies to identify and engage target populations and improve awareness.Both articles address the topic of research methodology. On the one hand, we have a paper on an international database covering a variety of patient medical data to improve our understanding of endometriosis. On the other hand, we have a paper evaluating the feasibility of community-based prevention of cervical cancer. The authors of these papers aim to reduce the morbidity of endometriosis and the incidence of cervical cancer. The WERF EPHect EPQ-M questionnaire, whose validation is presented by"} +{"text": "Efficient and secure supply chains are vital for effective health services worldwide. In low- and middle-income countries, the accessibility, affordability and availability of essential medicines, including antimicrobials, remain challenging. Ineffective supply chains often cause antimicrobial shortages, leading to inappropriate use of alternative agents and increasing the risk of antimicrobial resistance. Shortages, coupled with insecure supply chains, also encourage the infiltration of substandard and falsified medicines, leading to suboptimal treatment and further promoting antimicrobial resistance. Addressing antimicrobial supply-chain issues should be considered a key component of antimicrobial stewardship programmes. We have explored the link between medicine supply chains and antimicrobial use in seven focus countries: Kenya, Malawi, Nigeria, Sierra Leone, Uganda, United Republic of Tanzania and Zambia. We explored country medicine supply-system structures, national medicine supply-chain policy documents and global study reports. Our aim was to develop evidence-based strategies to enhance the effectiveness and efficiency of the medicine supply chains in supporting antimicrobial stewardship efforts. Better management of medical supply chains involves rational selection, quantification, forecasting, procurement, storage, distribution, use and stock management of antimicrobials. Important supply-chain considerations include pooled procurement networks to ensure consistent pricing of quality-assured antimicrobials, and improved resource utilization and information exchange among relevant stakeholders. We propose adaptable recommendations for integrating medicine supply chains as an essential part of antimicrobial stewardship programmes, with a call for action at the local, regional and national levels in low- and middle-income countries. Antimicrobial resistance disproportionately affects low- and middle-income countries.Health supply chains are the processes and operations required to get products and medicines from manufacturers to health-care staff and patients at the right place, price, time, cost, quality, efficacy and quantity. Strong and secure supply chains save lives. They are the fundamental building blocks of national welfare systems and are necessary for the achievement of the sustainable development goals. The coronavirus disease 2019 (COVID-19) pandemic drew attention to the importance of resilient supply chains in national emergency response efforts.A continuing challenge in low- and middle-income countries is inadequate access to essential medicines and medical supplies, including antimicrobial medicines.There is limited published information specifically on the supply chains for antimicrobials and access to these medicines in low- and middle-income countries. In this article we explore the impact of medicine supply chains on antimicrobial use, focusing on seven countries of the Commonwealth Partnerships for Antimicrobial Stewardship programme. We issue a call to action on incorporating supply-chain considerations into antimicrobial stewardship policies and processes.\u00ae articles published between 2015 and 2021. \u2013All seven countries obtain, fund and distribute essential medicines through a combination of health ministries, nongovernment organizations and the private sector. The existing systems are classified as tier systems, single agencies or devolved. Except for Nigeria, every country has a centralized supply chain. All seven countries have existing national essential medicine lists. Kenya, United Republic of Tanzania and Zambia have WHO AWaRe categories of antimicrobials recommended in their national essential medicine lists. All seven countries face challenges in the management of health products and technologies that are familiar to many high-income countries. Challenges reported in medicine supply chains include: inadequate quality assurance; weak regulation; poor enforcement of laws; unavailable and unaffordable medicines; transport and storage infrastructure; poor information and logistics management; inadequate human resources; and inadequate financing.Local supply chains for medicines and medical supplies in Kenya are dependent on three supply chains within the health sector: the health ministry; non-profit procurement agencies; and private distributors and wholesalers.\u2013Shortages of essential medicines in KenyaThe supply chain for essential medicines in Malawi follows a rigorous process that ensures compliance with the Public Procurement Act (2003) and the Public Procurement Guidelines (2004). The Central Medical Stores Trust sources medicines and other health commodities in accordance with the policies and guidelines of the Director of Public Procurement. Essential medicines are distributed from a central warehouse to three regional medical stores which supply public health facilities.Malawi has other parallel supply-chain systems for essential medicines, especially relating to disease programmes such as tuberculosis, malaria and reproductive health. Chronic stockouts of medicines at the central medical stores and in health facilities remain a challenge.There are two key agencies in Nigeria involved in medicine supplies: the National Agency for Food and Drug Administration and Control; and the Pharmacists Council of Nigeria. The pharmaceutical services division within the Nigerian food and drug authority is part of the health ministry and regulates and monitors the pharmaceutical supply chain, supporting access to quality medicines in Nigeria.Nigeria supplies agencies have faced difficulties with selection of medicines and vaccines, procurement and distribution of medicines, inventory management and storage infrastructure.,The National Medical Supplies Agency of Sierra Leone, formerly the Directorate of Drugs and Medical Supplies, undertakes the transparent and cost\u2013effective procurement, warehousing and distribution of drugs and medical supplies on behalf of all public institutions throughout the country.The impact of the COVID-19 pandemic on the local pharmaceutical industry resulted in severe drug shortages and medicine insecurity in the country due to the restrictions imposed on cross-border imports.The management of essential medicines and health supplies in Uganda is guided by the Essential Medicines and Health Supplies Management Manual of 2018. The National Medical Stores provide the public health-care facilities with the core antibiotics.As in many other low- and middle-income countries, Uganda faces challenges with enforcement of regulations, creating multiple nodes of entry for medicines into the market that may accelerate the proliferation of substandard and falsified products.The United Republic of Tanzania has a centralized procurement system for medicines. The Medical Stores Department, under the Public Procurement Act 2004 and Regulations 2005, is empowered to advertise, receive, evaluate and award successful bidders for government contracts. The price and quality of the product are given equal consideration when awarding the tender.The country has a higher use of antimicrobials compared with many other countries worldwide. Contributing factors include a relatively higher burden of infectious diseases; limited diagnostic services in health facilities; widespread availability of antibiotics without prescription; and the unexplained use of certain antibiotics in the animal health sector.Zambia has a three-tier public sector distribution system for essential drugs. The primary distribution of drugs and other health commodities is managed by the Zambia Medicines and Medical Supplies Agency, formerly Medical Stores Limited. The secondary distribution of commodities falls under the responsibility of district health management teams reporting to the health ministry. The national pharmacovigilance unit under Zambia\u2019s Medicines Regulatory Authority leads and coordinates the pharmacovigilance or drug safety monitoring programme in the country.According to Zambia\u2019s national health strategic plan, the key planning issues for the medicines, vaccines and medical supplies sector are weak coordination mechanisms and accountability in supply-chain management, and an inadequate quality management system for data in the supply chain.,Challenges within antimicrobial supply chains worldwide, including in low- and middle-income countries, make forecasting and mitigating antimicrobial shortages difficult.,Antimicrobials, especially antimalarials and antiretrovirals, are the most commonly falsified medicinal products worldwide.The main functions of countries\u2019 national medicines regulatory authorities include: (i)\u00a0control of pharmaceutical products through registration and post-marketing surveillance; (ii)\u00a0control of activities by licensing and inspection of manufacturers, importers, exporters, wholesalers, distributors, pharmacies and retail outlets; (iii)\u00a0control of clinical trials; and (iv)\u00a0control of promotion of pharmaceuticals. However, in 2010 the World Health Organization (WHO) estimated that 34 out of 38 national medicines regulatory authorities in sub-Saharan Africa were not enforcing basic regulatory functions.Drug shortages, combined with inappropriate prescribing and use of antimicrobials, accelerate the development of antimicrobial resistance and hence reductions in antimicrobial effectiveness.,Pharmacists have an important role to play.,Addressing supply-chain challenges requires consistent efforts at the global, national and regional levels, building on existing partnerships and legislation. We need to address ways to pool the procurement of medicines, improve the forecasting of supply needs and increase the commitment to improving processes and resources. Measures could include appropriate storage conditions, implementing efficient transportation and distribution systems, and maintaining reliable quality control measures throughout the supply chain. Sustainability of medicine supply chains remains an elusive goal that is yet to be integrated into discussions.We can improve antimicrobial stewardship and strengthen the knowledge and evidence base of factors contributing to antimicrobial resistance through ongoing surveillance and research.WHO AWaRe antibiotic book offers clear and evidence-based recommendations on the appropriate antibiotic choice, dosage, administration route and treatment duration for over 30 prevalent clinical infections in both primary health care and hospital settings. The book\u2019s information aligns with the antibiotic recommendations outlined in the WHO Model list of essential medicines and WHO Model list of essential medicines for children, as well as the WHO AWaRe antibiotic classification.African antibiotic treatment guidelines for common bacterial infections and syndromes also provide care workers with expert recommendations for antimicrobial selection, dosage and duration of treatment for common bacterial infections and syndromes among paediatric and adult patient populations in Africa.It is important to ensure that, as far as possible, appropriate Access and Watch antibiotics are available for the most common infections within hospitals across Africa. The Post-marketing surveillance and pharmacovigilance is needed to detect substandard and falsified medicinal products. Efforts are also required to improve medicine quality by strengthening the medicine distribution chain; ensuring the use of quality-assured drugs through improved pharmaceutical governance; and strengthening the technical capacity of regulatory laboratories, particularly in poor and rural communities.We propose that the basic principles of medicine supply-chain systems should be included in capacity-building for antimicrobial stewardship teams and health-care personnel at local, national and global levels. The managers of procurement systems within a country are responsible for ensuring the continuous availability of essential quality-assured medicines at an affordable price. Implementing monitoring and evaluation systems for antimicrobial resistance and antimicrobial use as part of national action plans could contribute to the use of quality-assured medicines, and reduce the distribution of substandard and falsified medical products.In the absence of stringent national and international regulatory oversight, ensuring the quality of medicines becomes a choice rather than a duty. As a result, there is a risk that poor-quality medicines will enter the supply chain, causing harm to individuals and public health.Box\u00a01Optimize appropriate antimicrobial use through pre-service and in-service training for health-care workers on effective medicine procurement, inventory control and distribution management.Designate local resource mobilization as a priority area in health ministries to build and sustain the medicine supply-chain systems.Engage the right human workforce into the local supply chains to ensure reliability of the systems .Establish or empower medicine and drug and therapeutics committees to act as an oversight mechanism in health-care facilities.Establish antimicrobial stewardship programmes that include supply-chain management as an essential component, to ensure rational antimicrobial selection, quantification and forecasting, procurement, storage, distribution, use and stock management of antimicrobials.Streamline and strengthen national medicine supply-chain systems. Use pooled procurement networks, to ensure consistent pricing of quality-assured antimicrobials and to improve resource utilization and information exchange between organizations.Harmonize drug master files and specifications required for antimicrobial resistance surveillance.Standardize pre-qualified supply mechanisms, including those from manufacturers, to ensure constant availability of antimicrobials.Increase the number of well-designed studies into medicine supply-chain management to identify gaps and challenges in low- and middle-income countries.Increase quality assurance programmes that conduct routine inspections of manufacturers, suppliers and warehouses to ensure medicines meet international quality standards.Consider approaches such as the Lom\u00e9 Initiative to criminalize the trafficking of falsified medical products.Increase regulatory capacity and reporting mechanisms to detect and tackle substandard and falsified medical products.Strengthen national medicines regulatory agencies and harmonize legislation, taking a collaborative approach through the African Medicines Agency.Increase local production of antimicrobials to strengthen supply-chain resilience and reduce the risk of infiltration of substandard and falsified antimicrobials.Encourage more national policies and government regulatory frameworks for the essential infrastructure, such as national warehousing, distribution and transport of quality-assured health products.Incorporate analysis of bottlenecks into national supply chains to identify underlying causes and human behaviours that influence procurement agencies and practices.Integrate digital health systems interventions, with the implementation and scale-up of logistics management information system software, to improve the forecasting, monitoring, evaluation, tracking and planning of medicine supply chains. Model list of essential medicines.Ensure that appropriate Access and Watch antibiotics are available for key diseases relevant to the national context and the World Health OrganizationSet up consumption surveillance systems for antimicrobials to ensure rational antimicrobial selection and use, particularly lower down the supply chain.Develop and implement antimicrobial national action plans to include supply-chain management.Ensure antimicrobial stewardship initiatives address over-prescribing and inappropriate prescribing; improve patient adherence to treatment regimens; and address potential environmental contamination, for example through inappropriate disposal of antimicrobials.Update mechanisms for the review and reporting of substandard and falsified medicines, providing a user-friendly and safe environment to encourage reporting and facilitate feedback."} +{"text": "A wide variety of traits is heritable and has genetic loading, including schizophrenia spectrum disorders (SSDs) and its associated neurocognitive features. The genetic architecture of SSDs is polygenic, with the contribution of thousands of single nucleotide polymorphisms of small effect with an estimated SNP-heritability of 24%. The same occurs with neurocognitive phenotypes such as intelligence or educational attainment. Therefore, the method of polygenic risk scores (PRS) is useful in estimating the genetic burden of such traits. Moreover, the use of PRS in a sample of genetically related individuals would allow analyzing the contribution of genetic and environmental factors involved in the development of the disorder and its candidate endophenotypes.To estimate PRS for schizophrenia, and polygenic scores for intelligence and educational attainment in patients with First Episode Psychosis (FEP), their first-degree relatives (siblings and parents), and a group of healthy controls.The sample is comprised of 579 participants of the PAFIP-FAMILIAS project in Santander, Spain . All provided sociodemographic information and completed the same neuropsychological battery. Participants\u2019 DNA was extracted from venous blood samples, and genotyping was performed at the Centro Nacional de Investigaciones Oncol\u00f3gicas (CeGen) by the Global Screening Array v.3.0 panel (Illumina). Data quality control, imputation, calculation of PRS, and genetic association analysis are being performed using PLINK, SHAPEIT, IMPUTE2, SPSS and R.Data analysis is currently in progress, at the quality analysis stage, in collaboration with the Institute of Psychiatric Phenomics and Genomics (IPPG) in Munich, Germany. We expect to find higher PRS for schizophrenia in FEP patients, while their first-degree relatives will potentially show intermediate risk scores between patients and healthy controls. A similar finding is expected regarding intelligence and educational attainment, as FEP patients may show more genetic burden for low intelligence and education.The estimation of PRS has demonstrated to be valuable in studying complex traits such as schizophrenia. We believe that by applying this method in a family design can provide interesting insights on the development of SSDs and its potential endophenotypes, and potentially useful in their prevention.None Declared"} +{"text": "We are delighted to publish the second volume of the Research Topic: Antimycobacterial Drug Discovery\u2014Molecular Therapeutics and Target Identification. The Research Topic continues the discussion with an emphasis on the identification of novel antimycobacterial compounds and, more broadly, antibacterial compounds isolated from natural products or derived synthetically. Studies on the mechanisms of action of these bioactive molecules provide insights into the design of safer therapeutics and antimicrobials for the treatment of multidrug-resistant infections.Khare et al. The authors provide a comprehensive summary of the effects produced by alkaloids, phenolic compounds, terpenes, and coumarins against drug-resistant pathogens, with a focus on the major determinants of antibiotic resistance, such as efflux pumps, cell permeability, and modification of the antibiotic targets. Rubio et al. report on the mechanism of cellular uptake of mycolactone, a lipid toxin produced by Mycobacterium ulcerans, from the circulating plasma Using a combination of dynamic light scattering and fluorescence spectroscopy, the authors demonstrate how mycolactone behaves in solution and how it interacts with serum albumin and lipoproteins in plasma. Monitoring plasma levels of complexes formed by mycolactone and albumin/lipoproteins could be useful for the early diagnosis of patients with Buruli ulcer disease. Wang et al. investigate the effect of the labdane diterpenoid andrographolide on the hemolytic activity of S. aureus. Andrographolide dose-dependently inhibits hemolytic activity by significantly downregulating the transcript levels of the Hla gene, which in turn is responsible for the expression of the crucial virulence protein Hla. Molecular dynamics simulations of Hla-andrographolide interactions provide valuable insights into the structural requirements for the observed activity and have the potential to design more potent andrographolide analogs. Hoffmann et al. demonstrate the repurposing potential of nitroxoline for the treatment of multidrug-resistant tuberculosis (MDR-TB). Originally approved for the treatment of urinary tract infections, nitroxoline was tested in a panel of MDR-TB cells and found to have MIC values of 4\u20138\u00a0mg/L. Finally, Korycka-Machala et al. report the synthesis of thiosemicarbazide-based compounds and their structure-activity relationship against Mycobacterium tuberculosis. The authors demonstrate the efficacy of these compounds in inhibiting the growth of intracellular M. tb and reducing biofilm formation. The selection of resistant mutants and their whole genome sequencing identified the mmpR5 gene as a target for these analogs.The second volume begins with a review of the antimicrobial properties of phytochemicals by Taken together, the second volume of this Research Topic: \u201cAntimycobacterial Drug Discovery: Molecular Therapeutics and Target Identification\u201d, provides recent advances in the development of antibacterial and antimycobacterial agents. We acknowledge the contributions of all the authors that made this research volume possible."} +{"text": "After the introduction of nanotechnology as a new science, there were tremendous changes in its application. Nanomaterials rapidly penetrate a diverse area of biomedicine and pharmaceutical research, including drug development, drug delivery, tissue engineering and medicinal chemistry. Its versatile use helps in alleviating complex difficulties faced with drug administration and absorption, controlled release, targeted delivery and cellular uptake. Due to their distinctive physico-chemical properties and ability to form various solid-state formulations, they find increased use in the preparation of new drug formulations, imaging techniques and particularly in medicinal chemistry as catalysts for the sensitive determination of drugs and other biologically active compounds. The role of nanomaterials as catalysts in the preparation of substances with pharmacological properties, the preparation of sensors, or the degradation and removal of medicinal compounds polluting the environment is undeniable.This special issue aims to cover recent advances in the preparation and application of nanomaterials in the above-mentioned fields. Its scope includes the role of nanomaterials in drug delivery and the development of new drug formulations, novel polymorphs and other solid-state forms, the influence of nanotechnology on the physico-chemical properties of importance to adsorption, distribution and metabolism of drugs, tissue and cellular uptake of nanomaterials and their treatment potential and application of nanomaterials as catalysts for the sensitive and selective determination of biologically active compounds.The special issue is guest-edited by Hassan Karimi-Maleh, Afsaneh L. Sanati, Rozhin Darabi. The whole issue will be split into two consecutive issues. This issue, the first of the series, consists of 5 review articles and 6 original papers. Two reviews address the synthesis of nanomaterials and their applications . A review by D. Pylypenko (\u201cLiposomes: from August Wassermann to vaccines against COVID-19\u201d) covers liposomal antigens as antigen-delivery systems for diagnosis and immunoprophylaxis. Two additional reviews tackled the use of nanomaterials as therapeutics (\u201cSupremacy of nanoparticles in the therapy of chronic myelogenous leukemia\u201d and \u201cInfections associated with SARS-CoV-2 exploited via nanoformulated photodynamic therapy\u201d). The original papers present the preparation and application of nanoparticles of different materials such as cyclodextrin, silica, selenium, silver, chitosan and polyvinyl alcohol."} +{"text": "The number of patients reporting the use of cannabis for medical purposes, whether through state-regulated medical marijuana programs or through over-the-counter hemp extracts, continues to grow. The growth in medicinal use of cannabis has in many ways surpassed the scientific data on the benefits and hazards of cannabis, and the scientific community has largely been left playing catch-up. Since 1996, when California became the first jurisdiction to legalize medical cannabis, the number of states following suit has grown and is currently at 37, while nearly 50 countries have legalized medical cannabis including Canada, Austria, Uruguay, Australia, South Korea, and Lesotho.Cannabis sp. produces a number of phytochemicals with potential medical benefits including terpenes, flavonoids, and a unique class of molecules called cannabinoids, of which \u03949-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most studied [ studied ,2. Amazi studied .Cannabis and Cannabinoid Research, in 2016, Medical Cannabis and Cannabinoids, in 2018, and The Journal of Cannabis, in 2019.The recent growth in cannabis and cannabinoid research is perhaps best highlighted by the establishment of three scholarly journals devoted solely to this topic in the past few years, namely, This Special Issue features fourteen original research articles across a wide range of topics and includes 10 reports on phytocannabinoids, 2 studies examining the endocannabinoid system, and 2 papers using synthetic cannabinoids. Three of these studies looked at the role of cannabinoids at mediating pain, two studies examined cannabinoids for treating mental illness, two studies addressed the potential safety of cannabinoids, two looked at cannabinoids as treatment options for gastrointestinal inflammation, and two studies examined the impact of cannabinoids on neurodevelopmental diseases. Other studies examined the impact of cannabinoids on cancer cell growth, anti-inflammatory activity in fibroblasts from patients with rheumatoid arthritis, regulation of matrix metalloproteases and cell proliferation, and regulation of neuroprotective genes in the brain. These various topics highlight the wide-ranging potential benefit of cannabis and cannabinoids to treat an array of human illness and disease.In a study by Moreno-Sanz and colleagues, the impact of inhaled cannabis to treat pain and anxiety was examined . The autIn addition to the Moreno-Sanz study described above, one other study examined cannabinoids in mental illness. A study by Zer-Aviv et al., found that inhibition of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) produces a stress-protective effect through activation of \u03b2-catenin in the nucleus accumbens region of the brain . The stuHajjar and colleagues examined the use of prescription and non-prescription medications in patients using medical cannabis, as self-reported by patients . The stuBacalia et al. examined the impact of CBD on intestinal inflammation, and they found that in female mice, CBD suppresses inflammation in the absence of estradiol, but it enhances inflammation in animals with estradiol . YekhtinG\u00e1ll and collaborators found that CBD increases the latency to the first seizure and decreased the mortality associated with the pentylenetetrazol (PTZ)-kindling model of epilepsy in rats . HoweverIn another study that examined the anti-inflammatory activity of cannabinoids outside of the gastrointestinal tract, Lowin et al. found that the impact of THC on inflammation in synovial fibroblasts from rheumatoid arthritis (RA) patients is dose dependent . TherefoCannabis and the potential therapeutic utility of some of these molecules to treat a number of medical conditions [Four review articles in this Special Issue summarize information on a wide array of topics related to cannabinoids. Duranti and collaborators review the current literature on the endocannabinoid system with regard to neuroprotection and neuroregeneration . The focnditions . Tudorannditions . Finallynditions .In a brief report by Sestan-Pesa et al. the authors explore the mechanism by which THC may lead to increased risk of schizophrenia, depression, and anxiety by looking at ghrelin signaling . GhrelinLicitra and colleagues performed a systematic review of the literature on cannabinoids in zebrafish . The autCannabis is a complicated plant that produces over 100 cannabinoids in addition to terpenes and flavonoids. Adding to the complexity of trying to address the mechanism of action for cannabis is the fact that the cannabinoids that have been studied have been reported to exhibit activity at a number of different receptors. This makes cannabinoids (and cannabis) a promiscuous drug. While typically viewed as a negative, promiscuous drugs do offer some advantages, most notably the ability to target different pathways of a disease with one medication [dication . The fie"} +{"text": "Editorial on the Research TopicAugmented-, virtual- and mixed reality in visceral surgeryTechniques such as Augmented Reality (AR), Virtual Reality (VR), and Mixed Reality (MR) are increasingly entering the medical workplace and, in conjunction with the field of visceral surgery, represent a potential paradigm shift that could reshape surgical strategies, training methods and patient education. For this reason, the present research topic serves to explore the interrelationship between these immersive technologies and the complex field of visceral surgery.The development of patient-specific, three-dimensional organ models using advanced imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) had enabled groundbreaking progress in this field, offering immense potential of immersive technologies in the field of visceral surgery.Enhanced by AR or embedded in a virtual environment by VR, these complex, patient-specific 3D models provide surgeons with unprecedented insight into the complexity of their patients\u2019 condition, potentially improving not only the precision of surgical planning but also providing an excellent opportunity for patient education. Furthermore, it provides surgeons, both experienced and trainee, with the unique ability to immerse themselves in immersive training scenarios that mimic real-world situations. These capabilities will allow these technologies to serve as cornerstones for the next generation of surgeons to train their skills in a risk-free environment.The collaborative nature of this research topic embodies the multi-faceted methodology essential for navigating the unexplored terrain of Extended Reality in the context of visceral surgery. This field brings together general surgeons, visceral surgeons, anatomists, biologists, and distinguished faculty members from renowned medical institutions. Their common effort is to advance the clinical, translational, and basic research that provides the foundation for these new technologies. Through the combined effect of our efforts, we aim to uncover the full spectrum of the potential of AR, VR, and MR, thereby finding solutions to both known and unforeseen challenges.Cetin et al. particularly address the utilization of a VR headset as a tool to assess the feasibility of an innovative illumination concept for the operating room. Meanwhile, Reinschl\u00fcessel et al. and Staubli et al. focus on the 3D visualization of patient-specific anatomical structures and the utilization of the generated models for preoperative planning. In addition, Pu et al. showed the possibilities of using SpyGlass in the treatment of complex pancreatic stones of the pancreatic duct.In this context, Cetin et al. describe a feasibility study regarding the utilization of automated lighting systems in the operating room. Both real-world and virtual tests were conducted to investigate the effectiveness of the automated lighting systems. The findings demonstrate that the application of automated lighting systems in the operating room presents a promising possibility for enhancing visibility during surgery and facilitating working conditions for medical personnel. In this paper, Virtual Reality assumes a central role, as a VR simulation was employed to assess the efficacy of an automated illumination system within the operating room. The VR simulation was executed on a computer, presenting an operating room-like scenario.Reinschl\u00fcessel et al. delineate in their work the utilization of VR technology for the planning of liver tumor resections. Two instances of liver tumor resections are expounded upon, wherein VR was employed for surgical planning and preparation. The authors deliberate upon the advantages and challenges relating to the application of VR technology within the domain of surgery.Staubli et al. outline a novel approach aimed at enhancing comprehension of biliary anatomy and facilitating surgical trainee education through the integration of Magnetic Resonance Cholangiopancreatography (MRCP) with VR. The authors have developed a VR application enabling users to visualize and manipulate biliary anatomy in a three-dimensional context. The application was subjected to case studies, demonstrating its capacity to augment the understanding of biliary anatomy and streamline the instructional process for surgical trainees.Pu et al. discuss the use of endoscopic retrograde cholangiopancreatography (ERCP) combined with SpyGlass technology for the treatment of pancreatic duct stones (PDS). The authors present a case study of a 54-year-old male with severe abdominal pain and pancreatic duct stones. The study emphasizes the advantages of SpyGlass-assisted ERCP, including improved visualization, accurate biopsy, and successful stone removal, particularly for complex cases.The integration of immersive technologies such as AR, VR and MR into the field of medicine, specifically within the complex field of visceral surgery, unveils a vast array of potential opportunities that have the capacity to revolutionize patient care and everyday clinical practices across almost all domains. The studies of this Research Topic serve as the initial step towards a series of upcoming research projects vividly demonstrate the range of potential applications of extended reality techniques."} +{"text": "The globalization of food trade and the emergence of disease outbreaks involving several foodborne pathogens and foods has focused the attention of both the research community and consumers on food safety. Microbial contamination can involve different stages of food processing and distribution, with a potentially dramatic impact on human health and food business. Several methods, involving culture-dependent and -independent techniques, were developed to detect foodborne pathogens in the food supply chain. In this respect, gold-standard reference methods are currently available for most pathogens, but some of them are time-consuming and expensive. Moreover, routine controls carried out by manufacturers and food safety authorities are normally focused on bacteria and not on viruses and fungi, which can have a significant impact on food safety. In the European Union, the number of human cases caused by Noroviruses and other Caliciviruses increased sharply in 2021 .w), are now known to allow the persistence of pathogens [The conditions imposed by the physical and chemical characteristics of food products, as well as by the hurdles adopted in food manufacturing, act as selective factors for the survival and the growth of pathogens . Howeverathogens . Dominanathogens ,6. Interathogens ,8. On thThe control of food-borne pathogens in food systems has evolved over time to promote the safety of food products and extend their shelf-life. The main control methods aim to inhibit the growth of foodborne pathogens by chemical and physical approaches. However, many of these methods affect the characteristics of food products, show low effectiveness over time, have a significant environmental footprint, and are not appreciated by consumers. New biocontrol methods have been proposed to maintain food appearance and acceptability, to preserve nutrients and to extend shelf-life . Among tSalmonella enterica, Campylobacter jejuni, enterohaemorrhagic Escherichia coli and Listeria monocytogenes are the most common foodborne pathogens in human cases [Aliarcobacter spp., Cronobacter spp., Vibrio spp., Clostridioides difficile, Mycobacterium paratuberculosis, Streptococcus suis, Helicobacter pylori, and Yersinia enterocolitica [Surveillance is a long- or short-term control and management measure, aimed to monitor foodborne pathogens and their socio-economic impact, which includes the systematic collection of relevant incident data, disease frequency and additional factors regarding the incidence and the spread of outbreaks . Trackinan cases ,17. HoweThis Special Issue aims to publish quality articles on the detection and control of foodborne pathogens, also considering the impact of innovative technologies and the emergence of new foodborne pathogens."} +{"text": "New England Journal of Medicine [The purpose of this perspective is to highlight potential unintended and adverse consequences of the increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in children and adolescents. We propose a set of activities suited in particular to the NIH National Center for Advancing Translational Science (NCATS) network of Clinical and Translational Science Award (CTSA) hubs to mitigate these possible threats to pediatric health. Our apprehension is heightened, ironically, because recent studies have corroborated in children and adolescents the remarkable effectiveness of the GLP-1RAs in the management of type 2 diabetes and, as satiety-enhancing medications, in obesity that had been previously demonstrated in adults. Two studies were published in the impactful Medicine . CurrentMedicine , their iA major element of our concern is that unbalanced and inappropriate reductions in caloric (energy) intake could be induced by GLP-1RA in children and adolescents. Energy in children and adolescents is expended not only on physical activity but also, unlike in adults, on growth and development. The balance of energy intake and energy expenditure influences growth and health across the lifespan. For example, with appropriate levels of exercise and diet during adolescence, bone mineralization is increased and the risk of osteoporosis and pathologic fractures much later in life is lessened . Almost Rapid development of oral-administration formulations of GLP-1RA and the proclivity among adolescents for risk-taking create aAnecdotal clinical experience of our group suggests that there is already widespread knowledge in the pediatric population about the GLP-1RA\u2019s effectiveness as satiety medication aiding weight loss, not helped by apparent widespread use documented in the popular media . Health et al. cited above in their publication on semaglutide effectiveness in pediatric obesity [Adding to our concerns about potential abuse and overuse of the new GLP-1RA medications is the increasing medicalization of pediatric conditions , many of obesity ,19. HoweWe recognize the challenges imposed by implementing truly effective lifestyle interventions in children and adolescents who are obese or suffer from frank type 2 diabetes. By the time such children or adolescents gain access to medical intervention (which is currently limited at best) or are eligible for clinical trials, the clinical trialist and primary care provider must overcome the years of poor diet, sedentary behavior, and lack of available, safe, and supportive venues for vigorous play and exercise that for the majority of these children paved the way for their conditions. In the classic 2002 NEJM study designed to prevent the transition of pre-diabetes to frank type 2 diabetes in adults [The pharmacokinetics and pharmacodynamics of certain GLP-1RAs like liraglutide have been studied in both adult and pediatric populations ; howeverBuild and support multidisciplinary teams of frontline clinicians, community partners, physiologists, and behavioral and pharmaceutical scientists to address the knowledge gap in GLP-1RA effects in children and adolescents , mandated in sixteen states covering \u223c 60% of American school children . SB-PFT Work with the FDA and other agencies to update guidelines for lifestyle interventions in pediatric clinical trials that incorporate state-of-the-art approaches to quantifying, monitoring, and evaluating physical activity, adherence to diet, and accurate measurement of body composition beyond the current reliance on the body mass index, a suboptimal metric of overweight and obesity in adolescents .Elevate and enhance training of the clinical trial workforce on state-of-the-art understanding of effective lifestyle interventions. Such training should also target primary care pediatricians whose exposure to exercise and nutritional science is currently quite limited .Develop, demonstrate, and disseminate learning modules for school personnel , parents, school-aged children, primary care pediatricians, and child mental health professionals about the GL1-RA medications, their appropriate uses, and possible abuse.The GLP-1RA class of medications will benefit children and adolescents with morbid obesity and type 2 diabetes. We also believe that their overuse and abuse are inevitable. The NCATS emphasis on the science of translation positions the network of CTSA hubs to mitigate these potential threats to child and adolescent health. Attention to real-world data, team science, community engagement, implementation and dissemination, and health disparities will be key in formulating research and policy planning. Accordingly, we propose the following elements as a call to action for CTSA hubs across the nation:"} +{"text": "This Special Issue of the journal Materials aims to gather recent advancements and novel developments in the field of finite element modeling of microstructures in composite materials. The primary focus of this Special Issue is to explore the intricate relationship between composite microstructure and its macroscopic behavior through the utilization of finite element modeling techniques. By showcasing the latest research, this Special Issue aims to enhance our understanding of the fundamental principles governing the mechanical response of composites at the microscale and their implications at the macroscale. Researchers from various disciplines are encouraged to contribute their valuable insights, methodologies, and findings, thus fostering a collaborative environment for advancing the field of microstructural modeling in composite materials.The microstructure of composite materials is incredibly intricate, encompassing the arrangement, distribution, and interaction of constituent components, such as phase materials, voids, and defects. It plays a crucial role in determining the macroscopic behavior of composites, and the relationship between microstructure and macroscopic behavior is highly complex. To investigate this relationship, various tools have been employed, including analytical analysis, mechanical testing, and numerical modeling. Among these, numerical modeling, particularly finite element simulation, offers numerous advantages. The development and refinement of finite element models for microstructures in composite materials have revolutionized virtual testing and prototyping. This approach significantly reduces the reliance on expensive and time-consuming experimental trials, making it a cost-effective and efficient tool for exploring different design configurations and optimizing composite structures. Finite element modeling excels in predicting and analyzing the failure mechanisms of composite materials. By simulating crack initiation and propagation, delamination, and other damage mechanisms, researchers can pinpoint critical regions, evaluate the structural integrity of the material, and propose strategies to enhance its durability and reliability. Leveraging finite element modeling empowers researchers and engineers to gain valuable insights into the effects of microstructure on composite behavior, enabling informed decision-making in composite material design and optimization processes.In terms of future implications, the advancements in finite element modeling of microstructures in composite materials hold immense potential for further progress. Continued developments in computational techniques, algorithms, and multiscale modeling approaches will contribute to even more accurate and efficient simulations. The integration of experimental data with modeling results will synergistically enhance predictive capabilities, resulting in more reliable and optimized composite materials.Moreover, the integration of finite element modeling with artificial intelligence and machine learning techniques opens up exciting opportunities for data-driven material design and optimization. The ability to rapidly analyze vast amounts of data, extract meaningful patterns, and generate novel microstructures with desired properties will revolutionize the field, accelerating the development of advanced composite materials.In summary, the field of finite element modeling of microstructures in composite materials is of paramount importance with far-reaching implications. Its impact extends from fundamental research to industrial applications, enabling improved material design, enhanced performance, and cost-effective solutions. The ongoing advancements in this area will undoubtedly shape the future of composite materials, driving innovation, and pushing the boundaries of their capabilities."} +{"text": "Tropical veterinary diseases remain a major global concern for the health and well-being of animals and humans. The hot-humid climate in many tropical and subtropical regions promotes the spread of diseases caused by pathogens such as viruses, bacteria, parasites, and fungi. Some of the tropical veterinary diseases include foot-and-mouth disease (FMD), hemorrhagic septicemia (HS), Newcastle disease, influenza, rabies, malaria, and dengue fever. The prevalence of tropical veterinary diseases is high in many parts of these regions, particularly in rural communities that rely on livestock for food and income.These diseases also pose risk to human health, either through direct contact with infected animals or through indirect contact with contaminated fomites, food, or water. Circumstantial factors, such as poverty, restricted access to veterinary facilities, and lack of preventative measures, have worsened the situation. The impact of these diseases can be significant, leading to economic losses for the livestock industry, and imposing severe threats to existing and future food security. To address this issue, effective control and prevention strategies, such as awareness of tropical veterinary diseases among the various stakeholders, improved biosecurity measures, strengthened veterinary services in affected areas, improved innovative technologies by incorporating surveillance AI in diagnostic tools, and sustainable vaccine programs, must be implemented. Nevertheless, there is still much work to be done to effectively address the situation, and ongoing research and strategic collaboration from affected countries are crucially needed.The advancement of modern biotechnology, including molecular biology techniques, has significantly contributed to the understanding of the pathogenesis of infectious diseases, specifically tropical veterinary diseases. Molecular pathogenesis research includes the study of the molecular mechanisms underlying the development and progression of a disease, and it has become a critical tool in the control and prevention of diseases. With this, it is possible to study host\u2013pathogen interactions and host immune responses, develop new vaccines and treatments, and improve monitoring and surveillance. For instance, molecular pathogenesis research has led to the discovery of new vaccine targets, the development of novel vaccine platforms, and the identification of new drug targets for the treatment of these diseases.Iurescia et al. conducted a multidisciplinary study to understand the cause of death of captive African penguins (Spheniscus demersus) infected by avian malaria. The approach includes pathological examinations of the penguins' tissues, molecular characterization of the Plasmodium species and lineages, and mosquito surveillance. The investigation reveals that P. matutinum was responsible for the deaths, and Culex pipiens mosquito, which is present in the region, was involved in the transmission of the disease. The study provides important information about the cause of death and highlights the importance of monitoring and preventing the spread of avian malaria in captive populations of African penguins.In captive bird populations, such as in zoos, the presence of mosquitoes and other vectors can facilitate the transmission of avian malaria, leading to outbreaks of the disease. In this collection, Wardhani et al. investigated the presence of viral neuropathogens in the brains of rabies-negative cats and dogs that were submitted to the Thai Red Cross Society (TRCS) with neurological signs before death. Based on the selective viral molecular screening, the study found that various viral neuropathogens were detected, including carnivore protoparvovirus-1 (CPPV-1) [canine parvovirus (CPV) and feline parvovirus (FPV)], feline calicivirus (FCV), feline bocavirus (FBoV), feline alphaherpesvirus-1 (FeHV-1), and canine distemper virus (CDV). Immunohistochemistry was also employed to further investigate the localization of each viral pathogen. The results revealed that CPPV-1 was present in most of the brain samples, which may have contributed to the neurological signs observed in the animals. The study highlights the importance of considering other viral pathogens in addition to rabies in the diagnosis of neurological diseases in animals.Moreover, Huang et al. elucidated the role of a specific amino acid in the non-structural protein 1 (NS1) on the virulence of the H5N6 influenza A virus (IAV). The study analyzed the pathogenicity of the H5N6 IAV strains isolate A/duck/Hubei/WH18/2015 (JX) and A/chicken/Hubei/XG18/2015 (XGD) in mice. Accordingly, the JX strain was more virulent than the XGD strain with substantial weight loss, severe damage to the lungs and heart, and increased lethality being observed in infected mice. Moreover, the pathogenicity of recombinant viruses demonstrated that 139D mutation in the NS1 could potentially have an impact on the virulence of the JX strain in mice. This study highlights that the amino acid 139D is significant for the virulence of the virus in mice and could serve as a marker for identifying different variants of the influenza virus.Liu et al., differentially expressed circular RNAs (circRNAs) were identified in various liver cells, including hepatic stellate cells (HSCs), hepatocytes (HCs), and Kupffer cells (KCs), after infection with the Echinococcus multilocularis parasite. The findings were validated using quantitative real-time polymerase chain reaction (qRT-PCR) on a selected set of circRNAs. The study also aimed to explore the circRNA\u2013microRNA\u2013mRNA network in these cells during the infection. The result found that the expression of certain circRNAs in the liver cells was changed after infection and that some of the circRNAs had a role in regulating the expression of microRNAs and mRNAs, which in turn play a role in the host response to the parasite. The study highlights the importance of understanding the role of circRNAs in the host response to parasitic infections, which may provide insights into the development of new therapeutic strategies.In recent years, the expression of circular RNAs (circRNAs) has been extensively studied especially for its biological functions in human cells. In the study reported by Macrobrachium rosenbergii, is highly exported and one of the most economically important seafood in Asia. Zhuo et al. analyzed the complete genome of highly pathogenic non-O1/O139 Vibrio cholerae strain GXFL1-4, isolated from freshwater prawn, Macrobrachium rosenbergii. The study identified the genes that contribute to the pathogenicity and antibiotic resistance of this strain. Based on the prediction, the genome contained multiple genes associated with pathogenicities, such as those involved in motility, adhesion, and toxin production. Multiple antibiotic-resistant genes, including kanamycin, ampicillin, tetracycline, aminoglycosides, and beta-lactams, were identified. The study provides valuable insights into the genetics of this strain of V. cholerae and highlights the presence of genes associated with pathogenicity and antibiotic resistance. The findings may aid in the development of more effective control and mitigation strategies for the disease.The giant river prawn, Wu et al. investigated integrated vector surveillance in Zhejiang Province, China, in 2020, to monitor the occurrence of tropical vector-borne diseases (VBDs). The aim was to identify potential vectors of VBDs, as well as investigate the pathogen infection rates among arthropod vectors and reservoir hosts, including mosquitoes, rodents, ticks, and chigger mites. A pathogen infection survey on mosquitoes and rodents and a drug resistance survey on Aedes albopictus were conducted. The survey demonstrated that the primary vectors of tropical VBDs in the region were mosquitoes and ticks and that the pathogens and reservoir hosts were present in certain areas of the province. The study highlights the importance of integrated vector surveillance programs in the early detection and control of tropical vector-borne diseases.In terms of surveillance in tropical veterinary diseases, Thus, the study of molecular pathogenesis plays a crucial role in enhancing the understanding of tropical veterinary diseases and developing new strategies for control and prevention. Studying the molecular basis of diseases helps in developing more accurate diagnostic methods, effective treatments, and strategies for disease prevention, leading to improved health and wellbeing of animals and humans in tropical regions. This collection will be beneficial in adding an in-depth insight into the molecular pathogenesis of tropical veterinary diseases.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "The neuro-developmental deficits of Attention-Deficit Hyperactivity Disorder (ADHD) including decreased attention span, hyperactivity, distractibility, and impulsivity are frequently observed in children, adolescents and adults with a range of conditions , Cochran et al. report (n = 734), contrary to previous studies, that maternal smoking during pregnancy and pregnancy associated hypertension are did not predict ADHD at 10 and/or 15 years.In the ELGAN Study sample of children born at extremely low gestational age , more than double the prevalence of ADHD in otherwise healthy pediatric populations, highlighting that the negative influence on neuropsychiatric functioning likely begins sooner in the disease course than previously anticipated. The authors propose these findings are of large practical importance as ADHD symptoms are likely to impact routine everyday decisions crucial for diabetes management .Several studies in this issue describe specific aspects of ADHD and ADHD \u201csymptoms\u201d in chronic pediatric conditions. Duquette et al. describe ADHD in children with Chronic Kidney Disease (CKD). Although the sample size was small, results from the current study provide some of the most comprehensive findings to date on the differential attention functioning of children with CKD. Taken together, these findings suggest the existence of specific types of attention dysfunction, particularly in the focus/execute, sustain, and encoding, components of attention .Uliel-Sibony et al. provide a comprehensive literature review of the common co-occurrence of ADHD and epilepsy, and describe the latest research regarding possible etiologies explaining the common co-occurrence. This review looks at the influence of medications on both disorders and the recommended treatment approaches in accordance with the latest literature .Sabag and Geva provide a neurobiological perspective on the very significant comorbidity of attention in autism spectrum disorder (ASD), describing the framework of attention network activation in ASD, and suggesting that this neurobiological perspective be considered for further investigation in naturalistic settings.Slobodin and Davidovitch highlight the associations and differences between children's self-reports, parents' and teachers' reports, and standardized continuous performance test (CPT) data, and discuss the clinical and ethical imperative of taking children's perspectives into account during ADHD diagnosis and treatment.Dakwar-Kawar et al. providing initial support for the efficacy of this combined method in improving processing speed in the presence of mental fatigue in pediatric ADHD.Novel treatment approach of trans-cranial electric stimulation combined with cognitive training is described by Dutta et al. complete the series with a bottom-up holistic approach to the psychopharmacology of ADHD in the context of recent models of attention and suggest that future studies are greatly needed to better appreciate the interactions among an ADHD diagnosis, stimulant treatment across the lifespan, and structure-function alterations in the aging brain.We hope this Research Topic will update our readers on both research and clinical aspects of ADHD.IB, AL, and YL conceptualized and conducted the project, collected the study data, drafted the manuscript, and reviewed the final manuscript. All authors have read and approved the final manuscript."} +{"text": "Frontiers in Nutrition Research Topic aimed to address various issues related to the robustness of nutritional science, from methodological issues with field-specific research and counseling, to managing conflict of interest and problems with scientific decision making in public health nutrition. Our Research Topic gathered 30 authors from North America, Europe and Asia that provided a mix of original research, review and perspective papers that timely suit co-editors invitation, exploring topics in nutritional epidemiology, food policy and economics, and nutritional methodology. Addressing the aforementioned topics holds the potential to fortify evidence-based knowledge within the realm of human nutrition as a scientific field, and perhaps pave the way for the establishment of elevated scientific standards and a heightened sense of public responsibility, echoing the sentiments expressed by Ioannidis delved into the international research landscape of the past decade concerning vitamin D and its implications on reproductive health. The researchers meticulously analyzed over 1,800 articles and reviews, revealing a significant diversity in terms of represented subdisciplines, authors' backgrounds, research frontiers, and the quality of peer-reviewed journals where these papers were disseminated. While the field of study has garnered substantial global attention, it has displayed an uneven progression, marked by multidisciplinary research hotspots primarily focusing on risk factors and detrimental consequences of vitamin D deficiency. Nevertheless, the report emphasizes the need for more robust investigations. Specifically, it suggests delving into the heterogeneity of vitamin D deficiency across populations, enhancing the utility of vitamin D-related biomarkers, and adopting a mechanistic approach to scrutinize the effects of vitamin D on health indicators. This significant report reiterates the call for the design of more comprehensive cause-and-effect studies within the realm of nutritional sciences. Furthermore, it underscores the importance of embracing personalized approaches, aligning with previous views of Bassaganya-Riera et al. . Through collaborative efforts involving federal and public stakeholders, as well as expert groups, and the meticulous execution of systematic reviews, NESR has emerged as a pivotal initiative in informing evidence-based decisions by the U.S. government concerning public health nutrition. This encompasses pivotal contributions to the development of the Dietary Guidelines for Americans. The article also underscores the imperative need for other organizations to contemplate adopting a similar approach, perhaps modeled after NESR, to ensure a collaborative process that adeptly addresses potential or perceived conflicts of interest among all stakeholders involved.Another review article within this Research Topic look into the systematic review process of the U.S. Department of Agriculture's Nutrition Evidence Systematic Review Branch (NESR), exemplifying the utilization of a diverse range of expertise and experiences while effectively managing potential conflicts of interest and randomized-controlled trials may offer a more favorable strategy for generating pertinent insights into the intricate interplay between nutrition and health.A thought-provoking perspective article by Ko et al. investigated the reliability and validity of the Korean version of the Children's Eating Behavior Questionnaire (K-CEBQ) for children with anorexia. This parent-reported measure is designed to assess variations in eating style, and the researchers conducted two rounds of the study, surveying over 350 participants online. They demonstrated good internal consistency reliability and temporal stability of the K-CEBQ, indicating its reliability for assessing the eating behavior of children with this eating disorder. The paper also calculated the optimal cut-off values for the two category scores of the K-CEBQ, food approach and food avoidance. This provides a practical tool for healthcare professionals that could aid in diagnosing children with anorexia and assessing their treatment progress. The article emphasizes the need for future studies to consider other confounding factors (besides age and gender) that may influence anorexia features in children.Finally, a research paper by The current Research Topic offers a comprehensive overview of advancements in the realm of scientific integrity within nutritional research, advocating for a robust and practical approach from both clinical and public health standpoints. By adopting optimal strategies for research data generation and analysis, while also embracing a personalized approach such as precision nutrition, and considering diverse diet-specific neuro-psychological factors, the field can be revitalized. This rejuvenation holds the potential to bolster public policy, shed light on the broader population, and ultimately contribute to a more informed and healthier society.SO: Writing\u2014original draft. N\u00d8: Writing\u2014review & editing."} +{"text": "The medical care costs for procedures, medications, and testing associated with atrial fibrillation (AF) in the United States are high and projected to increase markedly in the future as the number of Americans affected grows. The burden on patient quality of life, the health care system,and society are pharmacoeconomic considerations in managing AF.To identify key pharmacoeconomic considerations in managingAF and describe ways in which managed care pharmacists can improve the cost-effectiveness of and outcomes from drug therapy for AF.The high medical care costs of AF are largely the result of the high cost of hospitalization and inpatient procedures. Recurrence of AF dramatically increases costs, especially for hospital care.Managed care pharmacists have many opportunities to provide cost effective care to and improve outcomes in patients with AF. Policy and process review, population management, and case management are key strategies for improving outcomes in patients with AF. Pharmacist input into policy and process review, including pharmacy benefits design, formulary management, and the use of information technology, can help ensure that the use of drug therapy for AF is cost-effective. Population management strategies, such as development of clinical pathways and patient registries,seek to improve the quality, consistency, and cost-effectiveness of care and the likelihood that desired therapeutic outcomes are achieved through targeted interventions. Case management strategies focus on longitudinal care for individuals in order to improve quality. Pharmacist-managed anticoagulation services and antiarrhythmic drug monitoring are the 2 most widely known case management strategies for patients with AF. Managed care pharmacists can screen patients with AF for the use of anticoagulation,which is needed to prevent embolic stroke but is under-used, even though recommended by evidence-based guidelines. The clinical efficacy and cost-effectiveness of pharmacist-managed anticoagulation services forpatients with AF are well documented. Pharmacist-managed antiarrhythmic drug monitoring is a less well-known case management strategy that facilitates early detection and intervention to minimize toxicity.Managed care pharmacists can play an instrumental role in implementing strategies to improve the cost-effectiveness of and outcomes from drug therapy for AF."} +{"text": "The purpose of this paper is to describe NASA\u2019s approach to establishing and maintaining a set of Agency-level Space Flight Human System Standards managed by the Office of the Chief Health and Medical Officer (OCHMO) at NASA that enables space flight missions by minimizing health risks to astronauts, providing vehicle design parameters, and supporting the performance of both flight and ground crews. NASA standards capture and provide knowledge, guidelines, thresholds and limits for the successful design and operation of spacecrafts and missions. The NASA Space Flight Human-System Standard (NASA-STD-3001) consists of two separate volumes of technical requirements: NASA-STD-3001 Volume 1: Crew Health addresses the requirements needed to support astronaut health and provide medical care; NASA-STD-3001 Volume 2: Human Factors, Habitability, and Environmental Health addresses human-integrated vehicle system design and operational requirements that will maintain astronaut safety and promote human performance. These standards are managed by an OCHMO team who continuously works with national and international subject matter experts and with each space flight program to provide the best technical requirements and implementation documentation to support the development of new programs. Through partnerships across the space flight industry, these technical requirements are constantly evolving to enable successful implementation of NASA programs and the commercialization of human space flight. These primary hazards include:4, the impact of radiation on pharmaceuticals and food should be minimal, but additional research is being conducted to fully assess the impact6. Sources of increased radiation exposure include galactic cosmic rays, solar particle events, and onboard radioactive technologies. Vehicle design and engineering can provide a certain level of protection to crewmembers from radiation exposure, however not all types of radiation can be shielded from, and crewmembers are invariably exposed to higher levels of radiation during spaceflight compared to on Earth. Reference Radiation Protection NASA OCHMO Technical Brief for additional information7.Radiation Exposure: Outside of Earth\u2019s natural protection, radiation exposure is abundant in space. Crew exposure to the space radiation environment may pose health risks including the risk of neoplasm, damage to the central nervous system, altered cognitive functioning, reduced motor functioning, and acute behavioral changes. In addition, based on analysis and limited data from the International Space StationAcceleration, Acoustics, Artemis Lighting, Cabin Architecture, Carbon Dioxide, Decompression Sickness (DCS), Environmental Control and Life Support System (ECLSS), Food and Nutrition, Electrical Shock, Lighting Design, Sleep Accommodations, Vehicle Hatches, Waste Management, and Water NASA OCHMO Technical Briefs for additional information21.Hostile/Closed Environment: Spacefaring humans must depend on an enclosed vehicle to survive, which involves inherent risks due to engineering . The habitability of the spacecraft is imperative for astronaut health and safety. The spacecraft must also provide astronauts the essential elements they require to live and work in space, including food, body waste management, sleep accommodations, and exercise. Reference Behavioral Health and Performance, Behavioral Health Mishaps, Cognitive Workload, Usability, Workload, Error, and Sleep Accommodations NASA OCHMO Technical Briefs for additional information25.Isolation and Confinement: Crewmembers live and work within a small, enclosed environment with other crewmembers for extended periods of time during space flight. Even with careful selection of crewmembers and extensive training, interpersonal and behavioral health issues within the crew are expected. Workload considerations, circadian desynchronization and sleep disturbances, and lack of communication with Earth all play a role in potential performance decrements, negative health outcomes, and potentially loss of mission objectives. NASA has developed several methods to monitor crewmembers\u2019 behavioral health status during space flight and developed tools and technology to identify potential issues earlier and provide the appropriate treatment or intervention. Reference Spaceflight Experience and Medical Care Technical Brief26.Distance from Earth: As the future of space travel moves toward longer-duration missions beyond lower-Earth Orbit to the Lunar surface and Mars, distance from Earth will become one of the biggest obstacles of safe and productive human space flight. Lack of resupply vehicles, communication delays, potential medical emergencies, and equipment failures are just some of the obstacles that astronauts will face during future space flight missions. Reference Principles of Clinical Medicine for Space Flight27 for a comprehensive review of the human systems affected by space flight and microgravity. Appropriate countermeasures and interventions are imperative to keep crewmembers healthy, safe, and performing at their highest potential. Reference Bone Loss, Spaceflight Experience and Medical Care, and Pharmaceuticals and Medications NASA OCHMO Technical Briefs for additional information29.Altered Gravity Environment: The experience of astronauts transitioning from one gravitational field to another introduces a host of considerations for crew health, safety, and performance. Future missions will involve several changes in the gravity environment, thus operational parameters must implement all strategies available to mitigate these decrements as much as possible. In addition, humans living and working in space for extended periods of time leads to many health complications that makes returning to Earth\u2019s gravitational environment difficult. Changes to bones, muscles, eyes , and the cardiovascular system are just some of the problems that astronauts deal with when returning from space flight. Reference There are five primary hazards of space flightWhen combined, these five hazards of space flight create a complicated landscape and impact the ability to support the health, safety, and optimal performance of space flight crews. In addition, as mission duration lengths increase with a greater focus on deep space exploration, these hazards become even more important to address in order to enable the future of space travel.30. The Human System Risk Board (HSRB) was created to implement this process by the NASA Health and Medical Technical Authority. Its responsibility includes implementing a consistent process of gathering and assessing evidence, providing a likelihood and consequence of the risks, and in turn providing recommendations to updating the NASA-STD-3001 documents so that the set of technical requirements remains up to date with the most current knowledge.Over the past 50+ years of human space flight, NASA has collected an evidence base of medical, environmental and research data on the effects of space flight on the human body. However, even with years of collected data, NASA has a relatively small population of flown astronauts, making it difficult to fully understand the effects of space flight hazards. In order to address this difficulty, NASA implemented a new cross-discipline process to understand the hazards of space flight and gather, assess, and correlate evidence to better predict the probability of an event occurring and the level of consequence the event would have on human health and productivity. This strategy provides the ability to weigh the risks relative to each other and leads to effective tradeoffs to ensure maximal mission success with the least risk to human health31. It was first adopted by the International Space Station Program (ISSP) and written primarily for the International Space Station (ISS) infrastructure. As time passed and the development of new programs with needs separate from the ISS emerged, an updated set of standards with broader applicability was needed to replace NASA-STD-3000. Driving reasons behind this update included the fact that the original standard was too comprehensive, was too focused on design solutions, and raised questions on the verifiability of some technical requirements. After a second variation of NASA-STD-3000 and an accompanying handbook were created32, NASA-STD-3001 was baselined and implemented in 2009 by the NASA OCHMO. These standards are applicable to all human space flight programs and projects, enabling the creation of human-centered program-specific technical requirements. Each technical requirement within these documents includes a \u2018shall\u2019 statement that must be considered in the development of a program-specific set of human-systems design requirements. Technical requirements include rationales which provide additional information and justification for the purpose of the technical requirement, as well as some potential guidance on how to verify the technical requirements being met. Figure The first set of space flight human system standards was baselined Agency-wide in late 1980s and was known as NASA-STD-3000: Man-System Integration Standards (MSIS)Volume 1 of NASA-STD-3001 focuses on human physiological functioning and views the human system as an important part of the overall vehicle design process and mission design. It sets the standards for fitness for duty, space permissible exposure limits, permissible outcome limits, medical care, medical diagnosis, intervention, treatment and care, and countermeasures. Aerospace medicine is deeply rooted in preventive care in addition to being prepared to respond to known physiological and psychological challenges of space flight, as well as unexpected injury and illnesses that could impact crewmembers during their career as an astronaut. Volume 1 seeks to address this comprehensive approach through screening, preventive healthcare strategies, medical care, launch and landing contingencies, and post-mission care, reconditioning, and long-term monitoring. NASA-STD-3001 Volume 1 contains 72 technical requirements as of Revision B published in 2022 that are levied against all human-integrated space flight programs. Table Volume 2 of NASA-STD-3001 focuses on human-systems integration, including human physical and cognitive capabilities and limitations, and defines requirements for spacecrafts , internal environments, ground processing, facilities, payloads, and related requirement, hardware, and software systems. These include requirements to the design of systems that directly interface with the flight crew such as environmental support systems, architecture, controls and displays, and operations, as well as requirements for the design of systems that both ground and/or flight crew access during assembly, test, checkout, or troubleshooting procedures supporting ground processing, launch, landing, and recovery operations. NASA-STD-3001 Volume 2 contains 471 technical requirements as of Revision C published in 2022 that are levied against all human space systems and must be tailored for each individual system to ensure that the end product meets all the requirements. Table Each individual NASA program that will include human-rated systems must implement NASA-STD-3001 in the development of their specific program requirements. The program is responsible for reviewing the set of standards, identifying the technical requirements that are applicable to their specific program/design reference mission, and tailoring the standards into detailed requirements to be implemented in the program. In addition, the programs must provide verification information which details the program\u2019s plan to verify that their requirements are meeting their intent. Examples of a tailored 3001 technical requirement to program requirement and its related verification language is provided in Fig. 33 was developed to provide a tool to determine how individual technical requirements impact future missions and programs. It provides the ability to look \u201cacross\u201d all of the technical requirements and assess their impact on a mission\u2019s success in relation to loss of crew, loss of mission, and loss of mission objectives. The pyramid is broken down into six levels, with the base representing the most fundamental system needs (both vehicle and human) and the top-level representing optimization of human and mission performance. This hierarchy is useful in determining the applicability of technical requirements for programs during the formulation stage of development. The pyramid also helps to categorize technical requirements that increase the probability of achieving mission objectives.During the early formulation stage of a program, it is helpful to assess the cross-relationship of standards and how they impact specific missions and programs. The Human Space Flight Standards Hierarchy Fig. 33 was de32 is a companion document designed to accompany NASA-STD-3001 Volume 2. It includes information specific to human space flight history and lessons learned, design information, reference data and background information, and application guidance for the wide variety of disciplines and topic areas covered by NASA-STD-3001. The main purpose of the HIDH is to help requirements writers prepare program-specific human requirements and to help designers develop designs and operations for human interfaces in spacecrafts. The scope of the handbook encompasses all crew operations both inside and outside spacecrafts in space and on Lunar or planetary surfaces. It includes design guidelines for crew interfaces with workstations, architecture, habitation facilities, extravehicular activity (EVA) systems; information describing crew human capabilities and limitations ; and environmental support parameters. The potential users of the HIDH include program managers, program/system requirements writers, human factors practitioners, engineers and designers, crews and mission/flight controllers, and training and operations developers.The Human Integration Design Handbook (HIDH)34 that cover a range of topics. Each technical brief includes information regarding technical data, background, reference information, and application notes to aid with the development of hardware, systems, and vehicles, as well as human needs and limitations. This information is used by vehicle developers, program requirement writers, and medical professionals. These technical briefs integrate content from multiple technical requirements and provide a quick, informative resource to reference when working with NASA-STD-3001. Currently, there are 31 published human space flight technical briefs with additional topics being added on a regular basis. Stakeholders, NASA SMEs, and other potential users are encouraged to submit their ideas for future technical brief topics that would be informative and useful for ongoing work.The OCHMO 3001 Standards Team has developed a repository of human space flight technical briefsNASA Subject Matter Experts (SMEs) are invaluable resources for ensuring that current technical requirements include relevant and important content for each individual area of interest, utilizing the expertize and experience of the SMEs to provide the best available information to form new and update existing technical requirements.Human System Risk Board (HSRB) as described previously, helps to inform the standards through regular reviews of identified space flight human health risks which includes an overview of the related technical requirements and potential recommendations to update those technical requirements to address any changes or concerns regarding each specific risk.35. The results from HRP\u2019s research and findings helps to inform the technical requirements and provide important updates using new and updated knowledge,NASA Human Research Program (HRP) is a program dedicated to conducting ongoing space flight research in many facets of human space travel and includes five elements: the International Space Station Medical Projects, Space Radiation, Human Health Countermeasures, Exploration Medical Capability, and Human Factors and Behavioral PerformanceThe NASA-STD-3001 documents are reviewed and updated in a continuous cycle in order to keep the technical requirements current and up-to-date with the latest knowledge and guidance. Potential updates and recommendations for the technical requirements are identified through several different avenues, which include but are not limited to:The process for updating the NASA-STD-3001 documents and related handbooks includes a specific set of steps to be followed to ensure consistent and accurately documented changes to the standards. Figure The future of NASA and human space flight is undergoing significant changes, with the landscape of space travel and exploration turning toward longer-duration missions on the Lunar surface and eventual deep space to Mars. In addition, commercial partners have become the primary contributors to supporting ongoing human space travel and thus it is imperative to consider their role in the future of space flight. The NASA-STD-3001 documents are invaluable resources for the evolving space flight environment, providing commercial partners with the necessary knowledge and guidance to enable safe and effective human space travel. In addition, lessons learned and feedback from previous programs development activities and operations helps to inform future programs on how to appropriately integrate the 3001 technical requirements to achieve their goals and objectives and overall mission success."} +{"text": "There is a wide range of renewable materials with attractive prospects for the development of green technologies for the removal and recovery of metals from aqueous streams. A special category among them are natural fibers of biological origin, which combine remarkable biosorption properties with the adaptability of useful forms for cleanup and recycling purposes. To support the efficient exploitation of these advantages, this article reviews the current state of research on the potential and real applications of natural cellulosic and protein fibers as biosorbents for the sequestration of metals from aqueous solutions. The discussion on the scientific literature reports is made in sections that consider the classification and characterization of natural fibers and the analysis of performances of lignocellulosic biofibers and wool, silk, and human hair waste fibers to the metal uptake from diluted aqueous solutions. Finally, future research directions are recommended. Compared to other reviews, this work debates, systematizes, and correlates the available data on the metal biosorption on plant and protein biofibers, under non-competitive and competitive conditions, from synthetic, simulated, and real solutions, providing a deep insight into the biosorbents based on both types of eco-friendly fibers. Natural cellulosic (plant) and protein fibers from biological sources (biofibers) are remarkable for their renewability, biodegradability, variety, variability, carbon dioxide neutrality, and recyclability. They fold very well on the coordinates of sustainability, which is one of the most challenging goals of today\u2019s society. With an anticipated annual production of around 40 million tons per year by the middle of the 21st century [Biofibers have historically been used to produce textiles, ropes, carpets, fabrics, and wires . Today, Among the common methods for the removal of toxic metal ions from aqueous media, adsorption occupies a prominent position ,18,19,20The published reviews are either specifically devoted to biofibers and their sources for the adsorption of pollutants in water purification, or cover multifaceted applications of some natural fibers, of which those related to pollution control and remediation are briefly addressed . DespiteThe originality and novelty of this work is that it connects, for the first time, the information on the biosorption capabilities of both cellulosic and protein natural fibers for the removal and recovery of both toxic and valuable metals from diluted aqueous solutions. In addition to its integrative nature, this article is distinguished from the other reviews by the following elements: (i) focus on the ways in which the biosorption activity of natural fibers is affected by industrial competitive conditions; (ii) discussions and comparisons, from two different perspectives, namely natural plant and animal fibers as potential and practical biosorbents for metal uptake. After an overview on biofiber classification and properties, the major debated issues concern: (i) plant natural fibers for metal biosorption from mono- and multi-component aqueous synthetic solutions; (ii) protein natural fibers for metal sequestration from mono-metallic and poly-metallic synthetic solutions; and (iii) practical applications of metal biosorption on natural fibers to real solutions for decontamination and recycling goals.Given the wide range of green fibers, this article will be inevitably incomplete, but its aim is to provide a comparative analysis on practical coordinates, that will be helpful to guide and promote sustainable approaches based on natural fibers in the separation and recovery processes of metals.Biofibers, which are the predominant class of natural fibers can be described as polymeric materials of biological origin that are intact, thin, long, and easily bendable to form an elongated tissue . DependiNatural vegetable fibers originating from more than 2000 kinds of plants worldwide consist mainly of cellulose, hemicellulose, and lignin and are also known as lignocellulosic fibers . As can Bombyx mori.The second group of natural fibers includes animal fibers consisting of proteins (keratins). According to Natural plant and animal fibers possess a variety of properties of physical, chemical, mechanical, electrical, thermal, biological, optical, acoustic, or ecological nature, which make them very attractive biomaterials . The oveNatural fibers are characterized by their environmental friendliness, worldwide occurrence, low cost, air permeability, low abrasiveness, tunability, and low energy consumption, and have intermediate mechanical properties and higher moisture and temperature sensitivity than synthetic fibers . The maiThe presence of keratins, which are more sensitive to chemical attack and harsh environmental conditions than cellulose, weakens the properties of natural fibers of animal origin . Thus, cBiosorption is an environmentally friendly process of metal separation from a liquid phase as a result of its retention via physical and chemical bonds on a bio-based material (biosorbent) ,25. The As with all biosorbents, the most important property controlling the biosorption capability of natural fibers is their unique surface functionality with high reactivity. The uptake of metal ions on plant biofibers is due to the surface active functional groups, such as the carboxylic groups of hemicelluloses and lignin, the hydroxyl groups in cellulose, hemicelluloses, and lignin, the phenolic groups of lignin, and the carbonyl groups of hemicelluloses . The bioThe surface properties summarized in In addition, because of the remarkable ability of natural raw fibers to be subjected to various treatments, the improvement in the surface properties such as those listed in The successful use of fibers from renewable resources as biofilters for the biosorptive separation of metals depends on the extent to which they meet specific requirements expressed as high biosorption capacity, satisfactory selectivity at different concentrations, high efficiency in sequential or simultaneous removal of toxic metal ions, favorable kinetics, good stability, recyclability, and adaptability to different designs (batch and fixed bed column systems of biosorption) and environmental conditions ,30,32.From this point of view, batch equilibrium and kinetic studies provided most of the knowledge on the removal properties of natural fibers, such as the maximum capacity of metal biosorption and the biosorption rate. These involve immersing a suitable mass of biofibers in a known volume of a synthetic aqueous solution until equilibrium is reached, whereupon the phases are separated . Figure Hibiscus Canabicus kenaf fibers [Additionally, for practical purposes, the information provided by fixed bed column studies is much more relevant and useful. In fixed bed biosorption methods, which can be used to the treatment of large sample volumes, the aqueous metal solution flows continuously at a defined flow rate through a column filled with a given amount of biosorbent . Howeverf fibers , and woof fibers can be mLike all lignocellulosic biomasses, natural plant fibers proposed as biosorbents for the metal removal from mono-component synthetic aqueous solutions often showed performances very close to those of ion exchange resins . Their bLuffa cylindrica fibers [a fibers , okra fia fibers ,166, or a fibers ,168 modia fibers . The moda fibers .2O3 was reported to occur by electrostatic attraction and ligand exchange [Data analysis showed that the mechanism of the biosorption process of metal ions from mono-contaminated model solutions on untreated and modified forms of lignocellulosic fibers is complicated due to the involvement of a variety of cellulosic and non-cellulosic functional groups. At the same time, it is obvious that much research is still needed for a comprehensive understanding. Most proposed mechanisms are based on single or combined chemical interactions, such as ion exchange, electrostatic interactions, complexation, coordination/chelation, acid-base interactions, and precipitation. The dominance of ion exchange was highlighted for the mechanism of biosorption of Cu(II), Pb(II), and Zn(II) on flax fibers , retentiexchange .The strength of the bonds between the metal ions and the natural lignocellulosic fibers was also confirmed by desorption studies ,176,177.Research on the effects of the coexisting ions on the removal performance of the natural plant fibers is not very productive. The most addressed issues relate to the influence of the type, number, and initial concentration of the foreign ions on competitive biosorption. In this context, the studies published so far have mainly investigated the effects of bi-valent heavy metal ions ,198,199,3 [Pejic and coworkers reported efficiencies of 93.01%, 43.9%, and 43.84% for the removal of Pb(II), Cd(II), and Zn(II) from a multi-ionic solution containing Pb(II) (0.2 mmol/L), Cd(II) (0.2 mmol/L), and Zn(II) (0.2 mmol/L) by biosorption on hemp fibers modified with sodium chlorite, which showed almost the same uptake capacity for Pb(II) under competitive and non-competitive conditions . It was 3 . The pap3 . The max3 . Despite3 .Ficus carica fibers was unaffected by the presence of Na+, Cl\u2212, and SO42\u2212, decreased under the condition of Ca(II) and Mg(II) coexisting cations, and increased in the presence of HCO3\u2212 anions [3\u2212 and ClO4\u2212 anions [The reported slight decreases in the maximum biosorption capacity of carboxyl modified jute fibers for Pb(II), Cd(II), and Cu(II) in the presence of Na(I), K(I), Ca(II), and Mg(II) ions were correlated with the increase in light metal ion concentration from 0 to 500 mg/L . Gupta a\u2212 anions . The neg\u2212 anions . The cha\u2212 anions .It is worth mentioning recent works confirming the selective and advanced biosorption of U(VI) on some new biosorbents based on hemp fibers under the conditions of simulated seawaters. Thus, by using polyethylenimine and guanidinyl functionalized hemp fibers, an efficiency of more than 85% was achieved in the removal of U(VI) from artificial seawater with multiple coexisting ions and low initial uranium concentration (3.05\u201399.03 \u00b5g/L) . The neaAs can be seen from the above considerations, the consonant conclusion of all the studies is that the biosorbents based on natural plant fibers have a low biosorption capacity for the coexisting ions under competitive conditions, while they retain a pronounced affinity and selectivity for the metal ions of interest for removal and recovery.In contrast to lignocellulosic biofibers, information on the use of natural fibers of animal origin as biosorbents for water detoxification are scarce and mainly refers to wool, silk, and human hair. This limitation has been justified by the inferior kinetic properties and lower capacity of biosorption of protein biofibers compared to biosorbents based on polysaccharides . However-wool powder and oxidized wool powder performed better than waste wool fibers in biosorption of Cu(II) and Zn(II) from mono-component synthetic aqueous solutions, the optimum pH being 6 ;-Bombyx mori silk > wool order was determined for Co(II) uptake on different untreated protein fibers [tussah silk > n fibers ;-the removal efficiencies of some powdered biosorbents have shown the trends: silk powder > wool powder > cashmere guard hair powder and cashmere guard hair powder > wool powder > silk powder versus Zn(II) and Cr(VI), respectively ;-the efficiency of biosorption of Pb(II) from aqueous solutions with pH = 5.8 on human hair, goat hair and sheep wool has reached the highest value (33 mg/g) on human hair .Most biosorption studies have been conducted on one of the aforementioned biofibers, in the form of loose fibers, powder, or non-woven fabrics. Although accurate comparative analyses are sporadic, given their practical relevance to the selection of the most suitable biosorbent, the following ascertainments should be introduced:Against this background and taking into account the specifics of the properties of the individual fiber types, the metal removal and desorption properties of wool fibers, silk fibers, and human hair waste are discussed separately below.The most targeted protein fibers are wool fibers, through studies mainly concerned with the behavior of low quality native wool, wool waste from industrial processes, and recycled woolen textiles in the biosorption of heavy metal ions , Cd(II), Zn(II), and Cr(III)) from mono-metal synthetic aqueous solutions with initial metal concentrations below 10 mmol/L. As in the case of plant biofibers, the Langmuir isotherm model and the pseudo-second order kinetic model are the optimal solutions for the description of the metal uptake on wool fibers. The significant results of these works are presented in S. aureus and E. coli), anaerobic and sulfate-reducing bacteria, and C. albicans fungus [2 particles have been described as a precursor of a new class of biosorbents for recycling U(VI) from seawater.The focus was to find the best treatment method to improve the biosorption properties of wool fibers. To achieve this goal, wool fibers recommended as potential materials for wastewater treatment were often modified by the irradiation with accelerated electron-beam and graft copolymerization. The significant increase in metal uptake on electron irradiated wool compared to non-irradiated wool is strons fungus . With a s fungus , amidoxiTo obtain a complete picture, the promising desorption properties of some wool biosorbents are described in In addition to the high desorption efficiency, mostly with EDTA, the tested wool fibers have also shown no significant loss of biosorption activity over three to six cycles. For example, the wool graft polyacrylamidoxime exhibited a 5% decrease in Hg(II) desorption efficiency at the end of the fifth cycle . The levBombyx mori silk fabrics [Bombyx mori and Antherae pernyi silk fibers [Bombyx mori and Tussah silk on the fiber composition, the nature of metal ion, and the type of modifying agent [Unlike other natural fibers, the metal binding capacity of silk fibers is determined by the extent of degumming treatment that must be performed prior to use . For exa fabrics and Bombk fibers , untreatng agent . All theThe valorization of these properties for metal ion removal and recycling applications has been hindered by the high cost of raw silk fibers, which are less economical than natural plant fibers ,234,235.Although very rarely investigated for potential applications in the treatment of metal-contaminated aquatic systems, discarded human hair offers some significant advantages over analogous biosorbents. Aside from its universal availability, human hair waste could be used directly as a water filter, without the need for additional pretreatments such as pelletization or immobilization. The data on the performance of human hair waste to the removal of pollutant metal cations from individual synthetic aqueous solutions are systematized in 3 by means of the absorbed energy dose control was proposed [The studies on the behavior of protein biofibers in the uptake of metal ions from poly-metal aqueous synthetic solutions are by no means numerous. Those that already exist followed two lines of investigation: (i) description of the competitive effects in multi-component systems of biosorption ,246,247;proposed . In anotproposed . On the proposed . Chlorinproposed .The available information on the compatibility of biofibers with the real systems of metal-laden wastewater treatment is summarized in -expanding the range of natural fibers tested for biofilter function and target metals;-complete clarification and quantification of the relationships between chemical composition, structure, and properties of the bio-based fibers;-replacement of pollutant chemical methods applied for the treatment of biofibers with cleaner procedures;-a substantial increase in the number of studies on: (i) competitive biosorption; (ii) fixed bed column biosorption; (iii) desorption\u2013regeneration; (iv) disposal of exhausted biosorbents;-thorough deciphering of the biosorption mechanism;-expanding the process scale;-economic analyses;-strong expansion of work on real samplesThe expected transition of natural fibers from suitable candidates to practical biosorbents implementable in greener technologies for the removal, recycling, and reuse of metals requires extensive research focusing in particular on the following:A comprehensive analysis of the scientific literature was carried out, addressing the function of natural lignocellulosic and protein fibers as biosorbents for the removal and recovery of metals from synthetic and real aqueous solutions. Most attention has been paid to natural plant fibers, batch biosorption systems, and studies on the Cu(II), Zn(II), Cd(II), and Pb(II) ions uptake from mono-component synthetic aqueous solutions. In contrast, natural protein fibers, continuous biosorption systems, and multi-metal synthetic aqueous solutions have been much less studied. The proposed mechanisms of metal biosorption on natural fibers are dominated by interactions of ion exchange, electrostatic type, complexation, and coordination/chelation. The promising results of the desorption studies are strong evidence of the good recyclability of the biosorbents based on natural fibers, even if their number is very limited. The preliminary results of the tests with real effluents are encouraging for future industrial applications of biofibers for the severe reduction of water contamination with metal ions and the recovery of valuable metals. Research on the metal uptake capabilities of natural fibers, especially those of animal origin, needs to be continued and deepened, especially in the context of real-world scenarios and a pilot- and large-scale applications."} +{"text": "Africa faces both a disproportionate burden of infectious diseases coupled with unmet needs in bioinformatics and data science capabilities which impacts the ability of African biomedical researchers to vigorously pursue research and partner with institutions in other countries.The African Centers of Excellence in Bioinformatics and Data Intensive Science are collaborating with African academic institutions, industry partners, the Foundation for the National Institutes of Health (FNIH) and the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) in a public-private partnership to address these challenges through enhancing computational infrastructure, fostering the development of advanced bioinformatics and data science skills among local researchers and students and providing innovative emerging technologies for infectious diseases research. The emergence of innovative, genomic, and related-omics technologies has revolutionized how basic and clinical researchers are studying infectious diseases and vast amounts of diverse, large, and complex biomedical data are being generated at an unprecedented rate. Bioinformatics and data science-including powerful analytical tools-are providing tremendous opportunities for extracting knowledge from these data sets and accelerating research and discoveries in infectious diseases. Thus, increasing our understanding of pathogens and the diseases they cause impacts the development of new and improved therapeutic interventions and diagnostics. These incredible opportunities are aligned with challenges in storage, management, sharing, finding, visualizing, accessing, integrating, and analyzing data, and highlights the critical need for highly trained bioinformaticians, biostatisticians, and biomedical data scientists.Despite significant advances and recognition that bioinformatics and data-intensive science are essential research tools and critical skills for biomedical researchers in their efforts to pursue basic and clinical research in infectious diseases, Africa faces both a disproportionate burden of infectious diseases and unmet needs in the bioinformatics and data science capabilities ,2. ChallSome efforts to address these challenges in Africa are ongoing and have served to advance the understanding of the nature and etiology of infectious diseases and to inform efforts to develop and provide effective therapeutic interventions; and to improve treatment, healthcare, surveillance, and public health responses including COVID-19 pandemic in Africa . There hNIH career development and bioinformatics training programs supporting global health and data science include the Fogarty International Center\u2019s Nurturing Genomics and Bioinformatics Research Capacity in Africa (BRecA), the Eastern Africa Network for Bioinformatics Training (EANBiT), West African Center of Excellence for Global Health Bioinformatics Research Training program, and African Postdoctoral Training Initiative (APTI) in partnership with the Bill and Melinda Gates Foundation and the African Academy of Sciences. Industry programs such as IBM Research-Africa have worked across African countries to increase capabilities and training in data science and to promote data-driven strategies for healthcare in preventing, treating, and diagnosing infectious diseases. Investments by the World Bank such as the African Higher Education Centers of Excellence Project are also addressing national, regional, and local global health challenges and enhancing and building innovative capacities in training and research. The Developing Excellence in Leadership and Genetics Training for Malaria Elimination program in sub-Sahara Africa (DELGEME), sponsored by the Wellcome Trust in partnership with the Department of International Development, the Alliance for Accelerating Excellence in Science in Africa (AESA), and many other African partners, supports the development of analytical skills in bioinformatics, biostatistics, and emerging technologies for malaria control and elimination in sub-Saharan Africa. In addition, the establishment of the African Society for Bioinformatics and Computational Biology (ASBCB) has enabled the development of communities of bioinformaticians and data scientists across the continent.NIAID has significant experience and investment in supporting basic and clinical global research in infectious diseases and in building and sustaining partnerships, especially in low and low middle-income countries. These are key to fulfilling NIAID\u2019s mission and to improving the health of the global community. As part of this investment, NIAID has a long-standing commitment to supporting bioinformatics and data resources such as computational infrastructure, data platforms and repositories, hands-on-bioinformatics training, and computational tools development to provide the basic and clinical research community with access to state of the art and innovative research data resources. These resources stand ready to assist in the event of emerging diseases, global pandemics, and health emergencies. This community of scientists and trainees can work with tools at the highest level using these established data resources on which to learn and hone their skills.The achievements of NIAID\u2019s ICERs in Africa, as mentioned above, coupled with serious burden of infectious diseases and unmet bioinformatics infrastructure and training needs in Africa were the foundation for the establishment of the NIAID ACE consortium . AlthougThe first ACE Center was established in Mali in 2015 as a public-private partnership between the University of Sciences, Techniques and Technologies of Bamako (USTTB)-who was launching a master\u2019s graduate degree program-and with industry partners Intel Corporation, Hewlett Packard (through the Intel partnership), BioTeam, and EMC Corporation and the Foundation for the National Institutes of Health (FNIH). In 2019, a second ACE Center was opened in Uganda with Makerere University and the Infectious Diseases Institute (IDI), the Research and Educational Network of Uganda (RENU), the Texas Advanced Compute Center (TACC) and ENDUVO. Just as ACE-Mali serves as a regional bioinformatics resource center for research and academic institutions in West Africa, ACE-Uganda serves as a regional resource center for East Africa. ACE Centers offer high performance computing infrastructure for compute and storage capabilities; master\u2019s and Ph.D. degree-granting programs in bioinformatics in collaboration associated with academic partners; telelearning classrooms with over 20 workstations; and superior audio, visual, and networking environments for enhancing virtual, collaborative global research with ACE researchers and students. ACE-Uganda piloted a visualization laboratory featuring virtual reality-based technology with six virtual reality (VR) workstations for research and training. A similar VR laboratory was set up at ACE-Mali in 2020.The ACE Centers are built on a unique framework anchored in public-private partnerships that drive the support of computing infrastructure and bioinformatics training programs, both critical components for enhancing bioinformatics capabilities in Africa. This partnership allowed centers to be established, anchored by academic institutions with access to research space and environments, research and teaching faculty, degree-granting programs, and students interested in careers in bioinformatics. Industry partners provided in-kind contributions and donations for services, consulting, hardware, software configuration, internet connectivity, and software licenses. All the partners contribute to the Centers to support the objectives of ACE and to enhance research through education and infrastructure. For the universities in Mali and Uganda, their contributions included space in their institution\u2019s buildings, renovated classrooms, and the faculty and staff to support the activities. U.S. partners contributed infrastructure, support services, and licenses for software used in the ACE Centers.The ACE consortium is governed by the ACE Global Council, the Scientific Advisory Council, and the NIAID ACE Global Operations Team. The Global Council\u2019s members are outstanding and well-respected scientists with diverse expertise in bioinformatics and data science, infectious diseases, and biotechnology and include non-voting members from the NIAID and ACE centers. Additionally, individual ACE Centers have local management teams to oversee the day-to-day centers\u2019 operations. These are typically constituted by representatives from local collaborating institutions. As a partner, in addition to providing computational infrastructure, NIAID contributes scientific and technical staff to serve as members of the Scientific Advisory Council and Global Operations Team to assist the ACE Directors and faculty on Centers operations, teach courses and hands-on-workshops with faculty from African academic institutions, and provide scientific and technical support.The ACE centers provide a research and training environment with state-of-the-art computational and training facilities that foster networking and collaborations to strengthen research activities. Networking and collaborative activities include hosting workshops and symposia. For example, ACE-Mali and ACE-Uganda have co-hosted workshops with MRC-University of Glasgow on viral bioinformatics. ACE-Mali held the 1st Congress of African Associations for Research and Control of Antimicrobial Resistance on-site with attendees from across the continent and hold an annual Global Health in Bioinformatic Symposium with a training bioinformatics workshop on advanced topics in data science. ACE-Uganda hosted data science workshops in collaboration with the African Center of Excellence in Materials, Products, and Nanotechnology at Makerere University and most recently provided a Virtual Reality demonstration at ACE-Uganda for participants of a workshop organized by Health Education England on Immersive Technology in Emergency Medicine. The ACE consortium supports rapid and timely sharing and access to diverse data sets generated by ACE Centers collaborative research projects and activities that promote the sharing of data in open access data repositories, where data are easy to find, accessible, and can be used and reused. ACE is committed to adhering to the F.A.I.R. principles for data sharing and access and policies and guidelines of the NIAID, the NIH, and other funding agencies, as appropriate ,9. TheseThe ACE Centers offer bioinformatics and data science training programs and activities to enhance, foster, and sustain a diverse workforce of well-trained basic and clinical scientists with bioinformatics and computational expertise who can apply these skills to address global health issues in Africa. Sustaining a diverse workforce of well-trained scientists with bioinformatics and computational expertise and experience with advanced analytics such as artificial intelligence/machine learning will be dependent on increasing a wide range of training opportunities and degree-granting programs, and strong and committed mentors, coupled with career opportunities in Africa.A multi-faceted training program supports master\u2019s and Ph.D. degree-granting programs with academic partners USTTB, IDI, and Makerere University. Support includes curriculum and short and long course development, hands-on-train-the-trainer workshops, seminars, and lectures; all facilitated by ACE Centers\u2019 state-of-the-art telelearning environments for in-person and remote and digital learning with dedicated access to high performance computing infrastructure and internet. A NIAID team of computational biologists, structural biologists, genomic scientists and others in collaboration with ACE faculty members and staff, develops and teaches courses in bioinformatics and emerging technologies as well as organizes workshops and seminars. Since 2017, almost 100 students from across the African continent have enrolled in ACE associated master\u2019s and Ph.D. programs, and in ACE Mali 27 have completed advanced graduate degrees. Over two thirds of these MS graduates are either pursuing a PhD or have started working as Research Assistants in Malian laboratories and pursuing careers in data science or seeking advanced degrees. ACE-Uganda is currently supporting 58 Masters\u2019 students and 9 Ph.D. students. It is anticipated that first cohort of students will be graduating in 2023 and some have already secured data science related positions. Most recently, ACE-Uganda has begun supporting postdoctoral fellows. The ACE consortium has developed and supported more than 200 on-site or remote bioinformatics lectures and hands-on-training on technical topics such as \u201cIntroduction to Linux\u201d to introductory courses in bioinformatics, genomics, systems biology, structural biology, metabolomics, and proteomics. The students in both ACE Centers have been working on research topics that will have a direct impact on health, specifically on infectious diseases well known to their communities such as Malaria, Leishmaniasis, Retrovirus infection, and Tuberculosis. In addition, students are developing data analysis and bioinformatic workflows for broader use which leverages the knowledge acquired through ACE and compute infrastructure .ACE-Uganda is providing the computational infrastructure and data resources to students, faculty, and researchers in support of the new bioinformatics training program, co-hosted by the Department of Immunology and Molecular Biology, College of Health Sciences and Department of Computer Science at the College of Computing and Information Science at Makerere University. The \u201cNurturing Genomics and Bioinformatics Research Capacity in Africa\u201d (BRecA) program leverages highly skilled local and international faculty to increase the number of bioinformaticians in Africa and builds on the programs of the H3Africa-supported consortia . The first cohort of the BReCA program enrolled 50 students and second cohort 24 additional students. In addition to access to the ACE infrastructure, the faculty of the BRecA program works closely with the ACE Global Operations Team to provide bioinformatics training for faculty through train-the-trainer workshops and developing and participating in remote hands-on courses and lectures for students. For example, ACE-Uganda is providing computational infrastructure and services to BRecA for data analysis to develop a software tool that provides HIV risk scores through a telehealth platform as part of funding from the Ugandan government.ACE-Uganda hosted bioinformatics and data science training workshops, one with Makerere University and one with CUNY for postgraduate students and provided bioinformatics training on advanced computational tools related to areas such as structural biology and genomic data analysis. Currently, it is also supporting the development of the national sickle cell disease registry in collaboration with the Department of Pediatrics at Makerere University\u2019s College of Health Sciences. ACE-Uganda has provided high performance computational infrastructure and access to develop and test a bioinformatics training/mentorship model that uses local computational infrastructure. It aims at supporting the faculty from Makerere University and enrich the curriculum with additional hands-on-skills training and mentorship and has successfully served to mentor students . Since iAs an example of ACE Centers providing computational infrastructure and analysis to enhance research projects at partner academic institutions, one of ACE-Mali\u2019s research collaborators used the data resources available at the ACE Center to support their clinical and genetic studies of hereditary neurological disorders (HND) in Mali. Facing several challenges in computational infrastructure as data storage and reliable internet and availability of bioinformaticians for data analysis, ACE-Mali provided infrastructure and technical bioinformatics support for data analysis.Although there has been significant growth in Africa for enhancing computational infrastructure to accelerate biomedical research, significant gaps still exist that limit the ability of researchers and students to manage, use and re-use, access, and analyze data. The continuing lack of strong and reliable high-speed internet impacts the use of cloud-based data resources such as data repositories and advanced computational tools and platforms for data management and analysis. Technical support and maintenance are critical components in building a sustainable model for bioinformatics research and training centers in low-resource settings. The NIAID Global Operations team has been able to manage the infrastructure and classroom learning environments remotely using tools such as Git, Python, Salt and OpenStack to provide configuration management, versioning, and maintenance. The goal is to build sustainable support systems in Africa for training and research\u2013working towards the goal of infrastructure-as-code (IAC) that can allow configuration management and system administration in cloud platforms. The infrastructure leverages cloud operating systems to provision not just to the ACE Centers, but also cloud platforms such as Amazon Web Services, Google, or Microsoft Azure Stack. With this new infrastructure, ACE collaborators, students, and scientists have the data resources to develop and run scientific computing tools for data analytics needed to keep local research current and competitive.Over the last six years, the ACE Centers have become regional bioinformatics centers to support biomedical researchers and students. Using in-kind donations from public-private partnerships, the Centers are equipped and managed with state-of-the-art computational infrastructure that includes strong compute cores, high speed internet access, and a telelearning center with more than 20 stations. ACE-Uganda\u2019s cutting edge biomedically-focused virtual reality technology is available for research and training with six Virtual Reality (VR) stations and used to enhance learning and training for students and faculty. During the COVID-19 pandemic, ACE-Uganda took advantage of the VR stations and equipment and developed a training course in Infection, Prevention, and Control (IPC) which included using personal protection equipment (PPE) for frontline healthcare workers . The locThe ACE consortium serves as a model using a public-private partnership with industry, academic institutions, African governments and other governments as U.S. and non-profit organizations work together to address unmet needs in bioinformatics capacity in Africa and is uniquely poised to impact the training the next African generation of scientists in bioinformatics that are highly skilled to address key research questions in infectious diseases. The partnership includes the use of research facilities and degree-granting programs in academic institutions in Africa, in-kind donations from industry for consulting and computational infrastructure, the Foundation for the National Institutes of Health (FNIH) to facilitate the public-private partnership model, and NIAID\u2019s contribution of scientific and technical staff to assist the ACE Directors and faculty on day-to-day centers operations, teaching courses with faculty from African academic institutions, and provide considerable technical support.Despite the accomplishments of the ACE consortium and other related programs in Africa in reducing barriers in bioinformatics and data science capabilities by improving access to high performance computing and reliable internet, enhancing bioinformatics and data science training and mentorship, increasing the number of trained bioinformaticians in Africa, and advancing biomedical research, much remains to be done. Academic and research centers with strong bioinformatics capacity and training programs exists, yet data research resources and training are not consistently available across the African continent. The sustainability of the ACE Consortium is of highest priority to ensure continuous operation and provide innovative and state-of-the-art facilities and computational capabilities. Key to sustainability will be to enhance local capabilities and funding at ACE Centers for infrastructure, training, and faculty research projects and for the ACE Centers to develop local and international partnerships and seek funding opportunities from local governments, associated academic institutions, local industry, funding agencies, and nonprofit organization to support ACE consortium.The availability and accessibility of data research resources and bioinformatics training for African biomedical researchers and students as they tackle data-intense research projects is essential to leveraging data-driven strategies and transforming data into knowledge, thus impacting the development of new and improved therapeutic interventions, prevention strategies, and diagnostics to reduce the threat of infectious diseases and improve health care in Africa. These efforts need to be expanded across the continent and the key is sustainability through continuous commitment and funding to maintain state-of-the-art computational infrastructure and other data research resources and bioinformatics training programs."} +{"text": "Dear Editor,This case describes an 80-year-old female Caucasian patient, who sought dermatological evaluation for a lesion on the left foot after local trauma, with progressive growth over two years. Dermatological examination showed a nodular, vegetating, tumor-like lesion covered by hematic crusts on the left plantar region, overlapping an extensive area of deformities in the foot anatomy, caused by healing by secondary intention of burn lesions that occurred in childhood . HistopaThe lesion was completely excised, as well as the ipsilateral lymph nodes, after confirmation of a positive sentinel lymph node for metastatic melanoma. Imaging exams showed alterations suggestive of metastasis in face and skull bones. The patient died after eight months.Marjolin ulcer is a rare and aggressive tumor, occurs mainly in the fifth decade of life, and is prevalent in the male sex.In the epidemiology of melanomas, the nodular type represents the second most frequent one (approximately 15% of diagnosed melanomas), and 5% of nodular melanomas are amelanotic.Amelanotic acral melanoma has an incidence of 1.8% of melanoma cases,5The diagnoses of Marjolin ulcer and melanoma are defined by clinical history, physical examination, and histopathology. The therapeutic options depend on TNM staging, including excision surgery with wide margins or limb amputation, in addition to chemotherapy and radiotherapy.Scars are susceptible to trauma due to a lack of collagen organization and vascular supply compromised by fibrosis, which obstructs vessels. Virchow's theory attributes the development of malignancy in scars to repeated trauma in the area, which leads to chronic irritation, repeated re-epithelialization, and local damage to the skin immune system, with a reduction in Langerhans cells and production of toxins in the affected area, in addition to genetic predisposition.3A rare manifestation of Marjolin ulcer is presented in this case, which presented as a nodular acral amelanotic melanoma, reinforcing the need for advice to patients, care, and regular follow-up of burn scars, for early diagnosis and treatment, reducing morbidity and mortality.None declared.Valentina Louren\u00e7o Lacerda de Oliveira: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.Lucia Martins Diniz: Approval of the final version of the manuscript; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.Karla Spelta: Intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.Elton Almeida Lucas: Intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the manuscript.None declared."} +{"text": "Background: COVID-19 caused devastating effects on global healthcare systems. The elderly and people with chronic comorbidities were at a particularly high risk of mortality and morbidity. However, the evidence on the association of COVID-19 severity with noncommunicable diseases (NCDs) in the African population is scarce. Objective: The aim is to estimate COVID-19 severity among African patients with hypertension, diabetes, and cardiovascular diseases (CVDs) and its implications for case management. Methods: We will adhere to the extension for Scoping Reviews of PRISMA (PRISMA-ScR). The following electronic databases will be searched: PubMed, Scopus, Web of Science, Embase, CINAHL, and Joanna Briggs Institute. The search will be conducted after the publication of this protocol. Two reviewers will extract data from articles published after March 2020 without language restrictions. A descriptive analysis of the important findings and a narrative synthesis of the results will serve as the basis for interpretation. Expected results and conclusions: This scoping review is expected to determine the odds of patients with chronic comorbidities to progress to severe stages of COVID-19. The review will generate an evidence-based and set foundation for recommendations toward the establishment of surveillance systems and referral guidelines for the management of NCDs in the face of COVID-19 and future pandemics. Coronavirus disease 2019 (COVID-19), is an illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , there wThe effect of the COVID-19 pandemic on global healthcare systems has been profound. In particular, the impact of the pandemic on the elderly and people with non-communicable diseases (NCDs) has been devastating ,5,6,7,8.The increasing burden of NCDs along with the enduring burden of infectious diseases in Africa and other settings in low- and middle-income countries (LMICs) has been well noted . NeverthNonetheless, information on the effect of COVID-19 in Africa focused on health system challenges, and evidence on the effect of COVID-19 in African patients with hypertension, diabetes, and cardiovascular diseases (CVDs) was extrapolated from what was obtained in other parts of the globe. In order to properly allocate scarce resources and to support clinical decisions during the COVID-19 pandemic, it is important to have an evidence-based record, derived from available epidemiological and clinical data on the comorbidity between NCDs and COVID-19 among African patients. This is of particular importance as in many African countries, the demography is characterized by a large proportion of young people and a lower prevalence of lifestyle risks , which may prevent against severe SARS-CoV-2 ,19,20,21A preliminary search on International Prospective Register of Systematic Reviews (PROSPERO) , Open ScWhat type of severity outcomes were reported in the included studies?What relative impact did the selected NCDs have on the severity of COVID-19?Are there specific patient characteristics that increase the risk of COVID-19 severity among patients with the selected NCDs, namely hypertension, diabetes, and CVDs?What strategies and interventions have addressed the risk factors for COVID-19 severity in comorbid patients?Which of the three selected NCDs had a major impact on exacerbating COVID-19 severity in Africa?What impact did the COVID-19 response have on the services for NCDs in Africa?The overarching aim of this review is to focus on the potential factors related to the severity of COVID-19 for African patients with hypertension, diabetes, and CVDs and their implications for case management. The following research questions will guide to conduct this scoping review:http//:osf.io/e9r28 accessed on 12 May 2023) on 17 November 2022.The scoping review will be conducted in accordance with the guidance for pursuing systematic scoping reviews, put forth by Peters and colleagues from JBI in Australia . The metStudies focusing on COVID-19 patients meeting the following criteria will be included: (i) studies that estimated the quantitative relationship between COVID-19 and hypertension, diabetes, and CVDs; (ii) studies conducted on the African continent; (iii) and studies of both observational and interventional designs.Not considered will be studies that met at least one of the following exclusion criteria: (i) studies that evaluate COVID-19 patients without considering NCDs and vice versa; (ii) position papers, editorials, policy statements, case reports, case series studies, perspectives, commentaries, published abstracts, poster and oral presentations, and author reply articles; (iii) studies on the potential association between COVID-19 and other infectious diseases, malignancies, or autoimmune disorders, but not considering diabetes and hypertension; and (iv) articles that speculatively extrapolate findings from studies conducted outside Africa to explain the effects of COVID-19 in Africa.The literature search will include results from studies reporting on COVID-19 and NCD comorbidities among African patients. The review will include studies on adults aged \u226518 years, irrespective of their gender. Data on patients participating in clinical trials, cross-sectional epidemiological studies, or cohort studies (both retrospective and prospective) will be included in the review. Data on patients admitted to any healthcare facility, including outpatient departments, emergency rooms, and intensive care units (ICUs) and reporting to have comorbidities of COVID-19 and NCDs are eligible for the review. However, the review will not consider studies that report from African diaspora patients (living outside of Africa).The review will address the severity of COVID-19 symptoms among African patients due to either one or several of the selected NCDs. For pragmatism and homogeneousness, the review will consider the standard definitions of COVID-19 severities set forth by the World Health Organization (WHO). The common categories for the level of aggravation of COVID-19 among adult population are nonsevere (mild or early stage), moderate, severe, and critical . MoreoveThe systematic search strategy will mainly be aimed at published peer-reviewed articles. To identify potentially suitable articles, we will search documents from the following electronic databases: PubMed/MEDLINE, Embase/Elsevier, Scopus, Cumulative Index to Nursing & Allied Health Literature (CINAHL)/EBSCO, and Web of Science. Because the first COVID-19 case was confirmed in Africa on 14 February 2020, we will search the databases from March 2020 to 28 February 2023 (3-year period) without language restrictions.A three-step search strategy will be used in this review. First, an initial search of PubMed will be undertaken followed by an analysis of the text words contained in the title and abstract and of the index terms used to describe the article. Second, using all the identified keywords and index terms, we will search all the other databases. Third, we will undertake a hand search of the reference list of all the identified relevant documents for potential additional articles. An example of the terms and strings of words applied on PubMed is provided in Records retrieved through the aforementioned search strategy from all databases will be imported into the bibliometric software EndNote\u2122 X9 and screened for relevance and duplication. The criteria for relevance are based on the scope and objectives of the review. Using the inclusion criteria set above, two reviewers will conduct full assessment of the identified scientific publications, and any duplicates will be removed. Any disagreement will be resolved through discussion, and with a third reviewer, as the case might be.The reviewers will develop a data abstraction tool to capture relevant information from the selected documents. The tool will encompass detailed information that includes (i) participant characteristics, such as demographics of patients; (ii) study characteristics, such as study setting, study types, publication dates, authors, methodology, etc.; and (iii) outcomes and key findings related to the review objective. Two reviewers will independently chart information from each selected document to ensure charting consistency and inter-reviewer reliability. In case of disagreements, the two reviewers will resolve through discussion or in consultation with a third team member.\u00ae Excel 2016 . A draft data abstraction tool is provided in All extracted data will be exported to MicrosoftOutcome of the systematic search will be analyzed descriptively using frequencies and percentages. Moreover, graphical presentation including tables and charts will be used, whenever applicable. This will compare and/or reflect the effect of NCDs on the severity of COVID-19. Effect of comorbidities of selected NCDs will be mapped accordingly and will be presented in comparison to those without any comorbidities.In this section, we will summarize the results of the search strategy and the process of document selection, inclusion, and exclusion in both text and chart formats. We will tabulate and describe detailed information about the selected studies. Emphasis will be placed on the following information: authors, year of publication, country, aim of the study, study design, study setting, participant characteristics, sample size, main findings, measures of outcomes, and effect size (if relevant).The abstracted information in relation to the objectives of the review will be summarized and presented in detail. For example, we will present the number of studies that examined associations between COVID-19 and hypertension. We will describe the relative frequencies of the studies by geographical location and number and characteristics of the participants included in terms of age, sex, and severity of COVID-19. Moreover, the types of study designs and outcome measurements will be described. Additionally, the types and strengths of the reported relationships between COVID-19 and hypertension will be given, and the consistency of the findings will be reported. We will also recount the effect of the COVID-19 response measures on patients.After describing the reported relationship between COVID-19 and the three selected NCDs, we will report the relationship between COVID-19 and concurrent NCDs. The final synthesis will present the overall severity of COVID-19 in people with all the selected NCDs.This scoping review is expected to determine the odds of patients with chronic comorbidities to advance into severe stages of COVID-19 and to estimate the extent to which NCD services were affected during the COVID-19 response in Africa. In doing so, the review will provide new evidence and set foundations for recommendations toward the establishment of surveillance systems and referral guidelines for the management of NCDs during the COVID-19 pandemic and future pandemics. The outcome of the review will increase awareness of healthcare professionals, policy makers, and other key stakeholders. It will also enhance further collaboration among research, surveillance systems, and technological advancement to develop new advanced diagnostic tools and to set up policies that deal with the silent pandemic of the dual burden of NCDs and infectious diseases in Africa."} +{"text": "Chronic stress has far-reaching consequences on brain circuits, behavior, and mental health, often leading to abnormal behavior and psychiatric disease. The repercussions of chronic stress affect society as a whole, placing undue strain on the economy and increasing the risk of catastrophic events in communities with easy access to firearms. Developing innovative treatments and preventative measures for stress-induced abnormal behavior requires a more comprehensive understanding of how chronic stress impacts the brain.Neuroplasticity, the process of brain modification at the cellular and circuit levels, has traditionally been associated with learning and memory. However, recent research reveals its role in altering innate and adaptive behavioral responses, especially those influenced by stress. By inducing plasticity within specific brain circuits, many chronic stress-related effects can be mitigated.This Research Topic delves into the complex relationship between chronic stress, neuroplasticity, and abnormal behavior. It features original research and review articles that employ novel tools, pharmacological approaches, and various animal models to investigate the potential of augmenting plasticity within brain circuits as a means of treating symptoms caused by chronic stress. Topics span early life stress, synaptic remodeling, and epigenetic factors that increase susceptibility to stress-induced abnormal behavior.This Research Topic adopts an interdisciplinary approach, combining research from various disciplines to provide a comprehensive and multifaceted understanding of the relationship between chronic stress, neuroplasticity, and abnormal behavior.Shi et al. investigates the effects of direct and indirect stress on synaptic plasticity in the anterior insular cortex (aIC) using an observational fear mouse model. The results provide insights into the changes in synaptic plasticity in the aIC after physiological and psychological stress and suggest that different types of stress may have different underlying mechanisms, which could aid in the treatment of stress-related disorders. This study highlights the importance of understanding how various forms of stress impact neural circuits and contribute to abnormal behavior, ultimately informing targeted interventions.Bartsch and Nordman focuses on understanding the early signs and deterioration of perceived fatigue in healthy middle-aged individuals to develop preventive strategies for chronic fatigue (CF) and chronic fatigue syndrome (CFS). By understanding fatigue development in middle-aged adults, the study aims to contribute to the establishment of countermeasures for CF and CFS. This research underscores the significance of early detection and prevention of fatigue-related disorders, which can have debilitating effects on individuals' quality of life and productivity.Putra et al. discussed how NMDA receptor antagonists, such as ketamine and memantine, have emerged as promising alternatives for treating aggressive behavior due to their quicker onset of action, fewer observed side effects, and potential to serve as long-lasting treatment options. However, their effects on aggression are highly dependent on dosage, context, and personal experience. A study in this Research Topic explores the complexities of these factors and their impact on the effectiveness of NMDA receptor antagonists in managing aggressive behavior. The findings emphasize the need for further research and careful consideration of individual factors to ensure the responsible use of these drugs and to maximize their benefits while minimizing potential risks.Ronan et al. investigated the impact of intracerebroventricular administration of corticotropin-releasing factor (CRF) and vasopressin (AVP) on extracellular serotonin release in the central nucleus of the amygdala (CeA), shedding light on potential mechanisms underlying stress-induced affective reactivity in humans. This knowledge may prove useful in understanding and treating stress-related psychiatric disorders, such as anxiety, depression, and posttraumatic stress disorder. By examining the neurochemical changes associated with stress-induced affective reactivity, this research advances our understanding of the complex relationship between chronic stress and mental health disorders.Lastly, This broad scope offers a more complete picture of the complex relationship between chronic stress and mental health, with promising implications for the development of novel therapeutic interventions and preventative measures for stress-related disorders.In vivo pharmacological manipulations enable targeted drug administration to the brain, while novel behavioral paradigms, such as the observational fear mouse model, allow for exploration of different stress types on brain circuitry. Assessments of individuals in highly social and stressful environments emphasize the importance of early detection and prevention. Direct manipulations of plasticity in live animal models offer targeted approaches to understanding stress-induced effects. Examining the consequences of pharmacological interventions for treating stress-related aggression provides insights into potential benefits and risks. These cutting-edge methods significantly contribute to ongoing efforts in developing innovative treatments and preventative measures for stress-induced abnormal behavior.The Research Topic features innovative methodologies to study the relationship between chronic stress, neuroplasticity, and abnormal behavior. This Research Topic's implications are significant, contributing to our understanding of chronic stress and its impact on mental health while pointing to novel therapeutic interventions for stress-related disorders. The featured studies explore various aspects of the complex relationship between chronic stress, neuroplasticity, and abnormal behavior. They examine the effects of stress on brain circuitry, neurochemical changes, and early signs of fatigue, as well as the potential of NMDA receptor antagonists to treat aggressive behavior. Collectively, these studies contribute to a holistic understanding of the impact of chronic stress on mental health and wellbeing.As our understanding of the relationship between chronic stress, neuroplasticity, and abnormal behavior deepens, we become better equipped to address the pressing challenges of mental health and support individuals and society as a whole in coping with the often devastating consequences of chronic stress.We hope this collection of articles serves as a catalyst for further research and collaboration among scientists, clinicians, and policymakers, driving the development of innovative and personalized interventions for those suffering from stress-related disorders. Together, we can work toward a future where the adverse effects of chronic stress are better understood, managed, and ultimately, mitigated. With continued research and collaboration, we can make strides in developing effective treatments and preventative measures for stress-induced abnormal behavior, improving mental health outcomes and the overall quality of life for individuals affected by chronic stress.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "The pituitary hormone, oxytocin (Oxt), is gaining more and more interest from researchers in neuroscience over the years. Such attention is due to the multitude of heterogeneous effects on neural circuits and pro-social behavioral responses that Oxt elicits through its receptor, the Oxt receptor (OxtR). Imbalances in the oxytocinergic system are implicated in neuropsychiatric diseases associated with altered socio-emotional competence , but also in some neurodegenerative diseases, such as Huntington's Disease and amyotrophic lateral sclerosis. Understanding the complex neurobiology of the oxytocinergic system in physiologic and pathologic conditions is a still open scientific challenge. The potentiality of Oxt to be used as a drug treatment further increases the need to extend, collect, and organize knowledge concerning this molecule.In this special issue, we feature an assortment of contributions exploring through different approaches and from multiple angles the specific effects exerted by Oxt in the brain. This collection expands and collects current understanding in the neurobiology of Oxt and will provide direction and guidance for future studies in this field.Manjila et al. integrated brain wide connectivity of Oxt neurons with OxtR expression in mice. Accordingly, they provided insights for three functional circuit-based modules across the whole brain, modulated by the Oxt. These modules regulate respectively (i) the internal state , (ii) somatic/visceral responses , (iii) cognitive responses . The specific effects of Oxt on the neurons of one of these circuit\u2014the learning and memory circuit, involving the hippocampal formation\u2014have been finely investigated in multiple studies, as review in Talpo et al. Variations in the oxytocinergic functional modulation of the different neurons in each hippocampal subregion appear to account for distinct information processing tasks exerted by each subregion, comprehensively summarized in this review.Oxt is widely released in the brain, exerting specific neuromodulation of each cerebral region. Borroto-Escuela et al. reviewed the existence of D2R-OxtR, OxtR-GHS-R1a, 5-HT2AR-OxtR, and 5-HT2CR-OxtR heterocomplexes. In line with this evidence crosstalk between Oxt and other neurotransmitters should be seriously considered.An additional element of complexity in the neuromodulation operated by Oxt is due to the presence in many brain regions of higher order G-protein coupled heteroreceptor complexes of the OxtR. Triana-Del Rio et al., Coccia et al., Chen et al. and Muscatelli et al. described different aspects of these pro-social behavioral responses elicited by the Oxt. Triana-Del Rio et al. summarized how Oxt signaling in the limbic network modulates social and stress/threat-related behaviors, starting from the description of the underling cellular and molecular mechanisms. Authors describe how these responses are especially important in the interactions with conspecifics. Coccia et al. extended this concept by explaining the importance of empathy in social decision-making to survive in social environment. Indeed, Oxt modulates some of the major components of social decision-making and is associated to empathy-like and pro-social behaviors in rodents. In the context of conspecific interactions, strong evidence of the role of Oxt is offered by the analysis of the parental caregiving behaviors of male mice, as discussed in the opinion paper by Chen et al. Referring to a recent paper by Kazunari Miyamichi's team was significantly downregulated in periodontitis tissues compared to control tissues, suggesting a potential role for oxytocin-related pathways in the development and progression of periodontitis. However, further research is needed to understand the underlying mechanisms and the correlation between the expression of these genes and the pathological stage of periodontitis.Additionally, The papers in this Research Topic provide insights into the neurobiology of Oxt in health and disease, spanning from the delineation of the pro-social role of Oxt, to the description of the effect of Oxt on specific brain networks, the clarification of crosstalk phenomena between Oxt and other neurotransmitters, the identification of the intracellular pathways activated by Oxt. Then, they provide an overview of the current body of knowledge about Oxt in the brain and highlight the many potentialities of research in this field. In this view, we hope that this Special Topic can stimulate further studies unraveling the missing pieces of knowledge in the mechanisms of oxytocinergic brain modulation, possibly accelerating the development of therapeutic strategies and drugs that use this molecule.All authors contributed to this editorial and approved the submitted version."} +{"text": "The term \u201cbiological data\u201d refers to information derived from living organisms and their products. The unique characteristics of biological data make biological data management particularly challenging. Diverse biological research generates vast amounts of different types of big data, such as sequence data and protein structures, in a variety of research fields, including transcriptomics, genomics, proteomics, and metabolomics. The scale of biological data is growing exponentially due to rapid technological advances and declining prices for new technologies used to produce biological data. Biological information now plays an essential role in scientific progress. As such, it is very complex compared to other forms of data. The integrated analysis of different data types is attracting research interest these days.This issue contains an important article regarding a biological data repository in Korea by Lee et al. . Lee and his colleagues introduced a new biological data repository, the Korea BioData Station (K-BDS) for sharing biological data , GenBank, Protein Data Bank (PDB), and DNA Data Bank of Japan (DDBJ). These databases were built to share vast biological datasets and have played an important role in scientific research by storing, managing, and providing access to increasingly large datasets. The future of biological research is highly dependent on the proper use and management of data. However, the complexity of biological data and the unprecedented exponential rate of production present significant challenges in archiving, integrating, and translating big data.Despite the government's large-scale R&D investments in the field of biology, Korea has not previously taken active steps toward the establishment of a biological database. Recently, however, the Korean government officially announced a national strategy for sharing biological data generated with national R&D funding. The Korean government has funded the Korea Bioinformation Center (KOBIC) to develop a new data repository, the Korea Biodata Station (K-BDS).The K-BDS is a data repository for all types of data for biological research. It provides free access to various database resources to archive raw biological data and support research activities. The data structure of K-BDS uses international data standards and formats. The K-BDS will evolve through the optimization and automation of data submission, curation and analysis procedures, infrastructure upgrades for storing big data, and the migration and development of new tools and pipelines to support biological research. I hope that the K-BDS will become a centralized archive in Korea and support research activities in academia and industry around the world."} +{"text": "The COVID-19 pandemic has had an unprecedented detrimental impact on mental health in people around the world. It is therefore important to examine factors that may buffer or heighten the risk of mental health problems in this context.The current study explores the buffering effects of different flows of compassion and the magnifying effects of fears of compassion on the impact of perceived threat of COVID-19 on indicators of mental health and psychosocial wellbeing.4057 adult participants collected from the general community population across 21 countries from Europe, Middle East, North America, South America, Asia and Oceania, completed self-report measures of perceived threat of COVID-19, compassion, fears of compassion, social safeness, loneliness, depression, anxiety, stress, posttraumatic stress and growth.Self-compassion moderated the impact of perceived threat of COVID-19 on depression, anxiety and stress, whereas compassion from others moderated the effects of fears of COVID-19 on social safeness. Fears of compassion moderated the impact of perceived threat of COVID-19 on psychological distress. Only fears of compassion from others moderated the effects of fears of COVID-19 on social safeness. Furthermore, social connection predicted higher post-traumatic growth and traumatic stress, whereas social disconnection (fears of compassion and loneliness) predicted increased traumatic symptoms only. Social connection heightened the impact of perceived threat of COVID-19 on post-traumatic growth, while social disconnection weakened this impact. Social disconnection magnified the impact of the perceived threat of COVID-19 on traumatic stress. The effects were consistent across countries.Our findings highlight the universal protective role of compassion and social connection in promoting resilience and buffering against the harmful effects of the COVID-19 pandemic on mental health and psychosocial wellbeing. Furthermore, our results reveal that fears of compassion have a magnifying effect on the damaging impact of the COVID-19 pandemic on mental health.None Declared"} +{"text": "Post-Traumatic Stress Disorder (PTSD), with prevalence of 14%, causes disability and burden to the person, his/her close environment and whole society due to, among other factors, interruption in a range of daily life activities. To date little research was done to delineate comprehensive patterns of daily life participation among people with PTSD. Despite extensive research, our understanding of factors affecting the participation in PTSD is limited, given that relief in the PTSD symptoms does not guarantee returning to satisfying daily life activities.Investigate objective and subjective participation dimensions among individuals with PTSD in comparison to healthy controls; and explore the impact of personal and illness-related factors, body functions and environment on the participation in PTSD.Sixty two individuals with PTSD and matching by age and gender healthy controls participated in this cross-sectional study. They completed standard assessments for PTSD symptoms severity, general cognitive profile, executive functions (EF) based on self-report and performance, sensory processing, self-efficacy, capacity to perform everyday activities, environmental properties, and actual participation in daily life in objective and subjective dimensions.The participation was found to be inferior in PTSD in the following dimensions: number of activities, participation frequency, and enjoyment , and experienced low meaning within the participation. Number of participated activities was correlated with self-reported EF , and environment properties . Frequency of participation was associated with self-reported EF . In addition, number of activities, frequency and experience of meaning were inferior in those who reported on avoidance from sensory stimuli in daily life . PTSD symptoms severity was not correlated with the participation .The restriction in both objective and subjective dimensions of participation in PTSD raises major concern given the profound effect of participation on well-being, and individual and community burden. The study reveals unique patterns of association between the participation indices and personal and illness related factors in PTSD, suggesting that objective factors are of less impact in comparison to subjective ones; and aspects of cognitive and sensory regulation as well as environment are of particular importance for participation. This pilot study demonstrates a need for further research to expand our knowledge in the field with the ultimate goal of contributing to well-being and health of individuals with PTSD.None Declared"} +{"text": "A meeting, sponsored by the Bill and Melinda Gates Foundation (BMGF) and organised by Clinglobal, was held at The International Livestock Research Institute (ILRI) in Nairobi, Kenya, from 19th\u00a0\u2013\u00a0to 21st\u00a0October 2022. The meeting assembled a unique group of experts on tick control in Africa. Academia, international agencies (FAO and ILRI), the private Animal Health sector and government veterinary services were represented. The significant outcomes included: (i) a shared commitment to standardisation and improvement of acaricide resistance bioassay protocols, particularly the widely used larval packet test (LPT); (ii) development of novel molecular assays for detecting acaricide resistance; (3) creation of platforms for disseminating acaricide resistance data to farmers, veterinary service providers and veterinary authorities to enable more rational evidence-based control of livestock ticks. Implementation of enhanced control will be facilitated by several recently established networks focused on control of parasites in Africa and globally, whose activities were presented at the meeting. These include a newly launched community of practice on management of livestock ticks, coordinated by FAO, an African module of the World Association for the Advancement of Veterinary Parasitology (WAAVP-AN) and the MAHABA initiative of Elanco Animal Health. Ticks and tick-borne diseases significantly constrain livestock production globally, especially in Africa . The ecoRhipicephalus microplus is the most important ixodid tick species causing mortality or morbidity in livestock, multiple tick species transmit additional major livestock pathogens through sub-Saharan Africa. These include East Coast fever (ECF), caused by the protozoan parasite Theileria parva, which is transmitted by the tick Rhipicephalus appendiculatus, and heartwater, caused by the rickettsial pathogen Ehrlichia ruminantium and transmitted by several species of ticks in the genus Amblyomma [In contrast with other regions where mblyomma .R. microplus, originating from Southeast Asia.Ticks and tick-borne diseases in Africa have become increasingly severe because of the introduction of the invasive one-host tick,\u00a0Rhipicephalus microplus is now well established in tropical and subtropical regions, including Latin America, Australia and, more recently, Africa. The economic importance of this tick species results from its capacity to transmit the highly pathogenic protozoans Babesia bovis and B. bigemina and the rickettsial pathogen Anaplasma marginale. After introduction of R. microplus to Madagascar in 1959, the tick spread to South Africa and Tanzania, frequently displacing the indigenous \u2018blue tick\u2019 Rhipicephalus decoloratus, notably in Tanzania [R. microplus was introduced twice to West Africa (Benin and Cote D\u2019Ivoire) from Brazil [R. decoloratus in that country, [Rhipicephalus annulatus and R. geigyi (unpublished data). Data from Kenya similarly suggest R. microplus has displaced R. decoloratus from the coastal region [Tanzania . More rem Brazil , 5 and hcountry, and possl region .Given the absence of alternative control measures, the application of acaricides for tick and tick-borne disease control remains the main practical option. Several recent publications have reviewed the status of acaricide deployment and resistance in Africa together with the perceptions of livestock keepers regarding ticks, tick-transmitted diseases and control methods \u201311.However, as in other continents, resistance to the major classes of acaricides, synthetic pyrethroids, organophosphates, amidines and macrocyclic lactones , 13 has The goals of the meeting were to review the current knowledge relating to the prevalence of acaricide resistance in sub-Saharan Africa; learn from the progress of ongoing tick control initiatives; review updated protocols for standardisation of existing acaricide resistance diagnostics and assess the potential value of novel assays. There was also a discussion on enhancing the dissemination of accrued knowledge to farmers and national veterinary institute staff through digital and direct platforms for engagement with multiple clients .R. appendiculatus, which transmits T. parva (causing East Coast fever in cattle), and the recently introduced R. microplus, transmitting highly pathogenic B. bovis and A. marginale to livestock, particularly cattle. He reviewed the current techniques for acaricide resistance diagnosis, in particular the larval packet test (LPT) and adult immersion test (AIT). These are currently relatively expensive and require a network of laboratories with the expertise and resources to perform them. Doctor Vudriko further highlighted additional dimensions of the acaricide resistance problem, including lack of resources, appropriate infrastructure and government extension services, leading to the suboptimal application of acaricides, and even crop pesticides instead of acaricides. Maria Tumwebaze, also of the RTC unit, presented data generated using the LPT and adult immersion test (AIT), indicating that resistance occurs among all three major classes of acaricides that are currently widely marketed in Uganda: synthetic pyrethroids, organophosphates and amidines.The keynote presentation was given by Dr Patrick Vudriko, Director of the RTC at Makerere University in Kampala, Uganda. He emphasised issues constraining efficient tick control and detecting acaricide resistance in Uganda and other countries in the region. His major emphasis was on the mitigation of resistance to Thomas Bazarusanga of ACRE Africa confirmed that resistance, as indicated using LPT, is also present against multiple acaracide types in Rwanda, with Amitraz being the most frequently implicated product . As in Uganda, suboptimal application of acaricides was observed as well as the use of unsuitable crop pesticides. Doctor Bazarusanga\u2019s key recommendations for improvement of acaricide resistance surveillance (ARS) and the agencies with responsibility for this in Rwanda were summarised as enhanced extension services (RAB), enforcement of regulation at Rwanda Food and Drugs Authority (RFDA) and Licensing of Agrovet attendants from Rwanda Council of Veterinary Doctors (RCVD).Amblyomma variegatum and R. microplus, and the main techniques used for assessment are LPT, AIT and larval immersion test (LIT). Maps were presented showing the geographical distribution of resistance within the region. For R. microplus, resistance in the field has been confirmed using the LPT in Burkina, Faso, Cote-D\u2019Ivoire, Togo, Mali and Benin. As in Rwanda, Amitraz is the most frequently used product . Unlike East Africa, acaricide application in West Africa is primarily by brushing, rather than spraying, using backpacks, which may result in differences in the evolution of acaricide resistance between East and West Africa.Abel Biguezoton of CIRDES summarised the current situation regarding ARS for eight countries in West Africa. In this region, the major tick species of economic importance are R. microplus at the Kenyan coast. ILRI provides assay backstopping through quality control, training and, in future, the supply of reference susceptible tick strains. Trials of a similar collaboration between a dedicated centre of excellence, specifically the RTC at Makerere, and the District Veterinary Office of Kiboga, Uganda, were presented by Timbiira John Bosco, the regional DVO. Veterinarians were trained in tick collection, and subsequent analysis at RTC used the adult immersion technique (AIT).Doctor Naftaly Githaka of ILRI provided a preliminary example of how diagnostic assays for acaricides could be integrated into the programmes of departments of veterinary services (DVS) in Africa through his work on acaricide-resistant R. microplus but can be adapted for organophosphates and amidines. Although the most widely adopted assay, it is a lengthy undertaking involving field sampling followed by six weeks in a specialised laboratory, because of the requirement to generate larval ticks from engorged adults. Professor Frans Jongejan of FAO summarised the history of the test and its application in Africa. The LPT was originally described and adopted in 1960s [The LPT remains the gold standard assay for evaluating acaricide resistance phenotypes in ticks. It has primarily been applied to diagnosing acaricide resistance to synthetic pyrethroids in in 1960s and the in 1960s as an alThe two principal resistance mechanisms are metabolic resistance, associated with the enhancement of the detoxification enzyme system, or target-site resistance, associated with modification of the binding site of the acaricide. The tick proteins targeted by the most widely used acaricides are relatively well characterised. They are usually part of the nervous system and Single Nucleotide Polymorphism (SNP) at the target site have been correlated with resistance. The primary target sites for synthetic pyrethroids are the voltage-gated sodium channel; for organophosphates, the acetylcholinesterase receptor; and for macrocyclic lactones, the GABA-gated sodium channels. In the case of formamidines, which are Octopamine receptor agonists, the picture is the most complex, the octopamine/tyramine receptor contains SNPs implicated in resistance, but other genes, such as monoamine oxidases and ATP-binding cassette transporters, are also suspected targets. Professor Christine Maritz-Olivier presented the genetic complexity underpinning acaricide resistance phenotypes\u00a0as shown in\u00a0Table R. microplus isolates from Africa and North and South America, Clinomics has developed a preliminary PCR-based assay for field detection of synthetic pyrethroid resistance in R. microplus. Dr Francois Maree presented the assay details and coordinated a practical demonstration for workshop participants. The current objective of the project is to show proof of concept for a field-applicable assay capable of providing rapid diagnosis of the presence of markers for acaricide resistance. The approach has the potential for multiplexing, incorporating additional targets for other acaricide classes in a format that may be used to support conventional bioassays in the future\u00a0Fig. Based on sequence data derived from acaricide-resistant and susceptible The MAHABA programme , managed by Elanco Animal Health and GALVmed and supported by BMGF, was presented by Dr Chandra Bhushan. The MAHABA programme is intended to deliver a practical strategy for managing ticks and the impact of tick-borne disease and to equip small-scale producers in Uganda and Nigeria with the necessary tools (acaricides) and knowledge to realise livestock productivity gains. This represents a significant advance relative to companies maximising acaricide sales without corresponding client engagement.https://virtual-learning-center.fao.org/mod/page/view.php?id=7392).Doctor Ayo Majekodunmi (WAAVP-AN co-chair) and Dr Weining Zhao (FAO) presented details on developing regional and global networks to support future research and guidelines for tick control. The WAAVP-AN is an African network of experts in veterinary parasitology. It is intended to improve knowledge on veterinary parasites as well as communication and networking on parasitology in Africa. Recently, FAO has established a global Community of Practice that will underpin the development of a new set of guidelines on acaricide resistance and the management of livestock ticks which can be accessed at to central laboratories and validate the results with LPT and future molecular tests. LTT could be a transition bioassay until the molecular tests are fully developed and validated.Improved data collection and centralised management to improve mapping and the dissemination of information to farmers, veterinary services and policymakers.Continued refinement of field-based molecular assays to increase the number of markers, acaricide classes and tick species which the assay can support.Evaluation of integrated control, including evidence-based implementation of acaricide rotation and combination strategies.Organisation of follow-up meetings with inclusive African country coverage, involving veterinary authorities and research organisations, to review resistance data in more detail and develop country-specific or regional models for implementation of acaricide resistance surveillance.Additional priorities:R. microplus within the continent and the reliance on acaricides to control this tick. This initial meeting of multiple experts highlighted the potential to deploy technical and knowledge-based solutions to mitigate the acaricide resistance problem in African livestock ticks and the role of recently implemented networks in catalysing this process.Acaricide resistance is widespread in Africa, and the impact on the control of ticks and tick-borne diseases has severe implications for farmer\u2019s livelihoods. Multiple laboratories have confirmed the detection of resistance to all widely deployed classes of chemical acaricides. Furthermore, the problem is increasing because of the rapid spread of"} +{"text": "Therefore, the indiscriminate administration of fluids to allpatients with hemodynamic instability, in addition to not obtaining the possiblebenefits induced by the increase in cardiac output, has the potential to aggravateorgan dysfunctions, since the excess of fluids, represented by the accumulatedhydric balance, is an independent factor for an increase ICU length of stay,duration of mechanical ventilation, probability of acute kidney injury andmortality.-4Despite the different methodologies and definitions in the literature, the mostaccepted concept of fluid responsiveness (FR) is an increase in cardiac outputgreater than 10-15% induced by an increased preload. Thus, volume expansion is theinitial measure most frequently used to optimize tissue perfusion in ahemodynamically unstable patient. However, the prevalence of FR in the intensivecare unit (ICU) is approximately 50%. , in turn, is the ability of the body to receive an infusion offluids without progressing to organ dysfunction . PossiblThus, the combined evaluation of FR and FT is of fundamental importance in themanagement of hemodynamically unstable patients because the absence of FT, even in afluid responsive patient, can mitigate any benefit induced by volume expansion andeven aggravate or cause new organ dysfunctions.Considering the presence or absence of FR and FT, there are four hemodynamicprofiles:- A: FR present and FT present.- B: FR absent and FT present.- C: FR absent and FT absent.- D: FR present and FT absent.Depending on the hemodynamic profile in question, it is possible toindividualize, the most appropriate approach for hemodynamic resuscitation for agiven hemodynamically unstable patient, with the objective of preventing and/orreversing organ dysfunction .The following are basic principles:- Volume administration should not be performed in the absence of FR (profiles Band C). In the absence of FR and FT (C profile), the need for de-resuscitationshould be assessed. Fluid administration in a fluid tolerant patient but withoutFR criteria (profile B) can lead to the loss of FT, with the risk of newhypervolemia-induced organ dysfunction, thus requiring conservative managementwith regard to the administration of fluids.- In the presence of FR, volume administration with the greatest potentialbenefit and lower risk of inducing or worsening organ dysfunction will be in theconcomitant presence of FT (profile A).- In the presence of FR and absence of FT (profile D), volume administrationshould take into account the potential for inducting and/or aggravating organdysfunction, and early initiation of vasoactive drugs should be considered.Fluid tolerance should be evaluated in two different compartments; left,considering the left heart chambers filling pressures and the degree ofpulmonary congestion; and right, assessing the right heart chambers fillingpressures and the degree of fluid overload in the systemic venouscompartment.Static measures of filling pressure in right and left cardiac chambers, such ascentral venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP),depend on the interaction between venous return function and ventricularfunction, and are also influenced by increases in intrathoracic pressure insituations such as pneumothorax, cardiac tamponade and the use of positiveend-expiratory pressure (PEEP). Therefore, they have a limited role in theidentification of FR and volemic status; however, extremely low values (<6mmHg) increase the probability of FR. On the other hand, high values (CVP >12mmHg and PAOP > 18mmHg) may indicate a low FT capacity in certain clinicalcircumstances and are associated with an increased risk of peripheral edema,ascites, pulmonary edema, renal and hepatic dysfunction. In addition, themeasurement of these variables requires the use of invasive devices, such as acentral venous catheter for CVP and a pulmonary artery catheter for PAOP.Hemodynamic monitoring by transpulmonary thermodilution may assist in theevaluation of FT, especially on the left compartment, using variables such asglobal end-diastolic volume (GEDV), extravascular lung water (EVLW) and thepulmonary vascular permeability index (IPVP), and is useful in the differentialdiagnosis between inflammatory and hydrostatic alveolar-interstitial syndrome.Despite being a less invasive tool than a pulmonary artery catheter, theinsertion of central venous and arterial catheters is required and has high costlimiting its availability in most intensive care units. and the evaluation of left ventricular fillingpressures, as assessed by the relationship between the E wave and the A wave ofthe transmitral flow on pulsed Doppler and the E wave over the E\u2019 wave on tissueDoppler, help in the evaluation of left FT. Venous excess ultrasound score(VExUS) takes into account the diameter of the inferior vena cava and the venousflow pattern on Doppler ultrasound in the portal, suprahepatic and intrarenalveins ( and may be useful instrategies of resuscitation and management of ultrafiltration in patients onhemodialysis,(11.being an interesting tool for the evaluation of right FT (Point-of-care ultrasonography is becoming increasingly available in ICUs, withthe potential for wide application for evaluation of both left and right FT. Theestimation of EVLW using lung ultrasoundalveins , shows aright FT .The growing evidence in critically ill patients of aggravation of organ dysfunctionrelated to fluid overload implies that hemodynamic evaluations should advance beyondfluid responsiveness and begin to encompass fluid tolerance. The coordinatedevaluation of these two variables has the potential to prevent and reverse acuteorgan dysfunction and assigns a new obligation to intensivists: fluidresponsibility."} +{"text": "Evidence-Based Quality Improvement (EBQI) involves researchers and local partners working collaboratively to support the uptake of an evidence-based intervention (EBI). To date, EBQI has not been consistently included in community-engaged dissemination and implementation literature. The purpose of this paper is to illustrate the steps, activities, and outputs of EBQI in the pre-implementation phase.The research team applied comparative case study methods to describe key steps, activities, and outputs of EBQI across seven projects. Our approach included: (1) specification of research questions, (2) selection of cases, (3) construction of a case codebook, (4) coding of cases using the codebook, and (5) comparison of cases.The cases selected included five distinct settings , seven EBIs and five unique lead authors. Case examples include both community-embedded and clinically-oriented projects. Key steps in the EBQI process included: (1) forming a local team of partners and experts, (2) prioritizing implementation determinants based on existing literature/data, (3) selecting strategies and/or adaptations in the context of key determinants, (4) specifying selected strategies/adaptations, and (5) refining strategies/adaptations. Examples of activities are included to illustrate how each step was achieved. Outputs included prioritized determinants, EBI adaptations, and implementation strategies.A primary contribution of our comparative case study is the delineation of various steps and activities of EBQI, which may contribute to the replicability of the EBQI process across other implementation research projects. The conThe combination of community-engaged research and D&I, termed community-engaged dissemination and implementation (CEDI) research, reflects the intersection of community-partnered research in implementation research design, methods, and dissemination . The ovebest available research evidence at all stages of the process, from the \u201cdiagnosis\u201d of performance issues to the development and tailoring of implementation strategies . QI aims to improve local multi-level processes and outcomes by using data from the local context, local expert input and opinions, and local multi-disciplinary teams . A revierategies , and in rategies . Specifirategies and selerategies .deliberative, partnered, and evidence-driven process to inform the selection and tailoring of implementation strategies and EBI adaptations. This definition of EBQI reflects a conceptualization that EBQI would fit under the umbrella of more global approaches to research and could be operationalized with other methods . We acknowledge that EBQI can be applied across all stages of implementation the formation of local teams to consider data on barriers and facilitators to implementation and (2) drafting, iterating, and planning a locally contextualized implementation strategy to increase uptake of an EBI . Additio(1)What steps do researchers accomplish using EBQI in practice?(2)How do researchers accomplish the steps of EBQI? That is, what activities are used to accomplish EBQI steps?The purpose of this paper is to illustrate the steps, activities, and outputs of EBQI in the pre-implementation phase as operationalized across seven projects to illustrate common elements and variations in application of EBQI . This go2.To identify key steps, activities, and outcomes of EBQI methods, we retrospectively examined a set of seven case examples of EBQI application in research projects. Specifically, our goal was to use case examples to create a holistic description of EBQI and capture how each case selected and tailored implementation strategies and/or made EBI adaptations that would be subsequently tested in a research study . We applNatural variation and overlap in the cases were a key interest. Specially, cases were purposively included to maximize variation in the E2.1.The research team developed a case codebook to collect a standard set of information for each case and coded each case using this codebook. This codebook included basic features of the EBQI process , the progression of EBQI meetings, and activities that were used at each meeting. Using the codebook, the lead investigator for each case extracted details of their respective projects. When needed, the lead author solicited additional information or clarification from investigators. This directed template analysis approach allowed 3.The team completed a cross-case analysis to identify similarities, differences, and the range of steps, activities, and outputs across cases. We used this comparison to generate a list of the key steps of EBQI and corresponding examples of activities to accomplish each step. Cases were examined and compared for key basic features including the number of EBQI meetings held, types of partners included, and modality of meetings. Included case studies ranged in the number of meetings from 2 to 5 , 27, 31.Commonalities and variations across case studies suggest basic steps that are core to EBQI in the pre-implementation phase; these are presented in https://www.liberatingstructures.com/), live editing of documents], illustrating the flexibility of activities to achieve multiple purposes.The activities taken to achieve these steps were diverse See . Each stWe have expanded on the Swindle case to 4.This perspective examined 7 case studies of the application of EBQI in the pre-implementation phase. Comparison of cases suggested 5 common steps of EBQI to prepare for implementation. These steps cut across the variety of settings and EBIs included in our case examples, which illustrates the widespread applicability of these steps. For each step, we identified several activities. That is, various activities were used across the cases to achieve each step. The diversity of activities identified illustrates how each step may be achieved depending on the context and needs of the project. Commonly, the steps identified led to prioritized determinants of implementation, adaptations for EBIs, and fully specified implementation strategies ready for testing. As such, the primary contribution of our perspective is the delineation of steps and activities of EBQI, particularly when used as a deliberative, partnered, and evidence-driven process to inform the selection and tailoring of implementation strategies and EBI adaptations prior to implementation. Thus, our work answers a recent call to provide transparency and detailed descriptions for the process of tailoring in implementation science .Ultimately, the process of EBQI identified in included cases expands on steps of the EBQI model as laid out by early users . The 5 chow to move through EBQI in the pre-implementation phase. Key to many of our activities and an important recommendation for future application of EBQI is the inclusion of end users, which was present in 6 of our 7 cases. Other authors have made a compelling case for the importance of participatory approaches for optimizing fit of EBIs within context (Within each EBQI step, we identified several activities. This illustrates a non-exhaustive catalogue of options for context , address context , and adv context . Our cas context .Notably, EBQI has historically been and continues to be used beyond the pre-implementation phase. Work by Hamilton and colleagues illustraWe believe EBQI used at any phase of implementation is an example of quality CEDI work and fits with other recommended CEDI methods . However"} +{"text": "Elite athletes are continually subjected to a range of constraints specific to high performance, and these can have a negative impact on their health. Although many studies have explored the individual factors related to risky behaviors and disorders in elite sport contexts, and have provided prevention programs, few have focused on health promotion. Consequently, the interpersonal, institutional, and policy factors of the health-related behaviors of elite athletes are still poorly explored. Based on the socioecological model of health, this study aimed to identify the factors involved in the health-related lifestyle of elite athletes.Semi-structured interviews were conducted with 45 participants: athletes , their coaches and managers of elite sport centers . Interviews were audio recorded and transcribed verbatim. Both deductive and inductive thematic analyses were performed. This study was approved by the local Ethic Committee of the University.Our results highlight the different levels of factors related to the health-related lifestyle of elite athletes, using the socioecological model, as perceived by athletes themselves, coaches, and managers. Regarding intrapersonal factors, resilience qualities and health literacy appeared as key factors to influencing the health-related lifestyle of elite athletes. At the interpersonal level, parents and coaches were considered as the main sources of educational support. Regarding institutional factors, the health policies of the elite sport centers were key factors in supporting the athletes\u2019 healthy lifestyle. Similarities and specificities of the views of the different actors have been identified.These results show the interest of the application of the socioecological model in the elite sport domain. They encourage the development of health-promotion programs at different levels of intervention of the socioecological model, beyond traditional health prevention programs. In addition, this study suggests to consider the different perspectives of each actor to co-construct health promotion programs."} +{"text": "The EuResist cohort was established in 2006 with the purpose of developing a clinical decision-support tool predicting the most effective antiretroviral therapy (ART) for persons living with HIV (PLWH), based on their clinical and virological data. Further to continuous extensive data collection from several European countries, the EuResist cohort later widened its activity to the more general area of antiretroviral treatment resistance with a focus on virus evolution. The EuResist cohort has retrospectively enrolled PLWH, both treatment-na\u00efve and treatment-experienced, under clinical follow-up from 1998, in nine national cohorts across Europe and beyond, and this article is an overview of its achievement. A clinically oriented treatment-response prediction system was released and made available online in 2008. Clinical and virological data have been collected from more than one hundred thousand PLWH, allowing for a number of studies on the response to treatment, selection and spread of resistance-associated mutations and the circulation of viral subtypes. Drawing from its interdisciplinary vocation, EuResist will continue to investigate clinical response to antiretroviral treatment against HIV and monitor the development and circulation of HIV drug resistance in clinical settings, along with the development of novel drugs and the introduction of new treatment strategies. The support of artificial intelligence in these activities is essential. Although a cure for HIV cannot be achieved with available antiretrovirals (ARVs), the last 25 years saw dramatic improvement in the prognosis and management of HIV infection, thanks to the use of multiple drugs from different antiretroviral classes ,2,3. IndAs longer periods of follow-up data have become available, the clinician\u2019s attention has shifted towards treatment tolerability and durability. Nevertheless, the impact of pre-existent drug-resistant mutations has remained a challenge in clinical practice, especially in PLWH exposed to suboptimal regimens in the first ART era . In addiIn 2006, a multidisciplinary group of scientists created the EuResist consortium to fight ARV resistance and obtained a grant by the European Commission under the 6th Framework Programme. The project integrated three existing national cohorts from Italy, Germany and Sweden to form a large dataset of clinical and virological information from around 17,000 PLWH, thus giving rise to the EuResist Integrated DataBase (EIDB). By modeling these data via statistical learning, the EuResist project delivered a clinical decision-support tool for predicting the best ART for specific PLWH by leveraging curated real-world data. The multicohort EuResist Network was established in 2008 as a follow-up of the EuResist project to manage the EIDB and the EuResist ART response prediction system. Currently, the EIDB is one of the world\u2019s largest datasets suitable for training genotype-centered treatment-response models. The EIDB collects information about pseudonymized demographic and clinical characteristics of PLWH, including antiretroviral therapies, reasons for treatment change, AIDS defining events, viral co-infections, CD4 + T cells counts, viral load measurements, and HIV sequences.Originally, the EIDB was developed by integrating biomedical information from the three founding nationwide databases: ARCA , AREVIR (Germany), and InfCareHIV at Karolinska Institute, Stockholm (Sweden). Following the initial setup, other centers became partners of the EuResist Network and provided biomedical data to the EIDB. Most of these remain active contributors, together with the three founders; at time of writing, this includes: the Instituto de Higiene e Medicina Tropical ; the IrsiCaixa Foundation (Spain); the Laboratoire de R\u00e9trovirologie of CRP-Sant\u00e9 (Luxembourg); the Gamaleya Institute of Virology (Russia); the Koacaeli University Medical Faculty (Turkey); and the CoRIS cohort (Spain). Additionally, data from the Rega Institute (Belgium); the National Referral Laboratory of Rwanda; the DUET study conducted by Tibotec; and the Resist study conducted by Boehringer Ingelheim, from the Infectious Diseases, AIDS and Clinical Immunology Research Centre of the State Institution Centre Public Health Ministry of Health of Ukraine and from the Infectious Diseases AIDS and Clinical Immunology Research Centre (IDACIRC) of Georgia were integrated in the past . https://www.euresist.org/eidb accessed on 31 March 2022). Data integrity and updating have been ensured for the last 15 years and onwards through an iterative process of data cleansing and periodical refresh from the contributing centers. The key uses of the EIDB have included the training of a machine-learning-based engine assisting treatment choices and providing curated datasets for specific studies, focusing on HIV variability, treatment, and drug resistance [The EIDB is updated twice a year with new data from the contributing centers by using import routines maintained centrally by the EuResist IT staff. Currently, it contains data from 105,903 PLWH, contributing 102,851 viral sequences, 248,249 treatment regimens, 1,451,753 viral load measurements and 1,486,295 CD4 cell counts A. The masistance .The objective of this manuscript is to offer an overview of the main contribution provided by the EuResist multicohort initiative in the fight against HIV drug resistance during the last 15 years, based on the efforts of many researchers from different European countries.The EuResist Network complies with the General Data Protection Regulation (GDPR) and all applicable laws, rules and regulations, with particular reference to ethical issues concerning the collection of data belonging to HIV patients and the relative manipulation and sharing procedures. All the data contributors to the EIDB certify that: the data collection was approved by the local ethics committees in agreement with local requirements and written informed consent was obtained from all patients before participation when necessary; the procedures are performed under the guidance and responsibility of the contributing centers; personal data are lawfully processed and may be contributed to the EIDB for scientific purposes on the basis of the data subject\u2019s consent or another legal basis valid under the GDPR (art. 6 and art. 9).This study is performed in accordance with the ethical principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization.Data are securely stored in Italy. They contain sensitive human subject information and cannot be shared publicly because of privacy issues. Data are available under request to the EuResist Scientific Board, comprising all the data controllers. The EuResist Network has received research grants from the European Commission and unrestricted research grants from the following pharmaceutical companies: Abbott, Janssen Tibotec, Gilead Sciences, Merck Sharp and Dohme, Pfizer, Theratechnologies, and ViiV Healthcare. Neither the companies nor the patients had any role in the design, recruitment, or conduct of the studies.The emergence of antiretroviral drug resistance has long been a leading cause of treatment failure in PLWH. Particularly, before the advent of compact, high-genetic-barrier cART, the development of drug resistance was almost inevitable at some point in time. Thus, strategies for delaying the onset of resistance, preserving treatment options and avoiding cross-resistance were typically aided by algorithms interpreting HIV genotype. While these systems were mostly based on expert reviews of the literature, the EuResist consortium proposed a novel approach for predicting the in-vivo efficacy of antiretroviral drug regimens against a given virus isolate, based on statistical learning from a large amount of data correlating virus genotype and patient data on treatment response in clinical practice. vs human Experts) study in which 25 complete patient histories were provided to a panel of 10 global top experts in HIV drug resistance, who had to indicate whether the next ART regimen used would be effective or not. The EuResist system outcompeted nine of the experts in accuracy and equaled the most proficient one, demonstrating the strength and feasibility of the approach in a real-world simulation [Based on the analysis of the EIDB data, different predictive models have been developed over the years. In 2008, the first machine-learning engine was reported, which combined three models as follows: (a) generative-discriminative method, (b) regression with derived evolutionary features and (c) regression with a mixture of effects. The engine demonstrated an increase in the accuracy of prediction when taking into account clinical information and demographic factors in addition to genotypic information [mulation . In 2010, Bogojeska et al. developehttps://hivdb.stanford.edu/ accessed on 10 April 2023) provides an impressive number of options for querying a curated HIV sequence database derived from published HIV sequences, with novel features and services released on a regular basis.It must be noted that, despite considerable efforts to improve the algorithms for prediction of response to ART, the increase in accuracy with respect to standard systems based only on the interpretation of HIV genotype has been limited. Factors impeding higher benefits by applying advanced statistics have not been identified but likely include the sparse representation of data in the training datasets and the complete lack of data on one major determinant of response to treatment, namely adherence to therapy. Moreover, the gain in accuracy comes at the cost of additional data to be input into the system\u2014something that most doctors are reluctant to do. Additional bottlenecks for the transition from simple to improved yet more-complex methods include the lower degree of human interpretability of the latter and the globally decreased impact of drug resistance in modern ART . As a maThanks to the continuous and longitudinal accumulation of viral sequences and patient data, the EIDB has offered a tremendous opportunity to monitor the selection and spread of transmitted and acquired resistance-associated mutations (RAMs), the circulation of different viral subtypes, and their impact on treatment outcome, most often as measured by changes in viral load. In more recent years, non-B subtypes have become endemic in the European population, likely due to human migration from non-B areas. This may have had an impact on the global picture of drug resistance since most non-B areas have been characterized by a different coverage of ART regimens and consequently different patterns of emergent drug resistance. This effect has been later diluted and will continue to be diluted by the harmonization of ART regimens, particularly those based on high-genetic-barrier regimens, significantly limiting drug resistance and failure.A key issue in HIV drug resistance is the prevalence and incidence of multidrug resistance, resulting in an extensive loss of treatment options and the inability to control virus replication and halt disease progression. Two EuResist studies have shown a declining trend of resistance to the four main classes of ARVs, including protease inhibitors (PI), nucleoside (NRTI) and non-nucleoside (NNRTI) reverse transcriptase inhibitors, and integrase strand transfer inhibitors (INSTI). The first study analyzed viral sequences collected from 3414 individuals with at least 1 genotype test result available between 2008 and 2019 and found that high-level resistance to at least 1 drug in each of the 4 main ARV classes declined from 5.6% in 2008 to 2.4% in 2018, with only 2.5% of the patients accumulating four-class resistance over time . NotablyThe studies conducted by Lapokov et al. and NeshA recent study conducted by van de Klundert et al. showed, Over the years, the EIDB was used to explore the clinical impact of specific RAMs. For example, Theys et al. observedInspired by the updates of the international HIV treatment guidelines, the EuResist Network explored the real-world effectiveness of different treatment strategies. Understanding and predicting treatment efficacy and duration of effectiveness, i.e., how long an antiretroviral therapy can be sustained without changes, even in the presence of pre-existing RAMs, has become an important challenge in the context of addressing HIV treatment optimization. For example, the analysis of the EIDB data suggested that the efficacy of the innovative dual-drug strategy combining the NNRTI etravirine with the ritonavir-boosted PI darunavir was comparable to that of alternative regimens where etravirine was coupled with an alternative boosted PI . In 2019More recently, two studies explored the effectiveness and discontinuation rate of INSTI, a key component of most current ART regimens. Among 2976 INSTI treatments started by na\u00efve PLWH, elvitegravir- or dolutegravir-based first-line antiretroviral treatment was highly effective in routine practice across Europe, even in the presence of transmitted drug resistance for the accompanying NRTIs. However, the rate of INSTI discontinuation was much higher than the rate of virological failure . InteresAnother study by Miranda et al. investigThe EuResist Network has been collaborating with other non-European cohorts and global initiatives to investigate HIV-resistance-related issues, particularly in low-income countries. From 2010 to 2013 it participated in the ENEAA project (EDCTP JP.2009.10800.002), coordinated by Karolinska Institut and involving the Addis Ababa University, Ethiopia; the Muhumbili hospital, Dar-es-Salaam, Tanzania; and the World Friends Hospital, Nairobi, Kenya, integrating training activities and IT infrastructures to improve capacities in the eastern African area. The TenoRes collaboration included data from adult HIV treatment cohorts and clinical trials in Europe, Latin and North America, sub-Saharan Africa, and Asia. Among 1926 PLWH enrolled after virological failure with first-line tenofovir-containing ART, HIV drug resistance was detected in an alarmingly high fraction of cases, strengthening the need for the surveillance of transmitted drug resistance . AnotherThe EIDB can be accessed upon formal request by scientists aiming at investigating HIV treatment and drug-resistance-related topics. The EuResist Management Board processes requests in a reasonable time and asks the individual cohorts for permission to access the data for the specific study, which has to be well-defined and scientifically sound. EuResist encourages other clinicians and scientists, also from non-European countries, to collaborate for the advancement of knowledge on HIV drug resistance and treatment, and it is open for scientific studies. Karolinska Institutet ;Max Planck Gesellschaft (Germany);University of Siena ;InformaPRO s.r.l. ;Cologne University (Germany).EuResist Network is a non-profit European Economic Interest Grouping (EEIG) composed by:th Framework Programme (FP)), the EuResist Network participated in and guided several research projects funded by the European Commission, among which we can mention: CHAIN-Collaborative HIV and Anti-HIV drug resistance Network, a large scale integrated project ; CARE-Common Action against HIV-TB HCV across the Regions of Europe, ; and EuCARE-European Cohorts of Patients and Schools to Advance Response to Epidemics , where the focus moves to SARS-CoV-2 ad its variants.In addition to the already mentioned EuResist project (Grant n. IST-2004-027173, 6EuResist also runs dissemination and training activities. Further to the cited ENEAA EDCTP project, it offers training tools on its website; it participates in the annual ARCA Mentor School event, and has organized a EuResist Mentor School in Cologne in 2018 with the objective to bridge the gap between data science and medical/biological sciences.Since 2007, EuResist has contributed to the annual Arevir Meeting organized by the University of Cologne and Genafor, holding a EuResist session.The main strength of the EuResist Network is the inclusion of all PLWH followed at each of the participating centers, ensuring the full representativeness of the real-life setting, including individuals typically not enrolled in randomized trials due to, e.g., the presence of baseline drug resistance or past virological failures. The sample size of the cohort is also notable, with a total of 105,903 PLWH as of March 2022. Likewise, the geographic distribution of the participating centers is Europe-wide, with additional cases from Turkey, Russia, Ukraine, Georgia, and Rwanda. The observational, retrospective, and prospective multicohort design provides an extraordinarily large time span, with data collection starting as early as the late 1980s, translating into a unique opportunity to follow virus evolution and investigate very different treatment strategies across all antiretroviral treatment eras.The main limitation of the EIDB is that most contributing cohorts collect only routine clinical and viro-immunological data. Some data can be missing in the individual databases, making the overall data collection not uniform across areas and resulting in the exclusion of large datasets when specific variables are required. The lack of information on tolerability issues, adherence to ART, clinical non-AIDS-related events and concomitant medications make the cohort not suitable for many kinds of investigations. Lastly, although a semiannual update is planned, delays between local data collection and the availability of an updated centralized database often occur, postponing the possibility to study the most recent treatments, which are typically of maximum interest.The EuResist cohort was established with the purpose of developing a clinical decision-support tool predicting the most effective antiretroviral therapy for PLWH based on their clinical and virological data. Later, the cohort widened its activity to the more general area of antiretroviral treatment with a focus on virus evolution and drug resistance. Following its interdisciplinary vocation, EuResist will continue to investigate clinical response to antiretroviral treatment against HIV and monitor the development and circulation of HIV drug resistance in the clinical setting along with the development of novel drugs and the introduction of new treatment strategies. The support of artificial intelligence in these activities is essential."} +{"text": "Dear Editor,A 33-year-old male patient presented with multiple erythematous-brown papules measuring 1 to 5\u00a0mm, disseminated on the upper limbs, trunk and thighs . DermoscHistopathology showed proliferated capillary vessels with dilated lumen A and mulAfter he was instructed about the condition, the patient chose not to undergo treatment for aesthetic purposes and returned after one year with spontaneous significant improvement in the number, pigmentation, and size of the lesions .Figure 5Multinucleate cell angiohistiocytoma is a rare benign fibrous histiocytic proliferation, described in 1985.Treponema pallidum infection. Another theory proposes that MCA arises under the influence of female hormones due to the identification of estrogen receptor alpha expression in the interstitial and multinucleate cells of lesions in several patients.Since the first description of MCA, several hypotheses have been proposed for its etiology and pathogenesis. Most authors believe it to be a reactive process and reports of spontaneous remission further support this hypothesis.Dermoscopy can show some similarities with dermatofibromas, such as whitish areas and a fine peripheral reticulated pattern. Diffuse reddish areas with blurred edges, which likely represent the characteristic vascular dilation, may also be found.Histopathology shows proliferation of dilated capillaries, fibrous stroma with thickened collagen bundles, and the presence of multinucleate giant cells. The overlying epidermis may be normal or hyperplastic. The presence of at least three of the described in the adequate clinical context is highly specific for MCA and allows differentiation from fibrous papule and dermatofibroma. The criteria considered for the diagnosis were: a) Presence of atypical and multinucleate fibroblasts with at least two nuclei; b) Presence of superficial parallel dermal fibrosis; c) Presence of thickened superficial papillary dermal vessels; d) Absence of perifollicular fibrosis.Regarding immunohistochemistry, the multinucleate cells are typically negative for factor VIII and CD34 and positive for vimentin and factor XIIIa. There is a positive correlation between CD68-positive expression of endothelial cells and lesion size, and an inverse correlation between CD68-positive expression on multinucleate cells and the development of multiple lesions.2 laser.The biological behavior of MCA is progressive in most cases, albeit benign, with spontaneous improvement being rare. Treatment can be carried out for aesthetic purposes. The currently available therapeutic options include topical or intralesional corticosteroids, surgical excision, cryotherapy, argon laser, intense pulsed light, and COTreponema pallidum infection and suspected by dermoscopic findings. Because it is rare, it is important that dermatologists and pathologists are able to recognize it for a better approach and to provide recommendations to the patient. Multiple treatment options are available to improve the aesthetic appearance, most of which are supported by case reports.In conclusion, the authors describe a rare case of MCA possibly triggered by None declared.Patricia Mayumi Ogawa: Design and planning of the study; drafting and editing of the manuscript; collection, analysis and interpretation of data; critical review of the literature.Maria Cristina Arci Santos: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis and interpretation of data; effective participation in research orientation; critical review of the manuscript.Nilceo Schwery Michalany: Approval of the final version of the manuscript; collection, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; effective participation in research orientation; critical review of the manuscript.Renato Shintani Hikawa: Approval of the final version of the manuscript; collection, analysis and interpretation of data; design and planning of the study; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; effective participation in research orientation; critical review of the manuscript.None declared."} +{"text": "Reviews in ophthalmology 2022.\u201d This issue is dedicated to providing a comprehensive overview of the latest advancements, challenges, and future directions in the field of ophthalmology. As we navigate through the third decade of the 21st century, it is clear that our understanding of ocular diseases and their management has significantly evolved, driven by groundbreaking research and technological innovations.Welcome to the Research Topic, \u201cIn this Research Topic, we have compiled a series of reviews that delve into various aspects of ophthalmology, from the surgical management of corneal disorders to the genetic underpinnings of complex ocular diseases. These reviews provide a snapshot of the current state of knowledge, highlighting the strides we have made and the challenges that lie ahead.Each review in this Research Topic offers a unique perspective, reflecting the breadth and depth of research in ophthalmology. From exploring the effectiveness of different surgical techniques and treatment modalities to unravelling the genetic complexities of ocular diseases, these reviews represent the cutting edge of ophthalmic research.Reviews in ophthalmology 2022,\u201d we hope to foster a deeper understanding of the current landscape of ophthalmology, stimulate further research, and ultimately contribute to improving patient care. We invite you to delve into these insightful reviews, gain new knowledge, and join us in the ongoing quest to unravel the complexities of the human eye.As we present \u201cThe field of ophthalmology has witnessed significant advancements in understanding and managing ocular surface diseases. This Research Topic summarises recent research on various ocular conditions, including ocular graft-vs.-host disease (oGVHD), Dry Eye Disease (DED), Keratoconus (KC), paediatric keratoconus, pterygium, and Fuchs' endothelial corneal dystrophy (FECD).Salari et al. highlighted the effectiveness of superficial keratectomy (SK), a surgical procedure involving the manual dissection of the superficial layers of the cornea. The review emphasised the versatility of SK in addressing various ocular conditions, including corneal degenerations, dystrophies, scarring, recurrent corneal erosions, and retained corneal foreign bodies.Tappeiner et al. focused on the challenges and concepts in diagnosing and managing oGVHD, a condition characterised by tissue inflammation following allogeneic hematopoietic cell transplantation. The review underscored the importance of interdisciplinary treatment approaches to improve patients' quality of life and prevent potentially irreversible visual loss.Ling et al. discussed the increasing incidence of DED and the role of immune regulation defects in its pathogenesis. The review emphasised the need for anti-inflammatory drugs in treating moderate-to-severe DED and highlighted the potential of Traditional Chinese Medicine in managing the condition.Hao et al. provided a comprehensive analysis of the pathogenesis of KC, an aetiologically heterogeneous corneal ectatic disorder. The study identified several genes and pathways involved in the disease's development, offering an integrated insight into the gene-based aetiology and pathogenesis of KC.Li et al. conducted a meta-analysis comparing the efficacy of different corneal collagen cross linking (CXL) methods for paediatric keratoconus. The study concluded that standard epithelium-off CXL and accelerated epithelium-off CXL appear to be comparable in efficacy, with standard CXL providing greater changes in visual and pachymetric outcomes.Taher, Alnabihi et al. performed a systematic review and meta-analysis on the management of primary pterygium, a common ocular surface disease. The study confirmed the effectiveness of a single intraoperative topical application of 0.02% mitomycin C during excision of pterygium followed by conjunctival autograft in reducing the rate of pterygium recurrence.Tsedilina et al. conducted a systematic review of the role of variants in the genes SLC4A11, ZEB1, LOXHD1, and AGBL1 in the development of FECD. The study confirmed the causal role of SLC4A11 variants in FECD, but further evidence is needed to confirm the roles of ZEB1, LOXHD1, and AGBL1 variants.Lastly, In this Research Topic, we, also, explore the latest technological advancements, delve into the complex pathophysiological mechanisms, and discuss innovative therapeutic strategies that are shaping the future of retinal treatments.Ladha et al.'s exploration of subretinal therapy, we are introduced to the potential of robotic technology in enhancing the precision and standardisation of ocular gene and cellular therapy delivery. The authors highlight the limitations of manual delivery, including the risk of iatrogenic damage and variability in delivery. They also underscore the importance of understanding the immune response elicited by the introduction of exogenous viral vectors or transplanted cells to the eye. The use of microprecision medical robotic technology is proposed as a solution to these challenges, offering reproducible and standardised delivery independent of injection speed.Starting with Tang et al. provide a comprehensive review of the development of risk factors and cytokines in Retinal Vein Occlusion (RVO), the second most prevalent retinal disease. The authors emphasise the complexity of RVO mechanisms due to the interrelated nature of risk factors. They also highlight the role of cytokines as powerful mediators of pathological conditions such as inflammation, neovascularisation, and macular oedema. This review underscores the need for continued research into the mechanisms and treatment targets of RVO.Next, Casciano et al. then delve into the role of the mammalian target of rapamycin (mTOR) pathway in diabetic retinopathy (DR). They outline how chronic hyperglycaemia can lead to retinal neurodegeneration through overactivation or inhibition of the mTOR pathway. The authors highlight the mTOR pathway's role in coordinating multiple anabolic and catabolic processes, such as autophagy, oxidative stress, cell death, and the release of pro-inflammatory cytokines. This review provides valuable insights into the potential of targeting the mTOR pathway in the management of DR.Haydinger et al. provide a clinical overview of macular oedema, a complication of many retinal diseases that can lead to severe and permanent visual impairment and blindness. The authors discuss the mechanisms of disease, highlighting the dysregulation of the blood-retinal barrier as a key factor driving fluid accumulation in the central retina. They also discuss current treatments, including vascular endothelial growth factor blockers, corticosteroids, and non-steroidal anti-inflammatory drugs, and identify areas of opportunity for future research.Finally, In the realm of paediatric ophthalmology, two papers have made significant strides in understanding and treating conditions that affect the eyes of children.Gan et al., conducted a meta-analysis to evaluate the efficacy and safety of varying doses of atropine in slowing myopia progression in children. Myopia, or short-sightedness, is a common condition that affects a significant number of children worldwide. The study found that the efficacy and adverse effects of atropine are dose-dependent. High-dose atropine was found to be effective in slowing myopia progression, but its efficacy reduced after the first year of treatment. On the other hand, low-dose atropine showed better efficacy over a longer follow-up period. However, the higher the dose of atropine, the higher the incidence of adverse effects, such as photophobia. This meta-analysis provides valuable insights for clinicians in determining the appropriate dosage of atropine for treating myopia in children.The first paper, led by Taher, Ghaddaf et al., conducted a systematic review and meta-analysis to assess the efficacy and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections for the treatment of retinopathy of prematurity (ROP). ROP is a potentially blinding eye disorder that primarily affects premature infants. The study found that anti-VEGF monotherapy was associated with fewer adverse events than laser therapy. However, there was no significant difference between the two treatments in terms of recurrence rate, treatment switching, retreatment, and mortality rate. This study provides a comprehensive review of the current standard treatment for ROP and offers valuable insights for future research and clinical practice.The second paper, by The recent studies on the ocular implications of COVID-19 and other viral infections, as well as the effects of their respective vaccines, have shed light on a critical aspect of these pandemics that often goes unnoticed.Zauli et al. highlighted the potential therapeutic role of the MDM2 inhibitor Nutlin-3 in protecting the eye from SARS-CoV-2 infection. The study suggests that the protein p53, present in high levels in the cornea, conjunctiva, and tear film, could play a protective role against the virus. The authors propose that the topical use of Nutlin-3 might protect the anterior surface of the eye from SARS-CoV-2 infection, thereby reducing the spread of the virus.Akbari and Dourandeesh provided an updated overview of the ocular manifestations of COVID-19. The study emphasises the importance of paying attention to ocular manifestations during COVID-19, as they can be a presentation of life-threatening events such as stroke. Conjunctivitis is the most common presentation, which can develop at any stage of COVID-19, and there are also reports of life-threatening complications, such as rhino-orbital cerebral mucormycosis.Taha et al. conducted a literature review highlighting the ocular complications of recent viral pandemics, including Monkeypox, SARS-CoV-2, MERS, Ebola, H1N1, and Zika viruses. The review also discusses the ocular complications of the vaccines and treatments used during these pandemics, and the role of the eye as a significant route of viral transmission.Scalabrin et al. provided an overview of the ocular effects caused by viral infections and their corresponding vaccines, focusing on varicella zoster virus, measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2. The study aimed to establish a risk-benefit relationship from an ophthalmological point of view, comparing the pathological effects on the eye due to these viral infections with the possible ocular adverse effects of their respective vaccines.Abu-Ismail et al. discussed the impact of the COVID-19 pandemic and the wearing of face masks on ophthalmology practice. The study found that wearing face masks for long periods increases the chances of dry eyes and other ocular issues. The pandemic has also affected ophthalmology practices in managing patients, with new factors to consider, such as the risk of endophthalmitis, tests and symptoms of patients with glaucoma, and the emerging symptoms associated with the COVID-19 vaccination.Lastly, In conclusion, the reviews presented in this Research Topic provide a comprehensive overview of the current state of ophthalmology, highlighting the significant strides made in understanding and treating various ocular conditions. The reviews underscore the importance of continued research and innovation in addressing the challenges that lie ahead. The impact of the COVID-19 pandemic on ophthalmology, particularly the effects of prolonged face mask use, has emerged as a critical area of study. As we continue to navigate through these unprecedented times, it is crucial to adapt our practices and explore new avenues to ensure the best possible care for our patients. We hope that the insights provided in these reviews will stimulate further research and contribute to the advancement of ophthalmology.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "The COVID-19 pandemic highlighted some potential limitations of transmission-based precautions. The distinction between transmission through large droplets vs aerosols, which have been fundamental concepts guiding infection control measures, has been questioned, leading to considerable variation in expert recommendations on transmission-based precautions for COVID-19. Furthermore, the application of elements of contact precautions, such as the use of gloves and gowns, is based on low-quality and inconclusive evidence and may have unintended consequences, such as increased incidence of healthcare-associated infections and spread of multidrug-resistant organisms. These observations indicate a need for high-quality studies to address the knowledge gaps and a need to revisit the theoretical background regarding various modes of transmission and the definitions of terms related to transmission. Further, we should examine the implications these definitions have on the following components of transmission-based precautions: (i) respiratory protection, (ii) use of gloves and gowns for the prevention of respiratory virus infections, (iii) aerosol-generating procedures and (iv) universal masking in healthcare settings as a control measure especially during seasonal epidemics. Such a review would ensure that transmission-based precautions are consistent and rationally based on available evidence, which would facilitate decision-making, guidance development and training, as well as their application in practice. Standard and transmission-based precautions are essential elements of infection prevention and control (IPC) practices ,2. TransEmerging scientific evidence and revisiting previously available studies support the argument that the distinction between droplets and aerosols is artificial, and dogmatic size thresholds for \u2018large droplets\u2019 and \u2018aerosols\u2019 are not fully consistent with the physical properties that are relevant for the transmission of respiratory viruses -7. WhileMycobacterium tuberculosis, and the measles and varicella-zoster viruses, have traditionally been considered as being transmitted obligatorily or preferentially through the airborne route, thus necessitating precautions against airborne transmission, including the use of respirators and hospitalisation in single rooms with negative pressure [Only a few microorganisms, such as pressure . These rpressure ,12.Altogether, the relevant role of various routes of transmission, which includes the physical transport of an infectious particle leading to infection, has been challenging to assess. Efforts to define criteria of proof for each transmission route have been useful but it is difficult to draw any conclusion with certainty ,14. The Furthermore, the quality and certainty of evidence on the effectiveness of various elements of PPE used for transmission-based precautions remains low, as the evidence is based mostly on observational studies and only a few randomised controlled trials. Several systematic reviews and meta-analyses have been published but the certainty of the conclusions is limited by the bias of the underlying studies . This meLater variants of SARS-CoV-2 are characterised by higher transmissibility than previous variants . On the These observations indicate a need to revisit transmission-based precautions and their effectiveness for preventing transmission of SARS-CoV-2 in particular and other respiratory viruses in general, as well as a need to fund, design and execute high-quality studies to fill the evidence gaps for transmission-based precautions .On 16 March 2022, the European Centre for Disease Prevention and Control (ECDC) convened a group of 11 IPC experts to explore whether modifications in transmission-based precautions would be needed to address what we learned during the COVID-19 pandemic and to identify knowledge gaps and research needs. Experts were selected as a convenience sample from the ECDC Expert Directory based on declared expertise in hygiene and infection control. The discussion was structured based on the following elements of the Evidence to Decision (EtD) framework : (i) HowBoxA review of the theoretical framework, and definitions of terms, for modes of transmission underpinning the IPC paradigm;Risk assessment parameters for IPC measures based on risk of infection transmission inclusive of: transmissibility of infection, impact of infection, patient factors, staff risk factors, practice/procedure factors and environmental factors, while taking into consideration: healthcare workers\u2019 preference, desirable and undesirable anticipated effects and the balance between them, overall certainty of the evidence of effects, acceptability and ease of implementation;Design and implementation of high-quality applied clinical research to inform:- The use of respirators and medical face masks in various risk scenarios,- The impact of gowns, aprons and eye protection as part of transmission-based precautions,- Optimal masking strategies to reduce risk of transmission inclusive of sessional vs risk-targeted, wider masking policy, including behavioural insights to adherence, any unintended consequences for staff and patient safety, and staff preferences,- A risk-based approach to the selection of personal protective equipment considering the time of exposure, the proximity to the patient and the procedure/task.IPC: infection prevention and control.Given that neither the current droplet nor the airborne precautions address the role of aerosols at short distances, various options could be considered for adapting current transmission-based precautions. Droplet precaution measures could be expanded to address the theoretical risks linked to inhalation of short-range aerosols. A two-tiered risk-based approach could be applied, based on proximity, length of exposure, type of symptoms and type of care: (i) contacts with prolonged, close proximity to the patient, including the performance of high-risk procedures, are associated with higher risk and justify the use of high-efficacy respiratory protection; (ii) for contacts without prolonged, close proximity to an infectious patient in adequately ventilated spaces, the effectiveness of medical face masks would be sufficient.Gloves are part of contact precautions that have been recommended for the prevention of the transmission of respiratory viruses such as influenza and SARS-CoV-2. However, hand hygiene, including alcohol-based hand rubs, is an effective measure against SARS-CoV-2 and other respiratory viruses ,30, as wWhile the desirable anticipated effects from the use of gloves and gowns/aprons are small, the undesirable anticipated effects are at least moderate. Therefore, the balance of desirable and undesirable effects does not favour the routine use of gloves or gowns/aprons for the prevention of COVID-19 and other respiratory virus infections. An exception may be prolonged, close exposure to a case, especially a patient who is coughing or sneezing heavily, when high-risk procedures are required, or in cases when there is a high risk of exposure to infectious body fluids - as stipulated by standard precautions.There is emerging evidence that the increased risk of infection from some aerosol-generating procedures may be more related to proximity with the patient than to increased generation of aerosols by the procedure itself . SeveralGiven that the risk of transmission is related not only to the microorganism, but also to the duration and proximity of contact, the applied transmission-based precautions should ideally be selected following a point-of-care risk assessment, taking into account proximity, duration of exposure, risk of aerosol production and the type of task performed.Various forms of continuous face mask use, such as universal masking, applying to healthcare workers, patients, visitors and persons accompanying the patient, and targeted continuous masking, applying to healthcare workers , especiaThe eyes have been identified as potential routes of entry for respiratory viruses either directly, by infection of the ocular mucosa, or by transfer to the nasopharynx through the nasolacrimal duct . AvailabA limitation of the above suggestions is the low level of available evidence in epidemiological studies or clinical trials for the effectiveness of specific elements of transmission-based precautions, including elements of PPE. Emerging evidence may increase our certainty in the magnitude of their effectiveness. A better understanding of the physical processes of exposure does not automatically translate into more effective prevention measures, as infection is a more complicated process than the transfer of infectious particles, involving immune processes and the suitability of various exposed host tissues for the entry of viruses. The applied preventive measures aim at mitigating the risk of infection to an acceptable level, taking into account the assessed risk but also other parameters such as preferences, ease of implementation and unintended consequences. Studies which use various forms of modelling and laboratory experiments to investigate the role of procedures and behaviours in generating and dispersing respiratory particles are limited and ultimately do not provide adequate evidence to address transmission in the complex healthcare environment. There is a need for applied clinical research on the effectiveness but also the unintended consequences of preventive measures to support the development of evidence-based recommendations for guidance. Furthermore, human challenge studies, taking carefully into consideration any ethical issues , may proTransmission-based precautions are important but are not the only measures to control SARS-CoV-2 transmission in healthcare. It should be noted that PPE is only one among several control measures in the hierarchy that includes elimination and substitution, engineering and administrative controls . TransmiMeasures to prevent and control an infection with high morbidity and case fatality and without treatment options are influenced by the assessed risk of adverse outcome and ofteThe ECDC expert panel suggested that the IPC community should consider revisiting the current transmission-based precaution framework, including the theoretical background regarding various modes of transmission and the definitions of terms related to transmission, to account for available and emerging scientific evidence and the role that the consequence of infection plays on the choice of the precautions. Such a review would ensure that transmission-based precautions are consistent and rationally based on available evidence, which would facilitate decision-making, guidance development and training, as well as their application in practice to prevent transmission of SARS-CoV-2 and of other respiratory viruses. High-quality studies are imperative to address the current knowledge gaps and strengthen the evidence for any future revision of transmission-based precautions."} +{"text": "The National Agrobiodiversity Center under the Rural Development Administration (RDA) in Jeonju, Republic of Korea stands as the foremost national genebank in the country. Over the years, the National Agrobiodiversity Center has remained committed to enriching its collection with foreign genetic resources, elevating its status to a world-class plant genetic resources (PGR)- holding genebank. Currently, several steps are being undertaken to improve the accessibility of the collection to national as well as international researchers, improve the data available on the resources, and amend the passport information for the accessions. With the implementation of the Nagoya Protocol, the origin of genetic resources is being highlighted as an important input in the passport information. The RDA-Genebank actively responds to the Nagoya Protocol by supplementing passport data for resources lacking information on their origin. In addition, a large number of conserved resources are continuously multiplied, and agronomic traits are investigated concurrently. With the traditional methods of characterization of the germplasm requiring a significant amount of time and effort, we have initiated high-throughput phenotyping using digital techniques to improve our germplasm data. Primarily, we have started adding seed phenotype information followed by measuring root phenotypes which are stored under agronomic traits. This may be the initial step toward using largescale high-throughput techniques for a germplasm. In this study, we aim to provide an introduction to the RDA-Genebank, to adopted international standards, and to the establishment of high-throughput phenotyping techniques for the improvement of passport information. The National Agrobiodiversity Center in Jeonju, Republic of Korea, under the administration of the Rural Development Administration (RDA), plays a pivotal role in the collection, evaluation, conservation, and distribution of diverse plant genetic resources, including both seeds and vegetative germplasms. With the establishment of a low-temperature seed storage facility in 1975 and a seed management office in 1976, around 3300 germplasms were managed at local agricultural institutions. Later, in 1980, official documentation of 12,865 rice germplasms conserved by local agricultural institutions and universities was carried out, followed by their addition to the low-temperature seed storage collection. While seed germplasms were conserved at the genebank, external management institutions managed vegetative germplasms. In 1993, the RDA-Genebank began international cooperation starting with the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR) (1993\u20132019). At the RDA-Genebank, researchers aim to secure germplasm diversity by continuously collaborating with international joint research institutes including the Uzbek Research Institute of Plant Industry (UzRIPI) in Uzbekistan (1996\u20132004), the Department of Agriculture (DOA) Genebank in Thailand (1998), the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) (1998\u20131999) in Germany, the International Rice Research Institute (IRRI) in the Philippines, the Plant Science and Agricultural Research Institute (PASRI) in Mongolia, the National Bureau of Plant Genetic Resources (NBPGR) in India, and the Georgian Academy of Agricultural Sciences (GAAS) in Georgia. Adoption of international policies such as the Convention on Biological Diversity (CBD) at the United Nations conference on environment and development (UNCED) in 1992 and the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from Their Utilization in 2010 has further reinforced germplasm conservation efforts. Despite the limitations on data disclosure and international distribution of germplasms, Korea remains one of the significant countries conserving plant biodiversity. The Nagoya Protocol is an international agreement that aims to promote the fair and equitable sharing of benefits arising from the use of genetic resources, including those held in genebanks. The protocol was adopted in 2010 under the United Nations Convention on Biological Diversity (CBD) and entered into force in 2014 . The hisOverall, the Nagoya Protocol represents a significant milestone in the international effort to promote the conservation and sustainable use of genetic resources, including those held in genebanks, and to ensure that the benefits of these resources are shared fairly and equitably. In accordance with the Nagoya Protocol, RDA-Genebank continuously updates passport data on the origins of germplasms to actively respond to the utilization of genetic resources and the sharing of benefits accordingly. As a method of supplementing origin information, the passport data disclosed on the homepage of the relevant genebank was reflected on the basis of the original international genebank resource number.http://genebank.rda.go.kr/plantMain.do, accessed on 23 Mar 2023). Whereas the Korean version provides access to essential passport data, including conserved genetic resources of plants for distribution, the English version falls short in divulging the current status of resource conservation and the pertinent passport data. Consequently, this omission poses challenges for foreign researchers seeking to obtain and investigate our germplasms.The website of our institution presently offers visitors the option to select either the Korean or the English version were domestically distributed in the Republic of Korea, while only a small proportion (0.73%) was circulated internationally . The treIn 2018, the RDA-Genebank initiated a collaboration research program, the Technology Development Project for Customized Agricultural, Forestry, and Fishery Products and Services, partnering with agricultural organizations such as seed companies and private research institutions. The objectives of this program were to broaden and improve the characterization and evaluation information of the conserved germplasms, augment their diversity, propagate them, and concurrently conduct characterization research. Through chemical composition profiling or disease resistance evaluation, commendable genetic resources have been shortlisted from the outcomes of these research endeavors, to be recommended for breeding and further scientific investigations. During 2010\u20132013, a total of 1343 accessions were distributed for local propagation of rice to the IRRI, the Philippines. For the purpose of germplasm exchange with international genebanks, the RDA-Genebank has introduced 568 accessions in the ARS (2012) in the US, 995 accessions in the UzRIPI in Uzbekistan (2011\u20132014), 10 in the VIR in Russia (2014), 235 in the AVRDC in Taiwan (2013\u20132016), and 232 in the GAAS in Georgia (2015\u20132016) as a part of its germplasm exchange policy. We have also supplied to private entities, including the distribution of 62 sesame accessions to the Tainan District Agricultural Research and Extension Station in Taiwan. The distribution overseas can be categorized into two types: those sent through Korea Project to the International Agriculture (KOPIA) center as part of Official Development Assistance (ODA) projects, which provide country-specific farming techniques, and those distributed through the 3-FACI. The 3-FACI initiative includes the Asian Food & Agriculture Cooperation initiative (AFACI), the Korea\u2013Africa Food & Agriculture Cooperation initiative (KAFACI), and the Korea\u2013Latin America Food & Agriculture Cooperation initiative (KoLFACI). These programs aim to facilitate multi-continental research and collaboration to address common farming problems. Despite RDA-Genebank\u2019s possession of world-class germplasms, limited overseas distribution has occurred due to the unavailability of individual resource information on online platforms such as Genesys, managed by the Global Crop Diversity Trust. Exceptions to this pattern have occurred only when researchers with Korean affiliations have utilized publicly available history information to apply for resource distribution. Our institution is diligently making preparations, including the dissemination of passport information, to ensure the continuous availability and accessibility of our plant genetic resources for international distribution.In order to improve the utilization of the conserved germplasms, systematic passport data management is indispensable . GermplaGlycine max), the morphological characteristics of 650 landraces were investigated, about 40 of them were selected as a core collection, and a molecular genetic profile was promoted [Capsicum spp.), the analysis of capsaicin content, the cultivation of anthracnose-resistant intermediate seedlings, the evaluation of Chinese cabbage (Brassica rapa ssp. penkinensis) landraces, the cultivation of superior groups, and the cultivation of intermediate seedlings resistant to wart disease of cabbage [In response to consumer preferences, there is a notable increase in the incorporation of evaluation data concerning chemical composition profiles, such as glucosinolate levels in Brassica ssp. and disease resistance. This highlights the importance of considering these factors in the evaluation process. Since the 1990s, the RDA-Genebank has systematically investigated its conserved genetic resources for their qualitative and quantitative traits to promote the use of germplasms by consumers of the end product. During the early stages, the characterization centered on seed viability and primary characteristics of germplasms such as seed coat color, width, and length. From 1995, the organization was subdivided into several divisions for cereal crops, horticultural crops, and special crops, respectively, and their evaluation data was augmented. In addition, chemical composition profiles such as the oil and fatty acid content of sesame seeds; the protein content, amylose and amylopectin content, and starch characteristics of rice landraces; and the DNA polymorphism analysis of rice and barley were initiated . In the promoted . Among t cabbage . The gerB. rapa subsp. pekinensis), our studies focused on analyzing the individual glucosinolates of the mustard leaf (B. juncea) and the Choy Sum (B. rapa subsp. chinensis var. parachinensis) [Starting in 2019 with Chinese cabbage (inensis) ,14. The With further work carried out on expanding the information available in the evaluation data for germplasms conserved at the RDA-Genebank, substantial consideration has been given to using high-throughput techniques to study the germplasms. One such aspect is using digital phenotyping for largescale analysis and screening of the germplasms.r2) between image-based and actual height and the width measurements of soybean seeds [Glycine max), and diversity analysis was performed using origin and status [Glycine max) and adzyki bean (Vigina angularis) germplasms for the first time across international genebanks [Glycine max cv. Enrei Japanese varieties, which are known for their excellent nodulation characteristics. Additionally, these digital phenotyping techniques can be applied to various other crops conserved at the RDA-Genebank. For instance, in wheat, RGB images obtained from a digital camera can be utilized to measure agronomic traits such as tiller number per plant, canopy (including leaf number and length), phenotypic characteristics of wheat spike, and tomato internode length. In the future, RGB images captured using unmanned aerial vehicles can also be used to measure plant heights in crops such as rice, wheat, barley, and corn [The significance of seed traits is widely acknowledged, and seeds are selected on the basis of their phenotypic characteristics to improve crop yield and quality, making this one of the oldest phenotyping techniques . Phenotyctively) . Therefond wild) . Currentnd wild) . In geneenebanks ,23. Specenebanks . We confand corn .Hyperspectral sensors have been utilized to measure photosynthesis and respiration, which are directly related to crop growth and are currently being studied in tobacco, corn, and wheat . In addiThe augmentation of phenotype data with existing characterization information, as well as the integration of genomic, phenomic, and other molecular data, can significantly aid researchers in selecting optimal accessions for breeding and elucidating various evolutionary characteristics . In the Given the accelerating loss in biodiversity worldwide due to changing climatic conditions and anthropogenic activities, the importance of agricultural genetic resources is becoming more prominent. At plant genebanks throughout the world, continuous efforts are being taken towards improving the quality and quantity of germplasm collection along with ease of access. The germplasms we conserve at the National Agrobiodiversity Center are continuously investigated for agricultural traits and building an updated database. Recently, we have also concentrated on methods for investigating agricultural traits by applying digital techniques. We expect information on the germplasms conserved in the RDA-Genebank to be made accessible at an early juncture to researchers all over the world. Ensuring timely access to vital genetic resources will foster international collaboration and contribute to the advancement of research and agricultural development worldwide. By promoting transparency and facilitating the exchange of germplasms, plant biologists can collectively work towards enhancing global food security, biodiversity conservation, and sustainable agriculture. As custodians of invaluable genetic resources, the RDA is committed to promoting their widespread availability and fostering fruitful partnerships with researchers and institutions across the globe."} +{"text": "To describe the current knowledge on safety and effectiveness of the tumor necrosis factor (TNF)-a antagonists and identify current knowledge/evidence gaps for study by the Agency for Healthcare Research and Quality (AHRQ) Effective Health Care Program.Evidence-based Practice Centers (EPCs) and the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) network of AHRQ's Effective Health Care Program will study the safety and effectiveness of biologic and nonbiologic disease-modifying antirheumatic drugs . The current knowledge of safety and effectiveness of TNF-a antagonists is reviewed.Treatment of adult rheumatoid arthritis (RA) involves determining which agents are safe, effective, and cost effective for an individual. Each individual patient's health system may also play a role in which agents are chosen. Many agents are available for the management of RA, some with high cost and unknown safety. Section 1013 of the Medicare ModernizationAct of 2003 authorizes AHRQ to study comparative effectiveness and safety ofRA treatments through both EPCs and DEcIDE centers to develop scientific knowledge for RA management as well as through epidemiologic studies.Results will be compiled through a Clinical Decisions and CommunicationsScience Center, then disseminated to all appropriate stakeholders, including patients, payers, and health care professionals. The current knowledge of safety and effectiveness of TNF-a antagonists in the treatment of RA is reviewed. Increased rates of serious infections, including Mycobacterium tuberculosis (MTB), or tuberculosis reactivation, may occur with the use ofTNF-a antagonists. It is still unclear if RA increases the risk of developing cancer, or if use of TNF-a antagonists increases cancer risk.TNF-a antagonists are costly, yet effective treatments for early and late RA. Use of these agents provides rapid relief of RA symptoms and provides positive outcomes, defined as improvements in AmericanCollege of Rheumatology 20, 50, 70 scores; Health Assessment Questionnaire ratings; activities of daily living; joint space narrowing; erosions; and acute phase reactants. Reactivation of latent MTB or onset of other infections or cancers may occur in RA patients with TNF-a antagonists."} +{"text": "On any given day, almost 11 million people globally are deprived of their liberty. In 2020, the global female population was estimated to be 741,000, an increase of 105,000 since 2010. In order to investigate progress in the adoption of the Bangkok Rules since 2010, we conducted a legal realist assessment based on a global scoping exercise of empirical research and United Nations (UN) reporting, using detailed MESH terms across university and UN databases. We found evidences in 91 documents which directly relate to violations of the Bangkok Rules in 55 countries. By developing a realist account, we document the precarious situation of incarcerated women and continued evidence of systemic failures to protect them from custodial violence and other gender-sensitive human rights breaches worldwide. Despite prison violence constituting a complex and multifaceted phenomenon, very little research has been conducted on custodial violence against women since 2010. Although standards of detention itself is a focus of UN universal periodic review, special procedures (violence against women) and concluding observations by the UN committees, very few explicitly mentioned women, and the implications of violence against them while incarcerated. We highlight three central aspects that hinder the full implementation of the Bangkok Rules; the past decade of a continued invisible nature of women as prisoners in the system; the continued legitimization, normalization, and trivialization of violence under the pretext of security within their daily lives; and the unawareness and disregard of international (Bangkok and others) rules. On any given day, almost 11 million people globally are detained in prisons or other closed settings . In 2020Bangkok Rules; Tokyo Rules;Nelson Mandela Rules; Mandela Rules do not specifically refer to women (with Rule 7 referring to self-perceived gender identity), the Bangkok Rules as soft law principles lay the foundation for intensified efforts to support women deprived of their liberty . The 2015 UN Subcommittee on Prevention of Torture and other Cruel, Inhuman or Degrading Treatment or Punishment in the community, and the spotlight has been shone on torture and inhumane treatment in detention itself, very little has been dedicated to gender-specific aspects of countering interpersonal custodial violence against women deprived of their liberty , most particularly so when experienced as torture or cruel, inhuman or degrading treatment, or punishment within the power-imbalanced custodial setting. Under international law, rape constitutes torture when it is carried out by or at the instigation of or with the consent or acquiescence of public officials, with other forms of sexual abuse violating the prohibition on cruel, inhumane, or degrading treatment or punishment. Other identified forms of custodial GBVAW include strip searches conducted by men or in the presence of men, virginity testing, verbal sexual harassment, use of restraints (including during labor), psychotropic drugs and solitary confinement to control prisoners, inappropriate surveillance by guards during undressing or showers, and the denial of access to medical care by nonmedically trained officials and CEDAW observations at the global level since 2010. 101 UN CAT reports and 158 CEDAW reports were scrutinized, with human rights violations pertinent to the identified Bangkok Rules found in 15 UN CAT, 32 UN CEDAW, and 21 other domestic and UN Human Rights Council reports. Third, the academic literature was examined, and we found 23 relevant records where breaches of the Bangkok Rules were evident. In total, 91 documents related directly to violations of the Bangkok Rules in 55 countries. Despite prison violence constituting a complex and multifaceted phenomenon, very little academic research has been conducted on GBVAW in custodial settings since 2010, with the bulk of the evidence centering on Special Rapporteur and UN country-level reporting. Although standards of detention itself is a focus of UN periodic reports, very few explicitly mentioned women, and the implications of violence against them while incarcerated. See Empirical studies from the United Kingdom (UK) and the United States reveal that the female prison environment continues to be as emotionally suppressive, conflict-laden, and violent as in male settings, particularly relating to fighting and physical assaults, with inmate-on-inmate violence comparable across male and female facilities, including sexual assaults, transactional sex in return for protection, privilege or basic necessities, and intimate partner violence between prisoners . At the . The 2016 CEDAW report on Canada criticizes the presence of male guards in female prisons in Canada .With regard to the Middle East, the UN CAT documents allegations of gender-based violence, including torture, ill treatment and rape, against women in detention in Iraq in 2015 . There aBangkok Rules at the global level as they pertain to the conditions of women in detention since adoption, particularly the prevention of and protection from custodial violence when deprived of their liberty. Gender inequity and inequality is pervasive. Although custodial violence in essence violates the internationally recognized prohibition on cruel, inhuman or degrading treatment or punishment, it remains a largely hidden and sensitive topic for both genders when deprived of liberty, with insufficient surveillance of the issue, coercion threatening disclosure (particularly for women), very low rates of perpetrator accountability, and scant prevalence data available at the global level rules; and the task to organize different modes of incarceration environment for prisoners who committed nonviolent crimes. Human rights violations encountered by women in the criminal justice and penal systems continue worldwide. Many countries have not fully adopted the Bangkok and Tokyo Rules, leading to congestion and overcrowding in female prisons, lack of protection against violence, particularly when housed in nonsegregated prisons, either perpetrated by officials or by fellow inmates (of both genders), use of psychotropic and physical restraints, arbitrary detention and solitary confinement, and the lack of full access to gender specific medical care, trauma-informed and trauma-responsive mental health supports, and drug treatment . Inadvertently, our realist account highlights the continued lack of resourcing of female prisons, lack of implementation of noncustodial sentencing for minor and nonviolent offenses, lack of consideration of GBVAW, exploitation and trauma-related pathways into crime (largely poverty or drug-related), and overall lack of oversight in disclosure and penal complaint mechanisms where GBVAW is perpetrated in the closed setting.These insights give a well-founded basis for relevant UN agencies and the World Health Organization to provide technical assistance and promote further improvements and penal reforms worldwide. Moreover, this gives a substantiated starting point for human rights organizations such as Amnesty International, the Howard League for Penal Reform, Penal Reform International, and Harm Reduction International to appoint targeted and fitting actions to reduce GBVAW in custodial settings. See Further, we wish to underscore how this neglect not only constitutes grave human rights abuses but also fuels self-harm, suicide, psychiatric disorders and deaths, and the spread of disease bridging between prisons and communities. Addressing disease hinges on prison system approached and parameters to address physical and sexual violence in prisons, trauma-related mental health issues, and unsafe injecting of drugs. UN reporting continues to highlight such issues globally where women are discriminated and treated in an unequal manner, alongside the dearth of academic research and access of research teams into prisons . It is f"} +{"text": "With aging, the frequency of stress-related diseases, including mental, metabolic, cognitive, cardiovascular, and neurodegenerative disorders, increases dramatically. Despite this generalized phenomenon, there are notable individual differences in both vulnerability and resilience to stress and stress-related pathologies. Despite the plethora of studies in stress research, the mechanisms underlying individual vulnerability to stress and age-related diseases remain unclear.The HPA axis is a key modulator of both the endocrine and behavioral adaptation to stress, and dysfunction of the HPA axis can contribute to the development of various stress-dependent diseases. Function of the HPA axis deteriorates during aging both in basal conditions and in response to stress. However, the type and magnitude of HPA axis deterioration are not similar in all individuals and appear to be associated with different behavioral characteristics. In particular, a higher activity of the HPA axis has been noted in elderly individuals with depression and in non-human primates that exhibit depression- and anxiety-like behavior (DAB) \u20133. ThereGoncharova et\u00a0al. presents original data on the responses of the HPA axis to acute psycho-emotional stress exposure (ASE) in young and old female rhesus monkeys with standard healthy and DAB behavior under conditions of continuous constant lighting (CL) using LED lamps that are commonly encountered in offices and apartments. The unique findings were that CL reduces the cortisol (CORT) response to ASE applied in the afternoon (15.00-17.00 h) and also disrupts the circadian rhythm of CORT secretion in all animals, regardless of age and behavior.Here, we provide a brief editors\u2019 overview of the articles published in this field. The article by The mechanisms underlying this phenomenon, however, are age-dependent. In young animals, the transhypophyseal pathway mediates the effect, whereas in older animals the effect is mediated primarily by an extra-hypophyseal neural pathway. The effects of CL on the stress reactivity of the HPA axis in young individuals were similar to its influence on the corticotropin and the CORT responses to administration of arginine vasopressin. A number of individual differences were also noted in DAB animals compared to normal behavioral controls. The findings suggested a potential risk of reduced adaptive capacity under CL resulting in stress-dependent pathology and accelerated aging, especially in the DAB-compromised organism. Such findings are relevant in connection with intensive night lighting and work and other activities at night.Konstandi and Johnson presents important data on the role of the HPA axis in the regulation of hepatic cytochrome P450 (CYP)-dependent drug metabolism, which is largely genetically determined and not the same in different individuals. Genetic polymorphisms and mutations of CYP genes are observed among several ethnic populations, such as Africans, White and African Americans, Asians, Caucasians, and Europeans. Activation of the HPA axis during stress and aging can lead to disruption of CYP gene regulation and CYP-dependent drug metabolism with pronounced inter-individual variations in the effectiveness and side effects of standard treatment protocols. The implications are particularly important in the treatment of age-related diseases, such as depression, cancer, hypertension, and diabetes. Individual differences in CYP-dependent drug metabolism may also contribute to age-related individual differences in the functioning of the HPA axis.The review by Degroote et\u00a0al. focuses on the study of the relationship between individual differences in the daily activity of the HPA axis in middle-aged and elderly people and coronary heart disease (CHD). This is also a main risk factor for arterial hypertension. Both are widespread in these age groups. The authors examined the concentration of CORT in saliva in hypertensive and normotensive men and men with CHD at different times of the day. Additionally, they prospectively tested the cortisol awakening response (CAR) for association with biological risk factors for CHD. They found that lower total daytime CORT secretion and CAR independently predicted increases in cardiovascular risk, as evidenced by increases in the circulating levels of biomarkers of atherothrombotic risk. The findings confirmed the pathogenetic role of age-related disturbances in the HPA axis function in the development of age-related cardiovascular pathology.The article by Dai et\u00a0al. was to investigate the role of the HPA axis in the effectiveness of modified electroconvulsive therapy (MECT) for the treatment of drug treatment-resistant depression (TRD). A considerable amount of literature suggests that dysregulation of the HPA axis plays a key role in the pathophysiology of TRD. However, contrary to reports by other authors who identified an association of efficacious electroconvulsive therapy with normalization of the HPA axis dysregulation, these authors found no statistically significant differences in serum CORT levels before and after MECT in elderly patients with TRD. Adequate assessment of the HPA axis function, in this case, may require not just the determination of total blood CORT concentration but also measurement of, for example, dehydroepiandrosterone sulphate and corticotrophin as well. Other confounding factors that may play a role include the time of day when MECT is performed, such as in the evening, a period of reduced circadian HPA axis activity.One of the main aims of the study presented in Collectively, the articles presented here strongly suggest that the disruption of the HPA axis activity observed across aging has notable deleterious effects on the function of other physiologic systems, namely, 1) altered adaptation to the inhibitory effect of continuous lighting on the cortisol response in acute psycho-emotional stress, 2) modification of the intensity of CYP-dependent drug metabolism, 3) increased vulnerability to cardiovascular pathology, and 4) the daily activity of the HPA axis in basal cortisol concentration and the cortisol awakening response. The general premise supported by most studies is that\u00a0age-related dysfunctions of the HPA axis form the pathophysiological conditions for the development of age-related pathology and that individual differences in the characteristics and intensity of age-related dysfunctions of the HPA axis may underlie differences in vulnerability to age-related pathology.NG wrote the first draft of the manuscript, and DB and EJ revised the manuscript. All authors read and approved the final version."} +{"text": "Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of both children and adults. Undiagnosed and untreated, ADHD may have serious lifelong consequences. Research has identified diagnostic clues, neurotransmitter pathways, and psychiatric comorbidities related to ADHD, as well as effective pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have been the foundation of ADHD therapy for more than 50 years. Availability of new extended-release (XR or ER) and longer-acting (LA) formulations and novel agents allows for wider and more individualized treatment choices. Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing.Outcomes in ADHD treatment can be improved with the use of clear treatment guidelines and tools to aid clinicians in implementing them efficiently and effectively. The Texas Children's Medication Algorithm Project (CMAP)provides a system of algorithm-driven treatment decisions that is evidence based and easy to implement.To (1) review the psychological components of attention, the neurotransmitter pathways associated with ADHD, and the array of therapeutic options for ADHD, with an emphasis on the most recent introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric and cardiovascular side effects associated with stimulants; (3) review abuse liability,comorbidities, and suggested approaches to these issues; and (4) review the development and use of CMAP and offer resources for its implementation in clinical practice.The pathophysiology of ADHD is linked to dysfunction of front osubcortical networks and dysregulation of dopaminergic, noradrenergic, and nicotinic neurotransmitter systems. An additive effect of multiple genes as well as environmental influences contributes to the clinical picture.Treatment with stimulants and nonstimulants has proven effective in different subgroups, with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. Availability of XR, ER, LA, and transdermal stimulant formulations, as well as alternative nonstimulantagents, offers new options for the pharmacotherapy of ADHD. Major concerns associated with abuse liability of stimulants have been allayed by the availability of ER formulations, which have reduced reinforcing effects associated with short-acting preparations. Medication outcomes in ADHD can be enhanced by the use of evidence-based algorithms such as CMAP. Keys to success are adequate initial assessment and diagnosis, the use of sustained release products, sufficient dose titration, and the use of clinical rating scales with feedback from caregivers and teachers. Optimal treatment out comes can be achieved by appropriate pharmacotherapy combined with psychosocial interventions."} +{"text": "The advent of robotic-assisted thoracic surgery (RATS) has revolutionized the field of thoracic surgery, offering a new paradigm for personalized, precision, and individualized medicine. The unique capabilities of RATS, including enhanced dexterity, precision, and visualization, allow for a more tailored approach to each patient\u2019s specific needs. This personalized approach is particularly relevant in managing thoracic malignancies, where the surgical approach can significantly impact patient outcomes . As we cSakakura et al. report a novel approach to robotic lung resection, namely segmentectomy . The autBuilding on the concept of personalized surgical approaches, the second paper, from Okazaki et al., discusses the benefits of RATS for different types of mediastinal tumors, including anterior, superior, middle, and posterior mediastinal tumors . The autThe third paper emphasizes the importance of personalized surgery in the era of precision medicine. Eguchi et al. discuss the use of RATS in lung segmentectomy, highlighting the role of RATS in improving operative performance due to its core technological features . The autSakakura and Eguchi discuss the four phases of port placement variations, from the initial phase of mimicking video-assisted thoracic surgery (VATS) to the fourth phase of maximizing the functional features of the da Vinci Xi robotic system . They hiThe final paper, from Zhang et al., compares RATS and open thoracotomy in the context of non-small cell lung cancer treatment . The autThe future of RATS in thoracic surgery is promising, with ongoing advancements expected to further enhance the precision and personalization of surgical interventions. As technology continues to evolve, we anticipate further improvements in surgical outcomes, patient recovery, and overall quality of life. The integration of artificial intelligence and machine learning into RATS may also offer new opportunities for personalized medicine, potentially enabling more accurate preoperative planning, intraoperative navigation, and postoperative monitoring. As we continue to move forward in this exciting era of precision medicine, the role of RATS in providing personalized and optimal treatment for thoracic malignancies is expected to become increasingly prominent."} +{"text": "British Journal of Cancer 10.1038/s41416-020-01153-4, published online 16 November 2020Correction to: The original version of this article contained an error in an affiliation. Upon careful review of the paper, the authors noticed that the affiliation for Goran Malenkovic was not written correctly. The authors only submitted the following affiliation Gynecologic Oncology Department Clinic for Operative Oncology, Institute of Oncology of Vojvodina, Serbia but they missed to notice that the Faculty of Medicine Novi Sad, University of Novi Sad, Serbia should also be in the affiliation."} +{"text": "Incorrect AcknowledgmentsIn the published article, there was an error in the Acknowledgments statement.The authors gratefully acknowledge technical and financial support provided the Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia for funding this research work to publish through the project number (IFPIP:1166-662-1443). The authors extend their appreciation to VEGA1/0664/22 Mitigation of the effects of environmental stresses in photosynthesis and plant production.The correct Acknowledgments statement appears as follows.AcknowledgmentsThe authors gratefully acknowledge the technical and financial support provided by the Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia, to this research work through project number IFPIP: 1166-662-1443.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated."} +{"text": "Bone metastasis is a complex and challenging clinical problem, affecting patients with advanced stages of cancer . AccordiInternational Journal of Molecular Sciences includes a total of six contributions: five original articles and one review providing significant advances in the understanding and treatment of bone metastasis.In this scenario, the Special Issue entitled \u201cBone Metastasis Challenge: New Ideas and Future\u201d of the The study by Mbese and Aderibigbe reported the potential of bisphosphonate-based conjugates and derivatives as therapeutic agents for osteoporosis, bone cancer, and metastatic bone cancer . The autThe additive benefits of the combination of Radium-223 Dichloride and Bortezomib in a systemic multiple myeloma mouse model have been investigated by Suominen and colleagues . The resFurthermore, the osteoprotective effects of Loganic Acid on osteoblastic and osteoclastic cells and osteoporosis-induced mice were studied . ExperimIn addition, a research paper investigated the expression profile of new marker genes involved in the differentiation of canine adipose-derived stem cells into osteoblasts . This stCold atmospheric plasma (CAP) has also been investigated for its potential in promoting regeneration-associated cell functions of murine cementoblasts in vitro . The resFinally, the study of Panahipouret al. investigIn conclusion, studies published in the Special Issue \u201cBone Metastasis Challenge: New Ideas and Future\u201d provide valuable insights into the molecular mechanisms underlying the development and progression of bone metastases and offer promising strategies for the prevention and treatment of this devastating disease. Moreover, the combination of molecular, pathological, and imaging data could open new and intriguing perspectives for developing therapies based on personalized medicine principles ."} +{"text": "In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care.To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ\u2019s 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA).As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various combination therapies. Head-to-head comparisons of synthetic DMARDs generally revealed no significant differences in long-term clinical and radiographic outcomes, or in functional capacity or health-related quality of life. Two nonrandomized prospective cohort studies and 1 open-label effectiveness trial reported no differences in ACR20 and ACR50 response rates in patients treated with the tissue necrosis factor (TNF)-alpha inhibitors etanercept and infliximab. Comparisons of TNF-alpha inhibitors generally indicated no significant differences in rates of adverse events, including serious infections, and no increases in rates over time. In comparisons of a biologic agent combined with methotrexate versus a biologic agent alone, combination therapies were generally associated with better clinical response rates and better outcomes of functional capacity and quality of life. The most common adverse events observed in studies on biologic agents were diarrhea, headache, nausea, rhinitis, injection site reactions, and upper respiratory tract infections."} +{"text": "The authenticity of probiotic products and fermented foods and beverages that have the status of protected designation of origin (PDO) or geographical indication (PGI) can be assessed via numerous methods. DNA-based technologies have emerged in recent decades as valuable tools to achieve food authentication, and advanced DNA-based methods and platforms are being developed. The present review focuses on the recent and advanced DNA-based techniques for the authentication of probiotic, PDO and PGI fermented foods and beverages. Moreover, the most promising DNA-based detection tools are presented. Strain- and species-specific DNA-based markers of microorganisms used as starter cultures or (probiotic) adjuncts for the production of probiotic and fermented food and beverages have been exploited for valuable authentication in several detection methods. Among the available technologies, propidium monoazide (PMA) real-time polymerase chain reaction (PCR)-based technologies allow for the on-time quantitative detection of viable microbes. DNA-based lab-on-a-chips are promising devices that can be used for the on-site and on-time quantitative detection of microorganisms. PCR-DGGE and metagenomics, even combined with the use of PMA, are valuable tools allowing for the fingerprinting of the microbial communities, which characterize PDO and PGI fermented foods and beverages, and they are necessary for authentication besides permitting the detection of extra or mislabeled species in probiotic products. These methods, in relation to the authentication of probiotic foods and beverages, need to be used in combination with PMA, culturomics or flow cytometry to allow for the enumeration of viable microorganisms. Aimed at achieving an economic gain, food labeling or food products may be tampered with, substituted or misrepresented, thus committing food fraud. To overcome this problem, which causes an estimated burden of USD 10\u201315 billion per year on consumers and industry [As stated in the consensus statement on fermented foods by the expert panel of the International Scientific Association for Probiotics and Prebiotics (ISAPP), \u201cfermented foods are foods made through desired microbial growth and enzymatic conversions of food components\u201d . The EurEach fermented food and beverage is characterized by a peculiar microbiota originating from the raw materials, equipment and processing environment, whose composition and evolution is affected by biotic and abiotic factors that intervene during each specific process of production. Such a microbial consortium ensures both the primary fermentation activities, which guarantee the technological results of the transformation, and the accessory ones, which contribute notably to the definition of the characteristics of typicality and quality, bases of their notoriety. Different microbial fingerprints have been found to be specific to the geographic area of origin . For thiBut while in the case of fermented foods and beverages, only the detection of either microorganisms used as starter cultures/adjuncts or the whole microbiota is satisfactory, in the specific case of probiotic foods and drinks, the quantification of each probiotic mentioned in the label is also mandatory ,13,14. ITo date, several methods are available to qualitatively and quantitatively detect microbial markers of authenticity in fermented and probiotic foods and beverages. Among these, DNA-based methods, mainly due to their speed, robustness, sensitivity and specificity, are gaining ground in recent decades.Herein, we provide a review of the advanced DNA-based techniques currently in use or that can be used in the near future to evaluate the authenticity of fermented and probiotic foods and beverages.Since 1983, when the scientists of the Cetus Corporation of Emerville launchedThe authenticity of a technological or probiotic microorganism should be determined not only at the species level but also at the strain level, as stated in the guidelines proposed by the Council for Responsible Nutrition and International Probiotics Association , as wellRandom amplified polymorphic DNA (RAPD)-PCR, which employs an oligonucleotide primer to amplify anonymous DNA providing complex strain-specific banding patterns, and amplified fragment length polymorphism (AFLP)-PCR, which combines the restriction endonuclease of the genomic DNA with a PCR involving adaptor- and restriction site-specific primers, are genotyping techniques providing polymorphic banding patterns that allow for strain discrimination . HoweverRAPD-PCR, AFLP-PCR and REA-PFGE have been applied to ascertain the authenticity of probiotic foods ,36,37, tWhole genome sequencing (WGS) allows the identification of a target microorganism at both species and strain level. Furthermore, WGS data analysis provides a preliminary in silico assessment of microbial safety and probiotic potential ,42, evalAuthentic is any probiotic food or supplement whose content is consistent with that claimed on its label ,13,14.Assessing the authenticity of a probiotic food is crucial and requires verifying not only the presence and viability of the labeled probiotic but also the labeled amount of viable cells of the probiotic. The gold-standard method to quantify microorganisms is plating. However, plating is time- and labor-consuming and requires more days to achieve results. Moreover, the selective media used to enumerate microorganisms do not allow the enumeration of microbes in the viable but non-culturable (VBNC) state. To overcome this drawback, methods that combine the use of selective and non-selective media in one single system, such as the Lutri plate, the Overlay (OV), the membrane-transferring surface-plating and the thin agar layer (TAL) methods, firstly proposed to detect VBNC pathogenic bacteria, can be used ,71. UsinReal-time PCR, which is rapid, robust, sensitive and user-friendly, besides being high-throughput and multiplexing, is being widely applied to investigate the authenticity of probiotic and fermented foods. Using this technique, it is possible to monitor the emission of fluorescence by DNA-intercalating agents or labeled probes at each amplification cycle, which, being proportional to the DNA present in the reaction mixture, allows the real-time quantification of the target DNA and, thus, of the amount of the target microorganism. However, although more sensitive, intercalating dyes are not as specific as labeled probes. This drawback may be overcome by using the melting or the high-resolution melt (known as either hi-res melting or HRM) curve analysis of the obtained amplicons . To makeHowever, as stated above, DNA-based methods do not discriminate among viable or dead microorganisms, discrimination that can be achieved using culture-based approaches or flow cytometry methodologies ,72,93. PAmong the numerous diagnostic methods currently available to detect technological and probiotic microorganisms in food, biosensors are promising tools capable of providing high levels of faster and more automated surveillance. These analytical devices combine a sensitive biological element (the receptor) with a chemical or physical transducer to selectively and quantitatively detect the presence of a specific compound in a given environment . The selThe rapid evolution of micro- and nano-technologies has opened new horizons towards the integration and miniaturization of conventional sensing platforms, resulting in the so-called lab-on-a-chip devices that incorporate various laboratory processes in a miniaturized and semi-automated system. However, PCR requires a thermal cycler instrument, which significantly limits the potential miniaturization of the system . To overThe development and use of these integrated platforms for the detection and quantification of microorganisms are still limited to the detection of pathogenic microorganisms .The obvious advantages of these integrated and miniaturized technologies for the detection of technological and probiotic microorganisms lie in the reduction in the volume of reagents used and, therefore, the associated costs, as well as the reduction in time to results. Furthermore, the possibility of making the entire detection system portable and automated facilitates its use not only in the agri-food sector but also in other strategic sectors such as anti-fraud services, port and border control authorities, certification agencies/bodies of control of consortia for the protection of typical products, and public and private control laboratories.PCR amplification of variable regions of the 16S rRNA gene (for bacteria) or 18S or 26S rRNA gene (for yeasts and fungi) followed by denaturing gradient gel electrophoresis (PCR-DGGE) is another technique frequently used in recent decades to investigate the authenticity of probiotic and fermented foods and beverages. This PCR-based method is based on the separation, in a denaturing gradient gel, of amplicons of the same size but with different sequences, based on the differential denaturation (melting) profile . PCR-DGGBased on the same principle as PCR-DGGE, 16S metagenetic analysis and metagenomics may allow the characterization of fermented foods and the authentication of PDO and PGI products as well as that of probiotic foods. Metagenetics, also called amplicon sequencing, metabarcoding, metataxonomics, 16S metagenomics (targeting bacteria), 18S or 23S or ITS metagenomics (targeting fungi), consists of the PCR amplification of target genes from metagenomic DNA combined with sequencing and alignment against a reference database to detect the microbial composition of a microbial community .Lactobacillus helveticus dominated both natural whey starter cultures and the corresponding Caprino and Vaccino cheeses, two traditional cheeses produced in the same dairy farm, whereas Staphylococcus equorum and Streptococcus thermophilus dominated Cacioricotta and Pecorino cheeses, respectively, also produced in the same dairy plant. The parallel assessment of the enzymatic activities, degree of proteolysis, and concentrations of the main compounds involved in the sensory traits of these 4 traditional cheeses produced in the same dairy plant allowed the authors to highlight the distinctive features of these cheeses and to find the relationships between their microbiological and biochemical characteristics [As an example of using this technology to describe the microbial community of foods, Celano et al. , via 16Seristics . Also, 1eristics . For exaeristics combinederistics used a pHowever, metagenetics has drawbacks linked to the low discriminatory power of ribosomal RNA to identify phylogenetically closely related bacteria and fungi, apart from the biases of PCR amplification . These pDNA-based technologies are valuable tools to assess the authenticity of probiotic, PDO and PGI (fermented) foods and beverages. Several DNA-based methods are presently available , but, dePMA real-time PCR-based assays, being a multiplexed and high-throughput method, allow for the simultaneous qualitative\u2013quantitative detection of numerous probiotics or starter cultures directly from different food and beverage matrices. However, the primers and probes should be strain-specific to allow for the qualitative\u2013quantitative detection of the labeled probiotic strain or starter culture. In this context, the pangenome-based design of primers and probes specific to each target strain is worthwhile.If the necessity is to investigate the presence of extra species or of mislabeled species in probiotic food and beverages or to assess the authenticity of PDO and PGI fermented foods and beverages, it is necessary to use the whole microbiota as an authenticity marker. In this case, depending on the budget and equipment available, metagenomics or PCR-DGGE can be used. But while the sole microbial pattern of PDO and PGI fermented foods and beverages allows for their authentication, in the case of probiotic food and beverages, a quantitative detection method for viable microbes such as the use of PMA in combination with the above-mentioned methods or the employment of culturomics or flow cytometry in combination with these community fingerprinting techniques is mandatory."} +{"text": "The gut microbiota is the largest symbiotic ecosystem in the host and has been demonstrated to play an important role in maintaining intestinal homeostasis. The symbiotic relationship between the microbiota and the host is mutually beneficial. The host provides important habitat and nutrients for the microbiome. The gut microbiota supports the development of the metabolic system and the intestinal immune system's maturation. Intestinal microbes ingest dietary components such as carbohydrates, proteins, and lipids, and the metabolites are reported to directly or indirectly affect human health. Therefore, there is an inseparable relationship between the gut microbiota and the nutrition of the host.Gut microbiota not only participates in the digestion, absorption, and synthesis of some nutrients but also regulates host metabolism. A detailed understanding of this relationship between gut microbiota and animal nutrition physiology is necessary to rationalize dietary interventions targeted at the gut microbiota in the future. The emergence of omics methods and research on the animal microbiome has completely changed our understanding of gut microbiota and nutritional physiology. This Research Topic (RT) focuses on all aspects of the research on digestive tract microorganisms and nutritional physiology.Yang, Wang, et al. explored the impact of different dietary ratios of amylose and amylopectin on the gut health and microbiome of weaned pigs during feed transitions or after exposure to the lipopolysaccharide toxin of Escherichia coli. Wang M. et al. investigated the effects of an herbal extract mixture on the gut microbiota and intestinal antioxidant capacity of weaning piglets. Zhou H. et al. researched the effects of administering all-trans retinoic acid (ATRA) to pregnant sows on the gut bacterial community of neonatal piglets with different genetic backgrounds. Zheng et al. looked into the mechanisms underlying the effects of beta-hydroxy-beta-methylbutyrate (HMB) on lipid metabolism in Bama Xiang mini-pigs. Li et al. compared the effects of compound enzymes and antibiotics on growth performance, nutrient digestibility, blood biochemical index, and intestinal health in weaned pigs. All these studies demonstrated that the dietary interventions could lead to alterations in the gut microbiome of pigs and piglets, suggesting improved gut health and physiological functions like resistance to bacterial toxins, enhanced anti-oxidative capacity, growth performance, etc.Various research articles submitted on this RT focus on the impact of specific dietary interventions on the microbiome and the physiology of certain farming animals, including pigs and piglets, lambs and goats, ducks, chickens, bullfrogs, and shrimps. Wang Q. et al. assessed the impact of different dietary energy levels in male Hu lambs during the fattening period, and Yang, Zhang, et al. assessed the effects of dietary supplementation with mannan oligosaccharide (MOS) on the passive transfer of immunoglobulin G (IgG), anti-oxidative capacity, immunity, and intestinal microbiota in neonatal goats. The first study suggested that the medium rather than the high dietary energy levels could be more appropriate during the lamb fattening period based on the changes observed in rumen fermentation, gastrointestinal tract histology, and microbiome diversity. The second study concluded that MOS could improve all parameters tested and thus its addition as a feed supplement for neonatal goats is suggested.Furthermore, Liu et al. and Peng et al. explored the effects on gut microbiota, growth performance, and intestinal morphology among other physiological parameters of dietary ferulic acid or Bacillus and non-starch polysaccharase, respectively. He et al. studied the effects of incorporating black soldier fly larvae meal (BSFLM) into the diets of Xuefeng Black-Bone chickens on their gut microbiota and intestinal morphology. The studies mentioned above indicated that the dietary interventions tested had positive effects on the gut health and productivity of poultry.An additional three studies focused on dietary improvements in poultry. In ducks, Wang Z. et al. analyzed the effects of supplementing autochthonous gut bacteria in plant-based diets on the growth, nutrient digestibility, and gut health of bullfrogs (Lithobates catesbeianus). Wang W. et al. looked at the effects of dietary supplementation with Phaffia rhodozyma astaxanthin on growth performance, carotenoid analysis, biochemical and immune-physiological parameters, gut microbiota, and disease resistance in the giant tiger prawn Penaeus monodon. Again, a positive influence was recorded for each of the interventions in the two organisms which could be related to the gut microbiome, gut physiology, and growth performance.The final two studies on farming animals were on organisms related to aquaculture. Wen et al. investigated the effects of heat stress on the gut microbiota and metabolomic profiles in mice. Heat stress was found to have a negative effect on the gut microbiome composition and caused metabolic alterations which could be related to inflammation and oxidative stress. Zhuang et al. studied the effects of resveratrol on growth performance, intestinal morphology, gut microbiota composition, and metabolism in mice. Zhai et al. unraveled the mechanisms underlying the effects of Eucommia ulmoides leaf extract (EULE) on colonic epithelium integrity in rats. Zhou D. et al. tested the application of phytic acid-degrading bacteria on mineral element content in mice. Wan et al. checked the effects of caffeic acid supplementation on colonic inflammation, oxidative stress, and gut microbiota in mice. Resveratrol had a positive impact on all physiological and morphological parameters tested. EULE supplementation led to improvements in colonic epithelium integrity, accompanied by a reduction in inflammation and oxidative stress. EULE action was found to be mediated through the gut microbiota-bile acids-TGR5 axis. Degradation of the anti-nutrient phytic acid, which binds to minerals and inhibits their absorption in the gut, led to their increased absorption and utilization. This effect was accompanied by positive alterations in the composition of the gut microbiome. Moreover, caffeic acid supplementation led to reductions in colonic inflammation and oxidative stress along with positive changes in the gut microbiota composition. The antioxidant and anti-inflammatory effects of caffeic acid were associated with changes in the level of gene expression.The next five studies were performed in mice or rats as the model organisms. Lonicera japonica extracts (LJE) in animal production, with a focus on their effects on intestinal health. In this review, Tang et al. discussed the mechanisms underlying the positive effects of LJE on the gut microbiota, gut barrier function, and immune function. Overall, the review suggested that LJE has potential applications in animal production for promoting gut health, enhancing animal performance, and reducing the need for antibiotics. In the second review, Yang Y. et al. presented recent research on the relationship between cow's milk protein allergy (CMPA) and the gut microbiota in infants. The authors suggested a relation between CMPA and gut dysbiosis, as well as the potential use of probiotics, prebiotics, and synbiotics in the prevention and management of CMPA. In the third and final review, Hu et al. discussed the potential applications and functions of prophage activation in the intestine. The study highlighted that prophage activation could play a role in the modulation of gut microbiota composition and function, in the treatment of disease and infection , as well as in engineering the microbiome .Finally, three review articles were published in the RT. The first concentrated on the potential use of The studies featured in this RT encompass significant contributions from diverse authors, highlighting the multifaceted aspects between nutritional physiology and the gut microbiome in animal and human health.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "Infection of the bone is a difficult problem in orthopedic diseases. The key and basis of the treatment of bone infection is the effective control of local infection, as well as the elimination of infection focus and dead cavities. The most commonly used approach utilized for the prevention and management of bone infection is the application of antibiotic bone cement. However, the incorporation of antibiotics into the cement matrix has been found to considerably compromise the mechanical characteristics of bone cement. Moreover, some investigations have indicated that the antibiotic release rate of antibiotic bone cement is relatively low. Polyetheretherketone (PEEK) and its composites have been considered to perfectly address the challenges above, according to its favorable biomechanical characteristics and diverse surface functionalizations. This article provides a comprehensive overview of the recent advancements in the antimicrobial modification of PEEK composites in the field of antibacterial therapy of bone infection. Furthermore, the potential application of PEEK-modified materials in clinical treatment was discussed and predicted. Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Escherichia coli, Pseudomonas aeruginosa, Streptococcus, and others are prevalent pathogens , resembling that of bone tissue . FurtherIt was widely reported that poor osseointegration and bacterial infections had been identified as the primary factors contributing to the failure of PEEK and its composite implants . The bacThe initial stage in the pathophysiology of foreign body infection is thought to involve bacterial adhesion to the surface of biological material . Followicocci infections, owing to its ability to eliminate a vast majority of gram-positive bacteria and various drug-resistant bacteria , a glycopeptide antibiotic, can inhibit the synthesis of bacterial cell walls. This inhibits bacterial reproduction and proliferation. Van has emerged as an efficacious antibiotic for the treatment of drug-resistant bacteria . Van witubstrate . The Zn via PDA coating, followed by its combination with gelatin methacrylate (GelMA) and subsequent application onto the biologically inert sulfonated PEEK (SPEEK) (Gentamicin sulfate (GS) and tobramycin (TOB) are aminoglycoside antibiotics. TOB inhibits the synthesis of bacterial proteins. Polydopamine (PDA) possesses good adhesion and antioxidation , which c (SPEEK) . As show (SPEEK) . This in (SPEEK) .in vitro. The utilization of PEEK with co-administration of diverse antimicrobial agents had been shown to enhance the osseointegration and antibacterial efficacy of biomaterials, which exhibits considerable clinical potential.The simultaneous administration of multiple medications and the exploitation of the combined effects of antibiotics potentially enhanced the antibacterial and biocompatible properties of PEEK. S. aureus while maintaining outstanding mechanical properties and plant polyphenols have received a great deal of attention and research in recent years because of their clinical application potential for antimicrobial resistance and biocompatibility.via electrostatic contact. By regulating the immune response of the host, AMPs assisted in the indirect elimination of the pathogen from the host could proliferate osteogenically when the BMP/Smad signaling pathway was stimulated by KR-12 . The pos in vivo . To incr in vivo . It was in vivo . MBD-14 in vivo .in vivo are insufficient. Research in this field is still primarily focused on better AMP stability, higher selectivity, and reduced toxicity. Developing an effective dosing schedule, combining AMPs with other compounds to increase their antibacterial efficacy, and other measures will be necessary for the clinical application of AMPs was carefully prepared by cold pressing and sintering (E. coli and S. aureus in vitro because of the synergistic interaction between the -SO3H group and the continuous release of genistein. Plant polyphenol chlorogenic acid (CGA) was predominantly extracted from Fols Lonicerae. In order to solve the problem of large area defect and related infection in clinical bone grafting, CGA was loaded on the surface of SPEEK using a hydrogel system (E. coli and S. aureus and minimizing the probability of early implant infection. Curcumin (CR) is a polyphenol compound produced by turmeric extract that inhibits the replication of bacteria and fungi as well as inflammation and oxidation , a type of photothermal catalyst provided with unique single-layer carbon atomic nanosheet structure and excellent intrinsic antibacterial effect , has bee in vivo . Accordi in vivo . Ouyang,via electrostatic interaction, controlled cell adhesion, and stimulated specific gene expression. Consequently, the synergistic effect of GO/Dex-loaded liposomes increased cellular adhesion and migration, as well as improved cellular biocompatibility.Furthermore, the antibacterial activity and biocompatibility of PEEK were significantly improved by synergistic effect of photothermal catalysts and antimicrobial agents. Ouyang, et al. modifiedin vitro and in vivo. Meanwhile, bio-persistence of GO in the human body might have an impact on pathology and immunology Strategies including strong acid sulfonation, and 3D printing make sure the enhancement of the surface roughness of PEEK, augmentation of the hydrophilicity and promotion of the adhesion of osteocyte and bacteria. 2) Establishment of optimal dose and the appropriate controlled-released system to achieve the balance between therapeutic efficacy and cytotoxicity. 3) According to the characteristics of bone infection, such as dead cavity, local infection, bone defection, and so on, multifunctional formulation with antibacterial, osteointegration, and osteogenesis is also an important future direction of modified PEEK in bone infection."} +{"text": "Dear Editor,A 34-year-old white female complained of vertex alopecia for six years, associated with pruritus and local burning sensation. She reported that, since the onset of the condition, she observed the development of pustules at the periphery of the lesion. She denied comorbidities or ongoing medication use. She reported having had cycles of trimethoprim-sulfamethoxazole for 60 to 90 days, with partial improvement. The examination disclosed cicatricial alopecia area on the vertex region of the scalp, with follicular pustules at the periphery, erythema and areas with polytrichia . Dermosca)Folliculitis decalvansb)Folliculitis decalvans and lichen planopilaris phenotypic spectrumc)Centrifugal cicatricial alopeciad)Lichen planopilarisFolliculitis decalvans and lichen planopilaris phenotypic spectrum (FDLPPPS) is a recently described cicatricial alopecia, more prevalent on the vertex of the scalp in adults, which combines clinical and histopathological features of two other alopecias: lichen planopilaris (LPP) and folliculitis decalvans (FD), presenting with lymphocytic and neutrophilic inflammatory infiltrates, respectively.Staphylococcus aureus induces a biofilm that stimulates the innate immune response, perpetuating the neutrophil-mediated inflammatory process.3The pathogenesis of LPP and FD is still poorly understood; however, whereas in LPP there is activation of TCD8+ lymphocytes and loss of follicular immune privilege, in DF the presence of The etiology of FDLPPPS is still under discussion, given the coexistence of both inflammatory processes. It has been suggested that dysbiosis of the DF follicular microbiome may induce the exposure of follicular autoantigens, stimulating a Th1 response pattern.4As for the clinical picture, patients with FDLPPPS usually show a sequential biphasic process with the characteristics of FD preceding LPP, or even concomitant clinical characteristics: areas of cicatricial alopecia with follicular pustules, erythema and perifollicular desquamation, which may evolve with polytrichia, as in the present case.6Regarding histopathology, a mixed infiltrate is observed in the infundibulum region, with destruction and atrophy of the follicular epithelium and prevalence of plasma cells and histiocytes, in contrast to the predominance of neutrophils in the FD and lymphocytes in the LPP.8There is yet no standardized treatment for FDLPPPS, given its recent description. However, treatments used in FD and LPP are usually associated, such as corticosteroids, sulfonamides, doxycycline, retinoid antimalarials, and immunosuppressants, according to the predominance of clinical and trichoscopic characteristics. In this case, oral hydroxychloroquine 400\u202fmg/d and isotretinoin 30\u202fmg/d, and clobetasol 0.05% gel were introduced, with stabilization of the condition after six months. The rationale for choosing anti-inflammatory drugs and oral retinoids was based on the predominance of clinical and trichoscopic signs of the LPP spectrum, in this case, mainly after previous treatment with antibiotics, aiming to reduce the neutrophil activity intensity.The cases described in adults and children with FDLPPPS do not seem to reach a large area of the scalp, despite the delay in its diagnosis.8Dermatologists should be aware of the diagnosis of FDLPPPS in the presence of less characteristic cases of cicatricial alopecia on the vertex of the scalp, with pustules, erythema and follicular desquamation, in which the inflammatory infiltrate is mixed, or with alternating patterns in subsequent biopsies, and containing plasma cells.None declared.Miola AC: Design and planning of the study; collection, analysis and interpretation of data; critical review of the literature; critical review of the manuscript; writing and approval of the final version of the manuscript.Ramos PM: Critical review of the literature; critical review of the manuscript, writing and approval of the final version of the manuscript.Miot HA: Design and planning of the study; effective participation in research orientation; critical review of the literature; critical review of the manuscript, writing and approval of the final version of the manuscript.None declared."} +{"text": "The development of vaccines against the SARS-CoV-2 virus has become a big challenge for many countries in 2020-2022. mRNA vaccines were shown to be effective and safe and have been widely used worldwide in the fight against the COVID-19 pandemic. The fundamental factor in creating mRNA vaccines, which ensures effective delivery of mRNA to the host cells, is the composition of lipid nanoparticles, namely the presence of ionized charged lipids, which ensures the binding of mRNA molecules. However, the significant role of liposomes in the development of liposomal vaccines and identification of immunochemical reactions involving lipids should be assessed in the context of the development of the pioneering idea of August Wassermann about the use of liposomal antigens in the diagnosis and immunoprophylaxis of serious human diseases.The review is devoted to the use of liposomal antigens as antigen-delivery systems for diagnosis and immunoprophylaxis.Studies of cardiolipin antigen in serodiagnosis of syphilis became the foundation of antibodies in diagnosing various infectious diseases and pathological conditions, such as tuberculosis, lupus erythematosus, COVID-19, borreliosis, etc. Identification of antiphospholipid antibodies (mainly anticardiolipin) and today is the most important diagnostic tool for antiphospholipid syndrome.The liposomal system first proposed in 1906 for the diagnosis of syphilis evolved more than a century later into mRNA vaccines, which are used today in the fight against the COVID-19 pandemic. Treponema pallidum (syphilis) in humans using the complement fixation reaction with lipid antigens (Ag), called \u201cWassermann reaction\u201d , differing in qualitative and quantitative composition . . 9-11]. e.g. DPG, phosphatidylglycerol (PG), phosphatidylserine (PS) or phosphatidic acid (PA)), neutral lipid and Chol was offered ..55].Similarly to classical liposomes , the catThe algorithm for polylipid composition design of mRNA vaccine aims to form LNP and encapsulate the mRNA into its structure due to the interaction of the anionic phosphate backbone of the mRNA with the ionized lipid. In the design process, the mRNA contacts four lipids in a water-organic environment under the control of pH level and hydrophobic-hydrophilic balance to ensure the binding of the mRNA to the ionized lipid. Bound mRNA is identified in the inner cavity of multilayer LNPs formed by complementary lipid components. In this case, DSPC forms the main bilayer of the liposomal membrane, and the presence of PEG-lipid and Chol ensures optimal hydrophilicity, stability, and size of LNPs with encapsulated mRNA.A liposome-based vaccine candidate EG-COVID differs from the composition of Pfizer-BioNTech product, consists of DOTAP , DOPE and Chol, induces stable humoral and cellular immunity to the SARS-CoV-2 virus, and suppresses the SARS-CoV-2 viral infection in Vero cells . The optIn conclusion, the significant role of liposomes in the development of liposomal vaccines against COVID-19 and the identification of immunochemical reactions involving lipids should be assessed in the context of the development of the pioneering idea of August Wassermann about the diagnostic use of liposomal antigens in the creation of innovative liposomal preparations for the diagnosis and immunoprophylaxis of serious human diseases. Thus, the liposomal system first proposed in 1906 for the diagnosis of syphilis evolved Conflict of interest: The author declares no conflict of interest."} +{"text": "The COVID-19 pandemic has had significant consequences, impacting not only physical health but also mental wellbeing, social interactions, and economic stability . These eMental Illness, Culture, and Society: Dealing with the COVID-19 Pandemic\u201d builds upon the previous five volumes is a serious global issue that threatens healthcare workforce retention and health system resilience, especially during the fragile post-COVID \u201cnormalization\u201d period. The authors used a comparative approach, analyzing the epidemiological, political, and geographic contexts of Brazil, the United Kingdom, New Zealand, and Germany to identify similarities and differences in violence against HCWs. Overall, the results showed a general sensitivity of HCWs to violence, with women, nurses, and migrant/minority groups being particularly exposed. The authors emphasized the need for attention to this topic and to all forms of violence in the world.Huang et al. aimed to compare depressive symptoms among HCWs in high-risk areas (HRAs) and low-risk areas (LRAs) during the initial stage of the COVID-19 pandemic in China. The results showed that HCWs in LRAs had 1.96 times higher odds of having depressive symptoms than those in HRAs. There were also significant differences in workplace environment characteristics and the Health Belief Model between the two groups. The study highlighted the importance of considering the mental health of HCWs, especially in LRAs, and tailoring interventions to their specific needs.The study by Savu et al. aimed to determine the mediating role of HCWs' perception of their own health on pandemic stress, work-family conflict, work engagement, meaning and commitment to work, satisfaction of basic psychological needs, patient care, and burnout symptoms. The authors identified significant correlations between the investigated variables. In particular, HCWs with a positive perception of their own health were better at managing pandemic stress, burnout effects, and work-family imbalances.The study conducted by Ayub et al. reviewed the impact of the COVID-19 pandemic on religious activities and beliefs, and explored the potential role of religious leaders and communities in mitigating the pandemic's impact through public health measures and community engagement. The authors identified the following main themes: the relationship between religious practices, beliefs, and the spread of COVID-19, and the role of religious leaders and faith communities in coping with and mitigating the impact of COVID-19. The review highlighted the essential role of religious leaders, faith-based organizations, and faith communities in promoting education, preparedness, and response efforts during the pandemic. The importance of collaboration between religious leaders, institutions, and public health officials was also emphasized.Ryu et al. aimed to understand COVID-19 vaccine acceptance and related factors among 572 individuals with mental disorders residing in Korea. Clustering revealed three groups in relation to vaccine acceptance: totally accepting, somewhat accepting, and hesitant groups. Individuals in the high vaccine acceptance group were older, more likely to receive the influenza vaccine regularly, and more likely to trust formal information sources. The study highlighted the importance of understanding the behavioral and psychological characteristics associated with vaccine acceptance, to be able to effectively communicate its importance to individuals with mental disorders.Carbone and Knapp investigated the use of mandatory psychiatric treatments during the COVID-19 pandemic, with a focus on the first and subsequent phases. Interviews were conducted with mental health care professionals and scholars from four countries. The analysis identified four major themes: the culture of psychiatric care services, the effect of the pandemic on involuntary hospitalizations, exceptional management of hospitalization to reduce infection spread, and policies and suggestions for more inclusive mental health treatments. The study found that during the first wave, there was a decrease in the use of involuntary treatments, while a gradual increase was observed in the following months.Qiao et al. documented the unique challenges faced by rural black women during the COVID-19 pandemic and tried to highlight their needs for effective management of social, physical, and mental health challenges. The study aimed to inform evidence-based decision-making for policymakers and to contribute to the development of public health emergency preparedness plans. This would help promote the resilience of rural Black women and their families during future infectious disease outbreaks and other public health emergencies.With their study protocol, Park et al. examined the connections between pandemic-related factors and anxiety/depressive symptoms in young adults from South Korea and the U.S.. The findings from 1,123 participants collected during the COVID-19 lockdown period showed similar network structures in both countries, suggesting a consistent relationship between the pandemic and internalizing symptoms, irrespective of sociocultural differences. COVID-related stress and negative anticipation of the future were identified as key factors connecting pandemic-related elements to psychological distress.The study by Du discussed the impact of the COVID-19 pandemic on community-centered engagement and healthcare services. The author particularly described the experiences of migrant workers in Singapore and community volunteers in Shanghai and the effectiveness of coordinated community efforts in providing essential supplies and support during lockdowns Du. The article also emphasized the role of community health centers in testing and vaccination programs, especially among marginalized populations.Finally, In brief, the articles collected in the Sixth Volume of this Research Topic provide a novel perspective on the pandemic's impact on mental health, further emphasizing the role of sociocultural, economic, and individual factors in this interplay. The influence of COVID-19 on psychiatry and mental health is significant and enduring. Further clinical and epidemiological research is necessary to address the vulnerabilities of the most fragile segments of society.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "Nyatega et al.) \u20139. The d et al.) , 11. An et al.) , studies et al.) , 14, phy et al.) , 16 and et al.) . These t et al.) . Recent et al.) , 20 and Therefore, in this Research Topic, we present a collection of articles that showcase recent advances in neuroimaging and non-invasive brain stimulation techniques and their application to the study of the brain's structural and functional organization.Understanding the brain's structure and function is vital in the diagnosis and treatment of neuropsychiatric disorders. Advances in neuroimaging and NIBS techniques have enabled researchers to explore the underlying mechanisms of disorders such as depression, SCZ, anxiety and post-traumatic stress disorders , 21, 22.These articles demonstrate the applications of neuroimaging in studying drug abuse, bipolar disorder (BP), dysmenorrhea, white matter lesions (WML), functional dyspepsia (FD), and SCZ. The meta-analysis of cocaine addiction shows how drug abuse affects the brain. The study on BP reveals the relationship between cerebral WML and the incidence of BP. The investigation of primary dysmenorrhea offers insights into the relationship between pain and the brain, while the exploration of differential brain responses to meal ingestion in FD patients provides a better understanding of this meal-induced syndrome. Finally, structural magnetic resonance imaging studies provide insights into the pathophysiology of SCZ.Dang et al. These findings suggest that drug addiction is a complex neurobiological disorder and not solely a behavioral problem. Identifying the specific brain regions and circuits impacted by cocaine addiction can help develop new treatments targeting these neural mechanisms . These findings provide valuable insights into the structural and functional organization of the brain in individuals with BD . These findings provide insights into the structural and functional organization of the brain in FD patients and may have implications for the diagnosis and treatment of neuropsychiatric disorders involving visceral hypersensitivity and emotional dysregulation (gulation , 34. OveAdamu et al.'s structural MRI study sheds light on the pathophysiology of SCZ, showing that individuals with the disorder have structural brain abnormalities linked to specific symptom clusters and cognitive impairments. The study also highlights the use of machine learning to identify patterns of brain structure associated with symptoms and impairments. The findings contribute to our understanding of the structural and functional organization of the brain in neuropsychiatric disorders and could improve diagnosis and treatment (reatment , 36. By The articles in this Research Topic highlight the importance of continued research on the structural and functional organization of the brain and its potential impact on the diagnosis and treatment of neuropsychiatric disorders \u201341. The MT, MD, and SB contributed to conception and design and wrote sections of the manuscript. MT wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version."} +{"text": "Dear Editor,A 64-year-old female patient has complained of darkening and deformity of the nail of the third left finger for two years. On examination, onychodystrophy, slight subungual thickening, and irregularly pigmented longitudinal melanonychia (LM) measuring 3\u202fmm were observed A. Dermosin situ, has a variable record of its frequency, possibly due to failure in its recognition or underreporting. On the other hand, SCC is the most common neoplasm of the nail apparatus, often with late diagnosis. Typically, ungueal BD presents as subungual hyperkeratosis or a verrucous lesion of the nail plate or bed; with periungual erythema and paronychia associated with crusts, ulcerations, or fissures, onychocryptosis, and/or nail dystrophy, and rarely with LM.Ungueal BD, or squamous cell carcinoma (SCC) Exogenous pigment deposits , blood, and melanin are frequent causes nail plate and nail bed pigmentation, and melanocytic activation and benign melanocytic nevi are the most common causes of LM in adults and children, respectively. However, about 2/3 of ungueal melanomas present clinically as LM.Some clinical criteria should raise the index of suspicion of melanoma in acquired LM in adults: the presence of heterogeneous pigmentation in bands or lines of variable colors, fissures or clefts in the nail plate, especially in the distal region (triangular shape), the sudden appearance of nail plate pigmentation, and blurring of the nail fold edges.Digital pigmented BD mimics melanoma and may show a chaotic pattern on dermoscopy: atypical parallel pattern of grooves and ridges, and a chaotic pattern with segmental radial lines suggestive of melanoma, associated with other dermoscopic characteristics suggestive of BD, such as squamous surface and linear arrangement of dotted vessels.LM dermoscopy is limited to the observation of the distribution of pigment deposited in the nail plate, and the underlying lesions can be misinterpreted, which is why intraoperative dermoscopy becomes relevant. Hirata et al. defined four patterns of intraoperative dermoscopy of the nail matrix and nail bed in LM: regular gray, regular brown, regular brown with globules or spots, and irregular pattern.Among dermoscopy findings, hyperkeratosis located on the free edge of the nail plate was the criterion significantly associated with subungual SCC.Despite the clinical and dermoscopic findings of the nail plate, and intraoperative dermoscopic findings of the nail bed and matrix raising the suspicion of melanoma, histopathological evaluation did not show proliferation of atypical melanocytes, confirmed by negative immunohistochemistry for HMB45 and S100 protein. Positive immunohistochemistry for AE1/AE3, an antibody against human epidermal keratins, therefore, a marker of normal epithelial cells, carcinomas, and other tumors with epithelial differentiation such as BD, revealed the epithelial nature of the neoplasm in the present case.Pigmented BD of the nail apparatus is a rarely diagnosed neoplasia and should be considered in the differential diagnosis of LM, particularly in the differential diagnosis with nail melanoma.A careful evaluation and management of patients with nail pigmentation, taking into account clinical features, dermoscopy of the nail plate, and intraoperative examination of the nail matrix and nail bed can help rule out common causes of nail pigmentation; however, the histopathological examination still remains the reference to confirm the diagnosis of the lesion which is determining LM.None declared.Guilherme de Medeiros Holanda: Design and planning of the studied case; collection, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; critical review of the literature; drafting and editing of the manuscript.Bruno de Carvalho Fantini: Design and planning of the studied case; collection, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; approval of the final version of the manuscript.Guilherme Raya Ravelli: Approval of the final version of the manuscript; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case.Cacilda da Silva Souza: Design and planning of the studied case; collection, analysis and interpretation of data; critical review of the literature; drafting and editing of the manuscript; approval of the final version of the manuscript.None declared."} +{"text": "In this Research Topic, we explore health policy and systems research at the nexus between urbanization and health. The global trend of urbanization will not abate in the near future and the related challenges are many. Low- and middle-income countries (LMICs) are observing a continued expansion of informal settlements, residential segregation, a double burden of life-long conditions and (re-emerging) infectious diseases. Important socio-ecological challenges relate to urban sprawl, unregulated economic activities, pollution, and environmental degradation. A central concern in LMICs is the impact of urbanization on equity and social inclusion , 2.community, experiential, environmental, and structural policy level\u201d . Their study uses modeling in management of urban emergencies and illustrates how such techniques can improve decision-making in crisis situations when uncertainty is high.The occurrence of natural disasters and other large-scale emergencies represents another aspect of urban health that transcends sectors and dimensions. Almasi et al. and Banke-Thomas et al. report on the integration of geographical data in urban health policy and system analysis. Almasi et al. investigated the location of medical laboratories in Kermanshah (Iran) and its impact on access to laboratory services. The authors used a combination of GIS-based mapping of facilities and network analysis to map locations of laboratories and their accessibility for urban residents. They found coverage gaps in specific areas of the city, pointing to inequitable distribution of facilities and access problems. Banke-Thomas et al. investigated how, in big cities, the travel time of pregnant women requiring urgent care can be estimated using Google Maps data. The authors developed a method to estimate the travel time of women requiring Emergency Obstetric Care in Lagos (Nigeria). Next, they plan to co-create dashboards with urban health policymakers and data companies, which will combine data on travel time with data on the functionality of hospitals. Similar to Almasi et al., they highlight inequities related to the place of residence. Such approaches could contribute to a better understanding of how the urban advantage can become a disadvantage for those living in underserved areas developed local initiatives for evidence building and information distribution during the COVID-19 wave of July 2020. Family practitioners considered that the contact tracing system set up by the Flemish government would be ineffective in their superdiverse neighborhoods. In < 2 weeks and in close collaboration with city and provincial authorities, they set up a successful alternative system of COVID coaches in support of contact tracing and self-isolation. This study illustrates how in situations of high uncertainty, national responses can and must be adapted to local contexts. Yet, this requires a strong learning culture, embedded in adaptive governance arrangements, and the importance of incorporating local innovations into broader policies and programs identify systemic relations within the spatial context, (b) facilitate integration of quantitative and qualitative data, and (c) guide the formulation of policy recommendations, informing public and urban health planning.\u201d They illustrate this in a study on malaria in Jimma (Ethiopia) and on tuberculosis and COVID-19 in Lima (Peru). Fang et al. addressed another intersecting set of challenges: aging, rapid urbanization, and increasing digitisation of social spaces and resources. This requires cities and communities to develop age-friendly community ecosystems that put intergenerational relationships at the center. The authors adopted a community-based participatory research approach and co-creation methods to co-create recommendations for research, policy, and practice. The paper illustrates how Bronfenbrenner's ecological systems theory provides a multi-level framework to assess how wellbeing is shaped an interplay of micro- and macro-level factors.Unpacking the relationships between the social, political, economic, infrastructural, and ecological determinants of health in cities is key to understanding urban health. This requires multidisciplinary approaches and multi-actor knowledge production. Two papers address this methodological challenge. The papers included in this Research Topic present unique methodological, empirical, and practical contributions that speak to the complex nature of the urbanization-health nexus. Yet, they also show that research into urban inequities, residential segregation and social exclusion merits more attention. More research is also needed on the dynamic interplay between cities, the national and the global level regarding health. National development plans and urban policies shape cities. Cities have open boundaries through which people migrate continuously. Cities are also players in networked global markets and are hubs in global disease transmission patterns. Moreover, the interface between global warming and health calls for more research on intersectoral action for climate-resilient urban health systems.This Research Topic shows that interesting and innovative research is being done at the still little explored frontier of urbanization and health. In these turbulent times, the challenges confronting urban planners, managers, and researchers, as well as people, providers and communities are only amplified. The Health Policy and Health System Research community will need to rise up to contribute to making cities healthier for its people through more innovative studies.All authors contributed to the conceptualization, drafting, and final revision of this editorial."} +{"text": "Consumers are increasingly demanding higher quality meat products. However, meat products manufactured using traditional processing procedures are often perceived as unhealthy or hazardous foods, due to the significant amounts of sodium chloride added, the excessive accumulation of harmful substances, and the abnormal growth of spoilage microorganisms. Green processing is a new concept aiming to meet the challenges of the 21st century, and should be the result of a whole chain of values to protect both the environment and consumers. In the meantime, it will hopefully drive industries to be more ecologic, economic, and innovative. Green technologies show great potential in decreasing or preventing the formation of hazardous substances, increasing the shelf life, and maintaining the sensory attributes and nutritional qualities of meat products during the manufacturing of food. Thus, this topic will discuss the effect of green processing on the mechanism of quality development of meat and meat products from the perspective of chemical and biochemical composition and structure changes in molecules during the processing of meat products, as well as the chemistry related to the major components of meat products, and their nutritional, physiological, sensory, flavor, and microbiological properties.This Special Issue is made up of eighteen research articles aiming at providing up-to-date research on the abovementioned aspects related to raw meat, by-products, meat products, and advances made in meat quality assessment. The different works can be assigned to four distinct groups. One portion of these studies focused on the quality assessment of raw meat; another portion of these studies investigated the antioxidant, gelling, and emulsion properties of proteins; another portion characterized the spoilage of meat and meat products; and the remaining portion mainly evaluated the flavor and texture of processed meat products.Regarding the quality assessment of raw meat, Cao et al. highlighClostridium and Pseudomonas are the key genera involved in this process. Pseudomonas lundensis exhibited the strongest spoilage potential during the storage of chilled chicken [Clostridium was mainly responsible for the spoilage in deeply spoiled ham [Clostridium perfringens [Pseudomonas was also inhibited by the chitosan/collagen peptides/cinnamon bark essential oil composite coating [Green processing has a significant effect on the functional properties of meat proteins, and on decreasing or preventing the spoilage of meat products. The improvements in the gelling, rheology, and emulsion properties of meat protein were highlighted using typical green technologies, including ultrasonication, high-pressure homogenization, and isoelectric solubilization/precipitation ,7,8. Sev chicken ; Clostriiled ham . The comfringens . Further coating .Texture and flavor are the key parameters of fermented and spiced meat products. The addition of halogen and spicy flavors showed a positive effect for the relative content of alkanes and ketones during the processing of a Midu pork roll . Zhang e"} +{"text": "Energy management methods (EMMs) utilizing sensing, communication, and networking technologies appear to be one of the most promising directions for energy saving and environmental protection of fuel cell vehicles (FCVs). In real-world driving situations, EMMs based on driving cycle information are critical for FCVs and have been extensively studied. The collection and processing of driving cycle information is a fundamental and critical work that cannot be separated from sensors, global positioning system (GPS), vehicle-to-vehicle (V2V), vehicle-to-everything (V2X), intelligent transportation system (ITS) and some processing algorithms. However, no reviews have comprehensively summarized the EMMs for FCVs from the perspective of driving cycle information. Motivated by the literature gap, this paper provides a state-of-the-art understanding of EMMs for FCVs from the perspective of driving cycle information, including a detailed description for driving cycle information analysis, and a comprehensive summary of the latest EMMs for FCVs, with a focus on EMMs based on driving pattern recognition (DPR) and driving characteristic prediction (DCP). Based on the above analysis, an in-depth presentation of the highlights and prospects is provided for the realization of high-performance EMMs for FCVs in real-world driving situations. This paper aims at helping the relevant researchers develop suitable and efficient EMMs for FCVs using driving cycle information. Energy shortage and environmental pollution are urgent problems that all countries in the world need to face . AcademiPrevious studies have shown that driving cycle information can make a difference in vehicle energy management ,13,14. IDriving cycle information is very critical for the development of EMMs, mainly reflected in the current driving patterns and future driving characteristics. However, in real-world driving situations, the driving cycle changes in real time. Consequently, obtaining current and future driving cycle information is a difficult and inaccessible task. As a matter of fact, some papers have proposed some EMMs considering driving cycle information for FCVs, mainly based on driving pattern recognition and future driving characteristic prediction. It is noticed that recent reviews have stated the advances progress in energy management methods for fuel cell vehicles ,23,24,25Motivated by the literature gap, this review mainly focuses on the technologies and progress of EMMs for FCVs from the perspective of driving cycle information, and strives to be comprehensive and innovative. The main contributions of this review are as follows: (i) providing a state-of-the-art understanding of EMMs for FCVs from the perspective of driving cycle information; (ii) providing a detailed description for driving cycle information analysis, including driving cycle collection and processing; (iii) providing a comprehensive summary of the latest EMMs for FCVs, with a focus on EMMs based on driving pattern recognition and driving characteristic prediction; and (iv) providing an in-depth presentation of the important highlights and prospects regarding the innovation of EMMs for FCVs. This review hopefully accelerates the realization of high-performance EMMs for FCVs in real-world driving situations.The rest of this review is organized into several sections: As the driving cycle is discerned as the input of the EMMs for FCVs, its information would affect the control performance of EMM extremely ,26. In aWith the development of intelligent networking technology, information and communication technology and big data technology, it is no longer difficult to collect and analyze the driving cycle. In recent years, global positioning system (GPS) receivers , on boarDue to the influence of the driving environment, jamming signals, zero drift, and buildings, the driving information collected often exhibited bad data . Bad datThe preprocessed driving cycle can be divided into some kinematic segments to reduce the complexity of subsequent processing. This segmentation is performed for the driving cycle characteristics analysis . DrivingPrevious studies have shown that driving pattern can greatly influence the effectiveness of EMMs ,57,58. FIn other studies of this area, supervised algorithms are adopted to recognize the vehicle driving pattern , such asThe driving cycle of a vehicle can be predicted by driving characteristic prediction (DCP) techniques, and the results indicate the current or future driving characteristics of the vehicle, like velocity and acceleration ,71. The The other is DCP based on positioning, sensing, interaction-aware, and other traffic information service technologies, such as V2X, V2V, and ITS ,82,83. TAs mentioned above, FCVs are one of the most promising future vehicles , and suiPrevious studies have extensively studied the EMMs of FCVs to improve energy efficiency and durability. The EMMs of FCVs can be divided into three major categories: (i) rule based, (ii) optimization based, and (iii) other based, as shown in As a new research hotspot in the field of artificial intelligence (AI) and internet of vehicles (IOV), learning-based and cycle information-based EMMs have been applied to achieve the optimal fuel economy of FCVs in real time ,111. ProIn recent years, to improve the performance of the EMMs for FCVs, research on driving pattern recognition has been proposed ,119,120.Moreover, to further improve the comprehensive economy of FCVs and extend the life of the ESSs, optimization algorithms and learning algorithms were combined and adopted in the design of EMMs. In , a genetCompared to the related research on the EMMs for FCVs based on driving pattern recognition, research on the EMMs for FCVs based on driving characteristic prediction is more extensive and in-depth due to the promotion of the intelligent process of NEVs ,131,132.Accurate driving pattern recognition: The accuracy of driving pattern recognition is crucial for the development and implementation of EMMs. However, recognition accuracy and algorithm complexity are interrelated. Some advanced recognition algorithms in the existing literature have the problem of low recognition accuracy. In the future, the sampling time, the selection of characteristic parameters, and the recognition period can all be combined with advanced recognition algorithms to construct recognition methods with excellent recognition accuracy and efficiency.Short-term driving characteristic prediction: Affected by the impacts of real-world driving conditions, the driving characteristics of vehicles will change in real time. Therefore, short-term driving characteristic prediction remains a hot and challenging issue, as it depends on various factors like the prediction method and traffic conditions. In the future, with the help of V2V, V2X, ITS and predictive algorithms, driving characteristics like speed, mileage, slope, and traffic signal light states can be predicted in the short term.Real-time energy management optimization: Ideal energy management optimization methods can adaptively generate effective control decisions considering the DPR and DCP results. However, most current energy management optimization methods are difficult to apply to real vehicles. Advanced algorithms bring up more possibilities of real-time energy management optimization which are worth exploring. In the future, real-time/online/adaptive EMMs will be considered for supplying an excellent control effect.Integrated driving style recognition: Even the same driver can exhibit different driving styles under different road conditions, and different driving styles can directly affect the energy management of the FCVs. Therefore, introducing the influence of driving styles into the EMMs for FCVs will be valuable and crucial. However, driving style is often described qualitatively, and is not integrated into the EMMs. In the future, integrated driving style recognition of drivers in real social driving networks will improve the effectiveness of EMMs for FCVs.In order to improve the energy economy and prolong the powertrain system durability of FCVs, it is urgent and meaningful to develop suitable and efficient EMMs. As driving cycle information is extremely important in EMMs for FCVs, some studies have studied driving cycle information collection and processing, which lay the foundation for the development of EMMs based on driving cycle information. This paper provides a state-of-the-art understanding and a detailed overview of EMMs for FCVs from the perspective of driving cycle information. More specifically, this paper comprehensively reviews studies on driving cycle information analysis and the EMMs for FCVs, which mainly focuses on EMMs based on DPR and DCP. This paper can provide potential guidance for the design and development of EMMs for FCVs in real-world driving situations. Although great progress has been made in the EMMs based on driving cycle information for FCVs, there are still many challenges. The main prospects of this review are the following:Accurate driving pattern recognition algorithms, short-term driving characteristic prediction algorithms, real-time energy management optimization methods and integrated driving style recognition methods will improve the energy economy and prolong the powertrain system durability of FCVs. In the future, our work will focus on the development and application of EMMs for FCVs based on the ITS and DCP technologies."} +{"text": "Colorectal cancer (CRC) is the third most common malignancy in terms of global tumor incidence, and the rates of morbidity and mortality due to CRC are rising. Experimental models of CRC play a vital role in CRC research. Clinical studies aimed at investigating the evolution and mechanism underlying the formation of CRC are based on cellular and animal models with broad applications. The present review classifies the different experimental models used in CRC research, and describes the characteristics and limitations of these models by comparing the research models with the clinical symptoms. The review also discusses the future prospects of developing new experimental models of CRC. Colorectal cancer (CRC) is the most common malignancy worldwide, in terms of both morbidity and mortality . The undIn vitro models of CRC established using intestinal cells and CRC cells are frequently employed for obtaining rapidly growing cellular models of CRC and for facilitating experimental control. In vitro models of CRC can simultaneously generate several populations of homogeneous cells. Specific cellular targets of macroscopic systems can be conveniently studied using these models by analyzing the experimental results , including the cells and acellular components constituting the structural complexity of the in vivo environment. Altogether, these indicate that CRC cell lines fail to accurately mimic the in vivo growth characteristics of tumor cells.Although the characteristics of CRC cell lines are highly consistent with those of human cancer models, they have certain limitations. CRC cell lines facilitate the investigation of the molecular and phenotypic characteristics of CRC. However, as only one side of the cells is in contact with the medium during culture, the majority of cells gradually flatten, undergo abnormal division, and lose their differentiation phenotype following isolation from tissues and plate culture. Additionally, CRC cells continue to proliferate In vitro 3D culture models, including spheroids and organoids, are therefore used for overcoming the limitations of 2D cellular models. Spheroids comprise a mixture of single-cell or multicellular systems, while organoids are generally formed of specific stem cells or ancestral cells from organs , tumorospheres, tissue-derived tumor spheres (TDTS), and organotypic multicellular spheroids OMS; Weiswal.in vivo was used in the early 2000s for evaluating the differentiation capacity of tumors. However, because there are no morphological phenotypes associated with the phenotypic instability of CSCs, the tumorosphere model is unable to faithfully simulate the f tumors .in vitro 3D cell culture models of CRC culture models that are frequently used in CRC research. Organoids are self-organizing organotypic cultures that are produced from various stem cells, including tissue specific adult stem cells (ASCs), embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) . The steructures (Lancastructures .+) intestinal stem cells in a medium containing stem cell niche restatement factors and tissue-specific growth factors mutations, poor differentiation, or mucinous phenotypes related to CRC. The application of organoids to CRC research can be improved by employing the co-culture model of organoids in which immune cells and mesenchymal cells are co-cultured for simulating the in vivo TME.Organoids are typically used for investigating the mechanism underlying the development of CRC, screening anti-CRC drugs, and determining the efficacy and mechanism of action of drugs. However, there are various limitations to the application of organoids in studies on CRC, which are described hereafter. First, the current methods for organoid culture lack the technological means for maintaining the blood vessels, immune system, and peripheral nervous system of tumor cells, and organoids lacking these characteristics cannot be used in CRC research . Second,he tumor . Third, The establishment of models using the corresponding tumor cells is crucial for investigating the mechanism underlying the development of CRC and discovery of anti-CRC drugs . The appThe occurrence of diseases such as cancer that occur spontaneously in animals is largely attributed to genetic diversity and immune functions. Therefore, studying the methods for generating animal models of CRC can aid in elucidating the mechanisms underlying the development of cancer . Animal Rodent models are conducive tools for conducting cancer research, and are extensively used for elucidating the etiopathogenesis and molecular mechanisms underlying the development of CRC. Previous studies have demonstrated that the protein-coding genes of mice and humans share high homogeneity . AdditioAPC (adenomatous polyposis coli) are commonly inherited in adenoma-carcinoma transitions observed during the development of CRC , Kirsten rats arcomaviral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), F-box and WD repeat domain containing 7 (FBXW7), SMAD family member 4 (SMAD4), transcription factor 7-like 2 (TCF7L2), NRAS proto-oncogene (NRAS), AT-rich interaction domain 1\u00a0A (ARID1A), SRY-box transcription factor 9 (SOX9), and APC membrane recruitment protein 1 (FAM123B) can also increase the risk of CRC and western medicine are two different medical theoretical systems. The research model based on the etiological mechanism theory of TCM is applied to animal studies with TCM syndrome, as shown in Understanding the inherent advantages and limitations of the different models of CRC, and the appropriate application of these models in drug development and studies on the mechanism of tumor occurrence and development are important in CRC research.in vitro physiological or pathological models that closely represent the in vivo condition, and can be used for studying the interactions between cells, and between cells and the culture environment. It has been reported that 3D models can mimic the physiological characteristics of parental tumors, including tumor heterogeneity (in vivo.Human cell lines and xenograft models have been extensively employed over the past few decades owing to their low cost and ease of application. However, these models are incapable of reproducing the heterogeneity of CRC tumors . The celogeneity . Howeverogeneity . It is tThe intestinal microarray platforms used in CRC research, which consist of intestinal organoids and organic chips, can summarize the important structural features and functions of the natural duodenum. This platform can be applied for studying drug conveyance, metabolism, and drug-drug interactions . Multi-lin situ models and the cell and tissue transplantation models of CRC. Owing to the relatively simple modeling approach of human tumor xenotransplantation, this model is presently widely used for studying the efficacy of anti-CRC drugs. The effects of CRC xenotransplantation can be closely related to clinical activity via the rational application of these models. For instance, genetically engineered murine models have been used for studying the progression of tissue-specific molecular changes in CRC by determining the effect of specific molecular targets. Chemical induced-CRC animal model is one of the most commonly CRC models, in which CAC model is usually induced by AOM/DSS to study the mechanism of inflammation related-tumorigenesis and development (Animal models of CRC have been widely used for studying the complexity of CRC. There are primarily two types of animal models, namely, elopment . The CRCelopment . Mouse ielopment .The application of molecular tools and genetic strategies has aided the advancement of cancer research, and the cellular and animal models of CRC are being continually improved. Further understanding of the genetic and epigenetic events in CRC, including the alterations in molecular networks associated with the initial stages of development, are facilitated by high-resolution approaches.in vivo and in vitro models in CRC research, combined with advanced scientific techniques for simulating a more realistic tumor environment in vivo and in vitro, can help replicate the complex scenarios of tumor occurrence and development, identify novel therapeutic approaches for inhibiting tumor growth, and elucidate the molecular mechanisms underlying tumor formation.Although CRC research has advanced immensely in recent years, several clinical issues remain to be resolved to date, which is partly attributed to the absence of suitable preclinical research models. The application of"} +{"text": "The human exposome represents the totality of all environmental exposures over a lifetime, from conception to death, and the effect of these exposures on human health and disease , 2. In rIn this Research Topic, we invited original research, commentaries, and opinions to demonstrate the multidisciplinary nature of exposome research and the challenges in the use of metabolomics for this endeavor. Here, we highlight some of these aspects with emphasis on methodological and technological developments, data processing approaches, and the role of environmental, dietary, and occupational exposures.Price et al., aiming to address the lack of high-resolution electron ionization mass spectral libraries (HR-[EI+]-MS) for environmental chemicals, constructed a retention-indexed HR-[EI+]-MS library following analysis of authentic compounds via GC-Orbitrap MS. The library is freely provided alongside a compound database of predicted physicochemical properties and offers a significant resource to the research community as an open science and open-source tool. Currently, the library contains over 350 compounds from 56 compound classes and includes a range of legacy and emerging contaminants. The RECETOX Exposome HR-[EI+]-MS library expands the number of freely available resources for use in full-scan chemical exposure studies and is available as described in the manuscript.One of the greatest challenges of metabolomics and exposome research is metabolite identification and the lack of suitable metabolite libraries and databases for this purpose. In the field of GC-MS, EI mass spectra have been compiled in libraries for years, however, most of these spectra have been reported at low resolution. Nikou et al., the authors used state-of-the-art metabolomics methodologies to identify chemical biomarkers characteristic of geographical origin, cultivation practice, and production procedure of olive oil, a part of the Mediterranean diet that has been characterized as a healthy dietary pattern. Metabolomic profiling with Flow Injection Analysis - Magnetic Resonance Mass Spectrometry (FIA-MRMS) and LC-Orbitrap MS platform were used to analyze intact oil and the corresponding polyphenols of Extra Virgin Olive Oils. The methodology has the potential to offer a tool to tackle food fraud and adulteration and to also identify components of healthy dietary patterns.Metabolomics offers unique opportunities to identify food constituents and understand their role in the dietary exposome and food quality. In the manuscript by Borroni et al., the authors evaluated the effect of night shift work on the serum metabolome in a population of Italian female nurses working on night shifts and female colleagues not employed on night shifts, demonstrating differences in the levels of taurine, serotonin, aspartic acid, and some lipids, all of which offer clues on the biological alterations involved in shift work.An important part of the exposome is occupational exposures and patterns, including shift work, which in recent years has been associated with several physiological changes and potentially correlating with several diseases. In the manuscript by Barupal et al., the authors demonstrated that the re-processing of metabolomics datasets, already published and publicly available, can change the number of metabolite identifications made and potentially uncover new biomarkers that may have been missed during the initial processing. The authors used MS-Dial for data pre-processing, a publicly available software, and applied less stringent data processing thresholds compared with the original data pre-processing approach that used the mass spectrometer manufacturer's software. The manuscript demonstrated the opportunities and also the challenges that arise from the fact that different software and even slight changes in pre-processing parameters can impact the quality and volume of data reported. The manuscript initiated a lively debate with two further commentaries by Keski-Rahkonen et al. and Barupal, which contributed to the overall metabolomics community discussions about methodologies, software and parameters of data pre-processing, reporting standards and formats, and inter-comparability between data pre-processing methodologies.In the manuscript by The study of the exposome and metabolomics is remarkably multidisciplinary and fast-moving, and this Research Topic captured some of the recent exciting developments and concepts in the field. We believe that the reader will find this Research Topic to be a useful reference that can inspire future research and innovations.This manuscript was initially written by AS. Manuscript was revised and edited by HK, RK, BW, and LM. All authors contributed to the article and approved the final submitted version."} +{"text": "Among the neurophysiological methods of investigating the brain, electroencephalography (EEG) and quantitative electroencephalography (QEEG) are known for showing constant increases in sensitivity and specificity, and exponential advancement in clinical utility. Detection and interpretation of the human brain waves using EEG allows a deeper understanding of brain functioning. Building on this, QEEG involves the use of various algorithms leading to the transformation of brain waves into numerical data, which can be analyzed to gain insight into signal complexity, neural networks, and connections within the human brain. The technique has been applied extensively in clinical settings, including the study of neuropsychiatric disorders, human behavior, epilepsy, stroke, or traumatic brain injury.Neurotechnology connects a wide variety of fields aiming to diminish the existing gaps in neurosciences, from medicine and psychology to assistive technologies, engineering, and artificial intelligence. Its objective is to investigate brain principles from bench to bedside, promoting a thorough understanding of cerebral processes, and the development of innovative technologies with experimental and clinical applications.EUNeurotech, the European University of Brain and Technology, brings together nine prominent universities and a large variety of stakeholders covering all European regions. The goal is to facilitate collaboration among all interested stakeholders thus establishing a complex European network of neuroscientific excellence focusing on neurological research and technology. The project fosters a competitive, diverse, and multilevel approach to achieve its goals.EU and Erasmus+ Programme, the University of Medicine and Pharmacy Iuliu Ha\u021bieganu (UMFIH) organized the second edition of the QEEG Summer School (QEEGSS) between the 17th and 21st of July 2023 in Cluj-Napoca, Romania.After a successful first edition in 2022, developed as a Blended Intensive Program (BIP) in the framework of NeurotechEU Alliance, while one came on demand from Cologne University.The educational program, coordinated by Prof. Dr. Dafin Mure\u0219anu and Dr. Livia Popa, assembled 25 junior researchers from six countries: France \u2013 Lille University (7 delegates), Germany \u2013 Bonn University (3 delegates), Cologne University (1 delegate), the Netherlands \u2013 Radboud University (1 delegate), Iceland \u2013 Reykjavik University (4 delegates), Spain \u2013 Miguel Hern\u00e1ndez University (4 delegates), and Romania \u2013 UMFIH Cluj-Napoca (5 delegates). Most candidates had a bachelor\u2019s degree in medicine, psychology, bioengineering, biotechnology, industrial technology, or biological sciences. However, a few medical students were also admitted to the program. Among the participants, twenty-four were affiliated with universities from the NeurotechThe training adopted a basic-to-intricate approach, starting with the fundamentals of EEG and progressing to different types of QEEG analysis , and the association of QEEG with other technologies and eye tracking).The educational event was strategically designed to maximize engagement and active learning. Each day included morning lectures followed by interactive hands-on sessions in the afternoon in two locations: the RoNeuro Institute for Neurological Research and Diagnostic and UMFIH. This format was maintained over a four-day period. On the fifth day, the participants presented their projects and were evaluated regarding their understanding of the course content, acquired skills, approach to the project, presentation skills, and originality. Subsequently, the winning team was established and awarded for their efforts.BrainVision Analyzer 2 and MATLAB toolboxes , and engaged in team-oriented activities that promoted multidisciplinary learning and exchange of skills.During the program, the participants became familiar with various QEEG analysis tools, such as The curriculum content was structured in:EEG Basics;Theoretical Foundations of QEEG;QEEG Analyses;QEEG and Other Technologies;Group Projects on QEEG.To ensure seamless implementation, the following technical resources were made available: complete equipment for EEG recording on 21-channels (Neurosoft \u2013 LIAMED), respectively 32 channels , and BrainVision Analyzer Educational Licenses offered with the courtesy of Brain Products GmbH, wherewith the preprocessing steps were accomplished. Brainstorm application for feature analysis along with the R programming language was preferred for further processes.EU Alliance.The opening of the event took place at the RoNeuro Institute for Neurological Research and Diagnostic, a prestigious institution affiliated with UMFIH and a scientific partner of the NeurotechThe QEEGSS was organized under the guidance of Professor Dr. Dafin Fior Mure\u0219anu, the Chairman of RoNeuro, Chairman of the Neuroscience Department at the UMFIH, President of the Society for the Study of Neuroprotection and Neuroplasticity (SSNN), and President of the European Federation of NeuroRehabilitation Societies (EFNR). Dr. Livia Popa, neurophysiologist and researcher, lead of the QEEG Lab at the RoNeuro Institute, emphasized in the opening remarks the enthusiasm and motivation of the local team in organThenceforward Dr. Popa pinpointed the primary objective of the QEEGSS, which is to deliver a comprehensive introduction to the field of QEEG for a better understanding of brain activity and inform on its wide-ranging applications in clinical practice and research. The activities covered during the summer school were then presented, namely the exploration of data collection intricacies and analyzing techniques (preprocessing and processing) and acquisition of experience in QEEG interpretation, along with the possible integration of these findings into clinical practice and more advanced topics, such as source localization and connectivity analysis. The QEEGSS students were randomly assigned to teams and worked together for the following five days on common projects fostering a spirit of cross-disciplinary learning and multidisciplinary cooperation.The Paradigm of Brain Technology and Neuroscience focused on the importance of collaboration between neurodisciplines grouped around the technology-dominated core. As the main scope of the European University of Brain and Technology is bridging European communities of young neuroscientists, UMFIH Cluj-Napoca plays a key role in reinforcing this position by elaborating translational and clinical research projects in several centers of excellence, such as:The initial presentation, Centre for Translational Research in Neurosciences;Centre for Research on the Dissemination of Drug-Related Information;Centre of Research in Functional Genomics, Biomedicine and Translational Medicine;Centre for Experimental Medicine and Practical Skills;MedFUTURE \u2013 the Research Centre for Advanced Medicine.EU through its various research groups focusing on EEG, QEEG, TMS, Eye tracking, Cervical and Transcranial Sonography, besides the keen interest in Cerebrovascular Diseases, Cognitive Neurology, Neurotraumatology, Neurorehabilitation, and Neuroepidemiology.The RoNeuro Institute for Neurological Research and Diagnostic represents an additional fundamental pillar of support for neuroscientific research and education materialized by the close collaboration with UMFIH and NeurotechNeurobiology of EEG Signals. Dr. Livia Popa then offered a detailed presentation of the EEG Basic Concepts, where she illustrated the Montage selection \u2013 the arrangement of electrodes on the scalp to record EEG signals; the Acquisition of EEG signals \u2013 proper electrode placement, amplifying and filtering the signals to obtain accurate data; Patterns identification \u2013 recognizing different patterns, such as alpha, beta, theta, and delta brain oscillatory activity and/or epileptic discharges; Types of activity \u2013 alertness, resting state, drowsiness, sleep or seizure; Artifacts \u2013 electrode pop, electrode bridge, physiological artifacts , as well as noise coming from electrical interference; and Clinical applications \u2013 epilepsy, sleep disorders, brain tumors, traumatic brain injury, stroke, encephalopathies of different etiologies.After the introductory lecture that placed QEEG in the contemporary neurotechnological context, Dr. Diana Chertic explained the The second part of the day focused on analyzing a live EEG recording . SubsequData Preprocessing, Artifact Rejection, and Reduction . Her introduction to QEEG was complemented by a brief presentation by Dr. Diana Chertic on artifact removal through the application of Independent Component Analysis (ICA) and Principal Component Analysis (PCA). The theoretical part of the day was concluded by Dr. Victor D\u0103bal\u0103 with a captivating lecture about Frequency Domain and Time-Frequency Domain Analysis, referring to the Fast Fourier Transform (FFT), the Dot Product, the Convolution Theorem, and the Construction of Wavelets. During the afternoon hands-on session, each student performed QEEG Signal Preprocessing in BrainVision Analyzer 2 and Brainstorm.Dr. Livia Popa marked the start of the second day by highlighting specific methods of The third day of the intensive course brought a deeper perspective into QEEG's clinical and research applicability.Frequency-Domain Connectivity. She also covered the topics of correlation, cross-correlation, transfer entropy, mutual information, and Granger causality, which are included in Time-Domain Connectivity, along with explaining what a connectivity matrix represents. The theoretical discussions were complemented by clinical cases that illustrated the applications of QEEG in daily neurological practice. These cases sparked lively debates on differential diagnoses, ranging from neurodevelopmental to neurodegenerative disorders.The first two presentations, delivered by Dr. Hanna-Maria Drago\u0219, referred to the possibilities of neuronal communication through synchronicity modulation (coherence), which is included in Electrophysiological Source Imaging detection, providing several EEG source localization tools for participants.Dr. Diana Chertic continued the day with a presentation on Data \u2013 from Brainstorm to R, Stud. Vlad Chelaru demonstrated a workflow for the integration of Brainstorm computations with frequentist statistical analysis software, exporting QEEG-based indexes in a format compatible with other software packages such as R.Later on, through his presentation QEEG Feature Extraction, led by Dr. Victor D\u0103bal\u0103 and Dr. Diana Chertic concluded the day. Participants had the opportunity to transform the time series data into topographical maps and numerical data using BrainVision Analyzer 2 and Brainstorm algorithms.A workshop on The fourth day focused on blending Quantitative means of EEG analysis with complementary investigative technologies. Therefore, the presentation of Dr. Irina Vlad covered a wide array of technologies that might be utilized alongside QEEG: Functional Magnetic Resonance Imaging (fMRI), Functional Near-Infrared Spectroscopy (fNIRS), Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Magnetoencephalography (MEG). She provided a comprehensive introduction to these technologies offering additional means of exploration when paired with QEEG. Dr. Vlad`s overview encompassed their development, functionalities, and mechanisms, in addition to the research applications. Her display, followed by two other lectures \u2013 QEEG & Transcranial Magnetic Stimulation (TMS) delivered by Dr. Anca Demea and QEEG & Eye Tracking (ET) presented by Dr. Emanuel \u0218tef\u0103nescu \u2013 sparked considerable interest among the audience. The majority of the participants actively engaged by asking questions and sharing their own experiences.The second part of the day was dedicated to teamwork and project coordination. QEEGSS students had the opportunity to cooperate in 5-member groups, applying the knowledge and skills acquired during the first three days. While working on their project proposals, they utilized transversal competencies such as critical thinking, decision-making, problem-solving, and creativity.The fifth and final day of the QEEGSS testified to the power of collaboration, innovation, and relentless pursuit of knowledge. This day was dedicated to project presentation, as each team was randomly assembled at the beginning of the week to foster a spirit of cooperation and cross-disciplinary learning.Throughout the week, each team worked diligently on their assignments, their efforts extending into the evenings following the day\u2019s theoretical courses and hands-on sessions. The result was a rich tapestry of unique projects, reflecting the diverse skills and perspectives of the team members. The projects provided refreshing insights into EEG analysis, including innovative approaches to EEG signal cleaning through ICA, meticulous manual artifact-free epoch selection, and insightful comparisons of absolute and relative spectral densities.One team, demonstrating a commendable spirit of independence and technical acuity, chose to use the Python MNE package for their analysis in lieu of the BrainVision Analyzer and Brainstorm software. This decision allowed them to execute their analysis in a more controlled manner and across different operating systems, including macOS or Linux-based distributions. Another team engaged in a thoughtful critique of one literature study that focused on the same data set as the participants. They proposed several ways to mitigate the identified limitations, demonstrating a deep understanding of the subject matter and a critical approach to scientific research. This team's exceptional work earned them the winning position, and they were duly awarded for their achievement .A key takeaway from the day\u2019s presentations was the importance of standardizing analysis methods in QEEG research. Given the subjectivity of some steps, such as artifact interpretation, and the wide range of software available for analysis, one participant highlighted the need for clear and detailed descriptions of the steps used in QEEG analysis. This would ensure transparency and reproducibility, contributing to the robustness of the scientific literature in this field.At the end of the course, the students completed an online evaluation questionnaire that assessed learning outcomes and their level of satisfaction with the entire event.The closing ceremony was offiThe 2023 QEEG Summer School was a journey of discovery, a celebration of collaboration, and evidence of the power of innovative thinking in advancing scientific understanding.EU is an educational event that confirms the strong interest of young scientists from the European consortium in exploring the intricacies of the human brain. Year after year, quantitative means of exploring neural data will gain more ground on the boundary of neuroscience and biotechnology, defining a new area in exploring brain functionality.The second edition of QEEGSS in the fThrough the implementation of these intensive educational programs, the scientific alliance is empowered to foster an environment of academic excellence and intellectual growth as well as be a catalyst for significant achievements in the field of neurotechnology through multidisciplinary collaborative endeavors."} +{"text": "The Inter European Union Reference Laboratories (EURLs) Working Group on Next Generation Sequencing (NGS) involves eight EURLs for microbiological food and feed hazards and has been working since 2017 to promote the adoption of NGS by the National Reference Laboratories (NRLs) in the European Union. This work illustrates the results of the first 5\u2009years of activity. By working together, the EURLs involved have released guidance documents for assisting NRLs in all the steps of NGS, helping the transition from classical molecular methods towards whole genome sequencing while ensuring harmonization, with the final aim of improving preparedness in the use of NGS to characterize microbial hazards and trace the sources of infection. The authors confirm all supporting data, code and protocols have been provided within the article.The Inter European Union Reference Laboratories (EURLs) Working Group on Next Generation Sequencing (NGS) involves eight EURLs for microbiological food and feed hazards and has been active since 2017 on a mandate of the European Commission for promoting the adoption of NGS across the respective National Reference Laboratory (NRL) networks in the European Union, by building capacity and ensuring harmonization of procedures. Here, we present the main achievements of the working group at the current stage and plans for the future, mainly consisting of offering continuously updated resources as guidance documents, reference genome sequences and training opportunities, contributing to the growing ability of the NRLs to apply NGS technology for diagnosing and/or tracing microbiological foodborne infectious diseases in Europe.The global surveillance and outbreak investigation of infectious disease agents, including viral, parasitic and bacterial pathogens, and associated antimicrobial resistance (AMR) in a One Health context is currently amid a paradigm shift from traditional microbiology to genomics. The transition started around 2010 with the introduction of affordable benchtop next-generation sequencing (NGS) platforms. A decade later, this technology represents a powerful all-in-one solution to obtain complete characterization of microbial pathogens at lower costs and often in shorter time than with traditional microbiology. However, as with all molecular methods, its adoption in routine monitoring of infectious disease agents in food and animals and in outbreak investigations aimed at source tracking requires optimization and harmonization.The European Union Reference Laboratories (EURLs) for food and feed hazards are designated according to Regulation (EU) 2017/625 of the European Parliament [Escherichia coli including Shiga-toxin-producing E. coli, Listeria monocytogenes, coagulase-positive staphylococci, Salmonella, Campylobacter, foodborne parasites, AMR and foodborne viruses. The location of the EURLs involved in the WG is detailed in In 2017, the \u2018Inter-EURLs Working Group (WG) on NGS\u2019 was established based on a mandate by the European Commission (EC), with the aim to promote the use of NGS across the EURLs\u2019 networks, by building capacity and ensuring harmonization of procedures within the EU. The WG consists of representatives of eight EURLs for the following microbiological hazards: The WG meets twice a year, with the aim of coordinating activities and providing guidance documents for the organization of NGS-based proficiency tests (PTs), for the application of NGS laboratory procedures and analytical bioinformatics tools and for benchmarking analytical methods, while following the activities for the development of ISO 23418\u200a:\u200a2022 \u2018Whole genome sequencing for typing and genomic characterization of bacteria\u2019 [in vitro amplification steps.The level of adoption of NGS across the NRLs was estimated by launching a survey in spring 2018 and subsequently by monitoring the participation in the PTs for NGS-based methods organized by the EURLs . About hIn detail, EURLs for coagulase-positive staphylococci, parasites and foodborne viruses reported ongoing progress throughout their networks since 2018, when fewer than ten NRLs per network had declared as having access to NGS. This improvement was mainly achieved due to participation in research projects, which are expected to provide tangible preparedness in the next couple of years.E. coli website [The use of established protocols in the production and the analysis of NGS data is essential to achieve comparability of results, which is particularly important for example in the framework of an outbreak investigation. With the aim of supporting the NRLs, since 2020 the Inter-EURLs WG on NGS has released and routinely updated a collection of guidance documents, as detailed below. All these documents are published on the web pages specifically dedicated to the activities of the WG, present on the websites of each of the involved EURLs. An example is represented by the page included in the EURL for website , linkingThe availability of high-quality nucleic acids (DNA/RNA) is a prerequisite for the successful application of NGS methodologies. Due to the large biological differences among bacterial, viral and parasitic pathogens, different methods are required, in particular for uncultivable target organisms. A guidance document was prepared by gathering Standard Operating Procedures (SOPs) generated during previous EU projects, such as COMPARE , ENGAGE The bioinformatics tools most used for NGS data analyses, including quality checking, trimming, assembly, multi-locus sequence typing (MLST), virulotyping, serotyping and identification of AMR genes, were referenced in a guidance document . In addiA further guidance document that aimed to inform and support NRLs in the choice of methods to be used for cluster analysis was released . This doE. coli, L. monocytogenes, Salmonella, Campylobacter and AMR all performed PTs focusing on prediction of: (1) specific subtypes ; (2) determinants ; (3) phylogeny based on SNPs or gene-by-gene approaches; and (4) genome quality metrics.Standardization of WGS procedures from DNA preparation to the final genome is pivotal to provide reliable data for surveillance and outbreak detection. To ensure the production of reliable high-quality genomic data, laboratories routinely applying NGS technology should participate in inter-laboratory studies or external quality assurance schemes (EQAs)/PTs. A document describing the approach used in genomics PTs at each of the EURLs and the experiences collected during the organization was published and will be routinely updated . The EURIn the future, the organization of PTs focusing on metagenomics approaches could be useful for the networks dealing with difficult-to-grow hazards, such as viruses and parasites.Different approaches were used to collect the PT results, in some cases requiring the submission of sequence files, in addition to analysed results, which poses problems of heavy data exchange and of workload for the analysis needed at the EURLs for evaluation. In other cases, the analysed results are submitted without exchanging sequence files, which provides an easier solution, though not allowing control of the quality of the sequence file(s) produced.A reference genome collection, useful for the validation and benchmarking of bioinformatics tools, was compiled. Sequences of different pathogens produced by participants of PTs organized by the EURLs are listed in the guidance document .EURLs and NRLs need to document the performance of the laboratory procedures and bioinformatics tools with appropriate and comprehensive benchmarking. The document \u2018Guidance document for WGS-Benchmarking\u2019 was prepde novo assembly. The document also includes statistical analyses to perform the benchmarking.The wet bench component includes any of the following processes: handling of strains, extraction of nucleic acids, fragmentation, barcoding (molecular indexing) of isolates, enrichment of targets for exome or gene panels, adapter ligation, amplification, library preparation, flow cell loading and generation of sequence reads. Sequence generation is almost entirely automated, and the output consists of millions to billions of short sequence reads. The dry bench workflow is followed by intensive computational and bioinformatics analyses that use a variety of algorithms to align the short sequence reads to a linear reference bacterial genome sequence, and to perform As NGS practices are not yet routine for several NRLs and are also in constant update, there is a need for NGS training. Since 2018, EURLs regularly organize training courses for their respective NRL network and the first joint training session with all the EURLs that are part of the WG was organized in 2022 focusing on dry lab analysis, with the aim of bringing NRLs together to ensure exchange of opinions and establishing fruitful collaborations. Moreover, a document aimed atThis initiative has brought the EURLs together, allowing common strategies to be found to stimulate the adoption of NGS for monitoring microbiological foodborne pathogens. In 5\u2009years of activity, the WG has released guidance documents for assisting NRLs in all the steps of NGS, helping the transition from classical molecular methods towards genomics while ensuring harmonization. These resources are routinely updated on EURL websites, making them available for any laboratory wishing to follow the same path, with the aim of contributing to improve preparedness in the use of NGS to characterize microbial hazards and trace the sources of infection."} +{"text": "Salvia hispanica L.) and Lacticaseibacillus paracasei on intestinal functionality, morphology, and bacterial populations, in vivo [Acrocomia aculeata) pulp oil to prevent adipogenesis, inflammation and oxidative stress in mice fed a high-fat diet [Malus domestica) juice, pomace, and pulp and the modulation of intestinal functionality, morphology, and bacterial populations in vivo [Salvia hispanica L.) associated with high-fat diet on the intestinal health of wistar rats [Gallus gallus) [Zea mays L.) on cecal microbial populations in vivo [Gallus gallus) of catechin and its derivatives [Vitis labrusca L.) puree, juice, and pomace on intestinal morphology and functionality, and on bacterial populations in vivo [Gallus gallus) of genistein alters mineral transport, intestinal morphology, and gut microbiota [Gallus gallus) of nicotinamide riboside and its derivatives [This monograph, based on a Special Issue of Nutrients, contains 16 manuscripts\u20142 review manuscripts and 14 original research manuscripts\u2014that reflect the wide spectrum of currently conducted research in the field of Emerging Dietary Bioactives in Health and Disease. The manuscripts in this Special Issue collection include contributions from researchers from multiple countries, including the USA, Brazil, United Kingdom, Italy, Norway, China, and Israel. The presented manuscripts cover a wide variety and range of topics in the field of dietary bioactives in health and disease, with emphasis on the investigation of the effects hydrolyzed protein of chia ; the efftar rats ; the int gallus) ; the inv gallus) ; the dem gallus) ; the altivatives ; the per gallus) ; the demcrobiota ; the occivatives ; and an Plant-based diets contain wide varieties of metabolites that may impact on health and disease prevention. Most are focused on the potential bioactivity and nutritional relevance of several classes of phytochemicals, such as polyphenols, flavonoids, carotenoids, phyto-oestrogens, and frucrooligo-saccharides . These cThis Special Issue and collection of manuscripts constitutes a useful summary of progress in various areas related to emerging dietary bioactives in health and disease."} +{"text": "Ischemic heart disease is one of the leading causes of morbidity and mortality worldwide. Continuous advances in diagnostic, prognostic and therapeutic methods have led to an improvement in patient outcomesover the past few decades.In recent years, developments in molecular assessments, laboratory assays and imaging techniques have enabled a comprehensive characterisation of ischemic heart disease. Circulating biomarkers involved in the pathogenesis of CAD (coronary artery disease) have the potential to detect the disease in its early stages: inflammatory markers, biochemical markers (proteins), epigenetic markers , and transcriptional markers (gene expression) . CardiovThis Special Issue explores some of the latest research on the diagnosis of coronary artery disease.Calmac et al. discuss An important section of this Special Issue is dedicated to the implications of myocardial bridge in patients with CAD . The myoFinally, the systematic review by Kampmann et al. addresseAll papers presented in this Special Issue emphasise the importance of diagnostic techniques in CAD allowing for patient-tailored treatment, and thus reducing ischemic-heart-disease-related complications and improving patient outcomes. Advances in diagnostic techniques and the management of these patients may substantially reduce the burden of cardiovascular diseases in the future."} +{"text": "Obsessive-compulsive disorder (OCD) is a disorder diagnosed on the basis of the presence of obsessions and compulsions (compulsive and transiently satisfying actions performed in response to obsessions). A separate clinical phenomenon in the broadly understood anankastic spectrum is obsessive-compulsive disorder (OCPD). OCPD is characterized by scrupulousness, over-normative morality, perfectionism and an inability to make concessions in terms of cooperation. It is assumed that the incidence of OCPD in the course of OCD is 25-32% and it is a report with an unfavorable course and a more difficult therapeutic prognosis. It also means an early onset of OCD with a greater intensity of compulsions and a predominance of symptoms related to the sphere of purity, symmetry and gathering.The main aims of the study were as follows:1. To assess the prevalence of OCPD in OCD patients.2. To compare both groups of patients for the severity, level of insight, aggression, impulsiveness and affective symptoms.3. To verify whether the presence of OCPD depend on factors such as age, gender, treatment duration and delay in starting treatment.-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression-Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Buss-Perry Aggression Questionnaire (BPAQ), Barratt Impulsiveness Scale (BIS-11), Brown Assessment of Beliefs Scale (BABS) and DSM 5 criteria for OCPD.The study was conducted in a group of 78 patients diagnosed with and treated for OCD. The patients were divided into two groups: patients with OCD and OCPD and patients with OCD without OCPD . The groups were subsequently compared for the severity of anankastic symptoms, the level of insight, aggression, impulsiveness and its components and affective symptoms . The following tools were used for the diagnosis: YaleOur results confirmed that OCPD is common in OCD and occurred in 55,12% of patients with OCD . The study shows that the presence of OCPD in the course of OCD negatively affects the severity of obsessive-compulsive symptoms, the level of insight, the level of aggression and impulsiveness, and affective disorders. Patients with OCPD obtained higher scores on the YBOCS, BABS, HDRS, and YMRS scales compared to patients with OCD without OCPD. The occurrence of OCPD in the study group did not depend on gender, duration of OCD treatment, or delay in starting it.The occurrence of OCPD is common in OCD and can cause delay of treatment, worse course, greater intensity of egosyntonic symptoms, and thus worse insight. The presence of OCPD can lead to more hostility and more affective disorders. Screening for OCPD in patients with OCD should be an integral part of an OCD diagnostic process.None Declared"} +{"text": "The sudden and large-scale Russian invasion of Ukraine has caused significant stress not only in Ukrainians but also in citizens of countries which have received the largest numbers of refugees.The aim of the current study was to identify stress, resilience, and self-efficacy levels, as well as to examine the relationships between these variables, in a sample of women from Ukraine, Poland, Slovakia, and Romania during the third month of Russian aggression on Ukraine.Perception of Stress Questionnaire, the Brief Resilience Scale, and the Generalized Self-Efficacy Scale in May 2022.The study involved measuring a sample of Ukrainian (N = 82), Polish (N = 102), Slovak (N = 79), and Romanian (N = 42) women using the The results showed that during the third month of Russian aggression on Ukraine, stress levels and its components were the highest among Ukrainian women and the lowest among Polish women. The sense of self-efficacy was the lowest among Ukrainian women and highest among Polish women, while resilience was the lowest among Ukrainian women and the highest among Slovak women.Women from Ukraine reported being in the worst mental state compared to the rest of the sample. Moreover, a path analysis of the measured variables points to a multifaceted relationship between stress, resilience, and self-efficacy among women from Ukraine, Poland, Slovakia, and Romania during the third month of the Russian invasion.None Declared"} +{"text": "The Horn of Africa is a large area of arid and semi-arid land, holding about 10% of the global and 40% of the entire African livestock population. The region\u2019s livestock production system is mainly extensive and pastoralist. It faces countless problems, such as a shortage of pastures and watering points, poor access to veterinary services, and multiple endemic diseases like foot-and-mouth disease (FMD). Foot-and-mouth disease is one of the most economically important livestock diseases worldwide and is endemic in most developing countries. Within Africa, five of the seven serotypes of the FMD virus (FMDV) are described, but serotype C is not circulating anymore, a burden unseen anywhere in the world. The enormous genetic diversity of FMDV is favored by an error-prone RNA-dependent RNA polymerase, intra-typic and inter-typic recombination, as well as the quasi-species nature of the virus. This paper describes the epidemiological dynamics of foot-and-mouth disease in the Horn of Africa with regard to the serotypes and topotypes distribution of FMDV, the livestock production systems practiced, animal movement, the role of wildlife, and the epidemiological complexity of FMD. Within this review, outbreak investigation data and serological studies confirm the endemicity of the disease in the Horn of Africa. Multiple topotypes of FMDV are described in the literature as circulating in the region, with further evolution of virus diversity predicted. A large susceptible livestock population and the presence of wild ungulates are described as complicating the epidemiology of the disease. Further, the husbandry practices and legal and illegal trading of livestock and their products, coupled with poor biosecurity practices, are also reported to impact the spread of FMDV within and between countries in the region. The porosity of borders for pastoralist herders fuels the unregulated transboundary livestock trade. There are no systematic control strategies in the region except for sporadic vaccination with locally produced vaccines, while literature indicates that effective control measures should also consider virus diversity, livestock movements/biosecurity, transboundary trade, and the reduction of contact with wild, susceptible ungulates. The language in which the search was performed was specified as English. The search items were limited to fully accessible manuscripts or reports. The time period for the literature to be retrieved electronically was set between 1 January 1999, and 9 March 2023.The key words used per the sections were as follows: Introduction: Livestock production system in East Africa OR Horn of Africa OR animal Product supply and demand Horn of Africa OR Livestock provides milk, meat, draft power OR Livestock Sector Report Horn of Africa OR FMD host range and pathogenesis OR FMD prevalence in the Horn of Africa OR Ethiopia OR Kenya OR Uganda OR Eritrea OR Sudan OR South Sudan. Serotype or topotype diversity: Serotype/topotype O or A OR SAT 1, 2,3 Horn of Africa OR Ethiopia OR Kenya OR Sudan OR South Sudan OR Eritrea OR Djibouti OR Uganda OR East Africa. Acute and persistent infection: Acute infection in cattle FMDV epidemiology OR Between animal and farm transmission of FMD OR FMD in carrier and persistent state OR Acute and persistent infection. Livestock movement and trade: Foot-and-mouth disease livestock movement OR pastoralism and livestock disease in East Africa OR foot-and-mouth disease virus dispersal in East Africa OR Cross border livestock movement in Africa. Wild animals and FMDV: Wild animals and foot-and-mouth disease in East Africa OR Role of wild ungulates for foot-and-mouth disease epidemiology OR Viral disease and African ungulates. FMD vaccines: Foot-and-mouth disease vaccines in East Africa OR Foot-and-mouth disease vaccines in Ethiopia OR Foot-and-mouth disease vaccine strain selection in East Africa. For the remaining sections, global FMD distribution OR FMD distribution, was used. In total, 210 articles were retrieved, and after applying the inclusion and exclusion (outside the horn area and not related to the mentioned factors) criteria, 102 citations were considered potentially eligible for inclusion in this review. In addition, for the most recent laboratory reports on the WRLFMD web site , some articles were searched manually using the Google Search engine .Articles published in peer-reviewed journals were obtained via the online search engines: Pub Med, Google Scholar, and the World Reference laboratory resource for foot-and-mouth Disease (WMRLFMD) website is one of the most important contagious livestock diseases and has an important economic impact globally. FMD affects over 70 domestic and wild cloven-hoofed animals and exisIn general, the genetic diversity of ribonucleic acid (RNA) viruses such as FMDV results from the error-prone replication process of the RNA-dependent RNA polymerase (RdRp), large population diversity, and high replication rate as well In addition to the above, genetic recombination is another determinant in the generation of new variants. In FMDV 15, recombination events were more evident in the non-structural proteins than in the genes coding for the structural proteins (capsid) ,19. FurtExcept for Greenland, Iceland, New Zealand, and the smaller islands of Oceania, every region in the world has, at least once, experienced an FMD outbreak. The outbreak reports of 1929, 1952, 1954, and 1970 in the USA, Canada, Mexico, and Australia, respectively, marked the last outbreak of FMD in these countries. The last sporadic outbreak of FMD on the European continent dates from 2011, as the disease was eradicated in Europe in the 1980s ,28. GlobGlobally, FMD is distributed into seven virus pools, and within each pool, several serotypes of FMDV can be found ,30. AfriFMD is endemic in the Horn of Africa, with variable prevalence in different countries. In Ethiopia, seroprevalence studies using NSP ELISA range from 5.6% to 72.1% in cattle, from 4% to 11% in small ruminants, and 30% in ungulate wildlife ,39,40,41Syncerus caffer) was recorded to be 74% in Uganda .,62.59,62\u22123 nucleotide substitutions per site per year over 58 years was recorded (1958\u20132016) , inactivated with 0.3% of formaldehyde, and adjuvanted with saponin. The duration of protection of this vaccine is a maximum of six months concentrate that is adjuvanted with saponin [The FOTIVAX of the KEVEVAPI FMDV vaccine is in the form of an aluminum hydroxide gel [Al(OH) saponin and puri saponin . The FMD saponin . This va saponin . At leas saponin . For ser saponin ,51,71,89https://kevevapi.or.ke/fotivax/, accessed on 20 February 2023). However, in the Horn of Africa, vaccination does not always seem to be protective against FMD, not even in the peri-urban semi-intensive production system. Maintaining a sound biosecurity practice helps to prevent the introduction and spread of the FMDV into a particular farm or country [The KEVEVAPI duration of protection is 6 months, or every 4 months for better protection ( country .As reviewed by Ambaye Kenubih, the importance of both structural and non-structural proteins of the FMDV on both the cellular and humoral arms of the immune system should be studied for sterile and long-lasting immunity development . As reviFoot and mouth disease epidemiology in the Horn of Africa is complex as a result of serotype and topotype diversity. In addition to this, unrestricted animal movements and insignificant control approaches exacerbate the epidemiological dynamics of the disease. The Horn of Africa harbors five FMDV serotypes and more than twenty topotypes, with a continuous threat of the spread of new topotypes within the region. Countries such as Ethiopia, South Sudan, Sudan, and Kenya are known as hotbeds for the emergence of new FMDV strains in the region and in other regions as well. The livestock movement in the area within and between the regions is unrestricted due to diverse factors, of which the search for markets, watering points, and pastures is the most important. The presence of wild animals is the third major factor affecting the epidemiology of the disease. However, the presence of African buffalo in the Horn of Africa may have less of an effect on FMD infections in cattle in comparison to the southern part of Africa. The danger of FMD in the region is increasing because of high genetic diversity, poor husbandry, a poor control approach, no biosecurity practices coupled with unregulated trade, and pastoral herds movement in search of pasture and water as a result of recurring drought. To this end, early diagnosis and implementation of a suitable control approach need to focus on biosecurity."} +{"text": "The global burden of disease (GBD) has shifted from communicable, maternal, perinatal, and nutritional causes to non-communicable diseases such as atherosclerosis or metabolic disease within the last 20\u201330 years , 2. In 2According to reports of the Lancet Commission on Pollution and Health , the WorThe present special issue provides an overview of the health effects of tobacco cigarette and shisha smoking, E-cigarette vaping, usage of other novel nicotine delivery systems, sedentary lifestyle or over-nutrition, and alcohol use with a focus on adverse effects on endothelial function and cardiovascular health. The negative effects of the toxic constituents of these tobacco (replacement) products, as well as the beneficial effects of exercise or fasting on different biological pathways, will also be discussed, especially regarding their impact on key vascular processes such as nitric oxide signaling, smooth muscle proliferation, remodeling, and atherosclerosis, in part driven by oxidative stress and inflammatory cascades. With the present Special Issue, we want to highlight the pathomechanisms underlying cardiovascular and metabolic disorders in response to environmental risk factors and the existing research gaps. We will also emphasize emerging mechanisms based on dysregulation of epigenetic pathways by environmental lifestyle and behavioral risk factors.The overview provided by Daiber et al. highlights the threats and benefits of E-cigarette vaping in comparison with classical tobacco cigarette and shisha smoking . The toxFasipe et al. provide a review on the cardiometabolic health risks of sedentary lifestyle and the beneficial effects of physical exercise . The autLifestyle risk factors share common pathophysiological pathways centered on oxidative stress and inflammation. Oxidative stress and inflammation also represent hallmarks of all cardiovascular, neurodegenerative, and metabolic diseases. Due to this overlap of these central pathomechanisms, we may expect additive/synergistic adverse biochemical effects in response to environmental, lifestyle, and traditional health risk factors leading to aggravated pathogenesis of non-communicable diseases in a bonfire fashion , 33. Whe"} +{"text": "Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections resulting in a significant burden worldwide, particularly in children and older adults. This collection calls for original research papers that advance our understanding of the epidemiology, evolution, diagnosis, clinical management, and prevention of RSV infections. Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infection, including lower respiratory tract infection (LRTI). Before the coronavirus disease 2019 (COVID-19) pandemic RSV represented the fourth cause of overall disability-adjusted life-years at all ages .RSV annual epidemiology is also impacted by the alternation of the subtypes A and B and, within them, by genetic variations of strains or lineages . Indeed,Before the COVID-19 pandemic, the detection of RSV infections followed a predictable seasonal pattern each year. During the first year of the pandemic, respiratory viruses, including RSV, caused an unusually low number of infections and related hospitalizations in the first phase of the COVID-19 pandemic, due to the implementation of non-pharmaceutical interventions . The subCurrently, treatment of RSV infections relies on supportive care including supplemental oxygen, rehydration, and mechanical ventilation when critical. Antiviral treatment with aerosolized ribavirin is limited to severe infections in immunocompromised patients . Until rTM) for adults aged 60 and older and for pregnant women (AbrysvoTM) to protect infants from birth up to 6 months of age [On the vaccine front, after decades of troubled RSV vaccine development, four randomized clinical trials in older adults and pregnant women were recently published revealing a breakthrough in providing a high level of protection against RSV \u201315. The s of age .The recent advances and progress toward the prevention of RSV have re-energized the field and highlighted the need for continued research to better understand the disease as well as the epidemiology and evolution of RSV. Studies assessing the impact of the newly approved immunotherapeutic and vaccines on RSV burden and genetic diversity are critically needed. This collection calls for original research papers that aim to improve our understanding of RSV epidemiology, evolution, diagnosis, clinical management and prevention."} +{"text": "The rapidly evolving field of Behavioral Neuroscience has made significant strides in understanding the complex mechanisms that govern human behavior, decision-making, and wellbeing. One area of particular interest is the study of Motivation and Reward, which has the potential to provide valuable insights into the underlying processes driving these behaviors. This Research Topic aims to highlight the latest advancements, challenges, and future perspectives in this area of study by showcasing a diverse range of original research and review articles submitted by esteemed researchers.Bessa et al. used Siamese Fighting Fish (Betta splendens) as a biological model to study hormonal fluctuations during foraging. They found that an optimal level of cortisol maximizes foraging performance, while extreme levels of basal cortisol, both low and high, are associated with reduced average reward . Importantly, to model foraging decisions, the authors applied the \u03b5-greedy algorithm 2013 data was used by Aslam et al. to conduct a Latent Class Analysis (LCA) for the entire sample of teenagers, as well as separately for each sex. In this original research article, the authors identified five subsets of youth engaging in risky behavior: those who do not engage in risky behavior , those with depressive symptoms and suicidal thoughts (Class 3), those with a high likelihood of using cigarettes and liquor (Class 4), and those who are polysubstance users (Class 5). Gender variations were also detected in the higher risk of mood disorders and depression among females.The manuscripts collected here encompass various aspects of Motivation and Reward, demonstrating the interdisciplinary nature of this field. Topics explored in the three original research articles include the application of machine learning techniques to understand the impact of stress hormones on animal behavior, the study of the differences between males and females in the long-term learning deficit induced by the co-exposure to the main consumed drugs during adolescence , and the role of race and ethnicity in shaping risk-taking behaviors in adolescents. Specifically, a first study by Weinstein, enriches the Research Topic of a comprehensive analysis of the literature on the fMRI studies conducted on healthy subjects, both on motivation and reward in tasks such as the Sequential choice task (Symmonds et al., Monetary incentive delay task (Mori et al., Monetary and verbal reward task (Albrecht et al., Reaction-time task with goal-irrelevant expectancy violations in states of high- or low-reward motivation (Murty and Adcock, Kibret et al., which illustrates an up-to-date scenario of this contribution. The role of motivation and reward in promoting healthy behaviors was timely addressed by Michaelsen and Esch, who provide an insightful critical reading on the throughput that goal-oriented, stimulus-driven, and approach motivation play in nudging (Hansen and Jespersen, The current state of neuroimaging research in the context of motivation and reward, reviewed by Collectively, the potpourri of original research and reviews included in this Research Topic provides a comprehensive overview of the current state of Motivation and Reward research. By highlighting the latest discoveries, developments, and future challenges, this Research Topic seeks to inspire further research, promote funding opportunities, and guide researchers in their pursuit of unraveling the complex mechanisms that drive motivation and reward. Furthermore, this Research Topic emphasizes the importance of interdisciplinary collaboration, incorporating perspectives from biosciences, life sciences, medicine, psychiatry, and the mind to facilitate a more comprehensive understanding of motivation and reward mechanisms. By fostering an environment of curiosity and open-mindedness, we hope to encourage the development of innovative approaches and solutions to the challenges faced in this rapidly advancing field.We believe that this Research Topic will serve as a valuable resource for researchers, academics, and professionals interested in the study of motivation and reward, providing direction and guidance for future investigations, and promoting the growth of knowledge in this essential area of Behavioral Neuroscience.MK: Writing\u2014original draft, Writing\u2014review and editing. EA: Writing\u2014original draft, Writing\u2014review and editing. LF: Writing\u2014original draft, Writing\u2014review and editing."} +{"text": "The prevalence of oral squamous cell carcinoma (OSCC) has increased in recent decades, and its impact on the health system has become a new aspect. In addition to the well-known exogenous noxae like nicotine and alcohol consumption, as well as some distinct nutritional habits such as betel nut chewing and virus infection by the human papilloma virus (HPV), its transfer via sexual practices augmented the recent increase in the incidence of oropharyngeal cancer . FinallyIn parallel, our understanding of the initiation and development of oral cancer has also changed substantially. The molecular basis for the epithelial invasion mechanisms, including the epithelial\u2013mesenchymal transition (EMT) and remodeling of the extracellular matrix (ECM), not only intensified our knowledge concerning the underlying pathology but also brought more sophisticated diagnostic methods and prognostic tools, as well as promising therapeutic options for patients with OSSC ,3,4.The original research and review articles included in this Special Issue elucidate the diversity of molecular mechanisms involved in the onset, invasion, and progression of OSCC, with particular attention paid to the role of HPV infection and multimodal treatment. Finally, a state-of-the-art review of modern 3D-based microsurgical reconstruction following ablative oncologic surgery of the head and neck region enriches the scope of this Special Issue ,6. These"} +{"text": "Since the first report in March 2020, Kenya experienced five waves of coronavirus 2019 (COVID-19), with cases and deaths reported in all 47 counties, amounting to 323\u2009000 and 5600, respectively, in late March 2022 function as an instrument of international law and provide a legal framework that binds member states . Its mon functionThe first COVID-19 IAR was conducted in Kenya from 31 May to 1 June 2021. Ninety-five from national and county levels participants attended the meeting with the Ministry of Health and multiple stakeholders ). The IAR in Kenya identified best practices and challenges, suggesting recommendations based on nine COVID-19 response pillars:Country-level coordination, planning, and monitoring;Risk communication, community engagement, and infodemic management;Surveillance, case investigation, and contact tracing;Points of entry;National laboratory system;Infection prevention and control;Case management and knowledge sharing about innovations and the latest research;Operational support and logistics in the management of supply chains and workforce resilience;Strengthening essential health services during the COVID-19 outbreak.Best practices were summarised in four points:Strong political will and support at national and county levels, enabling smooth COVID-19 operations and resource allocation;Strong coordination and partnership mechanisms;Early development and dissemination of guidelines, policies and Standard Operating Procedures (SOPs);Utilization of existing structures and resources, such as a legal framework for emergencies, coordination structures, infrastructure, previous capacities developed through training, and existing supply chain management.Conversely, the key challenges identified were as follows:Funding gaps and delayed disbursements, leading to inadequate resources;Lack of strong monitoring and evaluation systems;Inadequate supply chain management and lack of capacity for local manufacturing ;Inadequate data management systems including paper-based systems;Fast-evolving pandemic requiring prompt adaption of systems, infrastructure, guidelines, policies;Surge in cases and deaths by waves, with 5180 health worker infections and 40 deaths reported from all counties.While these findings were largely similar to outcomes in other WHO AFRO countries , some stThe IAR process was not an evaluation, but an open, honest reflection of key stakeholders on their contribution to the response. It helped with critically reviewing the prolonged COVID-19 response in Kenya and identifying areas for improvement without assigning blame, making honest reflection possible. The findings were successfully shared with multiple partners and senior management decision-makers, helping with the development of a COVID-19 resurgence plan, the review of response policies, guidelines, SOPs, and the application for funding.However, due to insufficient implementation of IAR recommendations to address the discovered gaps, several challenges identified from mid-2021 still have to be addressed. Since June 2021, the variant of concern (VoC) Delta became dominant in Kenya, and inadequate resources in surveillance, rapid response, and case investigation brought higher SARS-CoV-2 test positivity rate and hindered timely information sharing, adequate risk assessment and projections, effective public health actions, and data-driven decision-making. The high demand for intensive care units (ICUs) and medical oxygen highlighted issues in health service delivery and workforce, including manufacturing, procurement, and supply chain of medical oxygen. Regarding infection prevention and control (IPC), sub-optimal allocation of personal protective equipment (PPEs) contributed to a higher number of COVID-19 patients among health care workers.The emergence of the Omicron VoC from November 2021 also exposed critical challenges in laboratory pillar to detect new variants. The number of genomic sequencings did not reach the optimal level of over 100 sequences per month . Due to The IAR was able to identify cross-cutting issues across response pillars. Attendance of health sector partners added value to the overall pandemic preparedness and response. Strong leadership and governance to strengthen incident management structure and response capacity is a key area to achieving an effective coordination at national and sub-national levels. The use of home-based care during COVID-19 has brought positive opportunities and contributed significantly to reduce the burden on health facilities in the country and facilitated the engagement with the community. It is promising that findings from IAR were incorporated into the resurgence plan and were internally reviewed for launching the National Action Plan for Health Security. However, as the COVID-19 pandemic is expected to continue for years, regularly conducting IAR and reviewing the responses across pillars will be beneficial as a monitoring and evaluation tool to continuously improve on identified weak areas for health emergency response. Integrating the vaccine pillar into the next IAR at the national level will enrich the discussion.These challenges need to be addressed in view of building resilient and sustainable systems for health. Findings from the IAR should inform the review of existing health policies, strategies, and preparedness plans. Despite an initial huge impact, Kenya could gradually mitigate the impact of COVID-19 on essential health services (EHSs), setting a good example . SeveralThere have also been multiple health emergencies in Eastern Africa, such as outbreaks of yellow fever, cholera, dengue, rift valley fever, and drought in the Horn of Africa. To mitigate their impact on the lives and livelihoods of citizens, Kenya can reinforce and exert its leadership in public health at the regional level. Encouragingly, Kenya will host a second logistic hub which will equip emergency medical personnel, stockpile commodities, and equipment and willIn conclusion, we recommend the following:The IARs, if conducted with participation of all responders and partners, enable countries to institute corrective measures during the emergency.Regular conduction of IAR and review of responses across pillars will help strengthen capacity in health emergency preparedness and response.Findings from the IAR must be fully utilised for health initiatives outside of health emergencies, as root causes of challenges are sometimes interlinked.The launch of new logistic hub and transfer of technology for vaccine production will elevate Kenya to exert its leadership in public health at the regional level."} +{"text": "Social inclusion is a multidimensional concept, referring to ample participation in key social, cultural, economic and political activities. Since the turn of the century, social inclusion has become a guiding principle in policy recommendations of many international and national bodies, aiming to improve the lives of people with mental ill-health. More recently, social inclusion has been increasingly used as an outcome measure, to test the effectiveness of complex interventions, especially in the field of global mental health.This presentation will focus on: (1) current definitions and controversies in research on social inclusion for and with people with mental ill-health; (2) measuring social inclusion; and (3) the evidence-base of interventions to improve social inclusion. Special attention will be given to recovery-oriented interventions in global mental health such as peer support.In summary, over the last years, impressive conceptual and methodological advances have been made to transform policy rhetoric into meaningful and effective interventions. However, challenges remain, including consensus on culturally appropriate measurement of social inclusion, and balancing the roles and responsibilities of all stakeholders across the entire exclusion-inclusion continuum to promoting social inclusion and mental health.None Declared"} +{"text": "Although mastectomy is a treatment for the cleaning of cancer cells in the breast, it can also cause psychological changes in women.This research was carried out to investigate the cognitive distortions, mental symptoms, and marital adjustment relationships in women with mastectomy.The descriptive and comparatice study was conducted in a public hospital with 90 mastectomies and 90 healthy female samples. The data were collected using The Cognitive Distortions Scale (CDS), The Brief Symptom Inventory (BSI), and Marriage Adjustment Scale (MAS) and were evaluated by descriptive statistical analyzes, t test, Mann-Whitney U test and Spearman Correlation Analysis.Women with mastectomy scored high in the healthy control group in all sub-dimensions of CDS and BSI and this difference is highly significant . Women with mastectomy scored higher in total agreement sub-dimensions than the healthy control group and the difference between them was statistically significant . There ara positive, very strong and statistically significant relationships between all sub-dimensions of the CDS and the total sub-dimension scores of the BSI . There are positive, strong and statistically significant relationships between the sub-dimensions of the CDS and the sub-dimension of the agreement and the total score of MAS (r=681 and 734). There are strong and statistically significant relationships between the total and sub-dimension scores of the BSI and the sub-dimension and total score of the MAS\u2019s agreement .Cognitive distortions and mental symptoms are significantly higher in women with mastectomy, and cognitive distortions are associated with mental symptoms. Cognitive distortions and psychological symptoms scores, marriage adjustment scores and agreement sub-dimension scores increase in women.None Declared"} +{"text": "Professor RNDr. Petr Nachtigall, PhD passed away on 28 December 2022. He was an internationally recognized expert in computational materials science; working at Charles University in the Department of Physical and Macromolecular Chemistry. We honor his memory. Professor Petr Nachtigall was an internationally recognized expert in computational physical and materials science. He received his PhD at the University of Pittsburgh. After returning to Prague, he worked at the J. Heyrovsky Institute of Physical Chemistry, later at the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, and since 2009 at the Faculty of Science of Charles University where he was a major leader in the Charles University Centre for Advanced Materials. Petr has regularly published in the most prestigious scientific journals: he is the author of 181 well-recognized publications.Petr was a computational chemist who liked to solve materials chemistry problems in close collaboration with experimentalists and he was very successful in that. Where necessary, he implemented techniques beyond routine methodology. In particular, he found ways to overcome the limitations of density functional theory. Petr had wide-ranging expertise in computational chemistry and he advanced the understanding of adsorption complexes and reaction mechanisms in zeolites and metal\u2013organic frameworks at the molecular scale. His studies of new types of two-dimensional materials lead to an improved understanding of their very interesting properties, for example the superior lithium-storage properties of silicene nanosheets or utilization of two-dimensional zeolites for fabrication of new materials.Petr\u2019s theoretical insight into the synthesis of new materials contributed significantly to the discovery and theoretical explanation of the new ADOR (assembly-disassembly-organisation-reassembly) method of zeolite synthesis, thanks to which more than 10 new types of zeolites have already been synthesized. Petr received several awards during his career, including the Bed\u0159ich Hrozn\u00fd Prize for Basic Research (2015), the Prize of the Czech Minister of Education, Youth and Sports for significant results of basic research in natural sciences (2019) and the Donatio Universitatis Carolinae (2021).In Petr Nachtigall we lose not only an outstanding scientist, teacher, and mentor, but also a great person, a dear colleague and friend."} +{"text": "The emergence of the infectious diseases, such as the novel coronavirus, as a significant global health threat has emphasized the urgent need for effective treatments and vaccines. As infectious diseases become more common around the world, it is important to have strategies in place to prevent and monitor them. This study reviews hybrid models that incorporate emerging technologies for preventing and monitoring infectious diseases. It also presents a comprehensive review of the hybrid models employed for preventing and monitoring infectious diseases since the outbreak of COVID-19. The review encompasses models that integrate emerging and innovative technologies, such as blockchain, Internet of Things (IoT), big data, and artificial intelligence (AI). By harnessing these technologies, the hybrid system enables secure contact tracing and source isolation. Based on the review, a hybrid conceptual framework model proposes a hybrid model that incorporates emerging technologies. The proposed hybrid model enables effective contact tracing, secure source isolation using blockchain technology, IoT sensors, and big data collection. A hybrid model that incorporates emerging technologies is proposed as a comprehensive approach to preventing and monitoring infectious diseases. With continued research on and the development of the proposed model, the global efforts to effectively combat infectious diseases and safeguard public health will continue. The coronavirus pandemic has had a devastating impact on the world, spreading to 188 countries and causing more than 1 million deaths. Governments have reacted by executing arrangement bundles, such as closing schools and limiting individuals to their homes, which have been effective in abating the development of the infection. In the subsequent sections, a detailed review of the hybrid models utilized for disease prevention and monitoring, analyzing their effectiveness by incorporating blockchain, IoT, big data, and AI, is presented. Furthermore, the proposed hybrid conceptual framework model, highlighting its potential to tackle the current pandemic through proactive and preventative measures, is discussed.The advent of the novel COVID-19 virus has prompted a substantial amount of research into the creation of useful methodologies for the prevention and monitoring of diseases. The primary objective of this literature review is to provide a comprehensive overview of the hybrid models utilized to tackle the issues presented by infectious illnesses, with an explicit emphasis on the emerging technologies, such as blockchain, IoT, big data, and AI.By combining these technologies, this model seeks to revolutionize the way we respond to public health crises, opening new possibilities for the future. Most importantly, the hybrid conceptual framework model advocates for a preventive strategy to reduce the spread of the virus and its impact on society. This paper seeks to explore the potential of this innovative framework and its ability to revolutionize our response to the pandemic.Blockchain innovation can be utilized to guarantee the secure and tamper-resistant capacity and sharing of sensitive well-being information. It provides a decentralized and straightforward stage where information can be safely stored and controlled through cryptography. Within the setting of irresistible illnesses, records, tests, inoculation information, and other pertinent data can be stored in the blockchain, guaranteeing the security and authenticity of the information . IndividInternet of Things (IoT) devices, including wearable sensors, environmental sensors, and medical equipment, can gather information about infectious diseases in real time. IoT devices, for instance, can track vital signs, such as respiratory rate, heart rate, and body temperature, to identify early signs of infections. Environmental sensors can track the air quality and look for pathogens nearby. The collected data can be securely transmitted by these IoT devices to the blockchain for additional analysis. Big data analytic techniques can be used to process and analyze the enormous amount of data gathered from IoT devices as well as other pertinent data sources, such as social media, electronic health records, and public health databases. Infectious-disease-related patterns, correlations, and trends can be found using this analysis. Using cutting-edge analytic algorithms, machine learning and data mining make it possible to detect disease events, forecast the spread of infections, and evaluate the effectiveness of prevention measures . IoT colArtificial intelligence (AI) algorithms can be employed to provide decision support in various aspects of infectious disease prevention and monitoring. For instance, machine learning models can predict the likelihood of an individual contracting a specific disease based on their health records and environmental data. AI can also help in contact tracing by analyzing data from multiple sources and identifying potential infection hotspots. Natural language processing (NLP) techniques can be used to extract relevant information from the medical literature and assist in drug discovery or treatment recommendations . AI techBig data offers an effective way to map and combine various data sources to gain insight into the tracking of the COVID-19 outbreak. Furthermore, it enables us to comprehend virus structure and treatment, as big data platforms can be equipped with sophisticated modelling tools that enable the construction of complex simulation models using the COVID-19 data stream. Therefore, text mining algorithms are essential. Nevertheless, the sheer amount of data and the speed at which it must be processed necessitates the use of AI-based intervention .A comprehensive review and comparison of existing techniques is presented in this section regarding the prevention and monitoring of infectious diseases. The objective is to provide a thorough assessment of the strengths, weaknesses, and effectiveness of various approaches employed in detecting and monitoring infectious diseases, particularly in the context of the COVID-19 pandemic. The review encompasses a wide range of techniques, including big data analytics, artificial intelligence, nature-inspired computing, blockchain, Internet of Things, and other emerging technologies. By systematically analyzing and comparing these techniques, the article aims to identify the most promising and effective strategies for disease prevention, contact tracing, and data management. Through this review and comparison, valuable insights and recommendations can be derived to guide future research and development efforts in the field of infectious disease surveillance and control.Agbehadji et al. discusseThe study in reviewedA theoretical model called virus epidemic prediction system (VEPS) was proposed for predicting infectious diseases . The modTopol highlighDeebak and Al-Turjman proposedEach study in the table demonstrates the utilization of emerging technologies to tackle different aspects of the pandemic. By summarizing the tools used and the outcomes achieved, the table provides a comprehensive overview of the research landscape in the field of infectious disease management. It showcases the diversity of approaches and the potential of these emerging technologies in combating the spread of infectious diseases and improving public health outcomes.The purpose of this matrix is to assess and compare different techniques in terms of their capabilities for managing and monitoring the spread of a pandemic. This quick comparison of these techniques based on their specific features aids researchers and practitioners in understanding the strengths and limitations of each technique within the context of a hybrid system for pandemic management.The proposed hybrid system is called hybrid disease prevention, monitoring, and management system (HDPMMS). This hybrid system, which combines emerging technologies, including blockchain, IoT, big data, and AI, provides a comprehensive solution for disease prevention, monitoring, and management see . The HDPBlockchain-based secure contact tracing and source isolation: The HDPMMS utilizes blockchain technology to enable secure and transparent contact tracing. It ensures that the transmission of infections can be effectively tracked, and source isolation can be implemented securely. By leveraging the decentralized nature of blockchain, the system enhances data privacy and security, reducing the risk of unauthorized access and tampering.Integration of IoT sensors for real-time data collection: IoT sensors are integrated into the HDPMMS to collect real-time data on vital health parameters. These sensors can monitor various physiological indicators, such as body temperature, heart rate, and respiratory rate. The continuous data collection allows for the early detection of potential outbreaks and enables proactive interventions.Big data analytics for data-driven insights: The HDPMMS incorporates big data analytic techniques to analyze the collected data from IoT sensors and other sources. Through data preprocessing, cleaning, and analysis, the system can derive meaningful insights and identify patterns related to disease dynamics. This enables researchers and healthcare professionals to make informed decisions and develop data-driven strategies for disease prevention and control.AI for symptom identification and drug manufacturing support: The HDPMMS employs AI algorithms to support symptom identification and drug manufacturing. AI algorithms can analyze vast amounts of patient data and medical records, identifying patterns and symptoms associated with specific diseases. This aids in early detection, accurate diagnosis, and timely interventions. AI can also assist in drug-manufacturing processes, such as predicting the efficacy of potential therapeutics and optimizing drug development.The HDPMMS represents a proactive approach to disease prevention and monitoring by integrating the power of blockchain, IoT, big data, and AI technologies. By combining these technologies, the system aims to provide real-time insights, secure contact tracing, early detection of outbreaks, and support for effective drug development. The HDPMMS has the potential to revolutionize disease control strategies, enabling timely interventions and proactive measures to combat the ongoing pandemic and future global health threats.The hybrid disease prevention, monitoring, and management system incorporates various functions to effectively address disease prevention and monitoring. Secure contact tracing: The HDPMMS utilizes blockchain technology to enable secure contact tracing. It allows for the recording and tracking of individuals\u2019 interactions, ensuring that the transmission of infectious diseases can be effectively monitored and traced. The decentralized and tamper-resistant nature of the blockchain ensures data integrity and privacy.Source isolation: The HDPMMS facilitates source isolation by identifying and isolating the origin of the infection. By leveraging blockchain technology, the system can securely track the source of infection and prevent further spreading. This function is crucial in containing outbreaks and minimizing the impact of infectious diseases.Real-time data collection: The HDPMMS integrates IoT sensors to collect real-time data on vital health parameters. These sensors monitor individuals\u2019 physiological indicators, such as body temperature, heart rate, and respiratory rate. Continuous data collection enables the early detection of potential outbreaks and provides real-time insights into individuals\u2019 health conditions.Data analytics and insights: The HDPMMS incorporates big data analytic techniques to analyze the collected data. Through data preprocessing, cleaning, and analysis, the system derives meaningful insights and identifies patterns related to disease dynamics. This function enables healthcare professionals and researchers to make informed decisions, develop data-driven strategies, and allocate resources effectively for disease prevention and control.Symptom identification: The HDPMMS employs AI algorithms to identify symptoms associated with infectious diseases. By analyzing vast amounts of patient data and medical records, AI algorithms can detect patterns and identify specific symptoms indicative of diseases. This function aids in early detection, accurate diagnosis, and timely interventions.Drug-manufacturing support: The HDPMMS utilizes AI to support drug-manufacturing processes. AI algorithms can analyze molecular structures, predict the efficacy of potential therapeutics, and optimize drug development. This function enables researchers and pharmaceutical companies to expedite the drug discovery and development process, thus leading to more effective treatments for infectious diseases.Overall, the HDPMMS combines secure contact tracing, source isolation, real-time data collection, data analytics, symptom identification, and drug-manufacturing support to provide a comprehensive approach to disease prevention and monitoring. By leveraging the emerging technologies, the HDPMMS aims to enhance early detection, proactive interventions, and effective response strategies, ultimately mitigating the impact of infectious diseases on a global scale.Implementing the HDPMMS framework can enhance disease surveillance capabilities by enabling real-time data collection and analysis. The integration of IoT sensors and the utilization of big data analytics allow for the early detection of outbreaks, prompt response to emerging threats, and accurate monitoring of disease trends. This leads to more effective disease surveillance and better-informed decision-making.Improved contact tracing and source isolation: The HDPMMS\u2019s secure contact-tracing function through blockchain technology enables the efficient and transparent tracking of individuals\u2019 interactions. By accurately identifying and isolating the source of the infection, the system helps to contain the spread of infectious diseases more effectively. This capability minimizes the risk of further transmission and contributes to the overall control of outbreaks.Timely symptom identification and diagnosis: The integration of AI algorithms in the HDPMMS enables timely and accurate symptom identification. By analyzing patients\u2019 data and medical records, the system can detect specific symptoms associated with infectious diseases, allowing for early diagnosis and appropriate treatment. This leads to improved patient outcomes and facilitates the implementation of targeted interventions.Facilitated drug-manufacturing and development process: The HDPMMS\u2019s AI-driven drug-manufacturing support function streamlines the drug discovery and development process. By leveraging AI algorithms to analyze molecular structures and predict drug efficacy, researchers and pharmaceutical companies can expedite the development of effective therapeutics. This accelerates the availability of treatments and improves the overall management of infectious diseases.Proactive and data-driven decision-making process: The HDPMMS provides decision-makers with data-driven insights and actionable information. By utilizing big data analytics, the system generates meaningful insights and patterns related to disease dynamics. This empowers healthcare professionals, policymakers, and researchers to make proactive decisions, allocate resources efficiently, and implement targeted interventions to prevent and control the spread of infectious diseases.The implementation of the HDPMMS results in improved disease surveillance, efficient contact tracing and source isolation, timely symptom identification, facilitated drug manufacturing, and proactive decision-making. These outcomes contribute to the overall effectiveness of disease prevention and monitoring efforts, helping to mitigate the impact of infectious diseases and safeguard public health.In conclusion, the HDPMMS presents a comprehensive and innovative approach to address the challenges posed by infectious diseases. By integrating blockchain, IoT, big data analytics, and AI, the HDPMMS offers a holistic solution for disease prevention and monitoring. Through the implementation of the HDPMMS, several key benefits can be achieved. The system enables secure contact tracing and source isolation, ensuring the effective control of disease transmission. Real-time data collection from IoT sensors facilitates the early detection of outbreaks and provides valuable insights into individuals\u2019 health conditions. The application of big data analytics allows for data-driven decision-making, enhancing disease surveillance and response strategies. Additionally, AI supports symptom identification and drug manufacturing, improving diagnosis and facilitating the development of effective therapeutics.The HDPMMS emphasizes proactive measures and preventive solutions, rather than over-reliance on treatments and cures. By leveraging emerging technologies, the system empowers healthcare professionals, researchers, and policymakers to take prompt actions, allocate resources efficiently, and implement targeted interventions to mitigate the impact of infectious diseases.The HDPMMS has the potential to revolutionize disease prevention and monitoring strategies, leading to improved public health outcomes. However, it is important to acknowledge that the implementation of such a hybrid system requires the careful consideration of ethical, legal, and privacy implications. Collaboration among various stakeholders, including healthcare organizations, technology providers, and regulatory bodies, is crucial to ensure the responsible and effective deployment of the HDPMMS.Henceforth, further research and development are needed to refine the HDPMMS and optimize its performance. Continued advancements in technology, data management, and algorithmic capabilities will contribute to the ongoing evolution of this hybrid system. By harnessing the power of emerging technologies, the HDPMMS offers promising prospects for addressing the ongoing pandemic and future global health threats, ultimately improving the health and well-being of populations worldwide."} +{"text": "To introduce Section 1013 of the Medicare Prescription Drug,Improvement, and Modernization Act (MMA) of 2003 and the Agency forHealthcare Research and Quality's (AHRQ) Effective Health Care Program.AHRQ, under Section 1013 of the MMA of 2003, has be encharged with conducting specific health care outcomes studies through the Effective Health Care Program. This research is aimed specifically at determining the safety and effectiveness of certain pharmaceuticals since comparative data is currently lacking. Highly utilized, high-cost (or both)treatments are the focus of the studies that will be conducted through AHRQ's Evidence-based Practice Centers (EPCs) and the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network. Current and completed projects are noted, including more detailed information on the reviews pertaining to treatment of rheumatoid arthritis with nonbiologic disease-modifying antirheumatic drugs (DMARDs) and biologics (anti-tumor necrosis factor[TNF]-a therapies).AHRQ's EPCs and the DEcIDE Network are studying safety and the comparative effectiveness of a number of different pharmaceutical-related topics, including the safety and effectiveness of biologic and nonbiologic DMARDS . The final reports, once complete, will be translated and then disseminated to all stakeholders."} +{"text": "This Special Issue is aimed to collect scientific papers that support holistic methodological approaches, both top-down and horizontal, for the correct application of various omics sciences because, when well-integrated, they can contribute to our understanding of the genotypic plasticity of plant species.The goal of molecular biology scientific research on agricultural crops is to use the developed technologies in order to recognize and manipulate the levels of metabolites for food applications such as nutraceutical, clinical therapeutic and pharmaceutical purposes and for the subsequent formulation of appropriate dosages, with positive effects on metabolic syndromes, including reduced risks of morbidity and mortality. In the field of bioinformatics and computational biology, high-throughput omics technologies, which can be used with tailored and even predictive approaches, such as genomics, transcriptomics, proteomics, lipidomics, metabolomics, interactomics and systems biology, are undertaking to develop and characterize specific molecular markers linked to loci of interest in order to decrease the time duration of specific breeding programs through the fast screening of thousands of genotypes for traits of interest, enabling researchers to produce intermediate and final metabolites in plants that are useful in translational biology ,2,3.In fact, the most readily transposable approach concerns the study of the aggregation of successive reactions in a model multienzymatic pathway within organelles , because it can be implemented without drawbacks. In fact, the instability of biological systems and low efficiency of non-compartmentalized metabolic pathways are often observed both when catalyzed by spatially separated enzymes and when crowding, the formation of nanodomains and altered local viscosities have effects on biochemical processes involving proteins ,5,6,7. TPhylogenetically, organellar enzymes show significant sequence similarity (homology) between plants and cyanobacteria and/or closely related lifeforms, which facilitates the isolation of species-specific genes. Therefore, the starting point is bioinformatics for a complete in silico study of both the known gene loci (which transcribe enzymes) and the metabolites (such as substrates or end products) involved in the highlighted pathway. In particular, comparative genomics studies of orthologous genes in pathways of interest, both between and within species, that are identifiable in public databases and already functionally characterized , should Today, the application of genomic, biochemical and physiological approaches for enhancing our knowledge of specific metabolic pathways and their related genes, include the systemized NGS, Illumina, Ion Torrent, PacBio and nanopore technology sequencing platforms; high-throughput genome annotation for genotyping purposes; phenomics platforms; high-resolution transcriptomics; and the bioinformatic analysis of DNA sequencing data , as well as RNA, micro-RNA and micro-transcriptomics via laser capture microdissection (LCM), chromatin immunoprecipitation (ChIP), in situ hybridization, proteomics, lipidomics and epigenomics. Several research consortia have pursued the aims of sequencing plant genomes and studying their structures, characterizing transcriptomes, identifying genes, regulatory elements and metabolomes, and developing new markers to enhance the potential of a species in order to re-evaluate and protect germplasms and to breed desirable genotypes required for productive, sustainable and resilient agriculture.It is my belief that well-designed and well-executed scientific experiments in the field of plant metabolism genetics can be used to answer questions and support hypotheses more promptly and effectively than the reductive but no less important conception and execution of in silico solutions, while supporting the validity of the predictive indication of the latter.By querying in databases, genomic sequences are identified from cDNA libraries based on the sequence homology of the exons. On the other hand, the certainty of identifying the two possible alleles at the gene locus of interest (tissue- and moment-specific), in both homozygosity and heterozygosity, is based on the sequence homology of the introns .The cloning and sequencing of the gene loci for germplasm genotyping lead to the identification of the variable allelic composition structure and reveal the alleles carrying high or low expressions of the traits. These processes also lead to the development of SNPs (Single-Nucleotide Polymorphisms), insertion/deletion and SSR databases which can represent the precious molecular markers within a plant species for the functional genotyping of varieties which show differential gene expressions for the production of metabolites of interest, which can be defined as real QTLs ,11,12. IqRT-PCR is used to analyze different correctly collected plant and fruit tissues in different stages of development , allowing us to determine the relative expression levels in the plant and the loci that behave as endogenous genes (housekeeping) that could act as the best controls a\u2013c. ThisThis research combines EST-cDNA (Expressed Sequence Tag) libraries and subtractive libraries, transcriptomes and RNA-Seq data on organs/tissue that are available with the quantification of the gene expression levels (RPKM) ,16,17. TThe data available on the gene sequences and the genetic factors that control the agronomic behavior of plants are still scarce and fragmentary, partly because the comparative genomes have not yet been obtained as secure assembling of chromosomes, especially in highly heterozygous plants with highly repeated genomes . HoweverFor the sake of methodological thoroughness, functional genomics studies are an attractive means of making significant progress in translational research . Thus, aThe applications of multiple molecular biology, computational and bioinformatics technologies in the scientific contributions accepted for publication in this Special Issue offer peculiar/specific demonstrations of the implementation of various desired and correct macro-approaches."} +{"text": "Brazilian National Survey on ChildNutrition (ENANI-2019) pointed out several advances but numerouschallenges. In this paper, we reflect on the implementation progress ofbreastfeeding, complementary feeding and young children malnutrition strategiesand programs in Brazil and how existing challenges can be overcome through thelens of implementation science. First, we present a brief history of suchprograms. Second, we selected two breastfeeding initiatives to illustrate andreflect on common implementation challenges. In these case studies, we used theRE-AIM frameworkto analyze the implementation and scaling up barriers and facilitators. We foundcommon barriers related to unclear goals about the reach of programs, challengesin assessing effectiveness and fidelity/quality during the real-worldimplementation, discontinuation or lack of funding, and lack of monitoring andevaluation impacting the sustainability of programs. We also discuss the use ofimplementation science to achieve adequate nutrition by 2030 and presentcritical elements for successful scale implementation of nutrition programsbased on global evidence. Despite the investment to implement different actionsaimed at facing infant feeding and malnutrition, high-quality implementationresearch must become a priority to catalyze progress in Brazil. Malnutrition in all its forms has risen on global agendas due to the recognitionof its magnitude and consequences for a wide range of human, social, andeconomic outcomes. Implementing strategies and programs with the needed scaleand quality is a major challenge. The Attention is drawn, for example, tothe increased consumption of ultra-processed foods in the first years of life The FederalConstitution of 1988 incorporated a concept of social security asan expression of the social rights inherent to citizenship through the guaranteeof a set of economic and social policies, including creating the BrazilianUnified National Health System (SUS) Law n. 8,080), which established the SUS, providedguidance for monitoring nutritional and dietary practices.In the 1980s, social movements focused on defending the return to democracygenerated the Brazilian Health Reform Movement. The At the end of the 1990s, the Brazilian National Food and Nutrition Policy (PNAN)was created and coordinated by the Brazilian Ministry of Health through theGeneral Coordination of Food and Nutrition Policy (CGPAN), currently theGeneral-Coordination of Food and Nutrition (CGAN) In this period, along with important achievements of the SUS, such as theexpansion of primary health care coverage, the reduction of infant mortalityrates, and the promotion of food and nutrition security, Brazil experiencedseveral changes in socioeconomic and demographic indicators that led to anepidemiological and nutritional transition Ordinance GM/MS n. 1,130 of August 5, 2015).Specifically, the second pillar explicitly promotes breastfeeding and healthycomplementary feeding. After the extinction of INAN in 1997, breastfeeding promotion, protection, andsupport were coordinated by the children\u2019s health area within the BrazilianMinistry of Health. In 2015, the Brazilian National Policy for IntegralAttention to Children\u2019s Health (PNAISC) posed a set of comprehensive actions andstrategies across seven pillars to promote child development and mitigatevulnerabilities , establishing principles and guidelinesfor formulating public policies to fulfill the rights of children, increase theeffectiveness of integrated policies, define strategies for intersectoralcoordination, and define food and nutrition as priority areas.Finally, the Legal Framework for Early Childhood was published (https://cadernos.ensp.fiocruz.br/static//arquivo/supl-e00053122_5122.pdf). We organized into three themes a brief historical overview of strategies andprograms on children\u2019s food and nutrition implemented in the health sector inBrazil: (1) child malnutrition and micronutrient deficiencies; (2) breastfeedingand complementary feeding; and (3) childhood obesity. A detailed description ofthese strategies and programs is presented in Supplementary Material Child malnutrition. Substantial declines in the prevalence of childundernutrition in Brazil have been attributed to gains in family income,maternal schooling, and expanded coverage of public education, sanitation,and health care services Over time, these programs have incorporated new approaches and been replacedby more comprehensive actions. The II PRONAN, in the late 1970s, announced aset of activities with a broader approach to combat hunger and malnutrition.However, many of these actions never came to fruition. The \u201cMilk is HealthProgram\u201d (PLS), launched in 1993, is one example of a food supplementationprogram. The goal of PLS was to reduce the prevalence of malnutrition byproviding free milk supplementation for specific groups (including childrenunder five years of age) identified through the SISVAN In the late 1990s, the Program to Combat Nutritional Deficiencies (PCCN) wascreated to replace the PLS. The PCCN included actions beyond foodsupplementation, such as promoting breastfeeding, monitoring nutritionalstatus, and preventing and treating iron and vitamin A deficiencies. Theestimates of the target audience for PCCN were based on statistical modelsprepared by the Center for Nutrition and Health Research, University of S\u00e3oPaulo (NUPENS/USP), which significantly changed the transfer of federalresources to the fight malnutrition, reversing traditional practices ofequal treatment for unequal situations In the 2000s, food supplementation programs were replaced with cash transferprograms, which had more significant potential for addressing the socialdeterminants of malnutrition ,,,,,In 2003, the Food Schoolarship Program was replaced by the Brazilian IncomeTransfer Porgram, in which social vulnerability was prioritized, defining afamily poverty cutoff as the criterion for eligibility accompanied by healthand education conditionalities. The health conditionality included a minimumof health care visits for children of beneficiaries\u2019 families and monitoringthe nutritional status. Evidence of programs to prevent and controlmalnutrition shows that positive responses to child malnutrition are closelyrelated to confronting social determinants of health and equity-orientedpolicies, i.e., the redistribution of income and guarantee of universalaccess to health, education, and basic sanitation OrdinanceGM/MS n. 894/2021).Despite reducing the prevalence of malnutrition in Brazil, the problempersists in some population subgroups, demanding focused attention andsocial investments. In 2012, the Brazilian Ministry of Health instituted theAgenda to Intensify Nutritional Care for Child Malnutrition targetingBrazilian municipalities with the highest prevalence of malnutrition amongchildren under five based on data from SISVAN. However, this strategy wasonly implemented and financed from 2012 to 2015 (b) Micronutrients deficiencies. The actions to combat micronutrientdeficiencies in the health sector were initially included in programs tocombat malnutrition At the end of the 1970s, following the international movement led by the WHOand UNICEF to return to breastfeeding, the II PRONAN included a proposal tocreate a program to promote breastfeeding. However, this proposal was onlyput into effect in 1981, creating the PNIAM. The PNIAM gained internationalattention for its diversity of actions aimed at promoting , protecting , and supporting breastfeeding Federal Constitution and the formationof the SUS in 1988 impacted children\u2019s healthcare in Brazil, evolving fromvertical maternal-infant programs of the 1970s and 1980s to the perspectiveof comprehensive care, aimed at ensuring rights, overcoming vulnerabilities,reducing morbidity and mortality, and promoting health and quality of lifeFederal Constitution guaranteed to workingwomen, with a formal employment relationship, benefits including 120 days ofmaternity leave, the right to two half-hour breaks during the workday tobreastfeed the child up to six months of age, and the right to daycare inthe workplace. In 2008, Law n. 11,770 established theCorporate Citizen Program, aimed at extending maternity leave to six-monthby granting a tax incentive. In addition, the Supporting Working Women andBreastfeeding (MTA) was adopted in partnership with the Brazilian Society ofPediatrics. It consisted of three strategic axes: extension of maternityleave to 180 days, implementation of daycare in the workplace, and creationof lactation rooms in the workplace The enactment of the ,Another milestone for legal protection was created in 1988 with the BrazilianCode of Marketing of Food for Infants (NBCAL) In 1988, the Brazilian Ministry of Health also regulated the human milk banksas centers for collecting, processing, and storing human milk and provingskilled lactation support Law n. 13,435/2017 established August as the Monthof Breastfeeding - \u201cGolden August\u201d In the early 1990s, Brazil was one of the twelve countries to adopt the BFHI.To leverage its implementation, the Brazilian Ministry of Health intensifiedthe availability of four courses proposed by the WHO: an 18-hour course formaternity teams; an 80-hour course to train monitors; a 40-hourBreastfeeding Counseling Course; and Quick Course aimed at raising awarenessamong managers ,The 2000s marked important advances to protect, promote, and supportbreastfeeding. The Kangaroo method, is codified in the Standard forHumanized Attention of Low-Birth Weight Newborns Dietary Guidelines for BrazilianChildren Under Two Years of Age (published in 2002 and revisedin 2010). These \u201cdietary guidelines\u201d were revised again in 2019 to respondto recent changes in social transformations and dietary practices and alignits approach and recommendations with the dietary guidelines for theBrazilian adult population The promotion of healthy complementary feeding was intensified by developingand disseminating various educational materials targeting healthprofessionals. These include the Decree n.9,759 of April 11, 2019, and was reactivated underOrdinance GAB/SAPS n. 13, 2022 as a Technical AdvisoryCouncil.To strengthen the governance of breastfeeding actions in 2006, the BrazilianNational Breastfeeding Committee was created. In 2012, the composition ofthis national committee was revised to include a representation of amothers\u2019 group, civil society, international organizations, andrepresentatives of educational institutions The Brazilian Breastfeeding Network (RAB) was created in 2008 and theBrazilian National Strategy for Healthy Complementary Feeding (ENPACS) in2010, both based on the principles of critical-reflexive education and theSUS Continuing Health Education Policy, which aimed to review and supportinterdisciplinary work processes in primary health units to increase theprevalence of breastfeeding and healthy complementary feeding Bases for Discussion of the National Policy onBreastfeedingAn analysis of the implementation of actions to promote, protect, and supportbreastfeeding concluded that the process which led to the successful scalingup of breastfeeding promotion in Brazil included investments in thefollowing areas: (1) baseline needs assessment including data on infantfeeding practices; (2) advocacy ; (3) national and local mass media campaigns,social mobilization ; (4) implementation and spread of the BFHI;(5) lactation management and communications/counseling training (developmentof human resources); (6) legislation ; and (7) monitoring and evaluation (includingmonitoring of the WHO code) In 2011, the PNAN expanded the concept of healthy eating and comprehensivecare for diseases related to food and nutrition, such as childhood obesity.It defined a set of actions within the health sector and other sectors toensure environments that favor healthy eating and active lifestyles. In thesame year, the Federal Government launched the Strategic Action Plan toCombat Chronic Noncommunicable Diseases (2012-2022), recognizing obesity asa disease and a risk factor for noncommunicable diseases. In 2014, theInterministerial Committee on Food and Nutrition Security (CAISAN), anintersectoral committee to articulate the ministries for the food andnutrition security agenda, launched the document Intersectoral Strategy forthe Prevention and Control of Obesity. Two initiatives that stand out to combat childhood obesity specifically werethe Brazilian Healthy Growing Program (2017) obesity prevention andtreatment requires a whole-of-government approach in which policiesacross all sectors systematically take health into account, avoidharmful health impacts, and thus improve population health and healthequity\u201d Importantly, both Brazilian actions to fight against child obesity arealigned to the recommendations published by the WHO Commission on EndingChildhood Obesity in 2016, which states that \u201cBrazil\u2019s long trajectory builds a robust framework for infant and young children\u2019snutrition policies and initiatives; however, there are still challenges for theirimplementation. We selected breastfeeding protection, promotion, and supportinitiatives - the BFHI and the EAAB - to illustrate and reflect on common implementationchallenges. In these case studies, we used the RE-AIM framework to analyze the implementation andscaling up barriers and facilitators Innocenti Declaration and the World Health Assemblyresolutions of 1994 and 1996, and in 2002 included in the Global Strategy forInfant and Young Child Feeding ,,,,The BFHI was conceived in the early 1990s by the WHO and UNICEF, ratified by theThe Brazilian BFHI accreditation follows the global criteria to comply with the\u201cTen Steps\u201d and three additional criteria: (1) compliance with the NBCAL, (2)the mother-friendly care practices, and (3) assurance that the mother or father remains with the newborn 24-hours. In 2022, the BrazilianBFHI will complete 30 years of implementation. However, despite considerableefforts made by the Brazilian Ministry of Health as well as State and MunicipalHealth Departments to mobilize managers and professionals from maternityhospitals to adopt the Ten Steps, its implementation at scale is still facingseveral challenges. ,,Law n. 11,265/2006 and do notdistribute breast milk \u201csubstitutes\u201d in the primary health clinics; (5)participation of at least 85% of the primary care professionals in thecontinuing education workshop; (6) comply with at least one activity toencourage breastfeeding, and one for healthy complementary feeding agreed in theaction plan The EAAB is the latest initiative of the Brazilian Ministry of Health focused oninfant feeding. Rooted in the critical-reflexive concept, the EAAB aims tostrengthen actions to promote, protect, and support breastfeeding and healthycomplementary feeding for children under two years of age, improving the skillsand abilities of health professionals within the scope of primary care Our implementation analysis identified essential elements across RE-AIM dimensionsthat could improve the implementation and sustainability of both programs andpractices. Documenting and paying attention to the RE-AIM elements have been provedto increase the likelihood of improving successful implementation and, ultimately,the health of the entire population ,,,Implementation science in nutrition is a body of systematized knowledge about how toimprove the implementation of nutrition-specific and sensitive interventions ,,In the last 30 years, Brazil has achieved nearly universal access to primary healthcare for the population, thanks to the expansion of the coverage of the FamilyHealth Strategy, which reaches 60% of the population However, fiscal policies implemented in 2016 ushered in austerity measures that,alongside the current Brazilian government\u2019s new environmental, educational, andhealth policy, could reverse the hard-earned achievements of the SUS, impacting theimplementation of infant feeding and nutrition policies ,,,,Although improving infant and young children\u2019s nutrition requires information aboutbiology and epidemiology, the increasing complexity and multisectorality ofnutrition initiatives highlight sociopolitical factors that determine which actionsare appropriate and acceptable The exercise of applying the RE-AIM, one of the most widespread frameworks inimplementation research, in the analysis of two brief case studies on breastfeedingpolicies in Brazil, allowed us to identify implementation barriers in differentdimensions. We found common barriers related to (1) unclear goals regarding thereach of programs; (2) challenges in assessing effectiveness and fidelity/qualityduring the real-world implementation; (3) discontinuation or lack of funding andlack of monitoring and evaluation, impacting the sustainability of programs.Therefore, implementation research can provide pragmatic programmatic lessons andguidance on how to scale up nutrition interventions by better understandingdifferent contexts, identifying barriers and facilitators, and allocating resourcesand funds for maximum impact ,Hence, high-quality implementation research within large-scale nutrition programsmust become a priority to catalyze progress. Implementation research for nutritionis not new but has not been prioritized"} +{"text": "BMC Medicine and BMC Neurology is to synthesize current concepts and most recent findings concerning the evaluation, etiology, pathophysiology and clinical relevance of the potential involvement of the extracranial venous system in the pathology of multiple CNS disorders and in aging.The extracranial venous system is complex and variable between individuals. Until recently, these variations were acknowledged as developmental variants and were not considered pathological findings. However, in the last decade, the presence and severity of uni- or bi-lateral jugular venous reflux (JVR) was linked to several central nervous system (CNS) disorders such as transient global amnesia, transient monocular blindness, cough headache, primary exertional headache and, most recently, to Alzheimer's disease. The most recent introduction of a composite criteria-based vascular condition named chronic cerebrospinal venous insufficiency (CCSVI), which was originally linked to multiple sclerosis, increased the interest in better understanding the role of the extracranial venous system in the pathophysiology of CNS disorders. The ultimate cause-consequence relationship between these conditions and CNS disorders has not been firmly established and further research is needed. The purpose of this article collection in http://www.biomedcentral.com/1741-7015/11/260.Please see related debate: The potential involvement of the extracranial venous system in the pathology of central nervous system (CNS) disorders and in aging is largely debated at this time ,2. This The extracranial venous system is complex with variability between individuals and is frequently asymmetric . Until ret al. examined 109 MS patients and found no evidence of an association between the presence and severity of CCSVI with cognitive impairment and depression in patients with MS [et al. evaluated 61 MS patients and found no association between CCSVI and cognitive impairment, fatigue, depression, bladder/sexual symptoms and self-reported quality of life [The debate article by Zivadinov and Chung provides with MS , while L of life . These f of life ,20.The limited understanding of the pathophysiology of the extracranial venous system may consequently underestimate the impact of cerebral venous drainage abnormalities in a variety of CNS disorders . Becauseet al.[One of the most convincing indicators towards a \u201cvascular origin\u201d for MS comes from neuropathological observations showing that MS plaques are exclusively perivenular and dimensions of the veins determine the shape, course and dimension of the lesions . This iset al. presentset al.[per se is not sufficient to increase the hydraulic resistance of the cerebral vascular bed but that other mechanisms must be at work, including the potential role of various precipitating risk factors.The pathophysiology of extracranial venous abnormalities may be further elucidated by exploring the role of precipitating risk factors ,5,25,26.et al. tested tet al. provide a comprehensive review of non-invasive and invasive imaging methods for the detection of extracranial venous abnormalities, including CCSVI [et al. evaluated the non-invasive and invasive multimodal imaging correlates of 20 MS patients with relapsing MS who were enrolled in the Prospective Randomized Endovascular therapy in Multiple Sclerosis\u201d (PREMiSe) study [At this time, there is no established diagnostic imaging modality, non-invasive or invasive, that can serve as the \u201cgold standard\u201d for the detection of any extracranial venous abnormalities . Howeverng CCSVI . They dee) study . They coet al. present a novel model in a clinical setting that suggests the pivotal role of the collateral network in draining the blood into the superior vena cava under CCSVI conditions [When there is narrowing of the principal pathways of the extracranial venous system, collateral veins usually form as physiological secondary compensation for the compromised venous system outflow ,4. The pnditions . One of et al. showed in 23 transient monocular blindness (TMB) patients who had no carotid stenosis and in 23 age- and sex-matched healthy controls that there was a greater severity of IJV compression/stenosis in TMB patients [While a link between the presence and severity of extracranial venous abnormalities and several CNS disorders as well as aging is emerging, it is to be determined whether those may play a potential role, as precipitating factors, to increased susceptibility for a number of CNS disorders. Although the presence and severity of JVR and CCSVI have been linked to a number of CNS disorders, the ultimate cause-consequence relationship has not been firmly established. In an original article, Cheng patients . Therefo\u2018Venous Involvement in Neurological Disorders and Aging\u2019 article collection in BMC Medicine and BMC Neurology has attempted to present a fair and balanced discussion of the examined topics. It is hoped that the contents of this collection will encourage the readers to continue their research on this subject.The CBF: Cerebral blood flow; CCSVI: Chronic cerebrospinal venous insufficiency; CNS: Central nervous system; CSF: Cerebrospinal fluid; ET-1: Endothelin-1; IJV: Internal jugular vein; JVR: Jugular venous reflux; MS: Multiple sclerosis; NPH: Normal-pressure hydrocephalus; PREMiSe: Prospective Randomized Endovascular therapy in Multiple Sclerosis; TMB: Transient monocular blindness.Robert Zivadinov received personal compensation from Teva Neuroscience, Biogen Idec, EMD Serono, Bayer, Genzyme-Sanofi, Novartis, Claret and General Electric for speaking and consultant fees. He received financial support for research activities from Biogen Idec, Teva Neuroscience, Genzyme-Sanofi, Novartis and EMD Serono.Robert Zivadinov, M.D., Ph.D., is a professor of neurology with tenure at the Department of Neurology, School of Medicine and Biomedical Sciences, University of Buffalo, State University of New York (SUNY) and clinical professor of neurology at the Florida International University College of Medicine. He is director of the Buffalo Neuroimaging Analysis Center and of the MR Imaging Clinical Translational Research Center at the University of Buffalo.He has performed extensive research in multiple sclerosis and imaging, having published more than 250 articles and 400 abstracts in leading peer-reviewed journals. He is currently pursuing research studies on quantitative magnetic resonance, ultrasound, angiography and optic coherence tomography imaging findings in multiple sclerosis, Parkinson\u2019s and Alzheimer's disease and aging. His current interests also concentrate on therapeutic interventions, including strategies towards assessing neuroprotective efforts in neurodegenerative disorders, as well as venous function, genetic and neuroepidemiology fields of these diseases.BMC Medicine and BMC Neurology with the aim of synthesizing most recent concepts concerning the evaluation, etiology, pathophysiology and clinical relevance of the potential involvement of the extracranial venous system in the pathology of multiple CNS disorders and in aging. Dr. Zivadinov is one of the leading authorities in the field on this topic, having published more than 30 original and review articles in peer-reviewed journals.Dr. Zivadinov guest-edited this article collection in All articles in this article collection have been independently prepared by the authors and have been subject to the standard peer-review processes of the journals."} +{"text": "Despite the need for a reduction in levels of childhood exposure to environmental tobacco smoke (ETS) being a recognised public health goal, the delivery of ETS preventive care in child health service settings remains a largely unstudied area. The purpose of this study was to determine the prevalence of ETS preventive care in child health services; differences in the provision of care by type of service; the prevalence of strategies to support such care; and the association between care support strategies and care provision.One-hundred and fifty-one (83%) child health service managers within New South Wales, Australia completed a questionnaire in 2002 regarding the: assessment of parental smoking and child ETS exposure; the provision of parental smoking cessation and ETS-exposure reduction advice; and strategies used to support the provision of such care. Child health services were categorised based on their size and case-mix, and a chi-square analysis was performed to compare the prevalence of ETS risk assessment and ETS prevention advice between service types. Logistic regression analysis was used to examine associations between the existence of care support strategies and the provision of ETS risk assessment and ETS exposure prevention advice.A significant proportion of services reported that they did not assess parental smoking status (26%), and reported that they did not assess the ETS exposure (78%) of any child. Forty four percent of services reported that they did not provide smoking cessation advice and 20% reported they did not provide ETS exposure prevention advice. Community based child and family health services reported a greater prevalence of ETS preventive care compared to other hospital based units. Less than half of the services reported having strategies to support the provision of ETS preventive care. The existence of such support strategies was associated with greater odds of care provision.The existence of major gaps in recommended ETS preventive care provision suggests a need for additional initiatives to increase such care delivery. The low prevalence of strategies that support such care delivery suggests a potential avenue to achieve this outcome. Children are particularly vulnerable to the harmful effects of environmental tobacco smoke (ETS) because of their relatively underdeveloped immune and pulmonary systems, their small body size, and their higher rates of ventilation ,2. ExposGiven that child exposure to ETS is most commonly associated with smoking by parents and other household member -8, interHealth facilities present an ideal opportunity to deliver ETS-prevention advice to parents . First, Limited international evidence provides an insight into the level of ETS prevention care routinely provided in child health care settings. Such evidence is primarily United States based and addresses care provided by physicians only ,21-23. ITo date, research describing the provision of ETS-prevention care by heath care professionals, and the prevalence of strategies to support such care is limited. Given this, a study was undertaken to determine the: prevalence of ETS preventive care in child health services; the differences in care provision by type of child health services; the prevalence of strategies to support such care; and the association between care support strategies and care provision.A cross-sectional survey of public child health care services in New South Wales, Australia was undertaken in 2002. Eligible services were firstly, those units within hospitals that primarily cared for children aged 0-15 years of age, including all paediatric, postnatal and neo-natal units, and secondly, all community-based child and family health services. The eligible respondent for each health service was the Senior Nurse Manager within hospital settings, or the Senior Manager of child and family health services.A self-report questionnaire was developed based on recommendations included in the United States' Clinical Guidelines for Treating Tobacco Use and Dependence , and on Pen and paper questionnaires were forwarded by the Chief Health Officer of New South Wales to all Health Services within the state. The Chief Executive of each service was asked to distribute the questionnaire to specified respondents within their organisation. Respondents were asked to complete the survey based on their knowledge of practices within their unit.Health Services that did not return the surveys within three weeks received a telephone reminder prompt by the Chief Health Officer's staff. Ethics approval for human research was obtained from the University of Newcastle's Human Research Ethics Committee.In the questionnaire respondents were asked to indicate if their unit assessed two forms of ETS risk: parental smoking status, and the ETS exposure of children . Those respondents, who indicated assessment was undertaken were asked to estimate the proportion of parents for whom each of form of assessment was routinely undertaken .Respondents were asked whether their unit provided two forms of ETS exposure prevention advice to parents of children at risk: quit smoking advice and ETS reduction advice ('yes' 'no' or 'unsure'). Those respondents who indicated that advice was provided were asked to estimate the proportion of parents for whom such advice would be routinely provided . Such respondents were also asked to indicate the type of advice offered ('yes' or 'no').Respondents were asked if the provision ETS preventive care was supported by: documentation in the form of written policies; staff training; or organisational prompts such as computer based prompts and medical record stickers .Respondents were asked to indicate the type of child health service that they were reporting on.Hospitals were categorised into one of two groups based upon their size and case-mix. Group 1 hospitals included principal referral and major metropolitan and non-metropolitan hospitals treating between 10,000 and 25,000 patients per year. Group 2 hospitals included district and community hospitals treating between 2,000 and 10,000 patients per year. As a consequence, all units were clasified as either a Group 1 or Group 2 hospital, or a child and family health service.Responses regarding the estimated proportion of parents that routinely received either form of ETS risk assessment, and the proportion of parents that routinely received either form of ETS exposure prevention advice were collapsed into four categories: 'none' (0%), 'less than 75%' (1-75%), 'almost all' (76-99%) and 'all patients' (100%). Based on these categories, the overall prevalence of both ETS risk assessment and ETS exposure prevention advice were examined. Differences in the prevalence of each form of care between the types of services were examined by chi-square analysis.The prevalence of each type of care support strategy is reported as a proportion. Differences in the prevalence of such strategies between the types of services were examined by chi-square analysis.p < 0.05). Evidence of confounding and possible interactions were investigated.Chi-square and logistic regression analyses were used to examine associations between the existence of care support strategies (independent variable) and each of the four forms of care (dependent variables). For these analyses, responses regarding the proportion of patients receiving each form of care were collapsed into two groups, 0-75% of patients (some) and 76-100% of patients (most) . ResponsAll analysis was undertaken using the statistical software package SAS 9.1.2 . A finitCompleted questionnaires were received from 153 of the 183 eligible units (83%). Response rates did not differ significantly between health service settings, or between hospital peer groups (range 81% to 84%). Seventy-two percent (n = 111) of respondents were from hospital units and 28% (n = 42) were from community-based child and family health services. Sixty one percent (n = 67) of hospital respondents were from Peer Group 1.p < 0.001).Twenty-six percent of all respondents indicated that their service did not assess the smoking status of any parents (see Table p < 0.001).Seventy-eight percent of all respondents, and 86%-87% of hospital units reported that their service did not assess the ETS exposure for any child. Fourteen percent indicated that their facility routinely assessed the ETS exposure for most children. A greater proportion of respondents from child and family health units reported assessing the ETS exposure of most children. Thirty-six percent of community-based child and family health respondents reported that they assessed the smoking status of most parents (>75%) compared to 4% of Peer Group 1 and 7% of Peer Group 2 respondents (p = 0.003).Nearly half of all respondents (44%) indicated that their service did not provide smoking cessation advice to any parents (see Table Of those units that reported providing smoking cessation advice to parents (56%), 86% provided brief verbal advice, 75% provided written materials, 30% offered referrals, 22% provided extended verbal advice, 19% provided advice regarding NRT, and 13% provided NRT. Eighty percent of such units reported providing more than one type of quit smoking advice to parents.p = 0.036).Twenty percent of respondents indicated that their service did not provide ETS-reduction advice to any parents of children at risk, whilst approximately one half (46%) reported that such advice was provided to most parents. A greater proportion of respondents from community-based child and family health services reported providing ETS-reduction advice to most parents. Sixty-three percent of child and family health respondents reported that they provided ETS-reduction advice to most parents of children at risk compared to 47% of Peer Group 1 and 25% of Peer Group 2 respondents (Of those units that reported providing ETS reduction advice to parents (80%), 88% provided brief verbal advice, 65% provided written materials, 27% provided extended verbal advice, and 19% offered referrals. Seventy six percent of such units reported providing more than one type of ETS reduction advice to parents.p = 0.356 and p = 0.839 respectively) or the existence of prompts for the provision of ETS-prevention care (p = 0.781). Community-based child and family health unit respondents (68%) reported a higher prevalence of staff training in the provision of ETS-prevention care compared to Peer Group 1 (41%) and Peer Group 2 respondents (36%) (p = 0.007).As shown in Table Independent of type of service, respondents who reported the existence of an ETS prevention policy had approximately twice the odds of assessing parental smoking status . Respondents who reported the existence of training regarding ETS prevention care had twice the odds of assessing parental smoking status and over four times the odds of assessing child ETS exposure .Independent of type of service, respondents reporting the existence of a quit smoking policy had nearly three times the odds of providing parental smoking cessation advice (see Table The existence of an ETS prevention care policy significantly increased the odds of providing ETS exposure advice (OR 3.0 CI 1.3-6.6). No other associations were evident between service support strategies and the provision of such advice.This study is the first that reports the prevalence of ETS preventive care routinely delivered by Australian public child health services. We found that a large proportion of such services failed to routinely assess ETS risks or provide ETS exposure prevention advice to parents of attending children. The results also suggest the limited existence of clinical practice strategies to support the provision of such care. The results indicate a considerable need and potential for additional clinical practice initiatives to realise the benefits of ETS prevention care for children.The results of this study, despite methodological differences, are consistent with those of research in other countries that suggest that approximately half of child health services fail to assess the smoking status of the majority of parents ,21,23,25The results of the current study suggest that most services fail to routinely provide smoking cessation and ETS reduction advice to parents, which is consistent with previous research ,21,23,25The results of this study extend previous research by examining and demonstrating differences in the prevalence of ETS prevention care between types of services and clinicians ,23. The Evidence suggests that intervention strategies that are most effective in increasing ETS prevention care are system level strategies such as policies , remindeThe findings of this study support such previous research, by suggesting that where clinical practice is supported by a written policy, training and care prompts, clinicians are more likely to assess children's ETS risk and provide ETS prevention care. Despite this positive finding, it is evident that the majority of child health services do not incorporate support strategies within their organisations. Training regarding ETS prevention care was the most often reported support mechanism (47%) followed by ETS care prompts (20%), the existence of a policy outlining the provision of smoking cessation care (22%), and policy outlining ETS reduction care (12%). Such outcomes are similar to those reported in the adult inpatient setting .The observed low levels of organisational support can be argued to have contributed to the finding that the majority of children attending child health services are not being assessed for ETS risk, or provided ETS prevention care. As these findings occur in the context of international and national guidelines that mandate the provision of ETS prevention interventions ,38, the The findings of this study should be considered in the context of a number of its methodological characteristics. First, the study relied on the use of an indirect estimate of care prevalence by utilising self-report data of senior unit managers. Results obtained from self-report studies can be confounded as respondents commonly over-report the routine provision of assessment and advice . If thisThere is a clear need to further enhance the provision of ETS prevention care in child health services. Considering the documented efficacy of care support strategies such as reminders, education and policy, the further dissemination of ETS preventive care guidelines should incorporate such strategies.The authors declare that they have no competing interests.TH contributed to: conception and design of the study, acquisition of data, analysis and interpretation of the data, drafting of the manuscript, provided statistical expertise, read and approved the final manuscript.JD contributed to: conception and design of the study, acquisition of data, analysis and interpretation of the data, drafting of the manuscript, provided supervision, read and approved the final manuscript.JB contributed to: conception and design of the study, analysis and interpretation of the data, drafting of the manuscript, revision of the manuscript for important intellectual content and provided supervision, read and approved the final manuscript.MF contributed to: conception and design of the study, analysis and interpretation of the data, drafting of the manuscript, revision of the manuscript for important intellectual content and provided supervision, read and approved the final manuscript.JW contributed to: conception and design of the study, acquisition of data, analysis and interpretation of the data, drafting of the manuscript, revision of the manuscript for important intellectual content, involved in obtaining funding, providing supervision, read and approved the final manuscript.This study was undertaken with the support of Hunter New England Population Health and infrastructure support from the Hunter Medical Research Institute.The sources of funding for the study, for each author, are as follows:TH: Hunter New England Population Health, New South Wales (NSW) Department of Health, Australia; Faculty of Psychology, The University of Newcastle, NSW, Australia; Hunter Medical Research Institute, NSW Australia.JD: Hunter New England Population Health, New South Wales (NSW) Department of Health, Australia; Faculty of Health, The University of Newcastle, NSW, Australia; Hunter Medical Research Institute, NSW Australia.JB: Faculty of Health, The University of Newcastle, NSW, Australia; Hunter Medical Research Institute, NSW Australia.MF: Hunter New England Population Health, New South Wales (NSW) Department of Health, Australia; the Faculty of Health, The University of Newcastle, NSW, Australia; Newcastle Institute of Public Health, NSW Australia; Hunter Medical Research Institute, NSW Australia.JW: Hunter New England Population Health, New South Wales (NSW) Department of Health, Australia; Faculty of Health, The University of Newcastle, NSW, Australia; Newcastle Institute of Public Health, NSW Australia; Hunter Medical Research Institute, NSW Australia.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/324/prepub"} +{"text": "Workshop on Carbohydrate Moieties as Vaccine CandidatesBethesda, MD, USAOctober 6-7, 2004Haemophilus influenzae b and pneumococcal conjugate vaccines. However, our understanding of several aspects of polysaccharide vaccines is limited, and more knowledge is needed to allow greater development and deployment. The goals of this workshop were to examine the mechanisms involved in generating an appropriate immune response to selected carbohydrate antigens, highlight recent and novel advances, and discuss how this information could be used in the development of effective vaccines. The workshop participants included national and international research scientists and clinicians from the National Institutes of Health, the Food and Drug Administration, academia, and industry.Whole microbes, microbial subunits and extracts, and peptide and protein antigens have been the focus of much vaccine research and development. While studies of peptide and protein antigens have been facilitated by the rapid advances in genomics and proteomics, studies of sugar chains, which are abundantly expressed on the outer surfaces of viral, bacterial, protozoan, and fungal pathogens and on the membranes of mammalian cells, have not kept pace with technologic advances. Polysaccharide-based vaccines have demonstrated efficacy in disease-prevention strategies, e.g., Francisella tularensis, a potential weapon of bioterrorism) to T cells. The evidence that CD1-restricted T cells contribute to immunity against microbial infection includes the observation that CD1 is expressed at higher levels in lesions of tuberculoid leprosy in comparison to lepromatous leprosy. The design of optimal vaccines against such pathogens should include lipid and peptide antigens.The meeting was organized into 7 sessions on such topics as genetic and cellular mechanisms of carbohydrate immunity, carbohydrate antigens for vaccines, and new tools for studying carbohydrates. Understanding the mechanistic aspects of the genetic control and the cellular pathways of the immune response to bacterial carbohydrate antigens should provide insights into ways to enhance the immune response and thus facilitate vaccine development. Studies were also presented on novel molecules involved in the recognition of carbohydrate antigens such as specific intercellular adhesion molecule (ICAM)\u2013grabbing nonintegrins, which are C-type lectins that show substantial expression in many tissues, and toll-like receptors, which function as pattern recognition receptors for conserved pathogen structures and serve as key links between innate and adaptive immunity. Investigations are ongoing to determine how these molecules function in bacterial clearance and in signaling innate and adaptive responses. A number of presentations were focused on the role of CD1 proteins, which present lipid antigens has been established at the Scripps Research Institute and has developed a novel glycan array format that uses covalent coupling of glycans to glass slides.New technologies such as carbohydrate microarrays, automated syntheses of oligosaccharides, and biophysical and computational methods for studying antigen-antibody interactions are now available for providing insight into the structure of and immune response to carbohydrate antigens. Additionally, peptide mimotopes may be used in carbohydrate technologies designed for proteins. An oligosaccharide synthesizer is now being used in the development of a number of vaccines, including those for malaria, leishmaniasis, HIV, tuberculosis, and leprosy. A Consortium for Functional Genomics elucidating the mechanisms of immunity to and regulation of carbohydrate antigens in adults, children, and neonates and using opportunities for modeling carbohydrate antigen-antibody interactions; 2) defining the molecular basis of enhanced immunogenicity with glycoconjugate vaccines and investigating the role of adjuvants; 3) examining the role of CD1-reactive T cells in the immune response to capsular polysaccharides; and 4) developing surrogates for in vivo immunity for the use of glycolipids as CD1-based vaccines in humans. Resource needs include the following: 1) enhanced availability of carbohydrate microarrays; 2) development of appropriate animal models and the availability of a transgenic mouse platform that allows generation of human antibodies; 3) development of tetramers and analytical chemistry to help in the identification of antigens, e.g., for the use of glycolipids as CD-1-based vaccines; and 4) enhanced good laboratory practice (GLP) resources to produce synthetic carbohydrate vaccines and GLP testing for vaccine candidate safety in animals and for production of good manufacturing practice vaccine candidates. As a result of the workshop, an open LISTSERV (GLYCOIMMUNOLOGY) has been established, and the Journal of Clinical Infectious Diseases will publish a review article. For additional information, contact ctaylor@niaid.nih.govThe workshop was sponsored by funds from the National Vaccine Program Office and the National Institute of Allergy and Infectious Diseases."} +{"text": "Normal placental structure and function is essential for a healthy pregnancy; the placenta is responsible for nutrient and oxygen transport, removal of waste products, protection from infection, modulation of the maternal immune system and hormone production to maintain pregnancy. The human placenta is structurally adapted to fulfil this role as it is haemomonochorial, minimising the distance between maternal and fetal circulations to maximise exchange. Disorders of the placenta including: FGR, pre-eclampsia, placental abruption and abnormal (velamentous) cord insertion are associated with over 50% of stillbirths and are frequently cited as the primary cause of death -3.Abnormal placental structure and function significantly increases the risk of stillbirth. Levels of pregnancy associated plasma protein A (PAPP-A) in the lowest 5% and alpha fetoprotein (AFP) in the highest 5% increase the risk of stillbirth by 50-fold and 2.8-fold respectively ,5. In woDue to its central role in determining pregnancy outcome, detailed examination of the placenta can give useful information about the cause of stillbirth and is recommended by the Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG) and Perinatal Society of Australia and New Zealand (PSANZ) ,13. ExamDespite the value of placental examination to identify conditions associated with stillbirth including: fetal thrombotic vasculopathy, chronic intervillositis, villitis, chorioamnionitis, funisitis, infarction, massive perivillous fibrin deposition, villous dysmaturity , villous immaturity and cord lesions further research is needed to increase the understanding of placental pathology in stillbirth. This is reflected in the research priorities for high-income countries synthesised by an international panel of experts which mention need for repositories of well-phenotyped samples from stillbirths and from well-matched controls and the need to understand the pathophysiological pathways in common conditions associated with stillbirth including: diabetes, cigarette smoking and maternal obesity .An important goal of translational medicine is to use the increased understanding of placental dysfunction to develop improved tests of pregnancy wellbeing. For example, factors derived from the placenta, such as human placental lactogen or placental growth factor may provide novel means to identify pregnancies at highest risk of stillbirth . Discove"} +{"text": "Jundishapur University of Medical Sciences (AJUMS) officiated as host to the second nanodrugs congress on March 2012, which was held by nanotechnology research center of AJUMS in cooperation with Shahid Chamran University of Ahvaz, Iran. This scientific event was scheduled to be held in a bid to create an appropriate environment for idea exchange among the specialists and researchers active in the field of drug delivery. The objectives of the organization of this congress was introducing the latest achievements in the field of nanodrugs, considering targeted drug delivery aim for the treatment of incurable diseases, improving the life quality and social health, and converting science and technology into wealth.One of the major scopes of the congress was the application of nanotechnology in the field of natural pharmaceutical products. Recently there have been considerable researches on developing biocompatible and biodegradable nanocarriers/nanodevices as novel drug delivery systems. Natural polymers or biopolymers are generally biocompatible, biodegradable, non-toxic and non-immunogenic. They occur widely in nature and are classified into 2 groups; polysaccharides and proteins . ChitosaLipids also are a broad group of naturally occurring molecules that include fats, waxes, sterols, phospholipids, fat-soluble vitamins, mono-, di-, and tri-glycerides which are advantageous to formulation of a wide range of lipid-based nanocarriers; such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid drug conjugates (LDC) to minimize the drawbacks associated with polymeric nanoparticles specially low drug loading for hydrophobic drugs .Moreover some research are being focused on development of novel drug delivery systems for herbal extracts or plant actives, such as polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes, to protect active herbal ingredients from physical and chemical degradation, enhance safety and pharmacological activity, and overcome solubility and bioavailability problems associated with plant medicine . Finally"} +{"text": "The aim of the study was to evaluate the prognostic value of Killip classification in terms of health-related quality of life (HRQoL).The sample consisted of 112 patients treated for myocardial infarction (MI), as onset manifestation of coronary artery disease (CAD), during 2008/09 in a prefectural hospital in northern Greece. At 1-year follow-up visit, HRQoL was measured using a generic and a disease-specific instrument. The 15D consists of a visual analogue scale (VAS) and a total score. The scoring algorithm of the MacNew generates a global score, and three separate domains scores: emotional, physical and social.Patients were grouped into the four Killip classes according to the degree of pulmonary congestion at admission Table . Mean HRPatients with MI as an onset manifestation of CAD present with varied degrees of pulmonary congestion. The prognostic value of the Killip classification is highlighted in terms of the extent of CAD (number of affected vessels and revascularization technique), of NYHA class and, last but not least, of HRQoL."} +{"text": "Long standing Hashimoto Thyroiditis (HT) causes shrinking and atrophy of the thyroid, but may also lead to diffuse enlargement of the gland and/or formation of nodules. These nodules should be differentiated from papillary thyroid carcinoma (PTC) and primary thyroidal non-Hodgkin lymphoma (PTL), which are possible complications of HT, and require pre-surgical diagnoses and different treatments.This study focuses on the role of fine-needle cytology (FNC) in the clinical surveillance and pre-surgical diagnosis of HT with diffuse and nodular enlargement of the gland in elderly patients.Thirty-four elderly patients (\u2265 65 yrs) with HT and diffuse or nodular enlargement of the thyroid underwent ultrasound (US)-guided FNC. Smears were routinely stained and evaluated; additional passes were used for flow cytometry (FC) assessment of lymphoid infiltrate in 6 cases.The cytological diagnosis was HT in 12 cases with prevalence of Hurtle cells in 2 cases, PTC in 1 case and PTL in 2 cases. FC assessed the reactive, non-lymphomatous nature of the lymphoid infiltrate in 5 cases and demonstrated light chain restriction, hence the lymphomatous nature of the lymphoid infiltrate in 2 cases of PTL.FNC plays a key role in the clinical surveillance and pre-surgical diagnosis of diffuse enlargement and nodular presentation of HT in elderly patients. FNC can correctly diagnose HT, PTC and PTL indicating the need for surgery and its extension in suspicious or neoplastic cases, leaving other cases to the medical treatment and clinical surveillance. Hashimoto Thyroiditis (HT) is the most common autoimmune disease; the typical clinical presentation is a painless diffuse enlargement of the thyroid, with high serum thyroid autoantibodies ,2. HT isBetween January 2010 and December 2012, 1.256 patients with thyroidal nodules or diffuse swelling underwent FNC in the outpatient clinics of the Azienda Ospedaliera Universitaria, University of Salerno. Before FNC, patients were informed of the diagnostic procedure and related risks; informed consent was obtained from all patients for the performance of FNC, diagnostic procedures and the scientific use of biological material. Sixty patients were diagnosed with HT or suspected HT because of the clinical, serologic, and/or ultrasound (US) presentation. Clinical signs and symptoms included swollen thyroid gland, with or without discrete nodules and, rarely, mild fever. US examination generally showed poorly defined hypoechoic areas, thin fibrous strands with diffuse hypervascular pattern or diffuse glandular enlargement with scattered nodules. Clinical, serological and US data were available for all patients and FNC produced a sufficient amount of cells to prepare adequate cytological smears and perform ancillary techniques, when needed. Whereas the definition of elderly is related to the pathophysiology of aging -33, the The diagnostic procedure and related risks were first discussed with the patients, who were also informed that 1 or 2 supplementary passes might have been needed, and their informed consent was obtained. FNC was performed under US control, as previously described ,36, and The cytological diagnosis was typical HT in 10 cases, HT with prevalence of Hurthle cells in 2 cases, PTC in 1 case and PTL in 1 case. Typical HT showed different cytological patterns due to the prevalence of lymphoid cells or follicular and Hurthle cells. Those with prevalence of lymphoid cells were characterized by small lymphocytes, either isolated or intermingled with histiocytes, occasional plasma cells, and stretched lymphocytes. This pattern was referred as ''lymphocytic'' (6 cases) (Figure HT clinical presentation reflects the pathological modifications of the gland over time. After an initial diffuse swelling, the gland undergoes progressive loss of thyroid follicular cells and replacement by lymphocytes, with the formation of germinal centres and fibrosis. Apoptosis is considered to be the main pathogenetic mechanism of follicular cell destruction; a predominantly Th1-mediated immune activity may promote apoptosis of thyroid follicular cells, leading to thyroid cell destruction and HT , althougFNC has a definite role in the clinical surveillance and pre-surgical diagnosis of thyroidal diffuse enlargement and nodular presentation of HT; it can be conveniently used in elderly patients. FNC can also indicate the need for surgery and its extension in selected cases, as well as the need for medical treatments and clinical surveillance in others.The authors declare that they have no competing interests.PZ, MV: conception and design, interpretation of data, AC, EV, VDS, MV, AG, VDC, MPC: acquisition of data, drafting the manuscript, PZ, MV: critical revision, given final approval of the version to be published.AC = Assistant of Pathology at University of SalernoEV = Assistant of Pathology at University of Naples \"Federico II\"MV = Associate Professor of Endocrinology at University of SalernoVDC = Aggregate Professor of Thoracic Surgery at University of SalernoMC = Aggregate Professor of Anatomy, University of Naples \"Federico II\"CC = Aggregate Professor of Oncology, University of Naples \"Federico II\"AG = Aggregate Professor of Pediatric Surgery at University of SalernoPZ = Associate Professor of Pathology at University of Salerno"} +{"text": "Recent advancement in genomic and genetic sequencing technology has ushered in a new era in which unprecedented amount of genomic sequence and transcript sequence data with extraordinary detail can be generated at incredibly short time. As part of this advancement, the approaches that utilize the powerful next generation sequencing technology, such as RNA-Seq, may have dramatically changed the field of non-coding RNA (ncRNA) research. Since these new approaches do not require prior knowledge of annotated transcripts for probes, theoretically the entire transcriptome of a given sample can be sequenced. This enables the detection of novel transcripts, including both protein coding and ncRNA, as well as RNA with somatic mutations and alternative splicing forms bases in the human genome are transcribed into genes that code for proteins , which is believed to be the transcripts of 1\u20133% of the human genome. miRNA is highly involved in brain development and plasticity at the neuronal level (Kapsimali et al., de novo gene mutations also provides valuable and necessary tools for the addiction research field.A much less tapped area in ncRNA research for the understanding of addiction of cocaine, or other substances of abuse, is the lncRNA; Wapinski and Chang, The complexity and abundance of ncRNA, especially lncRNA, mandate advanced non-traditional, large scale and high throughput transcript sequencing, and analysis. While microarray technology enjoys established base and proven utility, the next generation sequencing technology represented by RNA-Seq emerges as the future choice approach for the task because of its unbiased coverage of the entire transcriptome of the genome. In addition, RNA-Seq allows versatile experimental design for sequencing depth and adjustable detection sensitivity, using machines of different throughputs and multiplexing different numbers of samples on a sequencing lane. Furthermore, the inherited benefit of RNA-Seq (Mane et al.,"} +{"text": "The ninth author's name was spelled incorrectly. The correct name is: Leonidas Stamatatos.Additionally, the correct spelling of the name of the individual who provided SIL, mentioned in the SIL section of Methods, is Ralf Torsten-Pohl."} +{"text": "We report the development of an international registry for Neurodegeneration with Brain Iron Accumulation (NBIA), in the context of TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration), an EU-FP7 \u2013 funded project. This registry aims to combine scattered resources, integrate clinical and scientific knowledge, and generate a rich source for future research studies. This paper describes the content, architecture and future utility of the registry with the intent to capture as many NBIA patients as possible and to offer comprehensive information to the international scientific community. Rare mendelian disorders are being characterized with increasing success owing to the rapid development of tools for defining phenotypic and genetic determinants. The elucidation of disease pathogenesis may simultaneously trigger the identification of pathway-specific treatment targets, but the development of disease-modifying medications is often hampered by the fragmentation of efforts and the low number of available patients. The integration of scattered resources is, therefore, crucial for the success of future scientific accomplishments. Here we report the inception of a central data repository for a group of rare disorders collectively called Neurodegeneration with Brain Iron Accumulation (NBIA).6 and consists of several genetically-defined entities that clinically often overlap but also have unique features manages links to the deferiprone trial database, the NBIA image archive and biobank. The collected information includes demographics, family and patient history, clinical signs, neurological exam, laboratory results, brain iron assessment and volumetry by imaging, treatments and trials. The disease course is captured by standardized scales measuring dystonia severity, quality of life and sleep, functional independence, cognition, motor functioning and activity of daily living. The annually entered information enables a longitudinal reconstruction of the disease course, while genomic, transcriptomic, proteomic and metabolomic data from research on the biobank specimens contribute additional dimensions to the registry.As a central data repository of TIRCON, the NBIA registry will be entered into the registry database. Together with these patient pseudonyms, codes identifying biospecimens, images, and data in the deferiprone trial database are kept in the registry and safeguarded by a sophisticated security and privacy architecture.The registry\u2019s security and privacy concept builds upon the security architecture of the German mitoNET repository , which For the use of data and biosamples, agreements have been specified and approved by local ethics committees and data protection authorities. Future research proposals will be reviewed by the TIRCON\u2019s Scientific Steering Committee (SSC). If the proposal is approved, pseudonymous or anonymous data will be released to the future investigator, depending on the proposal and the vote of the SSC. As an additional safeguard, re-identification attempts are prohibited by the data use agreements.In summary, this registry longitudinally collects multi-dimensional information on NBIA disorders to provide a rich resource for future natural history studies, evaluations of clinical and paraclinical surrogates or potential predictors of the disease, and correlation analyses of clinical subentities with pathogenic mutations, alleles of disease modifying genes, results of \u201c-omics\u201d and environmental factors. It will support the design of placebo-controlled, randomized, double-blind clinical trials, and allow probing which clinical, imaging or laboratory features of the disease may be modified by a treatment modality. The NBIA registry represents a paradigm fostering integration of international resources for the enhancement of scientific synergism and future research activities in a group of rare diseases.Methods of Information in Medicine, the International Journal of Medical Informatics, it \u2013 Information Technology, and Informatics. He serves on the Scientific Advisory Board of OFFIS, Oldenburg, and he has served for the Austrian Accreditation Council. He receives funding from BMBF grants 01 GM 1113C, 01 KN 1104, 01 EX 1020 E, Z76010067200, 80005012, and EU grants 284209, 277984; Ronald Lautenschlaeger \u2013 Receives personal compensation from TMF e.V.: Umbrella Organization for Networked Medical Research in Germany; Dr. Thomas Klopstock - Has received research support from government entities and from commercial entities ; Has been serving on scientific advisory boards for commercial entities and for non-profit entities . He has received speaker honoraria and travel costs from commercial entities . He has been doing consultancies for the Gerson Lehrman Group, USA, and has been serving as a Section Editor for BMC Medical Genetics from 2011. Other co-authors declare that they have no competing interests.Dr. Bernadette Kalman \u2013 Received travel support and honoraria for giving lectures on MS from Biogen-IDEC and Novartis; Serves as an Associate Editor for BMC Neurology; Received research grants from the NMSS and EMD Serono in the past; Dr. Klaus Kuhn - serves/has served on the Editorial Boards of Bernadette Kalman: Drafted main part and created the final version of the manuscript, designed the clinical and scientific content of the registry.Ronald Lautenschlaeger: Implemented the content and participated in the design of the IT \u2013 architecture and data security concepts of the registry, reviewed and revised the manuscript.Florian Kohlmayer: Participated in the design of the IT - architecture and the data security concept of the registry, reviewed and revised the manuscript.Boriana Buechner: Reviewed and revised the manuscript.Tomasz Kmiec: Contributed to the content of the registry, reviewed and revised the manuscript.Thomas Klopstock: Principal investigator for TIRCON. Contributed to the content design of the registry, reviewed and revised the manuscript.Klaus Kuhn: Designed the IT - architecture and data security concept of the registry, drafted part of the manuscript, reviewed and revised the final manuscript."} +{"text": "Field trials are extremely important for all facets of research, breeding, and biotechnology. Tree physiology is distinctively different in greenhouses or growth chambers vs. field environments. Thus, results from non-field environments can be very misleading with respect to identification of promising biotechnologies and elite varieties. Large regulatory impediments to conduct of field tests of genetically modified (GM) trees will therefore tend to stifle scientific and technological development. This appears to be the case for genetically modified trees, where regulatory burdens to conducting field tests have grown in stringency in the USA and elsewhere in recent years ,2. Here,Information Systems for Biotechnology (ISB) maintainPopulus, Pinus, Eucalyptus, and Malus, with the first two accounting for approximately 60% of all field trials , Pinus, Ulmus (American elm), Prunus, Musa, Citrus, and Juglans. Forty field trials are being conducted by private companies, with ArborGen alone accounting for 36 of the 40 active field trials. Cornell University, North Carolina State University, Oregon State University, Purdue University, the United States Department of Agriculture (ARS) and the University of California, Davis are among the public institutions currently conducting field trials. One of ArborGen\u2019s field trials with cold tolerant Eucalyptus covers 197.2 acres. This is the largest current field trial in terms of acres and is being conducted in six different states. In terms of research objectives of current trials, marker genes dominate in terms of frequency of trials, with modification of wood quality the next most common objective.Currently, there are more than sixty field trials covering eleven different genera, with In the USA, transgenic trees are regulated in the same manner as agricultural crops , using rTM apples because of the color of their skin. The company has petitioned the Animal and Plant Health Inspection Service (APHIS) for deregulation of the product in the USA [A company known as Okanagan Specialty Fruits has taken the lead in the production of transgenic tree varieties produced by the insertion of cisgenes and intragenes . Non-bro the USA .Cold tolerant eucalyptus varieties were developed by ArborGen . The comA new two year pilot project has recently been announced by APHIS . Under t"} +{"text": "Despite increasing control measures, numerous parasitic and infectious diseases are emerging, re-emerging or causing recurrent outbreaks particularly in Asia and the Pacific region, a hot spot of both infectious disease emergence and biodiversity at risk. We investigate how biodiversity affects the distribution of infectious diseases and their outbreaks in this region, taking into account socio-economics , geography (latitude and nation size), climate and biodiversity . We show, among countries, that the overall richness of infectious diseases is positively correlated with the richness of birds and mammals, but the number of zoonotic disease outbreaks is positively correlated with the number of threatened mammal and bird species and the number of vector-borne disease outbreaks is negatively correlated with forest cover. These results suggest that, among countries, biodiversity is a source of pathogens, but also that the loss of biodiversity or its regulation, as measured by forest cover or threatened species, seems to be associated with an increase in zoonotic and vector-borne disease outbreaks. The Asia-Pacific region, and particularly Southeast Asia, is recognized as a hotspot for biodiversity Infectious disease (ID) incidence has clearly increased during recent decades et al.The increased interactions between humans and wildlife resulting from habitat fragmentation are also affected by changes in wildlife species richness and community composition. At the local level, a reduction in biodiversity may lead to an increase in the prevalence and transmission rates of certain vector-borne diseases as reviewed by Keesing The original level of biological diversity is also important to explain the overall richness of infectious diseases Here, we explored the effects of biodiversity on patterns of infectious disease richness and outbreaks in Asia-Pacific. We considered two predictions related to the diversity of infectious diseases and the number of infectious disease outbreaks. First, the richness of ID should increase with increasing biodiversity , supporting regionally the pattern observed globally by Dunn et al. www.gideononline.com), which contains information on the presence of human infectious diseases and occurrence of epidemics in each country. This source has regularly been used in comparative studies of pathogen diversity http://worldbank.org/ddp/home.do) included country area and population, per capita gross domestic product (GDP), per capita health expenditure, forested surface area and forest as a proportion of each country\u2019s total area. Data on bird and mammal species richness are from Bird Life International (http://birdlife.org/datazone/home) and the International Union for Conservation of Nature . Per capita healthcare expenditure and the number of diseases for which a survey has been conducted in a country (GIDEON) were used as measures of investigation effort. The increase in health expenditure through time is likely associated with an increase in surveillance detection and outbreak reporting. This information was obtained from the Total Economy Database (www.conference-board.org/data/economydatabase/). We restricted our analyses to 28 countries for which sufficient data were available using the package ade4 (version 1.5\u20132) implemented in the R freeware programming environment . Correlation analyses and PCA allowed the identification of highly correlated variables such as latitude and temperature, or evapo-transpiration and mean annual precipitation . This fiWe used general linear models (GLMs) using package lme4 implemented R 2.10 to explain disease richness and number of outbreaks as a function of our explanatory variables. In order to explain to explain the richness in infectious diseases, an initial model included the following explanatory variables : mean annual temperature, mean annual precipitation, bird and mammal species richness (in log), population size (in log), nation size (in log), number of surveys, GDP and health expenditure. These explanatory variables included the ones selected in the study of Dunn et al. A second initial model, in order to explain the total number of outbreaks, included the following explanatory variables: mean annual temperature, mean annual precipitation, bird and mammal species richness (in log), population size (in log), nation size (in log), number of survey, GDP, health expenditure and richness of infectious diseases. We added also two other variables that represent the importance of impacts on biodiversity, the number of threatened bird and mammal species and the percent forest cover of the country. Additionally, we separated the disease outbreaks into three types: total, zoonotic, and vector-borne, and modelled each category. Selection of the best models was done using a step forward procedure based on AICc criterion. Initial and intermediate models are given in In order to illustrate graphically the effects of patterns of biodiversity and biodiversity loss on the richness and total number of outbreaks, we used the residuals of the selected regression models.The best model showed that the richness of infectious diseases is positivey linked to temperature (i.e. climate), population size and richness in bird and mammal species see . A countUsing the GIDEON data base, and over the period from 1950 to 2008, 124 different diseases with epidemics were identified in Asia-Pacific countries. An increase in both the number of outbreaks and the number of different diseases causing outbreaks through time was observed .Three models were created to explain the number of total infectious diseases, the total number of zoonotic infectious diseases and the total number of vector-borne diseases with outbreaks and the occurrence of epidemics in order to investigate different scenarios for the effects of changes in biodiversity on infectious risks File S1(DOC)Click here for additional data file.File S2(DOC)Click here for additional data file."} +{"text": "India has made appreciable progress and continues to demonstrate a strong commitment for establishing and operating a disease surveillance programme responsive to the requirements of the International Health Regulations (IHR[2005]). Within five years of its launch, India has effectively used modern information and communication technology for collection, storage, transmission and management of data related to disease surveillance and effective response. Terrestrial and/or satellite based linkages are being established within all states, districts, state-run medical colleges, infectious disease hospitals, and public health laboratories. This network enables speedy data transfer, video conferencing, training and e-learning for outbreaks and programme monitoring. A 24x7 call centre is in operation to receive disease alerts. To complement these efforts, a media scanning and verification cell functions to receive reports of early warning signals. During the 2009 H1N1 outbreak, the usefulness of the information and communication technology (ICT) network was well appreciated. India is using ICT as part of its Integrated Disease Surveillance Project (IDSP) to help overcome the challenges in further expansion in hard-to-reach populations, to increase the involvement of the private sector, and to increase the use of other modes of communication like e-mail and voicemail. With the adoption of the International Health Regulations [IHR(2005)] by the World Health Organization (WHO), it has become obligatory for the Member States to put in place requisite manpower, money and material to comply with the provisions of the regulation. Each signatory country is expected to achieve identified capabilities, including developing and maintaining core capacities to detect and respond to potential public health emergencies of international concern (PHEIC) within its national borders. Use of modern tools of communication and international technology has helped to scale-up the rapid sharing of data.For rapid detection and response to any outbreak, natural or deliberate, a sensitive surveillance system is essential. A good communication system is the \u2018brain\u2019 of the surveillance system. It is the speed of communication which is most critical to contain or stamp out an outbreak, save lives, and prevent misery. It is challenging, however, to set up an effective communication system, and even more so in a country as large, populous, and technologically and linguistically varied as India.India, with an estimated population of 1.15 billion in 2010, supports almost one fifth of world\u2019s population on only about 2.5 percent of its surface area . This evThe Union Ministry of Health & Family Welfare adopted an Integrated Disease Surveillance Project (IDSP) to connect all district hospitals and state-run medical colleges to facilitate tele-education, training of health professionals and monitoring of disease trends. The disparity between states\u2019 urban and rural regions is bridged using modern information and communication technology (ICT). The goal of this World Bank-assisted project (USD 102 million), is to establish a decentralized, state-based disease surveillance system. The project aims to detect early warning signals of impending disease outbreaks and initiate effective and rapid health actions with the help of ICT at the district, state and national levels. The project is implemented through the Central Surveillance Unit within the National Centre for Disease Control (NCDC) at New Delhi .The IDSP is being strengthened to make it compliant with IHR(2005) requirements by supporting a nationwide effort for the immediate reporting of outbreaks. The establishment and operation of decentralized surveillance system meeting performance standards, with technical support from the WHO and the U.S. Centers for Disease Control and Prevention (CDC) in the areas of disease surveillance and outbreak investigations, health informatics, and laboratory-based surveillance, has been vital in implementation of IHR(2005). Several specific steps have been taken to:1) enhance the quality and frequency of use of communication network;2) further training for district level epidemiologists and data managers on use of portal;3) streamline the urban surveillance component;4) enhance networking of infectious disease hospitals;5) improve quality and timeliness of reporting.Some of the key components of the IDSP in India include:\u2022 Integration and decentralization of surveillance activities through establishment of surveillance units at national, state and district levels;\u2022 Human Resource Development through training of State Surveillance Officers, District Surveillance Officers, multi-disciplinary Rapid Response Teams, and other medical and paramedical staff on all aspects of disease surveillance;\u2022 Use of ICT for the collection, collation, compilation, analysis and dissemination of data through a web portal;\u2022 Strengthening of public health laboratories.In addition to monitoring diseases like vector borne infections, diarrhoeal diseases, respiratory diseases, and vaccine preventable diseases, the IDSP also has a category called \u2018unusual clinical syndromes,\u2019 which would alert public health professionals to an intentional release of any biological-agent. The local governments in each state have the option to add any other health condition to the list as deemed appropriate. The ICT network is then used for the collection, analysis, and rapid communication of data.Eight hundred sites have been identified to be part of an ICT satellite network. Sites include District Headquarters (604), State Headquarters 35), academic institutions like Government Medical Colleges (133), premier medical institutions (15) and Infectious Disease Hospitals (7). At the national level these are connected to the National Informatics Centre, the Central Surveillance Unit (at the NCDC) and the Ministry of Health & Family Welfare. [, academiThe India Space Research Organization (ISRO), through its Education Satellite (EDUSAT), has connected 360 of the 400 ICT network sites. The network operation centre is housed at the NCDC, and the Satellite Interactive Terminals (SITs) are located at State Headquarters, District Surveillance Units and Government Medical Colleges. ISRO connects all sites in northeastern states, hilly and island states, Tamil Nadu, Gujarat, and Maharashtra. The National Informatics Centre (NIC) has provided terrestrial (broadband) connectivity to 776 of the 800 sites. It has also provided high-end video conference equipments at all state and Union Territory headquarters. Upon completion, the network will enable 800 sites on a broadband network of which 400 sites will have dual connectivity with satellite and broadband ,6.http://www.idsp.nic.in) with options for data entry and analysis from the district level upwards related to disease surveillance. It is quicker, easier, and more powerful to update than print-based media. The portal can also convert data into charts and graphs. The data entry operators and data managers have been trained in data entry, analysis and transmission. The portal also has information on media and outbreak alerts.The NIC has created a single-stop web portal .The telecommunication industry is one of the fastest growing industries in India. The total telephone subscription base is approaching 600 million . The oveData is collected and reported on a weekly basis under the IDSP. When health workers at sub-centres suspect a case, they fill out Form-S (suspect case). The doctors at Primary Health Centres, Community Health Centres and Hospitals fill form P (probable case/presumptive case). The cases that are confirmed by the laboratory fill up Form L (lab-confirmed case). Data managers receive these completed forms from various centres, and data compilation and analysis is done at the district, state and national levels. Cases representing and unusual or rising trends are investigated by a Rapid Response Team (RRT) to diagnose and control the outbreak. Major hospitals and Infectious Disease Hospitals are also required to report surveillance data. Eighty-five percent of all districts are now reporting weekly data to IDSP ,6.To ensure preparedness and enhance the quality of disease surveillance, regular video conferences are organized by central surveillance unit of IDSP to discuss outbreak investigations and verification and control measures with various State Surveillance Officers, District Surveillance Officers and the Rapid Response Teams. Additionally, project review and monitoring for different aspects of the IDSP is undertaken periodically. Video conferencing facilities are also used for training purposes ,6.For efficient functioning of the surveillance system training of various IDSP functionaries is an on-going process. Educational satellite (EDUSAT) classrooms are available at State Headquarters, District Headquarters, Medical Colleges, Premier Institutions and Infectious Disease Hospitals ,9. The cThe call centre received 35,000 calls related to H1N1. The video conferencing facilities were used for training of medical officers in clinical management, infection control practices and laboratory support. The network also facilitated prompt receipt of test results.Appreciable progress has been made in putting together the infrastructure and development of skills to make the ICT network functional in disease surveillance programme. As previously mentioned, 776 out of 800 sites have been networked, 738 sites have videoconferencing facilities, about 850,000 sub-centres send weekly report on syndromes, about 150,000 Primary Health Centres, Community Health Centres, and hospitals send list of probable cases. Facilities for distance education have also been established. There are other areas which still need to be addressed, including encouraging private sector reporting, strengthening skills for data use and analysis at all levels, enhancing the convergence of information and communication technology with other national health programmes, improving media scanning and verification, and making data transmission all-inclusive by incorporating, mobile, text, voice, email and fax.CDC: Centers for Disease Control and Prevention; EDUSAT: Education Satellite; ICT: Information and Communication Technology; IDSP: Integrated Disease Surveillance Project; ISRO: Indian Space Research Organization; NCDC: National Centre for Disease Control; NIC: National Informatics Centre; PHEIC: Public Health Emergencies of International Concern; SIT: Satellite Interactive Terminals; WHO: World Health Organization; IHR: International Health Regulations.The authors declare that they have no competing interests.LK: developed the concept, drafted and finalized the manuscript. SKK: provided information, revised the manuscript.Both authors read and approved the manuscript."} +{"text": "There is a dearth of evidence regarding the impact of urban regeneration projects on public health, particularly the nature and degree to which urban regeneration impacts upon health-related behaviour change. Natural experiment methodology enables comprehensive large-scale evaluations of such interventions. The Connswater Community Greenway in Belfast is a major urban regeneration project involving the development of a 9 km linear park, including the provision of new cycle paths and walkways. In addition to the environmental improvements, this complex intervention involves a number of programmes to promote physical activity in the regenerated area. The project affords a unique opportunity to investigate the public health impact of urban regeneration.The evaluation framework was informed by the socio-ecological model and guided by the RE-AIM Framework. Key components include: (1) a quasi-experimental before-and-after survey of the Greenway population , in tandem with data from a parallel Northern Ireland-wide survey for comparison; (2) an assessment of changes in the local built environment and of walkability using geographic information systems; (3) semi-structured interviews with a purposive sample of survey respondents, and a range of community stakeholders, before and after the regeneration project; and (4) a cost-effectiveness analysis. The primary outcome is change in proportion of individuals identified as being regularly physically active, according to the current UK recommendations. The RE-AIM Framework will be used to make an overall assessment of the impact of the Greenway on the physical activity behaviour of local residents.The Connswater Community Greenway provides a significant opportunity to achieve long-term, population level behaviour change. We argue that urban regeneration may be conceptualised meaningfully as a complex intervention comprising multiple components with the potential, individually and interactively, to affect the behaviour of a diverse population. The development and implementation of our comprehensive evaluation framework reflects this complexity and illuminates an approach to the empirical, rigorous evaluation of urban regeneration. More specifically, this study will add to the much needed evidence-base about the impact of urban regeneration on public health as well as having important implications for the development of natural experiment methodology. Most people in high income countries lead inactive lives, fuelling the rise in non-communicable diseases . PhysicaA review of gaps in the evidence for physical activity promotion highlighted a need for socio-ecological studies of community interventions . A systea priori hypotheses, clear definitions of target populations, explicit sampling criteria and the use of valid and reliable measures of outcomes [Given the scale, it is impossible for researchers to implement built environment interventions and therefore the use of natural experiments has often been the only option to evaluate the impacts of such interventions on health and wellbeing. Natural experiments are interventions that are not under the control of researchers, but often employ observational methods to understand the effects, compared to a control or comparison group . The metoutcomes .The aim of this study is to determine the impact of a systems-wide community intervention to promote physical activity in the context of a major inner city urban regeneration project.Specific objectives include evaluating:(i) The impact of a suite of community-based interventions to promote physical activity;(ii) The role of the local built environment, and of individual, community and organisational networks in sustaining change; and,(iii) The cost-effectiveness of this socio-ecological and systems-based approach to effecting physical activity behaviour change.The Connswater Community Greenway (CCG) is an exThe PARC Study is a before-and-after evaluation of the effects of the CCG on physical activity and health, and comprises of four main elements:1. A quasi-experimental before-and-after survey of the CCG population , utilising data from a parallel Northern Ireland-wide survey for comparison;2. Assessment of change in the local built environment and walkability using geographic information systems (GIS);3. Semi-structured interviews with 60 residents, and a range of community stakeholders before and after the regeneration project;4. A cost-effectiveness evaluation.The study has been approved by the Office for Research Ethics Committees, Northern Ireland (09/NIR02/66).A survey of a random selection of households will be conducted before-and-after the regeneration of the CCG. The target area was selected as 29 electoral wards identified during the development of the CCG project Figure\u00a0. The samThe survey content is informed by, and reflects the various levels of, the socio-ecological model comprising measures of individual, community and environmental factors Figure\u00a0. The priOutcomes which may moderate/mediate the relationship between changes in the built environment and physical activity will be assessed. These include (i) perceptions of the characteristics of the environment associated with active travel and physical activity, including aesthetics, safety and walkability - a \u201cwalTo control for the possible influence of weather patterns on physical activity, data for the seven days preceding interview will be collated from the nearest weather station via the UK MET office. This will include daily rainfall, hours of sunshine, minimum and maximum temperature and wind speed.In addition to participating in the household survey, a randomly selected sub-sample of 100 residents will be invited to wear an Actigraph GT3X accelerometer at both time points (before and after CCG construction) to provide an objective measure of physical activity for comparison with self-reported questionnaire data (GPAQ). Participants will be asked to wear the accelerometer from the time they wake-up to the time they go to bed, for seven consecutive days. Standard cut-off values for moderate and vigorous physical activity will be used to calculate total minutes of moderate and vigorous physical activity per week .Comparison data will be drawn from Northern Ireland-wide surveys of physical activity in approximately 4,000 randomly selected individuals from the general population at the same two time points . This wiThe sample size was estimated using the same method as Cochrane et al. , based o2 test. Multinomial logistic regression will be used to test a prediction model for categories of change in physical activity by area/age/income bracket, allowing a comparison of odds ratios for the various categories of physical activity by area [Area-by-category classifications of change in the proportion of the population meeting the physical activity guidelines will be compared by cross-tabulation and the difference in distributions assessed for statistical significance using the \u03c7 by area . A key sIn addition to the household survey, a comprehensive process evaluation, informed by the socio-ecological model, will be conducted before and after CCG construction Figure\u00a0.A purposive maximum variation sample of 60 households representing varying distance from the Greenway, and individuals of a range of age, gender and socio-economic position (SEP) will be selected and invited to participate in detailed semi-structured interviews. Participants will be identified from respondents to the household survey. The interviews will explore the effects of key determinants on physical activity behaviour. Specific topics will include (i) perceptions of own health, its determinants and lifestyle behaviours, (ii) perceptions of the barriers and facilitators to healthy lifestyles, (iii) effects of local environment on behaviours, motivation and personal health, (iv) knowledge of the Greenway and related local health promotion initiatives, and (v) perceptions of the quality of the local environment, including safety issues and expectations from the urban regeneration. The same participants will be interviewed at two time points, pre and post CCG construction. The qualitative data emerging from this series of interviews will add richly to the explanatory power of our quantitative data .Physical activity intervention design and implementation can benefit from meaningful participation of the community and relevant agencies. Focus groups (n=14) will be conducted with community stakeholders utilising the networks and knowledge of local community agencies. This collaborative approach will facilitate purposive sampling to recruit adults for the focus group discussions representing the diverse population of the study area . Topics explored will include engagement in physical activity, barriers and facilitators to physical activity in the local area, views on local facilities and opportunities for physical activity and the perceived usefulness of the proposed Greenway to encourage local residents to be more active. Focus groups will be audio-recorded and data will be analysed using a mixture of text-based content analysis and thematic analysis ,37.The sustainability of any efforts to support behaviour change at both individual and organisational levels will depend on the strength and empowerment of the community and inter-organisational networks. An assessment of the processes that facilitate or inhibit the effective implementation of the intervention strategy will form an integral part of the overall design . The evoIn order to examine the specific influence of changes to the built environment, GIS data of the environmental features in the area at the finest available spatial level pre- and post-regeneration will be collected. This will include mapping of the footpath network across the study area, topography, transport features, physical activity opportunities, for example, green space, local amenities, parks, using a mix of aerial photography, and checked using open source spatial data and aerial photography. The network will be tested and validated by peer checking of mapped elements and ground-truthing to assure its quality. The development and validation of the Real Walkable Network will be the subject of a future publication. These data will be used to revise the \u201cwalkability index\u201d for a 500 m and 1000 m buffer zone around the household of each respondent to the household survey. Analysis will include an assessment of the changes in walkability of the neighbourhoods and the influence of distance decay (exposure to the regeneration project) on physical activity behaviour. We will also map and describe individual household level change in objectively measured accessibility to the regenerated, environmental physical activity opportunities and examine the association between change to the built environment and change in physical activity and other health-related outcomes.Direct observation of usage of the Greenway will be conducted in two ways: (i) conducting before-and-after Intercept Surveys of CCG use (at four locations on the Greenway), adapting SUSTRANS methodology; (ii) employing the SOPARC (System for Observing Play and Recreation in Communities) methodology, a validated technique to assess the use being made of green space and parks in the area before and after the construction of the CCG . We willFurther, effective mechanisms are in place to collect information to assess the reach, \u2018dose\u2019 and fidelity of intervention implementation and of the resources used. The Belfast Health and Social Care Trust and the East Belfast Community Development Agency will collect core data on the number of people enrolling and completing various physical activity promotion initiatives in the CCG area.During the construction of the Greenway, aspects of local or regional transport infrastructure and policy may change, with implications for the active travel behaviour of local residents. Changes will be monitored using routinely available information, including bus timetables and traffic survey data collated by the Department for Regional Development (DRD). The latter will yield comparative information on average annual distances travelled by all forms of transport and access to and use made of public transport. DRD also collects routine information on bicycle use via electronic monitors dispersed throughout the city. In addition, effects on road traffic accidents will be monitored using routinely available statistics, compiled by the Police Service of Northern Ireland (PSNI). The effect of the urban regeneration on tenancy turnover rates, the quality of local social housing stock, and crime statistics in the target area and in neighbouring areas will also be monitored using Northern Ireland Housing Executive and PSNI data respectively.Conducting an economic evaluation of environmental interventions that promote physical activity is fraught with methodological difficulties and multiple approaches have been recommended . FirstlyReach, Effectiveness, Adoption, Implementation and Maintenance of any changes wrought by the regeneration [The RE-AIM Framework will be used to make an overall assessment of the impact of the Greenway on the physical activity behaviour of local residents, so that we have a clearer understanding of the neration ,48. ThisA major urban regeneration project has afforded a unique opportunity to evaluate a \u2018real world\u2019 natural experiment. The CCG is a complex intervention with multiple interacting components affecting a diverse population. Many challenges must be overcome in the development and implementation of an evaluation of such an intervention, requiring both methodological innovation and development.In response to the Foresight report and WanlThe RE-AIM Framework has been used to guide the evaluation of interventions that address the different levels of the socio-ecological model, including individual, community, organisational, and population level. King and colleagues have refA comprehensive evaluation framework has been developed by a multi-disciplinary research team comprising of academics from public health, economics, sociology, psychology, statistics and spatial planning. The research team has actively engaged with the local community partnerships, city council, health practitioners and a variety of government departments in planning the evaluation framework. Previous research suggests that building meaningful partnerships of diverse communities can improve health outcomes . The PARCCG: Connswater Community Greenway; DRD: Department for Regional Development; EAPRS: Environmental Assessment of Public Recreation Spaces; EQ-5D: EuroQol-5D; GIS: Geographic Information Systems; GPAQ: Global Physical Activity Questionnaire; ICER: Incremental Cost-effectiveness Ratio; PAF: Postcode Address File; PARC: Physical Activity and the Rejuvenation of Connswater; PSNI: Police Service of Northern Ireland; RE-AIM: Reach, Effectiveness, Adoption, Implementation, Maintenance; SEP: Socio-economic Position; SF-8: Short Form 8 Health Survey; SOPARC: Systems for Observing Play and Recreation in Communities; SportNI: Sport Northern Ireland.The authors declare that they have no competing interests.All authors contributed to the development of the study protocol and to the critical revision of the paper and approved the final version. FK had the original idea for the study and led the design of the study and the application for grant funding. MT, HMcA, GE, GH, LP, MD, MS, and MC (co-investigators) contributed to the design and writing of the original protocol and funding application. RH and MT wrote the first draft of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/774/prepub"} +{"text": "In silico methods are used in genome studies to discover putative regulatory genomic elements . Although a number of methods have been developed for motif discovery, most of them lack the scalability needed to analyze large genomic data sets.An important focus of genomic science is the discovery and characterization of all functional elements within genomes. word space and (2) scores words with a distributed Markov chain model.This manuscript presents WordSeeker, an enumerative motif discovery toolkit that utilizes multi-core and distributed computational platforms to enable scalable analysis of genomic data. A controller task coordinates activities of worker nodes, each of which (1) enumerates a subset of the DNA Arabidopsis thaliana; the results of the analysis were integrated into The Arabidopsis Gene Regulatory Information Server (AGRIS). A public version of WordSeeker was deployed on the Glenn cluster at the Ohio Supercomputer Center.A comprehensive suite of performance tests was conducted to demonstrate the performance, speedup and efficiency of WordSeeker. The scalability of the toolkit enabled the analysis of the entire genome of WordSeeker effectively utilizes concurrent computing platforms to enable the identification of putative functional elements in genomic data sets. This capability facilitates the analysis of the large quantity of sequenced genomic data. The importance of discovering the patterns and features in genomic sequences is motivated by a number of scientific contexts. The Encyclopedia of DNA Elements project (ENCODE) seeks \u2018to identify all functional elements in the human genome sequence\u2019 . Anotherwords) or sets of related substrings in DNA sequences. Most enumeration methods create a data representation of the input sequence(s) that provides fast retrieval of elementary word statistics. The representation serves as a central data structure for a number of other analyses, including statistical word scoring, word-clustering, and motif discovery. A number of algorithmic techniques for word space enumeration have been proposed. Each of the enumeration algorithms can be classified as either index-based range.Figure Figures Speedup and efficiency experiments were performed to assess in detail the scalability and the performance boundaries of the WordSeeker implementation. Figures The speedup and efficiency results show a drop in performance for very short words (5bp) and for very long words, (50bp and 75bp), but yield good results for word lengths of 10bp and 20bp. The performance drop for short word lengths occurs because the parallelization overhead outweighs the computational benefit; for longer word lengths, cache inefficiency and front-side bus contention cause performance to decrease (see for a deWordSeeker is a general purpose, scalable, open source approach to word enumeration. It supports an important set of use cases, has been applied to interesting case studies, and effectively exploits parallel and distributed computing hardware to provide scalable performance.WordSeeker is being used currently to perform complete word space enumerations on a genomic scale; to construct word and motif encyclopedias for whole genomes; to perform word-based characterizations of pathways, tissues, and co-regulated genes; and to identify motifs in ChIP-Seq data. Ongoing work includes the construction of OpenMotif, a project that combines a number of motif discovery open source projects into a cohesive framework.ENCODE: Encyclopedia of DNA Elements; DNA: Deoxyribonucleic acid; AGRIS: The Arabidopsis Gene Regulatory Information Server; UTR: Untranslated Region; ChIP-chip: Chromatin Immunoprecipitation with microarray technology; ChIP-Seq: Chromatin Immunoprecipitation with massively parallel DNA sequencing; OWEF: Open Word Enumeration Framework; MPI: Message Passing Interface; A, C, G, T: Adenine, Cytosine, Guanine, Thymine; RAID: Redundant Array of Independent Disks.The authors declare that they have no competing interests.JL contributed to the design, implementation and validation of the algorithms and models, the generation of the results and the writing of this document. KK, LN, LJN contributed to the development and implementation of the models and algorithms and the generation of the results. XL, RA contributed to the generation of the results. JDW, EJ and TB contributed to the development and implementation of the models and algorithms. KE and SSL contributed to the development of the models and algorithms. LE contributed to the development of the biological models. In addition to conceptualizing the architecture employed in this research, FD and LRW contributed to the design and validation of models and algorithms, and to the writing of this manuscript."} +{"text": "The health system in India suffers from low level of public spending and high out of pocket payment. Public health facilities are funded on a fixed and uniform basis irrespective of their needs and performance. The National Rural Health Mission has introduced an innovative approach of flexible financing to public health facilities under Untied Funds (UF), Annual Maintenance Grant (AMG) and Aarogya Raksha Samithi Corpus Funds (ARS). Funds are currently allocated @ of INR 10000 at village level, INR 20000 at subcentre level, INR 175000 at Primary Health Centre, INR 250000 at community health centre and INR 500000 at district hospital level. Though funds are allocated to health facilities with adequate guidelines and flexibility, utilization of these funds is poor. Given the limited resource available for healthcare in the country, there is a need to rationalize the distribution of funds and allocate them efficiently. We undertook a study to propose a differential financing model for public health facilities.We conducted a cross sectional study of 46 primary and secondary level facilities in two districts of Karnataka in the year 2011-12. Retrospective data on resources, finance and performance of 2008-09, 2009-10 and 2010-11 were collected. In addition, interviews were conducted with members of ARS committee responsible for taking decisions on utilization of funds.The study found that utilization of funds in health facilities are influenced by several factors. These included per-capita allocation, distance from district headquarter, availability of equipment and infrastructure.We observed that there was no definite trend of impact of availability of human resources, number of beds, staff residing at the facility compound, training, cooperation among members and availability of guidelines on utilisation of funds at health facilities.The study strongly advocates the need for a more rational and systematic planning for utilization of funds allocated to health facilities taking into consideration other health system constraints. The study proposes a formula for allocating funds on differential financing method: at the village level committee at INR 10 per-capita, at the sub-centre level at INR 4 per-capita, for primary health centre at INR 6 per-capita, at the level of community health centre at INR 1.04 per-capita and at INR 4167 per functional bed and the current norm of INR 500000 per district hospital. Such a model would result in efficient utilization of funds, leading to better of quality of delivery of services.None declaredThe study was funded by the Karnataka State Health System Resource Centre, Bangalore and the Centre for Budget and Policy Studies, Bangalore."} +{"text": "AbstractPossibilities of the assessment of a landscape with the use of succession development stages, monitored with the value of the Mean Individual Biomass (MIB) of carabid beetles and the occurrence of bird species are discussed on the basis of an example from Poland. Higher variability of the MIB value in space signifies a greater biodiversity. Apart from the variability of MIB, it is suggested to adopt the occurrence of the following animals as indicators, (in the order of importance), representing underlying valuable landscapes: black stork, lesser spotted eagle, white-tailed eagle, wolf, crane and white stork. The higher number of these species and their greater density indicate a higher value of the landscape for biodiversity and ecosystem services, especially carbon sequestration. All these indicators may be useful to assess measures for sustainable land use. As part of the ongoing discussion on the sustainable use of landscapes and ecosystem services we give here an overview on the relationship between biodiversity and carbon sequestration in forests as revealed by a long-term study in north-western Poland with particular reference to carabid beetle diversity.From the very beginning of life, environmental resources on Earth have been shaped by natural succession processes, influenced by climate, and by various disturbances such as orogenic movements, windfall, floods and fires. Depending on latitude and the geological base, these disturbance factors vary among various places on the globe. The lack of catastrophes entails the buildup of organic substances, which can be measured simply with the content of carbon. The content of carbon in a single hectare of natural forest of the moderate climatic zone shaped by succession processes for thousands of years, exceeds 350 tons/ha with upper limits estimated between 500 and 700 tons/ha . Half ofCaprimulgus europaeus), skylark (Alauda arvensis), northern dune tiger beetle (Cicindela hybrida) and, with the appearing pine wilding, the sticky bun (Suillus luteus) can strive (PageBreakPageBreakIn such old forests (old ecosystems created by nature), ecosystems have a specific composition of plant, animal and fungal species. Species that are linked to old trees, old decaying wood, and well developed soil, occur here . In suchn strive . The cren strive . Such spn strive .Camprimulgus europaeus) and woodlark (Lullula arborea) would have had no place to nest and the majority of birds of prey nesting in old trees would not have been able to hunt. Carabid beetles like Carabus nitens, Bembidion nigricorne, Pterostichus lepidus, Calathus erratus, Masoreus wetterhallii and Harpalus rufitarsis would not have occurred in this region (Suillus luteus), sulfur tufts (Hypholoma fasciculare) or, slightly later, chanterelles (Cantharellus cibarius) and porcinis (Boletus edulis) would not have been possible (PageBreakPageBreak(about 250 mg) is higher compared to a young pine plantation (Fringilla coelebes), great tit (Parus major) and coal tit (Parus ater). Carabids characteristic for this stage of succession include Carabus arcensis, Carabus nemoralis and Pterostichus niger and the most frequent and numerous fungi include the sickener (Russula emetica), brown roll-rim (Paxillus involutus), false morel (Gyromitra esculenta) and the cauliflower mushroom (Sparassis crispa). The planting of beech as undergrowth in ca. sixty year old pine stands followed by the removal of the pines ten years later results in the creation of beech stands, several of which in Poland are about eighty years old (Drycopus martius), stock pigeon (Columba oenas) and chaffinch (Fringilla coelebes). Characteristic carabids include Carabus coriaceus, Carabus hortensis and Carabus intricatus. Characteristic fungi are the dotted stem bolete (Boletus erythropus), fleecy milk-cap (Lactarius vellereus) and the death cap .Humans play a similar role in shaping ecosystems and landscapes. Ecological catastrophes can destroy the effects of our economic activities and constitute a danger our its safety. This is why humans manage the environment by trying to reduce floods, fires and windfalls. However, to preserve the full range of biodiversity, humans replace the forces of nature and mimic its destructive role by active management. This can clearly be illustrated for forests in Poland. If it was not for the interference with natural succession and the reduction of the carbon content of up to a few dozen tons per ha due to cs region . Additiopossible . The despossible , carbon antation . The speears old , Fig. 4cCiconia nigra) and the lesser spotted eagle (Aquila pomarina) and the wolf (Canis lupus) (Grus grus) and white stork (Ciconia ciconia) . These bs lupus) . The exiciconia) . Cranes in space . In lighin space .Landscape quality includes biodiversity (highest in mosaic landscapes) and carbon storage (highest in peat bogs and old forests) and sequestration (highest in regenerating forests), as well as other ecosystem services. Sustainable land use is essential in maintaining or creating landscapes with high natural qualities. There is a need to assess measures of sustainable land use, and various animals mentioned in this paper, including carabid beetles and their MIB values, may serve as important indicators for this."} +{"text": "Natural product medicine (NPM) has been used to prevent and treat various human diseases in China, India, Japan, and other countries for centuries. Due to its long historical clinical uses and excellent therapeutic efficacy, NPM more and more attracts global attention, and many research institutes and pharmaceutical companies have been actively exploring NPM as a source for new drug discovery and development . HoweverWith the development of globalization and modernization of NPM, an important issue is the consistency and control ability of quality of NPM. Traditionally, identification of NPM is performed according to its morphological character, one or a few markers' thin-layer chromatography identification, and/or content determination , 4. HoweThe characteristics of action of NPM are synergistic action of multicomponents and multitargets . By a coIn this special issue of quality control of NPM and nutrient supplements, 15 research papers have been published by the previously mentioned chromatographic or spectroscopic methods and contributed to quality control of NPM. These papers focused on the quantification analysis of multiple chemical components, bioactivity and their mechanism of actions of chemical components, and pharmacokinetics and tissue distribution studies.Evodia rutaecarpa has been completed by HPLC-DAD method. The results indicated that the quality control of Evodia rutaecarpa could be simplified to the measurement of four constituents and that limonin, 1-methyl-2-undecyl-4(1H)-quinolone, and dihydroevocarpine should also be served as the chemical markers together with evodiamine for the quality control of Evodia rutaecarpa.Firstly, multicomponents determinations play a critical role in evaluating the quality of NPM and understanding the synergistic action of multicomponents and multitargets. Multicomponents quantitative methods of NPM were reported in this special issue. Among the analytical methods for NPM, HPLC with easy operation, high accuracy, and wide suitability is still the most popular method for the qualitative and quantitative analyses of NPM. For example, simultaneous quantification of limonin and six alkaloids in in vitro or in vivo experiments in this special issue. Secondly, active components of NPM should be clarified by different methods in order to achieve better quality control of NPM and nutrient supplements. The bioactivities of pure compounds or crude extract form NPM have been evaluated by Last but not least, with the development of pharmacy, more and more researchers focus their attention on pharmacokinetics in drug discovery. Pharmacokinetics including absorption, distribution, metabolism, and excretion is regarded as the foundation of new drug discovery. Pharmacokinetics encompasses a broad spectrum of experiment and connotation. Five articles devoted to pharmacokinetics and identification of metabolites from pure compounds or crude extract of NPM. The complexity of single herbs or compound preparations causes diverse pharmacokinetics, and these articles provide key information for researchers in the future studies.All in all, the published research papers will contribute to the development, improvement, validation, and/or extension of application of analytical methodology in the natural medicine sciences and nutrition supplements. Quality control of NPM has to establish reasonable analytical methods for analyzing the active constituents in NPM in order to clarify their therapeutic basis and mechanism of action more clearly. Shuang-Qing ZhangShuang-Qing ZhangFeng WeiFeng WeiYu-Ming FanYu-Ming FanFeng SunFeng SunYing-Yong ZhaoYing-Yong ZhaoShuhua BaiShuhua Bai"} +{"text": "Coronary heart disease (CHD) is the leading cause of death. As the main treatment of CHD, modern medicine has improved dramatically in recent years. Although researches of TCM and integrative medicine on CHD are witnessed encouraging progress in many respects, the role TCM playing in the prevention and treatment of CHD has been unprecedentedly challenged under such circumstance of the very fast development of modern medicine. In order to share mutual complementary advantages of TCM and western medicine, this review summarizes the relatively prominent researches of TCM and integrative medicine on CHD in recent years, and illuminates the issue of the orientation of the further research of integrative medicine on CHD, including (1) original innovation of TCM etiology and pathogenesis, (2) combination of disease and TCM syndrome, (3) biological basis of TCM syndrome of CHD, (4) clinical design and quality control of integrative medicine research, (5) herb-drug interaction, (6) difficulties and hot issues of modern medicine. So far, there are so many researches of TCM and integrative medicine on CHD, however, with insufficient enhancement of clinical effectiveness. If the work on blood-stasis syndrome (BSS) is a milestone of TCM and integrative medical research on CHD, activating blood circulation by removing blood-stasis and its derived therapies have significantly improved the clinical effectiveness of TCM therapy on CHD , when co Combining disease with TCM syndrome is an important treatment model in TCM clinical practice. The theory of combining disease with syndrome reflects the principle of inheritance and innovation, which has been widely accepted by TCM and integrative medical practitioners for the advantages of scientificity and operability. Thus, it is the important breakthrough point of integrative medicine research on CHD. Previously, most of the TCM syndrome researches on CHD are cross-sectional studies focusing on syndrome distribution characteristics of CHD and different subgroups, which have made certain progress. Many results have shown that patients with CHD have the syndrome of asthenia in origin and asthenia in superficiality, and blood-stasis is the main syndrome element of CHD, followed by qi deficiency , 12. The It is worth mentioning that in the process of the occurrence, development, and prognosis of CHD, TCM syndrome is always in a dynamic change, so the research on the evolution law of CHD syndromes may help us understand the pathogenesis and prognosis of CHD in each stage or population and then improve clinical syndrome differentiation and treatment. But research in this field is still less and need to be strengthened. Mei et al. conducte\u03b3 are the possible marker proteins that might play crucial roles in the occurrence and development of BSS patients with CHD. Zhao et al. [\u03b2-hydroxybutyric acid, oleic acid, glucose, and alanine. The results showed that CHD-BSS is related with lipid metabolism, glycometabolism, as well as the stress induced by hypoxia and agonia. Applying various omics technologies, we can conduct researches in the holistic level, and provide strong technical support for the research on biological basis of TCM syndrome. Treatment based on syndrome differentiation is one of the characteristics and advantages of TCM in preventing and treating disease, but how to conduct syndrome differentiation exactly is the key to improve the clinical efficacy. The rapid development of modern medicine has provided technical support and good opportunity for the expansion and extension of the four methods of diagnosis of TCM and the organic combination of traditional macroscopic and modern microcosmic syndrome differentiation. In recent years, Chinese scholars have studied relevant factors affecting TCM syndrome differentiation of CHD and the biological basis of syndrome in the aspects of coronary artery lesion, cardiac function, changes in ECG, blood lipid, insulin resistance, homocysteine and inflammation factors, related gene, and so on . They hao et al. also appo et al. proposedo et al. found th In recent years, with the concept of evidence-based medicine (EBM) widely accepted, a number of multicenter, randomized controlled trials (RCT) with large sample focusing on the prevention and treatment of CHD have been carried out successively both in the fields of Chinese medicine and integrative medicine, for example, the randomized, double-blind, placebo-controlled trial on the effect of Xuezhikang (XZK) for regulating blood lipids and secondary prevention of CHD . The resStrengthen the top-level design of clinical trials and choose appropriate clinical research methods based on the clinical demands and research objectives. For most intervention studies, RCT including explanatory randomized controlled trial (ERCT) and pragmatic randomized controlled trial (PRCT) is usually the first choice. Recently, real-world study (RWS) , which iOutcome measures should be appropriate . Avoid mTrials are designed and conducted according to good clinical practice (GCP) principle. Strengthen the implementation of process management and quality control of clinical trials, such as the international registration of clinical trials, ethical approval, the third-party evaluation of end point, and data management, and reported trials in accordance with the consolidated standards of reporting trials (CONSORT) statement 2010 , in orde When conducting clinical trials of integrative medicine on CHD, we should pay attention to the following three points.If the combination of disease and syndrome is the integration of TCM and Western medicine in diagnostic level, then interaction of Chinese and Western medicine can be the practical problem we face in treating disease with integrative medicine. As the integrative medical model of patient-centered healthcare and combined application of botanical and chemical drugs evolving into a new trend of modern medicine in preventing and treating disease nowadays, the combined application of Chinese and Western medicine is increasing, and the potential interactions are drawing more and more attention .Herb-drug interaction has two meanings. One is the advantageous function of effect-enhancing and toxicity-reducing. CHD and other chronic noncommunicable diseases are often related to multiple risk factors, complex interventions, and multitarget treatment are more appropriate. Combination therapy with a TCM formula has been the feature and advantage of TCM. Some international scholars also proposed the concept of \u201cpolypill\u201d , which hhypericum perforatum, motherwort, ginseng, gingko biloba, salvia miltiorrhiza, garlic, and aconite, can possibly increase the risk of adverse events in patients with cardiovascular diseases by the interactions with other drugs, particularly in elderly patients who always consume multiple prescription medications in the same time for comorbidities [Another meaning of herb-drug interaction is the potential of increased risk of adverse reactions. International researches discovered that some botanical drug products including Chinese herbal medicine, such as bidities . In clinSo, herb-drug interaction is the issue that cannot be ignored in the research of integrative medicine on CHD. In clinical practice, doctors should notice the reference application of evidence-based medication , 49, pay Meanwhile, the firsthand material should be accumulated in routine clinical practice, as there is an important way to discover the meaningful clues of herb-drug interactions through the real-world data analysis. On this basis, design experiment scientifically, carry out the relevant studies involved in drug metabolism, pharmacokinetic, efficacy, toxicology, and the relevance of toxicity and efficacy, and conduct in-depth study of herb-drug interactions and their mechanism from drug absorption, distribution, transformation, metabolism, excretion, and so on.The development of modern medicine has brought new hope for the prevention and treatment of CHD. However, some new problems have unavoidably been presented, such as aspirin resistance (AR), restenosis after PCI, late thrombosis of drug-eluting stent (DES), the no-reflow phenomenon after revascularization, vulnerable plaque, contradiction of therapeutic angiogenesis, the viability and differentiation ability of transplanted cells when operating stem cell transplantation, and residual cardiovascular risk. These are still challenges which modern medicine has to face positively. Focusing on these key issues that influence the curative effect, we should give full play to the characteristics of TCM, complement each other's advantages of Chinese and Western medicine, and conduct researches scientifically.For instance, to the clinical problem of AR, we may screen potential Chinese herbals which have antiplatelet effect, then explore its material basis and active ingredients, illustrate the target point of drug action, find the lead compound, and optimize its structure. An effective Chinese herb with high-efficacy and low-toxicity will be of great significance in the prevention and treatment of cardiovascular disease. Some domestic scholars have recSalvia miltiorrhiza combined with bone marrow mononuclear cells autotransplantation through cardiac catheter to the model of myocardial infarction in swine, it promoted transplanted cell to survive, differentiate, and amplify, and many new myocardial cell and myocardial small vessel emerged. These facilitated the repair of damaged myocardial cells by synergies and complementing each other's advantages [Stem cell transplantation is also a hot issue. It may be a new dawn for the treatment of myocardial infarction, and its preliminary clinical study outcome was inspiring. A study indicatevantages and predIn conclusion, integrative medical research on CHD has made great development. Present studies shed light on the orientation of integrative medicine. From the progress of integrative medicine on CHD, in order to further complement each other's advantages of Chinese and Western medicine, researches should keep focusing research on original innovation of TCM etiology and pathogenesis, combination of disease and TCM syndrome, biological basis of TCM syndrome of CHD, difficulties and hot issues of modern medicine such as stem cell transplantation and strengthen clinical design and quality control of integrative medicine research. In addition, herb-drug interaction should not be ignored."} +{"text": "Background: Firefighters have a high probability of being exposed to a variety of traumatic events. Potentially traumatic events can occur during a single rescue such as: providing aid to seriously injured or helpless victims. Moreover, firefighters who are injured in the line of duty may have to retire as a consequence of their injury. The psychological cost of this exposure may increase the risk of long-term problems, such as post-traumatic stress disorder (PTSD) symptoms, depression, and anxiety. Objective: The purpose of this study was to investigate the prevalence of PTSD symptoms, depression, anxiety, and assess related variables such as coping strategies and social support among Saudi firefighters. Method: Two hundred firefighters completed the Fire-fighter Trauma History Screen (FTHS) to measure the number of traumatic events, Screen for Post-traumatic Stress Symptoms (SPTSS) scale to assess the prevalence of PTSD symptoms, Hospital Anxiety and Depression Scales (HADS) to assess depression and anxiety, Brief Cope (BC) scale to measure coping strategies used, and Social Support scale was used to evaluate the firefighter's support received. Results: The results showed that 84% (169/200) of firefighters were exposed to at least one traumatic event. The result presented that 57% (96/169) of exposure firefighters fully met the DSM-IV criteria for PTSD with high levels of depression and anxiety; 39% (66/169) partially met the PTSD criteria. However, only 4% participants have not met the PTSD criteria. The results also revealed that adaptive coping strategies and higher perceived social support was associated with lower levels of PTSD. Conclusion: The high prevalence rate of PTSD related to the type and severity of the traumatic events and years of experience in the job. Accordingly, many firefighters were severely affected by their experiences, and we should be developing methods to help them."} +{"text": "Salmonella-contaminated animal feed and their impact on public health. The workshop followed an article published in Clinical Infectious Diseases, which provided three recommendations to reduce human foodborne disease caused by Salmonella-contaminated animal feed on January 23, 2004, to discuss issues pertaining to Salmonella-contaminated feed, and data showing how contaminated animal feed contributes to human foodborne illness.A variety of organizations were represented at the workshop, including international government agencies, the United States Department of Agriculture (USDA), the United States Food and Drug Administration (FDA), and consumer groups. Speakers offered perspectives on bacterial contamination of animal feed, including examples of human illnesses traced to Salmonella in animal feed. Officials from the National Veterinary Institute of Sweden and the Norwegian Agriculture Inspection Service gave an overview of the control measures implemented in Sweden and Norway to ensure Salmonella-negative animal feed. Norway and Sweden have extensive surveillance programs for Salmonella control in animal feed. The measures implemented in Norway and Sweden are important contributing factors to the virtual absence of Salmonella in the food supply in their countries.The opening plenary session focused on international experiences in controlling Salmonella in food animals.Several U.S. government agencies, including CDC; USDA; and the National Institutes of Health, National Institute of Allergy and Infectious Diseases, presented research findings at the workshop. Presentations included results from animal feed commodity studies that look at the factors contributing to microbial pathogens, mycotoxins, and chemical residues in animal feed. Researchers from FDA and Washington State University also provided data indicating that contaminated animal feed continues to be a source of Salmonella-contaminated animal feed. Collaboration among all groups was stressed as a useful measure in controlling contaminated animal feed in the future.Further studies are necessary to document the precise contribution of contaminated animal feed to human illness. Nevertheless, some presentations suggest that practical interventions are available to reduce the prevalence of http://www.cdc.gov/narms/mce/animalfeeds.htm.A compact disk, including all of the presentations, agenda, and list of participants from the workshop, is available online at"} +{"text": "Bifidobacterium and Bacteroides manifested the difference between SE and TE types. For anthropometry, body weight, body mass index, and waist circumference of the TE type were significantly higher than those of the other types. Overall, findings indicated a possible link between SC types and gut microbiota within a narrow age range. Further investigations are deemed necessary to elucidate the influences of age, gender, and other factors in the context of SC types and gut microbiota.The Sasang constitutional medicine has long been applied to diagnose and treat patients with various diseases. Studies have been conducted for establishment of scientific evidence supporting Sasang Constitutional (SC) diagnosis. Recent human microbiome studies have demonstrated individual variations of gut microbiota which can be dependent on lifestyle and health conditions. We hypothesized that gut microbial similarities and discrepancies may exist across SC types. We compared the difference of gut microbiota among three constitutions , along with the investigation of anthropometric and biochemical parameters. Firmicutes and Bacteroidetes were predominant phyla in all SC types. The median plot analysis suggested that Firmicutes and Bacteroidetes appeared more abundant in SE and TE, respectively, in the male subjects of 20\u201329 years old. At the genus level, Individualized treatment according to the patients' \u201csyndrome\u201d pattern is one of the characteristics of traditional oriental medicine in the East Asian countries. The Sasang constitutional medicine, a holistic approach based on the unique constitutional typology, has long been applied to diagnose and treat patient with various diseases. Characteristics pertaining one's physical, psychosomatic, and emotional aspects are integrated in the determination of Sasang constitutional (SC) types. The SCM deals with biological and psychological traits in individuals and explains individual differences in behavioral tendencies, physical characteristics, and varying levels of vulnerability to disease and responsiveness to environmental stimuli. Diagnosis under the SC typology divides human beings into four categories according to their inherited traits, including appearance, physiology, susceptibility to disease, and personality. Traditional Korean medical doctors classify patients using SC for diagnosis and treatment in clinics. However, like other forms of complementary and alternative medical systems worldwide, the identification of SC has been subjective and fallible because of lack of standardization and scientific evidence for a long time . Therefo12 cells per gram) in the intestine, and the diversity of microbes was higher in the intestine, compared with other sites .Supplementary Figure 3: The double pie chart of bacterial communities obtained from each sample of So-Yang. The inner circle indicates the composition of the phylum, and the outer circle indicates the composition of the genus.Supplementary Figure 4: The composition of bacterial communities obtained from each sample of So-Eum in the double pie chart. The inner circle indicates the composition of the phylum, and the outer circle indicates the composition of the genus.Click here for additional data file.Click here for additional data file."} +{"text": "Musca domestica L.The correct version of the title is: Insecticide Mixtures Could Enhance the Toxicity of Insecticides in a Resistant Dairy Population of The first author Hafiz Azhar Ali Khan should also be affiliated with the institution: Institute of Agricultural Sciences, University of the Punjab, Lahore, Pakistan"} +{"text": "There are some evidences in Brazil and others countries pointing out insufficient resources and actions to promote prevention and rehabilitation for substance abuse related disorders. Also the lack of professional qualification contributes to this scenario, generating knowledge deficiencies and inadequate practices. The study evaluates the Regional Reference Centre on Drugs of Juiz de Fora, Brazil (CRR-JF). The CRR-JF aims to train professionals of the local health sector (NHS) and social care system increasing their knowledge of screening and brief intervention (SBI) practices on the use of drugs and strengthening health care activities. Five courses are provided: Motivational Counseling and Brief Intervention, Case Management and Social Reintegration of Drug Users, Improvement of Medical Practices about Drugs, and Comprehensive Drug Care for Hospital\u2019s Professionals. Questionnaires were applied measuring participant satisfaction and changes in the practices. The added workload of the courses was 360 hours. A total of 180 professionals attended the courses . According to results, 83.2% of participants were satisfied or very satisfied about the courses attended; 61.3% evaluated the content of the courses as good, 28% as great, and 60% were very satisfied or satisfied with the applicability of the course content. Regarding SBI, the participants showed a significant increase in their level of trust and ability to approach users of psychoactive substances and counsel them to reduce or stop their consumption. Besides providing knowledge acquisition, participation in the CRR-JF enabled greater discussion of the practices carried out, reflecting on the work of professionals in the development of more effective interventions in prevention, promotion, and psychosocial rehabilitation of users of psychoactive substances. Acknowledgments: National Secretary of Policy on Drugs (SENAD), Coordination for the Improvement of Higher Education Personnel (CAPES)."} +{"text": "E. coli was discussed from the points of view of enzyme level regulation, and gene level regulation. Then the effects of the specific pathway gene knockout such as pts, pgi, zwf, gnd, pyk, ppc, pckA, lpdA, pfl gene knockout on the metabolism in E. coli were overviewed from the systems biology point of view with possible application for strain improvement point.Recent metabolic engineering practice was briefly reviewed in particular for the useful metabolite production such as natural products and biofuel productions. With the emphasis on systems biology approach, the metabolic regulation of the main metabolic pathways in The concept of metabolic engineering has been proposed back in 1991 Bailey, .Escherichia coli, Saccharomyces cerevisiae, Corynebacterium glutamicum, Bacillus subtilis etc.; (4) metabolic pathways available in the strains from the available carbon source(s) to the target metabolite(s), (5) introduction of the heterologous pathways by recombinant DNA technology; (6) reduction of the flux to undesirable by-products; (7) enhancement of precursor metabolites production together with necessary cofactors production; (8) modulation of transporters for exporting the target metabolite(s) to the extracellular medium; (9) understanding the metabolic regulation mechanism by both allosteric regulation of enzymes and transcriptional regulation by global regulators; (10) robust and responsive genetic control system for the desired pathways and the host microbe, (11) methods for debottlenecking the chosen pathways; and (12) ways to maximize yields, titers, and productivities available raw materials such as cellulosic biomass, algae, and waste materials, which can be converted to glucose, xylose, fructose, galactose, mannitol, and glycerol etc. by the appropriate saccharification methods and their processing costs; (2) enhancement of the substrate uptake rate and co-consumption of multiple carbon sources (for the enhancement of the target metabolite production rate); (3) appropriate host microbes such as E. coli by probably considering the advantages of high cell growth rate and well-known characteristics etc. In the field of biofuel production, much interest has centered on S. cerevisiae. Corynebacterium glutamicum is also frequently employed as platform cell factories in industry in particular for amino acid production. An overview of the recent advances in engineering the central carbon metabolism of such industrially important bacteria as E. coli, C. glutamicum, B. subtilis, Streptomyces sp., Lactococcus lactis has been reported Fell, may be ain silico gene knockout simulations for succinic acid fermentation. Trinh et al. system and the MglBAC system for the case of using a mixture of multiple carbohydrates, an early attempt was to knockout Gosset, . Thus Gapgi gene, which codes for the first enzyme of Embden-Meyerhof-Parnas (EMP) pathway, was knocked out, the glucose catabolism occurs exclusively through the oxidative pentose phosphate (PP) pathway. As a result, NADPH is overproduced, and inhibits allosterically the activity of G6PDH, thereby reducing the glucose uptake rate, resulting in the low growth rate pathway is activated, and the flux through G6PDH is reduced for the gnd mutant .The effect of d mutant , PEP is accumulated, which causes the activation of Ppc and increases the Ppc flux. This in turn causes the increased fluxes through MDH (reverse direction) and Mez, and the reduced PYR (caused by Pyk disruption) could be backed up by these alternative pathway fluxes both activate the aromatic amino acid biosynthetic pathways is regulated by the phosphorylation /dephosphorylation of ICDH by aceBAK, and the decrease in OAA becomes dominant for the activation of glyoxylate pathway due to the importance of cell synthesis.If either the pathway . The metabolic flux analysis of lpdA gene knockout mutant indicates that glyoxylate pathway was activated, while glycolysis, the oxidative PP pathway, and the TCA cycle activities were down-regulated accumulates and in turn glycolysis intermediates accumulate, and thus the glucose consumption rate decreases. Moreover, the accumulation of PYR activates Pox pathway producing acetate, and in turn AcCoA is backed up by ACS pathway from acetate (aceBAK operon was induced to activate glyoxylate pathway. If sucA gene, which codes for subunit of \u03b1KGDH, was knocked out, the metabolism is a little different from the case of lpdA gene knockout (Li et al., If acetate (Li et apflA, B gene knockout caused overproduction of lactate (Zhu and Shimizu, pfkA and pykF gene expressions, and thus the glucose uptake rate was increased (Zhu and Shimizu, ldhA gene was knocked out, the fluxes toward the production of acetate, formate, and ethanol were increased as expected (Kabir et al., Under anaerobic or microaerobic conditions, NADH balance and the substrate level phosphorylation for the production of ATP may control the metabolic fluxes at the branch points such as PEP, PYR, and AcCoA (Zhu and Shimizu, E. coli. The metabolisms of other microorganisms have also been investigated by Fuhrer et al. (13C-metabolic flux distributions, where the changes in the metabolic flux distributions are caused by the regulation of enzymes and the intracellular metabolite concentrations. In addition to allosteric regulation, the enzyme activities are controlled by their corresponding gene expressions. Since gene expressions are under control of global regulators or transcription factors, it is quite important to understand how these control the metabolism for metabolic engineering (Matsuoka and Shimizu, The above explanation is for r et al. . The aboAlthough most of the metabolic pathway engineering practices have focused on the modulation of the metabolic pathways of interest, the present analysis indicates the importance of understanding the overall main metabolic regulation in response the specific pathway mutation for the efficient metabolic engineering. It may be also considered to modulate transcription factors for the significant strain improvement."} +{"text": "Fasciola hepatica on the structures of the blood vessels and biliary tract in the sheep liver.The aim of this study was to evaluate the functional capacity of the liver based on the activity of specific enzymes and bilirubin in serum and also to investigate the influence of mechanical and toxic effects of F. hepatica, corrosion cast technique was used.Blood samples and liver of 63 indigenous sheep of Pramenka breed, slaughtered in the period from March to December 2009 were used. Based on parasitological findings in the liver, all animals were divided into two groups: control (n = 34) and infected group (n = 29). For investigation and description of pathological changes in sheep liver, naturally infected with P\u22640.05) of serum gamma-glutamyl transferase (GGT), total bilirubin (TBIL) and direct bilirubin (DBIL) in infected sheep group comparing with the control group. No significant differences were observed for activity of aspartate aminotranferase (AST) between groups. Vascular and biliary systems of the liver were found to be affected.Biochemical analysis of tested parameters showed a significant elevation (F. hepatica.Results of biochemical analysis are consistent with pathological findings and measuring of tested parameters could be used in early diagnosis of sheep fasciolosis and to test the effectiveness of anthelmintic therapy. Corrosion cast technique is very useful for investigation of pathological changes and neoangiogenesis of vascular and biliary system in sheep liver, caused by mechanical and toxic effects of Fasciola hepatica , which is mainly localized in the liver, bile ducts and gallblader of domestic and wild ruminants, especially in sheep. In animals, the subclinical and chronic disease usually results in decreased production of meat, milk and wool, secondary bacterial infections, fertility problems and great expenses with antihelmintics (Fasciolosis (Fascioliasis) is one of the most common parasitic disease in domestic animals, with a cosmopolitan distribution, particularly prevalent in countries with developed sheep production and very low socio-economic status, such as Bosnia and Herzegovina. It is caused by the hepatic trematode lmintics .F. hepatica, affect the complex vascular and biliary system in the liver. Properly functioning of these two systems is the most important factor for preservation of normal liver functions.The pathogenic effects of these flukes on the host organism begins with the ingestion of encysted metacercaria with vegetation or freshwater. After migration of juvenile forms through the hepatic parenchyma, flukes reside and graze on the mucosa of the bile ducts, which result in the massive tissue damage , 4. The Due to the complexity of vasular and biliary system examination, there are a number of different laboratory tests, which are based on biochemical analysis of serum parameters. These tests usually include the determination of serum transaminases , which are the most sensitive indicators of hepatocellular injury. Alkaline phosphatase (ALP), gamma-glutamyl tranferase (GGT), serum proteins and bilirubin are also used to evaluate the degree of cholestasis and syntetic capacity of the liver \u20138.Corrosion cast technique is usually used for anatomical investigations of three-dimensional vasculature and ductal architecture of some organs, and it has rarely been used for study of pathological changes in the liver caused by parasites or other pathogens .In only a few studies authors have used a corrosion cast technique for investigation and description of pathological changes in liver in natural and experimental induced fasciolosis in sheep and cattle \u201312.F. hepatica on the structures of the blood vessels and biliary tract in the sheep liver, using corrosion cast technique.The aim of this study was to evaluate the functional capacity of the liver based on the activity of specific enzymes and bilirubin in serum and also to investigate the influence of mechanical and toxic effects of F. hepatica. After that, all examined sheep, based on parasitological findings, were divided into two groups: control (n = 34) and infected group (n = 29).The study included serum and the liver of a total of 63 indigenous sheep of Pramenka breed, slaughtered in the period from March to December 2009. All sheep were from 1 to 3 years of age and body weight ranged 45 - 65 kg approximately. During the study, liver of the slaughtered animals was inspected for presence of PLUS with commercial kits . Direct bilirubin (DBIL) was determined by spectrofotometer BTS-330 , using modified Jandrassik/Gr\u00f3f method .Before the animals were slaughtered, blood samples for biochemical analysis were collected from the external jugular vein into marked vacuum tubes and transported at +4 \u00b0C to the laboratories of the Veterinary Faculty in Sarajevo. The blood tubes were centrifuged at 3.000 rpm for 10 minutes for serum separation. Due to poor stability of enzymes and bilirubin in the serum, the samples were analyzed within 6 hours. Liver enzymatic activities of aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and total bilirubin (TBIL) were measured according to standard procedures using automatic analyzer DIMENSION - Xpand F. hepatica. After dissection and fine preparation the blood vessels were rinsed with saline solution and heparin to remove remaining blood and the clots. The biliary tract was rinsed also. To prepare corrosion cast models, blood vessels and bile ducts of each liver, were injected with acryl resin . Powder and solution of acrylat were mixed in a ratio of 1: 2 and then colored with different Biodur pastes. The portal vein, hepatic arteries, hepatic veins and bile ducts were stained green, red, blue and yellow, respectively. After hardening of resin at room temperature for 24 hours, the livers were macerated in 33% hydrochloric acid for 7-10 days. Later, corrosion casts were washed under tap water and air-dried . Differences were considered as significant when P\u22640.05.All statistical analyzes were performed using Minitab 15 software. Significant differences between infected and control group of animals were determined by Student's F. hepatica infected and control sheep and reference intervals are presented in The mean values of AST, GGT, TBIL i DBIL in serum of F. hepatica, revealed dilated, rough and wrinkled bile ducts. Smaller ducts on the edges of intermediate and cranio-ventral segments of the left lobe were lost terminal branches and 3. IFasciola hepatica causes the release of reactive oxygen species producing a damage of cell wall and hepatic tissue necrosis at the early stage of the infection could be related to the hepatocellular necrosis and degenerative changes produced by migration of juvenile flukes through the liver parenchyma , 17, 18.F. hepatica.Serum GGT values in infected sheep group were significantly higher than in the control group . Some auF. hepatica infected sheep recorded in the present study were confirmed by corrosion cast study.In the present study, concentration of TBIL and DBIL were significantly higher compared to the control group , but theChanges observed on the casts of bile ducts, arterial and venous blood vessels of the sheep liver from infected group, completely correspond to changes described by Rushton and Murray , 12 and According to Rushton and Murray , duct diObserved narrowing of the secondary and terminal branches of portal vein along changed bile ducts is most probably a consequence of exudation and inflammation (edema), as well as, secondary proliferation of connective tissue in the chronic phase of the disease . The samMalformations such as curved (serpentine) shapes, dilations, and loss of continuity on the casts of hepatic artery , we beliF. hepatica.Activities and concentration of AST, GGT, TBIL and DBIL in serum are reliable indicators of the stage of sheep fasciolosis and could be used in early diagnosis and to test the effectiveness of anthelmintic therapy. Corrosion cast technique is very useful for investigation of pathological changes and neoangiogenesis of vascular and biliary system in sheep liver, caused by mechanical and toxic effects of"} +{"text": "Interest is growing in integrated systems of e-care for the frail elderly. The present project promotes cognitive training and assessment using ICT tools, stimulates the socialization, shares and monitors the situation of the elderly by different professionals, care givers and relatives.Within the frame of the European Commission funded SOCIABLE Project, 348 elderly are participating in the trial.The approach was pilot in seven different sites, across Italy , Greece , Spain (1 University) and Norway .SOCIABLE pilot study is a multi-national, multicenter, non-randomized, placebo-controlled efficacy study. Its primary objective is to evaluate the effects of a computer-based cognitive training and social activation program on the cognition, the affection and the functional abilities of cognitively intact elderly, patients with MCI and patients with mild AD. Conclusions: Two types of models of integrated care delivery for the frail elderly have been tested; one was characterized by group sessions in the pilot center assisted by caregiver or psychologist, another was stipulated in the use of ICT tools by the elderly at home. The first results of the trial will be illustrated.Integrated care delivery can be achieved in various ways. Irrespective of which model is adopted were detected high levels of satisfaction and performance by all groups and an important ability to monitor results by medical experts and care givers."} +{"text": "In the past few decades the knowledge of the key pathogenic mechanisms of the disease has improved, but it remains far from being fully understood. Traditionally, the diagnosis of AD has been based on clinical symptoms, and accuracy studies of the current clinical criteria conducted in referral have shown high sensitivity for AD. However, identification of the disease, in particular in the early stages, remains difficult as pathological alterations may be apparent several years before the clear-cut clinical picture. Alzheimer's disease (AD) is the most frequent neurodegenerative disease in the elderly. It is characterized by progressive impairment in multiple cognitive domains, in particular memory, leading to severe impairment in daily living followed by progressive physical deterioration and death. The neuropathological hallmark of AD is the presence of cortical intracellular neurofibrillary tangles (NFT) and extracellular There is growing evidence that the use of biomarkers will increase our ability to identify AD earlier in the disease process and with higher accuracy. In addition, biomarkers will help elucidate the underlying biological and molecular changes, improve the detection of patients suitable for specific treatments, research studies or drug trials, and will contribute to a better management of the disease in the clinical practice. In this special issue on early clinical and molecular detection of AD, we have invited manuscripts that specifically address issues related to early and improved diagnosis of AD. The first two articles address the usefulness of current biological and neuroimaging markers for the diagnosis of AD, including genetic variation, plasma, serum and CSF biomarkers, brain atrophy measures, functional MRI measures, and amyloid burden evaluated by PiB compound. The third paper reevaluates the usefulness of common clinical rating scales for AD, frontotemporal dementia, and vascular dementia using factor analysis. In the fourth paper, the sociocultural impacts of novel molecular technologies for the early diagnosis of AD are addressed. The paper outlines three steps to assess sociocultural impacts. First, conceptual analysis of the ideas underlying technological developments shows how these technologies redraw the boundary between AD and normal ageing and between biological and social approaches of ageing. Second, scenarios are designed depicting different possible futures of AD diagnosis and societal ways to deal with ageing. Finally, the paper reviews the possibilities for deliberation on the potential sociocultural impacts. CDKN2A and CDKN2B on AD. Finally, the last paper assesses the effect of siRNAs silencing on gene expression. While commonly studies use RNA interference (RNAi) to investigate the effect of silencing of specific genes on their expression and effect on cell metabolism, the current paper takes this technology further by assessing the effect of allele-specific silencing of a particular mutant allele, in this case mutation L392V in PSEN1.Manuscripts five and six are original research studies assessing the effect of specific genetic variations on AD and AD endophenotypes. While the study by Swaminathan et al. explores the effect of copy number variation (CNV) derived by genome-wide screening in the ADNI cohort on AD and MCI, the study by Tedde et al. explores the effect of genetic variation in Benedetta NacmiasBenedetta NacmiasChristiane ReitzChristiane ReitzThomas ArendtThomas Arendt"} +{"text": "The other two presenters suggested some practical methods for globalization of SCM on the basis of their experiences. After the three main presentations, there was a panel discussion session for further development of workshop topics, extended by five other external experts. They discussed the benefits, limitations and essentials for globalization of Korean Traditional Medicine, specifically SCM, from bench to bedside.The workshop on \u201cStrategic Approach to the Globalization of Sasang Constitutional Medicine (SCM)\u201d was held in the Korea Institute of Oriental Medicine (KIOM) on September 18, 2009. This workshop was designed to discuss and brainstorm the strategic approach to the globalization of SCM, one of the unique systems in Korean Traditional Medicine, with three topics and an extensive panel discussion. Professor Edwin Cooper, Editor-in-Chief of This isedicine\" . A brilledicine\" . Among sedicine\" . The othedicine\" , perspecedicine\" , currentedicine\" , the intedicine\" and curredicine\" . The thredicine\" , the assedicine\" and the edicine\" . The addedicine\" , quantitedicine\" and relaedicine\" .The publication of this special issue led to conduct aworkshop on \u201cStrategic Approach to the Globalization of Sasang Constitutional Medicine\". This was held in the KIOM, the unique government-funded institute for Korean Traditional Medicine in Korea, on September 18, 2009, in Deajeon, Korea supported by the Division of Constitutional Medicine, KIOM . This workshop was designed to discuss and brainstorm the globalization of SCM, one of the unique systems in Korean Traditional Medicine, with three presentations and a panel discussion.eCAM, gave a commemorative lecture on publication of the second supplement of eCAM. He made a brief introduction to this supplement and gave a 1-hour lecture about how to globalize SCM. He showed the print version of supplement with beautiful cover of \u201cBanquet of Seowangmo, Joseon dynasty (the name of Kingdom in Korea from 1392 to 1910)\", which was reproduced with the kind permission of the Los Angeles County Museum of Art. He introduced the content of this supplement briefly and introduced SCM as a unique contribution to the growing field of CAM. According to Prof. Cooper, the supplement to eCAM represents a milestone, in that it is the first publication in this area of alternative medical practices. He also described the rigorous peer-review process for the supplement and summarized how SCM represents a potentially fruitful modern approach to an ancient practice that will probably attract more and more attention. In conclusion, he finished his talk with the promise of that this application of an ancient system to international human health would be forthcoming.Professor Edwin L. Cooper, the Editor-in-Chief of Dr. Myeong Soo Lee of KIOM presented practical strategies for the publication of CAM researches in Science Citation Index journals. His main topic and contents were drawn from his personal experience of submission, publication and peer review of other scientist's papers. His talk started with the main factors for successful publication and the procedures for submission and the peer-review process. In particular, he showed several submission platforms of online journals and gave many personal tips for successful publication.Professor Han Chae from Pusan National University focused on how to enhance the publication of Sasang typology based on personal experiences in Korea and the United States. He also discussed how the uniqueness of SCM made publishing articles on the subject really tricky. He highlighted the most common errors that authors make in writing for publication, for example, trying to explain the whole subject in one manuscript, without giving enough reliable references supporting the underlying notions. His issue was the research model and operational definition that should be built up with sufficient references.After the three main presentations, there was a panel discussion session for further development of workshop topics, extended by five other external experts: Profs Young E. Earm , Byung Hee Koh (Kyung Hee University), Heon M. Lim , Kwang-Sup Soh and Jong Yeol Kim (KIOM). They discussed the benefits, limitations and essentials for globalization of Korean Traditional Medicine, specifically SCM, from bench to bedside.eCAM and the future role of editorial members for eCAM.The next day, I hosted a meeting of the Editorial Board in Seoul. The attendees were Profs Edwin L. Cooper (Editor-in-Chief), IL-Moo Chang (Kyung Hee University), Byung Hee Koh (Kyung Hee University), Sanghoon Lee (Kyung Hee University) and Myeong Soo Lee (KIOM), with Prof. and Dean, Seung-Hoon Choi (Kyung Hee University) as observer. We discussed several topics, including the second quarter's reports from"} +{"text": "Phosphate plays a central role in the pathophysiology of CKD-MBD and the progression of chronic kidney disease (CKD) and contributes to the disproportionate cardiovascular risk faced by patients with CKD. Adaptation of nephrons attempting to preserve phosphate homeostasis requires endocrine tradeoff that fuel adverse events of hyperphosphatemia in CKD\u2014secondary hyperparathyroidism, calcium and vitamin D derangements, vascular calcifi cation, and metabolic bone disorder.In fact, in advancing CKD there is a multitude of biochemical, physiological, and clinical alterations, and mechanistic understanding of secondary hyperparathyroidism, vascular calcification, and regulation of phosphate metabolism in CKD has advanced significantly in the past five decades. The principal hormones that regulate renal phosphate handling are parathyroid hormone (PTH), which is produced by the parathyroid gland, and fibroblast growth factor (FGF)-23, which is produced by osteocytes and osteoblasts in bone. In healthy individuals, increasing serum phosphate concentration induces secretion of PTH and FGF-23, and Kloto decline.It has been established (and now accepted by nephrologists) that observational studies strongly suggest that phosphorus is associated with cardiovascular risk, and definitive prospective animal studies are supportive. However, prospective studies demonstrating that modulation of the putative risk factor affects clinical outcomes are lacking, and phosphorus, as yet, does not qualify as a cardiovascular risk factor.This special issue provides an identification of the complex mechanisms that determine the phosphorus and calcium metabolism in CKD-3 and CKD-4; a verify the association of serum phosphate and related factors in ESRD-related vascular calcification. It has also addressed mineral metabolism in patients with CKG in the Era of KDIGO Guidelines, the effect of vitamin D on clinical outcomes in chronic kidney disease, and the effect of paricalcitol on vascular calcification and cardiovascular disease in uremia. Finally, were also discussed the effect of the use of non-calcium-phosphate binders in the control of vascular calcifications; the clinical significance of FGF-23 in patients with CKD, the the relationship between arterial stiffness and vascular damage; the treatment of severe metastatic calcification and calciphylaxis in dialysis patients; the clinical impact of hypercalcemia in kidney transplant patients.Biagio Raffaele Di IorioBiagio Raffaele Di IorioMarkus KettelerMarkus KettelerDomenico RussoDomenico RussoAngela WangAngela Wang"} +{"text": "Health research programs targeting the population of Gabon and Equatorial Africa at the International Center for Medical Research in Franceville (CIRMF), Gabon, have evolved during the years since its inception in 1979 in accordance with emerging diseases. Since the reemergence of Ebola virus in Central Africa, the CIRMF \u201cEmerging Viral Disease Unit\u201d developed diagnostic tools and epidemiologic strategies and transfers of such technology to support the response of the National Public Health System and the World Health Organization to epidemics of Ebola virus disease. The Unit carries out a unique investigation program on the natural history of the filoviruses, emergence of epidemics, and Ebola virus pathogenesis. In addition, academic training is provided at all levels to regional and international students covering emerging conditions that favor the spread of viral diseases. The International Centre for Medical Researches of Franceville (CIRMF) was founded in 1974 by His Excellency El Hadj Omar Bongo Ondimba, President of the Gabonese Republic, and Mr. Pierre Guillaumat, the chairman of the petroleum company, Total Gabon. The Centre was inaugurated on December 5th, 1979 with the participation of numerous internationally eminent scientists .In the 1990s, viral hemorrhagic fevers became a focus of attention in Equatorial. The decision to develop a high security laboratory for the study of Ebola virus disease came after a 1996 Ebola virus disease outbreak in Mayibout area, Gabon. The main objective was to develop the potential for rapid and specific diagnosis on viral hemorrhagic fevers and to have a backup for field investigation of severe viral hemorrhagic fever epidemics. Because the unique expertise and interaction of the CIRMF team along with the international World Health Organization (WHO) teams for Ebola virus disease, the Gabonese government agreed to such a project. The first BSL3+ (including negative pressure and glove box) laboratory was built in 1997, mostly financed by the Foreign Ministry of France . This lai.e., Ebola, Marburg, and Crimean-Congo hemorrhagic fever viruses). Research, including isolation and characterization of these highly pathogenic viruses is performed in accordance with international rules defined by WHO on the handling Risk Group 3/4 Agents Updated equipment includes a double door autoclave, thermo regulated cabinet, a high security centrifuge system, a conventional photonic microscope, a virus isolation unit, and two independent rooms the can be shut down alternatively after decontamination when necessary. An uninterruptable controlled electrical supply for refrigeration, computer systems, and other systems is ensured by two back-up power plants. The telecommunication network consists of mobile phones and the Internet through a dedicated satellite antenna. Other service units consist of a Primate Center, the Gorilla and Chimpanzee Study Station in Lop\u00e9 National Park, and the Dienga Health Observatory. Investigators from this observatory conduct field studies on the prevalence of viral and parasitic diseases and their implications for public health [On 45 hectares, the CIRMF campus has a working space of 2,500 square meters composed of a main building, laboratories, service buildings, and living accommodations . The prec health Pan troglodytes), gorillas (Gorilla sp), mandrills (Mandrillus sphinx), guenons (Cercopithecus sp.), collared mangabeys (Cercocebus torquatus), greater spot-nosed monkeys (Cercopithecus nictitans), vervet monkeys (Chlorocebus pygerythrus) and an Asian macaque (Macaca sp.) colony. One of the largest primate centers in Africa, the Primate Center is equipped with level A2 and A3 animal facilities for scientific research protocols. The Great Apes are housed in large open-air facilities. Semi-free living colony of twelve forested hectares harbor about half of the primates at the Primate center. At the Gorillas and Chimpanzee Study Station, researchers study ecological approaches to the emergence of zoonotic diseases, inter-species transmission of pathogens, and disease outbreaks in humans and wild animals [Dedicated to medical research, the Primate Center houses more than 450 primates belonging to ten different African species , Marseille, and other European agencies. The Scientific Council presided by Professor Patrice Debr\u00e9 recommends scientific policy to the Board of Directors .Running costs are funded by the Ministry of Economy, Gabon, the national petroleum company of Total-Gabon, and the Ministry of Foreign and European Affairs, France. Several international agencies participate in a variety of financial supports including scientists\u2019 salaries, equipment, research projects, and academic grants .Technical laboratory training support of Gabonese teams and other African countries has been one of the major aims of CIRMF. The UMVE actively participates in the academic training at the Regional Graduate School and the different State universities of Equatorial Africa. A special relationship with the \u201cHealth Sciences University\u201d of Libreville and the \u201cSciences and Technology University\u201d of Masuku in Franceville encourages collaborative research projects with teachers and supports students of the Faculties of Medicine and Sciences in the preparation of doctoral theses. CIRMF receives doctoral and post-doctoral scientists from other universities of developed countries . Continuing medical education in the form of post-doctoral workshops are held at the CIRMF for discussion and demonstration of modern techniques. As a National reference laboratory, CIRMF has the following roles: diagnosis of suspected cases during outbreaks of viral hemorrhagic fevers or severe clinical infectious syndromes; development of new methods for diagnosing such infections; surveillance of animal fatalities in reservoir or intermediate hosts; and intervention during outbreaks of unknown etiology. CIRMF diagnosed infections of more than 70 pathogens that could not be identified in other biology laboratories throughout the country. CIRMF maintains close ties to several components of the National Healthcare system, such as Amissa Bongo Regional Hospital in Franceville or the Sino-Gabonese Friendship Hospital. i.e.,: Military Hospital, Libreville; General Hospital, Libreville; A. Schweitzer Lambarene Foundation).In order to facilitate national and international scientific exchanges including scientists, equipment, biological specimens, the capital of Gabon, Libreville, is part of CIRMF operational system. Hosted by the University of Health Sciences, Libreville, one laboratory is now operational. Tight connections with other scientific teams in Libreville are under development to respond to all Ebola virus disease epidemics in Africa. CIRMF aims to use laboratory and field expertise be a regional focal resource in conjunction with local health authorities to organize epidemic responses. CIRMF expertise is also offered from by entering into laboratory-to-laboratory agreements. Also, an informal international laboratory network for the diagnosis and surveillance of severe infectious clinical syndromes includes: the Institut National de Recherche Biom\u00e9dicale, Democratic Republic of the Congo; Laboratoire National de Sant\u00e9 Publique de Brazzaville, Republic of the Congo; Metabiota/Laboratoire des Maladies Emergentes, Yaound\u00e9, Cameroon; Pasteur Institute, Bangui, Central African Republic; Institute of Virology, Bonn University, Germany; and P4 Jean M\u00e9rieux Lyon, France. Exchange of materials, equipment, and personnel is facilitated through memorandums of understanding. CIRMF holds more than 250,000 samples of various origins in a biological repository, which is accessible to the International scientific community. The UVME assists the National Public Health System in consolidating and formalizing microbiological monitoring of the Equatorial African sub-region. Ultimately, CIRMF will be positioned as a Center of Excellence for microbiological surveillance and research in a global network. Developing diagnostic tools and strategies is the main driver to improve surveillance and research of emerging viral diseases. A strategic choice was made to link syndromes to an etiological agent, including hemorrhagic syndromes. To isolate and diagnose highly pathogenic viruses, a progressive and diversified methodology was applied. The first approach used real-time virus-specific PCR (qRT-PCR). If the first approach was not successful, conventional RT-PCR was implemented using degenerate consensus primers targeting conserved regions of the genome. Ultimately, random amplification of nucleotide sequences was directly applied to the original biological material ).Hypsignathus monstrosus, Epomops franqueti, Myonycteris torquata) in Gabon and Republic of the Congo (Rousettus aegyptiacus) in Gabon, suggesting that bats might be reservoirs for filoviruses [UMVE studied the factors implicated in the three steps that led to Ebola virus and Marburg virus diseases emergence in humans. These steps include: the identification of reservoir species, the circulation within the natural host, the crossing to intermediary animal species, and finally the direct transmission to humans from great apes and fruit bats. Antibodies and nucleotide sequences specific for Ebola virus were detected in the liver and spleen of fruit bat belonging to three species , cold chain with the necessity to maintain in situ a unit of liquid nitrogen production (repository), and purified water supply.CIRMF is geographically isolated from the capital of Gabon, Libreville. The Libreville office is essential to the Franceville headquarters as it coordinates visits from staff on field missions, and forwards imported equipment to headquarters. The capital is accessible by a 12-hour ride in a four-wheel drive vehicle or in a train (three times/week schedule) covering 641 km. Due to tropical weather, four weekly domestic plane rotations often fly on an inconsistent schedule. Ultimately CIRMF needs to be largely autonomous in term of electrical power (CIRMF is uniquely suited to study infectious diseases of the Congolese tropical rain forest, the second world\u2019s largest rain forest. As a central point of a North-South transect of the rain forest, the Center is able to study the biodiversity of Africa including animal species, microbes, and parasites. CIRMF is dedicated to conduct medical research of the highest standard, and is the only facility of its type in Equatorial Africa. With unrivalled infrastructure, multiple sites, and multidisciplinary teams, the Center promotes a modern healthcare system in Gabon. CIRMF teams are engaged in trans-disciplinary projects bringing together specialists from the health sciences, biological sciences, veterinary medicine, conservation, the humanities, and environmental sciences. The Center welcomes partnerships from around the world to work on global human health issues."} +{"text": "Anellovirus genus), and descriptions of new technologies that have profoundly affected the field of virology. This comprehensive desk reference provides concise definitions of virologic terms; enables quick fact checking; and provides useful, often difficult to find, information\u2014such as the origin of virus names, determination of ICTV-approved virus abbreviations, and locations and sources of viral isolations. An appendix of current ICTV-recognized virus families, subfamilies, genera, and type species is especially useful.Rapidly expanding technologies in the field of virology, identification of novel viral agents, and the 2005 report (8th edition) of the International Congress of Taxonomy of Viruses (ICTV) addressing reclassification of several viruses generated the 20% new material in Mahy\u2019s 4th edition of The Dictionary of Virology. The previous edition of this book was published in 2001; the 2009 edition includes recent advancements, such as newly described viruses human coronavirus, human metapneumoviruses, bocaviruses, and Rabensburg virus), reclassification schemes of viruses or viruses (the newly described virophages of mimiviruses). The increasing quantity of information about viruses of vertebrates ranging from fish to primates presented the author with considerable space difficulties. He compensated for this situation, however, by citing literature sources at the end of entries for readers seeking more information. Additionally, considerable cross-referencing enhances the utility of the book. On the basis of inclusion of new information in the field and my personal experience with previous editions of The Dictionary of Virology, I highly recommend this volume to students, virologists, microbiologists, and public health professionals interested in viruses of vertebrate hosts."} +{"text": "The reoperations in cardiac surgery are technically more difficult, and the mortality and morbidity increased. It is huge importance of operative techniques, preoperative planning and the skills of the surgical team in those cases. We like to detect the different pre- and intra-operative reasons of the elevated morbidity and mortality, and the opportunities, how we could to reduce them.It was 79 REDO cardiac operations in our department during the last 2 years. The previous operations were: mitral valve (n=33), aortic valve (AVR) (n=15), CABG (n=22), AVR and CABG operations (n=4). We recorded the ejection fraction (EF), right ventricular pressure (RVP), intra-operative and postoperative complications, mortality, and postoperative bleeding.The most common reason of major bleeding injuries (MBI) was the damage of right ventricle . In contrast to the literary data, in our cases the MBI were not increased the mortality, and the mean intensive care unit (ICU) time. The early ventricular fibrillation , the MBI intra-arterial balloon pump application and mortality was higher after previous CABG operations. The incidence of non-fatal complications, MBI and the mortality were significant higher in those patients who had lower EF before, or/and higher RVP.The lower EF and higher RVP increases the mortality and elongated the mean ICU time. Due to this objects the REDO operation is indicated in the first time of the detection of necessity. The high RVP increase the possibility of MBI. In those cases the possible serious complications can be prevented by peripheral canulation, and the use of external defibrillator paddles. With proper preoperative planning and meticulous surgical techniques, the mortality and the serious postoperative complications can be reduced."} +{"text": "Plasmodium falciparum. The efficiency of these treatments is however seriously compromised by the appearance and spread of drug resistance. Resistance is observed today to some extent against every available drug, including recent reports of resistance to artemisinin. Resistant strains of P. falciparum can spread in affected areas if they fare better than sensitive strains over the entire transmission cycle, including within-human and within-vector infection phases. Both hosts likely represent widely different environments for the parasite, particularly in terms of exposure to drugs and host-specific costs of resistance, which could notably affect the outcome of competition between resistant and sensitive strains and ultimately the evolution of drug resistance.Efforts to relieve the burden caused by malaria rely critically on the availability of drugs targeting To investigate this issue we present a model of malaria transmission combining between-hosts and within-hosts (human and vector) dynamics. The latter incorporates the impact of competition, treatment and immunity in a strain-specific fashion.P. falciparum, impact resistant strains . Finally we also investigate the effect of vector control methods on the prevalence of resistance.We show how costs of resistance, particularly within-vector costs, affect the selection for resistant strains. We also explore how different drugs, acting on specific parts of the within-human cycle of Weconclude that the evolution of resistance to antimalarial drugs is affected by biological specificities of the parasite across its entire life cycle, including dynamics within both hosts. Theoretical studies in this framework that incorporates parasites, humans and mosquitoes improve our understanding of the emergence and spread of drug resistance, and provide a better picture to investigate sustainable tools in the fight against malaria."} +{"text": "Cardiovascular diseases (CVDs) prevalence continues to increase, and it is still the number one killer so far. In 2002, nearly 17 million deaths all over the world were attributable to CVDs, which accounted for almost 30% of the total deaths. Despite treatment with percutaneous coronary intervention (PCI) and many other conventional medicines, CVDs patients are still confronted with certain risk of recurrent acute cardiovascular events, readmission to the hospital, and unfavorable quality of life. In recent years, more and more clinicians have successfully applied complementary/alternative medicine (CAM) in CVDs prevention and treatment based on standardized conventional therapy. Nevertheless, the role of CAM in CVDs still needs more clinical evidence and definite mechanism of actions. In this issue, a collection of several original research articles and reviews are presented that address the clinical application and the mechanism of action of CAM in the treatment of CVDs. These works were submitted by researchers from different parts of the world, including China, Japan, South Korea, Australia, and Sweden. In these studies, the effectiveness of Chinese medicine and some other alternative therapeutic methods in improving symptoms was demonstrated in patients with hypertension, chronic stable coronary artery disease, chronic heart failure, and so forth. Specifically, the use of Chinese herbal medicines was reviewed for the prevention of in-stent coronary restenosis after PCI. The study of Tanshinone IIA, a diterpene quinine extracted from the root of salvia miltiorrhiza, a Chinese traditional herb, was presented as a promising cardioprotective agent. The positive effect of Chinese food and herbal medicines in improving certain moderate dyslipidemias was described. The usefulness of Xuezhikang, an extract from Red Yeast Rice, was reviewed in the treatment of coronary heart disease complicated by dyslipidemia. A pharmacological and mechanistic study showed Naoxintong's effect on cytochrome P450 2C19. Further, one study showed the effect of berberine on improving insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. In the authors' opinion, the clinical research of Chinese medicine and other CAMs for CVDs still faces some major challenges. Issues such as overall quality of medical service and the unmet medical needs in the contemporary society are common to these medicines. A general guideline is required for practicing Chinese medicine and other CAMs, which should be developed based on solid evidence from well-designed and well-executed clinical studies. Such is the direction that the research of Chinese Medicine and other CAM should follow.Ke-ji ChenKe-ji ChenKa Kit HuiKa Kit HuiMyeong Soo LeeMyeong Soo LeeHao XuHao Xu"} +{"text": "Schistosoma mansoni infection in the northern-most islands of this archipelago, a follow-up survey was conducted to ascertain whether transmission was endemic to this island group, combining parasitological and malacological surveys. Prevalence of intestinal schistosomiasis was again observed to be high, as was intensity of infections which, combined with low reported incidence of treatment, suggests that chemotherapy-based control initiatives are not being maximally effective in this region as high levels of population movement between islands and districts are confounding. The local disease transmission was confirmed by the observations of high abundance of Biomphalaria, as well as field-caught snails shedding S. mansoni cercariae. DNA sequencing of 12 cercariae revealed common mitochondrial cox1 haplotypes, as well as, novel ones, consistent with the high genetic diversity of this parasite in Lake Victoria. Intestinal schistosomiasis is firmly endemic in parts of the Sesse Islands and more broadly, this island group provides an insight into the future challenges to be faced by the Ugandan National Control Programme in regularly reaching these rather remote, inaccessible and largely itinerant communities.The Sesse Islands, in the Ugandan portion of Lake Victoria, have long been considered a low transmission zone for intestinal schistosomiasis. Based on observations of high prevalence of Schistosoma mansoni which, as part of its life cycle, requires a suitable freshwater snail intermediate host ; the predominantly exposed, sandy beaches of the Sesse Islands, mostly almost devoid of vegetation, were thought to be unfavourable for such snails, thus limiting the potential transmission of the disease. In 2003, the Ugandan Ministry of Health initiated a National Control Programme, consisting of mass drug administration (MDA) with praziquantel (PZQ) to school-age children in high-prevalence and high-risk districts, based on baseline data from rapid mapping surveys [The Sesse Islands, in the Ugandan portion of Lake Victoria, have long been considered a low transmission zone for intestinal schistosomiasis, although until recently, few if any formal surveys had been undertaken in this archipelago. The disease is caused by the trematode parasite surveys ,2. Kalanhttp://globalnetwork.org/) funded an ambitious study to attempt to survey all islands in the Ugandan part of Lake Victoria which revealed an extremely heterogeneous distribution of intestinal schistosomiasis in school-aged children on the Sesse archipelago [in situ. Moreover, the survey, as well as previous rapid mapping exercises of the Ugandan Lake Victoria shoreline, revealed high levels of community itinerancy, with a substantial percentage of children travelling frequently between islands and the mainland [As part of a larger effort to monitor the efficacy and coverage of the National Control Programme, in January 2010 the Global Network for Neglected Tropical Diseases (GNTTD: hipelago . Notablymainland . As suchS. mansoni eggs. Egg counts were multiplied by 24 for estimation of numbers of eggs per gram of faeces (EPG). Infection intensity classes were based on WHO recommendations, whereby <100 EPG is considered a 'light' infection, 100-400 EPG is a 'moderate' infection and >400 EPG is a 'heavy' infection [To clarify the possibility of high transmission and local endemicity in this part of the Sesse Islands, in November 2010 a combined parasitology and malacology expedition was conducted throughout the northern islands of Bufumira sub-county, revisiting the sites that had been mapped in January earlier in the year. As with the previous survey, a lot quality assurance sampling method (LQAS) was attempted [nfection . Each chThe follow-up survey's findings confirmed the observation of high prevalence of intestinal schistosomiasis in this portion of Bufumira sub-county, based on 11 of the sites first surveyed in January 2010, plus an additional location , their genomic DNA extracted using published protocols [cox1 gene amplified and sequenced [S. mansoni haplotypes from Lake Victoria and Lake Albert [In contrast to the January 2010 survey of Bufumira sub-county, the follow-up expedition also included a malacological element. At 15 sites, 12 of which were associated with a location also examined for prevalence of intestinal schistosomiasis in local school-aged children, the shoreline of Lake Victoria was surveyed for the presence and abundance of rotocols , and theequenced . The edie Albert -10.Biomphalaria were found, at several of the surveyed locations inclusive of numerous other freshwater snail species , as well as, two novel haplotypes, named H139 and H140 (Genbank accession numbers HQ839767 and HQ839768). This is consistent with sampling elsewhere in Lake Victoria, where the high genetic diversity of the parasite frequently results in new haplotypes being observed; the identification of H1 and H23 suggests that the Sesse Islands are part of the wider Lake Victoria 'population' of S. mansoni, as the parasite shows little population genetic structure throughout the region, potentially due to the mixing effects of human population movement and migration [Contrary to previous surveys elsewhere in the Sesse Islands, large numbers of s Figure . The maxBiomphalaria and prevalence of infected snails was tested statistically against the environmental observations also recorded using a multivariate linear regression model; increased abundance of Biomphalaria was positively associated with low turbulence/sheltered habitats, suggesting that the exposed beaches elsewhere in the Sesse Islands might be contributing to the low numbers of snails seen there. No other variables were significantly associated with abundance or incidence of infected snails.The relationship between abundance of S. mansoni, suggest that Bufumira sub-county may be a local hotspot for intestinal schistosomiasis, and contradicts earlier evidence suggesting that this western portion of Lake Victoria is a much lower transmission environment than the eastern regions [Overall, the combination of parasitological and malacological surveys has clearly confirmed the endemicity of intestinal schistosomiasis to certain parts of the Sesse Islands, and emphasized the importance of maintaining control initiatives in Kalangala District. The high prevalence of the disease, combined with the observation of snails shedding various haplotypes of regions . In fact regions ,12. SincThe authors declare that they have no competing interests.The study was conceived by CJS, NBK and JRS. Fieldwork was undertaken by CJS, MA, FB and JRS; CJS, MA and FB collected parasitological samples and MA and JRS carried out malacological surveys. Molecular and statistical analyses were done by CJS; the manuscript was prepared by CJS and JRS, and all authors read and approved the final version."} +{"text": "Charcot neuro-arthropathy (CN) is one of the most devastating complications of diabetes. To date it appears that no clinical tools based on a systematic review of existing literature have been developed for the management of acute CN. Thus, the aim of this paper was to systematically review existing literature and develop an evidence-based clinical pathway for the assessment, diagnosis and management of acute CN.Electronic databases , reference lists and applicable websites were systematically searched for literature discussing the assessment, diagnosis and/or management of acute CN. At least two independent investigators then quality rated and graded the evidence of all identified literature. Consistent recommendations emanating from the included literature was then fashioned in a clinical pathway.The systematic search identified 267 manuscripts, of which 117 (44%) were assessed to meet the inclusion criteria for this study. As hypothesised, most literature discussing the assessment, diagnosis and/or management of acute CN constituted level IV or EO evidence. The included literature was used to develop an evidence-based clinical pathway for the assessment, investigations, diagnosis and management of acute CN.This research has assisted in developing a comprehensive, evidence-based clinical pathway to promote consistent and optimal practice in the assessment, diagnosis and management of acute CN. The pathway aims to support health professionals in making early diagnosis and providing appropriate immediate management of acute CN, ultimately reducing its associated complications such as amputations and hospitalisations."} +{"text": "The fourth international conference on emerging zoonoses brought together 180 scientists and healthcare specialists from 18 countries working to control diseases transmitted from animals to humans. The meeting took place under the auspices of the Center of Food Security and Public Health, USA, and the Institute for International Cooperation in Animal Biologics . Brucella isolates from feral swine in coastal South Carolina. Another presentation concerned the increasingly appreciated role of wildlife in the dynamic epidemiology of other zoonotic infections, such as tuberculosis. Scientists also explored the intricate routes prions follow between wildlife and domestic animals; between sheep, cattle, and humans; and between the tongue and brain of infected animals.A multidisciplinary and global approach shed new light on both old and new zoonoses. For example, brucellosis topics covered a wide range of material, from economic aspects of control in Mongolia to characterization of Since most agents of bioterrorism potential are zoonotic, a full session was dedicated to bioterrorism and biodefense. It included a global view, a report on national preparedness by Israeli hospitals, and examples of research that may eventually help experts coping with bioterrorism but would also unfortunately be accessible to persons with malicious intent.Innovative methods for preventing spread of foodborne pathogens were presented, including the use of fluorescence spectroscopy to detect fecal contamination on animal carcasses or the use of vaccination to reduce transmission of zoonotic pathogens and drug-resistant nonpathogens through the food chain to humans. In the field of xenotransplantation, key components of a source-animal production facility were described. The feasibility of breeding pigs free of designated pathogens offers hope for wide use of xenotransplantation in the near future.Mycobacterium avium subspecies paratuberculosis, the etiologic agent of Jhone\u2019s disease in cows, brought some hope in solving the long-lasting dispute on its role in the pathogenesis of Crohn\u2019s disease in humans.Participants also discussed current trends and challenges of protozoan parasitic zoonoses, including cryptosporidiosis, toxoplasmosis, African and Latin American trypanosomiasis, and leishmaniasis. Controversial zoonotic viruses were given an important place in the conference. These included hepatitis E virus, with similar strains causing liver disease in swine and humans; Borna disease virus, causing neurologic disease in various species of animals as well as, debatably, psychiatric disorders in humans; and the recently discovered severe acute respiratory syndrome\u2013associated coronavirus and its yet-undefined animal reservoir. The recent mapping of the genome of The value of using a global, multidisciplinary approach was highlighted in studies on the flow of genes among avian, swine, and other influenza viruses and on the ongoing intercontinental spread of arboviruses, exemplified by the evolving epizootic of equine West Nile encephalitis in the United States. Several papers dealt with the epidemiology of Nipah, Ebola, monkeypox, rabies, and Hantaan viruses.Escherichia coli O157:H7 or by species of Anaplasma, Bartonella, Borrelia, Campylobacter, Coxiella, Francisella, Pasteurella, and Salmonella.A series of presentations demonstrated how genomic fingerprinting and other sophisticated molecular biology techniques allow exceptionally fast development in understanding the epidemiology and pathogenesis of many zoonotic infections, such as those caused by http://www.zoonoses2003.com).The \u201cone-track\u201d meeting, by avoiding parallel and superspecialized sessions, gave an opportunity for fruitful and inspiring interactions among experts from multiple disciplines with a shared goal of mitigating human disease from emerging infections. More details on the meeting can be viewed online (available at:"} +{"text": "Chinese herbal medicine is increasingly widely used as a complementary approach for control of breast cancer recurrence and metastasis. In this paper, we examined the implicit prescription patterns behind the Chinese medicinal formulae, so as to explore the Chinese medicinal compatibility patterns or rules in the treatment or control of breast cancer recurrence and metastasis.This study was based on the herbs recorded in Pharmacopoeia of the People\u2019s Republic of China, and the literature sources from Chinese Journal Net and China Master Dissertations Full-text Database (1990 \u2013 2010) to analyze the compatibility rule of the prescription. Each Chinese herb was listed according to the selected medicinal formulae and the added information was organized to establish a database. The frequency and the association rules of the prescription patterns were analyzed using the SPSS Clenmentine Data Mining System. An initial statistical analysis was carried out to categorize the herbs according to their medicinal types and dosage, natures, flavors, channel tropism, and functions. Based on the categorization, the frequencies of occurrence were computed.The main prescriptive features from the selected formulae of the mining data are: (1) warm or cold herbs in the Five Properties category; sweet or bitter herbs in the Five Flavors category and with affinity to the liver meridian are the most frequently prescribed in the 96 medicinal formulae; (2) herbs with tonifying and replenishing, blood-activating and stasis-resolving, spleen-strengthening and dampness-resolving or heat-clearing and detoxicating functions that are frequently prescribed; (3) herbs with blood-tonifying, yin-tonifying, spleen-strengthening and dampness-resolving, heat-clearing and detoxicating, and blood-activating with stasis-resolving functions that are interrelated and prescribed in combination with qi-tonifying herbs.The results indicate that there is a close relationship between recurrence and metastasis of breast cancer with liver dysfunctions. These prescriptions focus on the herbs for nourishing the yin-blood, and emolliating and regulating the liver which seems to be the key element in the treatment process. Meanwhile, the use of qi-tonifying and spleen-strengthening herbs also forms the basis of prescription patterns. Breast cancer is one of the most common malignant tumors among women, and the incidence increases every year in both developed and developing countries . Every yToday, the standard therapies for breast cancer include surgery, chemotherapy, radiation therapy, and hormonal therapy. However, even though patients receive systemic treatment, there is still 10% to 30% chance of recurrence and metastasis. Among the patients with local recurrence, 75% to 93% will eventually develop distant metastasis with an extremely low 5-year survival rate . VisceraRecently, the use of natural Chinese herbal medicine with anti-tumor effects is receiving more and more attention from the public . In tradIn Chinese medicinal therapy, experienced Chinese medical practitioners prescribe a medicinal formula\u2014a combination of various single herbs\u2014for the treatment of ailments. According to TCM theories, pharmacological and pharmacodynamic relationship exists among herbs, which is deemed as Chinese medicinal compatibility. The compatibility of Chinese herbal medicine has particular rules and patterns. In Chinese medicinal database, there are over ten thousand medicinal formulae which enclose complicated information. However, a well-established and orderly system for organizing the information of Chinese medicinal formulae does not exist. This implies that a large amount of implicit prescription patterns behind the formulae have not been fully disclosed ,16.LHS\u21d2RHS, where LHS and RHS are sets of items, and the RHS set is likely to occur whenever the LHS set occurs. One of the applications of association rules mining is to mine association rules in medical record data [Association rules mining is one of the methods for discovering meaningful associations or correlations between variables in large databases. It identifies frequent item sets from the data sets, and then uses these frequent item sets to form their association rules. To select meaningful rules from the set of all possible rules, minimum thresholds on support and confidence are the two important constraints. An association rule has the form ord data ,18. Sincord data . The supord data .This study was based on Pharmacopoeia of the People\u2019s Republic of China recordedThere were five types of literature included, including literature: (1) related to clinical research on using Chinese medicine for the prevention and treatment of breast cancer recurrence and metastasis; (2) related to clinical research on using Chinese medicine for the treatment of advanced stage breast cancer; (3) related to clinical research on using Chinese medicine for the prevention of postoperative breast cancer recurrence and metastasis ; (4) with randomized controlled trials as the study design; and (5) where the clinical study aims to prove the efficacy of experimental group with Chinese medicinal treatment over control group.Literature with the following criteria were excluded: (1) small-sample-sized studies with less than 20 cases; (2) studies which primarily aimed to treat complications of operations or to reduce the side effects of chemotherapy; (3) studies without investigation into the use of Chinese medicine for the treatment and prevention of breast cancer recurrence and metastasis; (4) studies which provided only the names of formulae but without descriptions of herbal ingredients; (5) duplicate publications reporting the same group of participants; and (6) literature in which the clinical trial received a Jadad score of less than 2.Association rules mining is a popular and well-researched method for discovering interesting relations between variables in large databases . We usedTwo parameters (support factor and confidence factors) were essential in association rules mining. With regard to support and confidence in discovering the association rules, the user shall set the minimum support (min-sup) and the minimum confidence (min-conf) as critical values providing the baselines for discovery. Only the combinations that satisfy the minimum thresholds on support and confidence were considered to mine meaningful rules. The selection of thresholds (support and confidence) was always an issue. If the minimum confidence is set too high, a lot of useful data will be missed. To find an effective drug compatibility mode, we discovered central tendency of association rules to be more obvious at the support of 0.1 and confidence of 0.6 in the two correlation analysis of these herbs (used pairs of couplet herbs) and the pairs of herbal functions. So the minimum support of 0.1 and the minimum confidence of 0.6 were specified in this study.Based on Pharmacopoeia of the People\u2019s Republic of China, the ingredients of Chinese medicine were listed according to the selected medicinal formulae and were organized to establish a database. The computing software Microsoft ACCESS was used as a storage tool, and then the SPSS Clenmentine Data Mining System was used as a platform to analyze the frequency and the association rules of the prescription patterns. An initial statistical analysis of the database was carried out to categorize the herbs according to their medicinal types and dosage, natures, flavors, channel tropism, and functions. The frequencies of occurrence and use were then computed based on the categorization. In additionthe associations between different functions of Chinese herbs from the formulae were also examined using the association rules mining.The 180 herbs were categorized according to the Five Properties and Five Flavors Table . Based oThe results of the association analysis based on channel tropism theory among 180 herbs Table showed tThere are 96 medicinal formulae with a total of 180 herbs included in this study. The total cumulative occurrence of 180 herbs appearing in 96 formulae was 1001 times. The following 13 herbs were frequently prescribed (over 20 times):a Principal function in qi-tonifying, including : Huang Qi , Bai Zhu , Gan Cao , Tai Zi Shen (Radix Pseudostellariae), Dang Shen (Radix Codonopsitis Pilosulae)b Principal function in spleen-fortifying and dampness-resolving, including : Fu Ling (Sclerotium Poriae Cocos), Yi Yi Ren (Semen Coicis),c Principal function in heat-clearing and detoxicating, including : Shan Ci Gu (Pseudobulbus Shancigu), Bai Hua She She Cao (Herba Hedyotidis Diffusae), d Principal function in blood-tonifying, including: Dang Gui (Radix Angelicae Sinensis), u e Principal function in yin-tonifying, including: Gou Qi Zi (Fructus Lycii), f Principal function in blood-activating and stasis-resolving, including: E Zhu (Rhizoma Curcuma Phaeocaulis), andg Principal function in qi-regulating, including: Chen Pi (Pericarpium Citri Reticulatae) (Table e) Table .Herbs with tonifying and replenishing , blood-activating and stasis-resolving, spleen-fortifying and dampness-resolving or heat-clearing and detoxicating functions appeared to be most frequently prescribed for the treatment and prevention of breast cancer recurrence and metastasis Table . The topAssociation rules mining was applied to investigate the associations between pairs of herb functions from the formulae, and to examine the Chinese medicinal compatibility patterns Table . The minThe top three pairs of herbal functions with the highest confidence included the blood-tonifying paired with qi-tonifying functions (93.18%), the qi-regulating paired with qi-tonifying functions (93.10%) and the yin-tonifying paired with qi-tonifying functions (92.50%).Couplet herbs are two herbs used in pair to increase the therapeutic effect or reduce the toxic effect. To further examine the compatibility patterns of couplet-medicinal prescriptions, we targeted the herbs for healthy-qi reinforcement , and the herbs for pathogenic-factor elimination , which were frequently prescribed for the treatment and prevention of breast cancer recurrence and metastasis Table . The minFrom the herbal perspective, breast cancer is the local manifestation of a whole-body disease, referred to as an intrinsically deficient but extrinsically excessive syndrome. Based on TCM theories, deficiency of spleen qi, inadequate source of engendering transformation, deficiency of qi and blood, and excess of phlegm-dampness are believed to be the main mechanism responsible for development of breast cancer ,25.The 180 herbs were classified according to the Five Flavors, and herbs that were sweet or bitter were the top two most frequently prescribed herbs in the formulae. In TCM theories, herbs that taste sweet can be used for supplementation, moderation and harmonization, referred to as tonifying and replenishing herbs. Herbs that taste bitter can be used for discharging and downbearing, referred to as heat-clearing and detoxicating herbs. However, sweet tasting herbs with spleen-strengthening functions were prescribed and used more frequently than herbs with a bitter taste for clearing heat.Breast cancer is different from the other cancer types, as the onset of this disease usually peaks at menopausal . The patAmple clinical research of Chinese formulae reinforces the spleen to regulate qi and soothe the liver to alleviate pain. Thus, they do not only resist tumor and strengthen the body, but also have anti-cancer effects on metastatic breast cancer ,28.From the TCM perspective, the etiology of breast cancer is due to deficiency of the healthy qi, which is related to spleen qi deficiency, and liver-kidney depletion. This deficiency will result in malfunctioning of spleen, liver and kidney for transportation and transformation, and free coursing. Without the proper functioning, stagnation and obstruction of the breast collaterals will ultimately be developed and transformed into breast cancer .Restoration of healthy qi is an effective way to treat diseases and to prevent further progression. The use of qi-tonifying and spleen-fortifying herbs is to replenish the source of engendering transformation for qi and blood, and to achieve qi-tonifying, blood-replenishing and harmony of the five visceral functions. This is particularly essential for nourishing the liver and smoothing the qi movement. At the same time, spleen-strengthening and qi-replenishing herbs also have the functions for resolving dampness and dispelling phlegm. Therefore, the formulae prescribed herbs such as Huang Qi, Bai Zhu, and Fu Ling, among others.. From the association rules mining, the results showed that the combination of the herbs should also focus on the functions for qi-tonifying. The use of couplet herbs involving Huang Qi and Bai Zhu is to achieve the effects of spleen-strengthening and qi-replenishing, and dampness-drying and water-draining; the use of couplet herbs involving Bai Zhu and Tai Zi Shen is to achieve the effects of fluid-engendering and lung-moistening; the use of couplet herbs involving Bai Zhu and Fu Ling is to achieve the effects of dampness-resolving. The effectiveness of these tonifying and replenishing herbs on tumor resistance and immunity enhancement has also been proven by clinical studies ,31.The results showed that recurrence and metastasis of breast cancer is considered to have a close relationship with liver dysfunctions. These prescriptions focus on the herbs for nourishing the yin-blood, and emolliating and regulating the liver. Strengthening of liver function seems to be the key to successful treatment. Meanwhile, the use of qi-tonifying and spleen-strengthening herbs also forms the basis of prescription patterns. It is also noteworthy that liver function is promoted by strengthening the spleen.The authors declare that they have no potential and competing interests.YH performed the study; JC was in charge of the study work, advice in the study design and modified in manuscript writing.XZ, CS, ZW, TX, BJ, QY and KT equally conducted and performed the study. LC and WTYL gave expert advice in the study design and participated in manuscript writing."} +{"text": "To develop an empirically-based framework of the aspects of randomised controlled trials addressed by qualitative research.Systematic mapping review of qualitative research undertaken with randomised controlled trials and published in peer-reviewed journals.Medline, Premedline, Embase, The Cochrane Library, Health Technology Assessment, PsychINFO, CINAHL, British Nursing Index, Social Sciences Citation Index and ASSIA.Articles reporting qualitative research undertaken with trials published between 2008 and September 2010; health research; reported in English.296 articles met the inclusion criteria. They had a wide international authorship. Articles focused on 22 aspects of the trial within five broad categories. Some articles focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled ; the design, process and conduct of the trial ; the outcomes of the trial ; the measures used in the trial ; and the target condition for the trial . A minority of the qualitative research was undertaken at the pre-trial stage .A large amount of qualitative research undertaken with specific trials has been published, addressing a wide range of aspects of trials, with the potential to improve the endeavour of generating evidence of effectiveness of health interventions. Researchers can increase the impact of this work on trials by undertaking more of it at the pre-trial stage and being explicit within their articles about the learning for trials and evidence-based practice."} +{"text": "ST among populations, testing population differentiation, and performing principal component analysis (PCA) and correspondence analysis (CA). All analyses revealed a low but significant differentiation between the Amami Islanders and the mainland Japanese population. Furthermore, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using six loci included in both the Pan-Asian SNP (PASNP) consortium data and the J-MICC data. This analysis revealed that the Amami and Okinawa Islanders were differentiated from the mainland population. In conclusion, we revealed a low but significant level of genetic differentiation between the mainland population and populations in or to the south of the Amami Islands, although genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study.Uncovering population structure is important for properly conducting association studies and for examining the demographic history of a population. Here, we examined the Japanese population substructure using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC), which covers all but the northern region of Japan. Using 222 autosomal loci from 4502 subjects, we investigated population substructure by estimating F Uncovering population structure is a crucial step in properly conducting association studies because neglecting to correct for population structure can lead to both false positive results and failures to detect genuine associations It is generally accepted that the modern Japanese population was formed by the mixture of two major ancestral groups who came to Japan by different routes at different times. The mainland population of Japan shows genetic influences from both groups but appears to be predominantly descended from the second ancestral group, whereas two contemporary indigenous groups in Japan, the Ainu and Ryukyu peoples, are recognized as remnant populations descended from the first ancestral group A previous study of the Japanese population substructure, based on genome-wide association study (GWAS) data, revealed the clear differentiation between the Ryukyu and mainland populations and partially confirmed the dual structure hypothesis described above Therefore, the aim of this study is to examine the genetic differentiation between the Amami Islanders and other Japanese subpopulations . For thiGenotype data were obtained from 4514 Japanese subjects in the J-MICC study, which is one of the largest population-based cohort studies in Japan In addition to the J-MICC data, the Pan-Asian SNP (PASNP) consortium genotype data The ethics committees of all participating institutions approved the protocol for the J-MICC study, and all participants provided written informed consent.The participating institutions included:Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, Chiba, Japan,Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, JapanDivision of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan,Department of Public Health, Nagoya City University Graduate School of Medicine, Nagoya, Japan,Department of Health Science, Shiga University of Medical Science, Otsu, Japan,Department of Epidemiology for Community Health and Medicine, Kyoto, Japan,Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan,Department of Preventive Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan,Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan,Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan,Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan andLaboratory for Genotyping Development, Center for Genomic Medicine, RIKENThe J-MICC data: All genotypes were determined using the multiplex PCR-based Invader assay at the Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN 2>0.5; 52SNPs) were excluded from the data set. The remaining polymorphisms had call rates of >90% and were not excluded. Subjects with a call rate less than 90% (12 subjects) were excluded. Thus, the final data set for further analyses consisted of 221 autosomal SNPs and one autosomal indel for 4502 subjects originally designed for association studies subjects .The PASNP data: We also used all 54794 autosomal SNP genotypes available in the PASNP data. After applying the same filtering procedures used for the J-MICC data to the PASNP data, 46485 SNPs remained. Of these SNPs, only six were contained in the J-MICC data; thus, these SNPs were used for comparison between populations of the mainland, Amami Islands and Okinawa Islands.Data filtering, the calculation of basic summary statistics, and Hardy-Weinberg equilibrium (HWE) tests were performed with the R package SNPassoc STST estimates were averaged over all loci, and 95% confidence intervals (CIs) of the average FST were calculated by bootstrap resampling with 10000 replications. We used this computational method so that this study would be comparable with that of Yamaguchi-Kabata et al.ST over all loci was also estimated as the ratio of sums of the variance components in the numerator and denominator ST, variance components were estimated to reflect intra-individual, inter-individual and inter-population differences in genetic variation.To measure the differentiation between populations, the widely used statistic FTo test for differentiation between two populations based on multiple loci, Goudet's G statistic was used with 10000 permutations of individuals between populations principal components.A principal component analysis (PCA) was performed to visualize the relationship between populations; this type of analysis summarizes information for multiple loci into a few synthetic variables called For the same purpose, correspondence analysis (CA) was performed on a contingency table of minor allele counts per population. Importantly, as in any analysis carried out at a population level, all information about the diversity within populations is lost in this analysis. In contrast, PCA was performed at the individual level and not at the population level.ST estimations, variance component estimations and tests of population differentiation at multiple loci were all performed with the R package hierfstat FST over all loci and its 95% CI between each pair of subpopulations in the J-MICC data are shown in ST values between the Amami Islanders and other mainland Japanese subpopulations (0.0067\u20130.0086) were much larger than the FST values between mainland Japanese subpopulations (0.0001\u20130.0007).The average FST values for all loci; the resulting distribution is shown in ST and its 95% CI between the Amami Islanders and a population grouped across all subpopulations in the mainland. Once again, a substantially large FST value was observed . Furthermore, this genetic differentiation was statistically significant according to the G statistic (p<0.001) ST was estimated as the combined ratio estimate over all loci than the Amami Islanders are , and both Islanders groups are similar to each other . The difference in the p-values for comparisons of each Islanders group with the mainland population reflects the different sample sizes of the Islander populations (only 49 Okinawa Islanders vs. 515 Amami Islanders).Next, we examined the genetic differentiation between the mainland population, Amami Islanders and Okinawa Islanders using the same methods used for the J-MICC data. The average FST values with respect to the distance separation among the three groups.The variance component between both Islanders is 0.2%, which is about one order of magnitude less than that between the mainland population and either Islanders group ST value (\u22480.008) is slightly larger than that obtained in a previous study of the Japanese population substructure based on GWAS data (\u22480.003) In this study, a low but significant FAlthough we can separate the Amami Islanders and the mainland population using correspondence analysis (CA), we cannot separate the two groups using principal component analysis (PCA) because the number of polymorphisms (222 loci) used in this study is not large enough to classify individuals according to the two subpopulations. According to the study that first proposed regression to the principal components of the PCA to correct for population stratification Finally, it should be noted that the low coverage of study areas in this study might exaggerate the sharpness of the observed genetic boundary between the mainland population and the Amami Islanders, although the true pattern of genetic variation might be clinal. Therefore, we think that it is necessary for further studies to include individuals from the southernmost mainland part of Japan (southern Kyushu) and a few other islands between the Amami Islands and the mainland.In conclusion, we have revealed a low but significant level of genetic differentiation between the mainland population and population in or to the south of the Amami Islands, including the Okinawa Islands, although the genetic variation between both populations might be clinal. Therefore, the possibility of population stratification must be considered when enrolling the islander population of this area, such as in the J-MICC study.Figure S1ST values per locusbetween the Amami Islanders and the mainland population (JPEG).Empirical distribution of F(TIF)Click here for additional data file.Figure S2Empirical distribution of heterozygosity per locus for the Amami Islanders and the mainland population (JPEG).(TIF)Click here for additional data file.Figure S3Scree plot of principal component analysis for the mainland population and the Amami Islanders in the J-MICC (JPEG).(TIF)Click here for additional data file.Figure S4Principal component analysis plot for the mainland population and the Amami Islanders in the J-MICC. (a) PCA plot of the first and second principal components, (b) PCA plot of the first and third principal components (JPEG).(TIF)Click here for additional data file.Figure S5Principal component analysis plot of the first and second principal components for the mainland population and the Okinawa Islanders in the PASNP data. Principal component analysis was conducted for the mainland population and the Okinawa Islanders in the PASNP data, using (a) all 46485 loci and (b) 5000, (c) 1000, (d) 900 and (e) 800 loci that were randomly selected from all loci. Scree plots are shown in each figure.(TIF)Click here for additional data file.Table S1(DOC)Click here for additional data file.Table S2(DOC)Click here for additional data file.Table S3(DOC)Click here for additional data file."} +{"text": "The availability of fully sequenced genomes and the implementation of transcriptome technologies have increased the studies investigating the expression profiles for a variety of tissues, conditions, and species. In this study, using RNA-seq data for three distinct tissues , we investigate how base composition affects mammalian gene expression, an issue of prime practical and evolutionary interest.We present the transcriptome map of the mouse isochores (DNA segments with a fairly homogeneous base composition) for the three different tissues and the effects of isochores' base composition on their expression activity. Our analyses also cover the relations between the genes' expression activity and their localization in the isochore families.This study is the first where next-generation sequencing data are used to associate the effects of both genomic and genic compositional properties to their corresponding expression activity. Our findings confirm previous results, and further support the existence of a relationship between isochores and gene expression. This relationship corroborates that isochores are primarily a product of evolutionary adaptation rather than a simple by-product of neutral evolutionary processes. The genomes of vertebrates are mosaics of isochores, long regions that are fairly homogeneous in base composition. The isochores belong to a small group of families characterized by different GC levels -4. In thThe emergence of the isochores is an open debate of relevant evolutionary importance, where in addition to the selectionist model , other in silico compositional analysis of expression vectors and DNA carriers, showed that aside from the GC3 level (GC level in the third codon position) of the coding sequences, the genomic compositional context in which a gene is embedded affects its expression. Additionally, the Human Transcriptome Map (HTM), using SAGE data, revealed domains of highly and weakly expressed genes [Previous studies have investigated the effects of base composition on gene expression, both in human and mouse tissues, through an exhaustive use of expression data from techniques based on sequencing and/or hybridization -21, and ed genes , namely ed genes ,25. The ed genes ,27. In aed genes ,29. Nexted genes -32. Moreed genes -36. In ted genes in orderThe results of aligning each tissue's reads to the reference mouse genome and to the coding sequences are shown in Table GC > 53% -- marked with a vertical line in the red box in Figure Rbrain = 0.72, Rliver = 0.62, and Rmuscle = 0.65 -- see Additional file Additional file R = 0.42). Having shown the positive effect of high GC levels to the isochoric expression and between GC levels and gene density, we also looked into the direct relation between the gene density and the expression level of the individual isochores. We found a positive correlation, with similar coefficients for all tissues .It is well-known that in vertebrates, including the mouse, GC-richer isochores have higher gene densities compared to the GC-poorer ones (see the Background Section). This is confirmed by the positive linear correlation we found between the gene density of the isochores and their respective GC level , and we found a very strong preference for them to be located in the L2 family (over 50% of these genes), with decreasing presence in families of subsequently higher GC and genic compositional properties in gene expression, in the context of specific tissues or biological processes, and reveal valuable information on the implicated regulation mechanisms.To produce the transcriptome map of the isochores, we used publicly available RNA-seq data of three distinct mouse tissues , obtained in a recent study by Mortazavi et al using thlog2 of each normalized read count was calculated as a representation of the expression level. This is represented by Equation (1), where EL represents the expression level normalized over the length L of the isochore, Ri the read count of the isochore, Rt the read count of the tissue, and f the scaling factor.To investigate the expression levels of the mouse isochores, the aligned reads were assigned to the isochores containing their mapped location. The locations and GC-spans of the isochores were extracted from . To elimBecause the normalized counts are very small, the logarithm produces negative values, however, higher expression still corresponds to peaks. Details on the isochores' coordinates, GC levels, aligned reads, and expression levels, for each of the three tissues, can be found in Additional file D we denote the gene density of the isochore and by ED the isochoric expression normalized over the gene density, Equation (1) is modified as shown in Equation (2).As we report in the Results Section, the expression levels were also further normalized by the respective gene densities to account for the higher concentration of genes in isochores with higher GC level. If by To investigate the expression at gene level, the coding sequences for the mouse were retrieved from the Consensus Coding Sequence Database (CCDS) . From thECDS) was produced with Equation (3), where RCDS represents the count of aligned reads in the exons of each CDS, Similarly to the procedure followed for the expression levels of isochores, the expression level of a CDS and their respective expression levels (EL -- Equation (1)) for the brain, liver, and muscle tissues . High expression corresponds to peaks in the lines.Click here for fileCorrelations between GC level and expression activity of the isochores. The correlations between isochoric expression level ) and their GC. The red plot is for brain, the blue plot for liver, and the green one for muscle tissue.Click here for fileIsochoric expression levels for each tissue normalized over gene density. This table reports the name of each isochore, the GC level , the length , the number of genes (CDS-count), the gene density (GeneDensity -- number of genes within an isochore over its length), the count of aligned reads for each tissue , the ratio between the count of aligned reads for each tissue within each isochore over the total number of reads of that tissue , and finally the isochoric expression level normalized over the gene density (LogBr(GeneDens), LogLiv(GeneDens), and LogMusc(GeneDens)).Click here for fileDistribution of the coding sequences across the five isochore families. Within each isochore family, the % of the isochores containing at least one gene (grey bars) and of the isochores with no genes at all (light grey bars).Click here for fileDistribution of the expressed CDSs in the isochore families. For each tissue, the % of the expressed genes (in histogram -- upper panel) within each isochore and the corresponding count (in table format -- lower panel) using as expression threshold \u2265 10 aligned reads per gene. In the histogram, the red bars indicate the genes expressed in brain, the blue bars the genes expressed in liver, and the green ones in muscle.Click here for fileIsochoric expression levels for each tissue normalized over length. This table reports the name of each isochore, the GC level , length , the number of genes (CDS-count), the gene density (GeneDensity -- number of genes within an isochore over its length), the count of aligned reads within each isochore for each tissue , the ratio (%) between the count of aligned reads within each isochore for each tissue over the total number of reads of that tissue , and finally the global isochoric expression level normalized over the isochoric length (LogBr(Length), LogLiv(Length), and LogMusc(Length)).Click here for fileGenic expression levels for each tissue. This table reports the isochoric localization of each coding sequence. Specifically, the first column shows the chromosome, the second indicates the isochore in which the gene is embedded, followed by its GC level and the genomic coordinates (Start (Mb) and End (Mb)). Afterwards comes the id of each coding sequence, the genomic coordinates of the coding sequence (cds_from and cds_to), the level (GC_ccds), the GC3 (GC3_ccds), the length of the coding sequence (Length_ccds), and the count of aligned reads for each tissue within each coding sequence. The three last columns report the genic expression level for each tissue (LogBr(genic), LogLiv(genic), and LogMusc(genic)).Click here for file"} +{"text": "Sir,Biceps brachii muscle (BB) is one of the most variable muscles in the human body in terms of the number and morphology of its heads. In contrIn this report, we present a rare case of bilateral hypoplasia of the long head of the BB found during the anatomical dissection of a 58-year-old female cadaver. In both arms, the most remarkable findings were the strange-looking long heads Figure \u2013b, compoAnomalies of the long head of the BB include absence, duplication, deficiency and various origins . Embryolo3The variations of the long head of the biceps tendon could also create diagnostic difficulty in MRI. However, awareness of their existence and MRI appearance can help prevent misdiagnosis, correct prospective MRI diagnosis and avoiding unnecessary surgery."} +{"text": "The maintenance of highly regulated mechanisms to control intracellular levels of reactive oxygen species (ROS) is essential for normal cellular homeostasis. Indeed, most ROS, including free radicals and peroxides, are produced at low level by normal aerobic metabolism and play an important role in the redox-dependent regulation of many signaling processes. In contrast, excessive accumulation of ROS, resulting from an imbalance between ROS production and scavenging, leads to a condition of oxidative stress that can cause extensive oxidative damage to most cellular components, including proteins, lipids, and DNA, and may have pathophysiological consequences. Remarkably, oxidative stress has been clearly implicated in aging and the pathogenesis of several human diseases, including cardiovascular, metabolic, inflammatory, and neurodegenerative diseases and cancer. Thus, ROS may function as friends or foes of signal transduction depending on specific threshold levels and cell context.To highlight the important topics in this evolving field the Journal of Signal Transduction presents a special issue on the involvement of ROS in physiological and pathological signal transduction processes from prokaryotes to low and high eukaryotes.Neurospora crassa light signal transduction (in the second paper), the interplay between ROS and mitochondria in the control of cell death and aging (in the third and fourth papers) and cancer progression (in the fifth and sixth papers), the role of ROS in nuclear transport (in the seventh paper), the interplay between ROS and Ras GTPases (in the eighth paper), the role of ROS in the crosstalk between integrins and cadherins (in the ninth paper), integrin signaling (in the tenth paper), and skeletal muscle signaling (in the eleventh paper). These articles describe our current understanding of this field. Furthermore, this special issue highlights the importance of gaining a greater understanding of the physiological and pathological role of ROS in the perspective of defining new therapeutic strategies based on redox regulation of signal transduction processes.In particular, the topics covered in this special issue include ROS-mediated signaling in bacteria (in the first paper), the mechanisms by which ROS affect Saverio Francesco RettaSaverio Francesco RettaPaola ChiarugiPaola ChiarugiLorenza TrabalziniLorenza TrabalziniPaolo PintonPaolo PintonAlexey M. BelkinAlexey M. Belkin"} +{"text": "The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements in tumors as compared with normal tissue of the mammary gland.Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA , were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer.Regardless of the diet , DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found - irrespectively of the diet applied - great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue.Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium content in the cancerous tissue in comparison with the healthy mammary tissue. The application of combined diet supplementation with zinc ions and resveratrol considerably promoted the rate of carcinogenesis and increased the number of DMBA-induced mammary tumors. DS planned, designed and carried out the experiment, AT coordinated the study. All authors read and approved the final manuscript."} +{"text": "Increasing evidence indicates that miRNAs are essential in the development, diagnosis, treatment and prognosis of a variety of tumors. The utility of miRNAs as biomarkers for diagnosis and of target molecules for the treatment of cancers is increasingly being recognized. With the discovery of circulating miRNAs, a non-invasive approach for the diagnosis and treatment of cancer has been identified. This review summarizes the role of miRNAs in the development of different tumors, as well as a variety of other biological events. Moreover, this review focuses on analyzing the function and mechanism of gastric cancer-related miRNAs and investigates the importance of circulating miRNAs in gastric cancer, as well as their origin. Finally, this review lists a number of the problems that must be solved prior to miRNAs being used as reliable non-invasive tools for the diagnosis, treatment and prognosis of gastric cancer. The incidence of gastric cancer ranks fourth in males and fifth in females, while the mortality ranks third in males and fifth in females among all cancers worldwide . The incet al observed that in gastric cancer cell lines 17 miRNAs were upregulated and 146 miRNAs were downregulated compared with normal gastric mucosa (microRNAs (miRNAs) are becoming increasingly recognized as important in cancers, including gastric cancer. To date, >1,400 miRNAs have been described in humans . Yu et ac mucosa . miRNAs c mucosa . ConsequC. elegans in gastric cancer cells Determining the source of circulating miRNAs; ii) validating a classical pathway of circulating miRNA transmittance; iii) clarifying the mechanism of the action of various circulating miRNAs in gastric cancer; iv) determining how the circulating miRNAs in different stages of gastric cancer development are expressed and how miRNAs develop in this development process; v) highly specific and sensitive detection of miRNA pre- and post-operatively, as well as at various stages of gastric cancer; vi) clarifying the mechanism of synergy/antagonism of various circulating miRNAs in the occurrence and development of gastric cancer; and vii) determining the feasibility of certain miRNA target therapies at different stages of gastric cancer according to associated miRNA specificity."} +{"text": "The classical concept of PTSD has been criticized for many reasons, including its cultural limitations and negligence of long-lasting changes to personality, which has been documented in cases of chronic interpersonal trauma. The concept of complex PTSD has addressed these shortcomings and specifies \u201calterations in self-perception\u201d as one of the characteristic changes in functioning following extreme and chronic trauma. Torture survivors and refugees are a population particularly affected by cumulative traumatization. The experience of torture comprises the deliberate and systematic devastation of values, beliefs, self-concept, and personality development. It has severe effects on the survivors\u2019 fundamental trust, self-identity, and attachment. Meanwhile, refugee trauma involves the long-term experience of discrimination, persecution, helplessness, and humiliation, which also has a significant impact on the individual's personal and collective identity. A number of studies and theories now exist, which describe the psychological effect of torture and refugee trauma on identity. However, the issue of torture and life in exile is generally discussed separately. The present research aims at integrating the two phenomena and focuses on the unique and combined effect that torture and refugee trauma has on the survivors\u2019 identity. The qualitative study comprises narrative in-depth interviews with refugee torture survivors and applies a psychoanalytic framework for interpreting the data."} +{"text": "The safety of patients is not yet in the priorities of the health system in DRC despite the country is with Nigeria and Ethiopia, the head of the African countries that are at high risk of complications and maternal mortality against 1.34 10-4 in developed countries. Under these conditions, achieve the Millennium Development Goals to reduce by 2/3 of maternal mortality in 2015 is impossible, unless efforts are made in huge areas.To assess the proportion of hospital infections in maternal morbidity and mortality observed in the maternity Lubumbashi.Descriptive cross-sectional study conducted in two maternity second (10 deliveries / day) and third levels (30 births / day) of the city of Lubumbashi. The relevant parameters are maternal mortality, hospital hygiene, quality of care, performance of biomedical laboratories, supplies of antibiotics.It was noted:In terms of hygiene: sanitary conditions are deplorable with no water points, disinfectants, antiseptics or gloves (unarmed deliveries). In terms of patient safety: No respects procedures during blood transfusions, infusions, injections, often performed cesarean section without asepsis emergency. In epidemiological terms: maternal mortality rate higher in the maternity tertiary level, especially related to the intra-hospital infections after cesarean section despite a higher skill level.Improving patient safety in maternity services in DR Congo through the implementation of emergency measures post-crisis to address issues related to the disruption of the health system, the morale and training of health personnel, and the paucity of hospitals.None declared"} +{"text": "The global supply of food has led to an increasingly connected planet, not only in terms of food products but also in terms of risks for foodborne diseases. The fourth edition of Morris and Potter\u2019s Foodborne Infections and Intoxications delivers an in-depth look at the global effects of foodborne illnesses, provides pathogen-specific information, and describes processes and policies intended to prevent these illnesses. The text is a well-written and well-referenced guide to foodborne illnesses, containing contributions from >70 experts in epidemiology and the basic sciences of foodborne diseases.The text has been organized into 6 sections. The first section describes the epidemiology of foodborne disease, highlighting the most common illnesses in the United States and abroad with country-specific data as well as the most common outbreak-associated foods and microbial risk assessment. The next 4 sections encompass microbe-specific illnesses; each section comprises chapters on specific pathogens. The sections are organized to include bacterial pathogens, viral pathogens, parasites , and agents involved with food intoxications. Each chapter is specific to a given pathogen and includes a clinical description of the disease, the microbiology of the pathogen, exposure risks, and disease prevention. Escherichia coli O104:H4 infections in northern Germany. This outbreak illustrates the importance of food safety and the critical role of public health officials, clinicians, and scientists in identifying new outbreaks and limiting the spread of newly identified illnesses. The final section of the book outlines prevention of foodborne diseases and discusses food safety and the legal basis for food safety regulation.Chapters have been written by leading researchers in their respective fields and are filled with up-to-date references on each pathogen. One example, in Chapter 8, includes a description of the 2011 outbreak of This edition of Foodborne Infections and Intoxications updates the third edition, published in 2006, with increased emphasis on global disease prevention and a risk-based approach to food safety. This text is particularly valuable for students and practitioners in the fields of public health and food safety. It can also serve as a useful reference for public health investigators and officials."} +{"text": "This special issue of Nanoscale Research Letters contains scientific contributions presented at the International Conference \"Micro&Nano2010 - Special Symposium on Nanomaterials for sensing and energy harvesting devices\", which was held in Athens, Greece, from December 12-15, 2010.http://www.micro-nano.gr). The Conference aims at gathering together in an interactive forum scientists and engineers working in the challenging field of Microelectronics, Nanoelectronics, Nanotechnologies and MEMs and to stimulate discussions in last achievements and new developments in this rapidly evolving field. One of the key objectives of the Conference is to promote collaboration and partnership between different academia, research and industry players in the field. The Conference combines an extensive scientific programme, including oral and poster sessions, with an exhibition and social events.Micro&Nano2010 was the fourth of a series of Conferences on Microelectronics, Nanoelectronics, Nanotechnologies and MEMs held in Athens-Greece every three years and organized by the \"Micro&Nano\" Scientific Society (Within \"Micro&Nano2010\" a special Symposium was organized on nanomaterials for sensing and energy harvesting devices. A selected collection of papers of this Symposium are found in the present special issue. The full volume of the Proceedings, including micro- and nanomaterials, technologies and devices, will appear as a special issue of the journal \"Microelectronic Engineering\".The guest editor of this issue and Chairperson of \"Micro&Nano2010\"Androula G. NassiopoulouHead of the Nanostructures for Nanoelectronics, Photonics and Sensors Research groupTerma Patriarchou Grigoriou, Aghia Paraskevi153 10 Athens, GreecePresident of Micro&Nano Scientific SocietyDirector of Research, IMEL/NCSR Demokritose-mail: A.Nassiopoulou@imel.demokritos.gr"} +{"text": "Graves' orbitopathy, despite of the results of recent researches concerning pathomechanism of the disease, is still a therapeutic challenge. Corticosteroids are the treatment of choice for active, moderate to severe Graves' orbitopathy.The aim of the study is to evaluate the effects of treatment of patients with GO with novel protocol of steroidotherapy designed and introduced in Department of Endocrinology, Metabolism and Internal Medicine. The management protocol consists of 3 g of methylprednisolone administered intravenously followed with methylprednisolone injected intramuscularly in divided doses every 3 weeks .The study group consisted of 50 patients. Assessment of efficacy of therapy was performed before and immediately after the therapy and 6 months later. Thyroid function parameters , titers of thyroid autoantibodies , thyroid volume (V) were analyzed. Moreover, ophthalmological findings and disease activity on magnetic resonance imaging of orbits were evaluated.The therapy significantly improved the degree of soft tissue involvement, CAS, diplopia and decreased the autoimmune disease activity in oculomotor muscles. Moreover, significant decrease of TRAb titer was observed.To conclude, novel protocol of glucocorticoid therapy is effective and safe."} +{"text": "Nanoscale Research Letters features selected papers presented at the Symposium E: \"Nanoscaled Si, Ge based Materials\" of the EMRS Fall meeting, held in Warsaw, Poland from September 13-h16, 2010.This special volume of The symposium was organized by Fabrice Gourbilleau , Artur Podhorodecki and Nicola Daldosso . CNANO North West kindly sponsored the symposium.The goal of the symposium was to describe exciting, state-of- the- art applications of Si or Ge nanoparticle-based materials, doped or not with rare earth ions, in the fields of (i) information storage, (ii) optoelectronic devices, (iii) telecommunications, as well as (iv) life sciences. using the. The origin of such intense research activity in these different domains can be explained by the potential of Group IV nanostructures to lead to either (i) future chips with optical interconnects in which CMOS compatible electronic and photonic and/or biosensing components aree integrated or (ii) the future generation of solar cells with lower cost and/or higher efficiency.The four-day symposium included 13 sessions in which 48 oral and 18 poster presentations gave a comprehensive overview of progress toward a wide range of applications as well as the development of new promising techniques for microstructural investigations at the atomic scale. The papers published in this special volume have been selected after careful peer review, and form an authoritative reference for future applications.The organizers wish to thank the EMRS staff for their help in the organization of the symposium."} +{"text": "Plasmodium falciparum malaria. ACT combines two effective antimalarial drugs and is the cornerstone of successful malaria control and ultimately, elimination. Fixed-dose combinations (FDC) of ACTs are preferred, as they promote adherence to treatment and reduce the risk of selecting for drug-resistant parasites.The World Health Organisation (WHO) currently recommends the use of five artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated initiative (DNDi), together with the WHO Special Programme for Research and Training in Tropical Diseases (TDR), launched the FACT (Fixed Dose Artesunate Combination Therapy) project in 2002, with original funding from INCO/DEV. The FACT core group also included the Brazilian government-owned pharmaceutical company, Farmanguinhos/Fiocruz, the University of Bordeaux, Universiti Sains Malaysia, Mahidol University and the Shoklo Malaria Research Unit in Thailand, the Centre National de Recherche et de Formation sur le Paludisme in Burkina Faso and the University of Oxford, combining epidemiological and drug development expertise. Additional competencies in clinical studies, clinical supplies and regulatory matters strengthened the core team. Through innovative collaborations with this variety of partners, the FACT project delivered FDCs of Artesunate (AS) plus Amodiaquine (ASAQ), and AS plus Mefloquine (MQ). Key contributions in scale-up, industrial production and regulatory filing were still needed to make the products available to patients, and different strategies were set up for each product. Both strategies were based on an initial development within the public and not-for-profit sector, with an extension to the private sector when a viable product was available, for registration, production and distribution.In order to strengthen the ACT portfolio of FDCs, which at the time was minimal, the Drugs for Neglected Diseases Sanofi took over the last steps of industrial development and regulatory filing for ASAQ and the product was pre-qualified by WHO in 2008. Since then, ASAQ has been registered in over 30 countries, mostly in sub-Saharan Africa and over 120 million treatments have been delivered - making this the second most widely used ACT. Deployment was accompanied by a risk-management plan, together with an extensive training and educational programme developed by Sanofi. ASMQ FDC production was scaled up by Farmaguinhos/Fiocruz and registered in Brazil in 2008. A large intervention study involving over 23,000 patients was performed by the National Malaria Control Programme in Brazil showing the efficacy of the product in real-life conditions. Through a South-South technology transfer, ASMQ FDC production was transferred to the Indian pharmaceutical company Cipla to ensure availability in India and South East Asia. ASMQ FDC was registered in India in 2011 and in Malaysia in early 2012 and is under review for WHO prequalification.The FACT project demonstrates that alternative drug development strategies can make safe, affordable and sustainable treatments available to patients. Diverse partnerships gathering a wide range of expertise, from national programmes ensuring the most appropriate therapy is used in endemic areas to industrial partners for product implementation and wide distribution, were key to success. Both ASAQ and ASMQ FDCs are critical drugs for malaria control across Africa, Latin America and South East Asia."} +{"text": "The purpose of this article is to reflect on the proceedings of the ALMA working session.In 2009 a total of 153,408 malaria deaths were reported in Africa. Eleven countries showed a reduction of more than 50% in either confirmed malaria cases or malaria admissions and deaths in recent years. However, many African countries are not on track to achieve the malaria component of the Millennium Development Goal (MDG) 6. The African Leaders Malaria Alliance (ALMA) working session at the 15Working methods of the session included speeches and statements by invited speakers and high-level panel discussions.The main bottlenecks identified related to the capacity of the health systems to deliver quality care and accessibility issues; need for strong, decentralized malaria-control programmes with linkages with other health and development sectors, the civil society and private sector entities; benefits of co-implementation of malaria control programmes with child survival or other public health interventions; systematic application of integrated promotive, preventive, diagnostic and case management interventions with full community participation; adapting approaches to local political, socio-cultural and administrative environments.The following prerequisites for success were identified: a clear vision and effective leadership of national malaria control programmes; high level political commitment to ensure adequate capacity in expertise, skill mix and number of managers, technicians and service providers; national ownership, intersectoral collaboration and accountability, as well as strong civil society and private sector involvement; functional epidemiological surveillance systems; and levering of African Union and regional economic communities to address the cross-border dimension of malaria control.It was agreed that countries needed to secure adequate domestic and external funding for sustained commitment to malaria elimination; strengthen national malaria control programmes in the context of broader health system strengthening; ensure free access to long-lasting insecticide treated nets and malaria diagnosis and treatment for vulnerable groups; strengthen human resource capacity at central, district and community levels; and establish strong logistics, information and surveillance systems.It is critically important for countries to have a clear vision and strategy for malaria elimination; effective leadership of national malaria control programmes; draw lessons from other African countries that have succeeded to dramatically reduce the burden of malaria; and sustain funding and ongoing interventions. Dr Gro Harlem Brundtland, the then Director-General of the World Health Organization (WHO), identified Roll Back Malaria (RBM) as a priority project of the renewed WHO and established it as such on 23 July 1998 [In September 2000 the UN added efforts to fight malaria to the Millennium Development Goals (MDGs) . The AfrAt the Abuja Summit in 2006 African Union Heads of State and Government called for universal access to HIV/AIDS, tuberculosis and malaria services by a united Africa by 2010 and for a long-term vision on malaria elimination .In 2008 the Global Malaria Action Plan was developed, and the malaria endemic countries developed road maps to scale up cost-effective interventions towards achieving the MDGs . This inIn September 2009 the 59th WHO Regional Committee for Africa adopted a resolution on Accelerated Malaria Control, Towards Elimination in the African Region, which calls for, among other actions, integration of malaria control in poverty reduction strategies and all national health and development plans and mobilization of local resources for sustainable implementation of the strategies .On 23 September 2009 His Excellency President Jakaya Kikwete of Tanzania, Past Chairman of the African Union, launched the African Leaders Malaria Alliance (ALMA) during the Sixty-fourth Session of the United Nations General Assembly . The purThe ALMA working session at the 15th African Union Summit in Kampala was held 25\u201326 July 2010 in the context of calls for increasing efforts to accelerate progress towards MDGs 4 , 5 and 6 and was in line with the theme of the Summit, \u2018Maternal, Infant and Child Health and Development in Africa\u2019. The session agenda was also well aligned with the issues discussed at the previous satellite session on health financing.The purpose of this article is to reflect on the proceedings of the ALMA working session.The session included speeches and statements by invited speakers and high-level panel discussions. It was chaired by His Excellency Jakaya Mrisho Kikwete, President of the United Republic of Tanzania. The panel comprised the host of the African Union Summit, President Yoweri Museveni of Uganda, President Robert Mugabe of Zimbabwe and ministers of health and officials from African Union Member States. Invited speakers included Mr Raymond G. Chambers, UN Secretary General's Special Envoy for Malaria; Mrs Asha-Rose Migiro, UN Deputy Secretary-General; Mrs. Obiageli Ezekwesili, World Bank Vice President for Africa; Professor Michel Kazatchkine, Executive Director of the Global Fund to Fight Aids, Tuberculosis, and Malaria (GFATM); Mr Kapembwa Simbao, Minister of Health of Zambia and Chairman of the Roll Back Malaria Partnership Board; Dr Luis Gomes Sambo, WHO Regional Director for Africa; and Mrs Johannah-Joy Phumaphi, Executive Secretary of ALMA.In his opening remarks, President Jakaya Mrisho Kikwete, stated : \u201cI see President Kikwete underlined two strategic goals: (i) to achieve universal mosquito net coverage by the end of 2010 and (ii) to eliminate preventable malaria deaths by 2015 by scaling up coverage of all other available interventions .He acknowledged that these were audacious goals, but with more than 680,000 African children dying each year from malaria, audacity was a moral imperative. He strongly advocated for malaria control as a step towards achieving MDGs 4 and 5 . As convener of ALMA, President Kikwete noted the tremendous contribution of the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) and the World Bank in helping to finance malaria control in Africa. He expressed ALMA support for the full replenishment of funding to both GFATM and the International Development Association of the World Bank.Finally, President Kikwete called upon African leaders, communities and partners to make a final push to reach universal coverage of interventions against malaria.The UN Secretary General Special Envoy for Malaria focused his statement on the need to achieve universal coverage with essential interventions to end preventable deaths due to malaria . He highThe UN Deputy Secretary-General, addressing the AU leaders, indicated that the fight against malaria was boosting women\u2019s and children\u2019s health . She appThe World Bank Vice President for Africa indicated that the World Bank was making investments in malaria control that would have returns both in terms of lives saved and well beyond the health sector . Those iThe Executive Director of GFATM presented recent evidence on the impact of GFATM supported national programmes in saving lives and contributing to health systems and development . He stroDr Luis G. Sambo informed the session that the African Region accounted for 85% of malaria episodes and 89% of malaria deaths worldwide . He remiDr Sambo reported that over the last decade, African countries had scaled up proven malaria interventions, which include vector control using long-lasting insecticide-treated nets ,20, indoDr Sambo highlighted the encouraging achievements of Botswana, Cape Verde, Eritrea, Namibia, Rwanda, Sao Tome and Principe, South Africa, Swaziland, Zambia and Zanzibar (Tanzania) in reducing the number of malaria cases by at least 50% between 2000 and 2008 . This suHe informed the meeting that some countries were contemplating the transition from sustained control to elimination of malaria owing to their very low malaria transmission levels and based on robust epidemiological evidence and feasibility assessments. Governments contemplating the pursuit of malaria elimination will need to secure adequate domestic and external funding for sustained commitment; strengthen national malaria control programmes in the context of broader health systems strengthening; strengthen human resource capacity at central, district and community levels; establish strong logistic, information and surveillance systems as well as early detection mechanisms for response to malaria epidemics and complex emergencies; and forge effective cross-border and trans national malaria control collaborative initiatives.According to Dr Sambo, the use of oral artemisinin monotherapy was a potential driver in emergence of resistant malaria parasites. In May 2007 the World Health Assembly adopted Resolution WHA60.18, which urged Member States to deploy recommended artemisinin-based combination therapies (ACTs) and withdraw oral artemisinin-based monotherapies. He informed the meeting that by July 2010, 30 countries in the African Region had taken regulatory measures to withdraw oral artemisinin-based monotherapies. He urged the remaining countries to urgently develop similar policies to stop the marketing of oral artemisinin-based monotherapies.Dr Sambo cited a study that estimated at US$ 3 billion per year Africa\u2019s need for global resources to attain international malaria control goals. Financial support to African countries for prevention and control of malaria totals approximately US$1.6 billion per year and comes from GFATM, the US President\u2019s Malaria Initiative (PMI), the World Bank Booster Programme for Malaria Control in Africa, the United Kingdom Department for International Development (DFID), Bill and Melinda Gates Foundation and other agencies and foundations. He indicated that based on the cost of an essential package of interventions, this support represents 53% of the estimated financial resources needed to reach global malaria control targets . He appeHe concluded by appealing to the Heads of State to foster leadership for improved intersectoral collaboration to eliminate malaria as a public health problem in Africa; increase domestic funding for malaria control and accelerate progress towards MDGs 4, 5 and 6; support viable initiatives for local production of quality medicines and other commodities; eliminate taxes and tariffs on antimalarials and other public health essential commodities; and ensure free access to malaria diagnosis and treatment for vulnerable groups such as children and pregnant women, in addition to universal access to long-lasting insecticide treated nets.Mrs Johannah-Joy Phumaphi reported on the ALMA call for immediate acceleration of procurement, shipment and distribution of malaria commodities . She expMrs Johannah-Joy Phumaphi expressed concern that the high tariffs on commodities, such as bed nets and antimalarial drugs, make them expensive and hamper access. She cited the latest data that indicated that only five African countries had completely eliminated these tariffs.In his remarks to ALMA, Mr Kapembwa Simbao, Minister of Health of Zambia , expressZimbabwe, Zambia, Rwanda, Nigeria, Mozambique, Kenya and Mauritius presented their experiences in scaling up of malaria control interventions, cross-border collaboration and malaria elimination challenges. These experiences revealed the link between malaria control and maternal and child health. The debate provided insights on the importance of implementing comprehensive programmes, including community involvement, the need to build adequate capacity for vector control, and the use of rapid diagnostic tests. The role of nongovernmental organizations (NGOs) and public-private partnerships was also covered. The innovative approaches highlighted included involvement of school children and teachers in Mozambique, building capacity of village health workers in Zimbabwe, fostering cross-border collaboration among Mozambique, Swaziland and South Africa, and establishing model health centres in Kenya. Mauritius talked on its efforts to prevent reintroduction of malaria by using active surveillance and enforcing travel health regulations.th October 2010, the ministers of health from the republics of Benin, Cameroon, Central African Republic, Chad, Equatorial Guinea, Niger and Nigeria met in Abuja and signed the Abuja Commitment on Cross-Border Public Health Issues. The countries represented agreed to establish a joint initiative that permits multi-sector involvement in prevention and control of multiple public health problems in participating countries; promote communities-based initiatives on information, education and communication for disease prevention and control; promote cross-border initiatives in early detection of epidemics and improvement of water supply, sanitation and hygiene; advocate for operationalization of the African Public Health Emergency Fund to support emergency and cross-border public health activities; strengthen National Disease Surveillance Systems and share information on cross border health issues; establish National Agency for Drug Control and inter-country multi-disciplinary committees to monitor the quality of medicines and the circulation of counterfeit medicines across borders; provide (on request) technical and logistics support to any of the participating countries in the management of public health emergencies; and appoint focal persons to constitute a committee to follow-up recommendations made in the inter-ministerial meeting [Cross-border collaboration is necessary for malaria control in Africa because of the large negative externalities involved. Elimination of malaria in one country will not be sustained if the neighbouring countries experience high transmission of malaria, as citizens mix freely along borders, re-introducing malaria through travel and migration. Cross-border mechanisms that could be leveraged for controlling malaria already exist in the African Region. There are two recent examples. First, on 18 meeting .th March 2011, the ministers of health of the Republic of Angola, Republic of Congo, Democratic Republic of Congo, Republic of Namibia and Republic of Zambia met in Lusaka and signed a Memorandum of Understanding (MOU) on Cross Border Public Health Issues. The MOU touches on progress towards achievement of health related MDGs; strengthening health systems to support cross border public health issues; prevention and control of cholera and other epidemic prone diseases; polio eradication; surveillance and international health regulations; fake and counterfeit medicines; and monitoring and evaluation of cross border public health issues. Such mechanisms can be used to mobilize domestic and external resources, design, implement, monitor and report on cross-border public health action against infectious diseases [Second, on 18diseases .The country presentations echoed the sentiment of the high-level panel that the burden of malaria should be addressed as a priority health, social and developmental issue and no longer as a fatality threat for Africa. The need of tackling vector, parasite and host factors in the context of specific environmental and climatic conditions also was highlighted during the debate. Speakers at the session emphasized the necessity of multi-pronged approaches as the way forward to sustain the gains in reduction of malaria morbidity and mortality. There was agreement that the old but still valid notion of the pathogenic malaria complex must remain at the core of malaria control and elimination strategies .The main bottlenecks identified by country representatives related to the capacity of the health systems to deliver quality care and to issues of ensuring universal access to diagnostic services and treatment. The participants unanimously agreed on the need for strong, decentralized malaria-control programmes with linkages with other health and development sectors, the civil society and private sector entities. Recent publications highlight the benefits of co-implementation of malaria control programmes with child survival or other public health interventions ,32-34. FHowever, it is important to acknowledge the challenges that have to be overcome in ensuring universal access to malaria prevention and control services; and getting people to use those services once access has been assured. The first challenge is to develop sustainable health financing mechanisms that assure free access to diagnosis, treatment and insecticide treated nets for the poor. Such mechanisms may entail a combination of social health insurance and tax funded health services. In addition, health development partners can complement government efforts by paying social health insurance premiums on behalf of the poor. Furthermore, partners can reinforce national governments capacities for providing free access for the poor through general budget support. The second challenge draws attention to the fact that even with free access, utilization may be a problem because non-financial barriers to use of diagnostic services and medication can be significant . The nonThe success mentioned above has been made possible by a number of enabling factors. First, existence of a clear vision and effective leadership contributed to improvement in the governance, stewardship and success of national malaria control programmes. Second, high level commitment has ensured relatively adequate capacity in expertise, skill mix and number of managers, technicians and service providers, including for community interventions and case management. Third, national ownership, intersectoral collaboration and accountability, as well as strong civil society and private sector involvement, are important attributes of well-performing malaria control programmes. Fourth, successful programmes have the capacity to adjust to the rapidly changing malaria epidemiology. Fifth, several regional initiatives initiated with the support of AU and regional economic communities contributed in addressing the cross-border dimension of malaria control.The panellist\u2019s emphasized countries that had achieved significant reductions in the malaria burden required support to undertake programme assessments to ensure sustained control and evidence-based transition to elimination of the disease. This requires in-depth programme reviews, strengthening of capacity for surveillance monitoring and evaluation and intensification of cross-border collaboration. It will entail contribution of research and research based institutions in the collection, analysis and dissemination of information for better control, adjustments, and policy guidance.The meeting was informed that the WHO regional framework for the acceleration of malaria control towards elimination and the guidelines on malaria elimination were available to guide the countries in planning, implementation, monitoring and evaluation of malaria programmes . Moreove\u2022 Securing adequate domestic and external funding for sustained commitment to malaria elimination;\u2022 Strengthening national malaria control programmes in the context of strengthening the broader health system;\u2022 Ensuring free access to malaria diagnosis and treatment for vulnerable groups such as children and pregnant women in addition to universal access to long-lasting insecticide treated nets;\u2022 Strengthening human resource capacity at central, district and community levels;\u2022 Establishing strong logistics, information and surveillance systems as well as early detection mechanisms for response to malaria epidemics and other public health threats.A number of conclusions emerged from the discussions. First, ALMA working sessions at the African Union Summit were critically important for sustaining the focus on accelerated malaria control and elimination vision and strategy in support of actions at the country level. Second, there is need for documenting and sharing lessons learnt from African countries that have succeeded to dramatically reduce the burden of malaria. Third, the achievements in some countries clearly indicate that the Abuja and MDG malaria targets are achievable if funding and ongoing interventions are sustained. Lastly, there was a strong indication that the next MDG summits will also offer a forum for strategic projections and consolidation of financing and implementation pledges ,51.ACTS: Artemisinin-based Combination Therapies; ALMA: African Leaders Malaria Alliance; GFATM: Global Fund to Fight AIDS, Tuberculosis and Malaria; MDG: Millennium Development Goal; NGO: Non-governmental Organization; UN: United Nations Organization; WHO: World Health Organization.The authors declare that they have no competing interests."} +{"text": "As part of a Berlin-based research consortium on health in old age, the OMAHA study aims to develop a conceptual framework and a set of standardized instruments and indicators for continuous monitoring of multimorbidity and associated health care needs in the population 65 years and older.OMAHA is a longitudinal epidemiological study including a comprehensive assessment at baseline and at 12-month follow-up as well as brief intermediate telephone interviews at 6 and 18 months. In order to evaluate different sampling procedures and modes of data collection, the study is conducted in two different population-based samples of men and women aged 65 years and older. A geographically defined sample was recruited from an age and sex stratified random sample from the register of residents in Berlin-Mitte for assessment by face-to-face interview and examination. A larger nationwide sample was recruited for assessment by telephone interview among participants in previous German Telephone Health Surveys. In both cohorts, we successfully applied a multi-dimensional set of instruments to assess multimorbidity, functional disability in daily life, autonomy, quality of life (QoL), health care services utilization, personal and social resources as well as socio-demographic and biographical context variables. Response rates considerably varied between the Berlin and German OMAHA study cohorts (22.8% vs. 59.7%), whereas completeness of follow-up at month 12 was comparably high in both cohorts (82.9% vs. 81.2%).The OMAHA study offers a wide spectrum of data concerning health, functioning, social involvement, psychological well-being, and cognitive capacity in community-dwelling older people in Germany. Results from the study will add to methodological and content-specific discourses on human resources for maintaining quality of life and autonomy throughout old age, even in the face of multiple health complaints. Multimorbidity, e. g. the concurrent existence of multiple health problems in the same person, is a highly prevalent phenomenon in old age and of growing public health impact in aging societies -3. The tDue to methodological challenges and limited epidemiological data, the prevalence, patterns, determinants, correlates, and consequences of multimorbidity are not well researched ,6. A firAgainst this background, the Federal Ministry of Education and Research (BMBF) launched a long term research initiative on 'Health in Old Age'. A total of six research consortia qualified for an initial three-year funding period (2008-2010) to provide insight into the epidemiology and socioeconomic consequences of multimorbidity in older people in Germany . Among tThe population-based AMA subproject OMAHA aims to develop a conceptual framework and a set of standardized instruments and indicators for continuous monitoring of multimorbidity and associated health care needs in the population 65 years and above. Main specific goals are: (1) to develop an algorithm for the comprehensive assessment of multi- and comorbidity, (2) to analyze patterns, correlates, determinants, and consequences of multi- and comorbidity; (3) to evaluate an innovative instrument for preference-based QoL assessment among elders with multimorbidity; (4) to examine the effectiveness and efficiency of different recruitment strategies and to characterize difficult-to-reach subgroups of the population 65 years and older. We describe here the design, methods, study population, and data base of the OMAHA study.The OMAHA study is designed as a population-based longitudinal epidemiological study of multimorbidity in the population aged 65 years and older. With regard to methods applied for continuous nationwide health monitoring in Germany , the OMAThe study was approved by the local ethics committee at Charit\u00e9 - Universit\u00e4tsmedizin Berlin and conducted in compliance with data protection and privacy regulations as requested by the Federal and Berlin Offices for the Protection of Data. Study participants were informed in detail about the study objectives, interview and examination procedures as well as pseudonymized record keeping and subsequent data analysis. Persons participating in the personal interview and examination gave written informed consent prior to study inclusion. A subset also provided written permission to contact their family doctor for validation of specific self-reported medical conditions . Oral informed consent to study participation was obtained from participants in previous German health telephone surveys before conducting the OMAHA baseline CATI.For the Berlin OMAHA cohort, we drew an age and sex stratified random sample of 2000 men and women aged 65 years and older from the official register of residents in Berlin-Mitte as of July 15, 2008. All individuals of the population sample who were then verified as alive, still living in Berlin-Mitte and available during the study recruitment period were eligible for the study. Exclusion criteria were: death, permanent change of residence outside of Berlin-Mitte or to an unknown address, and continuous absence from Berlin during study recruitment period. Anticipating an overall response rate of about 20% and an overall proportion of unverifiable contacts of 5-10%, the total sample size was sufficiently large to achieve a study population of n = 300 for the main study and of n = 100 for preceding pre-test evaluation.To assure public support of the study, we communicated the study goals and logistics to members of the Berlin Medical Association via the official journal of the Berlin Medical Association and to community officials via telephone contacts.Individuals belonging to the main sample were initially contacted by post. The letters contained a brief description of the study, an invitation to participate, and a prepaid self-addressed envelope together with a return sheet to fill in telephone numbers, preferred contact times, and choice of home or study centre visit for the assessment. Participants were offered a small monetary incentive (\u20ac 10) plus reimbursement for travel expenses. Foreign nationals were offered a brief description of the study in seven different languages .In order to identify and further characterize persons who did not participate, we explicitly asked family members or caregivers to respond in case that an eligible person was not able to participate due to cognitive impairment or severe illness and to consent to proxy telephone interviews.Among persons who did not respond to the initial mailed invitation, we conducted a randomized controlled trial which evaluated the effectiveness and efficiency of three different intensified recruitment strategies: (a) personal visits, (b) telephone calls, or (c) mailed reminder letters including the initial invitation letter and enclosures. Statistical analysis of this comparative evaluation of recruitment strategies is completed and results are currently prepared for publication in a separate paper.German OMAHA cohort was recruited from a pool of persons who had previously participated in the German Telephone Health Surveys 2004 or 2006. Nationwide telephone health surveys have been conducted in Germany annually by the Robert Koch Institute since 2002/2003; sampling procedures and recruitment strategies have been previously described in detail [The n detail . In brien detail . This men detail ; 2682 won detail ). The maOf the total Berlin sample, 519 persons (26.0%) had initially been contacted for preceding pre-test evaluation, leaving a total of n = 1481 persons for the main study was drawn from the German Telephone Health Survey sample 2007 .N = 1552 participants in previous German Telephone Health Surveys 2004 and 2006 were selected for the OMAHA study potential consequences of multimorbidity, including impairment of body functions and frailty, autonomy, quality of life, and health care services utilization, (c) personal and social resources likely to modify the association between multimorbidity and outcome measures, (d) socio-demographic and biographical context variables.Within the conceptual framework depicted in Figure Selection of instruments was based on extensive literature review and feasibility pre-testing. Table multimorbidity is composed of two domains: (a) health status as assessed by self-reported physician-diagnosed health conditions, history of surgical procedures, history of fractures past age 50 years, medication use within 7 days prior to the interview, and standardized measures (Berlin cohort only) of height, weight, waist and calf circumference, and blood pressure; (b) self-reported current symptoms and complaints including sensory limitations (vision and hearing problems), urinary and faecal incontinence, constipation, back pain, and joint complaints. Overall, 31 specific health conditions were covered in the CAPI and CATI following a standardized sequence of questions on first and last time of occurrence of symptoms, medical treatment within the past 12 months, and perceived level of condition specific limitation in daily life was assured by scanning the original containers brought to the examination site for that purpose. All drugs were automatically coded by an underlying software system to the WHO-ATC system. Details on medication use also included self-reported indications, form of administration, frequency of intake, origin of the medicine, and duration of use.Autonomy is conceptualized twofold as (a) absence of disability in daily life and dependence on care, and (b) perceived self-determination. Disability and dependence on care were assessed by standardized CAPI or CATI, covering questions on limitations in activities of daily living , and everyday competence. Questions on subjective self-determination were covered in the self-administered questionnaire and are hence limited to the Berlin cohort.Quality of life comprises the following domains: self-rated health, subjective well-being and vitality, pain, health-related QoL, global life satisfaction, and preference-based quality of life. All of these except preference-based quality of life were assessed in both OMAHA cohorts by validated instruments via standardized interview (CAPI or CATI) or self-administered questionnaire. Preference-based QoL was assessed only in the Berlin cohort by the newly developed tool FLQM as part of the CAPI. Additional instruments to measure global life satisfaction and subjective well-being were administered in the Berlin cohort only.Resources can roughly be divided into personal, social and organizational resources. As facets of personal resources, individual health-related behaviours , educational status, and income as well as housing and environment were assessed in both OMAHA cohorts by standardized self-administered questionnaire or CATI. Proactive coping as another important personal resource was assessed by the Proactive Coping Inventory (PCI) via self-administered questionnaire in the Berlin cohort only, since the PCI is not suitable for administration via CATI. As part of the social resource domain, social contacts were assessed in both OMAHA cohorts by the same validated instrument (MILVA). In lack of a validated instrument for administration by CATI, the assessment of subjective social support (by BSSS) was restricted to the Berlin OMAHA cohort. Organizational resources assessed were health insurance, family doctor, housing and environment, and nursing care level within the German healthcare system. Additional context variables covered age, critical life events, and migration background.Due to the exploratory nature of the study and the multiplicity of outcomes, no power calculation was considered.A statistician supervised, validated, and where necessary corrected the data throughout the process of data-collection. Cleaned final data sets were provided by the statistician within less than 6 months after the completion of data collection. A detailed documentation of the process was continuously accessible to the research team.To achieve a high degree of standardization in the survey, the study nurses for personal interviews (CAPI) were initially trained and continuously supervised. Additional training sessions took place before the 12-months follow-up. Telephone interviewers were highly experienced in carrying out telephone health surveys and received specific training before the baseline interview as well as before the 6-month and 12-month follow-up interviews. Standard operation procedures (SOPs) were supplied for all parts of the computer-assisted interviews (CAPI and CATI), functional assessments, and anthropometric measurements. Quality standards and requirements for internal quality control were developed according to recognized epidemiological guidelines and standards applied in German Health Interview and Examination Surveys .The OMAHA project is a longitudinal epidemiological study in two population-based cohorts of older people aged 65 years or older using different methods of data collection. In the urban cohort (Berlin cohort), an age- and sex-stratified sample of residents of an inner-city district of Berlin was assessed by face-to-face interviews, self-administered questionnaires and measurement of physical functions and body measures. In the nationwide cohort (German cohort), participants of former German Health Telephone Surveys were assessed by telephone interview.Our research is focused on the development of a comprehensive assessment of multi- and comorbidity and the analysis of patterns, correlates, determinants, and consequences of these. Also, an innovative instrument for preference-based QoL assessment among elders suffering from multimorbidity will be evaluated. On the methodological level, we examine the effectiveness and efficiency of different recruitment strategies and will characterize difficult-to-reach subgroups of the population 65 years and older. Data collection comprises four waves in each of the two cohorts: two more extensive waves at baseline and 12-month follow-up, and two very brief waves at months 6 and 18 from baseline assessment. This opens up a wide range of opportunities for analyses on trajectories of health states, longitudinal relationships of outcome determinants, and, most importantly, causal relationships between conditions and trajectories over a period of 18 months.The parallel application of instruments in the two cohorts and modes of administration (CAPI and CATI) will on the one hand allow us to identify those tools that are most suitable for telephone administration. On the other hand, we will also be able to make comparisons between the urban Berlin cohort and the nationwide cohort with respect to selected variables cross-sectionally as well as longitudinally. The wide variety of measures relating to similar constructs allows us to soundly determine the psychometric properties of adaptations and new developments for geriatric and gerontological assessments in older age groups. After the completion of analyses relating to validity and reliability of (1) adaptations of existing measurement tools and (2) the newly developed quality of life assessment tool (FLQM) we will be able to provide a wide-ranged set of instruments and tools for personal and telephone assessment in population-based health surveys.Clearly, the samples are subject to selective inclusion. Within the Berlin cohort, there were considerable differences in sample structure with respect to different major sub-populations, such as migrants or people living in nursing-homes and socio-economically deprived areas. In addition to the specified sub-populations, people suffering from dementia or cognitive impairment and those who are heavily restricted in their sensory capacity are not likely to be adequately represented in both cohorts. Because determining barriers and evaluating recruitment strategies are among our goals, we did not expect the participating sample to be representative. In contrast, analyses of the effectiveness and efficiency of the three different recruitment strategies in the Berlin cohort and detailed analysis of participant/non-participant characteristics in both cohorts will enable us to derive strategies on how to get better access to, and response from, these groups. In future studies, a strategy of oversampling underrepresented, yet notably prevalent and politically important groups could serve as one means to minimize selection bias.OMAHA offers a wide spectrum of data related to health, functioning, social involvement, psychological well-being, and cognitive capacity throughout old age in Germany, opening up new opportunities for further gerontological and geriatric research. Results from the study will add to methodological as well as content-specific discourses on human resources for maintaining high levels of autonomy and quality of life in old age, even in the face of multiple health burdens and morbidity.The authors declare that they have no competing interests.MH and CSN conceptualized and supervised the study, analyzed the data and wrote the final manuscript. JF, MB and PM conceptualized and supervised the study, analyzed the data and made substantial contributions to the writing of the final manuscript. JWelke, JSM, HK, UH assisted in the conceptualization of the study, provided specific knowledge, made substantial contributions to the acquisition and quality assurance of the data and contributed to the final manuscript. RD, NS, IKS, JWiskott provided specific knowledge, made substantial contributions to the acquisition and quality assurance of the data and contributed to the final manuscript. AE assisted in the conceptualization of the study, analyzed the data and contributed to the final manuscript. BG analyzed the data and contributed to the final manuscript. MW made substantial contributions to the acquisition and quality assurance of the data and contributed to the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/11/47/prepub"} +{"text": "MLH1, 206 MSH2, 39 MSH6, 26 PMS2). Carriers of mutations in these genes are at high risk of colorectal, endometrial and other cancers.Literature on the ethics of returning research-generated genetic results to research participants has not reported on the practical experience of this activity. The Colon Cancer Family Registry (Colon CFR) has recruited participants from the US, Canada, Australia and New Zealand. Colon CFR-wide molecular testing has identified deleterious germline mutations in a DNA mismatch repair (MMR) gene for members of 424 families (see Table The variation in uptake of genetic information could be related to the variation in the potential for insurance discrimination and/or the differences in the cost to consumers of genetic testing in the research and clinic setting.The return of genetic results and collection of uptake data has provided valuable information about the translation of these research findings and has led to translational research proposals. Delivering research-generated genetic results in the research setting, especially when sampling is population-based, provides both challenges and opportunities."} +{"text": "Leptospirosis is a tropical neglected disease that is highly under-diagnosed and under-reported, mostly because of a lack of diagnosis capacity. The Institut Pasteur International Network includes researchers and physicians that have a recognized expertise in the field of leptospirosis epidemiology and diagnosis. Taking advantage of this international and widespread network of expertise, we currently aim at implementing the diagnosis of leptospirosis in institutes, countries or regions where it was not available. With the financial support of the Institut Pasteur International Network, biologists and researchers from French Guyana, Cameroon, Guadeloupe (West Indies), Cote d\u2019Ivoire, Cambodia, New Caledonia and France currently work at implementing and inter-calibrating leptospirosis diagnosis in their respective institutes.Leptospira spp., the early diagnosis of leptospirosis increasingly relies on PCR. Using its own molecular platform and expertise, each institute implements the PCR or qPCR method of its choice for the detection of pathogenic Leptospira spp. Common Leptospira suspensions are shared to commonly evaluate the sensitivity of the PCR assays.Because of very slow and delicate culture of The serological reference method uses the Micro Agglutination Test (MAT), a method that requires continuous culture of live leptospires and experienced staff for interpretation. Therefore, commercially available serological tests (Elisa for the detection of anti-Leptospira IgM) are used as a first diagnosis approach. The French National Reference Center then validates the results and identifies the infecting serogroup using a reference MAT panel.These diagnostic tools are then offered to patients hospitalized with predefined leptospirosis-like symptoms, as a way to (re-) evaluate the contribution of leptospirosis to non-malarial febrile illnesses in these countries and regions.The global architecture and goals of our Lepto-network will be presented, together with epidemiological research perspectives using the tools and expertise developed through this network."} +{"text": "They function in metabolic processes, signal transduction, transport of small molecules and polymers across endo- and plasma membranes, and inter-compartmental trafficking of proteins, lipids, and cell wall components. During these highly integrative processes, dynamic interactions of membrane proteins with other membrane or soluble components are thought to provide a high degree of flexibility that usually characterizes higher plants. This concept is supported by the recent release of a first, partial Arabidopsis interactome by the Arabidopsis Interactome Mapping Consortium [Frontiers in Plant Transport and Traffic and Frontiers in Plant Physiology reflects well this outcome of the Arabidopsis Interactome Mapping Consortium. It embraces outstanding current research efforts with a series of reviews and original papers that highlight conserved and plant-specific mechanisms of post-Golgi trafficking, exocytosis and endocytosis and the role of the actin cytoskeleton from an evolutionary perspective. This research topic is comprised of reviews on PILS and AUX/LAX transmembrane auxin carriers and reviews, original articles, and hypothesis and theory articles on plant channels, including potassium channels, slow and quick anion channels, and glutamate receptors. This research topic concludes with an integrated view on how membranes shape plant nodulation and Arbuscular mycorrhizae.With no surprise, this current research topic co-hosted by As such, this research topic is a timely update presenting advances in research in the evolution of membrane signaling and trafficking in plants, encompassed of outstanding contributions that address fundamental questions in these essential processes in plants."} +{"text": "The development of vaccines is one of the most important public health achievements. However, as the incidence of vaccine-preventable diseases has decreased, the general public has become increasingly concerned about vaccine safety. Vaccine safety is evaluated extensively through animal safety studies, clinical trials, and post-licensure surveillance. Safety monitoring in post-licensure surveillance has relied mainly on passive reporting systems such as the Vaccine Adverse Event Reporting System in the United States and epidemiological studies.Vaccine safety profiles cannot necessarily be generalized to developing countries, where the incidence, type and severity of serious adverse events may differ significantly because of local environmental and genetic influences. With thThe recent and novel use of YF vaccine for preventative mass vaccination campaigns in sub-Saharan Africa has increased the urgency of establishing functional PV systems. Between 2006 and 2013, the YFI will distribute vaccines to residents of high-risk areas in 12 West and Central African countries. A condition of funding from the GAVI Alliance is the implementation of AEFI surveillance. To address this requirement, AMP and WHO have provided technical support, including the development of surveillance tools , the introduction of active case finding methods, and the creation and training of national expert committees to review and classify suspected serious AEFIs. Reference laboratories, including the Institut Pasteur in Cameroon, and the Robert Koch Institute in Germany provided diagnostic test results to facilitate the YF AEFI classification process. Best practices have been shared between different countries and African-based consultants have been trained to become local experts. Their expertise is now being requested for AEFI surveillance of additional vaccines such as the serogroup A meningococcal conjugate vaccine."} +{"text": "An additional interesting fact is that miRNAs are highly developmental stage-, tissue- and cell-specific, even in adjacent cell types, and mean abundance of these individual species may fluctuate as do the levels of transcription factors which regulate pre-miRNA transcription , and the biological actions of these ribonucleotide entities in the developing, aging, and pathological human central nervous system (CNS) has opened a novel and fascinating vista into our appreciation of human brain epigenetics, the role of sncRNAs on homeostatic and pathogenic gene control, and the potential role of single stranded, 22&nt signals in shaping the transcriptome of the human CNS (Lukiw et al., s Lukiw, . Table 1convergence, and conversely, a single miRNA may interact with multiple mRNAs in a regulatory process known as miRNA divergence (Lukiw and Alexandrov, Another poorly understood layer of complexity in miRNA signaling is that several miRNAs may regulate a single mRNA in a neurogenetic control process known as miRNA"} +{"text": "This Editorial announces a new section in the Journal of Translational Medicine: Patient-Targeted Molecular Therapies. This section is dedicated to the dissemination of targeted molecular therapies in context of patient-centered outcomes research and evidence-based clinical decisions. The focus on patient-targeted molecular therapies \u2013 spanning small molecules and biomolecules alike \u2013 stems from the unprecedented growth in this arena. This is consonant with the overall objective of the Journal of Translational Medicine, which seeks out to expand firmly to other vast areas of medicine in the domain of translational science, viewed here as the transaction between translational research and translational effectiveness. As we inaugurate this new section in Journal of Translational Medicine, with its mission described in detail in this Editorial, we invite interested scientists to submit their work for publication. Analyses of current limitations and deficiencies in health care in the context of the Affordable care Act, signed into law by President Obama in March 2010 [There has been unparalleled and continuous progress in research and development in broad areas of molecular medicine resulting in novel platform technologies, drugs, biomolecules and companion diagnostics on the market and in development. Additionally, post-approval testing of novel medicines or therapeutic combinatorial modalities with the aim to improve the standard of care has been a steady continuous source of information with impact to the healthcare. Key to these advances is the dynamism of this process, and the magnitude and complexity of resulting informational output, warranting iterative application of appropriate research and evaluation tools across entire domains of medicine, to identify and promote standard of care or outline state of the art.Therefore, innovative models of evidence-based patient-centered molecular-targeted interventions are timely and critical. Evidence-based medicine/dentistry/nursing, through the process of comparative efficacy and effectiveness research and review for clinical practice (CEERAP) pursues the identification of the best available evidence gained from the scientific method to clinical decision-making ,3. CEERAPatient-Targeted Molecular Therapies, which is dedicated to the dissemination of targeted molecular therapies in the context of patient-centered outcomes research and evidence-based clinical decisions. Therefore, the focus on patient-targeted molecular therapies \u2013 spanning small molecules and biomolecules alike \u2013 stems from the unprecedented growth in this arena, fueled by scientific progress in understanding the molecular pathogenesis of disease.In response to this urgency, the Journal of Translational Medicine now inaugurates a new section, entitled Patient-Targeted Molecular Therapies provides avenues for the discussion of translational effectiveness pertaining to diverse therapeutic areas including inflammation, degenerative disorders, cancer, infection, metabolism, neurologic, cardiovascular to genetic disorders. The section considers pathologies that pertain to the micro-environment and local immunoregulation and epigenetics, as well as systems immunophysiology. The section addresses chronic and acute immune-related pathologies, from autoimmune disease, to HIV/AIDS, from immune deficiencies to osteo-immunopathology, from inborn errors of immune metabolism to psycho-neuroendocrine-immune pathologies. This section also considers non-immunological disorders, and conditions that are at the interface with immunopathology with both facets: the drug (or therapeutic intervention) and the companion biomarkers.The section Patient-Targeted Molecular Therapies will be complemented by an interest in prognostic and predictive biomarkers, as well as companion diagnostics as they are a critical tool in the assessment or application of molecular targeted therapeutics, and emphasize patient-targeted research for personalized medicine, now subsumed under the terminology \u201cpatient-centered outcomes research\u201d. As molecular targeted therapies \u2013 through an increased potential for clinical benefit and data-rich clinical design - carry the benefit of yielding informative data sets in individual patients during smaller trials in early development, a focus will be to outline emerging evidence of efficacy or toxicity for innovative drug candidates.The purpose of this new section is consonant with the overall objective of the Journal of Translational Medicine, which \u2013 with traditional and diligent interest in immune therapies - seeks out to expand firmly to other vast areas of medicine. This section on Patient-Targeted Molecular Therapies in Journal of Translational Medicine specifically addresses the best available evidence about the translational effectiveness of biomarkers-guided targeted molecular therapies of established medical and dental clinical conditions.In brief, as the informational output regarding more mature or approved molecular targeted therapies evolves across multiple development programs and studies, the specific content of this section will include research products in the form of systematic reviews, clinically relevant complex systematic reviews and meta-analyses. It will also include reviews of the best available evidence, in the form of critical evidence reviews and evidence-based policies. The scientific focus of this section on With this opening editorial, we announce and inaugurate this new section in Journal of Translational Medicine. We invite interested scientists to submit their work for publication."} +{"text": "The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This crosstalk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency. Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in liver , metabolic , and sex-differentiated functions in liver. The influence of estrogens is executed at the level of pituitary GH secretion and the regulation of GHR-JAK2-STAT5-SOCS signaling pathway. Therefore, the complex estrogen/GH interplay is relevant because physiological roles that these hormones have in mammals, and the widespread use of estrogen-related compounds. In the general population, the endocrine and metabolic consequences of long-term exposition to estrogens or novel estrogen-related compounds and their influence on the GH axis are largely unknown. Understanding this complex interaction in physiological and pathological states could contribute to prevent health damage and improve clinical management of patients with growth, developmental, and metabolic disorders.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Because of their evolving nature and inherent scientific uncertainties, outbreaks of emerging infectious diseases can be associated with considerable fear in the general public or in specific communities, especially when illness and deaths are substantial. Mitigating fear and discrimination directed toward persons infected with, and affected by, infectious disease can be important in controlling transmission. Persons who are feared and stigmatized may delay seeking care and remain in the community undetected. This article outlines efforts to rapidly assess, monitor, and address fears associated with the 2003 severe acute respiratory syndrome (SARS) epidemic in the United States. Although fear, stigmatization, and discrimination were not widespread in the general public, Asian-American communities were particularly affected. Public health strategies that deal with rapidly evolving disease outbreaks of new and emerging infectious diseases require a delicate balance between protecting the public\u2019s health and initiating exclusionary practices and treatments that can lead to fear and stigmatization of, and discrimination against, specific populations. The outbreak of severe acute respiratory syndrome (SARS) illustrates these difficulties. SARS spontaneously appeared in the southern province of Guangdong, People\u2019s Republic of China, in November 2002 at the Centers for Disease Control and Prevention (CDC) formed a 14-member, multidisciplinary NCID/SARS Community Outreach Team as part of its emergency response to the global SARS outbreak. While other NCID/CDC response teams dealt with laboratory investigations, surveillance, communication, and clinical infection control practices, the Community Outreach Team worked to implement rapid public health strategies to document, monitor, and assist in ameliorating specific problems associated with fear, stigmatization, and discrimination attributed to the SARS outbreak in the United States.In creating a rapid public health intervention to mitigate behaviors and practices associated with SARS-related fear, the team recognized the need to address the experiences of persons at greatest risk for experiencing SARS-related fear, stigma, and discrimination. The team monitored stigmatizing ideas and behaviors in the general population and the media, particularly toward Asian Americans, who were disproportionately reporting fear, stigmatization, and discrimination compared to the general public. The team began working with Asian-American communities to develop a culturally tailored intervention that 1) promoted community understanding of the facts related to the transmission and prevention of SARS; 2) contributed to the strengthening of community resiliency and capacity to mitigate fear, stigmatization, and discrimination; and 3) encouraged appropriate health-seeking behaviors for those who may have been exposed to SARS and were experiencing early symptoms. The team also worked to dispel myths; keep the general public better informed; prevent discrimination against SARS-affected communities; and provide guidance for institutions, agencies, and organizations hosting international visitors from SARS-affected countries.During the first 3 weeks of April 2003, the NCID/SARS Community Outreach Team conducted a rapid situational analysis to determine the impact of SARS-related fear, stigmatization, and discrimination within the Asian-American community in the United States. The team carried out the following activities: 1) facilitated group discussions with key opinion leaders within the Asian community in the United States; 2) collected and monitored the CDC Public Response Service data; 3) collected and monitored Asian-language newspapers, Internet sites, and other information sources; 4) reviewed polling data and other communication information; 5) conducted community visits, panel discussions, and media interviews; 6) solicited information from state and regional minority health liaisons nationwide; 7) developed ongoing relationships with the Asian-American communities; particularly in major metropolitan areas throughout the United States; and 8) determined new data-gathering strategies as needed.The team conducted group interviews through teleconferences with national, state, and local influential leaders in the Asian-American community throughout the United States. The team also conducted group interviews with Chambers of Commerce and trade association members, school officials and representatives, state public health department staff, academicians at universities, mental health professionals, and others. The 11 teleconferences the team conducted reached more than 70 persons who represented more than 50 agencies, organizations, and communities. The goals of the group interviews were the following: 1) determine the impact of SARS-related fear on the Asian community; 2) document examples of fear, stigmatization, and discrimination; 3) determine strategies for identifying and reaching \u201chidden populations\u201d; 4) develop partnerships with leaders and community members of the affected populations; 5) determine the needs of affected populations; and 6) respond appropriately to those needs through a targeted intervention with activities and Asian-language materials.Five major recommendations were derived from the facilitated group discussions with key informants: 1) develop simple, tailored SARS prevention messages; 2) develop SARS information materials in various Asian languages; 3) disseminate SARS information through multiple and culturally appropriate channels, including (but not limited to) community visits, town hall meetings, and health education and communication channels to complement mass media messages; 4) establish partnerships with local Asian-American community\u2013based organizations to educate the community; and 5) ensure that CDC would continue to provide leadership and coordination in preventing and controlling SARS. The relationships developed during these group discussions allowed team members to monitor and document ongoing stigmatizing situations related to the disease outbreak in real time and to deal more effectively with intentional and unintentional discrimination.CDC operates the Public Response Service (CDC PRS) under contract with the American Social Health Association. This contract provides hotline service to the general public requesting information via telephone and email about bioterrorism and other disease emergencies, including SARS. The NCID/SARS Community Outreach Team worked with the CDC PRS to track a daily sample of incoming SARS-related calls, specifically noting questions associated with fear, stigmatization, and discrimination directed toward the Asian-American community. This system allowed the team to help determine specific answers to frequently asked questions for hotline staff and to develop simple, prerecorded Asian-language messages. Passive data collection of SARS fear-related concerns began on April 29, 2003. During May 2003, 7,327 SARS-related calls were received; 4,013 (54.7%) of these calls were passively sampled. Of these sampled calls, an average of 10% of callers expressed concerns related to fear, stigmatization, and discrimination. A caller could express more than one concern. Major concerns included the following: fear of buying Asian merchandise ; working with Asians ; living near Asians ; going to school with Asians ; and more generic issus such as being on a cruise ship or airplane ; and church, school, or workplace issues . Most SARS calls related to transmission, symptoms, and treatment of disease and travel advisories.One critical component of the team\u2019s activities was determining where members of the Asian-American community were getting SARS-related information. Team members monitored English-language and Asian-language electronic, print, and television media coverage and informal chat rooms in the United States and other countries to stay abreast of changing information about the nature of the SARS outbreak that could influence fear, stigmatization, and discrimination. The assessment showed that many people within the Asian-American community were getting information from Asian-language newspapers, television, and Internet sites directly from China, Hong Kong, Taiwan, and other Asian areas\u2014usually hours ahead of information providers in the United States. The information provided by these Asian-language sources was often inconsistent with newspaper, television, and Internet coverage in the United States, thus creating fear and suspicion that the United States government might not be telling the truth about the outbreak in this country. Independent content-analysis research conducted by InterTrend Communications compared four of the most popular Chinese language newspapers in the United States with two popular national mainstream English-language newspapers from March 21 to April 3, 2003 advised other SARS emergency response teams on how to minimize the risk of stigmatizing groups in their own communications by focusing messages on the virus and the relevant behavioral risk factors; 2) assisted with developing culturally tailored health education materials; and 3) conducted community visits, panel discussions, and media interviews to positively influence negative behaviors occurring in communities. These visits and other contacts with the Asian-American community allowed CDC to develop ongoing relationships and helped the team determine new data-gathering strategies.During a disease outbreak, information changes rapidly as scientific evidence is collected and analyzed. Vital components of the team\u2019s activities were prioritizing and translating existing information and guidance documents and developing health education materials to address the specific needs of the Asian-American community. An in-house translation service did not exist, and the rapidly evolving scientific evidence challenged the turnaround time for developing, translating, and disseminating information. The team worked to identify priority documents for translation and to ensure Asian-language translation for Web and print products tailored to the Asian-American community. To ensure accurate translations, CDC contracted with professional translation services and had all documents back-translated. Web-based information on SARS included documents in traditional Chinese, simplified Chinese, Korean, Vietnamese, and Japanese, as well as French and Spanish. The team also created brief, recorded educational hotline messages in Chinese and Vietnamese. The main messages for people in the United States were the following: 1) the risk of SARS is low; 2) severe cases of SARS have been uncommon, and there have been no deaths in the United States; 3) methods for disease prevention in the general public are like those of other viral diseases; and 4) although no evidence of community spread currently exists, continued vigilance, aggressive case management, and infection control are needed.Team members conducted field visits to Asian communities in Boston; New York City; Oakland, California; San Francisco; Washington, D.C.; Edison, New Jersey; and Los Angeles to respond to the direct needs of the communities and gather information. The team met with community leaders, toured the communities, informally gathered further information, and gave community SARS presentations in seven cities, reaching approximately 500 persons. Through community visits, the team was able to 1) provide the latest in evidence-based information on SARS with Asian-language education materials; 2) dispel misconceptions, myths, and rumors; 3) act as a catalyst for bringing together a broad spectrum of organizations and persons in the community to create local networks to promote community resiliency; and 4) provide credibility and reassurance to those who felt vulnerable. Speakers also presented a public health model for mitigating fear, stigmatization, and discrimination that could be instituted by public health officials, clinicians, and community members. Through open discussion sessions and informal information gathering in the community, the team found that SARS-related stigmatization was occurring more frequently within the Asian community than from outsiders directed toward the Asian community. The team also found that those persons with SARS-like symptoms who used traditional herbal physicians and pharmacies were less likely to be referred to, or seek out, public health officials, suggesting that further research into strategies to reach this population is needed. Conducting community visits also showed that CDC was responding to the needs of the community at risk for SARS-related fear, stigmatization, and discrimination and was modeling positive behaviors to the public.Other infectious disease epidemics have been associated with specific ethnic groups. Fear, stigmatization, and discrimination plagued Russian Jewish immigrants when the 1892 outbreaks of typhus fever and cholera in New York City were traced to Russian Jewish immigrants from Eastern Europe (Protecting the health of the public while preventing stigmatization of segments of the population during a rapidly evolving disease outbreak is complex. The team\u2019s experience during the recent SARS outbreak demanded anticipatory insight, perceptive planning, and a rapid response to a targeted audience with specific cultural perspectives and influences. It also required us to recognize the distinctive features of SARS in a medical, social, and cultural context. Weiss states, \u201cPreventing fear and stigmatization depends on controlling or treating the target health problem, countering tendencies of those who stigmatize others, and supporting those who are stigmatized through emotional support and social policies\u201d (The data collected during the rapid situational assessment were critical in guiding activities of the team. Both the data and the data collection process assisted the team in establishing interpersonal relationships with community leaders, determining priority needs, identifying responsible intervention strategies, and developing effective communication channels. The team was able to better understand community perceptions and attitudes by identifying the communities\u2019 trusted sources of information. When conducting community visits, the team was able to address discordant information, myths, and rumors; provide simple Asian-language messages and materials; and act as a catalyst to build community resiliency and prepare for the possibility of future emerging diseases. The team was also able to keep CDC/NCID leaders informed and to intervene when they identified discriminatory policies, practices, and actions that were inconsistent with evidence-based public health recommendations and guidelines.Quelling fear-driven stigmatization and discrimination during the SARS outbreak required tailored intervention strategies carried out by the SARS Community Outreach Team. These activities complemented traditional risk communication for the general public. To be effective, behavioral intervention approaches, messages, and materials had to be salient for the affected population, in this case Asian-American communities within the United States. Further, these interventions aimed at promoting an accurate understanding of the epidemic both in the general population and within the affected community, that is, the dynamic nature of the outbreak and its cause, treatment options, and prevention strategies. Through interpersonal connections, the team members worked to promote reassurance and enhance community resiliency.Public health professionals must understand the necessary balance needed to protect the public\u2019s health with appropriate exclusionary practices, while at the same time preventing fear, stigmatization, and discrimination of specific segments of the population. As we prepare for the next new or reemerging disease outbreak, we should also be preparing to deal with the fear epidemic that will likely accompany it. By developing effective behavioral and health education strategies and providing timely attention to the special needs of affected populations, we can ensure that, no matter what the infectious disease, we can limit the associated epidemic of fear and stigmatization."} +{"text": "One of the most significant features of healthcare-associated infections (HAIs) is the high frequency of multidrug-resistant bacterial strains (MDRBSs). Even modern chemical antimicrobials (CAMs) are not efficient enough; a totally different way of prevention of HAIs caused by MDRBSs is necessary.To develop a monobacteriophage (MBP)-based way of prevention of HAIs caused by MDRBSs.Pseudomonas aeruginosa (PA), methicillin-resistant Staphylococcus aureus (MRSA), Salmonella spp., Shigella spp., and Klebsiella spp. were sprayed on various surfaces in different healthcare settings (HCSs) in the case of spread of HAIs caused by these agents. We compared efficiency of MBPs on different surfaces and in different conditions of phage circulation. Finally, we assessed the influence of the MBPs on incidence and mortality of HAIs caused by MDRBSs. The efficiency of the MBPs was evaluated in the terms of absence of the target bacteria in the environment, that, in turn, was assessed by classical bacteriological methods.MBPs against Salmonella-caused infections, 4-fold reduction of incidence of Shigella-caused infections, and 2-fold decrease of incidence of Klebsiella- and MRSA-caused infections. Finally, CAMs did not influence the efficiency of MBPs, and no side effects were registered.Application of MBPs sprayed on surfaces in hospital environment is significantly more efficient method of elimination of MDRBSs compared to their usage by any other way. MBPs possessed greater efficiency on glass, metal, and plastic surfaces compared to textile and paper. Duration of MBP circulation was determined by time frame, MBP strain, and lytic activity of the MBP, but not by dose of MBP on the surface. The greatest effect was revealed against PA; even the single usage of MBP provided total elimination of PA from the hospital environment. The application of MBPs led to 15-fold decrease of incidence of The MBP-based way of prevention of HAIs caused by MDRBSs has certain advantages over CAMs. It may be used without limitations in different HCSs, particularly in intensive care units, it allows the efficient elimination of MDRBSs from the hospital environment in short terms, it provides termination of the outbreaks caused by MDRBSs, reduces the incidence and mortality from HAIs, and it is much cheaper compared to CAMs.None declared."} +{"text": "After publication of this work , we noteThe authors declare that they have no competing interests.JvA was responsible for the conception and design of the study, researched data, and wrote the manuscript. HPH contributed to acquisition of data, discussion and reviewed/edited manuscript. MCRFvD contributed to acquisition of data and reviewed/edited manuscript. CPHL and ICCH coordinated inclusion of individuals with CAD and reviewed the manuscript. CJZ coordinated inclusion of individuals with PAD and reviewed the manuscript. MGV contributed to acquisition of data, discussion and reviewed/edited manuscript. BHRW coordinated inclusion of diabetic individuals and reviewed/edited the manuscript. HvG contributed to discussion and reviewed/edited manuscript. JLH was responsible for the conception and design of the study, researched data, contributed to discussion and reviewed/edited manuscript. All authors read and approved the final manuscript."} +{"text": "Since the late 1990s, natural language processing (NLP) has seen a massive shift from high-precision, low-recall systems based on small sets of hand-written rules, to methods based on the statistical analysis of large corpora. The field of chemoinformatics, likewise, is dominated by statistical and machine-learning approaches. In recent years, however, pharmaceutical companies have been engaging more and more with Semantic Web technologies, which are largely built around the sorts of hand-written systems that NLP has moved away from this century. We discuss where our current text analysis and Semantic Web efforts at the Royal Society of Chemistry are headed and how we're making use of the unreasonable effectiveness of data."} +{"text": "The total synthesis of natural products, a field of organic chemistry that is both historical and contemporary, has undoubtedly entered a new paradigm over the past decade with the advent of revolutionary new synthetic methods and innovative synthetic concepts. Putting aside the downstream applications of natural-product synthesis in the interrogation of biological processes, elucidation of biogenetic origins, structural assignments and many others, its fundamental and indispensable value as a vehicle for the discovery of new synthetic transformations is well-testified and unparalleled by any other research discipline over the history of chemical science. These transformations, largely concerning carbon\u2013carbon/carbon\u2013heteroatom bond formations, asymmetric induction, and catalysis, constantly expand the repertoire of powerful tools available at the organic chemist\u2019s disposal, and enable more challenging synthetic problems to be investigated. As such, this catalytic cycle of discovery fueled by natural-product synthesis continues to capture and captivate the imagination of both practitioners and students of organic chemistry around the world and will do so far beyond the foreseeable future. In particular, the recent discovery of novel transitional-metal complexes and their associated chemical transformations, and rediscovery of the unprecedented reactivity of previously documented transition-metal complexes with subtle changes in the reaction conditions and the reacting substrate have been extremely fruitful since the turn of the millennium, most notably in promoting reactions of unfunctionalized and unactivated chemical bonds. Furthermore, the application of organic compounds as promoters of chemical transformations has also witnessed increasing sophistication, substrate scope, and efficiency together with new modes of activation, which rival or at times surpass those exhibited by transition metals. Last but not least, the judiciary combination of transition-metal and organic mediators, together with tandem processes encompassing multiple reaction cycles in a programmed sequence, represents a new horizon with vast potentials that have yet to be fully understood and exploited.In this Thematic Series, selected examples of metal- and organic-compound-promoted chemical processes that render the preparation of architecturally complex natural products, natural-product subdomains, or natural-product-like scaffolds, are presented. These illustrative synthetic studies are intended to showcase the most recent developments, at the same time highlight the state-of-the-art and current limitations, and in doing so set the path for the future. It is our great anticipation that this Thematic Series will instigate and inspire further investigations in this field, and challenge the existing technologies and our current mindset in target-oriented synthetic design. Ultimately, we wish that the newly acquired knowledge will translate to further advances in synthetic organic chemistry and provide more enabling tools for synthetic-chemistry-dependent research fields and beyond.David Yu-Kai Chen and Dawei MaSeoul, Shanghai, June 2013"} +{"text": "Chlamydomonas reinhardtii disrupted for selected target genes. The approach relies on the generation of thousands of transformants followed by PCR-based screenings that allow for identification of strains harboring the introduced marker gene within specific genes of interest. Our results highlight the strengths and limitations of two independent screens that differed in the nature of the marker DNA used (PCR-amplified fragment containing the plasmid-free marker versus entire linearized plasmid with the marker) and in the strategies used to maintain and store transformants.A method was developed to identify insertional mutants of Chlamydomonas reinhardtii (Chlamydomonas throughout) dCTP by PCR amplification of a 360 bp fragment using the PARAU (5'-GAGGATCTGGACGAGGAGCGGAA-3') and PARAL (5'-CCCTCAGAAGAACTCGTCCAACAGC-3') primers.Isolation and enzymatic digestion of genomic DNA, electrophoretic fractionation of the DNA fragments, transfer of the DNA fragments to a nylon membrane, labeling of specific DNA probes, hybridization of the probes to the immobilized fragments and washing of the hybridized membrane were performed as previously described ,34. LabeThe authors declare that they have no competing interests.DGB is the main intellectual author of this work, has participated in the designing, coordination, construction and screenings of both libraries, collected data from some transformants, and wrote this manuscript. WP has made important intellectual contribution to this work, has participated in the designing, coordination, construction and screening of Library 1, collected data from the sulfate transporters mutants, and participated in the writing of this manuscript. FM, WY, CC, LM, and MP have participated in the construction and screening of Library 1, and collected data from many transformants enlisted in Tables"} +{"text": "The State of infections acquired during care procedures whose prevalence rate is estimated at about 15% in some benchmark institutions reflects the alarming situation of provision of care and patient safety in DR Congo.Conduct an inventory of patient safety in health facilities in the city Kinshasa.Study conducted using survey and observation checklist covering the different aspects of patient safety: institutional, medical technical equipment, medical devices, blood products, drugs, biological graft, waste management medical needles and treatment materials.At the institutional level: the lack of standards and policies on patient safety except on injection safety; lack of policy on the fight against nosocomial infections; reporting system for adverse events.Technically: Absence of risk management procedures, training non-existent on the quality and safety of patients in Kinshasa (90% of staff) and 89% of patients do not know their rights and lack of association of patient safety care.The implementation of a policy of promotion of hospital hygiene and the fight against adverse events associated with their care requires a partnership challenging multiple states, civil society, communicators, the private sector and international institutions.None declared."} +{"text": "The advancement of diabetes treatment has gone from crude extracts of insulin and accidental discovery of sulfa-like drugs in antibiotics to the development of drugs based on improved understanding of the pathophysiology of diabetes mellitus. This article will review the history of the discovery and development of insulin. A companion focusing on non-insulin diabetes agents will follow in the next issue of JCHIMP. Ebers Papyrus and N , were marketed.Because the insulin preparation required several injections daily, investigators worked to find ways to prolong its duration of action. In the 1930s, H.C. Hagedorn, a chemist in Denmark, prolonged the action of insulin by adding protamine . In ToroOnce patients with diabetes started to live longer, chronic complications of diabetes became prevalent. In 1993, the Diabetes Control and Complications Trial showed for the first time without any doubt the linear relation between the degree of glycemic control and complications . To reduTo have an alternative delivery method for insulin, exubera, the first inhaled insulin, was developed by Sanofi-Aventis and Pfizer and marketed by Pzifer in 2006 . The inhThe discovery of pancreatic crude extracts gave hope to patients with diabetes mellitus. The subsequent development of precisely engineered insulin analogs, which are more physiologic, improved diabetes control and reduced or delayed complications. Insulin continues to be the cornerstone of therapy. Newer medications complement and enhance insulin action tailored toward different mechanisms in the pathophysiology of diabetes mellitus.Meanwhile, in the next issue of JCHIMP, we will review the other agents for diabetes care."} +{"text": "The first Biennial International Symposium on Colorectal Disease held in Phuket, Thailand, from Dec 8 to Dec 10, 2013, was hosted by the governor of the International College of Surgeons, assistant professor and chief of the colorectal department of the Bangkok Hospital Phuket, Dr. Art Hiranyakas on behalf of the International College of Surgeons, the Society of Colon and Rectal surgeons of Thailand, Vachira Phuket Hospital and Bangkok Hospital Phuket. It was undoubtedly a unique opportunity to hear from internationally acclaimed speakers and experience the most exotic and exceptional Phuket beauty. The three-day exhilarating meeting agenda focused on rectal cancer treatment and advances in colorectal surgery. On the first day, a stimulating live surgery session, moderated by Dr Giovanni Milito, Professor of Surgery, Tor Vergata University Hospital, Rome, Italy, was held showcasing parallel laparoscopic and robotic low anterior resections for distal rectal cancer performed by Drs. Steven Wexner and Seon-Hahn Kim, respectively. The cases were followed by a live demonstration of total mesorectal excision specimen examination and an assessment of mesorectal integrity by the expert gastrointestinal pathologist Dr. Mariana Berho, Chairman of the Pathology and Laboratory Medicine, Cleveland Clinic Florida. This lively and highly informative session prompted an excellent exchange among experts and the attendees.The Honorary Lecture on \u201cColorectal Surgical Education\u2014A Prescription for the Future\u201d by Steven Wexner inaugurated the second day of the conference with a comprehensive review of colorectal surgery education and standards of training, followed by an eye-opening exposition of the challenges and goals for future colorectal training around the world. Dr. Steven Wexner\u2019s lecture served as a perfect prelude to the remainder of the day, which highlighted the complex expertise required for state-of-the-art rectal cancer treatment. The multidisciplinary nature of successful rectal cancer was elegantly taken into account throughout the entire meeting with sessions that discussed the complex role of diet in colorectal carcinogenesis, minimally invasive options and outcomes for rectal cancer surgery, radiologic preoperative rectal cancer staging, and pathological staging after neoadjuvant therapy. A sober discussion on sphincter preservation by Dr. Hiranyakas topped the session with a well-balanced review of the oncologic and functional outcomes, highlighting the advantages and disadvantages of this approach. The controversial topic of the benefits of robotic compared to laparoscopic low anterior resection for rectal cancer was presented by Dr. Francis Seow-Choen and was followed by an edifying and interesting debate with excellent audience participation. The challenges of advanced rectal cancer management were also thoroughly discussed including presentations that reviewed the most recent trials and outcomes for the management of stage IV disease by Yik-Hong Ho, cytoreductive surgery and HIPEC for carcinomatosis peritonei and the liver-first approach for metastatic rectal cancer.The program also included a wide-ranging overview of the diagnosis and treatments of frequent anorectal disorders including pelvic floor disorders, fecal incontinence, and complex anal fistulas. These sessions were coupled with a hands-on endoanal ultrasound course taught by Art Hiranyakas and a live LIFT procedure demonstration by Arun Rojanasakul, Chulalongkorn University, Thailand, who initially developed and reported the procedure. Hemorrhoidectomy techniques and indications followed high-yield topics including management options for complex anorectal fistulas and fecal incontinence. The third day of the meeting also included updates on a potpourri of common anorectal and colorectal issues, including rectal trauma, management of anastomotic leak, and an excellent presentation on enhanced recovery after colorectal surgery protocols and updates, presented by Drs. Varut Lohsiriwat, Mahidol University, Thailand, and Fabio Potenti, Cleveland Clinic Florida, respectively. In addition, a poster walk-around session displayed scientific research abstracts from Asia, Europe, and North and South America.The meeting attendance surpassed expectations and absolutely fulfilled the aim of providing an in-depth and stimulating scientific update of rectal cancer management and advances in colorectal surgery. The world-class exchange of knowledge and experience from international leaders in the field of colorectal diseases and live demonstrations made this an outstanding educational meeting. Taken together, with the fascinating natural beauty of Phuket during the most beautiful time of the year, and the finest Thai hospitality, we are all certainly looking forward to participating in the 2015 meeting. Anyone who did not attend in 2013 should indelibly mark the dates of December 9\u201311, 2015, in their calendar. Anyone with an interest in attending a highly informative meeting and in visiting one of the most beautiful areas in the world should plan to attend. The topics for the next meeting include multidisciplinary approach to colorectal cancer, colorectal imaging, histology, genetics and molecular biology, minimally invasive colorectal surgery including robotics and laparoscopy. Controversies in the management of rectal prolapse, advanced surgical management of fecal incontinence, constipation, anorectal fistulas, and hemorrhoids are also a part of the agenda which includes live surgery and hands-on workshops in surgery, imaging, and histology as well. Save the date! (Fig."} +{"text": "This report is the collective product of word-leading experts working in the branches of integrative medicine by predictive, preventive and personalised medicine (PPPM) under the coordination of the European Association for Predictive, Preventive and Personalised Medicine. The general report has been prepared as the consortium document proposed at the EPMA World Congress 2011 which took place in Bonn, Germany. This forum analyzed the overall deficits and trends relevant for the top-science and daily practice in PPPM focused on the patient. Follow-up consultations resulted in a package of recommendations for consideration by research units, educators, healthcare industry, policy-makers, and funding bodies to cover the current knowledge deficit in the field and to introduce integrative approaches for advanced diagnostics, targeted prevention, treatments tailored to the person and cost-effective healthcare."} +{"text": "Integration can take a variety of forms at the macro-, meso- and micro-levels. On the macro-level systems aim to deliver integrated care on a high-level of performance to the population they serve. Meso-level systems focus on the integrated care needs of a particular group or population with same diseases or same conditions. Consequently, integrated systems on the micro-level seek to improve care co-ordination for individual patients and carers.Based on experiences from the USA, UK, and Europe the report comprises successful integrated systems and summarizes relevant evidence about high-profile systems.The book is technically divided into five parts. Following usual convention in the literature, the first and the last section include Introduction and Discussion/Conclusion. The three middle sections, however, are each concerned with one specific level of integration: macro-, meso- and micro-level. For reasons of clarity and comprehensibility this review follows this structure.In Chapter I the authors provide a comprehensive overview of the meanings of different terms, diverse forms of integration in health care and their differentiation and interrelationships. Definitions include \u2018fragmentation\u2019, \u2018integration/integrated care\u2019 as well as its forms of organizational, functional, service, clinical, normative, systemic, horizontal, vertical, real, virtual/contractual and commissioner integration.In the report macro-level integration is described using examples from the US. These systems have high levels of organization and tend to perform better than the fragmented forms of care. Each of the described approaches can be categorized as either complete provider and commissioner integration or provider integration or integrated medical groups.Based on a clear and reasonable research structure consisting of a detailed explanation and description of the integrated systems followed by an assessment of the system\u2019s impact in the national health system based on evaluations, survey data and national ranking the following five integrated care programs are examined:Kaiser Permanente: Virtually integrated system in which provider remain distinct organizations that co-operate based on exclusive contracts.Veterans Health Administration/VA: Real integrated system of regionally based integrated service networks across all care settings.Geisinger Health System: Hospital system, partially integrated in terms of provision and commissioning.Mayo Clinic: Multispecialty groups practice consisting of hospitals and medical offices without own health plan.Integrated Medical Groups : Composition of primary, community physicians from diverse specialties that are either directly employed or have an exclusive contract or have the budget responsibility. Kaiser, VA and Mayo Clinic are seen as integrated medical groups.Moreover, the individual systems are compared among themselves and to the NHS in the UK.Meso-level integration seeks to integrate care for particular groups of patients and population. These programs are mostly focused on older people and those suffering from specific conditions.Following this dichotomy the authors present examples of integration for older people and condition-specific integration. As in the 2nd section of the report the structure of description and impact-analysis based on evaluations and performance measures is used to examine nine systems:Program for all-inclusive care for the elderly: US-based integrated provider model aimed at maintaining frail older people in the community.System of integrated services for aged persons: Canadian integrated provider model seeking to overcome fragmented health and social care for elderly. Ended in 2001.PRISMA: Canadian model of integration and co-ordination of services across provider network to ensure functional autonomy.Rovereto: Italian model aimed to integrate medical and social services in a continuum of care using case managers. Pilot in 1990s.Vittorio Veneto: Italian model aimed to improve the integration and co-ordination of older people\u2019s health and social care. Pilot in 1990s.Torbay: UK-based model using integrated health and social care teams proactively managing the care of vulnerable elderly in cooperation with GPs.Disease management programs: Mostly multicomponent, consisting of a variety of different elements and aim to reduce deficits in the care for long-term conditions such as coronary health disease, COPD or diabetes.Chains of care: Swedish-based way of co-ordination and integration of care across organizations and professions. Focused on certain conditions and based on clear care pathways to improve quality of care.Managed clinical networks: Scottish system seeking to broker care across providers from all sectors that does not require the creation of new organizational entities.The first six examples display ways of integration for older people. In addition to the detailed description the authors also provide a very clear table summarizing the key features and impacts of each system.Micro-level integration is focused on the co-ordination of care for individual patients and carers. Responsibility for care co-ordination is often assigned to a specific individual or a team of care providers trying to decrease fragmentation.Six ways of micro-level integration have been identified by the authors:Care planning and care coordinators: Refers to the planning, coordinating, managing and reviewing an individual\u2019s care. The process of care planning is basically done by a care coordinator.Case management: Assignment of a case manager/care team to each patient that is responsible for assessing needs, developing care plans, organization of care, monitoring the quality of care, and the maintaining of the contact with the patient/family.Patient-centred medical homes and virtual wards: US-based system based on an accountable individual/care team and shared information systems and focused on care delivery for individuals with special care needs.Personal health budgets: Shifting of autonomy over care to patients by giving them responsibility to administer own health budget. Also referred to as self-directed care or individual budget.Use of information technology: Facilitates the timely and efficient flow of information across provider.Use of telecare and telehealth: Enable integrated care especially for long-term conditions by focusing on reducing avoidable and costly use of healthcare resources.The final, fifth chapter of the report takes a closer look at the situation in the UK as well as the implications resulting from the examples. The authors clearly state that action is needed at all three levels to ensure that integration and cooperation deliver better outcomes.This report reviews ways of achieving closer integration for individual service users and carers through care coordination. Very positive: Each section closes with a summary of the key messages of the section. This provides a valuable overview to all readers, allowing them to get first useful information in a short period of time.The reader has to be aware that the paper is primarily aimed at NHS personnel confronted with the re-organization of the UK-system. However, this report has a special value for all policy-makers faced with the question of overcoming fragmentation of care."} +{"text": "The great success in the prevention and treatment of pediatric HIV in high resource countries, and now in low resource countries, has changed the face of the HIV epidemic in children from one of near certain mortality to that of a chronic disease. However, these successes pose new challenges as perinatally HIV-infected youth survive into adulthood. Increased survival of HIV-infected children is associated with challenges in maintaining adherence to what is likely life-long therapy, and in selecting successive antiretroviral drug regimens, given the limited availability of pediatric formulations, limitations in pharmacokinetic and safety data of drugs in children, and the development of extensive drug resistance in multi-drug-experienced children. Pediatric HIV care must now focus on morbidity related to long-term HIV infection and its treatment. Survival into adulthood of perinatally HIV-infected youth in high resource countries provides important lessons about how the epidemic will change with increasing access to antiretroviral therapy for children in low resource countries. This series of papers will focus on issues related to management of perinatally infected youth and young adults. The remarkable success in the prevention and treatment of paediatric HIV infection in high-resource countries has changed the face of the HIV epidemic in children from a fatal disease to that of a chronic illness. With widespread access to antiretroviral therapy in high-resource settings, many perinatally infected children are surviving into adolescence, young adulthood and beyond . With inThese successes pose new management challenges as perinatally infected youth survive into adulthood. There have been significant difficulties in maintaining adherence to life-long therapy, and in selecting successive antiretroviral drug regimens, given the limited availability of paediatric formulations, pharmacokinetic, and safety data in children and development of extensive drug resistance in multi-drug-experienced children. Long-term survival of youth with perinatal HIV infection has been accompanied by unanticipated needs. These include management of long-term complications of therapy, sexual and reproductive health, mental health needs, and issues of higher education and career training ,5.How to transition from complete dependence on adult caregivers and health services provided in paediatric HIV care settings, which are often multidisciplinary, family-centred and include extensive support services, to adult HIV care systems and assuming responsibility for their own care has received little attention . These yTo optimize the psychosocial well-being and treatment outcomes of perinatally infected adolescents and young adults as well as enabling them to lead long, meaningful and productive lives, there is an urgent need to understand the factors that either facilitate or serve as a barrier to the health and well-being of HIV-infected children and youth, and the complications of HIV and therapy as they age. The articles in this series provide a comprehensive evaluation of the issues related to perinatal HIV infection in both high- and low-resource settings.One common theme is the paucity of research in the area of adolescent perinatal HIV infection, including a lack of epidemiologic data to better define this population of youth on a global basis, and the general lack of data regarding potential impacts of gender on HIV disease in this population.Sohn and Hazra discuss the changes in the global paediatric HIV epidemic as children receiving antiretroviral therapy age into adolescence, highlighting our lack of knowledge regarding the global numbers of perinatally infected youth over 15 years of age because global reporting does not differentiate between perinatal and behaviourally infected youth . They diAgwu and Fairlie discuss the multiple challenges of antiretroviral therapy in perinatally infected youth, with a focus on adherence issues and a review of clinical, immune and viral outcomes . ChildreMellins and Malee discuss mental health issues in perinatally infected youth, reviewing the literature in this area, risk as well as protective factors, treatment modalities and need for further research . Infectein utero and behaviourally based, such as substance use). The authors note the paucity of data in infected adolescents and in youth from resource-limited settings.Laughton and colleagues discuss neurodevelopmental issues in perinatally infected youth, noting that infected youth exhibit problems on general cognitive tests, processing and visual-spatial tasks and are at high risk for psychiatric and mental health problems as discussed by Mellins ,13. WhilLipshultz and colleagues discuss the cardiac effects of HIV and its treatment in perinatally infected children and adolescents, including the range of cardiovascular disease in children, the clinical manifestations, pathogenesis and monitoring, including cardiac biomarkers, and treatment . They emBarlow-Mosha and colleagues discuss the myriad of metabolic complications of HIV and its treatment that are being observed in youth . While pPuthanakit and Siberry discuss issues related to the effect of HIV infection and antiretroviral therapy on bone. They discuss normal bone development and non-HIV factors affecting development as well as HIV and treatment-related factors impacting bone, and approaches to detection, prevention and management of these problems in youth . Bone unBhimma and colleagues discuss the problem of kidney disease in youth with perinatal infection . They noA number of studies have found that many perinatally infected adolescents may not be aware of their HIV status in both high- and low-resource settings \u201323. We rWeber and colleagues note the emerging data and high prevalence of chronic lung disease in adolescents with perinatal HIV infection, as well as the need for more detailed prospective studies. They note that bronchiectasis and bronchiolitis obliterans are important problems in these children, with lung function tests showing significant impairment. The importance of co-infection with tuberculosis and the emergence of chronic lung disease is discussed, emphasizing the need for early antiretroviral therapy in children to minimize the risk of chronic lung problems. Lastly, they provide guidance for the evaluation of lung health and the need for more prospective data.This series of articles serves to focus attention on the growing population of perinatally infected adolescents and young adults globally, the complexities of their care, and helps to identify the future research needs. A holistic approach to improve the long-term health of these youth is needed to ensure that our success in achieving survival of HIV-infected children from infancy is maintained into adulthood."} +{"text": "Questions have been raised in screening, brief intervention, and referral to treatment (SBIRT) research concerning the role the assessment process may serve in contributing to behavior change. However, most SBIRT trials have not been designed in a way to disaggregate the impact of assessment versus the combined effect of assessment plus brief intervention. We describe the design of the National Institute on Drug Abuse-Clinical Trials Network (NIDA-CTN) Screening, Motivational Assessment, Referral, and Treatment (SMART-ED) trial, with a focus on the screening and assessment instruments used and three treatment conditions to which participants have been randomized: minimal screen only (MSO); screening, assessment, and referral to treatment (if indicated) (SAR); or screening, assessment, and referral plus a brief intervention (BI) with two telephone follow-up booster calls (BI-B). The screening and assessment measures are relatively brief in the context of a clinical trial to minimize participant burden and assessment reactivity. The design allows a comparison of the impact of assessment as an independent factor over and above minimal screening (SAR versus MSO) as well as an evaluation of the incremental benefit of the BI with booster calls over and above assessment without BI (BI-B versus SAR). Assessment reactivity is of concern, especially in BI studies, because it may reduce effect size and conceal therapeutic benefit. On the other hand, if found to contribute independently to behavioral change, assessments could be designed to maximize the therapeutic benefit they provide. The design used in the SMART-ED trial will allow an evaluation of the independent and incremental contribution of the assessment process to behavior change."} +{"text": "Acute respiratory infections remain a leading cause of morbidity and mortality in Sierra Leone; however, similar to other African countries, little is known regarding the contribution of influenza. Routine influenza surveillance is thus a key element to improve understanding of the burden of acute respiratory infections in Africa. In 2011, the World Health Organization (WHO) funded the Strengthening Influenza Sentinel Surveillance in Africa (SISA) project with the goal of developing and strengthening influenza surveillance in eight countries in sub-Saharan Africa, including Sierra Leone. This paper describes the process of establishing a functional Influenza Sentinel Surveillance (ISS) system in Sierra Leone, a post-conflict resource-poor country previously lacking an influenza monitoring system.Sierra Leone utilized a systematic approach, including situational assessment, selection of sentinel sites, preparation of implementation plan, adaptation of the standard operating procedures, supervision and training of staff, and monitoring of influenza surveillance activities. The methods used in Sierra Leone were adapted to its specific context, using the Integrated Disease Surveillance and Response (IDSR) strategy as a platform for establishing ISS.The ISS system started functioning in August 2011 with subsequent capacity to contribute surveillance activity data to global influenza databases, FluID and FluNet, demonstrating a functional influenza surveillance system in Sierra Leone within the period of the WHO SISA project support. Several factors were necessary for successful implementation, including a systematic approach, national ownership, appropriate timing and external support.The WHO SISA project demonstrated the feasibility of building a functional influenza surveillance system in Sierra Leone, integrated into existing national IDSR system. The ISS system, if sustained long-term, would provide valuable data to determine epidemiological and virological patterns and seasonal trends to assess the influenza disease burden that will ultimately guide national control strategies. Influenza remains an important global public health concern. Annual influenza epidemics are estimated to account for 3 to 5 million severe illnesses and 250,000 to 500,000 deaths worldwide . Though In 2011, the World Health Organization (WHO) funded the Strengthening Influenza Sentinel Surveillance in Africa (SISA) project in which eight countries were selected to receive support to implement or strengthen influenza sentinel surveillance (ISS) and improve epidemiological and virological data collection and reporting through the global databases FluID and FluNet ,8. The pThe objectives of this paper are threefold:to describe the approach used in Sierra Leone in the development and implementation of a functional ISS system; to illustrate the challenges and solutions encountered in developing a surveillance system in a resource-poor country previously lacking an influenza monitoring system; and to provide resource-poor countries, external funders and implementers with a better understanding of the opportunities and challenges of developing new surveillance activities.The SISA project was implemented in Sierra Leone using a common methodological framework including development of initial situation assessment and recommendations for improvement; drafting of relevant country-specific surveillance protocols and standard operating procedures (SOPs); training of sentinel surveillance and data management staff; and supervision of surveillance activities . The metAn initial briefing meeting at the start of the project brought together national program managers and other stakeholders concerned with surveillance activities. All relevant information concerning influenza, including the background, situation analysis, objective and proposed process for implementation of the ISS system in the country, was provided. This initial meeting was instrumental in identifying designated personnel to be involved in the assessment exercise and to ensure leadership at the national level. Throughout the course of implementation,particular attention was placed on training and regular supervision of sentinel surveillance staff. Monthly review meetings were conducted to closely monitor and support the initial phase of implementation of ISS activities.The systematic approach followed in establishing a functional ISS system is described below.Initial activity focused on understanding the organization of surveillance function, including data management at various levels, laboratory support services and availability of suitable health facilities for integrating ISS into existing disease surveillance systems. The methods included the review of relevant documents, visits to the National Ministry of Health of Sierra Leone (MOHS), the Directorate of Disease Prevention and Control (DPC), the National Disease Surveillance Programme (NSD), the District Health Management Team (DHMT) of the Western area, the Central Public Health Reference Laboratory (CPHRL) and the health facilities in the district. Figure\u00a0Sierra Leone has implemented the IDSR strategy, coordinated by the National Surveillance Unit (NSU) within the DPC; IDSR promotes the integration of resources through the coordination and streamlining of common surveillance activities. By integrating multiple surveillance systems, limited personnel and scarce resources can be used more efficiently. In the IDSR implementation framework, epidemiologic surveillance is linked with laboratory support in order to produce relevant information for taking public health action . UltimatAt the time of the assessment, it appeared that the IDSR infrastructure was an appropriate platform in which to integrate the ISS system to ensure sustainability. The sustained laboratory support from diverse partners including the WHO, CDC, Association of Public Health Laboratories (APHL), UNICEF and the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) had gathered momentum to upgrade the CPHRL laboratory capacity to Bio-safety Level 2 (BSL-2) standards. The laboratory was in the initial stages of conducting testing of bacterial meningitis samples for surveillance and HIV polymerase chain reaction (PCR) testing for the early infant diagnosis of HIV. The available PCR machines could ideally be used to identify influenza viruses. However, prior to initiation of influenza testing, building of laboratory human resource capacity and supply of primers would be required.Based on the findings of the assessment, it was feasible to establish an ISS system in Sierra Leone without delay. Consequently, health facilities for the ISS system were selected based on WHO criteria, which included administrative division, geographical location, public-private mixture, institutional capacity to carry out surveillance activities, and staff interest in participation . RecommeApplying the WHO criteria, the following four health facilities in the Western area of Freetown were selected as initial sentinel sites for implementation of the ISS: Jenner Wright Children\u2019s Clinic, Ola During Children\u2019s Hospital, Lumley Government Hospital, and Blue Shield Hospital (private). Surveillance information flow within the health system, which included upwards transmission of data and reports, as well as communicating feedback to sentinel sites and stakeholders, was as follows:The responsibilities of sentinel site staff included collecting epidemiological and laboratory data, transmitting these data to the District Surveillance Officers (DSOs), and collecting, storing and delivering patient specimens to staff at CPHRL.The molecular unit of the CPHRL served as the National Influenza Reference Unit (NIRU) and was responsible for developing protocols for influenza specimen chain of custody and transport, and for training of sentinel site laboratory personnel in specimen handling, bio-safety measures and cold chain maintenance. The CPHRL was also responsible for collecting samples from sentinel sites, logging information, packing and shipping samples to the Institut Pasteur in Dakar, Senegal, and entering laboratory data into the WHO FluNet database.The NSU was responsible for analyzing the epidemiological and laboratory data supervision and providing feedback to sentinel site staff and other stakeholders. The NSU was also responsible for entering epidemiological data into the global database FluID. The DSOs were in charge of reviewing and compiling weekly sentinel site data.The Sierra Leone national influenza sentinel surveillance protocol and SOPs for influenza sample collection, sample handling, packaging, shipping and transport, and data handling and sharing were developed based on the generic WHO guidelines. Additional protocols were adopted for entering epidemiological and virological data into the global databases, FluID and FluNet, which are key tools in monitoring global influenza trends in real-time. Information from FluID and FluNet is available to health professionals and policy makers to assist in making informed decisions regarding influenza management. Using these databases, surveillance activity in Sierra Leone is incorporated into a global network for influenza epidemiological data collection.Standardized case definitions were adopted to identify influenza-like illness (ILI) and severe acute respiratory infection (SARI) cases. An ILI case was defined as \u201ca person with respiratory illness with a measured temperature greater than 38\u00b0C and an onset of a cough within the last seven days\u201d. A SARI case was defined as \u201ca person with respiratory illness with a history of or measured temperature greater than 38\u00b0C, a cough, and onset of shortness of breath or difficulty breathing that required hospitalization within the last seven days\u201d.The training workshop targeted all staff involved in surveillance, including surveillance officers at the national and district level, clinicians, laboratory technicians, monitoring and evaluation officers in charge of data at the selected health facilities, and staff at CPHRL. The topics covered in the training included an overview of influenza epidemiological patterns, clinical and virological diagnosis of influenza, and specimen collection, handling and transportation. Data management, including data collection, collation, analysis and flow, was also discussed. At the national level, additional information on weekly summary reporting and data analysis using EpiInfo software was discussed.On-site support at sentinel sites covered practical demonstration of nasal swab sample collection, data recording, compilation of weekly summaries, and transfer of samples. Additional support included demonstration for correct sample handling, storage, and assurance of cold chain integrity and usage of sample custody forms.The NSU conducted regular supervision to facilitate smooth operation of the implementation. The DSOs in charge of collecting and compiling weekly sentinel site data also provided additional support to sentinel sites, including cleaning data to maintain data quality and timeliness. Regular review meetings were held, bringing together all staff engaged in sentinel influenza surveillance from sentinel sites, CPHRL, MOHS and WHO. The objectives of the meeting were to determine the progress of implementation, identify challenges, and propose solutions and elaborate subsequent steps in the process of implementation.The sentinel surveillance system formally began on August 19, 2011. The implementation was closely monitored and supported through onsite technical assistance, regular supervision and monthly review meetings.A sampling method was used for ILI cases based on the patient load at health facilities and the capacity of the laboratory to process samples. Accordingly, a nasal swab sample from every fourth ILI patient was collected. For SARI, a nasal swab was collected from all cases. Prior to sample collection, an explanation of the procedure was provided and verbal consent was obtained from the patient or guardian. Nasal swabs were collected according to the procedures described in the SOPs. The following data were recorded for each patient sampled: sentinel site identification number, date of symptom onset, date of specimen collection, date of hospitalization (for SARI cases), sex, age, temperature, pregnancy status, seasonal influenza vaccine status, antiviral use, and any comorbidities.Specimens were stored at sentinel sites in appropriate viral transport media at 2-8\u00b0C until collection by the CPHRL. Sentinel sites notified the CPHRL regarding samples that were collected and ready for pick-up. Samples were picked up by the CPHRL within 48 hours of collection. At the CPHRL, the specimens were logged and packaged for shipment to the Institut Pasteur in Dakar, Senegal.Reverse transcriptase PCR (RT-PCR) testing for influenza A and B was conducted at the Institut Pasteur in Dakar, Senegal. The results were communicated to the MOHS and also back to the sentinel sites from which the sample originated.During the SISA project surveillance data collection period in Sierra Leone, from August to December 2011, 1,235 ILI cases and 282 SARI cases were identified in the four sentinel sites \u2022Securing additional funding to cover specimen collection, laboratory costs, consumables, etc.\u2022Close monitoring of progress with update and feedback at regular review meetings\u2022Motivation of staff through recognition and other non-monetary incentivesThe project was implemented using a deliberate systematic approach, beginning with a thorough assessment of Sierra Leone\u2019s existing surveillance system capabilities. The national IDSR network was used as a platform to integrate the ISS and demonstrated that building on an existing framework was the most appropriate approach.Training, which began after all stakeholders were identified and committed to be part of the sentinel site, occurred at multiple levels and ensured that all involved with surveillance activities were properly trained before progressing to the implementation phase. A similar approach was used in data collection. The roles, responsibilities and reporting timelines were clearly defined on the surveillance data flow for each level to avoid confusion and to ensure regular submission of data. Using this approach ensured that the project was fully prepared to successfully implement the sentinel site surveillance.Another important factor for the success of the SISA project was the ownership and active leadership of the government of Sierra Leone. The ISS system implementation began with a briefing at the national level to ensure the participation of decision makers and staff involved in surveillance activities at various levels. Following the initial assessment, a consensus-building meeting was held where important information was communicated and the national action plan was developed using a participatory approach. The monthly review meetings that brought together focal persons from the various sentinel sites, CPHRL, and surveillance officers from the district and national levels served for sharing experiences, providing feedback and troubleshooting problems. Allowing staff members to directly participate in the evaluation and management of the surveillance activities and openly recognizing their work, increased staff motivation and dedication.The timing of the project coincided with the strategic planning for IDSR, which allowed for its integration with the overall surveillance function and provided additional support for the activity. Most importantly, the project benefited from the national leadership, committed partners, team approach and continuous engagement and motivation of all staff involved. The introduction of the SISA project also coincided with the ongoing efforts of partners, such as WHO and CDC, in building the capacity of the CPHRL. Additionally, partnerships such as the Institut Pasteur in Dakar, Senegal, and the Ghana National Influenza Center were beneficial in providing laboratory services unavailable in-country.The focused technical and financial support through the SISA project was critical for the success of establishing the system for ISS in Sierra Leone. However, continuation of project support following the initial phase could have allowed for better consolidation of the achieved results and detailed analysis, including seasonal variation, of the information from the epidemiological and virological data in the country. Despite the above limitation of the project, the integration of the ISS into the IDSR is an effective and efficient approach that will allow for sustainability. These efforts will require the continued support of partners such as WHO and CDC in order for Sierra Leone to maintain generation of influenza surveillance data that is critical for disease control efforts at local and international levels.The WHO SISA project demonstrated the feasibility of building a functional influenza surveillance system in Sierra Leone, integrated into the existing national IDSR system and generating relevant surveillance data within a seven-month in-country project phase and sustained with support of local partners.Although the collaboration with influenza laboratories in the region was a useful initial step, the reliance on an out-of-country laboratory for testing required additional organization, time, and increased funds. Strengthening and accreditation of the CPHRL of Sierra Leone will enable the national ISS system to function more efficiently and independently. Future laboratory related work should ensure a system for efficient specimen handling, regular supply of markers, and participation in quality assurance to ensure that the CPHRL is advanced to the list of National Influenza Center status.Despite the challenges and limitations, the ISS system in Sierra Leone produced valuable results that were incorporated into the global databases FluID and FluNet. Additionally, one year following cessation of active external technical support by SISA, the system continues to be operational and effective in monitoring the burden of influenza. National ownership was demonstrated to be a critical element in the success of the project and is critical for sustainability of the ISS system and other future surveillance activities. The ISS system, if sustained long-term, would provide valuable data to determine epidemiological and virological patterns and trends to assess the influenza disease burden that will ultimately guide national control strategies.APHL: Association of Public Health Laboratories; CDC: US Centers for Disease Control and Prevention; CRHRL: Central Public Health Reference Laboratory; DHMT: District Health Management Team; DPC: Directorate of disease prevention and control; DSO: District surveillance officers; IDSR: Integrated disease surveillance and response; ISS: Influenza sentinel surveillance; MOHS: Ministry of health and sanitation; NSD: National disease surveillance program; RT-PCR: Reverse transcriptase - polymerase chain reaction; SISA: Strengthening influenza sentinel surveillance in Africa project; SOPs: Standard operating procedures; WHO: World Health Organization.CA Steffen works for the Agence de M\u00e9decine Pr\u00e9ventive (AMP), which receives unrestricted support from Sanofi-Pasteur and grant-specific support from Crucell, GlaxoSmithKline, Merck, Novartis Vaccines, Pfizer and Sanofi Pasteur. All other authors have declared that no competing interests exist.SK and IC conceived the study. CA was the overall SISA project coordinator for AMP and provided scientific advice and technical input to the manuscript as well as revision work. SK, IC, CA, IW, and FD organized and coordinated collection of field data. SK, IC, and FK analyzed data. SK drafted the manuscript. SK, CA, WA, and KV finalized the manuscript. AJ, AY, FK provided feedback to the manuscript. All authors read and approved the final manuscript."} +{"text": "Chronic cough is a very common complaint in clinics throughout China. Clinical and basic science research on chronic cough started late, but in recent years the effort has yielded promising findings regarding the etiological diagnosis, treatment and pathogenesis. We found that inflammation in nonasthmatic eosinophilic bronchitis has some similarities to cough variant asthma but also a number of distinct differences. Recent evidence has also suggested a mechanistic link between airway neurogenic inflammation and and gastroesophageal reflux cough (GERC). Cough-related animal models have been developed, including models for esophageal reflux, nonasthmatic eosinophilic bronchitis and allergic rhinitis. Normal reference values for differential cell counts in induced sputum, cough sensitivity and esophageal 24-h pH monitoring in Chinese healthy subjects have been established. By using a modified algorithm for the etiological diagnosis of chronic cough, the causes of chronic cough have been investigated across a number of cities in China. The most common causes of chronic cough are cough variant asthma, eosinophilic bronchitis, upper airway cough symptoms, atopic cough and GERC, however, there are some regional variations. The Chinese National Guidelines on Diagnosis and Management of Chronic Cough were drafted in 2005, updated in 2009, and have been widely publicized and disseminated through many channels since their publication. In the clinical setting, chronic cough is defined as cough being sole or predominant symptom and lasting for more than 8 weeks with normal chest X-ray. Chronic cough is a common complaint in China, as it is in Europe, America and Japan. An epidemiological study demonstrated a 3.3% incidence of chronic cough among college students in Guangzhou. It is aSince the description of an anatomy-based diagnostic protocol for chronic cough in 1977 by Irwin and colleagues, many studies have been undertaken in America, Europe and Japan, concerning the pathogenesis, etiologic diagnosis and management of chronic cough with the subsequent development of national guidelines-6. Since4), histamine, prostaglandins, and eosinophilic cationic protein (ECP). Despite the similarities between EB and asthma, there are a number of disparities:Airway inflammation in EB shares some similarities to asthma regarding the recruitment of inflammatory cells such as eosinophils (Eos), T lymphocytes and mast cells, as detected using the induced sputum test, bronchoalveolar lavage fluid (BALF) cytology and airway mucosal biopsy. In addition, airway inflammation is attributable to the pro-inflammatory mediators released from these cells, which include leukotriene C4 in induced sputum in both EB and asthma,13. HoweLiu et al. found that gastroesophageal reflux is an independent cause of cough, and that reflux of the distal esophagus may induce cough in most cases with GERC. In patients with GERC, distal reflux episodes accounted for 88.23% of all reflux events during 24-hour pH monitoring, and were positively correlated to the onset of coughs. In guinAnimal cough models include models of isolated cough and those of cough-related diseases. Several specific cough-related animal models currently available in China are described below.Animal models of reflux esophagitis with concomitant inflammation in the tracheal and bronchial mucosa were successfully established in guinea pigs by repeated esophageal infusion of HCL and pepsin. These animal models provide a basis for studies on the pathogenesis of reflux-related respiratory disorders.An eosinophilic bronchitis model in BALB/c mice has been established for the first time. To establish the model of this kind, all the mice were sensitized by intraperitoneal ovalbumin (OVA) and subsequently challenged by either intranasal drip or inhalation of OVA. This moAn allergic rhinitis model was successfully established by sensitizing mice with intraperitoneal OVA and then challenging them with an intranasal OVA drip. In addiEarly studies in Europe and America indicated that the most common causes of chronic cough in specialist clinics were postnasal drip syndrome (PNDS), bronchial asthma and gastroesophageal reflux (GER), which accounted for more than 93.6% of all causes. ReferriThe definition of atopic cough was first proposed in 1989 by Fujimura. In JapaOur previous study showed that about 5% of chronic cough can be attributed to chronic bronchitis. ChronicIn 2003, analysis of differential cell count in induced sputum samples was introduced into the diagnostic protocol for chronic cough in China. This teIn China, the assessment of cough sensitivity is not yet an established part of the diagnostic algorithm for chronic cough, and is available in only a few medical institutions. The normal lower limit of cough sensitivity has been primarily established (C5 \u226562.5 \u03bcmol/L) using a single metered-dose inhalation of capsaicin. IncreasIn the Chinese National Guidelines on Diagnosis and Management of Cough, detection using spirometry and airway hyperresponsiveness is recommended as the first-line tests for the diagnosis of chronic cough. While sAmbulatory 24-h esophageal pH monitoring has some value in the diagnosis of gastroesophageal reflux disease and to assess the association between reflux events and cough episodes. The normal Demeester score is <12.70 for healthy Chinese subjects, slightlThe algorithm for the etiological diagnosis of chronic cough has been re-structured to adapt to the clinical picture of this condition in China Figure, with reNB: 1) ACEI: angiotensin converting enzyme inhibitor; UACS: upper airway cough syndrome; PNDS: postnasal drip syndrome; CVA: cough variant asthma; EB: eosinophilic bronchitis; SPT: skin prick test; IgE: immunoglobulin E; GERC: Gastro-esophageal reflux-related cough; AC: atopic cough. 2) Empirical treatment can be initiated in grass-root institutions or to individuals with low income. Patients who fail empirical treatment should be referred for thorough investigations of underlying etiologies at institutions with sufficient access to medical resources, to prevent a delay in treatment.Along with increasing concern in this field, a series of studies addressing the etiologies and treatment of cough have been conducted in Europe, America and Japan over the past 30 years. These efforts have shed light on the common causes of chronic cough and have given rise to the development of guidelines on the diagnosis and treatment of cough-6. In ChSince their release, the Chinese cough guidelines have been widely publicized and disseminated through journals, newsletters, conferences, internet and many other channels. A Cough Forum has been held annually around China since 2007, which provides a platform to discuss the cough research hot topics. A cough symposium has also been added to the agenda of the Annual Conference of Chinese Society of Respiratory Diseases. In addition, several reputable national journals have launched columns or published special issues on chronic cough to introduce the state-of-the-art advances in this field worldwide. Furthermore, keynote speakers from America, Europe and Japan are invited to China on a regular basis to share their expertise on chronic cough.Looking to the future, we still have a long way to go until the mystery surrounding chronic cough is unraveled. The closer communication and collaborations between Chinese and international specialists will improve our understanding of the diagnosis and treatment of chronic cough in the future.Chronic cough is a common complaint in the clinic in China. In the last decade, the etiological diagnosis and pathogenesis of chronic cough have been widely studied in China, and promising findings have been reported. The pathophysiology and causes of chronic cough in China have local characteristics. Whether genes, geography and lifestyle diversity contribute to these differences is unknown. We have developed cough-related tests, such as the induced sputum test and capsaicin challenge test. With the release of the Chinese Guidelines on the Diagnosis and Treatment of Cough, we believe many more patients are being correctly diagnosed and receiving the appropriate treatment. However, the cause and pathogenesis of some types of chronic cough need to be further elucidated.The authors declare that they have no competing interests.NSZ and KFL conceived the study. KFL and WL carried out the literature review and drafted the paper, GQZ drafted the paper and provided writing support. All authors read and approved the final manuscript.KFL: M.D. PhD., Professor of Internal Medicine, State Key Laboratory of Respiratory Diseases, 1st Affiliated Hospital of Guangzhou Medical College, and PhD tutor of respiratory medicine.WL: Master Degree in immunology, senior research fellow, State Key Laboratory of Respiratory Diseases, 1st Affiliated Hospital of Guangzhou Medical College.st Affiliated Hospital of Guangzhou Medical College; Editorial Director, Journal of Thoracic Disease.GQZ: M.D., Associate Professor of Medicine, Professor of Editology and Publishing, State Key Laboratory of Respiratory Diseases, 1NSZ: Academician of Chinese Academy of Engineering, Professor of Internal Medicine, State Key Laboratory of Respiratory Diseases, 1st Affiliated Hospital of Guangzhou Medical College, and PhD tutor of respiratory medicine."} +{"text": "I read with interest the timely article by Rasoli and colleagues, who reviewed the literature on the efficacy of antioxidant vitamins in the management of atrial fibrillation (AF) . Those aInhibiting the major source of excess ROS is a different therapeutic approach that may prove effective in the management of various types of arrhythmia. The major sources of cardiac ROS are nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the mitochondria electron transport chain, and uncoupled endothelial nitric oxide synthase. Those sources of ROS are interrelated, and the activation of one may result in the increased production of ROS by other sources, particularly by mitochondria (ROS-induced-ROS release) . Under d"} +{"text": "Rather, the available evidence indicates that these disorders are associated with subtle abnormalities distributed throughout the brain , major depression, bipolar disorder, post-traumatic stress disorder (PTSD), and Alzheimer's disease, and showcases the diverse range of methods used to interrogate these brain changes.This Special Topic of The article by Fornito and Bullmore overviewThe remaining articles illustrate the application of specific techniques to study different disorders. Independent component analysis (ICA), a popular data-driven technique for decomposing fMRI data into distinct components with characteristic anatomy and temporal dynamics (Calhoun et al., Seed-based techniques are featured in the work of Mills et al. , Mennes In a second study of MDD, Almeida et al. use dynaGraph analytic techniques are featured in the work of Xie and He and CollFinally, Lungu and Stip present Collectively, the research presented in this Special Topic provides the novice reader with exposure to the diverse array of methods available for interrogating brain network structure and function in health and disease, and offers the expert reader prime examples of cutting-edge applications of these methods to understand psychiatric disorders. The continued development of novel connectivity mapping techniques (Bassett et al.,"} +{"text": "The BITS2011 meeting, held in Pisa on June 20-22, 2011, brought together more than 120 Italian researchers working in the field of Bioinformatics, as well as students in Bioinformatics, Computational Biology, Biology, Computer Sciences, and Engineering, representing a landscape of Italian bioinformatics research.This preface provides a brief overview of the meeting and introduces the peer-reviewed manuscripts that were accepted for publication in this Supplement. The Italian Society of Bioinformatics (BITS) was founThe main aim of the Society, which is a Regional group of the International Society for Computational Biology (ISCB), is the fostering of Bioinformatics in Italy. Its activities include the organization of an annual scientific meeting, the maintenance of a web site and of a mailing list for the distribution of news of interest for the involved community of researchers, the coordination of educational initiatives in Italy, from bachelor to PhD degrees, the coordination of research activities among members, and the improvement of the participation of Italian researchers, both senior and junior, to international events and projects of relevance.The Eighth Annual BITS Meeting, BITS 2011, was held in Pisa at the Research Campus (Area della Ricerca) of the National Research Council (CNR), on June 20-22, 2011. The meeting was organized by Marco Pellegrini of the CNR Institute for Informatics and Telematics and by Roberto Marangoni of the Computer Science Department of the University of Pisa.Over 120 scientists actively working in bioinformatics and related fields or strongly interested in its development met and discussed their work, state of the art and future perspectives. A total of 98 abstracts were accepted: 23 of them were selected for oral presentation by the Scientific Committee after a well established peer-review procedure based on three reviews and scores per paper. The remaining 75 were presented in the poster sessions.Four keynote talks were given by distinguished scientists. Marie-France Sagot, INRIA-Lyon, France, gave a talk on \"Towards an Algorithmic and Mathematical Exploration of Symbiosis\". \"How not to Become a Systems Biologist\" was the title of the \"Giuliano Preparata\" Lecture given by Arthur Lesk, Penn State University, USA. Bud Mishra, New York University, USA, gave a provocative talk on \"Why we Keep Assembling...\". \"Using the T-Coffee Multiple Sequence Aligner in the High Throughput Era\" was the title of the keynote given by Cedric Notredame, Center for Genomic Regulation (CRG), Barcelona, Spain. The last talk was co-sponsored by the Italian Network for Bioinformatics Oncology (RNBIO).The conference was organized into thematic sessions that reflected the following conference topics: Genomics, Molecular Evolution and Comparative Genomics, Protein structure and function, Proteomics, Transcriptomics, Metagenomics, Systems Biology, Biological Databases, Biobanks, Algorithms for Bioinformatics, Biophysics, and Synthetic Biology.An \"industrial track\" was also organized under the form of a round table focused at opening a dialogue between the industries and the academic world on bioinformatics. The round table was participated by deputies of University of Pisa, CNR, industrial accelerators programs, and computing and/or life sciences companies in Tuscany. It ended with the decision to open a permanent table of discussion on the advancement of bioinformatics in the Innovation Poles in Tuscany.The web site of the mTwo tutorial lectures were also given on the last day of the meeting at the Computer Science Department of the University of Pisa. Giorgio Valentini, from the University of Milan , gave a tutorial on \"Machine learning methods for gene function prediction\" and Andrea Bracciali, from the University of Stirling , gave a lecture on \"Formal Models in Systems Biology\".Shortly after the conference, 42 papers were submitted for publication in this BMC Bioinformatics Supplement. An Editorial Board was formed, including all members of BITS Programme Committee. Associated Editors are listed here:\u2022 Rita Casadio, University of Bologna, Bologna, Italy\u2022 Gianni Cesareni, University of Rome \"Tor Vergata\", Rome, Italy\u2022 Francesca Ciccarelli, European Oncology Institute, Milan, Italy\u2022 Domenica D'Elia, CNR Institute for Biomedical Technologies, Bari, Italy\u2022 Diego Di Bernardo, Telethon Institute of Genetics and Medicine, Naples, Italy\u2022 Angelo Facchiano, CNR Institute of Food Sciences, Avellino, Italy\u2022 Manuela Helmer Citterich, University of Rome \"Tor Vergata\", Rome, Italy\u2022 Sabino Liuni, CNR Institute for Biomedical Technologies, Bari, Italy\u2022 Roberto Marangoni, University of Pisa, Pisa, Italy\u2022 Marco Pellegrini, CNR Institute for Informatics and Telematics, Pisa, Italy\u2022 Graziano Pesole, University of Bari, Bari, Italy\u2022 Paolo Romano, IRCCS San Martino IST, Genova, Italy\u2022 Giorgio Valle, University of Padova, Padova, ItalyA stringent reviewing procedure was then adopted. Associate Editors handled the process according to their recognized knowledge in specific meeting topics. At least three referees, of a high reputation at an international level, were selected for each submission. Overall, 67 referees from 20 different countries were involved in the selection of papers. We opted for a two step peer review procedure, offering authors the possibility to submit a new version of their paper, revised according to the referees' comments.At the end of this process, 22 papers were accepted and are now included in this Supplement. They cover different aspects of theoretical and applied Bioinformatics. For sake of readability, they are presented in this Supplement grouped by topic.et al [et al. [et al. [In the context of \"Algorithms for Bioinformatics\", we present three contributions. \"Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee\" from Chang et al reports [et al. presents [et al. presentset al [In the context of \"Biological Databases and Biobanks\", this Supplement includes the following four papers. \"GIDL: a rule based expert system for GenBank Intelligent Data Loading into the Molecular Biodiversity Database\" by Pannarale et al presentset al [\"An ICT infrastructure to integrate clinical and molecular data in oncology research\" by Segagni et al presentset al [\"OREMPdb: a semantic dictionary of computational pathway models\" by Umeton et al presentset al. [\"Towards Linked Open Gene Mutations Data\" by Zappa et al. presentset al [et al [et al [In the context of \"Biophysics and Synthetic Biology\", the paper \"Fine-tuning anti-tumor immunotherapies via stochastic simulations\" by Caravagna et al uses siml [et al presentsl [et al offers al [et al copes wiCarthamus tinctorius and Cynara cardunculus\" [et al [et al [For the \"Genomics\" topic, three papers were selected. In the first one, \"In-silico and in-vivo analyses of EST databases unveil conserved miRNAs from unculus\" , Catalan\" [et al , the autl [et al describeet al [For the \"Molecular Evolution and Comparative Genomics\" topic, \"Primates and Mouse NumtS in the UCSC Genome Browser\" from Simone et al describeet al., in \"Intuitive representation of surface properties of biomolecules using BioBlender\" [et al. [et al. [radii. A version of the software running on Linux is also made available for download as supplementary material. The last paper in this topic, by Vangone et al [The topic \"Protein Structure and Function\" had four works selected. Andrei Blender\" , describ [et al. , describ [et al. , describne et al , reportsThe \"Systems Biology\" topic is represented by the work of Fioravanti and co-authors , where set al [et al. [Finally, the \"Transcriptomics\" topic has two papers selected. The work by Consiglio et al describe [et al. describeThe next Annual meeting of the Italian Society of Bioinformatics will be held in Catania, May 2-4, 2012. Further information about BITS 2012 is available on its purpose web site , as well"} +{"text": "The xylem vascular system is composed of fused dead, hollow cells called tracheary elements (TEs) that originate through trans-differentiation of root and shoot cambium cells. TEs undergo autolysis as they differentiate and mature. The final stage of the formation of TEs in plants is the death of the involved cells, a process showing some similarities to programmed cell death (PCD) in animal systems. Plant proteases with functional similarity to proteases involved in mammalian apoptotic cell death (caspases) are suggested as an integral part of the core mechanism of most PCD responses in plants, but participation of plant caspase-like proteases in TE PCD has not yet been documented.Confocal microscopic images revealed the consecutive stages of TE formation in Zinnia cells during trans-differentiation. Application of the caspase inhibitors Z-Asp-CH2-DCB, Ac-YVAD-CMK and Ac-DEVD-CHO affected the kinetics of formation and the dimensions of the TEs resulting in a significant delay of TE formation, production of larger TEs and in elimination of the 'two-wave' pattern of TE production. DNA breakdown and appearance of TUNEL-positive nuclei was observed in xylogenic cultures and this was suppressed in the presence of caspase inhibitors.To the best of our knowledge this is the first report showing that caspase inhibitors can modulate the process of trans-differentiation in Zinnia xylogenic cell cultures. As caspase inhibitors are closely associated with cell death inhibition in a variety of plant systems, this suggests that the altered TE formation results from suppression of PCD. The findings presented here are a first step towards the use of appropriate PCD signalling modulators or related molecular genetic strategies to improve the hydraulic properties of xylem vessels in favour of the quality and shelf life of plants or plant parts. Maintenance and structuring of tissues and organs, homeostasis and defence in biological organisms are controlled by well coordinated and active cellular processes of death and survival. Programmed cell death (PCD) is a cell suicide genetically programmed, developmentally associated and environmentally stimulated mechanism and has been found throughout animal and plant kingdoms -6. PCD iIn vascular plants, PCD is involved in embryogenesis, developmental processes, senescence, hypersensitive response to pathogen attacks and in the response to abiotic stress stimuli ,5,19,27.Zinnia elegans) cell cultures, derived from leaf mesophyll cells, has revolutionized the understanding of the xylem differentiation process butane; (NAA): \u03b1-naphthalene-acetic acid; (BA): NPT and ETI shared their participation in the experimental design of the study, pharmacological analysis, light, fluorescent, confocal and DIC microscopic observations and measurements, DNA analysis, data processing and manuscript drafting. ETI also contributed to manuscript revision. TQ participated in the experimental work as a MSc thesis student. WvI and JHNS acted as daily supervisors of the experimental work. AMCE and OvK were involved in the coordination of the research program on xylogenesis and plant quality, OvK as chair of the Department Horticultural Production Chains and AMCE as chair of the Department of Plant Cell Biology. Both participated in the progress meetings.EJW conceived and co-ordinated the study on PCD in xylogenic Zinnia cultures and drafted and revised the final version of the manuscript. All authors read and approved the final manuscript.Zinnia elegans: from cellular development in vitro to performance in planta\" of which this study is a part. He is currently appointed as Lecturer at the Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. ETI is qualified in plant physiology with a focus on programmed cell death, cell cultures, phyto hormones, stress and post-harvest physiology. In this study she participated through 21 months EC FP6 Marie Curie Intra-European Fellowship project \"Regulating plant quality by controlling xylem vessel dimensions during xylogenesis\" at Wageningen University, Agrotechnology and Food Science Group (AFSG), Wageningen, The Netherlands. At present ETI occupies a position of Associate Professor at the Institute of Ornamental Plants, Sofia, Bulgaria. TQ participated in the work when she was a MSc student, currently she is a PhD student at Wageningen University. WvI is Assistant Professor at Wageningen University, Department Horticultural Production Chains, his expertise is, among others, in effects of environmental conditions on plant growth and product quality and is an expert in xylem vessel functioning and its relation to quality of detached plant parts. JHNS is Associate Professor in the Laboratory of Plant Cell Biology, with a main expertise in structural plant cell biology and embryogenesis. AMCE is Professor of Plant Cell Biology of Wageningen University with main expertise in cytoskeleton and cell wall formation. OvK is chair holder of the Department Horticultural Production Chains of Wageningen University with main expertise in chain management and non-destructive measurements of processes related to product quality. EJW is Professor in the Department Horticultural Production Chains and project manager at the Wageningen University Research Institute \"Food and Biobased Research\". EJW has a broad background in (postharvest) plant biology and has long term experience in plant programmed cell death research using, among others, different types of cell cultures.PT was employed as a PhD student at Wageningen University, Department Horticultural Production Chains from 2003 to 2007 and successfully defended his PhD Thesis \"Hydraulic properties of"} +{"text": "Eucalyptus: Collaborating Center in Agriculture Defense Relative to the Biosafety of Genetically Modified (GM) Eucalypts\u201d is to gather, assess and validate the existing information concerning GM and non-GM Eucalyptus and its derivatives in the Brazilian environment, both in laboratories and field test experiments. Accordingly, the purpose of the present research activity is to provide a binary plasmid collection containing different versions of the gene encoding green fluorescent protein (GFP), originally from Aequorea victorea, for the future generation of easily detectable GM plant phenotypes. Using commercially available plasmids encoding blue (ECFP) and yellow (EYFP) versions of GFP for expression in bacteria, the initial strategy was to transfer the coding sequences to the intermediate plasmid pSport1 (Invitrogen) and, subsequently, to pART7 plasmid, which contains the promoter and terminator sequences for gene expression in plants. Although recombinant bacteria have been obtained for both genes, DNA sequencing showed that success was achieved only with pSport1-eyfp. So far, pART7 versions were not obtained. A new cloning strategy was proposed, which involves the binary plasmid pCAMBIA1302 (Cambia). This plasmid already contains one version of the gfp gene for expression in plants. The intention is to replace the gfp gene by ecfp, eyfp and mCherryFP versions. As soon as plasmids are finished, plants will be transformed via Agrobacterium tumefaciens, and their transgenic state will be confirmed by the fluorescence of the encoded proteins. Thus, the fluorescence of the GFP different versions will be used to monitor seeds, pollen, leaves and transgenic plants as a whole in the environment.The main purpose of the \u201cCDA Financial support: Brazilian Ministry of Agriculture, Farming & Supply (MAPA), and The National Council for the Development of Science & Technology (CNPq), Brazilian Ministry of Science & Technology (MCT)."} +{"text": "Analysis is lacking on the management of vector control systems in disease-endemic countries with respect to the efficiency and sustainability of operations.Three locations were selected, at the scale of province, municipality and barangay (i.e. village). Data on disease incidence, programme activities, and programme management were collected on-site through meetings and focus group discussions.Adaptation of disease control strategies to the epidemiological situation per barangay, through micro-stratification, brings gains in efficiency, but should be accompanied by further capacity building on local situational analysis for better selection and targeting of vector control interventions within the barangay. An integrated approach to vector control, aiming to improve the rational use of resources, was evident with a multi-disease strategy for detection and response, and by the use of combinations of vector control methods. Collaboration within the health sector was apparent from the involvement of barangay health workers, re-orientation of job descriptions and the creation of a disease surveillance unit. The engagement of barangay leaders and use of existing community structures helped mobilize local resources and voluntary services for vector control. In one location, local authorities and the community were involved in the planning, implementation and evaluation of malaria control, which triggered local programme ownership.Strategies that contributed to an improved efficiency and sustainability of vector control operations were: micro-stratification, integration of vector control within the health sector, a multi-disease approach, involvement of local authorities, and empowerment of communities. Capacity building on situational analysis and vector surveillance should be addressed through national policy and guidelines. Vector-borne diseases cause a major burden in the Philippines. Main diseases are malaria, dengue, lymphatic filariasis, schistosomiasis and Japanese encephalitis ,2. The PVector control has the potential to play an important role in reducing transmission of these diseases and in reaching critical low levels of vectorial capacity required for elimination of disease -9. To beThe technical and operational sustainability of vector control is of major concern, given the threat of insecticide resistance -12, and Numerous reports are available on the effectiveness and costs of individual vector control interventions, with some of these interventions having an application value in diverse epidemiological settings ,14. HoweThe World Health Organization promotes the principles and approaches set out in the strategic framework on integrated vector management (IVM) to improve the efficacy, cost-effectiveness, ecological soundness and sustainability of vector control . A recenThis study was initiated on the assumption that lessons could be learnt about operational efficiency and sustainability by studying vector control systems established at different levels of public administration because at each level, distinct conditions for decision-making and integration would apply. The outcomes were evaluated in relation to the five key elements laid-out in the framework on IVM: evidence-based decision-making; an integrated approach; collaboration within the health sector and with other sectors; advocacy, social mobilization and legislation; and capacity building . As the Three locations were selected, at different administrative levels, i.e. province, municipality and barangay; a barangay is the smallest administrative division in the Philippines and is equivalent to a village.The first case study location, Cagayan Valley in north-eastern Luzon, comprises the provinces of Isabela and Cagayan (combined population 2.4 million). This area was selected as an example of a malaria elimination programme showing promising results in the reduction of malaria cases. The programme in Cagayan Valley was implemented under the National Malaria Control Programme, with main support from the Global Fund. The second case study location was the municipality of Mati City , in Davao Oriental province in south-eastern Mindanao. This location was selected because of its known local efforts in developing an epidemic response system for vector-borne disease control. The third case study location, the barangay of Simbalan , in Buenavista municipality, Agusan del Norte province in northern Mindanao, was selected as a known example of a barangay with active involvement of local leaders and communities in vector control.The case studies were conducted on site in June 2011. Data on programme achievements in terms of training, supervision and interventions and data on disease incidence rates were gathered through meetings at health offices at regional, provincial and municipal level. Focus group discussions were held in selected municipalities and barangays with local government officers, barangay health workers and members of civil society to obtain qualitative data on the recent history, structure, organization and management of local programmes.Anopheles flavirostris and Anopheles maculatus, which breed at the edges of streams in foothills, especially near human habitation [The main malaria vectors in Cagayan Valley, as in most of the Philippines, are bitation -20. In 2Plasmodium falciparum. The purpose of the micro-stratification, to be updated every three years, was to aid programme managers in their planning, choice of interventions and efficient use of resources for case detection and vector control in accordance with the disease situation in each barangay.These malaria incidence data have enabled micro-stratification of malaria epidemiology, with the barangay as stratification unit. The micro-stratification, conducted in 2010, categorized individual barangays as having 'stable transmission', 'unstable transmission', 'sporadic transmission' or being 'malaria prone', defined on the basis of monthly patterns of malaria transmission using criteria presented in Table The results showed that the distribution of malaria was highly focal, with 'stable transmission' occurring in less than 1% of the barangays and the majority of barangays being classified as 'malaria prone' , with a population of 2,675, and Mabuno , with a population of 2,640. Both barangays had been malaria hotspots Table . MicroscClose examination of case reports revealed that in Antagan, the malaria cases were mostly male (92%), from 11 to 30 years (77%), occupational loggers (53%) or farmers (32%), and that 65% of all cases occurred during the months of June and July, coinciding with the planting season of rain-fed crops in the hills. Men staying out in the hills to plant and cultivate these crops during the rainy season, or to log trees, are apparently at risk to be infected with malaria, because these are the known habitats where the main mosquito vectors breed. Hence, it is likely that the remaining malaria transmission in Antagan occurred not within the barangay proper but out in the hills. The causes of the recent drop in cases need further investigation.Conversely, in Mabuno, malaria cases did not decline even with high coverage of LLINs and IRS. Here, the majority of cases were indigenous people, living in make-shift houses in the foothills, which were areas not covered under recent LLIN-distribution campaigns, and reporting to the barangay health centre for treatment when they were ill. This suggests that transmission has continued among indigenous people living unprotected from infectious bites outside of the barangay proper.The examples of Antagan and Mabuno indicate that information other than basic epidemiological data was important for evidence-based decision-making. Entomological data and information on personal protection behaviour among those staying in the foothills could help adapt the malaria control strategy to achieve further reductions in disease incidence. For example, increased attention could be paid to mobile indigenous populations and temporary agricultural workers, developing appropriate control methods , and targeting the interventions at times and places when and where these groups are most at risk of malaria transmission. Also, entomological surveillance to confirm the absence of malaria vectors within the barangay proper will help improve the efficient allocation and use of resources for vector control and personal protection.Summing up, the case from Cagayan Valley demonstrates a model for planning and adapting malaria control strategies to the epidemiological situation in each barangay. The benefits of micro-stratification were three-fold: it resulted in more efficient use of resources; it allowed for more in-depth understanding about malaria transmission within the barangay; and, it stimulated the involvement of local leaders. An important lesson is that this model could be improved further by collecting entomological data and determining which sections of society are most at risk of malaria transmission.The municipality of Mati City has been affected by both malaria and dengue. Malaria control has been well structured through the National Programme, with support from the Roll Back Malaria Project and Global Fund for case finding, treatment, and vector control through LLINs and IRS as well as capability building for local health staff and volunteers. These efforts were accompanied by a decline in malaria prevalence during the period 2005-2010 , began to organize weekly clean-up drives and conduct vector larval surveillance at monthly intervals. Second, a disease surveillance unit was created to enact and coordinate weekly reporting of cases of all notifiable diseases, including vector-borne diseases, from the city's two hospitals and from all 26 barangay health centres. These two measures helped safeguard the regular allocation in City budgeting for the detection and control of vector-borne diseases, notably dengue. In addition, in 2011, the City mayor's office began sponsoring the rapid deployment team, driven in part by the economic burden of dengue, due to costs incurred by the mayor's office for transport, treatment and referral of dengue cases to specialized hospitals.In the event of an increase in dengue cases or a local dengue outbreak, the relevant agencies were alerted to respond. The response consisted of intensified health promotion and weekly rounds of vector surveillance and concomitant source reduction in 100 houses in the vicinity of detected cases. The weekly rounds were repeated for up to 10 times, until the 'house index' (i.e. % of houses being positive for dengue breeding) dropped below the locally set threshold margin of 2-5% and the 'Breteau index' (i.e. the number of positive containers per 100 houses) dropped below the value of 20 . Hence, Aedes larvae are found on their compound. The resolution was adopted by the entire barangay, and the generated income went into a trust fund to treat dengue patients.There were other partners in vector control. The department of education created their own vector control task force with monitoring by brigades at schools. Moreover, barangay chiefs and councillors, having been among those trained on dengue prevention, provided support for health promotion and clean-up drives, issued permits to search people's compounds for vector breeding sites and, in one instance, formulated policy. After four child deaths due to dengue in one sub-barangay in 2009, the local councillor introduced a resolution that households must pay a fine of 50 pesos if Hence, the case of Mati shows how in-kind contributions for malaria control benefited dengue control activities through a joint malaria-dengue system of detection and vector control response. Even though dengue was the only prevalent vector-borne disease at the time of the case study, the system was prepared to respond to outbreaks of malaria and other diseases, thus increasing the efficiency as compared to single-disease systems. To safeguard the operational sustainability, the detection and response system was integrated within the health infrastructure. Cases of dengue fever dropped from 185 in 2010 to 108 in 2011; the coming years will show whether the strategy leads to a further reduction in disease cases and whether the political commitment can be sustained.sitios in a poorly accessible mountainous area. Sporadic cases of lymphatic filariasis were reported in the past, but dengue has been absent.Buenavista municipality has been relatively free from malaria, with the exception of a pocket of 'stable transmission' of malaria around Simbalan, a barangay composed of a number of scattered sub-barangays or sitios, and in that year the number of confirmed malaria cases was determined at 490 . In recent years, full coverage of the population with insecticidal nets has been achieved, whereas IRS was started in 2010 in the western-most part of the barangay where transmission risk through imported cases was considered to be highest. The number of malaria cases dropped to zero and evaluation of bed net utilization . Hence, surveillance data were readily utilized. Nevertheless, gaps remained in the evidence base needed for decision-making on vector control. Particularly, data on the cost-effectiveness of stream clearing against irostris , and on irostris ,27, wereng sites , and by ng sites .An integrated approach to vector control, aiming to improve the rational use of resources, was evident in the case of Mati where elements of a multi-disease strategy of detection and response had been established Table . Also, tCollaboration on vector control can improve operational efficiency within the health sector and lead to reduced disease risks in other sectors. Collaboration within the health sector was apparent from the involvement of barangay health workers in vector-borne disease control in each case study, but was most obvious in Mati, where the job descriptions of barangay health emergency response teams were modified and staff reoriented towards vector control and where a central unit was created for weekly surveillance of notifiable disease cases, including vector-borne disease cases Table . Health Advocacy and social mobilization were common features in each case study Table . SpecifiCapacity building is a major challenge to the improvement of vector control systems. The case examples indicate that a national strategy for capacity building on detection and diagnosis of malaria was in place, but competencies on situational analysis and vector surveillance appeared to be inadequate. These aspects should be addressed in national policy and guidelines.Considering the current reliance on external funding support, the operational sustainability of vector control remains uncertain. It will be particularly challenging to sustain vector control during and beyond the elimination of disease, after the public health problem has diminished -8; howevThe case studies have suggested several other mechanisms to sustain vector control: integration within the health sector, involvement of local authorities, and empowerment of communities. In Mati, financial support for dengue control was coming to an end, which prompted the municipal health authorities to incorporate dengue control within their health system, utilizing local infrastructure and safeguarding regular allocation of funds for vector-borne disease control in local budgeting. Yet, many municipalities with dengue prevalence may lack such resources and, thus, sufficient national funds should be allotted to the control of this neglected disease.bayanihan, a common tradition in Philippine towns [The engagement of barangay leaders and existing community structures helped mobilize local resources and voluntary services for vector control. Barangay authorities and the community in Simbalan were actively involved in the planning, implementation and evaluation of malaria control actions, indicative of local programme ownership. Moreover, their vision statement to become independent from external resources for malaria control is particularly relevant in the context of malaria elimination because continued commitment to surveillance and outbreak response will be needed . Neverthne towns . This suMicro-stratification based on epidemiological data resulted in improved efficiency of disease control operations, but should be accompanied by further capacity building on the selection and targeting of vector control interventions at barangay-level. The case studies suggested several mechanisms to improve operational sustainability of vector control: integration within the health sector, a multi-disease malaria-dengue approach, involvement of local authorities, and empowerment of communities. Local programme ownership on vector-borne disease control could potentially be replicated if adequate training and guidance are given.LLIN: Long-lasting insecticidal nets; IRS: Indoor residual spraying; ITN: Insecticide-treated nets; IVM: Integrated vector management; RDT: Rapid diagnostic test; SARS: Severe acute respiratory syndrome; WHO: World Health Organization.The authors declare that they have no competing interests.HvdB, RV, AE, BHGC, RT, MT and JH all participated in field visits and data collection. JH conceptualized the study. HvdB analysed and interpreted the data and drafted and revised the manuscript. JH, RV, BHGC, AE, RT and MT contributed to revising the manuscript. All authors have read and approved the final manuscript."} +{"text": "The gamma-secretase complex is an intramembrane aspartyl protease comprised of at least four known subunits: Presenilin (PS), Nicastrin (Nct), Aph, and Pen2. Presenilin is the catalytic subunit of the complex. Mutations in PS1 and PS2, which lead to familial early-onset Alzheimer disease, alter the activity and specificity of gamma-secretase. Investigation of gamma-secretase specificity and development of gamma-secretase based therapies have been a huge challenge because of its nature of intramembranal catalysis and macromolecular complex as well as cleavage of multiple substrates. We have developed an integrated approach of biochemistry, chemical biology and cell biology for the study of gamma-secretase structure and function. We will discuss how to apply this approach to elucidate the role endogenous and exogenous factors in regulation of gamma-secretase. We will focus on the development of chemical probes and utilize them to define the mechanism of action of gamma-secretase modulators."} +{"text": "Integrated analysis of both methods highlighted the extensive impact of moderate-severe LBP, the paucity of effective interventions, the pivotal nature of the midwife-patient relationship, and physiotherapists\u2019 concerns about using acupuncture for pregnant women, despite their use of it for other musculoskeletal problems. Results informed phase 2 in terms of patient information, recruitment and consent procedures. They also helped shape the training programme for physiotherapists delivering the interventions, to directly address issues of safety and side effects. Findings highlight the role mixed methods can play in preparing for randomised trials and ensuring they are sensitive to the needs of patients and practitioners. The phase 2 pilot trial is currently underway.EASE BACK is an NIHR HTA funded feasibility pilot trial to inform a large randomised trial evaluating the clinical and cost-effectiveness of acupuncture for pregnant women with low back pain (LBP). Mixed methods were employed to generate a breadth of data. In phase 1, interviews and focus groups explored the views of pregnant women with LBP about the acceptability of the proposed interventions, the content and delivery of participant information, important outcomes, and timing of outcome measurement; and the views of health professionals (midwives and physiotherapists) about standard care, using acupuncture for this patient group, proposed trial design, and recruitment methods. A total of 52 individuals were interviewed. In addition, a postal survey of UK based physiotherapists was undertaken (response rate 57.5%:"} +{"text": "Its unparalleled in vivo and quantitative capabilities offer a broad range of applications covering from noninvasive morphologic measurements, tissue microstructural characterization, hemodynamic and vascular characterization, metabolite measurements, sub-system physiologies, brain functions to monitoring of cell migrational dynamics. This presentation will illustrate these technological developments with some of the ongoing rodent brain MRI projects in our laboratory, highlighting the capacity of MRI as a platform technology to visualize the central nervous system (CNS) in vivo from molecules to systems levels. They include diffusion characterization of neural tissue microstructure; functional study of molecular pathways by spectroscopy; functional study of brain development and injury; monitoring of endogenous neural stem cell activities; and novel contrast agents for brain imaging.With advances in engineering and computing, an extraordinary body of imaging technologies and applications has developed over the last 35 years. One of the most important applications of such technologies is the study of anatomy, physiology, pathology and functions in humans and animal models of human development and diseases. Among the various"} +{"text": "To the Editor: Norovirus (NoV), the distinct genus within the family Caliciviridae, is a major cause of sporadic cases and outbreaks of acute gastroenteritis in humans . Polymerase chain reaction with specific primers resulted in the identification of astrovirus, rotavirus, sapovirus, adenovirus, and NoV genogroup I (GI) and GII successful co-infection of a single host, 2) successful co-infection of a single cell, 3) efficient replication of both parental strains, 4) template switching, and 5) purifying selection (The NoV capsid is predicted to be well suited for genotype classification (In conclusion, our results described the genetic characterization of novel, naturally occurring recombinant NoV and increased evidence for the worldwide distribution of recombinant NoV. This report is the first to describe acute gastroenteritis caused by recombinant NoV in China and warns of the threat it poses."} +{"text": "Although obesity is a risk factor for many chronic diseases, we have only limited knowledge of the magnitude of these associations in young adults. A multiethnic cohort of young adults was established to close current knowledge gaps; cohort demographics, cohort retention, and the potential influence of migration bias were investigated.For this population-based cross-sectional study, demographics, and measured weight and height were extracted from electronic medical records of 1,929,470 patients aged 20 to 39 years enrolled in two integrated health plans in California from 2007 to 2009.The cohort included about 84.4% of Kaiser Permanente California members in this age group who had a medical encounter during the study period and represented about 18.2% of the underlying population in the same age group in California. The age distribution of the cohort was relatively comparable to the underlying population in California Census 2010 population, but the proportion of women and ethnic/racial minorities was slightly higher. The three-year retention rate was 68.4%.These data suggest the feasibility of our study for medium-term follow-up based on sufficient membership retention rates. While nationwide 6% of young adults are extremely obese, we know little to adequately quantify the health burden attributable to obesity, especially extreme obesity, in this age group. This cohort of young adults provides a unique opportunity to investigate associations of obesity-related factors and risk of cancer in a large multiethnic population. In 2007Managed care systems are a unique system to study associations between rare outcomes in young adults due to their large populations and the potential for long passive follow-up periods. However, lack of generalizability due to healthy worker bias and the potential loss of subjects in epidemiologic studies using members of managed care systems are of concern because these factors can be a major of source of bias. Study subjects may lose their health insurance coverage or migrate out of the coverage area but also may re-enroll based on their employment status or other financial decisions and life events. If subjects who leave the health plan are systematically different from those who remain in the health plan in terms of exposure and the association with health outcomes, the estimates of association between exposure and outcome may be systematically biased. The potential of bias exists in all epidemiologic studies due to low and selective responses to recruitment attempts, survey fatigue, migration of subjects, and other factors. However, the control of this bias can be addressed through careful study design and interpretation of the data. As part of the study design, the potential existence of such bias has to be acknowledged, appropriate measures to assess such bias have to be made, and potential effects of such bias for direction and magnitude have to be estimated. Therefore, these potential biases are extremely important to understand.The long-term goal of this large prospective cohort of young adults is to investigate the relationship between weight class, metabolic syndrome, diabetes, and obesity-related cancers and their risk factors. The analyses presented here show the detailed cohort demographics, as well as cohort retention and the potential influence of migration bias.The present project was initiated to study the consequences of obesity in young adults (OBAYA) including cancer and leverages the resources of the Cancer Research Network (CRN), an ongoThe cohort is followed by passive follow-up through linkage with data extracted from the KP electronic health records. Information on occurrence of cancers comes from linkage of cohort members to KPNC and KPSC tumor registries, which are compliant with data requirements of the NCI Surveillance, Epidemiology, and End Research (SEER) Program and the North American Associations of Central Cancer Registries (NAACCR). Additional data come from probabilistic linkage to the National Death Index (NDI) and to the state cancer registry. The maximum follow-up on December 31, 2010 was four years, the minimum being one year.The study used information that is routinely assessed during most ambulatory and hospitalization visits. This information captures administrative datasets containing membership and benefit information including all medical encounters at Kaiser Permanente facilities, out-of-system claims, laboratory and radiology test results, and dispensed prescription pharmaceuticals. The address information is routinely geocoded to the census block level, providing the ability to link to census-based group-level socioeconomic information. Laboratory data are also available from electronic medical records. Using the cohort members\u2019 unique medical record numbers, incident diseases can be identified from electronic records, internal disease registries such as the cancer registry, and also from the state cancer registry and state death files.Body weight and height are routinely measured during almost every medical encounter and were extracted from the electronic health records. BMI was calculated as weight (kilograms) divided by the square of the height (meters). Based on a validation study including 15,000 patients with 45,980 medical encounters, the estimated error rate in body weight and height data was <0.4%[th, 2011).Population counts for California were retrieved from Census 2010 data for California for individuals who were 20 to 39 years of age , linkage with state death files (restricted to death cases), and linkage with state cancer registries (restricted to those who remain in the state and limited to cancer diagnosis).Planned future research on the young adult cohort will develop these quality measures in order to identify person-level characteristics associated with both variations in services related to cardiovascular disease, diabetes, and cancer in young obese adults and variations in the care they receive and its consequences for incident morbidity, mortality, and health care utilization. This planned research will also examine differences in the effectiveness of that care in demographically and medically defined subpopulations.BMI: Body Mass Index; CRN: Cancer Research Network; NCI: National Cancer Institute; KPNC and KPSC: Kaiser Permanente Northern and Southern California; KP: Kaiser Permanente; IRB: Institutional Review Board; NCI: National Cancer Institute; SEER: NCI Surveillance Epidemiology, and End Research; NAACCR: North American Associations of Central Cancer Registries; NDI: National Death Index.Lawrence H Kushi reports a relevant relationship as Adjunct Professor at the UC Davis Medical School, which is not his primary employment.Design and conduct of the study: CK, LHK; Collection, management, analysis and interpretation of data: CK, LHK, NS, MPM, KH, HAC, AEW; Preparation of the manuscript: CK, MPM, NS; Critical revision of the manuscript for important intellectual content: LHK, KH, HAC, AEW. All authors read and approved the final manuscript."} +{"text": "Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness.The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway.A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients.The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. Standardization of the clinical care process through integration of evidence-based knowledge has proven to be an effective strategy for reducing unwanted variations in treatment and for minimizing the probability of medical errors . HoweverA possible tool to facilitate implementation of evidence into practice is a care pathway. Care pathways are complex interventions for mutual decision making, organization, and standardization of predicTable care for a well-defined group of patients during a well-defined period -8. One oCare pathways induce change at different levels of the organization ; consequently, variability at individual level outcomes may reflect the impact of higher-level complexity processes. To deal with these multilevel effects, cluster randomized designs are strongly recommended when studying the impact of care pathways ,11. ImpoIn 2009, the European Pathway Association (E-P-A) launched the European Quality of Care Pathways (EQCP) study, an international cRCT addressing the impact of a care pathway for chronic obstructive pulmonary disease (COPD) exacerbations [et al.[The clinical content of an evidence-based care pathway for COPD exacerbation was developed based on the process design methodology developed by Berry et al., and theet al., the Woret al. and the et al.. Subsequet al..A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Both sets are displayed in Additional file The patient population under study was specified as \u2018Patients hospitalized with COPD exacerbation\u2019. To ensure clinical validity and feasibility of the end product, an expert panel was involved in each step of the development method. This panel was composed of the following: (i) three clinicians with internationally recognized clinical and scientific expertise in COPD exacerbations: a respiratory physician (MD) who is also president of the European Respiratory Society, a physiotherapist (TT) who specializes in pulmonary rehabilitation, and a clinical nurse specialist in COPD (CL); (ii) an epidemiologist (MP) who specializes in organization of primary and secondary chronic care; and (iii) two professors in patient care management who have extensive clinical and scientific expertise in development and implementation of care pathways ,18-21. ATo identify all available evidence for integration in the evidence-based COPD care pathway, an extensive literature review was conducted by the main researchers, CL and KV Figure . First, http://www.thoracic.org); British Thoracic Society (BTS) (http://www.brit-thoracic.org.uk); European Respiratory Society (ERS) (http://www.ersnet.org); Global Strategy for Diagnosis, Management, and Prevention of COPD (GOLD) (http://www.goldcopd.org); National Institute for Health and Clinical Excellence (NICE) (http://www.nice.org.uk); Scottish Intercollegiate Guidelines Network (SIGN) (http://www.sign.ac.uk); (II) Public resources for evidence-based clinical practice guidelines ; (III) electronic databases including Medline and Embase and Cochrane; (IV) available process flow diagrams founded on evidence-based medicine .The following resources were explored: (I) websites of international respiratory societies: American Thoracic Society (ATS) \u2018practice guideline\u2019, (ii) \u2018disease exacerbation and patient care management\u2019, and (iii) \u2018outcomes\u2019. For Embase, we used the MeSH terms \u2018chronic obstructive lung disease\u2019 combined with (i) \u2018practice guideline\u2019 and (ii) \u2018disease exacerbation and patient care\u2019, and (iii) \u2018outcomes\u2019. Non-MeSH terms used in Embase were \u2018COPD\u2019 in combination with \u2018exacerbation and management\u2019. Search limit parameters included: (i) published between 2005 and 2011, and (ii) written in English, French, German, Italian or Dutch.Second, we performed a two-phase screening evaluation of publications selected from websites of the respiratory societies, Map of Medicine and the electronic databases. In the first phase, publications were appraised for relevance based on appropriateness of the title and abstract. If relevance was unclear, or if the abstract was unavailable, the publication was included for further appraisal of the full text. In the second phase, two independent researchers (CL and KV) reviewed the full text of the selected guidelines, reviews or process flow diagrams. The following inclusion criteria were used: (i) reportage of clinical processes and outcomes regarding in-hospital management of COPD exacerbation; (ii) evidence was reported in terms of guidelines, process flow diagrams, reviews or overview papers; (iv) published between 2005 and 2011; (v) published in English, French, German, Italian or Dutch; and (vi) quality of underlying evidence can be appraised by in-text references. The literature research revealed initially three guidelines, one process flow diagram, and 2,939 digital records from the electronic medical databases and 10 of 21 outcome indicators (47.6%). Highest consensus was reached for the process indicators for oxygen therapy (100%), pulmonary rehabilitation (100%), and patient education (94.5 to 88.6%), and for the outcome indicators for understanding of therapy (91.4 to 85.7%) and self-management (88.6 to 88.2%) .First, the list of 58 extracted clinical activities (step 2), together with the Delphi results (step 3), were sent to the clinical experts of the panel with a request to complete two tasks: (i) to review the 58 identified activities for validity and feasibility; and (ii) if indicated, to propose any additional clinical activity they believe is essential for in-hospital management of COPD exacerbations and which is lacking in the current activity list of clinical activities. Second, a consensus meeting was held with the entire expert panel in order to make a final selection of the clinical activities. As a result, all 58 clinical activities were appraised to be valid and feasible. In addition, 19 clinical activities beyond the 58 original ones were included clinical activities are inextricably linked to each other ; (ii) clinical activities need to be performed by a specific team member ; (iii) clinical activities need to be performed at a specific time point or within a specific time span of the care process . As a result, the 77 clinical activities were clustered into 38 key interventions, with 9 of them comprising 2 to 15 subcomponents.Second, the key interventions were categorized into three core processes , and subsequently presented by means of a process flow diagram. In addition, within each of three core processes, key interventions were grouped into care blocks based on the overall content of these key interventions . The process flow diagram with the 38 key interventions is displayed in Additional file For each key intervention, the following components were included in the detailed description: (i) rationale, which addresses why it is of crucial importance that the key intervention is performed, and which describes expected impact on patient outcomes; (ii) description, which defines the exact content of the key intervention; (iii) in-text references and reference list; and (iv) grading of evidence. An example of a detailed description of a key intervention on arterial blood gas measurements is provided in Figure Besides the set of key interventions, a set of process and outcome indicators needed to be developed to verify compliance to key interventions and to follow up the impact on outcomes. First, to select the final set of indicators, the expert panel convened for a consensus meeting. The selection process was based on the (updated) literature search step 2), the Delphi survey (step 3), and the developed set of 38 evidence-based key interventions (step 5) . As a re, the Delhttp://www.qualitymeasures.ahrq.gov) and the Joint Commission (http://www.jointcommission.org), each indicator and baseline variable was defined in an indicator protocol by the main researcher (CL). This process included defining of description, rationale or relation to quality, type of indicator , nominator and denominator, data collection method, data elements, data reporting , criteria to meet expected outcomes, and references. An example of an indicator description is detailed in Additional file Subsequently, the selected indicators and baseline variables were operationalized into objective measurements . Based oThe set of 38 key interventions, and the set of 24 process and 15 outcome indicators, were piloted by nine Belgian experimental COPD teams in the context of the EQCP study . The mulSecond, during a workshop in which team members of all nine multidisciplinary COPD teams attended, the process flow diagram, including the 38 key interventions, was presented. Subsequently, all key interventions were extensively discussed. Third, the detailed set of key interventions was provided to the study coordinator of each hospital. We requested all members of the multidisciplinary COPD team to extensively review the key intervention set and subsequently to provide feedback within two weeks. As a result, the feedback given during the workshop and provided after extensive appraisal by all teams showed that teams were very enthusiastic about the process flow diagram and underlying key interventions. Moreover, they agreed by consensus that the set of key interventions was valid and applicable for use in their practice.However, the teams provided four main remarks regarding: (i) usefulness of spirometry during exacerbation because results may be inaccurate due to the compromised condition; (ii) feasibility of referral to pulmonary rehabilitation with regard to condition of the patient and availability of a rehabilitation center; (iii) type of inhaler medications and device ; and (iv) finally content, workload and feasibility of patient education. First, with regard to spirometry, no hard evidence about accuracy and, thus, usefulness of spirometric tests during exacerbation is available and, thus, no specific guidance on whether or not to perform spirometric tests could be provided to the teams. This issue was specifically emphasized in the detailed set of key interventions. Concerning pulmonary rehabilitation, all teams were convinced about the importance of referring patients to rehabilitation, and consequently, during the workshop some alternatives with regard to availability of a rehabilitation center were discussed. Finally, with regard to inhaler therapy and patient education, a teaching workshop was organized and education tools for COPD teams and ready-to-use patient leaflets were provided.Finally, the nine multidisciplinary COPD teams implemented the set of key interventions as an active component of their care pathway for in-hospital management of COPD exacerbation in the context of the EQCP study . Six monA set of 38 evidence-based key interventions for in-hospital management of COPD exacerbation was developed and pilot testing (step 8). However, results of the Delphi survey and piloting are essential to ensure that the key intervention set is widely, clinically applicable. This is especially important when conducting a cRCT, in which the \u2018same\u2019 care pathway intervention needs to be implemented by different teams at different sites and possibly in different countries . Teams dA surprising finding is that, based on review of the literature (Step 2), the Delphi study, and face-to-face expert opinion, advanced care planning was not included in the set of 38 key interventions. On one hand, this can be explained due to the focus on management of acute COPD exacerbation. On the other hand, it is essential that advanced care planning and end of life discussions are initiated in advance of a life threatening situation, which can arise after COPD exacerbation . TherefoAn important limitation in the current strategy is the lack of patient involvement . PatientWe believe that developing the clinical care pathway content by using this newly developed and validated eight-step method will facilitate adequate integration of evidence-based knowledge into daily practice. Since the beginning of the 1990s, evidence-based clinical practice guidelines for almost all domains of medicine have been available worldwide, accessible more recently via the Internet ,70,71. HFinally, we want to emphasize the potential role of professional medical associations in clinical content development for evidence-based care pathways. Many national and international societies have extensive clinical and research experience in the patient population of their clinical field, comprise a global network of experts in the field, have funding available and, last but not least, have comprehensive understanding and experience in synthesizing evidence-based knowledge and making this knowledge usable for daily clinical practice. Therefore, we believe that professional societies could play a major role in developing the clinical content of future evidence-based care pathways, especially in terms of clinical support, expert networking and input of resources.The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways.1: Forced expiratory volume in one second; FVC: Forced vital capacity; GOLD: Global Strategy for Diagnosis Management, and Prevention of COPD; HICPAC: Healthcare Infection Control Practices Advisory Committee; HRQL: Health-related quality of life; LOS: Length of stay; LTOT: Long-term oxygen therapy; NICE: National Institute for Health and Clinical Excellence; QALY: Quality-adjusted life expectancy measure; SIGN: Scottish Intercollegiate Guidelines Network; WHO: World Health Organization.ABGs: Arterial blood gases; ACCP: American College of Chest Physicians; ATS: American Thoracic Society; BMI: Body mass index; BTS: British Thoracic Society; COI: Cost of illness; COPD: Chronic obstructive pulmonary disease; cRCT: Cluster randomized controlled trial; DALY: Disability adjusted life years; E-P-A: European Pathway Association; EQCP: European Quality of Care Pathways; ERS: European Respiratory Society; FEVThe authors declare that they have no competing interests.CL KV, WS, SD and MP contributed to the draft and the final version of the paper. MD supervised and was closely involved in the development of the clinical content of the care pathway intervention. MP, KV and WS have the scientific lead of the EQCP study. KV is international coordinator of the EQCP study. All authors have read and approved the final manuscript.Process flow diagram for in-hospital management of COPD exacerbation. This Additional file displays a process flow chart including 38 key interventions that should be performed for every patient entering the hospital with COPD exacerbation. The key interventions are classified under three core processes: Diagnostic, Pharmacological and Non-pharmacological management.Click here for fileSet of Process and outcome indicators for in-hospital management of COPD exacerbation. This Additional file displays a set of validated process and outcome indicators for audit of care for in-hospital management of COPD exacerbation.Click here for fileExample of description of an indicator. This Additional file displays the detailed description of an indicator according to the guidance of the Agency for Health Care Research and Quality and the Joint Commission (http://www.jointcommission.org).Click here for file"} +{"text": "Background: Legislation and regulation of pesticides used in public health are essential for reducing risks to human health and the environment.Objective: We assessed the global situation on legislation and regulatory control of public health pesticides.Methods: A peer-reviewed and field-tested questionnaire was distributed to 142 member states of the World Health Organization (WHO); 113 states completed the questionnaire.Results: Legislation on public health pesticides was absent in 25% of the countries. Where present, legislation often lacked comprehensiveness, for example, on basic aspects such as labeling, storage, transport, and disposal of public health pesticides. Guidelines or essential requirements for the process of pesticide registration were lacking in many countries. The capacity to enforce regulations was considered to be weak across WHO regions. Half of all countries lacked pesticide quality control laboratories, and two-thirds reported high concern over quality of products on the market. National statistics on production and trade of pesticides and poisoning incidents were lacking in many countries. Despite the shortcomings, WHO recommendations were considered to constitute a supportive or sole basis in national registration. Also, some regions showed high participation of countries in regional schemes to harmonize pesticide registration requirements.Conclusions: Critical deficiencies are evident in the legislative and regulatory framework for public health pesticides across regions, posing risks to human health and the environment. Recent experience in some countries with situational analysis, needs assessment, action planning, and regional collaboration has signaled a promising way forward. Major vector-borne diseases such as malaria, lymphatic filariasis, dengue, leishmaniasis, Chagas disease, and Japanese encephalitis, as well as nuisance pests in and around human habitations, cause tremendous suffering and impede the alleviation of poverty and constrain economic development. Thus, attaining the United Nation\u2019s Millennium Development Goals is diffiInternational Code of Conduct on the Distribution and Use of Pesticides [Food and Agriculture Organization of the United Nations (FAO) 2005], hereafter referred to as the Code of Conduct, and two recent World Health Assembly (WHA) resolutions, WHA 63.25 and 63.26 ]. This is a response rate of 80% of the number of targeted countries PDFClick here for additional data file."} +{"text": "Governance and leadership in health development are critically important for the achievement of the health Millennium Development Goals (MDGs) and other national health goals. Those two factors might explain why many countries in Africa are not on track to attain the health MDGs by 2015. This paper debates the meaning of 'governance in health development', reviews briefly existing governance frameworks, proposes a modified framework on health development governance (HDG), and develops a HDG index.et al also does not include macroeconomic and political stability as a separate principle. The Siddiqi et al framework does not propose a way of scoring the various governance domains to facilitate aggregation, inter-country comparisons and health development governance tracking over time.We argue that unlike 'leadership in health development', 'governance in health development' is the sole prerogative of the Government through the Ministry of Health, which can choose to delegate (but not abrogate) some of the governance tasks. The general governance domains of the UNDP and the World Bank are very pertinent but not sufficient for assessment of health development governance. The WHO six domains of governance do not include effective external partnerships for health, equity in health development, efficiency in resource allocation and use, ethical practises in health research and service provision, and macroeconomic and political stability. The framework for assessing health systems governance developed by Siddiqi et al's framework to make it more relevant to the broader concept of 'governance in health development' and to the WHO African Region context.This paper argues for a broader health development governance framework because other sectors that assure human rights to education, employment, food, housing, political participation, and security combined have greater impact on health development than the health systems. It also suggests some amendments to Siddigi A strong case for broader health development governance framework has been made. A health development governance index with 10 functions and 42 sub-functions has been proposed to facilitate inter-country comparisons. Potential sources of data for estimating HDGI have been suggested. The Governance indices for individual sub-functions can aid policy-makers to establish the sources of weak health governance and subsequently develop appropriate interventions for ameliorating the situation. An Editorial in the African Journal of Health Sciences delved into the 'The essence of leadership in health development' . HoweverThe World Health Report 2000 dictionaUnlike stewardship, governance is the sole prerogative of a national government, i.e. the executive policy-making body that exercises political authority over a country. A government through its system(s) rules or governs a country. HarperCollins dictionaThe United Nations Development Programme (UNDP) five principles of good governance include: legitimacy and voice (participation and consensus orientation), direction (strategic vision), performance , accountability (and transparency), and fairness .The World Bank's three clusters (with six domains) of governance include: processes by which those in authority are selected and replaced ; ability of government to formulate and implement sound policies (government effectiveness and regulatory burden); and respect of citizens and the state for institutions which govern their interaction (rule of law and control of corruption) .The World Health Report 2000 [The slightly amended World Health Organization health set al [et al [Siddiqi et al frameworl [et al frameworet al [The governance domains of the UNDP and the World Bank are very pertinent but not sufficient for assessment of health development governance. That is understandable since they were developed for assessing general governance. The WHO six domains of governance do not include effective external partnerships for health, equity in health development, efficiency in resource allocation and use, ethical practises in health research and service provision, and macroeconomic and political stability. Siddiqi et al also doeIn this paper we are arguing for a broader health development governance framework. Why? This is because of the fact that other sectors that assure human rights to education, employment, food, housing, political participation, and security combined have greater impact on health development than the health systems. For example, the significant negative impact of political and macroeconomic instability on health development has been starkly demonstrated in the diminished health indicators of the African countries that have undergone various forms of political and macroeconomic turmoil.et al [et al's framework to make it more relevant to the WHO African Region context.Siddiqi et al does notet al [Table et al refers tet al [Third, community participation and responsiveness function has four sub-functions, i.e. participation in NHP and NHSP development process, participation in NHSP implementation, participation in tracking progress in implementation of NHSP, and responsiveness to community's legitimate non-medical expectations -14. Siddet al principlFourth, effective internal and external partnerships for health function has ten sub-functions, namely: inter-sectoral action ,16, publFive, horizontal and vertical equity in health systems function has three sub-functions, i.e. horizontal equity in access of health services -20, vertEight, evidence-based decision-making function has four sub-functions, i.e. national health research systems ,32; healTen, macro-economic and political stability function is divided into three sub-functions, i.e. link between national economic development plan (NEDP) , PovertyThe health development governance (HDG) framework discussed above has 10 functions and 42 sub-functions. Each of the functions can be measured using a governance thermometer scale of 0% (very poor) to 100% (excellent) such as leadership responsibilities, existence of health-related legislation, inter-sectoral action, horizontal equity, allocative efficiency, existence of transparent results-oriented reporting and assessment frameworks, bioethics review system, national health research systems, etc.For example, the Leadership Responsibilities index (LR) can be expressed as follows:where LRI is the leadership responsibility index, Actual (LR) is the actual Leadership Responsibility score, Minimum (LR) is the minimum leadership responsibility score, and Maximum (LR) is the maximum leadership responsibility score. For example, assuming the global minimum leadership responsibility score and the global maximum responsibility scores are set equal to 0% and 100% respectively and the actual leadership responsibility score for a hypothetical country in Table The indices for each of the remaining 41 sub-functions can be calculated in a similar manner. And once individual sub-functions indices have been obtained, the overall Health Development Governance Index (HDGI) can be obtained using the following formula:where Since governance is measured on a scale of 0 (or 0%) to 1 (or 100%), the above HDGI of 0.35 implies that the health development governance in this hypothetical country is below average. If instead, the hypothetical country's HDGI was 50%, it would have signified average health development governance. The above formula is similar to that used by the United Nations Development Programme in calculating the Human Development Index . In realThe Governance indices for individual sub-functions can aid policy-makers to locate the sources of poor governance and then to develop appropriate interventions for ameliorating the situation. Those indices could be conducted every two or three years among all countries in the WHO African Region. Therefore, every two or three years, the WHO Regional Committee Ministers of Health from the African Region can have peer review. Since Regional Committee meets every year, there would be no additional cost for organizing the peer review sessions. Such peer review mechanisms would motivate countries to improve health development governance and also share good practises.Countries that choose to estimate the HDGI may need to set up a national multi-disciplinary stakeholder Technical Working Group (TWG) to assess the current status of HDG. In addition, they might consider establishing a Steering Committee (SC) to oversee and facilitate the work. The TWG ought to be made up of appropriately qualified staff from all relevant sectors and programmes that deal with the ten functional domains of HDG. It is critically important for all relevant government sectors , health development partners, civil society organizations, and private health sector to be represented in both the TWG and SC. Wide participation will ensure that the results will be used to improve national HDG.Public health leadership and management: Comprehensiveness of the NHP and NHSP can be assessed by reviewing the two documents against the WHO/AFRO guidelines [Table idelines . The datExistence of health-related legislation can be assessed through review of existing health-related laws. The questions for assessing level of enforcement of health-related legislation may be included in the survey questionnaire for public health leadership and management.Firstly, data for use in assessing the level of community participation in formulation of NHP/NHSP and monitoring their implementation can be generated through administration of a questionnaire among parliamentarians and civic leaders or administrative leaders, e.g. chiefs. Secondly, responsiveness of health service providers to communities' non-medical expectations can be assessed through administration of responsiveness module of the World health survey questionnaire among saFirstly, data for assessing inter-sectoral action can be generated from in-depth interview with either prime minister's or president's office, depending on who chairs the cabinet. Secondly, review of health-related legislation and interviews with leaders of faith-based and private-for-profits health services providers can yield information on the extent to which legislative and policy environment fosters public-private partnerships.Thirdly, interviews with Ministry of Finance and health development partners could yield information on percentage of aid flows for health development channelled through general government budget support. Fourthly, interviews with ministries of health would yield information on the existence of sector-wide approaches, multi-donor steering committees or equivalent donor coordination mechanisms.th March 2011, about 30 WHO African region countries had reports on the PEFA Secretariat website. Where such information does not exist, there may be need to conduct assessment using the PEFA framework [Fifthly, the Public Expenditure and Financial Accountability (PEFA) initiative reports ramework .Information on whether there has been sufficient integration of global programmes and initiatives into NHSP can be obtained by conducting interviews with Directors of Policy and Planning at Ministry of Health, health sector focal persons in Ministries of Finance, and country representatives of GAVI and GFATM.The data needed for accountability and transparency in health development should be collected together with that on effective international and external partnership.et al [Estimation of health inequality requires data on health variables (e.g.) and ordinal living standards measure . Equity et al is an exet al .Malmquist total factor productivity analyses have been carried out in continental Africa national health systems [Estimation of technical efficiency (TE) requires data on quantities of health system inputs, e.g. numbers (or time) of different cadres of health workforce, annual expenditure on pharmaceuticals, annual expenditure on non-pharmaceutical supplies, number of hospital beds; and volume of health service outputs, e.g. number of outpatient curative visits, outpatient preventive visits, community health outreach activities, inpatient admissions, inpatient discharges, and hospital deaths. In order to estimate allocative efficiency (AE), information on average inputs prices is needed in addition to data needed for TE. Calculation of productivity change requires all abovementioned input and output data for a number of time periods, e.g. a number of years. In the African region TE studies have been undertaken in Benin , Burkina systems , Angola systems , Botswan systems , Seychel systems and Sout systems . Therefo systems ,64.Firstly, the national health research systems analysis (HRSA) data can be obtained through review of existing HRSA reports. Where such data does not exist, it can be obtained through an assessment of national health research systems using HRSA toolkit -67. SecoData on dissemination of international ethical guidelines for medical practise and health research, bioethics review system, and institutionalization of ethics training should be collated simultaneously with that on HRSA (mentioned above) and using the same toolkit . The modFirstly, the linkage between NEDP, PRSP and NHP/NHSP can be ascertained through a review of those documents. Secondly, a review of Medium-Term Expenditure Framework (MTEF) document will help to determine whether it contains a clear health component derived from NHSP. Finally, a review of the national constitution and in-depth interview with chairperson of the national legal bar association can facilitate identification of the extent to which a non-violent process exists by which those in authority are elected and replaced. This information can be complemented with a review of data on the Economist Intelligence Unit Democracy Index and the The weak governance and leadership in health development might explain why many countries in Africa are not on track to attain the health MDGs by 2015 ,70,71. TOne of the possible reasons for inadequate governance and leadership in health development in Africa is largely because many health leaders and managers, at various levels of national health systems, were never trained to govern and lead. Thus, whereas they may have had very good training on disease prevention and control, their curricula might not have featured training on governance and leadership. Therefore, there may be need to revise the curricula of schools of public health, medical schools, nursing schools and other schools of health sciences in Africa to reflect the recent developments in health systems performance assessment, including leadership and governance. In addition, leadership and governance should feature prominently in the continuing education programmes for medical and public health practitioners which are organized by the national professional associations .The list of abbreviations include: AE: Allocative efficiency; CTP: Household's capacity to pay; DHS: Demographic and Health Surveys; GAVI: The Global Alliance for Vaccines and Immunization; GFATM: Global Fund to Fight AIDS, Tuberculosis and Malaria; HDG: Health development governance; HDGI: Health Development Governance Index; HDGSFI -Health development governance sub-function index; HE: Household expenditure on health; HFC: Health fairness in financial contribution; HKMS: Health knowledge management systems; HRSA: National health research systems analysis; ICT: Information, communication and technology; LR: Leadership Responsibilities index; LSMS: Living Standards Measurement Study; MDGs: Millennium Development Goals; MICS: Multiple Indicator Cluster Surveys; MTEF: Medium-term expenditure framework; NEDP: National economic development plan; NHIS: National health information system; NHP: National health policy; NHSP: National Health Strategic Plan; PEFA: Public Expenditure and Financial Accountability; PRSP: Poverty Reduction Strategy Paper; SC: Steering committee; TE: Technical efficiency; TWG: Technical Working Group; UNDP: United Nations Development Programme; WHO/AFRO: World Health Organization Regional Office for Africa; and WHS: World Health Surveys.The authors declare that they have no competing interests.JMK and DGK contributed equally to the design, analysis and writing of various sections of the manuscript. Both authors read and approved the final manuscript.JMK has a PhD in economics from the University of York, UK; MA and BEd in Economics from the University of Nairobi, Kenya; and a Diploma in health economics from the University of Tromso, Norway. DGK holds a MPH from the London School of Hygiene and Tropical Medicine, UK; and a PhD in Public Health from the University of New South Wales, Australia. Currently, JMK works at the World Health Organization, Regional Office for Africa, B.P. 06, Brazzaville, Congo. DGK is CDC/WHO Consultant, P.O. Box 529, Freetown, Sierra Leone."} +{"text": "The risk of infection and epidemiological surveillance and control of legionellosis depends on the challenges of detecting the Legionella pneumophila DNA in the hospital environment.The aim was to compare the various hospital departments in according to the features of existence of L. pneumophila in the environment of hospitals.We conducted real-time PCR of 963 swabs from 40 objects of the environment, 156 samples of water from the centralized water supply and swimming pools in 27 departments of 10 healthcare setting in the Nizhny Novgorod Region.We have distinguished the following types of the departments.Type 1: territories of high risk of health-care associated legionellosis due to high susceptibility of patients, usage of artificial lung ventilation and moisturing the oxygen and air mixture. It includes intensive care units, surgical, obstetrical departments, operating theaters. Type 1 is characterized by the high contamination of environment by L. pneumophila DNA , by presence of reservoirs \u2013 the oxygen moisturizers and water taps , by a frequent isolation of Legionella pneumophila from water .Type 2: departments with patients suffering from outpatient pneumonias: therapeutic, pulmonological, thoracic departments. They are characterized by the low contamination of environment and a frequent isolation of L. pneumophila from water .Type 3: departments of high risk of nosocomial legionellosis. They have favorable conditions for L. pneumophila and air-borne mechanism of transmission by means of aerosol-producing facilities. They are balneological departments which have a high contamination of environment ; reservoirs of L. pneumophila such as the Jacuzzi, therapeutic baths and showers ; a rare isolation of L. pneumophila from water .That is, there are different types of hospital departments for the risk of legionellosis depending on the frequency of detection of Legionella DNA the hospital environment, data about patients, their treatment and diagnostics. Different departments require different approaches to organizing and conducting surveillance of legionellosis.None declared"} +{"text": "One-third or more US adults, and similar numbers elsewhere, use complementary and integrative medicine (CIM). The results of previous systematic reviews of the economic impacts of CIM are limited and now out of date. The purpose of this comprehensive review is to capture and highlight for policy makers what is currently known about the economics of CIM, and to make recommendations for future research.PubMed, CINAHL, AMED, PsychInfo, Web of Science, and EMBASE were searched through December 2010 using a comprehensive search strategy. In addition, bibliographies were searched, and key researchers contacted. All full economic evaluations published 2001-2010 were also subjected to five study quality criteria and one indicator of whether the study\u2019s results were transferable .A total of 340 economic evaluations of CIM were found, of which 206, covering a wide variety of CIM for different populations, were published 2001-2010, and 134 of those were full economic evaluations. Despite the fact that most CIM users utilize more than one type of CIM, almost all (88%) of these studies were of single CIM therapies and only one evaluated coordinated care across CIM and conventional practitioners. Of the recent full evaluations 32 (24%) met all five study quality criteria, and 17 of these also met the minimum criterion for study transferability.This comprehensive review identified a substantial number of economic evaluations of CIM and emerging evidence of cost-effectiveness in at least a few clinical populations. Therefore, instead of more studies, what is actually needed are higher quality studies\u2014both in terms of enhanced study quality and better transferability (to increase the usefulness of results to other decision-makers in other settings). To this end, eight specific recommendations are made."} +{"text": "Prevalence of childhood asthma has worldwide increased in recent decades. Different genome-wide studies have identified that more than 100 genes in 22 chromosomes were associated with asthma. Different genetic backgrounds in different environments might modulate the susceptibility of asthma. This has been attributed to industrialized environment such as air pollution and microbial-deprivation ecology that polarize the immune response towards allergy sensitization in perinatal stage. Recently, evidence has shown that allergy sensitization may occur in fetal life, and influence of fetal environment may cause epigenetic programming of diseases in adults. Apparently, asthma is not an exception from the Developmental Origins of Health and Diseases (DOHaD), in which both the pre- and postnatal environments could shape the developmental programming of asthma developed in infancy, childhood, and even adulthood.The association between prenatal environment and disease risk in adults is first demonstrated by Barker showing low birth weight was linked to ischemic heart disease in adult life in 1986 . They alIn this special issue, we included 8 papers depicting effects and potential mechanisms of perinatal environments including intrauterine growth trajectory, maternal exposure of cold and herb medication, perinatal exposure to pets, perinatal gut microbiota, bottle feeding, genetic determinant of cockroach allergy, interaction of parental atopy and genes, and gene-environment interactions on the development of asthma. These papers together have highlighted different epigenetic and genetic effects of perinatal environments and parental genetic backgrounds on the perinatal programming of asthma. As summarized from these articles and shown in Another review article on whether perinatal diets such as vitamins, polyunsaturated fatty acid, protein-hydrolyzed infant formula, or the time and types of complementary foods are protective from the development of asthma is not included in this issue because of its complex controversy and the paper submitted for this issue was not good enough for publication. Neither the hygiene hypothesis for the development of asthma nor the persistence and remission of childhood asthma in adolescents are included in this issue. This guest editor team including K. D. Yang, MD, PhD, from the Department of Medical Research and Development, Show Chwan Health Care System, Taiwan; S.-K. Huang, PhD, from Johns Hopkins Asthma Center, Johns Hopkins University, Baltimore, USA; H.-J. Su, PhD, from Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; J. Abe, M.D., Ph.D., from the Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan anticipates that another issue of perinatal programming of asthma including advances in the knowledge of DOHaD depicting influence of nutrition and hygiene on the development and remission of asthma will come not far in order to provide a prospect for early prediction and prevention of childhood asthma."} +{"text": "All models harbor mutations in relevant tumor suppressors and/or cell-type specific expression of potent oncogenes, which initiate de novo carcinogenesis in the targeted tissues. In all these models deletion of cathepsin B led to suppression of the aggressiveness of the respective cancer phenotype. Cathepsin B is networking with other proteases as it was shown for cathepsin X/Z. In contrast, deletion of cathepsin L was beneficial in the RiP1-Tag2 model, but enhanced tumorigenesis in the APCmin, and the K14-HPV16 mice. A logical consequence of these results would be to further pursue selective inhibition of cathepsin B. Moreover, it became clear that cathepsins B and S derived from cells of the tumor microenvironment support cancer growth. Strikingly, delivery of broad spectrum cysteine cathepsin inhibitors in the tumor microenvironment disrupts the permissive ecosystem of the cancer and results in impaired growth or even in regression of the tumor. In addition, combination of cysteine cathepsin inhibition and standard chemotherapy improves the therapeutic response of the latter. Taken together, the next preclinical challenges for developing cathepsin inhibition as cancer therapy might be the improvement of inhibitor selectivity and targeted delivery to the tumor microenvironment and investigation of the biological context of the individual factors within the complex proteolytic network.Lysosomal cysteine cathepsins belong to a family of 11 human proteolytic enzymes. Some of them correlate with progression in a variety of cancers and therefore are considered as potential therapeutic targets. Until recently, the contribution of individual cathepsins to tumorigenesis and tumor progression remained unknown. By crossing various types of mouse cancer models with mice where specific cathepsins have been ablated, we contributed to this gap of knowledge and will summarize the results in this report. The employed models are the Rip1-Tag2 model for pancreatic neuroendocrine tumors, the K14-HPV16 model for squamous skin and cervical cancers, and the MMTV-PyMT model for metastasizing breast cancer, the KPC model for pancreatic ductal adenocarcinoma, and the APC Cysteine cathepsins are papain-like peptidases of which cathepsin B, C, F, H, L, K, O, S, V, W, X/Z have been identified in the human genome and are well defined in molecular, biochemical, and structural terms have been used to study the role of cathepsins in early stages of intestinal neoplasia (Moser et al., The focus of this review are studies, in which cathepsin knock-out or transgenic mice with overexpression of cathepsins have been crossed with transgenic mouse models of Hanahan, , the K14Hanahan, , and theHanahan, . All thrmin mice reduced formation of intestinal neoplasia (Gounaris et al., de novo tumorigenesis showed consistently that cathepsin B is a tumor-promoting protease and, therefore, a potential therapeutic target.Accumulating clinical and experimental data indicate that cathepsin B is a cancer-promoting protease (Poole et al., furless mice, which harbor a spontaneous active site mutation of cathepsin L, with APCmin mice increased the multiplicity of premalignant intestinal polyps significantly (Boudreau et al., min and K14-HPV16 models is an impressive example for the context-dependent consequences of a gene knock-out (Kruger, Single deficiencies for cathepsins B, L, S, and H perturbed the development of Rip1-Tag2 pancreatic islet cancers, while deletion of cathepsin C did not affect tumor progression in this model (Gocheva et al., Kruger, . The rea Kruger, . The relThe active roles of the tumor microenvironment in carcinogenesis and tumor progression have attracted considerable attention during the past decade. It emerged that tumor-promoting inflammation and induction of angiogenesis are hallmark characteristics of activated tumor stroma (for review, Hanahan and Weinberg, Overexpression and extracellular re-dislocation of cysteine cathepsins have been associated with multiple stages of tumorigenesis and tumor progression (Vasiljeva et al., Despite the important role of tumor cell-derived cathepsins in cancer progression, there is an increasing body of evidence confirming the up-regulation of cysteine cathepsins by macrophages in the tumor microenvironment, such as macrophages (Mohamed and Sloane, Taken together, the accumulated evidence in the literature strongly supports the concept of the use of cathepsins, in particular cathepsin B, as targets for cancer therapy targets. Therefore, inhibitors with improved pharmacokinetic properties and improved selectivity, possibly combined with appropriate delivery systems, and their use in combination with established chemotherapeutic treatment strategies, will have the potential to become valuable therapeutics for the treatment of metastatic malignant disease in the clinic.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Purpose of the study is to define the role of conventional radiology and MRI in the evaluation of pelvic floor hernias in female pelvic floor disorders.A MEDLINE and PubMed search was performed for journals before March 2013 with MeSH major terms 'MR Defecography' and 'pelvic floor hernias'.The prevalence of pelvic floor hernias at conventional radiology was higher if compared with that at MRI. Concerning the hernia content, there were significantly more enteroceles and sigmoidoceles on conventional radiology than on MRI, whereas, in relation to the hernia development modalities, the prevalence of elytroceles, edroceles, and Douglas' hernias at conventional radiology was significantly higher than that at MRI.MRI shows lower sensitivity than conventional radiology in the detection of pelvic floor hernias development. The less-invasive MRI may have a role in a better evaluation of the entire pelvic anatomy and pelvic organ interaction especially in patients with multicompartmental defects, planned for surgery. Pelvic floor disorders represent a significant cause of morbidity and reduction in quality of life that appear to be increasing in frequency during the last few years . PregnanPelvic floor disorders may be associated, with an incidence ranging from 18% to 45%, to the so-called midline pelvic floor sagittal hernias (MPH) that represent the herniation of the peritoneum and/or peritoneal viscera in the Douglas', Retzius', and retrorectal spaces.Although anamnestic and physical examination represents the first approach in the evaluation of the patients with pelvic floor dysfunction, the diagnostic limitation of the pelvic examination alone has led to the need to use more direct and comprehensive diagnostic methods -6.Purpose of the study is to define the role of conventional radiology and MRI in the evaluation of pelvic floor hernias.A MEDLINE and PubMed search was performed for journals before March 2013 with MeSH major terms 'MR Defecography' and 'pelvic floor hernias'. Non-English speaking literature was excluded.Entero-colpo-cysto-defecography (ECCD) is considered the gold standard for the evaluation of the patients with pelvic floor disorders and diagnosis of MPH -9. For tMRI Defecography should be performed on 1.5-T closed magnet using a body-phased-array receiver coil. To ensure an adequate bladder filling, all patients are invited to drink 500-700 ml of water 10-15 min before the examination. The rectum and vagina should be filled with 200 mL and about 25-30 mL , respectThe reference line used for conventional radiology and MRI is the Pubococcygeal line (PCL), extending from the most inferior portion of the symphysis pubis to the tangent of the sacrococcygeal joint.The diagnosis of descent of the bladder, vagina, and rectum is based on measurement of the verticaldistance between the PCL and the bladder base, the vaginal vault, and the anorectal junction, respectively.According to Yang's classification , the limRectocele could be defined as an out-pouching of the anterior rectal wall occurring during evacuation or straining -17 Figu.Pelvic floor hernias could be classified, basing on the content, into enterocele, omentocele, and sigmoidocele, whereas, according to the hernia development they could be classified as elytrocele, edrocele, retrorectal, and Douglas' and Retzius' hernias Figure .Enterocele, sigmoidocele, and omentocele represent the herniation below the proximal one third of the vagina of the peritoneal sac containing ileal loops, part of the sigmoid, or peritoneal fat, respectively -21. If tOn evaluation of conventional radiology, the diagnosis of an enterocele/ sigmoidocele/omentocele is made if the picture obtained during evacuation compared with that during rest showed an increase in the distance between the vagina and rectum Figure .This expansion should extend below the PCL reference line and shows a sagittal diameter of more than 2 cm.Anyway, the distinction between sigmoidocele, enterocele, and omentocele is made basing on the presence of contrasted small bowel in the expanded recto-vaginal space for the enterocele, on the presence of distinguishable bowel gas bubbles without contrast for the sigmoidocele alone, and on the absence of contrasted small bowel and bowel gas bubbles in the expanded recto-vaginal space, for the omentocele.-28On MRI-defecography, the relationship between the lowest point of the peritoneal border line and the PCL should be assessed. A descent of parts of the peritoneal content below this line and the identification of herniated contents allowed the distinction in enterocele, sigmoidocele, and omentocele . The herIn our experience, the specificity of MRI versus conventional radiology is of a 100%; the sensibility of MR-D in the detection of an omentocele, sigmoidocele, and enterocele is, respectively, 95%, 82%, and 65%, showing an inferior diagnostic capacity if compared with conventional radiology ,30. The In conclusion, MRI defecography shows lower sensitivity than coventional radiology in the detection of pelvic floor hernias. The diagnostic efficacy of conventional radiology is significantly higher than that of MRI Defecography in the detection of both hernia content (enteroceles and sigmoidoceles) and hernia development .However, the less-invasive MRi defecpgraphy may have a role in a better evaluation of the entire pelvic anatomy and pelvic organ interaction especially in patients with multicompartmental defects, planned for surgery .The authors declare that they have no competing interests.AR: conceived the study, analyzed and interpreted the data, drafted the manuscript.GDG: conceived the study, critically revised the manuscript.GG: critically revised the manuscript.FI: critically revised the manuscript.CR: critically revised the manuscript.MG: analyzed the data and critically revised the manuscript.FC: analyzed the data and critically revised the manuscript.LB: conceived the study, analyzed and interpreted the data, critically revised the manuscript.All authors read and approved the final manuscript.AR: Post-Doctoral Fellow in Radiology at Second University of NaplesGDG: Resident in Radiology Training Program at Second University of NaplesGG: Assistant Professor of Radiology at Second University of NaplesFI: Resident in Radiology Training Program at Second University of NaplesCR: Resident in Radiology Training Program at Second University of NaplesMG: Associate Professor of Radiology, University of FerraraFC: PhD Student at University of PalermoLB: Full Professor of Radiology, University of Molise"} +{"text": "With its increasingly large pool of expertise across 19 countries including 13 EU member states, Australia, Canada, China, Norway, Thailand and the USA, the consortium provides forums and collaboration platforms on quality control, extraction technology, component analysis, toxicology, pharmacology and regulatory issues of Chinese herbal medicine (CHM), as well as on acupuncture studies, with a particular emphasis on the application of a functional genomics approach. The project officially started in May 2009 and by the time of its conclusion in April 2012 a Europe-based academic society dedicated to TCM research will be founded to carry on the mission of GP-TCM.Traditional Chinese medicine (TCM) is widely used in the European Union (EU) and attracts intense research interests from European scientists. As an emerging area in Europe, TCM research requires collaboration and coordination of actions. Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era, also known as GP-TCM, is the first ever EU-funded 7 Traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM) and acupuncture, is an ancient medical system used in China and other Asian countries for thousands of years ,2. In cost May 2009. This is a three-year coordination action project funded under the EU Seventh Framework Programme (FP7) with a total budget of \u20ac995,100. The central hypothesis of the consortium is that, using functional genomics technology, which allows high-content observations of whole profiles of molecules at different levels, eg DNA, mRNA, protein and metabolites, and furthermore linking them to clinically relevant biological functions, we might be in a better position than ever before to interpret and validate the scientific value of TCM in a holistic and function-oriented manner [The Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (GP-TCM) consortium was launched by the European Commission on the 1d manner -11.Focusing on research of CHM and acupuncture, we especially emphasise studies of CHMs, their complex chemical ingredients and their holistic impact on the functional genomics of patients. The overall aim of the consortium is to inform the best practice and harmonise research on the safety and efficacy of TCM using a functional genomics approach through exchange of opinions, experience and expertise among scientists in EU member states, China and other parts of the world. Specifically, we aim to undertake the following objectives:\u2022 Develop a European-Chinese network, collaborating on functional genomics research of TCM;\u2022 Review current practice of TCM research, identify problems and propose solutions;\u2022 Propose standard protocols of methodology;\u2022 Propose priority areas for future research;\u2022 Develop online resources to support and enhance pan-European studies of TCM research;\u2022 Facilitate and foster a sustainable European collaboration by founding a European society dedicated to TCM research.in vitro and in vivo pharmacology (WP4-WP5), clinical studies (WP6), as well as international regulatory issues of CHM (WP7). WP9 is dedicated to organising the Final Conference of the consortium at the end of the project and WP10 is charged to manage consortium-wide matters, such as appointment and coordination of WP leadership, recruitment of additional experts, editing website and newsletters, drafting standard operating procedures, providing scientific and technological support and guidance, organising internal review and quality assurance, as well as liaising with the Commission and other stakeholders and external authorities.As shown in Figure ie funded) partner organisations across ten EU member states and China, which is an International Cooperation Partner Country (ICPC) of the EU. The consortium has additional 60 non-beneficiary (ie unfunded) collaborating partner organisations as well as two independent experts from Australia, Austria, Belgium, China, Denmark, Finland, Germany, Italy, Luxembourg, the Netherlands, Norway, Thailand, the UK and the USA , the management team (WP10) has coordinated a highly successful team build-up and re-construction. With the ever-strengthening expertise pool, WP10 has developed a number of committees and panels that lead the consortium with clear divisions of labour. WP10 has led the design and updates of the professional GP-TCM website and all WPs have established their homepages and online discussion facilities. Periodic newsletters have enabled members to share information and stay as a united team. Significantly, a series of face-to-face meetings, including consortium and WP kick-off meetings and the 1paozhi (processing) in the production of CHM. WP3 produced a list of toxic plants for further literature study and identified 3 major fields of action: (i) investigation of methods applicable to toxicity evaluation; (ii) study of toxicological reports available on a series of CHM; (iii) review of pharmacovigilance safety data. WP4 established evaluation criteria for scoring scientific articles and began the creation of an appropriate database of literature encompassing functional genomic applications in CHM research. WP5 performed reviews on CHM literature involving animal models, especially models of cancer and its conclusions have laid a solid foundation for further literature analysis on application of functional genomics in CHM research and proposing good practice in animal studies of CHM. WP6 gathered literature on seminal studies in clinical CHM studies and drafted a guideline on clinical trials of CHM. WP6 and WP8 collaboratively designed an online survey targeting TCM practitioners and the survey is currently undergoing in collaboration with 30 professional acupuncture and TCM organisations. WP7 brought together wide-ranging experiences and expertise in drug development and registration from Europe, China, Australia and North America to discuss the legislative and regulatory issues relevant to CHM. Together they are developing a comprehensive document providing comparisons of different practices on CHM regulations and this will be extremely helpful for the EU to develop its future policies and for companies to develop products for the global market. WP9 discussed the time and format of the Final Conference and preliminary bookings of venue has been made.Noteworthy WP-specific achievements are as follows. WP1 led the creation of a list of nearly 300 species of plants and fungi commonly used in TCM in Europe and China and a priority list of 11 species will be used by all WPs in their initial literature analysis. WP2 worked jointly with WP1, linking quality control, extraction technology and chemical analysis, with special emphasis on the important role of The major difficulty encountered by the consortium is unsurprisingly the language barrier. There is a lack of accessibility to original Chinese publications in Europe, and even if they are available, fast and accurate translation of these materials is impossible, preventing the consortium from extensively studying classic Chinese medical literature and evaluating a great deal of modern Chinese medical literature. While we strongly encourage our members to master both English and Chinese languages, we welcome members from various linguistic, ethnic and cultural backgrounds to work in close collaboration.As the first ever EU-China collaborative consortium dedicated to TCM research, we will continue to promote EU-China dialogues and collaborations in this important emerging supra-disciplinary area. As a network of principal investigators, we will collaborate to train the next generation of scientists who are more comprehensively equipped to study complex drugs such as CHM and personalised medicine such as TCM. As a coordination action involving much literature review and evaluation, we acknowledge the huge importance of good practice in scientific publication and will continue to support open-access publications.As an EU-China collaboration dedicated to TCM research, we are keen to incorporate ourselves into the worldwide landscape of TCM research community and serve as a constructive member. We sincerely support the international TCM community to bundle forces to improve TCM research funding from both the public and private sectors and to help shape the medicine of tomorrow together.CGCM: Consortium for Globalisation of Chinese Medicine; CHM: Chinese herbal medicines; EU: European Union; FP7: Seventh Framework Programme; GP-TCM: Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era; ICPC: International Cooperation Partner Country; ISCM: International Society for Chinese Medicine; TCM: Traditional Chinese medicine; WFCMS: World Federation of Chinese Medicine Societies; WPs: work packages.The authors declare that they have no competing interests.The authors are the Project Manager (HU), the Coordinator (QX), Deputy Coordinators and Assistant Coordinator (HE) of the GP-TCM Consortium. HU and QX jointly drafted the manuscript. All named authors took part in the revision and approved the final version of the paper."} +{"text": "Efforts to engage traditional, complementary, and alternative (TCA) health providers in the public health workforce are gaining increasing attention in India. Evidence from studies evaluating the efforts to integrate TCA health providers into the formal public health system highlights numerous lacunae in policy and practice. This study was undertaken to diagnose operational and ethical challenges in the implementation of current policies for integration of TCA health providers in order to derive lessons to strengthen integration strategies.We used qualitative data collection methods and an interpretive policy analysis approach in three states of India: Kerala, Delhi, and Meghalaya. Health policy documents, including bills, acts, orders, inter-institution communications, and publicly available material on TCA health providers, were examined. We also carried out direct observations of healthcare delivery facilities to map the workings of the health system in each of the study states. In-depth interviews were conducted with a range of stakeholders, including policy elites, health administrators, TCA health providers and allopathic (modern medicine) providers appointed in government health facilities, local traditional healers, community health workers, village elders, opinion leaders, and representatives of community organizations. Interviews explored the stakeholders\u2019 experiences and perceptions related to their roles, job responsibilities, and interactions with the various players in the health system. While 73 in-depth interviews were conducted in Kerala and 46 in Meghalaya, data collection is ongoing in Delhi. Further data collection is also planned in Kerala and Meghalaya.Major hurdles in mainstreaming of TCA health providers in essential health service delivery include absence of, or limited, formal communication and coordination between actors representing different systems of medicine; diverse levels of collegiality, ranging from hostility to harmony; and dissonance between the expectations placed on TC.A health providers and the amenities provided to them. Further observations included contestations by different strata of actors on validity and reliability of medical evidence from alternative systems; lack of coherence in the range of medical evidence across different systems of medicine; and weak conformance by state to the national policy in certain states, and limited action in communicating policy directives across the systems of medicines. Conflicting loyalties, to systems of medicine, patients, and the public health system, emerged as a key finding in the experiences and perceptions of TCA health providers in one state. Local health traditions implemented through family-based practice, although acknowledged as resonating deeply with the local culture, were found to have little, if any, place in the official health system. These gaps are compounded by the limited opportunities for formal collaborative work across different systems of medicine.Preliminary findings suggest that on the one hand, national policy articulations are not adequately translated into the state context. On the other hand, these articulations leave unresolved larger ethical questions of validity and reliability of evidence, and inter-system coherence that could more concretely support integration efforts. There is a profound need to understand and amend state-specific health governance processes and institutional capacities, and engender receptivity in mainstream health systems to alternative approaches, for the evolution of a truly integrated workforce for health services in India and other low- and middle-income countries. This may require institutionalizing incentives and opportunities for routine interaction between practitioners across systems of medicine in training, and ideally, in practice.Members of the research team for this study included allopathic (modern medicine) and homoeopathic doctors.This study was funded by the Wellcome Trust Capacity Building Large Research Grant (No. F012/RG/KS/02)."} +{"text": "Geographic information systems (GISs) with emerging technologies are being harnessed for studying spatial patterns in vector-borne diseases to reduce transmission. To implement effective vector control, increased knowledge on interactions of epidemiological and entomological malaria transmission determinants in the assessment of impact of interventions is critical. This requires availability of relevant spatial and attribute data to support malaria surveillance, monitoring, and evaluation. Monitoring the impact of vector control through a GIS-based decision support (DSS) has revealed spatial relative change in prevalence of infection and vector susceptibility to insecticides and has enabled measurement of spatial heterogeneity of trend or impact. The revealed trends and interrelationships have allowed the identification of areas with reduced parasitaemia and increased insecticide resistance thus demonstrating the impact of resistance on vector control. The GIS-based DSS provides opportunity for rational policy formulation and cost-effective utilization of limited resources for enhanced malaria vector control. In Sub-Saharan Africa, malaria remains a major cause of morbidity and mortality . Its traSince malaria distribution is not homogeneous, much effort needs to be expended towards defining local spatial distribution of the disease precedenWhile vector control interventions are being deployed according to the World Health Organization-led Integrated Vector Management Straandtegy , 13, 14,Until recently, very few malaria endemic countries had incorporated the GIS technology into operational malaria control programmes, that is, in South Africa and the Lubombo Spatial Development in Mozambique in Southern Africa, where it has been harnessed for case mapping and monitoring of vector control coverage , 19. In An. gambiae s.s, An. arabiensis, and An. funestus, including the comparative impact of main stream vector control interventions, has been conducted in Zambia.The integration of operational and logistical data for malaria control program planning with epidemiological data will serve to strengthen both the epidemiological analysis and the planning and execution of control programs. GIS facilitate the integration of quantitative malaria determination and control data with data obtained from maps, satellite images, and aerial photos. A comprehensive review of data collected through nationally representative malaria indicator surveys and insecticide resistance data in major malaria vectors: 2 (Syngenta and Bayer) and DDT at 2\u2009g/m2 (Avima) at the beginning of the peak malaria transmission period ..32].ad hoc basis driven by limited empirical evidence and undoubtedly resulting in misdirection of the limited resources available.Given the spatial heterogeneity in the distribution of malaria vectors and variations in the inherent malaria risk, GIS has potential applications in deployment and monitoring of interventions. For resource-constrained malaria-endemic Sub-Saharan African countries, like Zambia, the need for a GIS-based malaria information system cannot be overemphasized. Until recently, decisions in the malaria control programmes were taken on an Following the increased funding for malaria control particulThe use of GIS in Zambia has enabled detection of spatial trends of parasite prevalence following extensive deployment of front line vector control interventions. Cross-sectional prevalence surveys show continuous prevalence increase in children from 2008 to 2010 in Chongwe district. In Kapiri mposhi, Mumbwa, Mazabuka and Kafue districts, prevalence dropped between 2008 and 2009 but increased in 2010. However, progressive reduction in malaria prevalence was detected in Monze, Kabwe, and Chibombo districts from 2008 through to 2010 .The GIS has introduced new dimensions to the understanding, prediction, analysis, and dissemination of spatial relations between disease, time, and space , 44. It An. funestus. At Myooye and Chimoto, ITN deploying sites with high kdr mediated crossresistance to pyrethroids and DDT in An. gambiae s.s, prevalence was reducing and remained at a low level across the three years. However, Rufunsa, another ITN deployment area with high pyrethroid resistance in An. funestus, exhibited constant increase in parasitaemia despite high coverage of ITNs (There was great heterogeneity in prevalence of malaria at sentinel sites relative to detected insecticide resistance in malaria vectors. At Chibombo, prevalence has been reducing despite high pyrethroid resistance detected in of ITNs . The usefulness of a GIS-based DSS for planning and managing control programmes is dependent on the availability of accurate and raw data on malaria transmission-related parameters. Monitoring and evaluation of malaria interventions and understanding of their true impact on disease burden is essential for measuring performance of a control programme. An effective system for monitoring and evaluation and continuous surveillance requires integration of spatially and temporally explicit data for entomological and epidemiological outcome indicators. This allows for identification of disease prevalence, planning of effective interventions, assessments of reduction of vector exposure and malaria burden resulting from implemented control measures. Continuous surveillance capturing real time data enables routine monitoring and evaluation of programme to demonstrate goals and impact on malaria burden. This is essential to increasing the efficiency and effectiveness of malaria control efforts . The effEffective implementation and monitoring and evaluation of malaria control interventions have resulted in redefinition of stratification of the country in three epidemiological zones for malaria transmission potential in Zambia , 45. ThiIn this case, the GIS-based DSS has not only streamlined evidence-based implementation of interventions, but has improved the tracking of entomological indicators: species characterization and insecticide resistance status, including parasite prevalence and impact assessment of ITNs and IRS. It has been greatly valuable in enabling the display of heterogeneities in malaria risk areas within low transmission intensities , 46, 47.The impact of main thrust vector control interventions on parasite prevalence in children between 1\u201314 years of age has been monitored through annual malaria surveys for three consecutive years at 19 sentinel sites . The useAlthough routine surveillance data have proved inadequate for monitoring control programmes , and havThe ability of GIS-based DSS to deal with large data sets and to incorporate satellite images increases the feasibility of studying transmission determinants of malaria and has resulted in prompt availability of data to support surveillance and policy formulation. The epidemiological mapping of high-risk areas of malaria transmission and insecticide resistance profiles of major vectors has facilitated the recognition of those populations and geographic areas where it is possible to identify the main determinants of malaria morbidity and mortality. The revealed trends and interrelationships have allowed the identification of high risk areas and facilitated decision making and rational utilization of limited resources in a cost-effective manner.In Zambia, an evidence-based decision support has created a more focused and purposeful approach to directing resources to areas of most need with reasonable returns for effort and resources invested. Monitoring the impact of malaria vector control interventions through the GIS-based DSS on relative change in prevalence of infection and vector susceptibility to insecticides over time has enabled measurement of spatial heterogeneity of trend or impact. The revealed trends and interrelationships have allowed the identification of areas with reduced parasitaemia and increased insecticide resistance thus demonstrating the impact of vector control. Targeting interventions based on entomological and epidemiological evidence have not only contributed markedly to the success of the Zambian Malaria Control Programme, but also have provided opportunity for rational decision making in deployment of interventions and cost effective utilization of limited resources for enhanced malaria control."} +{"text": "High risk prescribing can compromise independent wellbeing and quality of life in older adults. The aims of this project are to determine the prevalence, risk factors, clinical consequences, and costs of high risk prescribing, and to assess the impact of interventions on high risk prescribing in older people.The proposed project will utilise data from the 45 and Up Study, a large scale cohort of 267,153 men and women aged 45 and over recruited during 2006\u20132009 from the state of New South Wales, Australia linked to a range of administrative health datasets. High risk prescribing will be assessed using three indicators: polypharmacy (use of five or more medicines); Beers Criteria ; and Drug Burden Index (a pharmacologic dose-dependent measure of cumulative exposure to anticholinergic and sedative medicines). Individual risk factors from the 45 and Up Study questionnaire, and health system characteristics from health datasets that are associated with the likelihood of high risk prescribing will be identified. The main outcome measures will include hospitalisation ; admission to institutionalised care; all-cause mortality, and, where possible, cause-specific mortality. Economic costs to the health care system and implications of high risk prescribing will be also investigated. In addition, changes in high risk prescribing will be evaluated in relation to certain routine medicines-related interventions. The statistical analysis will be conducted using standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis, controlling for relevant confounding factors, using a number of different approaches.The availability of large-scale data is useful to identify opportunities for improving prescribing, and health in older adults. The size of the 45 and Up Study, along with linkage to health databases provides an important opportunity to investigate the relationship between high risk prescribing and adverse outcomes in a real-world population of older adults. In older adults, high risk prescribing can be defined as prescribing likely to lead to adverse clinical outcomes or prescribing that does not align with quality use of medicines principles. A range of indicators have been proposed to quantify high risk prescribing in older people. These include multiple medication use or polypharmacy, potentially inappropriate prescribing and exposure to high risk medicines, measured using different risk assessment tools.Although the concomitant use of multiple medicines is often indicated in the treatment and prevention of health problems, polypharmacy is generally considered as high risk prescribing in older adults, and is associated with increased risk of harm -3, incluHigh risk prescribing also includes potentially inappropriate prescribing, defined as the use of medicines whose potential harms to older adults may outweigh the benefits . PotentiHigh risk prescribing may also encompass exposure to \u201chigh-risk\u201d medicines such as those with anticholinergic and sedative properties. A number of anticholinergic and/or sedative scores have been developed to capture the cumulative exposure to these pharmacological classes . One sucStrategies to reduce high risk prescribing, including pharmacist-conducted medication reviews, educational interventions and policy approaches, have been trialled in older adults -22. HoweThe current evidence from pharmaco-epidemiological studies suggests that high risk prescribing increases the risk of adverse outcomes in older adults ,2. Howev1) Estimate the prevalence of high risk prescribing;2) Investigate the risk factors for high risk prescribing;3) Quantify the relationship of high risk prescribing to adverse health outcomes;4) Determine whether associations between high risk prescribing and adverse outcomes vary according to individual and/or health care system specific factors;5) Calculate the economic cost and implications of high risk prescribing to the health care system;6) Investigate whether certain routine medicines-related interventions, including the Home Medicines Review and Chronic Disease Management are associated with reductions in high risk prescribing.The proposed cohort analysis will utilise a population-based dataset combining self-reported questionnaire data linked to routine administrative health datasets. This project will utilise the following data sources: the 45 and Up Study baseline questionnaire; the Australian Commonwealth Medicare Benefit Scheme (MBS) claims data, Pharmaceutical Benefit Scheme (PBS) claims data, Aged and Community Care Management Information System (ACCMIS) database, National Death Index; and New South Wales (NSW) datasets including the Admitted Patients Data Collection (APDC), and the Register of Births, Deaths and Marriages Figure\u2009.The 45 and Up Study cohort includes 267,153 men and women aged 45 and over from the state of NSW, Australia, randomly sampled from the Medicare Australia database . ParticiMBS and PBS are part of the Australia's national health insurance arrangements . These sst 2012) towards the cost of their medicines. Since all PBS medicines cost more than the concession card holder threshold, they will always attract a Commonwealth subsidy. Therefore medication data from concession card holders are captured consistently in the PBS database. However, the co-payment threshold for general beneficiaries is $35.40 (as at January 1st 2012). There are a range of PBS-listed medicines that cost less than this co-payment threshold. When these medicines are dispensed to a general beneficiary, the general beneficiary is required to pay the full cost of the medicines and the government does not contribute to payment. Consequently, PBS-medicines falling below the co-payment were not captured in the PBS database for general beneficiaries. However, following a policy change, since April 2012 the PBS database now captures all PBS-dispensed medicines, regardless of whether the government contributes to the payment. To manage the potential incomplete capture of PBS-listed medicines dispensed to general beneficiaries we will restrict our analysis to healthcare concession card holders. Recent estimates indicate that over 90% of individuals aged 65\u2009years and over hold a government health care concession card [The PBS database contains information on Commonwealth subsidised claims for prescribed medicines listed on the Schedule of Pharmaceutical Benefits. There are two main groups of PBS beneficiaries, concession card holders and general beneficiaries. The PBS database records only PBS-listed prescription medicines that attract a government subsidy. Concession card holders are required to contribute a co-payment of $5.80 routinely links identifying details from 45 and Up Study participants to those from the NSW APDC and death records, to provide regular updates to events in the cohort. This is a part of an established program of linkage. Records are matched probabilistically using privacy-preserving current best practice with software , an algoMedication exposure will be measured using the 45 and Up Study predominantly using PBS dispensing data, validated and calibrated against self-reported medication use from the 45 and Up Study questionnaire. As the PBS database does not capture private prescriptions, medicines dispensed to public hospital inpatients, over-the-counter medicines and many complementary and alternative medicines, the extent to which PBS data reliably categorise high risk prescribing is not known. The authors are currently conducting the validation projects to estimate the extent and implications of any under-ascertainment of high risk prescribing using PBS data, compared with self-reported measures from the 45 and Up baseline questionnaire.High risk prescribing will be defined using three indicators: polypharmacy; Beers Criteria; and DBI. Polypharmacy will be defined as the concurrent dispensing of five or more medicines over a sThe DBI, a measure of exposure to drugs with anticholinergic or sedative effects will be calculated using the equation ,D is the daily dose, and \u03b4 is the minimum efficacious dose , an estimate of the dose required to obtain 50% of the maximal effect. The daily dose will be estimated from the total quantity dispensed, using a standard pharmaco-epidemiological approach [where approach , by multapproach . The minData on individual risk factors from the 45 and Up Study questionnaire , and health system characteristics from linked data will be obtained to identify factors associated with the likelihood of high risk prescribing.Data on a range of clinical outcomes will be obtained, including: hospitalisation ; all-cause mortality; and, where possible, admission to institutionalised care and cause-specific mortality. Follow-up will be from the date of recruitment, to the last available data on hospitalisation, death or institutionalisation, whichever occurs first. The 45 and Up Study recruitment was from February 2006 to April 2009, giving a range of follow-up duration of 2\u20135\u2009years, by end 2012 (accounting for linked data delays).Changes in high risk prescribing will be evaluated in relation to two health interventions: the Home Medicines Review , and theThe cost analysis will be undertaken from a health system perspective. Total annual health system costs will be estimated overall and for each type of health care resource utilisation for each individual in the 45 and Up Cohort, based on their hospital, Medicare and pharmaceutical utilisation data. Costs will be assigned to each type of resource utilisation based on standard Australian sources . Differences in total and average annual costs will be estimated for the high-risk and non-high risk prescribing groups using each of the definitions of high risk prescribing. Covariates will be included in the cost equations and interacted with a dummy variable for the high risk prescribing group. Differences in total health care costs and for each type of health care resource utilisation will be estimated.The statistical analysis will be conducted using the standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis , time-varying methods, and controlling for relevant confounding factors using a number of different approaches .To answer the first study objective, analysis will be performed to calculate the high risk prescribing indicators, using the 45 and Up Study cohort, linked to PBS data and restricted to concession card holders. The patterns of high risk prescribing will be summarised using proportions and means. To answer the second and third objectives, analysis will be performed to identify individual and health system based risk factors for high risk prescribing, using the same dataset in aim one. Univariate and multivariate analysis with relevant covariates will be used to quantify the risk for high risk prescribing compared to age and gender-matched controls. Using the same dataset, linked to other data sources, we will investigate the relationship of high risk prescribing indicators with hospitalisations, deaths and institutionalisation, allowing for a range of factors. Analysis related to the fourth objective \u2013 calculation of the economic costs and implications of high risk prescribing to the health care system \u2013 will be performed as outlined in the previous section. To answer the fifth objective, we will perform the analysis to evaluate the possible impact of policy-related interventions on high risk prescribing. In particular, we will compare the rates of high risk prescribing in participants with and without these interventions and the incidence of high risk prescribing before and after each of these interventions, within individuals.before and after the intervention.Using data available to the end of 2012, the project will be highly powered for the main outcomes, with the ability to detect a minimum relative risk of death (the least common outcome) of 1.12, for each of the three high risk prescribing indices ,15, at 5This study has been approved by the NSW Population and Health Services Research Ethics Committee . In addition, the 45 and Up Study also has overarching in principle ethical approval for data linkage from the University of New South Wales Human Research Ethics Committee , Sydney, Australia and the Department of Health and Ageing, Ethics Committee .The baseline characteristics of the 45 and Up study participants, and concession card holders are presented in Table\u2009High risk prescribing is a term used to describe a pattern of prescribing, which, for theoretical or empirical reasons, has been linked with adverse outcomes in older people. Identifying strategies to minimise high risk prescribing in older people requires a reliable evidence base on the magnitude of the problem and the relationship of high risk prescribing to adverse health outcomes, as well as the effectiveness of routine interventions to improve quality use of medicines. The Australian health system is well suited to this, because of a rich collection of large population-based and administrative databases. The size of the 45 and Up Study, along with linkage to routine health data will allow investigation of the relationship between high risk prescribing and adverse outcomes at the population level, including exploration of confounding, effect modification and intervention effects. In addition, opportunities to utilise other population-based datasets, including general PBS population and Department of Veteran Affairs\u2019 data will also be explored.It should be noted that the administrative datasets are not collected specifically to describe patterns of medicine utilisation or medical care and there are some important limitations to this cohort analysis, including generalisability, validity of data, bias and causality issues. Cohort studies often involve selected groups and produce results based on internal comparisons within the cohort. Theoretical and empirical work have shown these internal comparisons to be valid and reliable ,38, inclWhile the gold standard for evaluating the causal effects of medicines on clinical outcomes is the randomised controlled trial, randomising older individuals to high risk prescribing would be inappropriate. Therefore, observational studies are essential to elucidate the association between high risk prescribing and health outcomes in this population, and to ensure the necessary degree of heterogeneity. However, the quantification of causality requires judicious interpretation of observational data . A centrIn summary, the 45 and Up Study and its linkage with health databases will allow investigation of the relationship between high risk prescribing and adverse outcomes at the population level, which has not been possible in the past. The proposed study will generate an important, unique dataset for the quality use of medicines and will allow the identification of targets for improving prescribing in older people.ACCMIS: Aged and Community Care Management Information System; APDC: Admitted Patients Data Collection; ATC: Anatomical Therapeutic Codes; CHeReL: Centre for Health Record Linkage; DBI: Drug Burden Index; MBS: Medicare Benefit Scheme; NSW: New South Wales; PBS: Pharmaceutical Benefit Scheme; TGA: Therapeutic Goods Administration.The authors declare that they have no competing interests.DG and EB drafted the manuscript. EB, DLeC, SP, AM, RV, SH, DG, FB, and GJ contributed to the design of the study, and DLeC, SP, AM, RV, SH, FB, GJ were involved in reviewing the manuscript. All authors read and approved the final manuscript.Danijela Gnjidic: Faculty of Pharmacy, Bank Building A15, Science Rd, University of Sydney, Camperdown, NSW 2006 Australia.David Le Couteur: Centre for Education and Research on Ageing (CERA), Concord Hospital and University of Sydney, NSW 2139 Australia.Sallie-Anne Pearson: Faculty of Pharmacy, Bank Building A15, Science Rd, University of Sydney, Camperdown, NSW 2006 Australia.Andrew McLachlan: Faculty of Pharmacy, Bank Building A15, Science Rd, University of Sydney Camperdown, NSW 2006 Australia.Rosalie Viney: Centre for Health Economics Research & Evaluation, PO Box 123, Broadway NSW 2007 Australia.Sarah Hilmer: Royal North Shore Hospital and University of Sydney, Level 1, Acute Services Building, RNSH, St Leonards, NSW 2065 Australia.Fiona Blyth: Centre for Education and Research on Ageing (CERA), Concord Hospital and University of Sydney, NSW 2139 Australia.Grace Joshy: National Centre for Epidemiology and Population Health, Australian National University Canberra ACT 0200 Australia.Emily Banks: National Centre for Epidemiology and Population Health, Australian National University Canberra ACT 0200 Australia.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/115/prepub"} +{"text": "Descending necrotizing mediastinitis is a life-threatening complication of an oropharyngeal infection that requires prompt and aggressive medical and surgical therapy. Herein, we report unusual case of man suffering of sub-acute mediastinal infection due to odontoiatric abscess which exacerbated at 3 months after its first presentation. Chest X-ray and CT scan demonstrated soft-tissue swelling of the neck and encapsulated fluid collections with gas bubbles within anterior mediastinum, especially on the right side. Bilateral anterior neck dissections were performed and blunt dissection, irrigation and debridement were carried out to several centimetres below the sternal manubrium. Then, right standard thoracotomy was performed with debridement of the anterior mediastinum. Four tubes were placed in the mediastinum and pleural cavity on the right side, and two tubes were placed in the left thoracic cavity. Follow-up CT scans of neck and chest showed the resolution of infection. Descending necrotizing mediastinitis (DNM) is a life-threatening complication of an oropharyngeal infection that requires prompt and aggressive medical and surgical therapy. Delay of diagnosis and inappropriate drainage of the mediastinum are the main causes of mortality in this life threatening condition ,2. HereiA 50 year-old man was admitted in our institution for neck pain, dysphagia, high-fever, and chest pain. Such symptoms began following infected foot ulcer 7 days before. She had a history of diabetes, and chronic obstructive bronchitis; yet, three months before she was admitted to a local hospital for mediastinal abscess as complication of odontogen abscess. However, the patient refused further investigations, and started antibiotic therapy for a time not better defined. On examination she had bilateral diffuse neck erythema, oedema, and induration. Broad-spectrum antibiotics were initiated empirically. Chest X-ray and CT scan demonstrated soft-tissue swelling of the neck and encapsulated fluid collections with gas bubbles within anterior mediastinum, especially on the right side Figure .After review of the images, the patient was taken to the operating room. Bilateral anterior neck dissections were performed and blunt dissection, irrigation and debridement were carried out to several centimetres below the sternal manubrium. Then, right standard thoracotomy was performed with debridement of the anterior mediastinum. We irrigated the mediastinum and thoracic cavity with copious warm saline during the operation. Four tubes were placed in the mediastinum and pleural cavity on the right side, and two tubes were placed in the left thoracic cavity. Bacteriologic results from materials obtained from the neck, pleura, mediastinum, pericardium, and blood revealed in all cases a polymicrobial infection, with mixed aerobic and anaerobic organisms. A repeated bronchoscopies were attended ,4. FolloThe most dreaded and probably lethal form of mediastinitis is the diffuse necrotizing variety that occurs as a complication of infection of the oropharynx. The best term of such mediastinitis is DNM; descending because the infection uses fascial planes in the neck to gain access to the mediastinum, and necrotising because the infection is often polymicrobial and gas-producing . InfectiIntravenous broad-spectrum antibiotic therapy alone is not efficient without adequate surgical drainage of the cervical and mediastinal collections, extensive debridement and excision of necrotic tissue, and wide mediastinopleural irrigation -14.The most interesting aspect of the present case, not been reported before, is that our patient suffered of sub-acute mediastinal infection due to odontogen abscess treated with antibiotic therapy for three months. Then, an exacerbation of mediastinal infection is observed with concomitant presence of infected foot ulcer. In theory, the infection of foot ulcer may lead to septicemia which in addition with other risk factors as diabetes, and obesity may then cause the exacerbation of mediastinal infection.In the present case, diagnosis of cervical infection with increasing infectious symptoms, and respiratory insufficiency is clinically obvious; yet, radiological studies show the presence of cervical abscess with diffuse mediastinal collections. Thus, the diagnosis of DNM is confirmed in agreement of diagnostic criteria of Estrera et al. . These cIn reported cases of DNM, successful surgical management involves a combination of cervical and mediastinal drainage with or without open thoracotomy. Endo et al. proposedIn the meta-analysis by Corsten et al , patientRoberts et al report tThe authors declare that they have no competing interests.PL : conception and design, interpetration of data, given final approval of the version to be published. F. N.: acquisition of data, drafting the manuscript, given final approval of the version to be published. CC : acquisition of data, drafting the manuscript, given final approval of the version to be published. MD : acquisition of data, drafting the manuscript, given final approval of the version to be published. BA : acquisition of data, drafting the manuscript, given final approval of the version to be published. AG : acquisition of data, drafting the manuscript, given final approval of the version to be published. MV: acquisition of data, drafting the manuscript, given final approval of the version to be published. V.D.C.: critical revision, interpretation of data, given final approval of the version to be publishedPL: Resident in Department of Medicine and Surgery - University of Salerno. FN: Resident in Department of Medicine and Surgery - University of Salerno. CC: Resident in Department of Clinical Medicine and Surgery - University of Naples. MD: Aggregate Professor of Surgery in Department of Clinical Medicine and Surgery - University of Naples Federico II. BA: Associate Professor of Surgery in Department of Clinical Medicine and Surgery - University of Naples Federico II. AG: Assistant Professor of Pediatric Surgery - University of Salerno. MV: Associate Professor of Endocrinology - University of Salerno. VDC: Assistant Professor of Thoracic Surgery - University of Salerno."} +{"text": "These Centers foster collaboration among transdisciplinary teams of scientists with the goal of accelerating progress towards reducing cancer incidence, morbidity and mortality associated with obesity, low levels of physical activity and poor diet. This presentation will review key opportunities in transdisciplinary research, highlight lessons learned and note future challenges.The increasing recognition of the complex, multidimensional relationship between excess adiposity and cancer risk, coupled with the high prevalence of obesity in the US, has motivated the scientific community to seek new research models and paradigms. Compared to traditional unidisciplinary research, transdisciplinary research is seen as having the potential to accelerate both discovery and its translation to practice, and eventually policy. In response, the National Cancer Institute (NCI) developed a centers grant mechanism in nutrition, energetics, and physical activity; referred to as the Transdisciplinary Research on Energetics and Cancer (TREC) Initiative ("} +{"text": "In Japan, the Research Committee on Intractable Vasculitides, supported by the Ministry of Health, Labour and Welfare, has been promoting basic and clinical research on vasculitis since 1972. The present Research Committee on Intractable Vasculitides comprises 4 subcommittees under the direction of a Principal Investigator: Basic and Pathological Research Subcommittee, Clinical Research Subcommittee of Small and Medium-sized Vessel Vasculitis, Clinical Research Subcommittee of Large-sized Vessel Vasculitis, and International Cooperation Research Subcommittee. Since 2008, 9 nationwide clinical studies for vasculitis have been conducted and 8 clinical and basic studies are in progress. The Research Committee on Intractable Vasculitides, supported by the Ministry of Health, Labour and Welfare of Japan, has conducted and promoted basic and clinical research on vasculitis since 1972. We study 9 diseases: Takayasu arteritis, temporal arteritis, polyarteritis nodosa, Buerger disease, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, antiphospholipid syndrome, and rheumatoid vasculitis. Experts from several fields including nephrology, rheumatology, pulmonology, dermatology, cardiology, vascular surgery, pathology, epidemiology, and otorhinolaryngology work cooperatively. The present Research Committee on Intractable Vasculitides comprises 4 subcommittees under the direction of a Principal Investigator (Hirofumi Makino):Basic and Pathological Research Subcommittee of Vasculitis Syndrome (Yasunori Okada), Clinical Research Subcommittee of Small and Medium-sized Vessel Vasculitis Syndrome (Yoshihiro Arimura), Clinical Research Subcommittee of Large-sized Vessel Vasculitis Syndrome (Kazuo Tanemoto), and International Cooperation Research Subcommittee of Vasculitis Syndrome patients and a naTo describe the current treatment status and evaluate the effectiveness of these treatments for Japanese patients with all types of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), we conducted a nationwide prospective cohort study of remission induction therapy in Japanese patients with AAV (RemIT-JAV). Twenty-two university hospitals and referring hospitals participated in this study; consecutive patients newly diagnosed with AAV were enrolled from April 2009 to December 2010. The criteria of primary systemic vasculitis proposed by the European Medicines Agency (EMEA) algorithm was employed for enrollment [Based on our retrospective study elucidating the risk factors for relapse in patients with myeloperoxidase (MPO)-ANCA positive MPA , we are After RemIT-JAV, we conducted a nationwide, prospective cohort study of remission induction therapy in Japanese patients with ANCA-associated vasculitides and rapidly progressive glomerulonephritis (RemIT-JAV-RPGN) (UMIN000005136) including 47 university hospitals and referring hospitals. Enrollment of consecutive patients newly diagnosed with AAV began in April 2011 and will continue till December 2013. The primary and some secondary outcome measures are the same as those in RemIT-JAV, but pathological analysis of renal involvement and radiological analysis of pulmonary involvement will be added. Further, biological samples will be collected and offered to the Basic and Pathological Research Subcommittee for Research for identifying candidate biomarkers.We also conducted a nationwide Japanese prospective observational study on the current state and efficacy of therapeutics for large-vessel vasculitis (UMIN000010414). The subjects included patients newly diagnosed with Takayasu arteritis and giant cell arteritis. The study objective was to clarify the current state and efficacy of therapeutics for large-vessel vasculitis in Japan and to evaluate the utility of the current diagnostic criteria and classification for large-vessel vasculitis. The primary outcome measure of this study is remission rate. The study began in November 2012, and patients will be registered until March 2014. Final follow-up will be completed in March 2016.The International Cooperation Research Subcommittee is leading the effort to join some international collaborative clinical research studies: the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) (NCT01066208), the Plasma Exchange and Glucocorticoid Dosing in the Treatment of ANCA-Associated Vasculitis (PEXIVAS) Study (NCT00987389), and a comparison study of phenotype and outcome in microscopic polyangiitis between Europe and Japan.A genome-wide association study in AAV patients registered in the Japanese clinical studies RemIT-JAV and RemIT-JAV-RPGN, and a prospective study of the severity-based treatment protocol for Japanese patients with MPO-ANCA-associated vasculitis (JMAAV) , is also"} +{"text": "The disease causes progressive bilateral swelling of the lower legs Podoconiosis is widely distributed in certain countries on three continents: Africa, South America, and Asia Ernest Price, in the early 1970s, conducted extensive research in Ethiopia and in the eastern African region on the aetiology, natural history, distribution, and management of non-filarial elephantiasis In 2002, Gail Davey was first introduced to the problem of podoconiosis in one of the southern districts of Ethiopia. Since then, she has led podoconiosis research using a multi-disciplinary approach, including epidemiology, immunology, mineralogy, genetics, bioethics, social sciences, and economics, to describe the disease and its impacts. In addition to Price and Davey approaching podoconiosis from a multi-disciplinary perspective, Davey went the extra mile by partnering with local and international institutions that translated the research into disease prevention and treatment. Several factors have contributed to the success of Davey's program. Unlike Price, Davey has (i) embraced social science and public health research rapidly applicable to education of community members and clinical management, (ii) included service-providing institutions , and International Orthodox Christian Charities, Ethiopia [IOCC]), (iii) engaged a wider range of academic and other institutions in Ethiopia and from around the world , and (iv) most importantly, included local investigators . Contextual factors that have contributed to the success of this program have been increased awareness of the importance of partnership in North\u2013South research collaborations, and the recent global attention focussed on NTDs.The major accomplishments of the past decade fall into three interlinked categories: scientific research, inclusion of podoconiosis in national and international health agendas, and integration of research findings into clinical management of podoconiosis .de novo clinical staging system that could be used by community workers with little health training HLA\u2013DQA1, \u2013DRB1, and \u2013DQB1 confer risk for podoconiosis Considering first scientific research, the initial group of podoconiosis studies aimed to describe the burden of the disease in Ethiopia in terms of prevalence, economic cost, and social burden. Studies in different regions of Ethiopia have documented prevalence ranging from 2.8% to 7.4% http://www.who.int/neglected_diseases/diseases/podoconiosis/en/). In March 2012, Footwork, the International Podoconiosis Initiative, was launched, with the vision of eliminating podoconiosis (www.podo.org). In 2012, the civil society organizations (CSOs) that had been working on podoconiosis prevention and treatment in Ethiopia for over 20 years formed the National Podoconiosis Action Network (NaPAN), an umbrella organization that coordinates the work of its member organizations to work towards its vision \u201cto see Ethiopia free of podoconiosis.\u201dThe aforementioned research milestones contributed significantly to the second major accomplishment\u2014recognition of podoconiosis in national and international health agendas. In December 2010, the Ethiopian Federal Ministry of Health agreed to prioritize podoconiosis control. Subsequently, podoconiosis was included in the National Master Plan for NTDs and in the modules prepared by the Open University for the upgrading of Ethiopian Health Extension Workers. In February 2011, the World Health Organization included podoconiosis in its list of NTDs total dependence on CSOs for podoconiosis treatment services and limited involvement of government health services, making disease prevention efforts unsustainable, (ii) limited knowledge of mid- and high-level health professionals in Ethiopia about the causes and clinical management of podoconiosis and differential diagnosis from other causes of lymphoedema, (iii) neglect by global health advocates of non-infectious and non-fatal, but socio-economically devastating, diseases of the poor such as podoconiosis, thereby limiting the amount and sources of funding available for research and interventions, and (iv) absence of comprehensive data on the distribution and burden of podoconiosis and lack of diagnostic tools, which are necessary for negotiating funding and delivery of treatment and interventions.http://www.who.int/neglected_diseases/diseases/podoconiosis/en/), the Wellcome Trust (http://www.wellcome.ac.uk/News/Media-office/Press-releases/2012/WTVM054822.htm), and the US National Institutes of Health . The successes of the journey demonstrate the impact of ten years of community-oriented, intervention-linked, multi-disciplinary research to positively influence the lives of marginalized patients. It also shows that scientific research in a low-income setting and among marginalized communities can impact policy, raise disease profile, and touch hearts across the world. These rewarding accomplishments have also generated research questions that future enquiry may answer with huge dividends for scientific knowledge, disease elimination, and lessons for other diseases.The accomplishments of the past ten years have drawn podoconiosis from the book shelves where it was buried for a ten-year \u201cDark Age\u201d to some light. Podoconiosis is now a global health topic recognized as such by the World Health Organization (work, the International Podoconiosis Initiative.The success stories of the past ten years and the recent funding of further research projects such as the mapping of podoconiosis in Ethiopia, an evaluation of podoconiosis lymphoedema management, and a trial of behavioural strategies for promoting footwear imply that elimination of podoconiosis is achievable. Mapping of the disease burden of podoconiosis will help target resources, monitor control progress, and advocate for investment in podoconiosis prevention, control, and ultimately elimination. The studies evaluating lymphoedema management and behavioural interventions are a prerequisite for the scale-up of these interventions. Capitalizing on filarial lymphoedema management experience and research outcomes will help update the treatment options for podoconiosis"} +{"text": "Formed in 2008, the Southern African Centre for Infectious Disease Surveillance (SACIDS) is a One Health consortium of academic and research institutions involved with infectious diseases of humans and animals. Operating in partnership with world-renowned centres of research in industrialised countries, its mission is to harness innovations in science and technology for improving southern Africa's capacity to detect, identify, monitor (DIM) and manage the risk posed by infectious diseases of humans, animals, and ecosystems. The consortium's major capacity development activities include a series of One Health-based Master of Science (MSc) courses and a five-year DIM-driven research program. Additionally, SACIDS organized Africa's first One Health conference, in July 2011. This paper describes these and other major activities that SACIDS has undertaken to improve infectious disease surveillance across southern Africa. The paper also describes the role and collaboration of SACIDS with other national, regional and international consortia/networks that share a vision and interest in promoting novel approaches to infectious disease surveillance and outbreak response. It has become increasingly apparent that the most cost-effective strategy for addressing the high infectious disease burden and risk in southern Africa must be through the sharing of expertise and resources across institutions; through close collaboration between the human and animal health sectors; and, ideally, through an approach that is based on ecological systems, which in Africa often transcend administrative or national boundaries services the Southern African Development Community (SADC). Operating in partnership with world renowned research institutions in the United Kingdom, United States, and Asia, SACIDS : Burundi, Rwanda, Uganda, Kenya, and Tanzania. Together, the two regional economic communities (RECs) share not only a vision for inter-regional free trade, but also an abundance of wildlife animals in their savannah and forest ecosystems and an intense wildlife-livestock-human dynamic . Thus, sThe headquarters of SACIDS is located at the Sokoine University of Agriculture (SUA), Morogoro, Tanzania. SACIDS operates as a non-profit inter-institutional consortium through the legal framework of the SACIDS secretariat host and member institutions. At the national level, several virtual centers for infectious diseases have been formed. Collectively, these National Centres for Infectious Disease Surveillance (NatCIDS) form the core of SACIDS see . The undSACIDS seeks to enhance the effectiveness of existing official disease surveillance systems. Thus, at both national and regional levels, SACIDS is underpinned by sector ministries and regional inter-governmental organizations, especially SADC, the New Partnership for Africa's Development (NEPAD), and the African Union. At the national level, each NatCIDS includes as active members representatives of the Ministries responsible for human health, livestock and wild animal health; operates under the patronage of national chief medical and veterinary officers; and is linked to national offices responsible for responding to natural emergencies. At the regional, or SADC level, SACIDS is developing linkages with sections of the SADC Secretariat that deal with human and animal health matters, not only through desk officers but also directly with the communicable diseases and livestock technical committees that advise governments on priority diseases for regional priority.Provide training through two \u201cOne Health\u201d MSc courses, one at Sokoine University, Tanzania, with a focus on molecular biology; the other at the University of Zambia, Lusaka, with a focus on analytical epidemiology. Each course includes core modules on the understanding of key One Health challenges. The courses have been developed and are being delivered in collaboration with regional institutions and the University of London's London School of Hygiene and Tropical Medicine (LSHTM) and Royal Veterinary College (RVC).Develop research capacity, focusing primarily on five disease-driven themes: (i) climate-dependent, vector-borne diseases ; (ii) diseases with potential inter-species concern/spread between wildlife, livestock, and humans ; (iii) diseases of economic and food security importance ; (iv) bacterial rare diseases ; and (v) dangerous emerging diseases . The consortium's research on One Health policy is focused primarily on disease burden in the dry land ecosystems of southern and East Africa and its impact on livestock-dependent communities . AnotherShare expertise and resources across consortium institutions, especially for disease emergency situations See . The valExamine approaches and mobile technologies for improving the efficiency of disease alerts, surveillance and response .The initial focus of SACIDS is on capacity development through employment of the Community of Practice (CoP) principle . A CoP iOnderstepoort Journal of Veterinary Research is governed by a multi-sectoral steering committee whose members include representatives from the Ministry of Livestock Development and Fisheries, and efforts are underway to establish a veterinary stream of the Tanzania FELTP. TFELTP is a collaboration between MOHSW, Muhimbili University of Health and Allied Sciences (MUHAS), National Institute of Medical Research (NIMR), Centres for Disease Control and Prevention (CDC), World Health Organization (WHO), and African Field Epidemiology Network (AFENET) . It was Mycobacteria strains, the causative agent(s) of tuberculosis (TB), can infect both animals and humans. SACIDS's focus on TB exemplifies not only how SACIDS is focused on developing and implementing a One Health approach to infectious disease surveillance, but also how SACIDS seeks to enhance existing surveillance systems by prioritizing the same diseases that the official organs of SADC prioritize. SADC prioritizes TB because member states carry a disproportionate burden of the dual epidemic of TB and HIV/AIDS compared to the rest of Africa and the rest of the world. The region is home to 25 percent of the sub-Saharan human population but accounts for 50 percent of TB cases reported. The SADC Health Protocol includes a specific Article 12 on TB control, advocating for global and regional partnerships to respond to the TB epidemic in the SADC region , pathogen evolution, travel and trade, changing patterns of land use resulting in increased interactions between humans and both domestic and wild animals, increasing urbanization, population growth, and changing food consumption patterns. Together, these factors will create evolving One Health challenges, such as emerging zoonoses, and an increasing demand for scientific evidence in relevant policy decision-making. The challenges will be made more difficult if policy silos between human health, animal health, and agriculture prevent the type of inter-sectoral, inter-disciplinary collaboration that is needed for One Health infectious disease surveillance and response.But as the burden increases, so too do opportunities for reducing the burden. It is anticipated that SACIDS itself will continue to evolve as an initiative that promotes novel One Health approaches to infectious disease surveillance, such as the application of improved diagnostic and information technologies that can be used in remote rural settings. To be effective, SACIDS will need to strengthen its \u201cengagement\u201d and convening strategy for developing smart, shared-vision partnerships at national, regional, and international levels. CORDS helps to nurture that strength."} +{"text": "The development of novel, more precise instruments for the delivery of ionizing radiations, the accretive utilization of protons and heavy ions, and the emphasis on hypofractionated irradiation schemes have resulted in major improvements in locoregional tumor control. However, radiation therapy alone is still insufficient to cure locally advanced metastatic tumors. The heterogeneity of neoplasms and their microenvironment also affect the radiosensitivity of cancers. Thus, there is an urgent clinical need for innovative therapeutic concepts that may be translated into novel radio(chemo)therapeutic regimens. In order to develop new therapeutic strategies, a profound knowledge of tumors and their microenvironment is essential.In this e-book, the authors deal with various aspects of interrelationship between neoplasms and their microenvironments, including how high and low dose irradiation affects the immune system, the effects of targeted and non-targeted photon, and particle irradiation on tumor and normal tissues, as well as the impact of epigenetics on irradiation therapy. Furthermore, the authors report on the effects of irradiation on inflammatory pathways and on the microcirculation, two aspects that are highly relevant for the delivery of macromolecules and other therapeutics to irradiated tumors. A major focus of this e-book is to elucidate immunological facets of ionizing irradiation. It is indeed becoming clear that high- and low-dose irradiation elicit distinct immunological effects. Furthermore, the mode of irradiation-induced cell death has a major impact on anticancer immune responses. Overall, the e-book aims at review the current knowledge on the role of ionizing irradiation in antitumor immunity. This knowledge is instrumental for the development of innovative therapeutic modalities involving the combination of radio(chemo)therapy and immunotherapy in patients with locally advanced tumors."} +{"text": "Little is known physical health (PH), mental health (MH) and health-related quality of life (HRQOL) adaptation outcomes in AYA with SB, and the factors associated with them. The purpose of this presentation is to 1) describe the PH , MH , and HRQOL outcomes; and 2) delineate the direct and indirect relationships of risk and protective variables in the Ecological Model of Secondary Conditions and Adaptation in SB associated with these outcomes. This model includes SB Context , neuropsychological risk [NPR], and protective processes (adolescent resilience and family resourcefulness).This is an interdisciplinary descriptive cross-sectional study. AYA were between 12-25 years of age and from 4 clinical programs in the USA. They had no other major medical condition, no mental retardation, were English speaking and functioned at approximately grade levels. Parent and AYA report of PH and MH and AYA report of HRQOL outcomes were included. Study measures had reliability and validity data and most had been used in our previous studies. Structural Equation Modelling (SEM) analyses were used to assess the model.Mean parent and AYA basic functional status scores reflect need for supervision; self-management reflects need for substantial assistance. Mean parental report of IBP are higher than EBP and both are in the normative range. However, 13-18% of parent or AYA reports of AYA depressive symptoms were in the clinically significant range.Self-worth and HRQOL were both moderately high. Three SEM analyses revealed different predictive patterns for PH, MH, and HRQOL constructs. In the PH model only LOL was significantly related to FS. NPF mediated the impact of shunt status and LOL on self-management, and age, NPR, and functional status had direct relationships to self-management. In the MH model, SES and family resourcefulness had indirect paths to MH; whereas AYA resilience, secondary conditions, and age had direct paths to MH. In the HRQOL model SES, age, and family resourcefulness had indirect paths to HRQOL through AYA resilience and MH; whereas AYA resilience and MH had direct paths.Different direct and indirect relationships of the conceptual framework variables were identified for the three outcomes. Clinical interventions should be differentiated by outcome and targeted to risk and protective variables."} +{"text": "Segmented service delivery with consequent inefficiencies in health systems was one of the main concerns raised during scaling up of disease-specific programs in the last two decades. The organized response to NCD is in infancy in most LMICs with little evidence on how the response is evolving in terms of institutional arrangements and policy development processes.Drawing on qualitative review of policy and program documents from five LMICs and data from global key-informant surveys conducted in 2004 and 2010, we examine current status of governance of response to NCDs at national level along three dimensions\u2014 institutional arrangements for stewardship and program management and implementation; policies/plans; and multisectoral coordination and partnerships.Several positive trends were noted in the organization and governance of response to NCDs: shift from specific NCD-based programs to integrated NCD programs, increasing inclusion of NCDs in sector-wide health plans, and establishment of high-level multisectoral coordination mechanisms.Several areas of concern were identified. The evolving NCD-specific institutional structures are being treated as \u2018program management and implementation\u2019 entities rather than as lead \u2018technical advisory\u2019 bodies, with unclear division of roles and responsibilities between NCD-specific and sector-wide structures. NCD-specific and sector-wide plans are poorly aligned and lack prioritization, costing, and appropriate targets. Finally, the effectiveness of existing multisectoral coordination mechanisms remains questionable.The \u2018technical functions\u2019 and \u2018implementation and management functions\u2019 should be clearly separated between NCD-specific units and sector-wide institutional structures to avoid duplicative segmented service delivery systems. Institutional capacity building efforts for NCDs should target both NCD-specific units and sector-wide organizational units (for building program management and implementation capacity) in MOH.The sector-wide health plans should reflect NCDs in proportion to their public health importance. NCD specific plans should be developed in close consultation with sector-wide health- and non-health stakeholders. These plans should expand on the directions provided by sector-wide health plans specifying strategically prioritized, fully costed activities, and realistic quantifiable targets for NCD control linked with sector-wide expenditure framework. Multisectoral coordination mechanisms need to be strengthened with optimal decision-making powers and resource commitment and monitoring of their outputs. The burden of chronic non-communicable diseases (NCDs) is growing in low- and middle-income countries (LMICs) alongside persistent communicable diseases, poor maternal health, and fragile health systems. NCDs such as cardiovascular disease (CVD), cancers, diabetes, and chronic obstructive respiratory diseases are increasingly affecting people in the economically productive age- groups. NCDs also account for more than 50% of total premature mortality (i.e. deaths in those under 60\u2009years of age) in most LMICs ,2. The aEncouragingly, NCDs are now high on the global agenda with a series of high-level events, such as the Health Ministers' meeting in Moscow and a United Nations High-Level Ministerial summit, held in September 2011. Calls are being made to establish a Global Fund for NCDs and a global facility for NCD medicines . Past exThe organized response to NCD is still in infancy in most LMICs. There is limited published evidence on how this response is structured from governance perspective within the context of overall health systems. We examine the evolving response in terms of institutional structures and arrangements, policy content and development processes, and coordination across different actors and sectors.Although our research is focused on LMICs in the Western Pacific Region (WPR) of the World Health Organization (WHO), we hope the findings may be of wider interest.Governance and leadership is a central building block for health systems . The terGovernance structures: The roles and responsibilities, inter-relationships, and architecture of the institutional structures within Ministries of Health (MOH) that are involved in oversight, management, and planning for NCDs were examined. We conceptualize the institutional structures in two categories: NCD \u2013specific structures whose remit is confined to NCDs only, and the \u2018sector-wide\u2019 structures responsible for \u2018shared\u2019 health functions across different diseases and programs .Policy development and planning: Policies and plans may be NCD-specific and \u2018sector-wide\u2019 covering all the programs and diseases and other sector-wide issues . We examine the extent to which the content, and processes for development of NCD-specific and sector-wide health policies and plans are aligned.Multisectoral coordination, building coalitions and partnerships: Effective regulation of and influence over the life-style and other environmental determinants of NCDs require interventions across multiple sectors and stakeholders increasing the salience of multi-sectoral coordination. We examine the status, nature, roles and responsibilities, and outcomes of multisectoral coordination mechanisms, coalitions and partnerships both within and outside government.In addition, the conceptual framework envisages that the governance of health systems and disease-specific programmes, especially in aid-dependent countries, are influenced by architecture of funding flows, policies, accountability and reporting requirements at global and regional level .A qualitative desk-review of policy and programme documents (published between 2000 and 2011 and available in public domain) covering the health sector and NCDs was conducted for the five selected countries\u2014Cambodia, Fiji, Malaysia, Mongolia and the Philippines. These countries represent a range of contexts from low-income (Cambodia and Mongolia) to lower-middle income (the Philippines) to upper middle income countries . A specific focus of analysis was the most recent national NCD plan and sector-wide national health plan in each of these five countries -22. In aThe paper also draws on data collected in 2004 and 2010 from member states in the WPR as part of the WHO sponsored global key-informant surveys. The surveys assessed the capacity of member states to respond to NCDs in five areas: public health infrastructure for NCDs; the status of policies, strategies, action plans and programmes relevant to NCDs; health information systems, surveillance and surveys; the capacity of health care systems for early detection, treatment and care of NCDs; and health promotion, partnerships and collaboration ,24. BothThis paper also uses other peer-reviewed literature on governance of health systems and NCDs published since 2000 with special reference to Western Pacific Region.An increasing number of countries have established special units or departments specifically for NCDs, giving a clear institutional identity to control and prevention of NCDs within MOHs. Globally, countries reporting such structures increased from 70% to 95% between 2000 and 2010 . In the The location and remit of NCD units within the MOH varies across countries Table\u2009. In MalaCo-existence of different NCDs in a substantial number of patients, and the common risk factors that link major NCDs warrant integrated multidisciplinary approach to disease prevention and management. Integrated approaches can improve efficiency, which is especially important given the often limited human resources in LMICs. Yet disease- or risk-factor based governance structures, often separate and additional to the overall NCD specific structures described above, have developed over time in some countries. For example in Vietnam, the National Institute for Cardiovascular Disease manages the program on prevention and control of CVD; the National Institute of Oncology manages the program on prevention and control of cancer; the National Institute of Endocrinology and the National Institute of Psychiatry each manage the separate national programs on diabetes and mental illness, respectively . A similDisease- or risk-factor specific global or regional initiatives seem to have also influenced development of disease- or risk-factor specific organizational structures within MOHs. For example, much stronger global advocacy and funding flow for tobacco control under the WHO Tobacco Free Initiative has led to far more resourced tobacco control teams in LMICs, often separate and under different hierarchical control from the NCD teams described above. Encouragingly, some positive trends are observed in establishment of more integrated NCD programs. The Philippines merged the three vertical programs into an integrated NCD control and prevention program in 2000, and similar trends are seen in other countries such as Mongolia and Malaysia.The global key informant survey in 2010 elicited information about the planning, coordination of implementation, and monitoring and evaluation of NCD initiatives and almost all the member states in the WPR reported NCD-specific units responsible for these functions. However, the relationships and division of roles and responsibilities between NCD units and other sector-wide institutional structures, such as policy and planning units and health information units, are often not clearly specified. In some countries, the NCD related structures seem to function mainly as technical units and not as specific programme management and implementation entities. For example, in contrast to the situation in Vietnam described earlier, structures such as the National Cancer Centre, National Cardiovascular Centre, National Centre for Neurosciences and Psychiatry affiliated with Ministry of Health, Labour and Welfare in Japan and in many other developed countries including Malaysia mainly serve as leading technical and research institutions in their respective fields, rather than as programme management or operational entities .Many LMICs have other major organizational structures with NCD related functions such as health promotion centres and national centres for nutrition, and these are often distinct entities under different hierarchical control. For example, Cambodia and the Philippines have an autonomous National Centre for Health Promotion. In Mongolia the National Centre for Health Development has the key responsibility for health promotion. Many countries including Malaysia, Mongolia, and the Philippines have newly established, or plan to establish, health promotion boards or foundations to provide population-based primary prevention services for NCDs. However, relationships of these newly proposed structures with the existing organization structures for health promotion or the NCD units are not clearly specified. There is a potential overlap in the reported functions and responsibilities, as NCD units also reported health promotion as their key responsibility in the global key informant survey. For example, the National Centre for Health Promotion in Cambodia is the focal organization for tobacco and alcohol control and is mandated to lead on matters of behaviour change, working across multiple programmes . This soIf the common goals and targets articulated in sector-wide and NCD-specific policies and plans are to be pursued effectively and efficiently, clear specification of roles and responsibilities of each institutional structure involved may be required to align the NCD-related functions, activities and resources located in multiple and distinct organizational structures across the MOH.Neither the global key informant survey nor the qualitative review indicated the presence of formal institutional coordination mechanisms for these different organizational units within the MOH. The Philippines has a Sectoral Management and Coordination Team responsible for the overall development, monitoring and coordination of policies, mechanisms and guidelines for the health sector, but its role in coordinating NCD policies across the Department of Health is not known.Cambodia provides a \u2018typical\u2019 example of the situation witnessed in many countries on how additional \u201cvertical\u201d disease- or program-specific structures were created over time that evolved into self-contained units taking over sector-wide health system functions relative to only that particular disease/program leading to segmented service delivery.In the past, the MOH in Cambodia created special institutions such as the National Centre for HIV/AIDS and STDs, the National Centre for TB and Leprosy Control, the National Centre for Parasitology, Entomology and Malaria Control, and the National Centre for Maternal and Child Health (NCMCH), which respectively became responsible for HIV/AIDS, Tuberculosis, Malaria and immunization services Figure\u2009. These nCurrently, the Department of Preventive Medicine is responsible for NCD control and is expected to facilitate and coordinate the development of NCD policy, conduct surveillance of NCD risk factors, develop treatment guidelines and deliver health promotion, prevention and treatment services and training relevant to NCD prevention and control. Many of the reported functions of this NCD unit overlap with other sector-wide centres/departments that are expected to perform some of these functions across different programmes/services Figure\u2009.If the experience of other disease-specific structures mentioned above is repeated, these NCD-specific structures may start growing by having additional staff with expertise and responsibility in the areas such as planning, management, human resource training, supervision, medical supply, logistics and procurement, and health information systems to become self-contained programme implementation and management entities undermining overall consolidation of these sector-wide functions in MOH. Encouragingly, Cambodia sector-wide health plan recognizes the fragmentation of activities, funding, monitoring and supervision and administrative lines of authority . The NCDIn LMICs in the WPR, the sector-wide national health plans and policies increasingly mention NCDs and included at least one goal or objective related to NCD control, although the level of detail varies. In Malaysia, NCD policy agenda figures high up not only in the health sector plan or for a specific risk factor such as alcohol or tobacco use, unhealthy diet, obesity, and physical inactivity. In 2010, the highest number of countries reported a policy/strategy for diabetes mellitus (71%) and cancer control (66%) and the lowest number reported for chronic obstructive pulmonary diseases (11%). These developments do not necessarily reflect the relative public health importance of these diseases. For example, the estimated number of deaths from cardiovascular (4.1 million) and chronic respiratory diseases (1.5 million) is much higher than that of diabetes ( 0.2 million) in the WPR ,26. The A qualitative review of sector-wide and NCD-specific polices/plans in five countries showed weak alignment between the two groups of policies in terms of goals and targets, financial resource allocation, and implementation mechanisms, potentially reflecting the largely autonomous development process of these policies involving different constituents. The NCD-specific Plans do not necessarily expand on the directions set in sector-wide national health plan and may be completely independent. The development of NCD-specific plans are for the most part coordinated by the NCD unit in the MOH, the role and influence of the sector-wide policy and planning units in the development of these policies is not very clear.An important factor in ensuring the implementation of NCD-policies and plans is the extent to which political consensus and administrative undertakings to ensure implementation are in place. This might best be achieved by involving key stakeholders at the preparatory stages of NCD strategies but the extent to which this happens is not clear from our qualitative review and practice seems to vary. The 2007 National NCD control program document in Mongolia identifies all the policy actors and their roles, and was explicitly endorsed by the Ministry of Food and Agriculture, Ministry of Finance, and governors of the capital city and provinces , other non-health government ministries (83%), private sector (71%), other international organizations (66%), academe (60%) and UN agencies (51%).The most commonly reported mechanism in the global key informant survey for multisectoral coordination was cross-departmental or inter-ministerial committees (80%). However, the survey does not give details of the composition, roles, responsibilities, and effectiveness of these partnerships, or the extent to which these partnerships influence national strategies, plans and regulations for NCDs.Encouragingly, in all the five countries, both the sector-wide and the NCD specific plans emphasize the importance of multi-sectoral coordination and identify relevant stakeholders. The qualitative review showed that high-level multisectoral coordination committees exist in all these countries Table\u2009. HoweverThe roles and responsibilities, powers and legitimacy of decision-making, and resources of these coordination mechanisms were often unclear. Evidence is already emerging that suggests the limited functionality and effectiveness of these structures in influencing either policies or resource allocation in non-health sectors. For example, although never formally abolished, the national public health council chaired by Mongolia's Prime Minister is not active . A similEffective governance for NCD at national level requires the development of effective partnerships and coalitions to generate the demand for change and to catalyze political action. The range of actors and stakeholders for non-communicable disease control are complex and include food manufacturers and retailers, tobacco and alcohol industries, civil associations, disease/condition specific advocacy groups such as national diabetic associations, and professional associations. Although the multisectoral coordination mechanisms in both Fiji and the Philippines included membership of non-governmental organizations (NGOs) Table\u2009, LMICs mWhile, the implementation of programs for communicable diseases and maternal and child health in LMICs owe much to the financial and technical assistance of external donors, less than 3% of global development assistance for health currently goes to NCDs . DespiteIn the past, many global initiatives had required countries to establish coordination structures for specific health issues as a condition to receive the assistance. For example, the Global Fund required a Country Coordination Mechanism and GAVI Alliance required an Interagency Coordination Committee (ICC), often having similar membership, functions and mandates . SimilarThe analysis in the paper is limited by explicit information available in the public domain and may not be able to capture all the complex consultations or discussions that may be ongoing in the countries more recently. Hence the results should be interpreted in light of this limitation.The evolving response to NCDs in LMICs shows several positive trends. These include increasing institutional recognition of NCDs, a move from disease-based programs to integrated NCD programs, and an increasing inclusion of NCDs in sector-wide health plans. These developments reflect the increasing recognition of the high burden of NCDs, and an explicit acknowledgment of the need for multisectoral actions with the creation of high-level coordination mechanisms. The analysis also suggests substantial influence of supranational initiatives and processes on in-country governance structures and policy development processes, which offers both opportunities and challenges.Notwithstanding the above positive trends, the analysis highlights some areas of concern. Each of these areas of concern and potential strategies to address them are described below.The current directions in development of NCD-specific institutional structures in LMICs with their increasing direct role in planning, management and implementation may lead to segmented service delivery systems for NCDs, especially with increase in NCD-specific external funding, as experienced in the past with scaling-up of programs for immunization, malaria, Tuberculosis, HIV/AIDS.Two key strategies are recommended to pre-empt this undesirable outcome. The first strategy would be clear separation of the \u2018technical\u2019 and the \u2018operational and programme management\u2019 functions between NCD-specific units and sector-wide organizational units , respectively. The NCD-specific structures are justified to build much needed technical capacity for NCDs in MOH and to provide institutional identity and visibility, especially when similar structures exist within the MOH for other public health problems perceived to be important. However, it will be critical that these NCD-specific units are developed only as technical advisory bodies with strengthening of their capacity in analyzing up-to-date technical information, development of clinical guidelines, advising on suitability of different proposed interventions and research. In addition, NCD-specific units should focus on strategizing, guiding, coordinating policies and activities across different stakeholders within and beyond MOH. However, these units should not act as direct implementing bodies for NCD plans and management and delivery of NCD-related services which should be rather left to sector-wide organizational structures.Second, the resources to strengthen institutional capacity to respond to NCDs should not be solely targeted to NCD-specific units, but more importantly to sector-wide organizational units to build their capacity in effectively incorporating NCD-specific requirements in human resources development, health financing, medical supply and logistic and information systems.Three major concerns were identified in the increasingly complex NCD policy landscape in LMICs.First, out analysis suggest that the sector-wide health plans were not entirely informed by critical analysis of local disease burden and health needs. Often local evidence, even when acknowledged in situation analysis, was ignored in favour of global priorities and goals. Hence, NCD-specific units should be fully engaged in the sector-wide health policy and planning process to ensure inclusion of NCDs related activities as appropriate to their epidemiology, morbidity/mortality burden in the sector-wide health plans.Second, our analysis shows weak alignment Tables\u2009 and 3 amThird, NCD specific plans with no information on financial and implementation feasibility and no realistic quantifiable targets, as have been observed in some of the countries examined, may become simply technical papers or 'laundry lists' of desirable activities with limited reference value and no follow-up at the government level .Although the need for multisectoral coordination is acknowledged by most LMICs, the resources needed to organize and manage such coordination mechanisms appear to be inadequate. The inter-ministerial bodies\u2014the most common mechanism reported\u2014seem to be relatively fragile structures in most LMICs with limited effectiveness in influencing the policies, programs and resources allocation in different sectors . In someTo summarize, attention to evolving governance structures and policy development processes for NCDs is vital. It will aid pre-emptive and corrective action at an early stage for the effective, efficient, and sustainable scaling-up of response to NCDs within a health systems context.The authors declare that they have no competing interests.MR conceptualized the paper and wrote the first draft and the final version. SN assisted with the qualitative desk reviews of the data and other literature and reviewed various drafts. LH reviewed the draft of the paper and provided comments and inputs towards the final paper. All authors read, commented, and approved the final version of the manuscript.MR \u2013 Western Pacific Regional Office, World Health Organization SN\u2014University of Auckland, New Zealand LH-- Western Pacific Regional Office, World Health Organization.The views expressed in this paper are solely the responsibility of the named authors and do not necessarily reflect the decisions or stated policy of the organization they work for.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/877/prepub"} +{"text": "A brief history of training of traditional birth attendants (TBAs), summary of evidence for effectiveness of TBA training, and consideration of the future role of trained TBAs in an environment that emphasizes transition to skilled birth attendance are provided. Evidence of the effectiveness of TBA training, based on 60 studies and standard meta-analytic procedures, includes moderate-to-large improvements in behaviours of TBAs relating to selected intrapartum and postnatal care practices, small significant increases in women's use of antenatal care and emergency obstetric care, and small significant decreases in perinatal mortality and neonatal mortality due to birth asphyxia and pneumonia. Such findings are consistent with the historical focus of TBA training on extending the reach of primary healthcare and a few programmes that have included home-based management of complications of births and the newborns, such as birth asphyxia and pneumonia. Evidence suggests that, in settings characterized by high mortality and weak health systems, trained TBAs can contribute to the Millennium Development Goal 4\u2014a two-thirds reduction in the rate of mortality of children aged less than 14 years by 2015\u2014through participation in key evidence-based interventions. Every year, an estimated four million babies die in the first four weeks of life, and a similar number of babies are stillborn. Moreover, half a million women die from pregnancy-related causes. Most of these deaths occur at home during the first postnatal or postpartum week, especially within the first 24 hours of birth. Most occur in developing countries with weak or failing health systems, with South Asia and sub-Saharan Africa being especially hard-hit \u20133. For mAlthough TBAs have been trained since the late 1800s, important milestones over the last century illustrate the shifting policies on TBA training as a global public-health strategy. Credit for the first formal training programme is usually given to a British missionary midwife, Miss M.E. Wolfe, working in Sudan in 1921 . HoweverThe broad goals of TBA training programmes are to reduce maternal and child mortality and morbidity and to improve the reproductive health of women. The objectives include: enhancing the linkages between the modern health system and community, increasing the number of TBA-attended births, and improving the skills and stature of TBAs . TraininThe content of curricula of TBA training also varies. Most TBAs have been trained to upgrade their skills so as to be able to perform safe deliveries. Consistent with the emphasis on extending the reach of primary healthcare, many TBAs have also been trained to take on the expanded functions of prevention, screening, and referral , 13. VerThe answer to the question: is TBA training effective? depends on the objectives and content of a particular training programme and the outcomes measured. From 1997 to 2002, we conducted a meta-analysis of the available published and unpublished studies on the effectiveness of TBA training. We updated this review for selected topics in 2003 and 2004 \u201315. The Details of materials, methods, and statistical analyses have been described elsewhere \u201315. Brieh, representing the standardized difference between the trained and the untrained TBA group on the outcome of interest. The variance-weighted mean effect size for each sub-group of outcomes was then calculated, and homogeneity tests were performed on the distributions of the weighted mean effect sizes. With a few exceptions, homogeneity of variance was rejected (\u03b1=<0.05), and the weighted mean effect size and 95% confidence interval were calculated using formulae based on a random effects model. Sensitivity analysis was conducted to detect the presence of publication bias. In addition, stratified analyses, by study design and sampling procedure, were performed to examine the influence of these potential moderating variables on the weighted mean effect sizes. Lastly, sub-group analyses conducted to date include antenatal care, referral for emergency obstetric care, birthing and newborn-care practices, perinatal and newborn health outcomes.Most outcomes measured were reported as percentages. The percent difference associated with each outcome was converted to a common scale using the effect size index Cohen's The findings of the meta-analysis were positive for the sub-groups of outcomes measured . StratifTBA training is associated with moderate-to-large improvements in behaviours relating to selected intrapartum and postnatal care practices, and small but significant decreases in perinatal mortality and neonatal mortality due to birth asphyxia and pneumonia. The findings are consistent with the historical focus of TBA training on extending the reach of primary healthcare and a few TBA training programmes that have included management of birth asphyxia and pneumonia care. TBA training is also associated with small but significant increases in women's use of antenatal care and emergency obstetric care, suggesting that referral is a multi-faceted process, and influence of TBAs on care-seeking behaviour may be limited.Unfortunately, incomplete reporting by authors resulted in loss of studies and datasets and limited our ability to examine which intervention characteristics were associated with better outcomes, cost-effectiveness, and the association between training and maternal mortality\u2014the rationale for the policy shift away from TBA training. Moreover, due to the variable quality of studies included in our sample, we could not address causality and only the magnitude and direction of the association between training and the outcomes could be measured. More rigorous studies are now being conducted. In a recent cluster-randomized controlled trial from Pakistan, Jokhio and colleagues showed that TBA training, linked to outreach and facility-based care, resulted in a statistically significant reduction of 30% in perinatal mortality . The estMillennium Development Goal (MDG) 4 aims to reduce mortality of children, aged less than five years, by two-thirds between 1990 and 2015. MDG 5 aims to reduce maternal mortality by three quarters during this timeframe. Policy regarding the best strategies to meet these goals, however, swings between community-based care and facility-based care, while safe motherhood and child-survival advocates compete for limited resources . The finIn settings characterized by high mortality and weak healthcare systems, family and community care providers often include a mix of women, family members, TBAs, and other semi-skilled or skilled health workers. In these circumstances, \u201cAre TBAs the best choice, among others, for training in health promotion and delivery care?\u201d There are a number of considerations. One important consideration is the proportion of deliveries assisted by TBAs since this reflects, to a large extent, their number, distribution, role, status, presence of other providers, and preference of women and families. Our analysis of the 1994\u20132004 Demographic and Health Survey data from 44 countries for the period of three years preceding the survey showed tThe Lancet\u2014eloquently argued that women, newborns, and children all have lefts, and all would greatly benefit from a health system that delivers proven interventions through a continuum-of-care approach, i.e. from pregnancy through labour, birth, and the postpartum and postnatal periods, and into early childhood; and including home, peripheral health facility, and hospital \u2014must include interventions that prevent and treat complications that kill women\u201d . We beliThe meta-analysis of effectiveness of TBA training was made possible through funding support from the World Bank , USAID , USAID, DFID and the Bill and Melinda Gates Foundation (University of Aberdeen/IMMPACT Project), and the Bill and Melinda Gates Foundation (Save the Children/Saving Newborn Lives Project). The views presented here represent those of the authors."} +{"text": "The obstructive sleep apnea syndrome (OSAS), a form of periodic breathing, is highly prevalent disorder that affects at least 4% of adult male population and 2% of females and is associated with repetitive episodes of complete (apnea) or partial (hypopnea) occlusion of upper airway during sleep. These episodes result, among others, in loud snoring and in daytime symptoms such as excessive sleepiness, morning headache, irritability, cognitive impairment and lead to reduced quality of life. Varying degrees of transient oxygen desaturation follow the upper airway occlusion, and it is a common pathway for the development of several cardiovascular complications. Central Sleep Apnea (CSA) is another form of periodic breathing characterized by lack of respiratory effort during sleep and frequently coexists with OSA. One major underlying mechanism of CSA is unstable ventilatory drive during sleep. Treatment options for sleep apnea include continuous positive airway pressure (CPAP), oral appliances, and weight loss.In this special issue on sleep-related breathing disorders a number of distinguished scientists report on the following: the association between the duration of sleep and cardiovascular and metabolic comorbidities of patients with OSAS, the influence of age on clinical characteristics and polysomnographic findings of patients with OSAS in Greek population, the effect of weight loss by behavioural, pharmacological, or surgical approaches in the management of OSAS, the mechanisms that may trigger cognitive decline in OSA patients, the evaluation of two different mandibular advance appliances and the application of sclerosant agents for treatment of snoring, the presence of Cheyne-Stokes respiration (CSR), a form of central sleep apnea, in patients with radiologically-proven first-ever lacunar stroke, the implication of age in the pathogenetic link between sleep apnea and plasma homocysteine levels.All the above help us to better understand some mechanisms involved in pathogenesis, consequences, and treatment of sleep apnea syndrome and snoring, and clearly this special issue is a great contributor to our knowledge.Manos AlchanatisManos AlchanatisJames MacFarlaneJames MacFarlaneSofia SchizaSofia Schiza"} +{"text": "Diarrheal illness remains 1 of the top 5 causes of death in low-income and middle-income countries, especially for children <5 years of age. Introduction of universal childhood vaccination against rotaviruses has greatly reduced the incidence and severity of illness in upper-income and lower-income settings. For adults, norovirus is the leading cause of sporadic cases and outbreaks of diarrheal illness and is responsible for nearly 21 million episodes annually in the United States, of which 5.5 million are foodborne. Public health efforts to control and prevent norovirus illness have focused on rapid outbreak detection and source identification and control of transmission in institutional settings. Diarrheal illness remains 1 of the top 5 causes of death in lower-income and middle-income countries (For children <5 years of age, rotavirus is the leading cause of diarrhea-associated illness and death. Fortunately, safe and effective vaccines against rotavirus illness are now available in many countries. Introduction of universal childhood vaccination against rotaviruses greatly reduces the incidence and severity of illness in upper-and lower-income settings (In adults, norovirus is now recognized as the leading cause of sporadic cases (Public health efforts to control and prevent norovirus illness have focused primarily on outbreak detection and control. The implementation of CaliciNet, as described by Vega et al. (Because a large proportion of norovirus illness results from foodborne exposures, considerable effort has gone into development of methods for detecting and eliminating virus contamination from food items, particularly shellfish (Finally, several other viruses, including astrovirus, sapovirus, and as described by Drexler et al. ("} +{"text": "Translational Neurodegeneration will provide a perfect platform at the global level to share knowledge and experience of the latest research on the epidemiology, etiology, pathogenesis, diagnosis, management and prevention of neurodegenerative diseases.A common feature of current biomedical science is inter-disciplinary research and collaboration. Translational research, the basis for translational medicine, integrates the basic sciences and clinical medicine with the aim of optimizing preventive measures and patient care, is at the cusp for expansion. Translational medicine, in short, is the process of turning appropriate biological discoveries into drugs and medical devices that can be used in the treatment of patients. Vigorous efforts have been made to link basic scientific research with clinical investigations. Notably, in the area of neurodegenerative disorders, more basic and clinical researchers as well as nations have joined forces to explore the interface between basic neurosciences and clinical neurology and psychology. Thus, the newly established journal of Indeed, the prevalence of neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), has increased significantly as global populations age. Specifically, the number of cases of dementia in the developed world is projected to rise from 13.5 million in 2000 to 21.2 million in 2025, and to 36.7 million in 2050[The discovery and application of levodopa (L-dopa) is one of the best examples of translational research for neurodegenerative diseases. In 1910s, L-dopa was first isolated from seedlings of Vicia faba; and in 1938, L-dopa decarboxylase was discovered, which can produce dopamine (DA) from L-dopa. In 1959, DA was found enriched in the basal ganglia; and in 1960, a severe striatal DA deficit was demonstrated in PD patients. These major discoveries and a deepening understanding of the neurochemistry of DA and the neuropathology of PD led to the concept of \"DA replacement\" with L-dopa. In 1961, L-dopa was tried in PD patients by i.v. treatment. In 1967, oral administration of L-dopa was reported to produce dramatic improvements in PD patients with increasing amounts over long periods . Since tSubstantial progress has been made in understanding the pathogenesis of neurodegenerative diseases, but we are still a long way from applying it to clinical application. Translational research will definitely help overcome the bottleneck and barriers in 1) identifing and validating biomarkers for early or pre-clinical diagnosis as well as clinical progression; 2) promoting the innovative clinical technologies, such as neuroimaging, stem cell technology and nanotechnology; and 3) developing the novel drug candidates; and more importantly, to gain a multitude of new ideas and contacts back to research. Thus, launching a journal in translational neurodegenerative diseases is essential and timely.Translational Neurodegeneration. Notably, the articles are interdisciplinary and focus on many current issues facing translational neuroscience research.The latest research on the etiology, pathogenesis, potential diagnostic markers and treatment modalities of PD has been presented at the XIX World Congress on Parkinson's Diseases and Related Disorders. Almost 2500 distinguished scientists, clinicians and allied health experts gathered in Shanghai, China, December 11-14, 2011 to enhance collaboration in these important inter-disciplinary research areas. Organized by the Association of Parkinsonism and Related Disorders and the local host, the Department of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, the congress is the highest level of academic conferences in the field of PD and related disorders. Several speakers and attendees contributed review and original articles for the inaugural issue of Research of gene mutation, especially of alpha-synuclein, has provided important clues in understanding the pathogenesis of PD. In cell models, A53T mutation of alpha-synuclein can increase macroautophagy, which has not yet been detected in patients. Yue Huang et al . It gavePeter A. LeWitt discussed the wide role of norepinephrine (NE) in his review titled \"Norepinephrine: the next therapeutics frontier for Parkinson's disease\" . NE may Jon Stoessl introduced the latest progress in \"Neuroimaging in the early diagnosis of neurodegenerative diseases\" . SPECT aTranslational Neurodegeneration will promote the rapid conversion of basic research to clinical applications benefiting patients better and faster. The concept and spirit of translational research in the field of neurodegenerative disorders will spread through Translational Neurodegeneration and the authors.Translational research and knowledge of neurodegeneration are expanding at a fast pace. The potential to find causes, treatments and cures for many neurological and neurodegenerative diseases are available to us. This congress and our journal highlight the opportunities for interdisciplinary and global collaborations. By offering a high-visibility forum for new insights and discussions of translational research in neurodegenerative diseases, Translational Neurodegeneration; Rui Jin Hospital leaders, colleagues, team members and leaders of Shanghai Jiao Tong University School of Medicine, University of Nebraska Medical Center, Society for Neurology Chinese Medical Association and Chinese Society for Neuroscience, without whose help the success of this undertaking could not have been realized.We thank the authors, referees, and Springer and BioMed Central, our publisher, for their help in making this journal and first issue possible. Special thanks also go to Ms. Robin Taylor from the University of Nebraska Medical Center; Drs. Jianqing Ding and Yuyan Tan, managing Editors of"} +{"text": "Phaseolus vulgaris L.) is an important source of plant protein, and member of the legume family, which includes soybean, cowpea, and lentils. With its relatively small genome size, well-characterized cytogenetics, and recently sequenced genome, common bean serves as a good model for legume epigenetics. Accumulation of recent and ongoing bean community-wide genomic and transcriptomic sequence data along with advances in sequencing technology enables the further understanding of the roles of histone-DNA interactions, small RNAs, and cytosine methylation in gene regulation in common bean. Till date, there has not been much progress in studying various epigenomic marks in common bean, and therefore, the long-term objective of this research is to identify protein-DNA interaction sites in the common bean genome to include histones, as well as, non-histone proteins such as transcription factors involved in biotic and abiotic stress. The short-term objective of this work is to develop the first reference epigenomes in four common bean genotypes as related to histone modifications. Common bean genotypes can be broadly classified into those of Andean and Mesoamerican origin, and these genotypes were selected for their importance and use in genomics, as well as breeding. The immediate goal of this work is to identify the hierarchy of binding of histones H4K12ac and H3K9me2 in the common bean genome using Illumina sequencing. To achieve this goal, a chromatin immunoprecipitation (ChIP) protocol was developed for common bean, and chromatin from leaves of these four genotypes was isolated and used for ChIP and ChIP-sequencing (ChIP-seq). Sequence analyses of this data is enabling the understanding of the layout of these histone modifications across the genomes of these four genotypes when compared to the reference genome sequence of G19833. This work serves as the first reference histone-DNA interaction map in common bean and lays a foundation for comprehensive analyses and large-scale studies of histone modifications and global protein binding sites in this important plant species, further facilitating the annotation of the common bean genome.The common bean ("} +{"text": "Indeed, the remarkable achievements in contemporary integrative oncology only emphasize the need for a patient-tailored strategy of care attuned to the individual's biophysical, psychological, social, cultural, and spiritual needs and concerns. The integrative challenge is how to provide an evidence-based consultation and supportive treatment to patients who confront fear at the moment of breaking the bad news of cancer diagnosis; how to improve their well-being during chemotherapy, radiation, surgical, or palliative treatment; and how to support patients and their care providers along the survivorship pathway or across the threshold of life. In daily practice, integrative oncology may be employed to reduce nausea and vomiting in contemporary cancer care is an emergent field of clinical practice and research throughout the world. The use of herbs, nutrition, mind-body, and spiritual practices is deeply rooted in the cross-cultural mosaic of Middle Eastern and South Asian nations. The concept of integrative oncology has emerged in the last decade to signify the need to amalgamate traditional and complementary medicine practices with evidence-based research aiming to improve supportive cancer care. The integration of ancient s ginger ), to alls ginger ), and tos ginger ), mood ds ginger ), and maThe paper by H. Zaid et al. featured in this special issue reviews the concept of traditional Islamic medicine with regard to herbs with potential anticancer activity. This paper illuminates the importance of bridging ancient knowledge rooted in Greco-Arabic medicine and contemporary research. But, in addition to the extensive review presented by H. Zaid et al., this paper is also distinctive thanks to the contribution of the two other authors in this collaborative Israeli-Palestinian paper. Notable is the contribution of M. Silbermann, the director of the US National Cancer Institute-affiliated Middle-East Cancer Consortium (MECC), who has succeeded over the last 15 years in promoting supportive care collaborations that have included joint integrative oncology projects between MECC and other Middle-Eastern countries . The paper by E. Ben-Arye presents an integrative oncology program operated within conventional oncology services in northern Israel aimed at improving patients' quality of life during chemotherapy and advanced cancer. The authors address barriers to integration of traditional and complementary medicine in supportive care of Arab patients and propose six practical recommendations aimed at improving patients' access to integrative supportive care as well as compliance with treatments. This paper emphasizes the need to base integrative oncology on a sensitive cross-cultural approach that takes into consideration social, cultural, and spiritual elements.The paper by M. Schaltz et al. intensifies this cross-cultural theme by reflecting on palliative care from the perspective of Jewish and Islamic traditions. The collaboration in this paper between M. Schultz and K. Baddarni, two scholars in spiritual supportive care in northern Israel, highlights the richness of therapeutic dialogue between Muslim and Jewish health care providers who share faith in the role of the integrative dialogue. This paper summarizes ethical, religious, and spiritual insights gleaned in the management of patients in the community-centered Al-Taj organization and in the oncology department in Rambam health care campus, which is named for the renowned Jewish physician Maimonides.The paper authored by I. Cantarero-Villanueva et al. from Granada presents the flavor of the ancient cities of southern Spain, the backdrop for the Golden Age of collaborative Muslim and Jewish physicians, including Maimonides and the followers of Ibn-Sina, the most prominent Islamic medicine scholar. In this paper, the authors evaluated, in a randomized controlled trial, the effects of a multimodal exercise and massage program on the well-being of breast cancer survivors. The reduced fatigue, tension, depression, and improved vigor and muscle strength after intervention and 6 months after discharge are remarkable and support the need for other rigorous trials in the integrative oncology field.alternative) to CIM (with emphasis on integrative) that will enable patients and physicians to discuss complementary use in an open nonjudgmental context. Moving from West to East across the Mediterranean and West Asia, the paper by P. Puataweeponge et al. presents the notion of complementary medicine in Bangkok, Thailand. The authors present a study regarding CAM use by a large cohort of cancer patients attending outpatient radiotherapy treatment in Thailand. The high prevalence of CAM use of more than 60% is notable in light of the patient-oncologist communication gap illustrated by the high prevalence (58.3%) of patients who did not disclose CAM use to their doctors. This communication aspect should raise concern when 9.4% of patients in this study reported side effects of CAM treatments. Moreover, this study emphasizes the need for a paradigm shift from CAM (with emphasis on in vitro research elements needed to base any clinical integrative oncology activity. Zhang et al. from China report. the anticancer effects of the photochemical Zerumbone, isolated from the plant Zingiber zerumbet Smith. Although additional rigorous studies are warranted, the promising apoptosis induction effect of this plant on pancreatic carcinoma cell lines may suggest that ginger and related plants may have anticancer properties in addition to their beneficial effect in chemotherapy-related nausea and vomiting. In the paper by Y. H. Liu et al. from neighboring Taiwan, they studied Abrin, a protein purified from the seeds of Abrus precatorius, and reported that prohibitin, a tumor-suppressing protein, plays a role in abrin-induced apoptosis. These findings join the growing number of promising studies in integrative oncology that may support development of new and, in some cases, traditional medicine-based, therapeutic agents and modalities for the benefit of patients with cancer across the globe. Two papers in this issue present the fundamental"} +{"text": "The Western Palearctic (WP) is composed of Europe, Middle East and North Africa. In this territory, the Mediterranean Sea, and the land under the influence of the Mediterranean Sea is the most important geographical character for both migration and dispersion of organisms; especially for invertebrates including sand flies. Anatolia (Asia-Minor) takes place on the crossroads of this area and these events.The phlebotomine sand flies are vectors of several infectious pathogens causing leishmaniases and arbovirus infections due to phleboviruses. Several of these diseases have wide geographical distributions in the WP, and give rise to occasional epidemic outbreaks. In numerous countries, increasing risk factors are making sand fly-borne diseases a major public and veterinary health problem. Many studies on phylogenetic relationship among sand fly taxa, their distribution, population structure and diseases of phlebotomine species have been already published, but there are still many gaps waiting to be filled up in, especially, Anatolia. In this point, scientists have to discuss some deficiencies under cover of geography, history and phylogenetic studies to understand the mechanisms of distribution of both sand fly species and their pathogens in Anatolia.In this presentation, updates in distribution of sand fly species with state of art maps of EU-VBORNET project, possible new species, leishmaniasis and phleboviruses epidemiology will be discussed with an emphasis on several studies performed by our group between 2000 and present in Anatolia.Studies were supported by EU-FP7 Edenext project, HU-Scientific Research Foundation and Turkish Scientific and Technical Research Council."} +{"text": "Water-electrolyte disturbances are one of the most common complications of acute brain injury of various origins, threatening the life of the patient and requiring timely correction. In this work we studied the structure of water-electrolyte complications in patients in the neurological intensive care with acute brain injury.We analyzed 259 cases of water-electrolyte disturbances that developed in patients treated in the Department of Intensive Care of Russian Polenov's Neurosurgical Institute from 2001 to 2012. Patients were between 16 and 55 years old. A total of 142 patients were operated for brain tumor, 72 of them of basal-supratentorial localization; eight severe brain trauma; 62 of the hemorrhagic type of stroke, one herpes encephalitis. We excluded from this study the patients with heart and renal failure receiving diuretics. We measured BP, HR, CVP, hourly and daily urine output, level of K and Na in plasma, brain natriuretic peptide (BNP) one to four times a day, and levels of K and Na in urine in single and daily servings. All patients were receiving dexamethasone at a dose between 8 and 32 mg/day as an anti-edema therapy, and thus levels of ACTH and cortisol were not investigated.Central diabetes insipidus (CDI) developed in 106 patients. Against the background of substitution therapy, we did not observe the development of complications, hypovolemia, hypernatremia, or hyperosmolality. Out of 48 cases of CSWS, in 12 cases the symptoms interleaved with the symptoms of CDI. For 24 patients, CSWS was complicated by depressed consciousness, for three patients by convulsions against the background of hypovolemia, hyponatremia, or hypo-osmolality. No correlation between BPN level and absence of CSWS symptoms was found.In patients with acute brain trauma we observed two syndromes causing water-electrolyte disturbance - CDI and CSWS. CSWS generally is more severe than CDI. We could not determine a correlation between BPN level and the absence of presence of the CSWS symptoms."} +{"text": "Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde ), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer\u2019s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or N\u03b5-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD. Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. Increases are reported each year in the number of individuals with this hyperglycemic condition, which may result in life-changing complications. In addition to the 415 million adults (this will increase to 642 million adults by 2040) already estimated to currently have DM (a DM-related death occurs every 6 s), there are 318 million adults with impaired glucose tolerance (IGT), which places them at high risk of developing the disease in the future ,8,9. We Hence, a focus was placed on TAGE and a specific competitive enzyme-linked immunosorbent assay (ELISA) was developed, and the clinical utility of measuring TAGE as a biomarker for evaluating disease activity in LSRD was examined.In vivo AGE generation is affected by sugar concentrations, the rate of turnover of the chemically modified target, and the time available. Increases in glucose concentrations were previously considered to have a major influence on the Maillard reaction; however, glucose is one of the least reactive sugars found in biological organisms fluorodeoxyglucose-positron emission tomography (FDG-PET) in outpatients in vitro ammation ,82. In aammation ,84,85.in vivo tumor growth of G361 cells . T. T103]. We evaluated the amounts of AGEs and sugars in beverages and foods, which cause the generation of TAGE in the body. We evaluated the amounts of various AGEs in 885 kinds of beverages and 767 kinds of food, and found that the amounts of AGEs derived from Glu-AGEs/Fru-AGEs (particularly Glu-AGEs) more accurately reflected the amounts of AGEs in beverages and foods than those of CML . Our evaet al. prospectively examined the relationship between the consumption of SSB and risk of DM from 17 cohorts [Imamura n years) . They reThe findings of our studies suggest that sugars are present at appreciable levels in common beverages , and exoThese findings are promising in that the concept of the restricted intake of AGEs and sugars in beverages and foods may be a new strategy when considering the suppressed generation/accumulation of TAGE and prevention of LSRD.As described above, changes in serum TAGE levels are closely associated with MetS and IR, postprandial hyperglycemia, dyslipidemia, and hypertension, which are related to overeating, the lack of exercise, or excessive ingestion of sugars (HFCS and sucrose)/dietary AGEs . We propThe characteristics of modern dietary habits promote the generation and accumulation of TAGE in the body, and are strongly involved in the onset and progression of LSRD. Thus, our findings provide a new concept of preventative measures against LSRD, including aging."} +{"text": "Migration and trauma is a critical and timely area of inquiry given the enormous transnational migration occurring within the past year. The UN estimates there are over 244 million people living outside of their country of origin offer a unique look at the association between posttraumatic growth and dispositional optimism, perceived social support, and PTSD among 111 refugee and asylum-seeking adolescents. At least some PTG was reported by the sample. PTG and PTSD were not statistically significantly associated, but PTG was associated with higher levels of optimism and social support. This is one of the first studies conducted to explore these associations within an adolescent population and future research, especially longitudinal , People's Republic of ChinaBrian J. Hall Johns Hopkins Bloomberg School of Public Health Baltimore, MD, USA E-mail: brianhall@umac.mo; bhall31@jhu.eduDepartment of Health, Behavior, and Society Department of Psychiatry Academic Medical Center University of Amsterdam Amsterdam, The Netherlands Arq Psychotrauma Expert Group Diemen, The NetherlandsMiranda Olff"} +{"text": "The seas are continuously pervaded by a broad range of contaminants entering the marine environment from polluted soils, the atmosphere, sewage, water transport or river streams (Shahidul Islam and Tanaka, Biomass transfer among species of a food web can be modeled using allometric scaling rules describing body size, consumption and metabolism (Yodzis and Innes, Geobacter spp. (Mahadevan et al., Shewanella oneidensis (Fredrickson et al., Pseudomonas putida (Nogales et al., The described efforts facilitated generic estimations of contaminant flows in ecosystems, but largely neglected the contribution of microorganisms to pollutant degradation. Specifically, PCBs can be dechlorinated and degraded by a range of bacteria (Borja et al., P. putida. First, the authors conducted an extensive literature review to complement a food web reconstruction (Coll et al., P. putida for constraint-based simulation of microbial PCB degradation. The study integrated two methodologically similar modeling approaches within a reaction-based ecological/microbial network representation, relying on the parallels between representing PCB concentrations and flows on the ecosystem level, and metabolite concentrations and reaction fluxes on the microbial cellular level. Therein, marine species groups resemble the representation of metabolites, while contaminant flows are modeled as reactions. This approach enabled the seamless integration of ecological and metabolic modeling techniques, providing the basis for multi-scale simulations of ecosystems.Taffi et al. have recP. putida. Further, the impact of different bioremediation scenarios on global and local network indices was assessed. Importantly, the generality of the proposed approach facilitates the integration of measured data, the incorporation of established techniques from ecological and metabolic modeling and the direct application of the methodology to other ecological and microbial networks. Thus, it can be used to guide the selection of appropriate bacteria and consortia (Thompson et al., The modeling approach was used to predict the influence of different microbial bioremediation strategies on the fate and distribution of PCBs in marine species of the Adriatic Sea. The effect of varying oxygen levels on microbial PCB degradation revealed a tradeoff between PCB uptake and growth of The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Objectives: The objective of this post-hoc exploratory analysis was to examine the relationship between age and measures of cortical excitability and inhibition.Methods: Forty-six participants completed MT, SICI, ICF, and CSP testing in a cross-sectional protocol. Of these 46 participants, 33 completed LICI testing. Multiple linear robust regression and Spearman partial correlation coefficient were used to examine the relationship between age and the TMS measures.Results: In the overall sample of 46 participants, age had a significant negative relationship with motor threshold (MT) in both the right and left hemispheres. This significant negative relationship of age with MT was also observed in the sample of depressed youth in both the right and left hemispheres, but not in healthy controls. In the sample of the 33 participants who completed LICI testing, age had a significant negative relationship with LICI in both the right and left hemispheres. This negative relationship between age and LICI was also observed in depressed youth in both the right and left hemispheres.Conclusion: These findings suggest that younger children have higher MTs. This is more pronounced in depressed youth than healthy controls. LICI inhibition may also increase with age in youth. Transcranial magnetic stimulation (TMS) measures of cortical excitability and inhibition have shown initial promise as biomarkers and for the study of neurophysiology in youth with attention deficit hyperactivity disorder which is a single pulse TMS measure and intracortical facilitation (ICF) which is a paired-pulse TMS measure. Prior human pharmacologic studies indicate that the MT is at least partially dependent on voltage-gated sodium channels while ICF is an indirect measure of glutamatergic N-methyl-D-aspartate (NMDA) mediated neurotransmission and excitability (MT and ICF) were collected during a single session. A subgroup of this cohort completed LICI testing during the same testing session. Study design details have been previously published and excitability . The TMS measures were log transformed to obtain a more normal distribution (because of skewness).The primary independent variable was patient age in years. Sex and CDRS-R total score were included as covariates in the models to bolster precision in the evaluation of the relationship between age and each measure of cortical inhibitory or excitatory functioning. Some were used to examine the relationship between age and TMS measures of cortical inhibition and excitability in the overall sample, while adjusting for sex and CDRS-R total score, and then separately in depressed youth and healthy controls, while adjusting for sex. The estimated slope from the regression model indicates the mean change in each TMS measure per one-year increase in age, while the sample correlation coefficient indicates not only direction, but also strength of the linear relationship between age and each TMS measure. The Spearman partial correlation coefficient can also be interpreted as the effect size estimator in evaluating the magnitude of the relationship between age and each TMS measure.This was an exploratory study with the aim of investigating the impact of age on measures of cortical inhibition and excitability in youth. Analyses were performed on the entire sample and then on subgroups of healthy and depressed youth. The rationale for this approach was to maximize limited data and with the realization that the impact of depression or depression severity on these neurophysiological measures is not definitively known. Demographic and clinical characteristics for the overall sample of patients and for depressed youth and healthy controls were described using the sample mean and standard deviation for continuous variables and the frequency and percentage for categorical variables. Multiple linear robust regression (with MM estimation) and the Spearman partial correlation coefficient (post-hoc) regression models (similar to that described above) by evaluating the interaction effect of group with age on the TMS measure. Comparing the regression parameters (slopes) between groups was used to assess if the mean change in the TMS measure per one-year increase in age was different between healthy controls and MDD patients.Regression coefficients found to have statistical significance for each of the two groups in the abovementioned regression analysis, were then tested in subsequent . The level of significance for all tests was set at \u03b1 = 0.05 (two-tailed). We implemented the False Discovery Rate procedure with MDD completed MT, SICI, ICF, and CSP testing. Demographics of the sample are also characterized our prior publication. In comparing participants with MDD and healthy controls, there were no statistically significant differences in age, sex, or handedness and left hemispheres. This significant negative relationship of age with MT, while adjusting for sex, was also observed in the sample of depressed youth in both the right and left hemispheres, but not in healthy controls. Note that lower MT values reflect increased excitability. We also present scatterplots of the log transformed MT values (left and right hemispheres) against age, with a fitted regression line and 95% confidence limits, by depressed youth and healthy controls and left hemispheres. This negative relationship between age and LICI , while adjusting for sex, was also observed in depressed participants and left hemispheres and in healthy controls . Note that lower LICI values reflect increased inhibition. Scatterplots of the log transformed LICI values (left and right hemispheres) against age, with a fitted regression line and 95% confidence limits, by depressed youth and healthy controls are presented in Figures post-hoc results of the interaction of group with age indicated that the slope of the regression of LICI-200 ms on age was similar for both healthy controls and MDD patients in the left hemisphere in both the right the MT was unobtainable with maximum output of the stimulator had a statistically significant negative relationship with age in depressed youth, but not in healthy control participants. It is important to acknowledge the lack of a relationship may be attributable to low power, given the high degree of variability in the measure in general. Lower LICI ratios signify greater inhibition and increased GABAA receptors decreases from childhood to adulthood Great Neck, New York; and Pfizer Inc., New York, NY. He has served as a site subprincipal or principal investigator for Eli Lilly and Co, Indianapolis, Indiana; Forest Laboratories, Inc., New York, NY; Merck and Co, Inc., Whitehouse Station, New Jersey; and Pfizer Inc.Mustafa M. Husain has received research support from the National Institute of Mental Healthy, Stanley Medical Research Institute, Cyberonics, Inc., Pfizer, Inc., Neuronetics Inc., Magstim; has served as a consultant for AstraZeneca; served on speaker bureau for AstraZeneca, Bristol-Meyers-Squibb, and Abbott Laboratories.Graham J. Emslie has received research support from the National Institute of Mental Health, Biobehavioral Diagnostic Inc., BioMarin, Duke University, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Mylan, and Somerset; has served as a consultant for Alkermes, Inc., Allergan, NCS Pearson , Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, INC Research Inc., Lundbeck, Merck, Pfizer, Seaside Therapeutics, Shire, the Texas Department of State Health Services, University of Miami, Valeant, and Wyeth; and was on the Speakers Bureau for Forest Laboratories.In the last 5 years, Zafiris J. Daskalakis received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and a travel allowance through Merck. Zafiris J. Daskalakis has also received speaker funding through Sepracor Inc., AstraZeneca and served on the advisory board for Hoffmann-La Roche Limited and Merck and received speaker support from Eli Lilly.Drs. Paul A. Nakonezny, Charles P. Lewis, Michael J. Zaccariello, John E. Huxsahl, and Betsy D. Kennard have no disclosures.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "We report our experience in a University Hospital 2012-2013) and in the School of Medicine (2001-2013) in courses committed to promote original thought, to provide basic and operationally useful skills, to teach and to explore the possibilities of setting up networks and existing collaborations. The contribution of ideas, resources, skills and tenacity is the basis for strategic researches aimed at promoting quality, effectiveness and efficiency of health systems. The specific environments and healthcare organizations for which the research is a structural mission need quality and visibility, indicators of quality and efficiency. Vocational training integrated and participated within all the active components with a clinical profile will facilitate those who wish to plan projects also with international European profile 2-2013 an.1) Actual research ongoing in the individual clinical institutions, by the presentation of projects implemented or under way, regardless of specific funding.2) Strategies of Project Management through an analysis of the context (scenario), feasibility, impact and contingency plans.3) Realistic prospects for fundraising, public and private, building-up overviews of applied research with the contribution of all students. The course implements the explicit use of methodologies of data-mining and the subsequent elemental analysis of usable information:a) predictive models,b) assessments of sensitivity/specificity (diagnostic tests),c) comparative analysis of the risks in case-control or randomized studies, and the calculation of the required number,d) comparison of averages or changes of measures in sequential studies,d) definition of some possibilities for translational research with the development of models.The expertise in clinical research is limited in most institution and not fully oriented toward Predictive, Preventive, and Personalized Medicine (PPPM) concepts and goals. The consequence is that most funded research are addressed to innovative fields but show often limited attention to a shared patient-physician center strategy, to integration and even to outcome. These trainings to be comprehensive and effective must move along PPPM directives; these must be included in the projects that should be independently supported (such as EU funding) within competitive calls. The goal is overcoming the gap among predictive, preventive and personalized medicine training professionals \u2013 not only MDs -, for sustainable and rewarding research projects, including nutrition and lifestyle chance strategies by health psychology tools. The promotion of the professional quality in translational research is the pre-requisite for innovative best practices and their dissemination of the most high impact information."} +{"text": "This series of papers focuses on a quality of care framework for maternal health, and systematically reviews the evidence of interventions aimed at improving care at the community-, district- and factility-levels. While the systematic reviews highlight the effectiveness of specific quality improvement efforts on maternal and newborn health, it also illlustrates the dearth of evidence on community-, district- and facility-level interventions, particulary for issues specific to quality of maternal health care and maternal newborn health outcomes. Further evidence is now needed to evaluate the best possible combination of the strategies. Governments, stakeholders and donors need to work together to form these policies and develop models of health care to suit the needs of their own population. This series of papers focuses on a quality of care framework for maternal health, and systematically reviews the evidence of interventions aimed at improving care at the community-, district- and factility-levels. The approaches included in this paper had an effect on process and outcome measures for mothers and newborn health (MNH). Effects on other types of outcomes, while important, are not included in this analysis. In this final paper of the series, we summarize the most critical findings, and highlight the evidence gaps and research priorities identified through the analysis of the scientific literature. We also discuss the methodological quality of the existing evidence and areas for further advancement of the maternal and newborn health agenda, particularly in low and middle income countries (LMIC) -4.At the community-level, home visitation, community mobilization, women\u2019s support groups and the training of community health workers (CHW) and traditional birth attendants (TBA) have shown significant and positive impacts on MNH outcomes. The community-based generation of funds for transportation also had an effect on access to MNH care in resource limited settings of India and sub-Saharan Africa. Mid-level health worker based care (MLHW) has not only demonstrated outcomes comparable to routine non-MLHW care delivery but also reported better results for some of the outcomes. Many of the interventions, including specialized outreach clinics, continuing medical education, problem-based learning, clinical practice guideline implementation and critical appraisal, showed inconclusive and mixed results on the quality of MNH care or MNH outcomes. Table At the district-level, user directed financial incentives have shown to improve quality of care indicators, with conditional cash transfers and maternal voucher schemes having the most significant positive impacts across a range of MNH outcomes.At the facility-level, evidence suggests that standardized or individualized social support programs and continuity of specialized midwifery care throughout pregnancy, labor and postnatal period have the potential to improve a range of perinatal, maternal, and labor specific indicators. To maintain performance and motivation among the healthcare workers, stress management trainings, multidisciplinary meetings and feedback sessions can reduce work related stress and improve performance. There was limited and inconclusive evidence for the impacts of physical environment, exit interviews and organizational culture modification on any MNH process or outcome measures. Table As discussed in paper 1 [\u2022 In-service training and specialty teams have conclusive benefits in improving maternal health outcomes.\u2022 Social support during pregnancy interventions reduce antenatal hospitalization and caesarean delivery\u2022 Strategies to improve professional practice were reported to have a significant positive effect on the desired practice.While the systematic reviews highlight the effectiveness of specific quality improvement efforts on maternal and newborn health, it also illlustrates the dearth of evidence on community-, district- and facility-level interventions, particulary for issues specific to quality of maternal health care and MNH outcomes. This is particularly evident during the most hazardous time period for women (last trimester of pregnancy to the first week post-partum) when the majority of maternal deaths and severe morbidities occur.Community-based quality improvement interventions were widely assessed for their effectiveness in improving MNH outcomes in low and middle income countries (LMIC). At the district-level, evidence from financial incentives was available from both high-income countries (HIC) and LMIC settings. Other interventions at the district-level were mainly evaluated in HIC settings. Given the differences in LMIC and HIC countries\u2019 infrastructure and health systems, there is limited generalizability of findings across countries. There is also an information gap on the effectiveness of these interventions on different population groups that may represent within-country disparities.At the district-level, many of the components of leadership, supervision, health information systems and staffing models had limited evidence of impact on the quality of maternal healthcare, or on MNH outcomes. Overall, very few maternal health specific outcomes were observed at the district-level. Although financial incentives, both user- and provider-directed, have been widely evaluated for their effectiveness in improving MNH outcomes, audits, feedbacks and information systems are mostly evaluated in the context of general health outcomes. Moreover, reviews focusing on MNH specific interventions, like maternal and perinatal mortality audits, require strong, standardized data collection mechanisms to evaluate their effectiveness. Improving the health information systems in countries is necessary for any evaluation of the impact of mortality audits.From the facility-level evidence, most of the findings from social support and specialized midwifery teams programs during pregnancy and labor were limited to HIC. There is limited evidence on the effects of these interventions on maternal and newborn health outcomes in LMIC. There is also a lack of data evaluating the effectiveness of structural and cultural changes, educational interventions, and the facility mix of staff skills. Future research on the impact of these interventions (at the facility-level) on quality of maternal health care and specific maternal health outcomes in LMIC\u2019s is essential in order to make evidence-based recommendations for better policies, programs and practice.Very few of these studies provided evidence on sustainability and scale up, particularly in countries where resources are constrained and health systems are weak. Recent studies in Uganda and Ghana have highlighted the challenges in scaling up interventions that have been proven effective ,6. InterThere are currently several innovative interventions that are being implemented globally to improve the quality of maternal health services. The Maternal Health Task Force, for example, is currently supporting multiple research projects aimed to improve referral systems, increase the use of novel methodologies to train providers, introduce innovative approaches to supportive supervision and mentoring, increase access to blood products, develop professional organizations, among many others. The results of the evaluation of the impact of these programs on the quality of maternal care may fill many of the informational gaps in the Quality of Maternal Care Framework that this systematic review has utilized.Finally, qualitative data describing individual components of the interventions for reproducibility will be invaluable for scale up and sustainability. Further evidence is now needed to evaluate the best possible combination of the strategies. Governments, stakeholders and donors need to work together to form these policies and develop models of health care to suit the needs of their own population. This will further lead to outlining approaches that enable health care providers either in the community or in a facility, and program managers at the district-level, to adopt and implement patient-centered, evidence-based interventions to improve the quality of care during childbirth and the immediate postpartum period.Research and programming priorities are summarised in Table We do not have any financial or non-financial competing interests for this review.All authors contributed in writing the paper.Click here for file"} +{"text": "The mini-review stemmed from a recent meeting on national aging research strategies in China discusses the components and challenges of aging research in China. Highlighted are the major efforts of a number of research teams, funding situations and outstanding examples of recent major research achievements. Finally, authors discuss potential targets and strategies of aging research in China. China Aging Development Report (2013), the severity of the aging population China faced is rarely seen elsewhere in the world. By the end of 2012, China\u2019s elderly population (aged 60 and above) had totaled 194 million, taking up 14.3% of total population; the elderly population aged 65 and above had reached 123 million\u2014constituting one fifth of the world\u2019s elderly population. By 2030, China\u2019s elderly population is expected to reach 400 million, equivalent to the total population of 15 EU countries. China is the country with not only the world\u2019s largest population, but also a country holds the largest elderly population.According to The increases in age-related diseases and the consequent rise in health care costs caused by the decline in the health status along with the aging of the population have brought increasing pressure and burden to the society, families and individuals joint research.Research on aging and related diseases in China has received significant support from the National Natural Science Foundation of China (NSFC), the Ministry of Science and Technology of China (MOST), the National Health and Family Planning Commission of China (NHFPC), and local departments over the last decades. NSFC has supported approximately 55 million of US dollars on aging research over the past decade Fig.\u00a0. The supIn recent years, China has made significant progress in the research of aging and anti-aging, and the underlying mechanisms. A number of funding programs, such as \u201cThousand Talents\u00a0Program \u201d, \u201cNational Science Fund for Distinguished Young Scholars\u201d, distinguished professors of \u201cChangjiang Scholars Program\u201d, and \u201cHundred Talents Program of the Chinese Academy of Sciences\u201d have been in place to encourage biomedical research including aging and anti-aging research. A brief of made-in-China achievements and summaries in distinct aging research fields is summarized as the following.CETP 405\u00a0V is protective in Ashkenazi Jews but may be a risk allele against longevity in the Chinese population, and that the gene interaction between CETP and APOE polymorphisms confers higher risk of hypertriglyceridemia on Chinese women are closely related to the occurrence of aging and aging-related diseases from Terc\u2212/\u2212 SCNT embryos have stronger differentiation potential and self-renewal capacity compared with that of Terc\u2212/\u2212 iPSCs. It is noteworthy that the telomere lengths in SCNT cloned embryos are significantly lengthened, and the capping function of telomeres in Terc\u2212/\u2212 ntESCs is enhanced. In addition, the mitochondrial function of Terc/iPSCs and their differentiated derivatives is severely impaired, while the mitochondrial function in Terc\u2212/\u2212 ntESCs is considerably improved technology enables the creation of cell models of progeria and geriatrics in laboratory conditions, for studying disease mechanisms and drug screening. Meanwhile, human pluripotent stem cells and gene targeting technologies can assist the knockout or modification of any protein from human stem cells, therefore facilitating the functional study of the proteins in organisms with aging and diseases inflames surrounding cells of the same and other cell types leading to tissue degeneration, and continuous accumulation results in irreversible losses of differentiated function and pathological changes of the diseased tissue. Anti-aging is also a process involving corrections and/or removals of damaged molecules, the clearance of senescent cells, as well as proliferation and differentiation of stem/progenitor (precursor) cells. Aging and anti-aging process coexist as aging, anti-aging factors, and injury, repair and regeneration are also in parallel. For instance, interactions of inert and reactive bioactive assemblies and the consequent chemical reaction would free or slowly cross-link the biological molecules, and altered oxidative product may produce damaging molecules precipitating aging of the biological tissues. In addition, aging and damage of cellular organelles may be the pathophysiological basis of many neural aging-related diseases such as Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD), while the replication and regeneration of cells may be the promising approach to vanquish many mitotic aging-related diseases Liu, . MobilizAging of the organism, tissues, and organs is the main cause of functional decline, and the premature aging of tissues and organs is the utmost pathological basis for chronic degenerative diseases. Tissue and organ specificity of aging are common for most chronic degenerative diseases, such as AD, atherosclerosis, pulmonary fibrosis, muscular dystrophy, osteoporosis, obesity, diabetes, menopause syndrome, which are related to the premature aging of tissue-specific cells. Aging of organism, tissues, or cells is a complicated and irreversible process, but the time when it occurs and the pace of the process may be regulated. Facing the need to slow down the aging process of the organism and organs, as well as to prevent common chronic diseases, a fundamental understanding of the cause of aging and the causes of aging developing into diseases is a hot topic in the current medical biological research field has not been well recognized as the primary factors of most non-infectious chronic diseases. Although the central government has been increasing its research budgets continuously in aging research, contributions from the state governments and the private sections have not been considered as high priority to aging research and development. As a matter of fact, with improved living conditions and life expectancies in China, there are significant demands and interests of the general population in detecting premature aging and delaying aging occurrence. In addition, international collaborations in promoting aging research have until recently been on the agenda including our organizing the \u201cShuangqing\u201d forum and a number of other activities from universities, hospitals, and Chinese Academy of Science. Unfortunately, a national-wide database incorporating information of aging-related resources is yet to be established, which requires urgent actions from aging research organizations and researchers. On the other hand, collaborations between hospitals and basic research institutes are lacking which hinders the development of gerontology and geriatrics. The phenomenon of being more difficult for an aging disease to find its way to geriatrics than for ill children to be sent to pediatrics may well reflect currently poor understandings of the mechanisms and biomarkers of aging bodies for clinical practice, making the translational aging research struggle to develop. While many challenges and weakness of aging research in China may be shared by global situations, we highlight at least but not last the following a few that are particularly sought after for development in China:(1) The impact of particular environmental factors, various foods, and exercise levels on aging and lifespan, (2) Genetic traits and epigenetic specificities affected by stress in premature aging and aging related diseases including metabolic disorder and cancers in liver, digestive tracts, and lung, (3) Effect of endocrine/paracrine/autocrine hormones and cytokines, microorganisms, inflammatory/immune responses on tissue and organ aging, (4) Repair mechanisms of stem cells and key enzyme molecules in aging damages, (5) Tissue- and organ-specific mechanisms of aging and diagnostic markers.Numerous tasks need to be done prior to achieving the final goal of preventing and reducing aging-related diseases. By means of original innovative research, it would be important to achieve 3 major comprehensive objectives. Firstly, at the molecular and cellular levels, it would be important to understand the basis of aging, to clarify the molecular characteristics of different types of cellular aging and their roles in the aging of tissues and organs, regulatory networks, plasticity, and clearance mechanisms; to clarify the regulatory mechanism of the change of sub-cellular structure of eukaryotic cell aging in aging and anti-aging process; to clarify the basic structure and spatial conformation of different key molecules and to analyze the binding structural domain of interacting molecules and small molecules; to analyze direct and indirect (epi-)genetic regulatory network of different genes, especially to identify and control the key transcription factors mediating aging process; to unveil the regulation and effect of key environmental factors, especially the microflora in different tissues (such as intestine), excessive nutrients, toxic molecules, as well as exercises and sleep, etc. on the aging of tissues and organs.Second, at the levels of tissue- and organ-specific aging, it would be important to clarify the transition of aging damage to pathological damage and the composition and structural alteration; to clarify the source, function, and regulatory environment of triggers to aging and aging-related diseases; to clarify the susceptible parts of aging organelle/tissue/organ, and the complicated etiology of aging-related diseases; to rationalize and establish the relationship among the causes, to strengthen the research in the compensatory effect of aging development into aging-related diseases; to set out the mechanism, reagents, and methods for early intervention in the transition from aging to aging-related diseases in the micro environment; to clarify the definition of physiological aging and pathological aging of organisms as well as the definition of healthy lifespan; to clarify the similarities and differences in the lifespan regulation of non-vertebrates, invertebrates, and mammals and to clarify the disease susceptibility and resistance mechanisms of different models to aging-related diseases; to clarify the functional ingredients of natural medicine (including Chinese medicine), the role of new, small molecule compounds and clinical drugs , and the regulatory mechanism of other environmental factors to mammalian lifespan.Third, at the levels of particular diseases, it would be important to clarify the role of signaling pathway impairment and pathological basis in the occurrence and development of aging-related diseases through the analysis of animal/human disease models; to clarify the role of stem (precursor) cells and their aging in aging and different common aging-related diseases; to clarify the molecular biological characteristics and development in the research models of brain aging-related diseases , vascular aging-related diseases, marrow aging-related diseases, lung aging-related diseases, and ovarian aging-related diseases; to clarify the mechanisms of prevention of aging-related diseases via either inhibiting key aging molecules or activating anti-aging molecules, thus providing the basis and strategies for further research on the prevention and treatment.It is possible that senescence of a single or a group of cells in certain tissues and organs seeds tissue specific aging which paves, and is a prelude of, aging-related diseases. Such senescent cells suffer irreversible damages, therefore being amplified to cause loss of normal function of aged tissues and organs. Current aging research in China may need to collaborate with researchers in other countries to integrate the approaches of molecular imaging, stem cell biology, molecular genetics and genomics, molecular pathology, histology and embryology, systematic biology, bioinformatics, and clinical medicine to conduct research at different levels of aging and related diseases. Research of aging and aging-related diseases is a great challenge and opportunity in the 21st century. Although it has experienced a long history, aging research is still limited especially on the transition from aging to aging diseases. In-depth and extensive exploration on key molecules and critical mechanisms are still very much sought after. The complexities of various body tissues and differences in structures and functions bring massive difficulties in human anti-aging research. However, the discovery of stem cell plasticity, and continuous breakthroughs in verification of the causal relationship between molecules and aging-related diseases, for example, using different cell culture systems and animal models, have provided opportunity for collaborative innovation in the research on aging and aging-related diseases."} +{"text": "Comparison of epidemiological studies of JIA is challenging due to many influencing factors, mainly differences in classification criteria or study designs . Recently, longitudinal cohort studies have provided important contributions to the understanding of the disease course of JIA in the long run. Latest advances in research of incidence and prevalence of JIA will be highlighted and discussed to facilitate understanding the consequences of epidemiological knowledge of the disease.P. Lahdenne Speakers Bureau of: Consultancy and speaker\u2019s fees from Pfizer, Abbvie, Roche, Novartis"} +{"text": "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children are now available on the AIDSinfo website ( http://aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf ). These guidelines update the last version of the guidelines published in 2009. They are intended for use by clinicians and health care workers providing medical care for human immunodeficiency virus (HIV)-exposed and HIV-infected children in the United States.The The guidelines include a discussion of opportunistic pathogens that occur in the United States and ones that might be acquired during international travel, such as malaria. The section for each opportunistic infection (OI) includes a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of first episode of disease; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment, including immune reconstitution inflammatory syndrome (IRIS); management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. Recommendations are rated using a system that indicates the strength of each recommendation and the quality of evidence supporting it.Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy (ART) for preventing and treating OIs, especially those OIs for which no specific therapy exists; 2) increased information about the diagnosis and management of IRIS; 3) additional information about managing ART in children with OIs, including potential drug\u2013drug interactions; 4) updated immunization recommendations for HIV-exposed and HIV-infected children, including pneumococcal, human papillomavirus, meningococcal, and rotavirus vaccines; 5) addition of sections on influenza, giardiasis, and isosporiasis; 6) elimination of sections on aspergillosis, bartonellosis, and human herpes virus (HHV-6 and HHV-7) infections; and 7) updated recommendations on discontinuation of OI prophylaxis after immune reconstitution in children."} +{"text": "Development the personalized programs of rehabilitation for inhabitants of industrial cities with Chronic Fatigue Syndrome (CFS) and stress-induced diseases is actual up-to-date problem.85 patients with combined myofascial pain in the cervical part of the vertebral column and chronic fatigue syndrome were examined. Clinical neurological examination was conducted to identify the role of myotonic neck \u201ctunnel- syndromes\u201d and biomechanically significant biomarkers in the cervical spine for affect the cerebral blood flow. EEG- examination was carried out to assess the state of brain activity, the definition of cortical areas responsive to the effects of stress factors and hemispheric interactions, as correlates of memory. The NEC-method of visualization used to study the biochemical markers \u2013 the level of cerebral metabolism and adaptation possibilities. 15 patients used genetic test for indication genes of metabolism (genes of phase I and phase II).Main complains in patients were: headache, fatigue, memory, sleep problems. Disorders in the cognitive, personal, emotional status had all patients. Neuro-vertebral examination had revealed biomechanical markers-disturbances of muscular coordination, muscular hypertension, rigidity in the shoulder girdle, syndrome of upper aperture, kyphosis, postural displacement and the lymphodinamic disturbances \u2013 edematosity of the axillary and subclavicular areas. EEG and NEC analysis revealed signs of functional inter-hemispheric asymmetry of bioelectrical activity in 80% of patients and different levels of cerebral acidosis as biomarker for brain hypoxia. Genetic tests revealed decreasing genes activity of phase II detoxification in 7 patients. Clinical and instrumental observations allow us to offer some statements. New mechanisms of non-specific base of CFS are: stress \u2013 short term or long term muscle spasm and lack of oxygen increase the density of muscles and lead to 3-level \u201ctunnels\u201d intervertebral (compression of nerves), intramuscular (compression of blood vessels) and intrafascial (compression of lymphatic and nodes), Retrograde lymph flow and intoxication of the intersticial matrix are suppose to be the grain for CFS and specific pathologidcal processes. The personalized integrative schemes of rehabilitation were worked out for patients with different postural, neurovascular and lymphodinamic disturbances for correction of muscle-tonic syndrome in the neck, cranio-vertebral region, for improving the cerebral metabolism and liquorodynamics. Methods of intermitted hypoxia therapy were used in the case of cerebral acidosis; adoptive gymnastics was used for patients with postural problems; nutrigenomic diet was recommended to patients for increasing phase II of detoxification.Comprehensive personalized rehabilitation of the patients with CFS improved their clinical and emotional background, memory and cognitive functions. EEG and NEC examination marked the trends in recovery of inter-hemispheric connections, normalization of the bioelectrical activity in the brain and improvement of cerebral metabolism."} +{"text": "Nurses are in key positions to plan and implement alcohol screening and brief intervention (aSBI). To simultaneously advance aSBI of nurses in various roles, we developed a self-paced program for Clinical Nurse Leaders, Nurse Informaticists, Nurse Administrators, and Registered Nurses including Advanced Practice Nurses. The content for the program is based on the Centers for Disease Control & Prevention (CDC) 2014 Planning and Implementation Screening and Brief Intervention for Risky Alcohol Use: A Step-by-Step Guide for Primary Care Practices. The objective is to present the results of a cooperative agreement between the Centers for Disease Control & Prevention, Johns Hopkins School of Nursing, and the University of Pittsburgh School of Nursing. The framework used to design the aSBI Program and key aspects of the program will be demonstrated and discussed.The aSBI Program flow, depicted in the CDC guide defined the modules for learning: patient population, assess alcohol consumption, negative screen (and subsequent conversation), positive screen (and assessment of harm and dependence), brief intervention and referral to treatment. The modules were developed using Articulate Storyline, the premier rapid e-learning development platform, and hosted on a learning management system. Special focus was given to the assessment portion of the e-learning modules to ensure learners are provided with authentic assessments that accurately measure their mastery of real-world skills needed to be successful when applying the module educational materials.When finalized, the self-paced aSBI Program, funded by the American Association of Colleges of Nursing through the CDC, will be widely disseminated to the nursing community across the U.S.This easily accessible on-line educational program will bring evidence-based alcohol screening and intervention to current and future nurses."} +{"text": "Hystrix javanica) and its immunolocalization.To identify the types of endocrine cells in the pancreas of the Sunda porcupine in pancreatic tissues were detected using the avidin-biotin-peroxidase complex method.Five adult The fusiform, round, and oval form endocrine cells were detected in the islets of Langerhans and exocrine parts. Most of the insulin cells were found in the central area, glucagon cells were identified in the central and peripheral areas, and somatostatin and PP cells were detected in the mantle area of the islets of Langerhans. Glucagon and somatostatin cells were also detected in smaller numbers of peripheral parts of the islet. In all of the islet parts, glucagon endocrine cells were most prevalent cell type and then, somatostatin, insulin, and PP. In the exocrine parts, PP, somatostatin, glucagon, and insulin endocrine cells were found in the inter-acinus part with moderate, moderate, a few and rare numbers, in that order. In the pancreatic duct, glucagon and somatostatin cells were found between epithelial cells in rare numbers.H. javanica) contains four types of major pancreatic endocrine cells with approximately similar distribution patterns to the other rodents, except for abundant glucagon cells in the peripheral area of the islets of Langerhans.The pancreas of Sunda porcupine ( Hystrix javanica, belonging to the genus Hystrix in the family Hystricidae is one of the Old World porcupines [The Sunda porcupine, rcupines . There arcupines ,3.The pancreas is a composite gland consisting of exocrine and endocrine parts. The exocrine part consists of acini that secrete digestive enzymes into ducts. The endocrine part, the pancreatic islets (islets of Langerhans), consists of masses of endocrine cells embedded within the exocrine pancreas, where pancreatic hormones of insulin, glucagon, somatostatin, and pancreatic polypeptide (PP) are distributed into the whole body via blood vessels. The presence, distribution, and immunoreactivities of these regulatory hormones secreted by endocrine cells in the pancreas were well understood by histochemistry , immunofHystrix cristata), which belongs to the subgenus Hystrix of the genus Hystrix [H. cristata were limited on its basic morphology and localization of only 3 kind endocrine cells. There are no other data of pancreas on other porcupine species are available. In this research, the presences and semiquantitative distribution of all major endocrine cells types in the pancreas of Sunda porcupine, H. javanica which is endemic to Indonesia, were detected by employing the avidin-biotin-peroxidase complex (ABC) method.The recent studies on pancreas of porcupine have been conducted in crested porcupine .H. javanica, about 67 cm in length, were purchased from an extreme food merchant in Tawangmangu, Central java, Indonesia, were used as samples. Pancreatic tissues of H. javanica were fixed for 24 h in Bouin\u2019s solution, dehydrate in ethanol, cleared in xylene, and embedded in paraffin.Five pancreatic tissues of adult Sunda porcupines, 2O2 in methanol for 15 min. Primary antibodies , few (+), moderate (++), and numerous (+++).The presences of positif endocrine cell types were observed in 3 parts of the pancreas, (1) the islets of Langerhans, (2) the exocrine acini, and (3) the pancreatic duct. In addition, the presence and semiquantitatif number of endocrine cells types in the islets of Langerhans were distinguished into three locations: Central, mantle, and peripheral areas. The presence and semiquantitative number of endocrine cells types in the pancreatic duct were distinguished into two locations: inter-epithelial and sub-epithelial cells.H. javanica. Four types endocrine cells were detected in various pancreatic parts and areas with different semiquantitatif numbers as shown in Tables-H. javanica, was fusiform, round, and oval.The research clarified the presence of four types pancreatic endocrine cells including insulin, glucagon, somatostatin, and PP in the islets of Langerhans, exocrine acini and pancreatic duct of H. javanica contain fusiform and round form insulin cells which located in the central and mantle areas with a numerous and moderate numbers, respectively, but not in the peripheral area , has clarified base on the results of this research. They are insulin, glucagon, somatostatin, and PP of the endocrine cells types. The semiquantitatif number of endocrine cell types was grouped according to the pancreatic parts and the area of pancreatic islets . Specific spreading of endocrine cell types in the pancreatic tissues was also emphasized with references to other already known species.The presence of four main types of endocrine cells in the pancreas of the most exotic Indonesian endemic porcupine, the Sunda porcupine could exactly be distinguished from each other using immunohistochemical techniques . Previoue region . The preH. javanica, mainly in the peripheral area of the islets.PP cell is the other type of endocrine cell that can be found in the pancreas. It has been known that the location differentiation of PP cells in the pancreas can easily be recognized among species, although the cells, if they occur, were always located in the peripheral area of the islets of Langerhans. PP cells were demonstrated in the peripheral area of the pancreatic islets of the hamster , rat 1717, mouseH. javanica pancreas, insulin, glucagon, and somatostatin cells were found individually, whereas PP cells were detected in a form of cluster cells located between acini. Moreover, glucagon and somatostatin cells were detected in the inter-epithelial cells and sub-epithelial cells of pancreatic ducts, respectively. Unfortunately, the report of Timurkan et al. [H. cristata did not mention about this features. The present result, however, the first evidence on the individual form of insulin, glucagon and somatostatin cells, and cluster cells feature of PP cells in the exocrine parts of porcupines species.In the exocrine part of n et al. on pancrH. javanica, glucagon cells were found in inter-epithelial cells, and somatostatin cells were detected in sub-epithelial cells. The endocrine parts of H. javanica pancreas contain of those four types endocrine cells with variation on the form, location, and number of the cells depend on the area of the islets of Langerhans but in common is approximately similar to that of other rodents. The research elucidated the exception on the specific location of glucagon cells in the peripheral area in islets of Langerhans of H. javanica which differ from others mammals.The present research clarified the presence of four major endocrine cells, namely, insulin, glucagon, somatostatin, and PP cells in the islets of Langerhans and inter-acinar cells of the exocrine part. In pancreatic duct of TB prepared proposal and managed the research implementation. TB, YHF and GTM carried out the sample collections and laboratory works for histology and immunohistochemistry. TB critically analyzed the histological and immunohistochemical data and prepared the manuscript. All authors read and approved the final manuscript."} +{"text": "The prevalence of allergies has vastly increased over recent decades due to air pollution and climate change. The present study aims to identify any seasonal variations in the allergens, to help prevent and treat allergic diseases; and investigate any correlations between the reported allergens and other biotic parameters, namely age and sex. The study included 67 subjects who visit the Department of Pneumology and Oto-rhino-laryngology of the Regional Hospital of Gafsa, between August 2007 and September 2008. The allergic condition of these patients was confirmed by measuring allergen specific IgE levels using the multiple allergen simultaneous test-chemoluminescent assay (MAST-CLA). A total of 30 allergens were tested and classified into seven groups: tree and grass pollen, herbaceous pollen, animal dander, moulds, latex, cockroaches and mites.The seasonal distribution of allergens shows that the frequency of respiratory allergy was mainly observed during spring corresponding to the pollination season. However, the detection of some seasonal allergens, such as olive pollen, outside the pollination season can be explained by the cross-reactivity between allergens. The age range of patients with sensitivity was found to be between 10 and 73 years, with the most sensitive patients aged between 20 and 50 years. The sex variable was significantly associated with the studied allergens since sensitization was present more frequently in women than in men."} +{"text": "Eosinophilic chronic rhinosinusitis (ECRS) is considered a refractory and intractable disease. Patients with ECRS present with thick mucus production, long-term nasal congestion, loss of sense of smell, and intermittent acute exacerbations secondary to bacterial infections. Despite medical and surgical interventions, there is a high rate of recurrence with significant impairment to quality of life. The recent increasing prevalence of ECRS in south Asian countries and the strong tendency of ECRS to reoccur after surgery should be considered. The majority of cases need repeat surgery, and histological examinations of these cases show eosinophilic-dominant inflammation. The degradation and accumulation of eosinophils, release of cytokines, and mucus secretion have important roles in the pathogenesis of ECRS. ECRS differs from non-ECRS, in which eosinophils are not involved in the pathogenesis of the disease, and also in terms of many clinical characteristics, blood examination and nasal polyp histological findings, clinical features of the disease after surgery, efficacy of medications, and computed tomography findings. This review describes the clinical course, diagnosis, and treatment of ECRS as well as its pathophysiology and the role of eosinophils, mucus, cytokines, and other mediators in the pathogenesis of ECRS. Eosinophilic chronic rhinosinusitis (ECRS) is an inflammatory pathological condition of the nose and paranasal sinuses . PatientMultiple cytokines are involved in the pathogenesis of ECRS. Elevated levels of circulatory eosinophils and tissue eosinophils are prominent features of ECRS. Cytokines are essential for hematopoietic cell development, differentiation, and maturation. Interleukin (IL)-3, IL-5, and granulocyte/macrophage-colony stimulating factor (GM-CSF) are cytokines that are particularly important in regulating eosinophil development . MyeloidEosinophils also function as antigen-presenting cells and they can process and present a variety of microbial, viral, and parasitic antigens . In addiConversely, cytokines that have antagonistic effects, especially on Th2 inflammation, such as IFN-\u03b3 and transforming growth factor (TGF)-\u03b2, are down-regulated in ECRSwNP . The comA number of studies demonstrated that there is an association between peripheral eosinophilia and a high percentage of eosinophil infiltration in paranasal sinuses . EosinopA better understanding of the clinical features and specific characteristics of CT images will facilitate the diagnosis of ECRS. Researchers have found a direct association between the severity of paranasal cavity CT findings and an increase in the circulatory eosinophil count . Thus, aPatients with ECRS exhibit clinical characteristics that include long term nasal congestion, mucus production, olfactory disturbances, bilateral nasal polyposis, and intermittent acute exacerbation of secondary bacterial infections . A combiSince there is no approved medication to treat patients with ECRSwNP completely, surgery is often needed to clear the sinonasal passage, and repeated endoscopic sinus surgery (ESS) is often required . In caseMoreover, the presence of mucosal eosinophilia (>10 eosinophils/high-power field) at the time of ESS consistently predicts less improvement in both disease-specific measures and general quality of life compared to the absence of eosinophilia . AdditioThe effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) was reported for the treatment of CRS in Japan , 73, 74.As mentioned before, the treatment strategies for ECRS differ from those for non-ECRS; a diagnostic criterion for ECRS is thought to be very useful to decide a treatment strategy in an outpatient setting . If sinuSystemic deregulation of eosinophils is thought to be involved in the pathogenesis of ECRS . Once thAlthough, CRSwNP is characterized histologically by an abundance of eosinophilic inflammatory changes, the levels of leukotriene C4 in patients with recurrent sinonasal polyps after surgery are significantly higher than in healthy controls, and higher leukotriene C4 levels can be an indicator of the risk of recurrence of nasal polyps . Recent In European and UnitAlessandri et al. showed that AT7519, a novel cyclin-dependent kinase inhibitor, causes apoptosis in human and mouse model eosinophils, indicating that such inhibitors can have a therapeutic role in eosinophil-dominant allergic disorder treatment . A newlyECRS is an intractable and persistent disease of the nose and paranasal sinuses. Eosinophilic degradation and accumulation, the release of cytokines and chemokines, and mucus production have an important role in the pathogenesis of this disease. The clinical features reflect the complicated condition of ECRS that seems to be resistant to the current available medical therapies and has a high rate of recurrence after surgery. Further studies are needed particularly focusing on the function of cytokines, chemokines, and eosinophils and the production of eosinophils to achieve a precise treatment, prevention, and the required outcomes."} +{"text": "Budgetary constraints - with annual growth rates that peaked at 20% - fuelled by the upcoming economic crisis demanded a change in the pricing model for pharmaceuticals in the Republic of Macedonia. Several neighbouring countries were faced with similar challenges, so the Republic of Macedonia carefully looked into their policies and thus introduced external reference pricing in 2011, which led to a reduction of prices. The specific was that both the Ministry of Health for the \"unique price\" (i.e. the maximum price) and the Health Insurance Fund as a basis for reimbursement performed price comparisons. The country basket for the Ministry of Health includes Bulgaria, Croatia, France, Germany, Greece, the Netherlands, Poland, Russia, Serbia, Slovenia, Turkey and the UK whereas the HIF references Bulgaria, Croatia, Serbia and Slovenia.To show the trend of price reductions achieved for selected pharmaceuticals in the Republic of Macedonia as compared with the non-basket countries Hungary, Czech Republic and Austria.Policies targeted: Analysis of the effects of external price referencing in different countries.Stakeholders: Pricing and reimbursement authorities of the analysed countries.Region covered: International comparison focussing on Central and Eastern Europe countries.Ex-post cross-country evaluation of pricing trends between 2009 and 2014 for selected out-patient medicines that are reimbursed by the Macedonian HIF using the national Macedonian price database and the European Integrated Price Database EURIPID.The prices of the selected medicines were reduced in all analysed countries but the extents of tje decreases were different. It was also notable that some of the initially selected medicines (based on the Macedonian reimbursement list) were not marketed or reimbursed in the countries of comparison.The analysis showed that a more regular exchange of information and pricing policies could generate higher savings for national pricing and reimbursement authorities as the price development of similar products was quite diverse."} +{"text": "Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM) and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies. Vascular stiffness is a consequence of pathophysiological alterations involving endothelial cells (ECs), vascular smooth muscle cells (VSMCs), extracellular matrix (ECM), and other functional elements of the vessel wall analysis of pulse transit time; (2) wave contour of the arterial pulse; and (3) direct measurement of arterial geometry and pressure that corresponds to regional, systemic, and local determination of stiffness and sympathetic nervous (SNS) systems are all components of the cardiorenal metabolic syndrome, which is associated with vascular stiffness Sowers, . DysreguExcess adipose tissue, in particular abdominal adipose tissue, has been closely linked to the development of vascular stiffness and cardiovascular disease , and vasoconstrictor substances, such as angiotensin II (Ang II), and thromboxane A2 has a vasodilatory effect and anti-atherogenic properties, including inhibition of VSMC proliferation and migration, platelet activation and adhesion and leukocyte adhesion and migration and connective tissue growth factor (CTGF) are well-known profibrotic factors that can stimulate synthesis of ECM proteins, such as fibronectin and collagens, under conditions of obesity, insulin resistance, and T2D expression on the EC surface leading to reduced NO production that is associated with increases in cortical stiffness of the cytoskeleton oxidase activity and reduction of NO bioavailability, thereby promoting oxidative stress and vascular dysfunction can protect the vascular cells by immunosuppression, cell contact\u2013dependent suppression, and functional modification or killing of activated protein C (He et al., Vascular stiffness is associated with chronic inflammatory disease in the vessel wall characterized by an activation of both the innate and adaptive immune systems, which are composed of diverse cellular components, including granulocytes, mast cells, monocytes, macrophages, and natural killer cells (Aroor et al., Non-diabetic premenopausal women exhibit lower incidence of cardiovascular complications compared to age matched men. However, this protection is lost under the setting of obesity and T2D (Manrique et al., Although the mechanisms that contribute to vascular stiffness in obese premenopausal women are poorly understood, upregulation of RAAS signaling may be important in this regard (Aroor et al., Vascular stiffness is increased in conditions of insulin resistance and obesity and independently increases the risk of developing hypertension, coronary heart disease, and CVD morbidity and mortality. The underlying pathophysiology of vascular stiffness in insulin resistance and obesity involves activation of RAAS, adipocyte inflammation, abnormalities in vascular cells, ECM and maladaptive immune responses, all of which increase the risk of vascular stiffness associated CVD events Figure . Future The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Neglected tropical diseases (NTDs) affect more than 1,000,000,000 poor and marginalized people worldwide [An important element of targeted NTD intervention is the delivery of mass drug administration (MDA) for treating the five major \u201cpreventive chemotherapy\u201d NTDs, including lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), and trachoma . MDAs taInnovation to Application article, we describe the creation of an innovative NTD mapping tool (www.ntdmap.org) developed by a consortium of research and program partners for use particularly by program implementers. Its functionality and accessibility have been designed specifically to meet the needs of national programs and international partners. This tool provides an online resource allowing users to visualize and manipulate geographical data on a range of variables for the planning and managing of integrated NTD programs.In this Sharing data is challenging not only because of the complexity of the data themselves but also from the sheer volume of information. In an effort to meet these challenges, the NTD community has developed a range of resources that display epidemiological and treatment data in the form of maps . Data arWhile these disease-specific mapping projects are extremely helpful for visualizing predefined projects, they are of limited usefulness for integrated program planning, primarily because of the inability to customize maps through overlaying multiple variables highlighting cross-disease opportunities. These resources are also time-consuming to maintain, with data needing to be managed manually for each tool. In the rapidly changing NTD environment, the utility of maps erodes quickly with time. To become a useful operational resource, maps must be routinely updated. For NTDs, this need has been addressed in the development of an NTD mapping tool capable of integrating available epidemiological and programmatic NTD data into a single resource, which is both dynamic and easy to use.http://www.thiswormyworld.org/about/gahi-reports). Each platform was reviewed for content, quality, and functionalities offered. Results show that the main functionalities included were (i) ability to add different map layers, (ii) query the data underpinning each map, (iii) zoom and pan in the maps, and (iv) print and save maps.A first step in developing the tool was a stocktaking exercise of existing mapping platforms and an end-user survey to assess the needs of the tool\u2019s intended audiences. The exercise included a \u201cstate-of-the-art\u201d review of existing mapping applications, undertaken by independent consultants, Avia-GIS , provided high-level software expertise. The technical development of the tool included linking Structured Query Language (SQL) databases from multiple partners such as the Global Atlas of Helminth Infections (GAHI) [Finally, a series of meetings were held among partners in March, 2013. These meetings established the minimum criteria for the NTD mapping tool . To assis (GAHI) , Global s (GAHI) , Internas (GAHI) . These dhttp://www.thiswormyworld.org/training/modern-tools-for-ntd-control-programmes). Feedback received included the ability to adjust the order of layers, inclusion of administrative boundary layer, ability to query the source of data, and the ability to change the colors of layers. A second version of the tool was then released to selected partners on September 1, 2013 for additional feedback. The process of requesting feedback from both field managers and partner organizations ensured the usefulness of the tool to the broader NTD community. The completed tool was launched at the NTD Non-Governmental Development Organization (NGDO) Network (NNN) meeting in Brighton, United Kingdom, on September 19, 2013.A beta-version of the tool was piloted at an NTD training course in Nairobi in May 2013 for the different NTDs at the subnational level, whereas WHO typically reports coverage at the national level. Better understanding of the relationship between these two sources would be useful for filling knowledge gaps on treatment coverage. Third, the NTD Mapping Tool includes data on STH, schistosomiasis, and trachoma, as well as health district maps of access to improved water and sanitation. It is envisioned that in the future, data on LF and onchwww.thiswormyworld.org). Readers interested in the details of these data can consult this resource and contact this project.A second phase of development on this tool is underway. In the upcoming release, the technical features will be enhanced. This release will include an offline component where users with limited internet access can build their own maps. Users will also have the ability to input their own data into the offline maps, allowing the visualization of private data in the context of the publicly available data included in the tool. Future work will additionally investigate how best to make the data included in the tool available for download; at present, data on STH, schistosomiasis, LF, and Water Sanitation and Hygiene (WASH) can be downloaded from the Global Atlas of Helminth Infection (In conclusion, the NTD Mapping Tool provides an important new tool for the planning, implementation and evaluation of NTD control activities. The tool is simple and intuitive to use, with minimal requirements placed on the users. The development of the tool has brought together partners working on different NTDs and has involved extensive consultation with the global NTD community. Future roll-out of the tool will identify further needs which will guide subsequent revision. The experience of developing the NTD Mapping Tool provides a powerful example of how integrating data, expertise, and resources can provide new resources and tools to help improve decision making in, and implementation of, integrated health programs."} +{"text": "In 2008, the Global Health Research Initiative (GHRI) invited applications from teams of researchers and decision-makers who were interested in conducting research related to human resources for health and the implementation and use of integrated health information systems in Africa, with special attention to equity considerations. These thematic areas constituted the focus of the Africa Health Systems Initiative - Support to African Research Partnerships (AHSI-RES) program. GHRI is a partnership of three Canadian agencies: Foreign Affairs, Trade and Development Canada (DFATD), International Development Research Centre (IDRC), and the Canadian Institutes of Health Research (CIHR). It is hosted at IDRC.AHSI-RES is a five year, $5.9 million CDN research program (2008-2014) supported by Foreign Affairs, Trade and Development Canada ($5 million) and the International Development Research Centre ($900 000). AHSI-RES is the research component of the larger Africa Health Systems Initiative (AHSI) program. The AHSI program is a 10 year, $450 million CDN commitment (2006-2016) to strengthening national-level health strategies and architecture, and is being implemented by Foreign Affairs, Trade and Development Canada.The AHSI-RES program\u2019s purpose is to support policy relevant research, knowledge translation and exchange in the program\u2019s thematic areas. The AHSI-RES program emphasized the importance of ongoing interaction, collaboration, and exchange of ideas between researchers and decision-makers to maximize the likelihood that research findings would be used to inform programs and policies. A decision-maker was defined as \u2018an individual who makes decisions about, or influences, health policies or practices.\u2019IDRC program officers engage with grantees in framing research problems, improving research designs, and choosing methodologies. IDRC staff and funded researchers work as peers to contribute new ideas and theories, influence practice and policy, and strengthen research networks, bringing together grantees to share research results . This isTeams had to include one African researcher and one African decision-maker, both as co-principal applicants. The co-principal applicants had to be affiliated with an institution located in one of the AHSI-RES geographic areas of focus. Geographic areas of focus included: Francophone West Africa ; Great Lakes and Eastern Africa ; and, Southern Africa . Researchers and decision-makers affiliated with a non-African institution were eligible as co-applicants or collaborators, additional to the African co-principal applicants.Ten teams were selected from 57 proposals following a rigorous merit review process, where the review panel included international researchers and African decision-makers. Research teams that were successful in getting funding had to demonstrate: the ability to engage in interdisciplinary applied research to address complex policy-relevant questions related to the key themes of AHSI-RES; and, the ability to link research, policy, and action to improve health decision-making and programming. Gender, ethics, capacity development, and knowledge translation and exchange were cross-cutting themes that featured in AHSI-RES programming.Human Resources for Health. This supplement focuses on lessons learned from the uptake and impact of research for evidence-based practice.Research teams were based in: Burkina Faso, Mali, Kenya, Tanzania, Uganda, Malawi, and Zambia, and some involved Canadian researchers. Their research focused on two main areas: 1) the recruitment and retention of health workers and the shifting of certain services to less specialized health workers in response to a severe human resources crisis in the health sector in sub-Saharan Africa; and 2) the role of health information in ensuring greater equity in access to health care. The results of AHSI-RES research on the recruitment and retention of health workers is presented in a supplement to Health systems research can enrich the evidence base needed to inform the development and implementation of equity-oriented policies and interventions. The expected outcomes for AHSI-RES include: (i) improved and timely uptake of research evidence for health systems strengthening among decision makers in low- and middle-income countries; (ii) improved knowledge base for health systems strengthening that addresses the needs of vulnerable populations, focusing on priority global health issues in low- and middle-income countries; and (iii) strengthened individual and institutional capacity for doing and using research on health systems strengthening in low- and middle-income countries.. The research ranges from investigation into government policies to retain health workers in underserved areas, to the implementation and validation of health information systems in peri-urban and rural areas.The articles in this supplement present research results from Kenya, Malawi, Mali, Uganda, Tanzania, and ZambiaFindings from these research teams capture the complexity of challenges faced by decision-makers, health system managers, and health human resources in establishing, maintaining, and sustaining effective and functional health systems. The research serves to test, validate, and challenge policies at national and regional levels. Some of the policies and strategies incorporated in this supplement\u2019s research include, amongst others: Kenya\u2019s Community Health Strategy, Uganda\u2019s integrated Community Case Management (iCCM) strategy, as well as the World Health Organization and International Agency for Prevention of Blindness\u2019s program strategy for \u201cVISION 2020: The Right to Sight,\u201d a global initiative to eliminate avoidable blindness.For example, as described in the articles, the policy-relevant results and lessons learned include:\u2022 the Kenya Community Health Strategy is an effective approach to delivering community-based interventions: it can be successfully implemented and sustained in different socio-demographic contexts, with participatory community planning, based on household information, driving the improvement of health indicators. There were significant changes in essential maternal and newborn care practices such as antenatal care attendance and skilled deliveries because household members had been provided with the necessary information to make healthy decisions to be able to respond to maternal and neonatal health needs, based on evidence provided by the community based health information system .\u2022 a better understanding of the quality of eye care at primary health care facilities and influencing factors (e.g. staff turnover and absenteeism) in Kenya, Malawi and Tanzania, are urgently needed before continuing to invest resources in the scale up of the model of task shifting in Africa as it relates to VISION 2020: The Right to Sight, a global initiative to eliminate avoidable blindness. This study demonstrated the negative impact of the high turnover of primary health care workers and absenteeism in providing health services at the community level. This turnover and absenteeism also affects the integrity of research on interventions designed to improve health services .\u2022 in Uganda, specific iCCM training and support to a selected segment of community health workers (CHWs) within larger CHW village teams unexpectedly and negatively impacts \u2018basic\u2019 CHWs\u2019 work motivation, but not necessarily team functioning. The Ugandan Ministry of Health\u2019s national strategy calls for the employment of volunteer CHWs for the implementation of iCCM of common illnesses affecting children under five years of age. The researchers recommend that CHW programmers should consider minimizing segregation when introducing new program opportunities through providing equal opportunities to participate and receive incentives, while seeking means to improve communication, CHW solidarity, and motivation .The 10 teams supported by the AHSI-RES program worked to connect research with policy and action to improve health decision-making and programming in the sub-Saharan region, paying particular attention to the needs of disadvantaged segments of the population. Grantees benefited from opportunities to strengthen individual and institutional capacity for doing and using research on health systems strengthening. Research teams also benefitted from linking with African decision-makers to make the research collaborative and responsive, enhancing the likelihood of research uptake to inform current and future policies.Adrijana Corluka and Ren\u00e9e Larocque serve as Senior Program Officers, Marc Cohen serves as Program Officer, and Esm\u00e9 Lanktree serves as Program Management Officer, with the Global Health Research Initiative. The Global Health Research Initiative supported the assembly and publication of this supplement. The views expressed in this introductory article are those of the authors alone and do not represent the views of the Global Health Research Initiative, the International Development Centre, the Canadian Institutes of Health Research, nor Foreign Affairs, Trade and Development Canada."} +{"text": "Tobacco use in India is characterized by a high prevalence of smoking and smokeless tobacco use, with dual use also contributing a noticeable proportion. In the context of such a high burden of tobacco use, this study examines the regional variations, and socioeconomic, demographic and other correlates of smoking, smokeless tobacco and dual use of tobacco in India.We analyzed a cross sectional, nationally representative sample of individuals from the Global Adult Tobacco Survey in India (2009\u201310), which covered 69,296 individuals aged 15 years and above. The current tobacco use in three forms, namely, smoking only, smokeless tobacco use only, and both smoking and smokeless tobacco use were considered as outcomes in this study. Descriptive statistics, cross tabulations and multinomial logistic regression analysis were adopted as analytical tools. Smokeless tobacco use was the major form of tobacco use in India followed by smoking and dual tobacco use. Tobacco use was higher among males, the less educated, the poor, and the rural population in India. Respondents lacking knowledge of health hazards of tobacco had higher prevalence of tobacco use in each form. The prevalence of different forms of tobacco use varies significantly by states. The prevalence of tobacco use increases concomitantly with age among females. Middle-aged adult males had higher prevalence of tobacco use. Age, education and region were found to be significant determinants of all forms of tobacco use. Adults from the poor household had significantly higher risk of consuming smokeless tobacco. Lack of awareness about the selected hazards of tobacco significantly affects tobacco use.There is an urgent need to curb the use of tobacco among the sub-groups of population with higher prevalence. Tobacco control policies in India should adopt a targeted, population-based approach to control and reduce tobacco consumption in the country. Smokeless tobacco use consists of chewing pan , chewing gutkha or pan masala , and mishri (a kind of toothpaste used for rubbing on gums). India has one of the highest tobacco users in the world both in number and relative share. India is one of the fewer countries in the world where prevalence of smoking and smokeless tobacco use are high and is characterised by dual use of tobacco (use of both smoking and smokeless tobacco products) also contributes to a noticeable proportion. Using data from the National Family Health Survey second round , prevalence of tobacco use in India was estimated to be 37 percent among the population of 15 years and above Tobacco is used in India in many forms. Smoking of cigarettes and nd round of the NSS on Morbidity and Private Health Expenditure, conducted between June 1995 and June 1996 by the National Sample Survey Organization (NSSO) of the Government of India, collected information on current regular smoking and chewing of tobacco for all individuals aged 10 years and above. The survey estimated tobacco use prevalence among males to be at 51.3% and among females at 10.3% Establishment of effective tobacco control policies depends on precisely assessing the enormity of tobacco use in the country. Several national level studies have collected information on tobacco use to evaluate the prevalence of tobacco use. Tobacco use is a part of the consumer behaviour component of the National Sample Survey (NSS), held every five years All these studies were mostly limited to collecting some data on tobacco use as a component of health-based surveys. However, there was a lack of a large scale survey with comprehensive data on tobacco use among adults in India. Most of the past research work on tobacco was either based on localized studies with an urban bias or based on non-representative sample surveys with socio-demographic predictors of tobacco related behaviour mostly inadequately understood. These works were frequently limited to specific focus group in terms of their tobacco habit.The recent two rounds of the Global Youth Tobacco Survey were specially designed to collect tobacco related information, although for a very specific age group. The Global Adult Tobacco Survey (GATS) is a standardized household survey that enables countries to compile data on key tobacco indicators and assist states in the formulation, tracking and execution of effective tobacco control interventions and international comparisons as laid out in the MPOWER policy package of the WHO This study is based on the secondary analysis of the Global Adult Tobacco Survey India (GATS-India) 2009\u201310 data. This survey data was released for the general researchers by International Institute for Population Sciences. Global Adult Tobacco Survey is the global standard for systematically monitoring adult tobacco use (smoking and smokeless) and tracking key tobacco control indicators. GATS-India is conducted globally in around 14 countries. The Centers for Disease Control and Prevention (CDC), CDC Foundation, Johns Hopkins Bloomberg School of Public Health (JHSPH), Research Triangle Institute International , the World Health Organization and many countries throughout the world worked together to design and implement GATS. For each participating country, a standard protocol with respect to questionnaire, sample design, data collection and management procedures was used. Survey information was collected using handheld devices. The Ministry of Health and Family Welfare, Government of India, designated the International Institute for Population Sciences, as the nodal agency for conducting GATS Survey in India. The main objectives of the GATS India Survey were to measure the impact of tobacco control efforts through implementation of different provisions of COTPA 2003 and its regulations and to systematically monitor adult tobacco use and track key tobacco control indicators. Further information regarding the guidelines followed to collect the data is available in the GATS-India report GATS-India (2009\u201310) is a nationally representative household survey covering population aged 15 years and above, covering all the 29 states and 2 Union Territories (UTs) in India. Multistage sampling procedure was adopted independently in each state, and within the states, independently in urban and rural areas to select the sample. In the urban areas, three-stage sampling was adopted for the selection of households. At the first stage, a list of wards from all cities and towns of the state/UT formed the urban sampling frame from which a required sample of wards, i.e., primary sampling units (PSUs), was selected using probability proportional to size (PPS) sampling. At the second stage, a list of census enumeration blocks (CEBs) in every selected ward formed the sampling frame from which one CEB was selected by PPS from each selected ward. At the third stage, a list of all the residential households in each selected CEB formed the sampling frame from which a sample of the required number of households was selected. In the rural areas, two-stage sampling was adopted for the selection of households. The PSUs were villages selected using the PPS sampling method. At the second stage, a list of all the residential households in each selected village formed the sampling frame from which a sample of the required number of households was selected. From each eligible household, one respondent was selected.beedis, cigarettes, cigars, cheroots, rolled cigarettes, tobacco rolled in maize leaf and newspaper, hookah, pipes, chillum, and chutta. Smokeless tobacco included tobacco leaf, betel quid with tobacco, sada/surti, khaini or tobacco lime mixture, gutkha, pan masala with zarda, gul, gudaku, and mishri. Final sample included in the analysis were all the 69,296 respondents Complete data is available for 69,296 adult respondents age 15 and above, of which 33,767 and 35,529 were males and females respectively. The survey covered domains like tobacco use (smoking and smokeless tobacco), exposure to second hand smoke, cessation, economics of tobacco, exposure to media messages on tobacco use, and knowledge, attitudes and perceptions towards tobacco use. The survey was designed to provide estimates of the tobacco prevalence at the national and the state levels, and by certain specific background characteristics. Data for tobacco use was collected from the eligible respondents aged 15 years and above. The respondents were asked about their daily and occasional use of tobacco. Smoking tobacco included The main dependant variable in the analysis is the tobacco use categorized into four types, namely, smoking only, smokeless tobacco use only, dual use of tobacco (both smoking and smokeless tobacco use) and non-user of tobacco.The state level variations in type of tobacco use were assessed for the 29 states and 2 UTs of India. The relationship of age with use of tobacco in three forms was assessed by classifying age into age groups of five years. For the further analysis, independent variables used were age (four categories), sex , residence , education (four categories), occupation (four categories), region (six categories), knowledge that exposure to smoking causes heart attack, stroke and lung cancer (Yes/No), smokeless tobacco causes serious illness (Yes/No), and household asset scores (three categories). Six geographical regions, covering 29 states and 2 UTs, were included in the analysis. Included in the North were the states of Jammu & Kashmir, Himachal Pradesh, Punjab, Chandigarh, Uttarakhand, Haryana and Delhi; in the Central region, Rajasthan, Uttar Pradesh, Chhattisgarh and Madhya Pradesh were included; the East included West Bengal, Jharkhand, Odisha and Bihar; the North-east included Sikkim, Arunachal Pradesh, Nagaland, Manipur, Mizoram, Tripura, Meghalaya and Assam; in the West were included Gujarat, Maharashtra and Goa; and finally Andhra Pradesh, Karnataka, Kerala, Tamil Nadu and Puducherry were included in the South region. The household economic status was assessed using the household assets information provided. Since the information of assets was quite limited in nature, the scores of 10 household assets were summed up to give a final score between 0 and 10. These scores were divided into three parts based on their distribution, and households were categorised as poor, moderate and rich.The prevalence of tobacco use for each type namely, smoking only, smokeless tobacco use only, and dual use of tobacco (both smoking and smokeless tobacco use) is defined as the number of persons consuming tobacco in this manner per 100 adult persons 15 years and above. Bivariate analysis was used to estimate the prevalence of tobacco use in three forms by background characteristics. The state level variations in type of tobacco use were assessed by simple bivariate analysis in 29 states and 2 UTs of India. The relationship of age with use of tobacco was assessed by classifying age into age groups of five years. Further prevalence of tobacco use was analysed according to the background characteristics described in the earlier section. Both point estimates and robust 95% confidence intervals were given based on robust standard errors adjusting for strata and clustering at PSU. Multinomial logistic regression is used to estimate and assess the adjusted associations respectively of different socioeconomic, demographic and knowledge related characteristics. Multinomial logistic regression analysis was used to analyze the four outcomes-smoking only, smokeless tobacco use only, dual use of tobacco and non user in a single model. In multinomial regression each outcome is modelled relative to baseline outcome group: non-user of tobacco (in this study). Therefore, relative risk ratios (RRR) are reported rather than risk ratio or odds ratio. The RRR and their 95% confidence intervals were provided in the tables. Models are used after applying the sampling weights and adjusting for multistage sampling designs using svy command in STATA. STATA 11.0 was used to carry out the statistical analysis.GATS-India data provides an ample opportunity to study the tobacco use behaviour in the form of smoking, smokeless tobacco and dual use of tobacco among adults in India. Understanding the type of tobacco use behaviour has important health implications. The estimates of the tobacco use provided by GATS are considered to be reliable and representative enough as the survey was designed to provide only tobacco use indicators in India. The other studies suffer from the most important limitation that they were not designed to collect information on tobacco use. Surrogate responses were used which often produced bias and inaccuracies in the results Tobacco consumption among females was mostly in the form of smokeless tobacco, while that among males was distributed among the three types of uses. Tobacco use in India has been higher among males than among females in India. However, the male-female gap was lower in the case of use of smokeless tobacco. The use of smokeless tobacco was equally high among middle-aged and elderly males and females. This indicates that adult females in India were as vulnerable as males, and at a high risk of using smokeless tobacco, especially in the higher age groups. With an increase in age, the odds of using tobacco significantly increase in India. Elderly and middle-aged females had significantly higher odds of consuming every type of tobacco. Smoking and dual use of tobacco among males were more common in the younger and middle-aged adults. Age has been found to be an important determinant of tobacco use in earlier studies Tobacco use in India varies significantly by states and regions. A comparison of state-wise figures for smoking and smokeless tobacco use among adults aged 15 years and above, provided by another research study for India, beedis per day. Such figures were much higher for the uneducated and the male population Tobacco use in India is clearly a big burden in terms of its magnitude and use in different forms. There is also a need to check the dual use of tobacco in India. Dual users are at much higher health risks than those who consume the individual tobacco product. The higher prevalence of tobacco use among males, the uneducated and the poor is a matter of concern as these people even lack resources to combat the morbidity associated with tobacco use. At a time when India is experiencing a major mortality and epidemiological transition, these subgroups are likely to suffer more from the dual burden of communicable and non-communicable diseases. In addition to the differences in the prevalence of tobacco consumption between disadvantaged and better off groups, the type and amount of tobacco consumption, and its dependency may also vary between these groups, further aggravating the differences in the disease burden attributable to tobacco. GATS report shows that more than 60 percent tobacco users consume first tobacco of the day within half an hour of waking up. An ample proportion of daily smoker consumes more than 10 cigarettes or"} +{"text": "Journal of Hematology & Oncology is pleased to see the exponential growth in the number of publications from China, especially in hematology and oncology. This editorial calls for putting more weight on the quality of the future scientific output and invites rigorous dialogs among policy makers, granting agencies, academic leaders, physicians, and scientists, followed by concrete actions, to achieve such a goal. The number of scientific publications from China has exploded in the past 10 years. Multiple factors have propelled this exponential growth. Among these factors include but are not limited to a large scientific research base, increases in government funding through Natural Science Foundation of China, acute upholding of the publish-or-perish mantra, monetary reward for publications from local institutions, institutional requirement for publications in quality journals for awarding doctoral degrees, and faculty promotions. Dr. An-mei Deng\u2019s group from Shanghai performed a detailed and focused analysis of hematology research output from China in the past 10 years [China has succeeded in quantitative promotion of scientific research . The nex"} +{"text": "The development of multidrug resistance (MDR) in an increasing number of pathogens, including Pseudomonas, Acinetobacter, Klebsiella, Salmonella, Burkholderia, and other Gram-negative bacteria is a serious issue. Membrane efflux pump complexes of the Resistance-Nodulation-Division (RND) superfamily play a key role in the development of MDR in these bacteria. These pumps, together with other transporters, contribute to intrinsic and acquired resistance of bacteria toward most, if not all, of the compounds available in our antimicrobial arsenal. Given the enormous drug polyspecificity of MDR efflux pumps, studies on their mechanism of action are extremely challenging, and this has negatively impacted both on the development of new antibiotics that are able to evade these efflux pumps and on the design of pump inhibitors. The collection of articles in this eBook, published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy, aims to update the reader about the latest advances on the structure and function of RND efflux transporters, their roles in the overall multidrug resistance phenotype of Gram-negative pathogens, and on the strategies to inhibit their activities.The discovery of antibiotics represented a key milestone in the history of medicine. However, with the rise of these life-saving drugs came the awareness that bacteria deploy defense mechanisms to resist these antibiotics, and they are good at it. Today, we appear at a crossroads between discovery of new potent drugs and omni-resistant superbugs. Moreover, the misuse of antibiotics in different industries has increased the rate of resistance development by providing permanent selective pressure and, subsequently, enrichment of multidrug resistant pathogens. As a result, antimicrobial resistance has now become an urgent threat to public health worldwide focus on the outer membrane channel OprM of Pseudomonas aeruginosa, investigating the presence of N-terminal modifications. They present a new X-ray structure solved in a new space group, making it possible to model the N-terminal residue of OprM as a palmitoylated cysteine.RND transporters reside in the inner membrane, and in Gram-negative bacteria they form trans-envelope complexes together with periplasmic membrane fusion proteins (MFPs) and outer membrane factors (OMFs). As tripartite entities, these macromolecular complexes are powerful machines that expel multiple antibiotics across outer membranes. In recent years, much of the research efforts have been focused on the structures of the RND, MFP, and the OMF components. The assembly and disassembly of the tripartite efflux pump components is so crucial to their physiological role in resistance, that much research effort has been directed toward both the elucidation of the structures and functional dynamics of individual components and the Wang et al. use AcrAB-TolC of Escherichia coli as model to explore the mechanism of function recovery of the AcrBP223G variant, which compromises AcrB trimerization and drastically reduces the drug efflux activity. Their study highlights how modulation of several critical factors can lead to the proper functioning of the pump. Zgurskaya et al. further analyze how the reaction cycles of transporters are coupled to the assembly of the trans-envelope complexes. Using a combination of biochemical, genetic and biophysical approaches, the authors reconstruct the sequence of events leading to the assembly of transenvelope drug efflux complexes, and characterize the roles of periplasmic and outer membrane proteins in this process. In particular, they propose that OMF recruitment is triggered by binding of effectors (substrates) to MFP or MFP-RND complexes. Bavro and co-workers investigate in detail the architecture and roles of periplasmic adaptor proteins in tripartite efflux pump assemblies . They stress how recognition between the MFPs and OMFs is essential for pump assembly and function, and how targeting this interaction may provide a novel avenue for combating RND pump-mediated multidrug resistance. Picard and co-workers design a new test permitting investigation of the assembly of the MexAB-OprM efflux system of P. aeruginosa with only tens of microgram of protein . The method relies on the streptavidin-mediated pull-down of OprM proteoliposomes upon interaction with MexAB proteoliposomes containing biotinylated lipids. Their study gives clear evidence for the importance of MexA in promoting and stabilizing the assembly of the MexAB-OprM complex and the role of the proton motive force on the assembly and disassembly of the efflux pump.Several factors are critical for the proper function of the tripartite system: drug binding, interaction with MFPs and OMFs, proton relay through the transmembrane domain, and trimerization of the transporter. Regarding the latter process, in vitro work makes sense without an understanding of the occurrence, regulation, and interdependence of the efflux pumps in a physiological setting. Martins and co-workers summarize the current knowledge on RND efflux mechanisms in E. coli, a bacterium responsible for community and hospital-acquired infections, as well as foodborne outbreaks worldwide . They review the knowledge on Acriflavine (Acr), Multidrug Transport (Mdt), and Copper transporting (Cus) efflux systems. Chen and collaborators use clinical Salmonella typhimurium isolates to demonstrate how acquisition of the plasmid-mediated quinolone resistance (PMQR) genes oqxAB and aac(6\u2032)Ib-cr accelerates the development of fluoroquinolone resistance in this bacterium . Their analysis reveals that oqxAB and aac(6\u2032)Ib-cr are encoded on plasmids of various sizes and mediate resistance to ciprofloxacin, ultimately facilitating the selection of ciprofloxacin-resistant S. typhimurium. In their Perspective, Paulsen and collaborators summarize the current knowledge on the Acinetobacter chlorhexidine efflux (AceI) pump, a prototype for a novel family of multidrug efflux pumps conserved in many proteobacterial lineages . The discovery of this family raises the possibility that additional undiscovered intrinsic resistance proteins may be encoded in the core genomes of pathogenic bacteria.Little of the Morita and co-workers identify a novel MexS variant involved in up-regulation of the mexEF-oprN multidrug efflux operon in a clinical isolate of P. aeruginosa displaying multi-drug efflux-mediated resistance to fluoroquinolones, aminoglycosides, and most \u03b2-lactams. Their study constitutes the first genetic evidence that a MexS variant causes mexEF-oprN upregulation in P. aeruginosa clinical isolates. If the road toward understanding of efflux-mediated multi-drug resistance in E. coli, Acinetobacter baumannii and P. aeruginosa is rough, the characterization of efflux pumps in many other prominent pathogens, e.g., the members of the genus Burkholderia, lags even further behind. As in other non-enteric Gram-negatives, efflux pumps of the resistance nodulation cell division (RND) family are the clinically the most significant efflux systems in this genus. Schweizer and co-workers provide an excellent review of the current knowledge about efflux mechanisms in several Burkholderia species .Among the mechanisms that are not fully understood is the genetic regulation of efflux pumps. Venter et al. describe how available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse antimicrobial resistance in Gram-negative pathogens. Opperman and Nguyen analyze in detail the reasons why no compounds have yet progressed into clinical use. One of the major hurdles in the development of EPIs has been the lack of biochemical, computational, and structural methods that could be used to guide rational drug design. The authors review recent reports that have advanced our understanding of the mechanisms of action of several potent EPIs active against RND-type pumps.Last but not least, inhibition of efflux pumps is one of the current strategies being pursued by several groups attempting to reduce the impact of efflux on antimicrobial resistance. Efflux pump inhibitors (EPIs) could be used as adjunctive therapies that would increase the potency of existing antibiotics and decrease the emergence of multidrug-resistant bacteria. In their review, In summary, the articles in this research topic serve as a background to the search for a deeper understanding of the mechanisms by which RND efflux pumps limit the concentration of antimicrobial compounds inside the bacterial cell. This knowledge may in turn pave the way for new, more directed inhibitor and antibiotic design to ultimately overcome antimicrobial resistance in Gram-negative pathogens.All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.www.translocation.eu) and has received support from the Innovative Medicines Initiative Joint Undertaking under Grant 115525, resources that are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies. Work in the lab of KP on multidrug efflux is funded by the Canadian Institutes of Health Research and Cystic Fibrosis Canada.The research of AVV and KMP was conducted as part of the Translocation Consortium (The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Although D&I models identify several potential facilitators and barriers to adoption of evidence-based practices, the contextual characteristics that determine the relative importance of these factors remain largely unknown. The objectives of this study were to identify the most significant facilitators and barriers to innovation and adoption of EBPs as determined by agency and program directors; explore whether facilitators and barriers identified are associated with agency role and pace of adoption; and explore whether consensus on barriers is associated with pace of adoption.Semi-structured interviews were conducted with agency and program directors of 36 New York State-supported mental health clinics. Agencies were classified based on level of participation in different implementation activities ranging from no engagement to participation in a webinar, in-person training, or learning collaboratives. Data were analyzed using grounded theory analytic methods. Intra-organizational consensus was defined as the number of barriers identified by both types of directors divided by the total number of unique barriers.Three interconnected themes relating to barriers and facilitators were identified: costs associated with adoption, capacity for adoption, and acceptability of new practices. Agency directors were more concerned about financial and organizational capacity, and client buy-in and fit, while program directors were more concerned about time for training and staff buy-in. Concerns about cost, time for training, client buy-in, and organizational capacity were inversely associated and concern about reimbursement was positively associated with pace of adoption. Agency consensus on barriers and facilitators was associated with pace of innovation.Organizations assess EBPs and other innovations in terms of costs, capacity and acceptability. This assessment varies by role within an organization and by an organization's level of engagement in implementation activities. Consensus within an organization as to specific facilitators and barriers is a potential predictor of EBP adoption and implementation.NIH-NIMH P30 MH090322."} +{"text": "Physical activity is a vital component of good health, and it also helps reduce the severity of many chronic conditions . CurrentAlthough the study lacked conclusive evidence regarding the effect of medical school education and counselling knowledge/skill , it is a plausible assumption that doctors, having been taught how to prescribe exercise, would in turn counsel their patients effectively.However, the article does not consider other factors, in addition to medical school education, which can have an impact on physical activity counselling by healthcare professionals.One such factor is patient compliance. Justine et al. showed tIn addition, the lack of public facilities and initiatives to encourage people to exercise can also limit the amount of physical activity undertaken. From a different perspective, the organisation of the healthcare system of a country may impact the effectiveness of physical activity counselling on patients. For instance, in the United Kingdom, general practitioners (GPs) are the primary point of contact for many chronic conditions, and so educating all GPs about the effects of physical activity could have a greater impact on general health in a nation.These wider factors lie outside the remit of counselling from the clinician and therefore the actual clinical outcomes from educating medical students regarding physical activity counselling remains unknown.In conclusion, educating medical students about the importance of physical activity is an important aspect of the medical curricula, which is being omitted in many universities across the world. However, other factors need to be considered when assessing the clinical benefit of physical activity counselling.Shaan Rashid Imperial College London School of Medicine London, UK Email: sr3011@ic.ac.ukOmer A. Jamall Imperial College London School of Medicine London, UKSheeraz Iqbal Imperial College London School of Medicine London, UKAbeer F. Rizvi Imperial College London School of Medicine London, UKOsman Nayeem Imperial College London School of Medicine London, UKA. M. Hameed Khan Imperial College London School of Medicine London, UK"} +{"text": "Packenham, Director of the National Institute of Environmental Health Sciences (NIEHS) Office of Human Research Compliance, Clinical Research Program (CRP) and Vice-Chair of the NIEHS Institutional Review Board (IRB); Jane M. Lambert, NIEHS CRP IRB Administrator; and Craig Wladyka, NIEHS, CRP, IRB Protocol Coordinator, for their roles in the review and oversight of the GuLF STUDY. The comments they made during the review process were incorporated into the study protocol and consent documents and played an important role in ensuring ethical and regulatory oversight of the study.The authors regret this omission."} +{"text": "Escherichia coli, due to the reliability of the host and the ease of protein (over) production, in particular many enzymes, in a compatible host background. Consequently, coliphages such as T4 and lambda served as model phages in the development of molecular tools and the fundamental understanding of phage-host interactions. The advent of new generation sequencing technologies has in recent years provided a vast array of sequence data relating to Gram-positive phages and their hosts, which in turn has permitted the development of analogies between Gram-negative and Gram-positive phages. For example, sequence analysis of Bacillus subtilis and Lactococcus lactis phages SPP1 and Tuc2009, respectively, revealed genomes with a conserved gene and/or functional order relative to lambda, the main model for Siphoviridae phages. While the Gram-negative models have been extremely useful platforms, many questions have remained unanswered owing to the fundamental structural and compositional differences between the cell walls of Gram-negative and positive cells. In response to this knowledge gap, there has been a significant upsurge in research in the area of phages infecting Gram-positive bacteria and in particular, lactococcal phage-host interactions, which have now become one of the leading model systems along with the above-mentioned Bacillus subtilis phage SPP1 and the mycobacteriophage L5.Bacteriophage research has seen many peaks and troughs over the past century ascending with phage therapy and application in the early 1900's; a research peak which was largely overshadowed by the dawning of the antibiotic era, and which has now deservedly regained attention as an approach against the problematic rise in antibiotic-resistant pathogenic bacteria. Following this initial scientific highlight, the advent of molecular biology and biotechnology sparked a renewed interest in phages and their encoded enzymes and promoters, which are still employed as research tools today. Much of this research was conducted using phages of Gram-negative bacteria, particularly Leuconostoc, Oenococcus and Weissella (Kot et al., Listeria and Clostridium spp. (Hagens and Loessner, In the ensuing 11 articles, many key advances that now define our understanding of phage-host interactions of Gram-positive bacteria and their infecting phages are described. We collate these advances and define the current knowledge of cell wall structures that present the target molecule of phage attachment (Munsch-Alatossava and Alatossava, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The study of the microbial communities in the built environment is of critical importance as humans spend the majority of their time indoors. While the microorganisms in living spaces, especially those in the air, can impact health and well-being, little is known of their identity and the processes that determine their assembly. We investigated the source-sink relationships of airborne bacteria in 29 homes in the San Francisco Bay Area. Samples taken in the sites expected to be source habitats for indoor air microbes were analyzed by 16S rRNA-based pyrosequencing and quantitative PCR. The community composition was related to the characteristics of the household collected at the time of sampling, including the number of residents and pets, activity levels, frequency of cooking and vacuum cleaning, extent of natural ventilation, and abundance and type of vegetation surrounding the building.Diaphorobacter sp., Propionibacterium sp., Sphingomonas sp., and Alicyclobacillus sp. Source-sink analysis suggested that outdoor air was the primary source of indoor air microbes in most homes. Bacterial phylogenetic diversity and relative abundance in indoor air did not differ statistically from that in outdoor air. Moreover, the abundance of bacteria in outdoor air was positively correlated with that in indoor air, as would be expected if outdoor air was the main contributor to the bacterial community in indoor bioaerosols. The number of residents, presence of pets, and local tap water also influenced the diversity and size of indoor air microbes. The bacterial load in air increased with the number of residents, activity, and frequency of natural ventilation, and the proportion of bacteria putatively derived from skin increased with the number of residents. Vacuum cleaning increased the signature of pet- and floor-derived bacteria in indoor air, while the frequency of natural ventilation decreased the relative abundance of tap water-derived microorganisms in air.Indoor air harbored a diverse bacterial community dominated by Indoor air in residences harbors a diverse bacterial community originating from both outdoor and indoor sources and is strongly influenced by household characteristics.The online version of this article (doi:10.1186/s40168-015-0128-z) contains supplementary material, which is available to authorized users. The study of the indoor microbiome is of critical importance since humans spend the majority of their time indoors and thus regularly encounter microbes in this habitat. Microbes, including those present in indoor spaces, impact human health and well-being , 2. Whil3 of air a day . All additional files supporting the results of this article are included within the article and its additional files."} +{"text": "The Organizational Process Improvement Intervention (OPII), conducted by the NIDA-funded Criminal Justice Drug Abuse Treatment Studies consortium of nine research centers, examined an organizational intervention to improve the processes used in correctional settings to assess substance abusing offenders, develop case plans, transfer this information to community-based treatment agencies, and monitor the services provided by these community based treatment agencies.A multi-site cluster randomized design was used to evaluate an inter-agency organizational process improvement intervention among dyads of correctional agencies and community based treatment agencies. Linked correctional and community based agencies were clustered among nine (9) research centers and randomly assigned to an early or delayed intervention condition. Participants included administrators, managers, and line staff from the participating agencies; some participants served on interagency change teams while other participants performed agency tasks related to offender services. A manualized organizational intervention that includes the use of external organizational coaches was applied to create and support interagency change teams that proceeded through a four-step process over a planned intervention period of 12 months. The primary outcome of the process improvement intervention was to improve processes associated with the assessment, case planning, service referral and service provision processes within the linked organizations.Providing substance abuse offenders with coordinated treatment and access to community-based services is critical to reducing offender recidivism. Results from this study protocol will provide new and critical information on strategies and processes that improve the assessment and case planning for such offenders as they transition between correctional and community based systems and settings. Further, this study extends current knowledge of and methods for, the study of evidence-based practice adoption and implementation.The online version of this article (doi:10.1186/2194-7899-2-1) contains supplementary material, which is available to authorized users. Screening and assessment are clinical processes used to detect and then determine the extent, pervasiveness, or severity of presenting problems or issues by patients in a variety of health and other service settings. For individuals engaged in criminal justice or correctional systems, these screening and assessment processes should identify and evaluate criminogenic risks, including mental health and drug abuse problems, in order to tailor correctional supervision and rehabilitative services to those who need them that include individuals in staff and managerial positions from correctional and community treatment agencies. The objectives of this study are threefold: (1) improve the quality of the assessment and case planning processes of correctional-based agencies; (2) assess the effectiveness of an externally facilitated, interagency change team process in implementing targeted process improvements; and (3) evaluate the impacts and determinants of this change process upon staff behavior, attitudes, and quality of assessment and case planning processes.The social significance of this study lies in its context within criminal justice systems and its focus on the processes of offender assessment and case referral, an interagency juncture long recognized to be faulty and ill-devised from implementation strategies (those activities delivered to organizations and providers delivering the intervention strategy) while NIATx involves a single agency.The implementation strategy of the OPII is similar to the NIATx model that uses a change team and coach to bring about process improvements in behavioral health settings . The individual designated for this position was expected to have direct line communications to the chief executive officer of the corrections partner agency in which the OPII was being conducted. The LCTL served as the communication and decision-making pipeline with the corrections agency CEO and facilitated logistical and operational change processes identified by the LCT.The facilitator was an individual who worked with the LCT throughout the organizational improvement process. Each research center, in cooperation with the relevant correctional agency partner, selected facilitators who were under the employ of the RC. In general, facilitators had previously worked directly with agency providers in some capacity and possessed credentials and experience that provided credibility with the LCT.Facilitators helped LCTs stay on track and on task as they engaged in a structured, five-phase model of assessing and improving the quality of their interagency assessment and case planning mechanisms within correctional and community treatment systems. The five structured phases of the OPII and the planned duration of each phase were as follows: (1) Team Development (1\u20132 months); (2) Needs Assessment (3\u20134 months); (3) Process Improvement Planning (3\u20134 months); (4) Implementation (6 months); and (5) Follow-Up/Sustainability (6 months).During the Needs Assessment phase, the LCT engaged in a variety of information gathering and group decision-making techniques to critically examine and prioritize gaps or capacities in four core quality dimensions of their shared assessment and case planning processes: 1) Was the correctional agency using evidence-based and validated means for assessing the needs of offenders? (2) Were these needs identified and prioritized in the resulting case plans developed by the correctional agency? (3) Did the correctional agency share this assessment and case plan information with their referring community-based treatment providers, and did the providers find this information useful? (4) Did the community based agency provide services that addressed the needs of the offenders? The LCT, with assistance provided by the facilitator, used information gathered during the Needs Assessment to identify improvement goals, created a Process Improvement Plan (PIP), and carried out the implementation activities they had set out for themselves participated in this study, with each RC comprised of correctional/criminal justice (CJ) agencies, community-based treatment agencies, and researchers. The role of each RC in the OPII study was to create and participate in the implementation strategy and to participate in workgroups that addressed issues such as implementation, data collection and quality, analysis, and publication. Resources and incentives provided by the research centers to the CJ and community providers varied across centers, but included opportunity and nominal funding for education (continuing education units), improvements in delivery of services, and development of an implementation process that could be used after the research was completed.Evaluation of the OPII used a multi-site cluster randomized design. Organizational clusters consisted of linked correctional and one or more community-based substance abuse treatment agencies providing correctional and substance abuse treatment services to common clients. Nine research centers contributed at least two clusters both of which were located within the same state. In this design, one cluster was randomly assigned to an early start condition, and the other cluster was assigned to a delayed start condition introduce a design effect that must be estimated for sample size determinations and incorporated into analyses of study data of the participating correctional settings served adults, but two of them served juveniles. There are 10 sites (clusters) in each study condition, for a total of 21 study sites.The outcomes of primary interest were those related to change in the intervention being provided to offenders, namely, assessment and case planning processes. Measures of intervention outcomes included congruence between assessed needs and case plan recommendations, quality of the content of the case plan, conveyance of case plans to community treatment providers, and cross-organizational coordination.Also of interest were the implementation outcomes of the facilitated change intervention process itself, which are related to fidelity and acceptability of the activities of the OPII. It was hypothesized that success in achieving process improvement goals, with regard to the assessment and case planning process, were dependent upon commitment to the intervention by members of the LCT, satisfaction with the facilitation, executive management support, interagency collaboration, and the quality and intensity of facilitation.Quantitative data collected for this study included structured ratings of correctional agency offender case plans and surveys of members of the LCT and other organizational staff in the participating agencies.The Assessment and Recommendations for Treatment Rating Form (ART/RF) provided ratings of four quality dimensions of the case plans. These dimensions included: (1) Measurement (the problem or service needs assessed by a given agency); (2) Integration with the Case Plan (the degree to which the case plan targets needs identified); (3) Conveyance (evidence that the case plan was shared with the community based treatment provider); and (4) Services Activation (evidence that the community-based treatment provider delivered services in accordance with the needs identified in the case plan). Case plan ratings were collected before the start of the intervention (baseline), during the intervention , and during the Sustainability/Follow-up phase. In each period, research staff randomly selected five case plans per month from agency records and rated them using the ART-RF. Case plans from the Delayed-Start sites were rated during the same period of time as for the Early-Start sites. Composite scores for each of the four quality dimensions were calculated for the five cases sampled each month, generating four ratings per month.The Baseline Survey of Organizational Characteristics (BSOC) describes the organizational characteristics, climate, and culture of the participating sites across the three CJDATS studies . The BSOC was adapted from previously developed and validated instrumentation, including the TCU Survey of Organizational Functioning (TCU-SOF) of the participating agencies were conducted periodically throughout the OPII intervention, specifically at the end of the Process Improvement Planning Phases, the end of the Implementation Phase and at the end of the Sustainability/Follow-Up Phase. Respondent interviews were valuable to understand and clarify the experiences, motivations, and underlying attitudes of participants involved in change projects Tracy . The intInterviews were conducted by members of each research center, either in person or over the phone. Interviews were audio recorded, transcribed, fact-checked, stripped of identifying information, and then analyzed using a multi-part group and individual coding process.The level of congruence between transitional offender assessments and case plans.The level of presence of accepted principles of case plan development in case plans.The percentage of case plans forwarded from correctional agencies to community treatment programs.The level of the use of case plans by community-based substance abuse treatment programs.Staff perceptions of the assessment-case planning process.The primary hypotheses of the study are that enhancements or improvements in each of the following outcomes occur only after the introduction of a specific and structured process improvement initiative (OPII):The degree to which LCTs exhibit fidelity to the designated elements of OPII.The degree of commitment by LCT members to achieving the goals of the plan.The level of staff satisfaction with the implementation strategy.The degree of management support within the organization for the intervention.The strength of the working alliance between the facilitator and the LCT.Secondary hypotheses are concerned with factors affecting the degree of success that LCTs experienced in achieving the goals they established for themselves. LCTs\u2019 success in achieving the goals for their Process Improvement Plans (PIP) were expected to be positively related to:The implementation questions for the OPII study include: (1) How are implementation outcomes related to variations across states in system characteristics, configurations of LCTs, assessment processes, and study implementation? (2) Were the improvements in assessment and case planning procedures identified by each LCT implemented as intended? (3) What does the OPII cost in terms of staff time devoted to designing and implementing the PIP? (4) Are OPII-initiated changes in assessment and case planning sustained following the end of the intervention? (5) In what ways does collaboration between organizations involved in the OPII change over the course of the intervention?Each research center obtained Institutional Review Board approval through an established FWA-recognized entity. In most instances, approvals were also secured from participating correctional and/or treatment agency research/IRB committees. Informed consent was obtained by research participants, including staff and managers of participating agencies, at varying points of time throughout the study, depending upon data collection requirements. Baseline structured staff surveys and corresponding participant consent were administered at the time of the kick off meeting of the early start site for participants of both the Early-Start and Delayed-Start sites. Qualitative interviews occurred after the randomization. ART-RF case ratings samples began six months prior to randomization; since the ratings did not collect personal identifying information, but rather agency documentation patterns, offender consent was not required.The organizational intervention under study in this paper will extend the use of interagency LCTs and externally facilitated organizational coaching to enhance the shared processes of assessment, case planning, service referral, and treatment provision processes between correctional agencies and community based treatment agencies. This study will generate and extend knowledge related to the science of implementation and organizational change in at least four key areas.First, the study will provide some of the first evidence of the effectiveness of change teams and facilitated coaching strategies to bring about changes in organizational processes within correctional systems. While the utilization of organizational coaching and facilitation has been recognized as an effective organizational change process in correctional systems , but also nearly all of the survey measures, present major risks and challenges to the analysis and interpretation processes. Nonetheless, the focused efforts at construct triangulation, drawing upon multi-methods data collection provide the potential for advancing measurement sophistication in this nascent field of inquiry. The reflective nature of our intervention design, one in which the speed at which the LCTs progress through the planned phases of the intervention, as well as the targeting of the process improvement goals selected by each LCT, present significant risks and challenges to analysis and interpretation. Finally, given the local setting context within which these LCTs are formed, the potential for spillover or generalization effects between early start and local start sites is an area for concern. For each of these methodological risks and liabilities, we have taken efforts to anticipate and guard against the most egregious risks, and we hope, in the process, to make significant contribution to the study of organizational improvement and implementation in general and within the unique context of correctional settings in particular.aCopies of the Facilitator Manual can be obtained by contacting the corresponding author.bAlthough there were nine (9) CJDATS Researcher Centers, one Center had two sets of study sites in two states, while another Center had a total of three study sites. The remaining seven research centers fielded one cluster each, with two study sites per cluster (n\u2009=\u200914).The CJDATS Assessment Workgroup members who participated in the development of the Assessment protocol are : David Duffee, Cassia Spohn (Arizona State University), Karen McKendrick, , Matthew Hiller, Roger Peters, Ralph B. Taylor, Gary Zajac (Temple University), Wayne Lehman (Texas Christian University), Linda K. Frisman, Colleen Gallagher, Eleni Rodis (University of Connecticut), Steven S. Martin, Cynthia Robbins (University of Delaware), Jamieson Duvall, Erin McNees Winston, Michele Staton Tindall (University of Kentucky), Bennett W. Fletcher ."} +{"text": "While advances in neuroscience are helping to improve many aspects of human life, inequalities exist in this field between Africa and more scientifically-advanced continents. Many African countries lack the infrastructure and appropriately-trained scientists for neuroscience education and research. Addressing these challenges would require the development of innovative approaches to help improve scientific competence for neuroscience across the continent. In recent years, science-based non-profit organisations (NPOs) have been supporting the African neuroscience community to build state-of-the-art scientific capacity for sustainable education and research. Some of these contributions have included: the establishment of training courses and workshops to introduce African scientists to powerful-yet-cost-effective experimental model systems; research infrastructural support and assistance to establish research institutes. Other contributions have come in the form of the promotion of scientific networking, public engagement and advocacy for improved neuroscience funding. Here, we discuss the contributions of NPOs to the development of neuroscience in Africa. The centralised role of the nervous system in coordinating both conscious and unconscious bodily processes, actions and perceptions makes neuroscience an important discipline in biomedical research Lewis . Yet, adWhile these developments in neuroscience provide hope to improve our understanding of the biological basis of organismal health and development, large proportions of these advances have come from research laboratories in continents that are more developed than Africa sponsoring promising African researchers for short-term training in leading universities abroad, and (2) awarding scholarships for graduate training abroad , Korle Bu Neuroscience Foundation , NeuroLeadership Institute (https://www.neuroleadership.com), The Dana Alliance for Brain Initiatives (http://www.dana.org) and Seeding Labs (http://seedinglabs.org). We will also highlight how some of these NPOs have partnered with scientific societies, funding agencies and universities in the delivery of their support initiatives, and how other organisations and individuals can emulate such strategies.To ensure that more scientists in Africa benefit from outstanding neuroscience training and are also supported to conduct high-impact research, some science-based non-profit organisations (NPOs) have been partnering the African neuroscience community to provide modern research infrastructure and training courses conducted at African universities. Other contributions have come in the form of promoting pan-African scientific networking, public engagement and advocacy for improved neuroscience funding. In this article, we discuss the contributions of these NPOs to neuroscience capacity building in Africa. This discussion will focus on NPOs that have provided support specifically for neuroscience education and research within Africa. The NPOs, identified through their contributions to the specific areas of capacity building discussed later in the article, include; Teaching and Research in Natural Sciences for Development in Africa as powerful-yet-cost-effective model organisms for neuroscience research, the annual neuroscience summer courses also provide training in the development of experimental techniques for cutting-edge research , listing the equipment they need and the contact person for correspondence. TReND in Africa volunteers then appeal to leading institutions in Europe and North America which might have these equipment as surplus-yet-functional resources to donate. Upon donation, the equipment are packed and shipped to the African partner university; the receiving institution covers only the shipping cost. This approach provides a cost-effective means for African institutions to obtain research equipment. To date, KIU in Uganda has been the largest beneficiary of this support system, leading to the establishment of an Institute for Biomedical Research is one of the effective means of building neuroscience capacity in the continent. Learning from this, neuroscientists in Africa (and scientists in other disciplines) can devise similar strategies to develop mechanisms of overcoming the chronic challenges that have caused science in the continent to lag behind other parts of the world. This way, resident scientists in Africa would obtain improved access to urgently-needed tools and materials in order to promote their teaching and research activities. We also call on African governments, industries and other NPOs to increase investments in neuroscience in order to help advance healthcare, education, business, economics and social wellbeing in the continent.IBRO, International Brain Research Organization; KBNF, Korle Bu Neuroscience Foundation; KIU, Kampala International University; TReND in Africa, Teaching and Research in Natural Sciences for Development in Africa; NPO, non-profit organisation"} +{"text": "The Building Blocks trial [ISRCTN 23019866] assessed the short-term impact of an intensive programme of antenatal and postnatal visiting by specially trained nurses to support young pregnant women. This follow-on study, BB: 2-6, will assess the programmes' impact on longer-term benefits for mothers and children, through the linkage of routinely collected data, with a particular emphasis on the programmes' impact upon child maltreatment.Follow up will be by linked anonymous data abstraction from the Health and Social Care Information Centre (HSCIC), Office for National Statistics (ONS) and Department for Education, National Pupil Database (NPD). These information centres (ICs) will match participants to the information held in their databases, and send to a third party safe haven.Re-consenting of all mothers would have resulted in a drastic loss of participants therefore section 251 support was sought to allow the transfer of identifiers to ICs for matching. This support required participants to opt-out rather than consent in.This project will complete in 2018. What has been achieved thus far is the establishment of a regulatory compliant model of linking health, social care and education data to clinical data. This model of linkage offers the possibility for long term evaluation of trials, at lower cost, and with the potential to extend to other sources of routine data.This presentation will review the approach established in this study, reflect on the dis/advantages of the approach, summarise the conditions of s251 support, information governance compliance, IC requirements and finally the challenges (and solutions) faced thus far."} +{"text": "Despite the proliferation of evidence-based treatments (EBT), there is little evidence that they are successfully implemented in real world behavioral health systems, fueling an ongoing debate about whether and how systems should invest in infrastructure to support implementation of EBT and the use of data and research to inform policy. Ironically, however, there are few empirical studies of whether and how public systems are living up to the promise of data- and research-based decision-making. The current study used data from the National Association of State Mental Health Program Directors (NASHMPD) Research Institute's (NRI) longstanding effort to compile information on state mental health authorities to examine the degree to which state systems currently invest in EBT and data-driven decision-making, and how such investments have changed over the period from 2001-2012. The study focused on: (1) Rates of implementation of specific EBT programs; (2) Types of state-provided or-facilitated EBT training and workforce support; and (3) State investment in evaluation, data, and research use. Data originated from three NRI projects for which annual or semi-annual data relevant to the above research questions were available: the State Profiles System (SPS), the Revenues and Expenditures Study (R&E), and the Uniform Reporting System (URS). Results found that after an initial increase from 2001-2004, rates of implementation of both child and adult EBTs have been consistently flat for the last decade, with investment in EBTs for adults 2-6 times higher than for children's services. Data also show variability over time in the types of implementation supports being used, with states increasingly emphasizing EBT in contracts with providers, modification of IT systems, and \"awareness building,\" and less on specific budget requests for EBT implementation or financial incentives for EBT use. Of concern, state investment in research and evaluation capacity and database integration efforts appear to be decreasing. Results of this ongoing research initiative are intended to strengthen the D&I knowledge base on the use of research findings in public systems, informing future national priorities and state efforts, promoting additional research, and serving as a baseline metric for reform efforts."} +{"text": "Dengue outbreaks in the Guangdong province reached epidemic proportions in the last quarter of 2014. According to the Guangdong provincial health and family planning commission (Although dengue, one of the most strongly emerging, neglected tropical diseases worldwide and presently without widely available drugs or vaccines, has a geographical distribution in South China , this ouChina needs to tackle the increase in dengue. The lessons learnt from previous infectious disease outbreaks such as SARS and H7N9 can be of value. The Chinese government has taken the following surveillance and control measures for dengue: strengthening surveillance and situation analysis; reinforcing case management and medical treatment; and conducting risk communication with the public and releasing information. Of note, the Patriotic Health Campaign Committee Office is a government organisation in each city or county, which can organise the resources needed to address issues of community hygiene. The government should also advise travellers to areas with known dengue outbreaks to take precautions such as avoiding mosquitoes.Chengshen JiangMaryland Institute for Applied Environmental HealthUniversity of MarylandCollege Park, MD, USAJohn S. SchieffelinDepartment of PediatricsSection Adult & Pediatric Infectious DiseaseTulane University School of MedicineNew Orleans, LA, USAJian LiDepartment of Biostatistics and BioinformaticsTulane University School of Public Health andTropical MedicineNew Orleans, LA, USAWenjie SunSchool of Food ScienceGuangdong Pharmaceutical UniversityZhongshan, ChinaDepartment of Global Health and Environmental SciencesTulane University School of Public Health andTropical MedicineNew Orleans, LA, USAEmail: wsun3@tulane.edu"} +{"text": "Tension headache (TH) belongs to most frequent type of the idiopathic cephalalgies. Depression and serotonins metabolism disorders play a leading role in the pathogenesis of TH.Study the dependence of the intensity of the TH of degree of depression, anxiety and levels of serum serotonin.The complex algic, psychometric test and determination of concentration of blood serum serotonin (S) by the method of immunoenzyme analysis were performed in 140 patients with TH.At patients of first group the intensity of episodic TH (44 man) was 56\u00b14,32 mm according to 100-mm visual analogue scale. All patients of this group had high level of reactive anxiety , moderate level of depression and tendency to the decreasing of blood S concentration . The second group consists of 96 patients with chronic TH. Straight correlation between duration and intensity of ache, indices of reactive and personal anxiety , high depression level and significant decreasing of blood S concentration was determined in all patients of this group.Concentration of blood serum serotonin depends on duration and intensity of ache, level of depression and anxiety. Therefore, serotonin of blood serum can be used as biomarker of ache intensity, level of depression.No conflict of interest."} +{"text": "The aim of the present study is to empirically test the theoretical model, Positive Self and Relational Management (PS&RM), for a sample of 184 Italian university students. The PS&RM model specifies the development of individuals' strengths, potentials, and talents across the lifespan and with regard to the dialect of self in relationship. PS&RM is defined theoretically by three constructs: Positive Lifelong Life Management, Positive Lifelong Self-Management, Positive Lifelong Relational Management. The three constructs are operationalized as follows: Positive Lifelong Life Management is measured by the Positive and Negative Affect Schedule (PANAS), the Satisfaction With Life Scale (SWLS), the Meaningful Life Measure (MLM), and the Authenticity Scale (AS); Positive Lifelong Self-Management is measured by the Intrapreneurial Self-Capital Scale (ISC), the Career Adapt-Abilities Scale (CAAS), and the Life Project Reflexivity Scale (LPRS); and Positive Lifelong Relational Management is measured by the Trait Emotional Intelligence Questionnaire (TEIQue), the Multidimensional Scale for Perceived Social Support (MSPSS), and the Positive Relational Management Scale (PRMS). Confirmatory factor analysis of the PS&RM model was completed using structural equation modeling. The theoretical PS&RM model was empirically tested as defined by the three hypothesized constructs. Empirical support for this model offers a framework for further research and the design of preventive interventions to promote decent work and decent lives in the twenty-first century. Across the lifespan, individuals inevitably confront multiple challenges in the domains of work and relationship. While these are longstanding human challenges, recent economic, and social changes related to unemployment, globalization, and the changing nature of work have created a crisis involving underemployment, unemployment, and subsequent loss of financial security. The field of vocational psychology can assume a leadership role in responding to the current crisis by advancing theories, research, and practices that address the impact of these pressing social and economic challenges . Participants were predominantly White Italians from middle-class backgrounds.Participants are 184 Italian students of the University of Florence. Regarding gender, 81 participants were male (44%) and 103 participants were female (56%). The age of the participants ranged from 22 to 27 years and negative affect (NA), the Positive and Negative Affect Schedule . Concerning ethical standards for research, the study followed procedures consistent with the latest version of the Declaration of Helsinki revised in Fortaleza , NNFI = 0.93, CFI = 0.93.The goodness-of-fit indices for the best model are the following: \u03c7An evaluation of these indices in relation to the results of the analysis for this study reveals good fit and support for the PS&RM model.The aim of the present study was to provide empirical support for the conceptualization of PS&RM (Di Fabio, Structural equation modeling confirmed the hypothesized structure articulated by the three lower order latent constructs: Positive Lifelong Life Management, Positive Lifelong Self-Management, and Positive Lifelong Relational Management. The construct of Positive Lifelong Life Management integrates hedonic and eudaimonic well-being, meaning in life and authenticity. Given that rapid social, economic, technological, and career change can disrupt a sense of meaning, coherence, and well-being Masten, , the capThe second construct Positive Lifelong Self-Management emphasizes self and intraindividual resources considered important for coping proactively with the challenges of the post-modern era (Di Fabio, The third construct Positive Lifelong Relational Management includes personal (e.g., trait emotional intelligence; Petrides and Furnham, In sum, the current study provides empirical support for the conceptualization of PS&RM as Positive Lifelong Life Management, Positive Lifelong Self-Management, Positive Lifelong Relational Management. Considered collectively, the three dimensions consider the importance of advancing a state of well-being that benefits the individual and society and promotes personal skills to adapt to change and uncertainty while integrating and balancing individual, relational, and community concerns and interests. Together, the dimensions are supportive of decent work and decent life.Although the results of the present study test the PS&RM model (Di Fabio, If the PS&RM model is tested and validated in future research with diverse populations, it may offer a useful framework for preventive intervention. As a preventive framework (Hage et al., It is our hope that the preventive and relational framework specified by the PS&RM model can contribute to building decent work and decent lives for many people in the twenty-first century. We propose that life construction (Guichard, AD and MK conceptualized the study, chose the theoretical framework and chose the measures. AD collected the data and with MK wrote the methods and results. Then the authors wrote the paper together and read and revised the manuscript several times.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "To assess different methods for determining cause of death from verbal autopsy (VA) questionnaire data, the intra-rater reliability of Physician-Certified Verbal Autopsy (PCVA) and the accuracy of PCVA, expert-derived and data-driven algorithms were assessed for determining common causes of death in Ugandan children. A verbal autopsy validation study was conducted from 2008-2009 in three different sites in Uganda. The dataset included 104 neonatal deaths (0-27 days) and 615 childhood deaths (1-59 months) with the cause(s) of death classified by PCVA and physician review of hospital medical records (the \u2018reference standard\u2019). Of the original 719 questionnaires, 141 (20%) were selected for a second review by the same physicians; the repeat cause(s) of death were compared to the original,and agreement assessed using the Kappa statistic.Physician reviewers\u2019 refined non-hierarchical algorithms for common causes of death from existing expert algorithms, from which, hierarchal algorithms were developed. The accuracy of PCVA, non-hierarchical, and hierarchical algorithms for determining cause(s) of death from all 719 VA questionnaires was determined using the reference standard. Overall, intra-rater repeatability was high . PCVA performed well, with high specificity for determining cause of neonatal (>67%), and childhood (>83%) deaths, resulting in fairly accurate cause-specific mortality fraction (CSMF) estimates. For most causes of death in children, non-hierarchical algorithms had higher sensitivity, but correspondingly lower specificity, than PCVA and hierarchical algorithms, resulting in inaccurate CSMF estimates. Hierarchical algorithms were specific for most causes of death, and CSMF estimates were comparable to the reference standard and PCVA. Inter-rater reliability of PCVA was high, and overall PCVA performed well. Hierarchical algorithms performed better than non-hierarchical algorithms due to higher specificity and more accurate CSMF estimates. Use of PCVA to determine cause of death from VA questionnaire data is reasonable while automated data-driven algorithms are improved. Verbal autopsy (VA) is an indirect method of determining cause of death based on an interview with the caretakers of a deceased individual, which has been widely used to collect information on cause-specific mortality where vital registration systems are lacking and medical information on deaths is incomplete . DiffereThe most widely used method is physician review, known as physician-certified VA (PCVA), in which physicians are trained to review questionnaire data and determine cause of death. Although the validity of PCVA has been evaluated , concernAn alternative to PCVA for determining cause(s) of death from VA data are algorithms. Algorithms can be expert-derived or data-driven. Expert algorithms include a set of pre-defined diagnostic criteria developed by a panel of physicians,based on experience or review of existing literature . AlternaData from a VA validation study conducted in three epidemiological settings in Uganda were used to investigate the performance of different methods for determining causes of death from VA data. We evaluated the intra-rater reliability of PCVA, and also compared the accuracy of PCVA to that of two algorithms; one developed with the input of expert physicians and another data-driven .The VA data-set used to investigate the performance of different methods for determining causes of death was obtained from a VA validation study that was approved by the Ugandan National Council for Science and Technology, the Centers for Disease Control and Prevention, and the ethics committees of Makerere University Faculty of Medicine, and the London School of Hygiene and Tropical Medicine. Details of the VA validation study method are published elsewhere . BrieflyTwenty percent of VA questionnaires were systematically sampled for assessment of intra-rater reliability. Using a list of sequentially ordered identification numbers for each site, we systematically selected every fifth VA questionnaires with the corresponding COD originally determined by physician review of the data. VA questionnaires were re-evaluated by the original physician a second time. Re-determination of causes of death from VA questionnaires occurred 3\u20139 months after the original assessment, and physicians were blinded to the causes of death recorded in the original VA death certificate.The non-hierarchical algorithms were based on previously published expert algorithms ,21,29\u201331Hierarchical algorithms were developed by ranking the performance of the non-hierarchical algorithms to reach common causes of childhood deaths, including neonatal deaths. Ranking was prioritized based on specificity of causes of death as determined using expert algorithms. The cause of death with the highest specificity wasplaced at the top of the hierarchy while the least specific was placed at the bottom . NeonataOriginal) to the re-determined CSMF (CSMF Repeat).The cause of death determined by physicians upon repeat review of VA questionnaires was compared to the cause of death originally determined by the same physician. The percentage level of agreement and Kappa statistic was calculated using Stata 12 for each physician. Interpretation of Kappa values was based according to the criteria of Landis and Kock , who recA database comprised of responses to closed-ended sections of VA questionnaires, and the reference causes of death derived from medical records were generated. Causes of death determined by non-hierarchal algorithms were derived by applying non-hierarchal algorithms to the closed-ended sections of VA questionnaires. Non-hierarchal algorithms were capable of classifying more than one cause of death. Hierarchal algorithms were also applied to the same VA questionnaire database, generating a single cause of death for each questionnaire.PCVA), non- hierarchical algorithms (CSMFNHA) and hierarchal algorithms (CSMFHA). The difference between the CSMF determined using each of the three methods and the \u2018reference standard\u2019 (CSMFMR) was calculated for the common causes of death. For neonatal and childhood deaths, where algorithms were developed for five and four commonest causes of death respectively, causes of death that did not fit the commonest cause of death list were categorized as \u2018others\u2019 and were factored in all analysis.The sensitivity and specificity of each method for determining cause of death were calculated by comparing the cause of death assigned by each method to the \u2018reference standard\u2019 for causes of death derived from hospital medical records, including malaria, pneumonia, diarrhea, meningitis, malnutrition, and HIV. CSMF estimates of the leading causes of death were also calculated for PCVA , non-hierarchical algorithms , and hierarchical algorithms (1% and 2% difference respectively). Non-hierarchical algorithms (50% difference), and hierarchical algorithms (16% difference) overestimated the CSMF for septicemia deaths compared to PCVA (-3% difference) that performed best. On the contrary non-hierarchical algorithms (5% difference), and hierarchical algorithms (-4% difference) had better CSMF estimates for meningitis deaths compared to PCVA deviated greatly from the reference standard , with a tendency to overestimate the CSMF for the leading causes of death across all sites. The CSMF estimated by PCVA (CSMFPCVA) and the hierarchal algorithms (CSMFHA) approximated that of the reference standard (CSMFMR) for all cause(s) of death, performing far better than non-hierarchical algorithms. However, overall CSMF estimates of malaria deaths were best approximated by hierarchal algorithms (0% difference), exceeding performance of both PCVA (6% difference) and non-hierarchical algorithms (56% difference), which both overestimated the fraction of deaths attributable to malaria when compared to the reference standard of death and a marked decline in specificity.Hierarchical algorithms assigning a single cause of death from each VA questionnaire resulted in an increase in specificity of the algorithm in determining causes of death, but at the expense of sensitivity which declined. However, compared to the non- hierarchal algorithms, hierarchal algorithm estimates of the reference CSMF were accurate and as good as those of PVCA for all the common causes of death; a fact attributed to the high specificity levels of hierarchal algorithms. This finding, previously described by Anker et al , demonstSeveral computerized methods premised on different algorithmic methods , probabilistic approaches have been developed as alternative methods of determining cause(s) of death from VA questionnaires ,33,36\u201338InterVA uses a probability matrix, which was derived from clinical knowledge of group of physicians , and in Our study is not without limitation. Internal evaluation of the performance of the hierarchical algorithm may have biased results, showing good performance of the hierarchical algorithms. However, the results of our analysis are strengthened by the inclusion of three different study sites. Furthermore, the small sample of deaths among some of the causes of the death in both neonates and children, especially when stratified by site, may have undermined our ability to detect representative estimates of measures of performance.Our study provides insights into the performance of different methods for determining cause(s) of death from VA questionnaire data collected in three sites. Importantly, we demonstrate that repeatability of PCVA is high, contrary to expectation, and that overall PCVA performed well. Thus, based on our results and available evidence so far, PCVA remains a reliable method for determining cause of death from VA questionnaire data. Given the lack of consensus on the accuracy of recently developed CCVA methods, PCVA still has a place in determining cause of death in VA, while existing and newer automated data-driven algorithms, which undoubtedly would be more efficient, are further developed, refined, and evaluated."} +{"text": "A 70-year-old man referred for cataract surgery, had on examination a palette of colored needle-shaped opacities in the cortex and anterior nucleus of the lens, consistent with unilateral Christmas tree cataract. This type of cataract result from the accelerated breakdown of membrane associated proteins. The peptides and amino-acids accumulate in the lumen of the reticular meshwork, and cystine is concentrated beyond the level of crystallization, giving rise to growing crystals."} +{"text": "Inflammation in the face of harming stimuli protects the organism; as a result, it is an essential route for survival, in which both innate and adaptive immunity are involved. This process must be tightly controlled and terminated in order to warrant the reestablishment of body homeostasis. Therefore, activation of resident inflammatory cells and the recruitment and modulation of migrating inflammatory cells must be ceased. When failure in neutralizing acute inflammation occurs, there is augmented risk of development of chronic inflammation, leading to several metabolic consequences. In the present special issue, original research studies as well as review articles address the inflammatory process as a key contributor to disease onset and progression. In addition, pharmacological and nonpharmacological therapies are examined and the molecular and physiological mechanisms of the treatments are discussed.Among the 24 accepted papers, 7 approach nutritional therapy and inflammation . The selected papers discuss the effects of Macadamia oil supplementation attenuation of adipocyte hypertrophy and of the inflammatory response of adipose tissue macrophages. The protection induced by supplementation of chitosan coacervate whey protein against metabolic changes and obesity-related inflammation is investigated. Other papers examine Jussara supplementation-associated reversal of the adverse effects of perinatal intake of transfatty acids, the beneficial effect of red genistein extract on autoimmune arthritis, and the role of vitamin C in the resolution of inflammation. Finally, the promotion, by nutritional intervention, of the recovery of glucose homeostasis is discussed. In addition, results on the effect of microencapsulated probiotics on alcoholic liver disease are presented. Taken together, these papers show new encouraging results of nutritional therapy in counteracting the symptoms of obesity and insulin resistance.The ability of exercise to modulate chronic inflammation was the center of two papers . These studies report that a community-based exercise program results in decrease or maintenance of inflammatory biomarkers after 1 year and thus presents strong potential in public health approaches for chronic disease prevention.Inflammation and its mechanisms are discussed in the development and progression of many diseases, such as in ectopic fat deposition , acute and chronic kidney disease , and polymicrobial sepsis . The role of interleukin- (IL-) 18 in the regulation of toll-like receptors and mannose receptor expression is examined. Inflammation in the metabolic syndrome and the effect of metformin on autoimmune arthritis are debated. Gut microbiota participation in inflammation is addressed , and its regulation by short-chain fatty acids in diabetes contemplated. The contribution of circulating LL-37 and inflammatory cytokines in the setting of plaque and guttate psoriasis is commented on. Other papers consider ionotropic and metabotropic proton-sensing receptors in allergic asthma and autologous bone marrow stem cell transplantation in myocardial infarction . Flavocoxid and infliximab are examined in the context of classical and nutraceutical therapies . The role of IL-38 and related cytokines in inflammation is discussed, in addition to gingival inflammation and pregnancy and the contribution of the immune system in triplet repeat expansion diseases .Collectively, this issue provides insight on the role of acute and chronic inflammation in different diseases and discusses mechanisms and new treatment strategies.M. SeelaenderM. SeelaenderJ. C. Rosa NetoJ. C. Rosa NetoG. D. PimentelG. D. PimentelR. S. GoldszmidR. S. GoldszmidF. S. LiraF. S. Lira"} +{"text": "Infections of poultry species with virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), one of the most economically significant and devastating diseases for poultry producers worldwide. Biological engagement programs between the Southeast Poultry Research Laboratory (SEPRL) of the United States Department of Agriculture and laboratories from Russia, Pakistan, Ukraine, Kazakhstan, and Indonesia collectively have produced a better understanding of the genetic diversity and evolution of the viruses responsible for ND, which is crucial for the control of the disease. The data from Kazakhstan, Russia, and Ukraine identified possible migratory routes for birds that may carry both virulent NDV (vNDV) and NDV of low virulence into Europe. In addition, related NDV strains were isolated from wild birds in Ukraine and Nigeria, and from birds in continental USA, Alaska, Russia, and Japan, identifying wild birds as a possible mechanism of intercontinental spread of NDV of low virulence. More recently, the detection of new sub-genotypes of vNDV suggests that a new, fifth, panzootic of ND has already originated in Southeast Asia, extended to the Middle East, and is now entering into Eastern Europe. Despite expected challenges when multiple independent laboratories interact, many scientists from the collaborating countries have successfully been trained by SEPRL on molecular diagnostics, best laboratory practices, and critical biosecurity protocols, providing our partners the capacity to further train other employes and to identify locally the viruses that cause this OIE listed disease. These and other collaborations with partners in Mexico, Bulgaria, Israel, and Tanzania have allowed SEPRL scientists to engage in field studies, to elucidate more aspects of ND epidemiology in endemic countries, and to understand the challenges that the scientists and field veterinarians in these countries face on a daily basis. Finally, new viral characterization tools have been developed and are now available to the scientific community. Newcastle disease (ND) is one of the most significant diseases of poultry worldwide. It is caused by virulent strains of Newcastle disease virus (NDV), also known as avian paramyxoviruses of serotype 1 (APMV-1). The presence of virulent viruses in poultry must be immediately reported to the World Organisation for Animal Health . Whether in domestic poultry or wild birds, vNDV strains remain a threat to all producers of poultry.In 1998, the US Department of State (DOS) assisted selected former Soviet chemical and biological weapons scientists to redirect their efforts to peaceful, agricultural research and to help reduce the proliferation of weapons of mass destruction. Almost a decade later, the DOS Biosecurity Engagement Program (BEP) was implemented with the broader mission of providing financial and intellectual assistance to microbiological laboratories to enhance biosecurity, biosafety, and pathogen and disease surveillance, while decreasing biological threats, globally. The collaborations expanded past the former Soviet Union (FSU) to include South and Southeast Asia, the Middle East and Africa. One area of common mutual interest across these regions was scientific collaboration on avian influenza virus (AIV) and NDV, both notifiable and listed diseases to the OIE.In 2000, a long-standing collaboration between the ARS Southeast Poultry Research Laboratory (SEPRL) and Russian counterparts began on avian influenza and NDV and provided unique opportunities for surveillance and research in the region. In 2002, SEPRL began collaborating with partners in Kazakhstan; in 2010, collaborations began with Ukraine, Egypt and Indonesia; and in 2011, with Pakistan. From 2000 to 2015, SEPRL has collaborated on 14 bio-engagement research projects on avian influenza and ND with its global partners mainly funded by the DOS, but also more recently by the Department of Defense\u2009\u2013\u2009Defense Threat Reduction Agency. While most of the initial interactions with foreign laboratories often began with the training of collaborators at SEPRL, formal scientific collaborations often developed subsequently , Food and Agricultural Organization , US AgenDuring the research projects, SEPRL scientists visited their foreign counterparts in Russia, Kazakhstan, and Ukraine 32 times. SEPRL scientists also hosted 30 collaborators for scientific visits involving research and training. Under the auspices of the projects, SEPRL and foreign collaborators participated in over 25 international conferences in the US, Russia, Ukraine, South Africa, Spain, Germany, China, Latvia, the United Kingdom, and Thailand. In addition to the research projects, from 2008 to 2010, SEPRL provided training on molecular techniques to detect AIV and NDV to 57 scientists from 21 countries. Additional informal collaborations with scientists from Israel, Bulgaria, Nigeria, Tanzania, and Mexico have added to the body of knowledge on AIV and NDV epidemiology. Through training and collaborative research efforts, SEPRL has developed an extensive network of scientists around the world working on AIV and NDV.The initial objective of the scientific proposals between SEPRL and the collaborating laboratories included increasing the number of surveillance samples obtained from commercial and domestic poultry species, and also wild birds. Scientists from the participant laboratories processed these samples together with SEPRL scientists, identified and characterized the strains of NDV obtained. Subsequent testing of molecular diagnostic techniques documented if routinely used molecular assays were able to detect all of the viruses isolated. Additional characterization of isolates, such as pathogenesis studies in chickens, vaccine studies, or phylogenetic sequence analysis was performed depending on the scientific interests or industry concerns. The objective of the training was to prepare foreign scientists to be able to accurately and promptly detect vNDV and to identify what avian species the viruses are likely to be obtained from. Those skills were considered to be critical for preventing, containing, and controlling ND outbreaks. Furthermore, efforts were made in promoting safe, secure, and responsible use of biological materials that are at risk of accidental release or intentional misuse as the prevention of accidents improves the quality of life for people from all the countries involved.NDV of low virulence, also known as lentogenic NDV, are widely distributed worldwide and are present in multiple avian species that may be in contact with poultry. Lentogenic viruses are used as vaccines to prevent mortality and clinical disease from vNDV infections in poultry. However, some lentogenic strains produce respiratory infections that decrease productivity in poultry, and have the potential to become virulent upon mutation of the cleavage site of the fusion protein gene. The nucleotide sequence of the fusion gene is used to classify NDV strains into genotypes and the cleavage site sequence of the fusion protein of NDV is the accepted OIE identifier of virulence. Strains that have three or more basic amino acids at positions 113\u2013116 with a phenylalanine at position 117 are by definition virulent \u201310. As mA collaboration project with the National Scientific Center Institute of Experimental and Clinical Veterinary Medicine, Kharkiv, Ukraine was initiated to study the geographic distribution, wild host species distribution, and ecological factors affecting virus transmission of avian paramyxoviruses in Ukraine. Wild-bird surveillance was conducted in Crimea, Kherson, Zaporizhia and the Donetsk regions of Ukraine. The Black and Azov Sea regions are part of an intercontinental (north to south and east to west) flyway, and the similarity of the NDV strains isolated from these regions with other NDV from Northern Europe and Africa confirmed the importance of sampling birds in these regions for the early detection of viruses transported by wild birds .n\u2009=\u20099), APMV-4 (n\u2009=\u20094), APMV-6 (n\u2009=\u20093), and APMV-7 (n\u2009=\u20094) (Surveillance for hemagglutinating (HA) avian paramyxoviruses was conducted during 2006\u20132011 through different seasons of the year on 6,735 wild birds, representing 86 species, from 8 different orders. The presence of HA positive viruses in oral and cloacal swabs was obtained and the serotypes of the APMV were identified by hemagglutination-inhibition tests. The APMV obtained from swabs were serologically characterized and determined to belong to different serotypes as follows: APMV-1 ( (n\u2009=\u20094) . SurprisAs a result of an international collaboration that included the US Geological Survey at the Alaska Science Center in Anchorage, the Southeastern Cooperative Wildlife Disease Study group of The University of Georgia, Athens, GA, USA, the Research Center for Animal Hygiene and Food Safety, Obihiro University of Agriculture and Veterinary Medicine in Inada, Hokkaido, Japan, and the State Research Center of Virology and Biotechnology \u2018VECTOR\u2019, Novosibirsk Region, Koltsovo, Russia, the genetic diversity of APMV-1 isolated from migratory birds connected with Alaska and the continental US was studied . Swabs sAnalysis of the fusion protein sequence data revealed that none of the putative amino acid sequences for the fusion protein cleavage sites were consistent with those of previously identified virulent viruses. Besides the fact that five isolates of genotype I of class II formed a monophyletic cluster exhibiting previously unreported genetic diversity, which met criteria for the designation of a new sub-genotype, the most significant finding of this study was the close genetic relationship among selected isolates from wild-bird isolates from widely divergent geographic location. Close relationships were found among viruses of class II, with Russian NDV strains closely related to North American viruses (class II sub-genotypes Ib and Ic). More specifically NDV strains from Alaska (US) and Japan were related to NDV from Maryland (US), suggesting multiple opportunities where birds from different areas were exposed to each other\u2019s viruses. The relatedness of these viruses provided indirect evidence for possible intercontinental virus spread by migratory birds. Furthermore, the close relationship between NDV from class II genotype I, sub-genotypes Ib and Ic, confirmed that migratory bird movement is one of the possible mechanism for the redistribution of NDV strains . Due to The epidemiological factors responsible for the maintenance and spread of vNDV strains are largely unknown. It is suspected that vNDV may persist in vaccinated animals, however, repeated isolations of vNDV strains in wild birds also suggests the existence of natural reservoirs in birds species that either might not be susceptible to disease or may be partially resistant, such as parrots, cormorants and pigeons. Evaluating surveillance samples of domestic poultry species along with samples from wild-bird populations geographically surrounding them is critical for completely understanding the epidemiology of ND.The BEP collaborations between SEPRL and Pakistan involved two departments of the University of Veterinary and Animal Sciences, in Lahore; 1) Quality Operations Laboratory and (2) the Pakistan Institute of Biochemistry and Biotechnology, and another institution, the Poultry Disease Diagnostic Laboratory in Gakkhar, Gujranwala, Punjab. Efforts were focused on epidemiological studies designed to identify and characterize circulating strains of NDV in Pakistan. The first BEP collaboration with Pakistan characterized eight vNDV strains isolated from the years 1974, 1995, and 2004 through 2008 . Besides Quality The majority of the remaining Pakistani strains grouped with variants of NDV found in pigeons from genotype VIb, often called pigeon paramyxovirus-1 (PPMV-1). PPMV-1 are virulent by definition since they contain three or more basic amino acids at positions 113\u2013116 and a phenylalanine at position 117 of the fusion protein cleavage site and have an ICPI of equal to or greater than 0.7, thus are reportable to OIE has been gradually replaced by new viruses in some countries of Asia and the Middle East, these older viruses of VIId have continued to circulate worldwide. Three viruses isolated from chickens in Ukraine between 2003 and 2013 have been classified as members of sub-genotype VIId. Interestingly, these viruses resembled NDV isolates from backyard poultry in Bulgaria from 2006 and 2007 (unpublished data). These viruses were closely related to isolates from China from 2003 to 2007 and Serbia from 2007, further providing evidence for the distribution patterns of vNDV.113-R-Q-R/K-R-F-117) and ICPI values ranging from 1.05 to 1.87 .Thus, the evidence suggests that the simultaneous evolution of vNDV strains from multiple genotypes has continued in different locations and different hosts since the first vNDV were identified in 1926. However, increased surveillance, and prompt epidemiological characterization of new strains circulating in developing countries funded by BEP and other international efforts have allowed a better understanding of the evolution of vNDV and has increased awareness that ND is a global problem.One of the goals of the BEP collaborations was the evaluation of current diagnostic methods against new emerging strains of NDV. The constantly developing network of laboratories in different countries around the world, collaborating on the control of the ND, resulted in the increasing number of samples obtained from both poultry and wild birds. Thousands of collected specimens where tested by various serological, virological, and molecular methods. As a result, more than 350 NDV strains were isolated and most of them have been further studied and characterized. Most currently utilized rapid diagnostic methods based on rRT-PCR were effective in detecting ND viruses. The L-TET rRT-PCR designed to detect class I APMV-1 viruses and multn\u2009=\u200952) and class II (n\u2009=\u2009135) , 27 (unpNewcastle disease represents an international problem and a significant threat to poultry industries worldwide. The existence of a large number of countries with endemic virulent ND circulating in poultry and wild birds, the capacity of viruses for rapid intercontinental spread, the ability of viruses to gradually change, and the potential use for bioterrorism, require the development of more internationally funded epidemiological and veterinary research programs. The BEP collaborative projects have effectively contributed to the understanding of the threat and to the development of better tools to identify and characterize this agent.PM, KD, and CA defined the theme of the manuscript. All authors contributed on the data collection, writing of the manuscript and editing the manuscript. KD, PM, and DW-C created the tables. KD created the figure. DW-C, KD, and CA designed primers. All authors have seen and approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Sarcopenia and muscular dystrophy are both characterized by the loss of muscle mass and increased intramuscular fibrosis. The two conditions also share several pathophysiological mechanisms, including mitochondrial dysfunction, increased apoptosis, abnormal regulation of autophagy, decline in satellite cell function, increased generation of reactive oxygen species, and alterations of signaling and stress response pathways. Basic science researchers and clinicians working in the areas of sarcopenia and muscular dystrophy in human and animal models contributed to this research topic may well serve that purpose -dependent signaling , IBM with Paget\u2019s disease of bone and frontotemporal dementia (IBMPFD), and Krause, . MutatioThe five following contributions explored clinical aspects and evaluation methods. Harris-Love et al. provide Since a distinction between normal age-related weakening of muscle strength and clinically significant muscle disease is not always obvious, the correct diagnosis is easily missed. Palmio and Udd performeThe quantitative and qualitative domains of sarcopenia concur to the development of the clinical phenotype, dominated by muscle weakness, poor balance, and slow gait speed. This clinical picture shows substantial overlap with that of physical frailty , nutritional intervention, and physical exercise were discussed.The possibility of counteracting the age-related muscle decline was assessed through electrical stimulation (ES) of the thigh muscles (Kern et al., The origins of sarcopenia are multifactorial and only partly understood. However, protein-energy malnutrition is a well-known cause of muscle loss in advanced age (Calvani et al., Besides the optimization of nutrition, engagement in regular physical activity is widely recognized as an effective measure for preventing and treating sarcopenia (Landi et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Evidence-based, expert-driven, practical statements improve quality and effectiveness of the diagnostic and therapeutic process of patient care. Although the effectiveness of physiotherapy treatment strategies in ICU patients has been described, statements or guidelines of physiotherapy for ICU patients are not available . GuideliFor the development of this evidence statement, we used the EBRO method, as recommended by the Dutch Evidence Based Guideline Development Platform . This meThree expert-based relevant clinical questions were formulated within the physiotherapy clinical reasoning process and were classified according to the International Classification of Functioning, Disability and Health. In a systematic literature search, 129 studies were identified and assessed for methodological quality and classified according to the level of evidence. The final Evidence Statement consisted of recommendations for physiotherapy in ICU patients including safety criteria, a core set of instruments to assess impairments and activity restrictions and effective interventions.The Evidence Statement for physiotherapeutic diagnostics and intervention in ICU patients will contribute to the quality of clinical practice by supporting the clinical decision-making process."} +{"text": "The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria-endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial\u2014key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development and malaria elimination programmes. In 2015, an estimated 214 million malaria cases occurred globally, causing approximately 440,000 deaths . Su. Su36]. n Center , 70.TablEnforcement of drug regulations is another area in which collaboration is essential. National-level action against deliberately falsified medicines requires NMRAs to conduct collaborative investigations with police and customs. Operation Storm I and II, conducted in 2008 and 2009 in Cambodia, Indonesia, Laos, Myanmar, Singapore, Thailand, and Vietnam, offered an example of this sort of multisector collaboration. Coordinated by WHO and INTERPOL, these operations involved a synergistic partnership between customs authorities, police, NMRAs, and laboratories in participating countries . EncouraThe Global Fund has established a Joint Interagency Task Force (JIATF) to pro-actively engage with NMRAs and law enforcement authorities, and to provide information on the circulation of falsified medicines , training, and analytic technologies . SupportAction is needed at both the international and national levels to strengthen laws and law enforcement with regard to both falsified and substandard medicines. There have been calls for an international treaty, founded on considerations of public health , to define and differentiate in law the different forms of poor-quality medicines, provide a framework for criminal prosecution (commensurate with the relative seriousness of the offences and intentions of the perpetrator), and harmonize regulatory standards , 18. TheAt the national level, Attaran , 74 receIn 2013, the United Nations urged all states to establish national health and regulatory infrastructures and domestic management capacities to ensure that all citizens have access to medicines that are affordable, safe, efficacious, and of good-quality, and for the international community to continue to assist in achieving this goal . The WHOAccess to good-quality medicines is an essential human right and a top priority in the global fight against many life-threatening diseases including malaria . The coninternational and national political commitment and financing to drive these and other measures necessary to ensure access to quality medicines and thereby protect public health.Confer sustained international, public health-orientated legal framework or treaty on poor-quality medicines, with statutes integrated into national laws.Form a more comprehensive international efforts to strengthen governance of global medicines supply chains, harmonize regulatory standards and related procedures, and facilitate international cooperation between NMRAs and law-enforcement bodies.Provide further regional centres of excellence with common registration documentation, procedures, and decision-making procedures that are better aligned with public health needs.Develop harmonization of registration processes in Nationally, develop NMRAs that are adequately prioritized, resourced, structured, and trained to allow them to perform all regulatory functions in collaboration with the other national partner authorities.globally and nationally to support anti-malarial initiatives, particularly the detection of poor-quality medicines at all levels of the supply chain, and track-and-trace technologies that ensure a valid product from the manufacturing facility to the consumer.Invest in innovative technologies global and regional support to increase the number of prequalified standardized reference laboratories that can detect poor-quality anti-malarial medicines and also drive the validation and scaling-up of new field technologies for surveillance and analysis, particularly in malaria-endemic countries via appropriate training and resourcing.Arrange specific National and regional surveillance to be linked to effective routine and transparent reporting of incidents followed by an immediate withdrawal of products in the case of major findings by national authorities. Reporting of events should be made compulsory and a data-sharing policy involving public and private sectors, patient representatives, academics, non-government organizations, and international bodies should be developed accordingly.Given the current situation, urgent action is required by the international community across eight key areas:While it is not the intention of this publication to allocate responsibilities to defined organizations and initiatives, questions on strategic roles must be discussed and clearly assigned for future coherent actions. These eight key areas are considered as the priorities for all stakeholders, including the scientific and medical community and health policymakers, and the joint actions of these groups will be critical in driving forward effective malaria elimination programmes and global health development.The continued circulation of poor-quality anti-malarial medicines poses a significant threat to global advances in combating malaria. There are many ongoing initiatives designed to address different aspects of the problem; however, it is imperative that key unmet needs are addressed with urgent multisector action. The role of the international community is vital in extending and strengthening actions across eight crucial areas and reinforcing the fight against malaria."} +{"text": "Pre-labour Rupture of Membranes (PROM) is an important cause of maternal and fetal morbidity and increased rate of cesarean section delivery.The aim of this study is to investigate the clinical characteristics, PROM-delivery interval, mode of delivery, and early maternal neonatal outcome among pregnant patients presenting with pre-labour rupture of membranes.This prospective case control study is implemented at the Obstetric and Gynecology Clinic of the University Clinical Center of Kosovo. The study included 100 pregnant patients presenting with prelabour rupture of membranes of which 63 were primigravida and 37 patients were multigravida.The incidence of cesarean section in this study is 28 % and the most common indications for cesarean delivery were fetal distress, malpresentation, cephalopelvic disproportion, and failed induction. The most common maternal complications in this study are chorioamnionitis, retained placenta and postpartum hemorrhage. Neonatal infectious morbidity was present in 16 % of cases.PROM is a significant issue for obstetricians and an important cause of maternal and neonatal morbidity and increased rate of cesarean section delivery. Spontaneous rupture of membranes (ROM) is a normal component of labour and delivery , but theThe aim of this study was to investigate the clinical characteristics, PROM-delivery interval, mode of delivery, and early maternal neonatal outcome among pregnant patients presenting with pre-labour rupture of membranes in Republic of Kosovo.This prospective case control study was implemented at the Obstetric and Gynecology clinic of the University Clinical Center of Kosova and included 115 pregnant patients. This study was submitted and approved by the Ethical Review Committee of the University Clinical Center of Kosova and is in adherence to the laws and regulations of the country in which the research was conducted.Inclusion criteria for participant eligibility included that women were between 28-41 weeks of gestational age, not on either antibiotic or corticosteroid treatment, and experienced pre-labour rupture of amniotic membranes were assessed for eligibility. Women were excluded (N = 15) who had hypertensive disorders, diabetes mellitus, fetal malformations or other co-morbidities. The study was thus conducted on 100 women who met study eligibility criteria. Study participants were divided into two groups according to their gestational age at the time of rupture of membranes: 1) Term PROM with gestational age \u2265 37 weeks of gestation (69 cases), and 2) Pre-term PROM with gestational age 28-36 weeks+6 days (31 cases).After implementing informed consent process a detailed patient history and examination was performed and confirmation of the diagnosis of rupture of membranes was documented. The documenting of the rupture of membranes was done by sterile speculum examination confirming the pooling of amniotic fluid in the posterior vaginal fornix or/and direct visualization of fluid leakage from the cervical canal. A questionnaire and evaluation form was used to collect data at admission. Demographic data, clinical characteristics and data covering PROM \u2013delivery interval, mode of delivery and maternal neonatal outcome were recorded and compared between the two groups. Total hospital stay was also recorded and analyzed.A total of 100 patients with PROM were analyzed in this study. Demographic data, obstetrical risk factors for PROM respectively previous PROM, previous abortions and smoking in pregnancy are presented in The clinical characteristics of investigated patients with PROM are presented in Mode of delivery and maternal- neonatal outcomes are presented in The cesarean section rate was 28 % (N = 28). Comparison of the cesarean section rate between the Term Group and the Preterm Group did not show any significant statistical difference. Neonatal infectious morbidity was present in 16% (N = 16) of cases. Out of the N = 16 neonatal infection cases, 6 of them were in the Term Group and 10 were in the Pre-Term Group, which is a statistically significant difference (p = 0.003). Main maternal complications were chorioamnionitis, postpartum haemorrhage, and retained placenta. Both Term and Pre-Term groups showed similar rates of maternal complications (p = 0.680).Pre-labour rupture of membranes remains one of the important problems in obstetric practice. The etiology of PROM is multi-factorial and in some cases yet unclear. Infection is one of the exogenous etiologic factors thought preventable in some cases with proper antenatal screening and treating of genito-urinary infections. Management of pregnancies with pre-labour rupture of membranes varies depending on gestational age and obstetric status. Recent clinical trials support immediate labour induction in pregnant woman with PROM at term in absence of other maternal and fetal contraindications. Management of Pre-term PROM is more complex and carries risk of prematurity and other related fetal complications.Maternal complications, increased rate of operative delivery, increased rate of neonatal morbidity and mortality in pregnancies with PROM are reported in the literature, and PROM is also more frequent in developing countries. This study was conducted with the aim to evaluate these characteristics, mode of delivery and outcome of pregnancies with pre-labour rupture of membranes in a local setting. This study included one hundred patients of which 63 were primigravida and 37 patients were multigravida. Our findings suggest higher incidence of PROM in the primiparous than in the multiparous patients. The participants in this study had a wide variation in age, from 17 years to 37 years.The literature reports that PROM is associated with an increased risk of cesarean delivery . The resIn this study, fetal distress, malpresentation, cephalopelvic disproportion, and failed induction were the most common indications for cesarean delivery. Two of the 28 cesarean sections performed in this study were done so on the request of the mother. Of the studied cases maternal complications were present in 8% of cases. The most common maternal complications were chorioamnionitis, retained placenta and postpartum hemorrhage. There was no statistically significant different in maternal complication between the Term and Pre-Term PROM groups.Neonatal infectious morbidity was present in 16 cases. Of these cases, observed neonatal infectious morbidity was statistically significantly higher (p = 0.003) in the Pre-term PROM group (62.5 compared to Term PROM Group (37.5 %). In addition to the risk of prematurity the preterm infants of pregnancies with pre-labour rupture of membranes are at higher risk of infectious morbidity.In conclusion, pre-labour rupture of membranes remains an important cause of maternal and fetal morbidity and increased rate of cesarean section delivery. Postpartum haemorrhage, retained placenta, and chorioamnionitis are the most common maternal complications. Neonatal infection related to PROM is also an important factor of neonatal morbidity especially in pre term born infants. Fetal distress, malpresentations, cephalopelvic dispro-portion and failed induction are the most common indications for cesarean section delivery in pregnancies with pre-labour rupture of membranes. The results in this study indicate PROM is a significant issue for maternal and neonatal health in Kosovo. Future studies are warranted to improve maternal-neonatal outcomes."} +{"text": "There are currently many changes taking place in the health care system in the United States. Major transformations occurring in primary care settings strive to improve efficiency and effectiveness of health promotion and prevention activities, coordination of patient care, and management of chronic diseases. Team-based care is a major component of primary care redesign.The purpose of this study was to gain an in-depth understanding of how primary care practices in the United States are implementing team-based care. The study focused on understanding team-based care approaches, challenges to implementation, and successful strategies.A multidisciplinary research team used qualitative research methods to conduct in-depth case studies of eight primary care practices in various stages of practice transformation. The research team collected data from practices over a sixteen-month period using on-site interviews and structured telephone questionnaires (N=51), observation, and document review. In addition, key informant interviews were conducted with sixteen (N=16) leaders of primary care delivery organizations across the United States to obtain detailed information on team-based care models, such as team composition, roles and responsibilities of team members, and how teams function to meet the needs of their patients.The composition of teams and team member functions vary greatly across health care organizations. Team members typically include one or more providers , registered nurses (RN) or licensed practical nurses (LPN), medical assistants (MA), and administrative staff. In some settings teams include pharmacists, behavioral health specialists, social workers, community health workers, patient navigators and/ or care coordinators. Many organizations recognize the patient as an important member of the team.Organizational culture, values set by practice leaders, and other factors influence implementation of team-based care. Successful strategies for implementation include: leadership support and commitment, a multidisciplinary design and implementation team, careful review and redesign of processes, communication through formal policies and procedures and regular team meetings, and collection and review of performance data. Culture for team-based care models center on shared values and respect for individual team members\u2019 skills and contribution.The future of primary care in the United States will be characterized by many models of care that incorporate different types of health care professionals. Team-based care is a promising method for improving care coordination, medication management, patient education and self-management, and increasing the delivery of preventive services. Team-based care models may also improve productivity and boost employee morale."} +{"text": "The task force recommendation is based on strong evidence of effectiveness in 1) decreasing the prevalence of tobacco use, 2) increasing cessation and use of available services such as quitlines, and 3) decreasing initiation of tobacco use among young persons.Mass-reach health communication interventions target large audiences through television and radio broadcasts, print media, out-of-home placements , and digital media to change knowledge, beliefs, attitudes, and behaviors affecting tobacco use. The Community Preventive Services Task Force recommends mass-reach health communication interventions to reduce tobacco use and has posted new information about its systematic review at Established in 1996 by the U.S. Department of Health and Human Services, the task force is an independent, nonfederal, unpaid panel of public health and prevention experts whose members are appointed by the Director of CDC. The task force provides information for a wide range of decision makers on programs, services, and policies aimed at improving population health. Although CDC provides administrative, research, and technical support for the task force, the recommendations developed are those of the task force and do not undergo review or approval by CDC."} +{"text": "Juvenile idiopathic arthritis is a heterogeneous group of chronic inflammatory diseases with high risk of progressive articular damage. Clinical examination is the basis for assessing of the affected joints. Modern radiological techniques provide additional important information about the status of the damaged joints, allow the identification of subclinical inflammation.To investigate the additional capabilities of assessing local activity of finger joints of the hands and wrists in patients with different types of JIA by the modern methods of radiology diagnostic of articular pathology (magnetic resonance imaging (MRI) and ultrasonography (US)) in comparison with clinical research.20 patients with JIA were studied. Mean age was 12,3 years . Mean disease duration was 21,2 months (range 8-61). On clinical evaluation recorded the tenderness/pain on motion, swelling, limitation of movement. MRI (ESAOTE O-Scan) and US assessment of fingers and wrists joints was performed with the main focus of research on the signs of local activity: MRI - the presence of fluid in the joint cavity, US - the presence of joint effusion, synovial hyperplasia, power Doppler signal. We compared the results of clinical examination and radiology diagnostics.On clinical examination, synovitis was detected in 103 finger joints of the hands, in 9 wrist joints. On MRI and/or US synovitis was identified in 145 of finger joints of the hands, 13 wrist joints. Thus, by radiological methods subclinical activity was detected in 42 (28.9%) of finger joints of the hands, 4 (30.7%) - of wrists. Of them, 7 joints of the fingers and 1 of the wrists revealed a significant degree of activity on MRI and/or US, including a pronounced increase of vascularization of the synovial membrane (by means of power Doppler).In 20 finger joints clinically indicated only the presence of pain. Of them, in 6 joints revealed clear signs of activity on US: in 4 joints - small or moderate severity; in 2 joints - significant changes .In 2 patients the signs of synovitis associated with manifestations of dactylitis.In the studied group of patients with different subtypes of JIA, the use of MRI and ultrasound possible to detect subclinical synovitis in most patients. The use of modern radiological methods in patients with JIA can verify the exact local activity, improves detection of subclinical synovitis.None declared."} +{"text": "Spermatogenesis is a complex process of male germ cells proliferation and maturation from diploid spermatogonia, through meiosis, to mature haploid spermatozoa. The process involves dynamic interactions between the developing germ cells and their supporting Sertoli cells. The gonadal tissue, with abundance of highly unsaturated fatty acids, high rates of cell division, and variety of testis enzymes results very vulnerable to the overexpression of reactive oxygen species (ROS). In order to address this risk, testis has developed a sophisticated array of antioxidant systems comprising both enzymes and free radical scavengers. This chapter sets out the major pathways of testis generation, the metabolism of ROS, and highlights the transcriptional regulation by steroid receptors of antioxidant stress enzymes and their functional implications. It also deals with of the advantages of the system biology for an antioxidant under steroid control, the major selenoprotein expressed by germ cells in the testis, the phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) having multiple functions and representing the pivotal link between selenium, sperm quality, and species preservation. Spermatogenesis appears to be a fairly conserved process throughout the vertebrate series. The balance between spermatogonial stem cell self-renewal and differentiation in the adult testis grants cyclic waves of spermatogenesis and potential fertility. These replicative processes imply a highest rate of mitochondrial oxygen consumption and reactive oxygen species (ROS) generation. Enzyme complexes of the respiratory chain of the oxidative phosphorylation, localized on the crests of the mitochondria, as the xanthines, the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cytochrome P450, represent a source for a variety of ROS. As known, ROS are free radicals and/or oxygen derivatives that include superoxide anion, hydrogen peroxide, hydroxyl radical, lipid hydroperoxides, peroxyl radicals, and peroxynitrite. They have a dual role in biological systems, both beneficial than harmful depending on their nature and concentration as well as location and length of exposure . In this2O by glutathione peroxidase (GPx) or glutathione-S-transferase (GST) . The SODse (GST) , 6. In ase (GST) .In vertebrates, the spermatogenesis is controlled by a complex network of endocrine, paracrine, and autocrine signals \u201310 Recenin vivo, testosterone promote the expression only, as a consequence of the induction of spermatogenesis (The maintenance of a high redox potential is a prerequisite to maintain the reproductive systems in a healthy state . Reproduogenesis . The stuogenesis , suggestogenesis , 32.The overall objective of our mini-review was to highlight the beneficial and detrimental role of ROS that comparatively determine and influence the cyclic waves of spermatogenesis and the species preservation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The Materials Science and Engineering Laboratory (MSEL) of the National Institute of Standards and Technology (NIST), the Office of Industrial Programs of the Department of Energy (DOE), and the American Iron and Steel Institute (AISI) co-sponsored a Workshop on Intelligent Processing for Primary Metals held at NIST on August 29\u201330, 1989. Attendance was by invitation and the more than 80 participants were primarily senior technical staff and managers from steel, aluminum, and copper companies.Although the United States is a leading contributor to the world\u2019s materials science base, it is beginning to lag in the cost-effective implementation of this knowledge. U.S. industry does not enjoy leadership in the introduction of new materials technologies into consumer products, as it does in defense systems. Other nations have initiated government-industry programs aimed at the development of advanced processing technology. Advanced manufacturing techniques increasingly demand materials of greater reliability and uniformity at competitive cost. Specific demands for properties and performance can be met by control of the processing of the material from synthesis or raw material production to forming/finishing.Such process control, or \u201cIntelligent Processing of Materials\u201d (IPM), is based on four elements: a process model that relates specific materials properties at each stage of the processing to the final properties; sensors (measurement technology) which can measure the appropriate materials properties in real-time during processing; materials property data which must be coupled with the real-time measurements in the process model; and rapid computational capability for incorporation of sensor data, process model evaluation, and process variable control into an integrated, automated control strategy. The IPM concept differs greatly from conventional automated materials processing. In conventional practice, only the process variables are automatically controlled to pre-set values which, nevertheless, still allow the microstructure and properties of the material to deviate significantly from the desired values. A critical feature of intelligent processing is the shift from off-line measurements on finished products to on-line measurements in real-time to control processing.The past 5 years have witnessed extensive advances in the enabling technologies needed for intelligent processing of materials. These include: advanced sensors for on-line monitoring of material and process parameters, the knowledge base and materials characterization techniques to develop process models relating process parameters to material properties, and hierarchical computer control strategies for implementing artificial intelligence/expert systems concepts. Several recent national programs have been initiated to integrate elements of these advances to control the processing of advanced materials such as gallium arsenide crystals, powder metals, and composites. Similar opportunities now appear to exist in the primary metals industries.The goal of this industry-led workshop was to highlight the recent advances in sensing, modeling, and process control, to identify areas of need in the primary metals industries, and to develop a strategy for implementation of research results. Industry, university, and government participants assessed information provided by researchers and operating staff from industry to develop a research agenda for coupling the advancing state of materials processing in the primary metals industries.The genesis of this workshop may be traced to two events. First, the signing into law in late 1988 of the Steel and Aluminum Energy Conservation and Technology Competitiveness Act that authorizes DOE and NIST to carry out coordinated programs in support of the primary metals industries, primarily steel, aluminum, and copper. NIST would concentrate on providing instrumentation and measurement R&D. The second event was the January 1989 forum at Northwestern University to identify long-range research opportunities for the North American steel industry. The industry participants concluded that research opportunities could best be addressed in the context of three specific long-range development projects: direct production of liquid steel, near-net shape casting, and finishing and coating operations.To capitalize on these events, planning was initiated through a steering committee, chaired by Lyle H. Schwartz, Director, MSEL/NIST, with representatives from steel, aluminum, and copper trade associations, individual companies, the academic community, and Federal agencies. The consensus was to attempt to address the process control needs of the broad spectrum of primary metal industries and the role of intelligent processing concepts in solving these needs by focusing on three generic areas: primary metal production/refining, production of near-net shape products, and finishing/coating to final properties. Emphasis would be on future, advanced processes and technologies.The Organizing Committee, chaired by James G. Early, MSEL/NIST, was pleased to have participation by representatives of the aluminum and copper industries because the workshop structure is applicable to the processing of these metals. An overlap or commonality of process control needs is likely in some areas of processing. The success of this workshop could lead to other industries using this approach to develop process control priorities. Although the strategy was to achieve a workshop relevant to steel, aluminum and copper, the program contained a strong orientation toward steel-related issues. Since early in this decade, the steel industry has worked to develop a consensus on technical advances needed to improve traditional production practices and on identifying the future steel-making technologies. Thus, the steel industry was particularly well-positioned to play an important role and make major contributions to the workshop resulting in the strong emphasis on steel.Direct Liquid Metal ProductionNear-Net Shape CastingFinishing and CoatingThe core of the workshop was organized into three working sessions:Within these areas, the key elements of intelligent processing were stressed. The relationships between fundamentals and processing were explored through the integration of process modeling, sensor technology, and control strategies. Leading off the first day of the Workshop was an introduction to intelligent processing of materials concepts through applications to aerospace and other advanced materials followed by an overview of the process control research needs for the production of steel and aluminum. The three working sessions, responsible for Direct Liquid Metal Production, Near-Net Shape Casting, and Finishing/Coating, took place in the afternoon of the first day and the morning of the second day to permit a wide range of inputs from the participants. Coordinated presentations were given in these working sessions on the status of sensors, process models, and control approaches, the available technology, and the benefits to relevant research. After the morning sessions on the second day, a brief, verbal synopsis of the deliberations in each of the three working sessions was presented to the assembled workshop participants.Between the first and second days working sessions, Deputy Secretary of Commerce Thomas J. Murrin, spoke to the Workshop on \u201cNew Metals Technologies: Making the Government-Industry Connection Work.\u201d In his remarks, Mr. Murrin discussed the three key issues facing industry as it develops new metals technologies: the need to improve the quality of products and services; the need to take advantage of new technologies being developed overseas; and the need for continued and expanded government-industry-labor cooperation. While the metals industry\u2019s health will be determined primarily by its own efforts, there are appropriate areas in which the Federal Government can contribute. Deputy Secretary Murrin reported on a number of policy initiatives underway related to taxes and tax credits, antitrust laws, and a broad review of technology-innovation policies and programs to determine if other changes are needed.The first session was devoted to a series of invited presentations to prepare the participants in the three working sessions with the necessary background and global view needed to achieve the Workshop goal. The first speaker, W. Barker (DARPA) described the concept of intelligent processing of materials and reviewed the national programs supported by DARPA. In a companion talk, D. Backman reviewed the application of IPM concepts to advanced aerospace materials. The industry perspective was presented in the final two talks: I. Hughes (Inland Steel) \u201cLong Range Research -North American Steel\u2019s Competitive Edge\u201d; and R. Bonewitz (Alcoa) \u201cSensor, Process Models, and Control Needs in the Aluminum Industry.\u201dA. W. CrambCarnegie-Mellon UniversityJ. KorTimken CompanyCo-Chairmen:The session was organized into two parts: the first part was an information exchange between experts on sensor technology, process control, modeling, and the application of advanced computer decision making techniques, while the second part was to define and prioritize specific needs in the area of intelligent processing of liquid metals. Within each area specific needs were identified. Speakers included: J. Kor (Timken Company); P. Koros (LTV Steel Company); J. Fay ; A. McLean (University of Toronto); D. Hardesty ; C. Alcock (Notre Dame University); Y. Kim (Lehigh University); R. Guthrie (McGill University); M. Shah (IBM); and S. Ray (NIST).The sensor area was considered to be the area of highest importance and it was the consensus of the group that sensor development and implementation should be the major focus of any endeavor. Three separate groups of sensors were distinguished: continuous temperature sensors; continuous chemical sensors for liquid metal and hot, dirty gases; and, physical sensors to measure reaction intensity. The area of process modeling was identified as the second most important area for research at this time. Two separate groups of needs were outlined: Process Control Models; and In-Detail Process Models. In the area of process control there was a concern that current \u201cArtificial Intelligence\u201d techniques might not be applicable to on-line control in a broad sense; however, in certain well-defined circumstances it may be useful. In addition, it was felt that the computer science involved in process control and decision making was sufficiently rapid that a mechanism should be set up so that appropriate advances can be implemented within the industry in a reasonable time frame. Three separate groups of needs were identified: Operator Feedback and Instruction; System Integration; and Technology Transfer. A copper industry participant reported that many of the sensors discussed would also be of use to the copper industry and further identified the sensors that overlapped those needed by the steel industry.W. E. Eckhart, Jr.U.S. Department of EnergyR. SussmanARMCO, Inc.Co-Chairmen:This session was conducted in two parts. The first day was characterized by presentations made by experts in their respective fields. Each presentation generated a modest number of questions within the subject area. It is noteworthy that no process-specific problems were detailed during the first-day presentations, to the disappointment of some of the participants. The second day of this session was started by brief presentations made by individuals having hands-on experience with near-net shape casting of metal. Despite the obvious differences between the various casting methods, needs were categorized into three distinct areas: liquid metal handling, casting, and strip collection. Speakers included: M. R. Moore (USS Division of USX); R. A. Gleixner ; L. T. Shiang (Inland Steel Company); Y. Sahai (Ohio State University); H. N. G. Wadley (University of Virginia); and J. A. Walton .Eight sensors were identified as critical to the successful development of a commercial strip casting process: continuous temperature measurement of the meet; continuous temperature of the substrate surface; rapid on-line strip thickness sensing; on-line hot strip inspection system; continuous topographic sensing of substrate; liquid metal level sensor; liquid metal inclusion sensor; and liquid metal nitrogen sensor. It was recognized that each of these must be employed in a manner in which it could be actively used to control the outcome of the process, and not merely in a passive role to provide information. Attempts were made to determine the range and precision needed for each of the sensors. In many cases, the identified range was quite accurate, but the estimated precision reflected that required of the product; the sensor may require greater sensitivity. In the area of mathematical modeling, it was agreed that most models are process-specific. Nonetheless, there exist many commercially available models of the two principal phenomena involved in near-net shape casting, heat transfer and fluid flow. It was determined after considerable discussion that the industry would benefit from a comprehensive review of such models currently available, along with their respective strengths and weaknesses, and a strategy for implementation of selected models. In the area of process control, it was recognized that the overall state of knowledge of near-net shape casting makes it difficult to design a comprehensive control system at this stage of development. It was determined that it would be meritorious to undertake an intelligent process simulation project to serve as a model for the metals industry. Shortly after the close of the workshop, a participant from the copper industry submitted an analysis that summarized similarities and differences in the sensor/model/control needs for copper and steel near-net shape casting.D. WatanapongseInland SteelA. Van Clark, Jr.NISTCo-Chairmen:The session consisted of two meetings designed to facilitate interaction between national experts and industry experts. The goal of the first meeting was to understand and assess the states of knowledge in intelligent processing; namely, product/process knowledge, process modeling, sensors, integrated process control, and artificial intelligence. The product/process relationships for steel substrates and coated steel were presented along with the needs for future improvements. Subsequent presentations were in sensor development, process modeling, and advanced control. The goal of the second meeting was to address the issues and resolutions that can enhance the success of future research programs to develop and apply intelligent processing technologies. Speakers included: D. Reinbold (Bethlehem Steel); P. Southwick (Inland Steel); S. Denner ; K. Brimacombe (University of British Columbia); J. Monchalin (IMRI Canada); A. V. Clark, Jr. (NIST); L. Lowry (Jet Propulsion Laboratory); and A. Meystel (Drexel University).Although there is a wide range of sensor needs in the finishing and coating processes, five sensors were identified as having highest priority: continuous temperature measurement of strip; on-line measurement of chemical composition and phase identification in coatings; measurement of surface topography and surface chemistry of strip; measurement of lubricant film thickness; and measurement of mechanical properties/microstructure. Further attempts to prioritize among the five or to define specific ranges and accuracy of the sensors were considered inappropriate by the group because sensor requirements must be specified as an integral part of process modeling and control system development. Attempts were made, however, to estimate the developmental time for the sensors based on current understanding of available principles and technologies. In the coating processes, much work is needed to understand and model coating adherence mechanisms for a range of coating materials, steel substrates, surface morphology, and processing parameters. In addition, press performance of coated materials in terms of stampability and powdering characteristics must be studied and modeled. Engineered surfaces and microstructural engineering were cited as the important areas needing further modeling studies. Since intelligent processing involves implementation and also a wide range of multidisciplinary backgrounds, the significance of project team formation, technology transfer, designed-in safety and maintenance were discussed at length. Intelligent processing has definitive roles in the finishing and coating processes, in terms of new product and process design and on-line process control. Specific recommendations are: Develop real-time expert models for control to supplement process models; and develop implementable intelligent processing systems from hot rolling to coating, with emphasis on continuous processing.The research agenda developed at this industry-led workshop is summarized in NIST Special Publication 772, \u201cIntelligent Processing for Primary Metals.\u201d According to the participants, successful development and implementation of advanced processing concepts for the production of steel, from raw steel through finished steel products, will be enhanced through the formation of broad-based, multidisciplinary teams focusing on generalized approaches and solutions to well-defined tasks. Specific recommendations for critically-needed sensors, process models, and control strategies are reported for the three working sessions.For information on collaborative IPM research opportunities at NIST or a copy of the workshop report, NIST Special Publication 772, send a self-addressed mailing label to Dr. James Early, Materials Building, Room B309, NIST, Gaithersburg, MD 20899."} +{"text": "Health professional mobility in Europe has become a fast-moving target for policy-makers. It is evolving rapidly in direction and magnitude as a consequence of fundamental change caused by European Union (EU) enlargement and the financial and economic crisis.Health professional mobility changes the numbers of health professionals in countries and the skill-mix of the workforce, with consequences for health-system performance. Many of the so-called pull and push factors influencing mobility of individuals are in the remit of countries and organizations. In Europe, these pull and push factors are co-determined by EU policies on free mobility, the qualifications directive and many soft-law initiatives.This presentation is reviewing the current mobility trends in Europe and provides clues on how to strengthen governance for human resources for health at European and country level. A particular reference is made to mobility monitoring, workforce intelligence, workforce policies/ strategies, skills-initiatives and coordination mechanisms across sectors and levels."} +{"text": "Salmonella enterica typhimurium. The authors thank Dr. Claire Pearson for critical review of the manuscript.The authors thank Professor David Holden, Imperial College London, for the kind gift of GFP-Salmonella enterica typhimurium. The authors thank Dr. Claire Pearson for critical review of the manuscript and The Sir Jules Thorn Charitable Trust for their financial support.The authors thank Professor David Holden, Imperial College London, for the kind gift of GFP-The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The Computer Systems Laboratory (CSL), National Institute of Standards and Technology, sponsored the sixteenth North American ISDN Users\u2019 Forum (NIUF) at its Gaithersburg, Maryland site on October 26\u201330, 1992. About 250 users, implementors, and service providers of ISDN technology attended the meeting. CSL collaborated with industry in 1988 to establish the NIUF to ensure that emerging ISDN applications meet the needs of users. A Cooperative Research and Development Agreement (CRDA) with industry was established in 1991 to govern the management of the forum; the CRDA now has 36 signatories from industry and academia. CSL serves as chair of the forum and hosts the NIUF Secretariat. NIUFmembership is open to all interested users, product providers, and service providers; meetings are held three times a year at various locations throughout North America.International standards for ISDN support worldwide communications for the exchange of voice, data, and image information among users, independent of any manufacturer, service provider, or implementation technology. ISDN standards are developed by the International Telephone and Telegraph Consultative Committee (CCITT) and, for North America in particular, by the Exchange Carriers Standards Association (ECSA) accredited standards committee, T1, under the umbrella of the American National Standards Institute (ANSI).ISDN standards provide a broad variety of options and parameters to meet many potential needs and applications. To ensure interoperability and terminal portability within the ISDN network and its attendant equipment, a uniform subset of options and parameters must be selected for implementation. Each application usually requires only a subset of total functionality available in the standards; for ISDN products and services to work together in a multi-vendor environment, common sets of options must be selected.To cope with this proliferation of choices and to provide practical products and services which meet the needs of users, the standards specification process must be extended to include the development of Application Profiles, Implementation Agreements, and Conformance Criteria which will promote interoperability. The NIUF addresses all of these areas.To promote an ISDN forum committed to providing users the opportunity to influence developing ISDN technology to reflect their needs;To identify ISDN applications, develop implementation requirements, and facilitate their timely, harmonized, and interoperable introduction; andTo solicit user, product provider, and service provider participation in the process.The NIUF seeks to achieve three principal objectives:The actual work of the NIUF is accomplished in two workshops: the ISDN User\u2019s Workshop (IUW) and the ISDN Implementor\u2019s Workshop (IIW). The IUW produces Application Requirements which describe potential applications of ISDN and the features which may be needed. The IIW develops Application Profiles, Implementation Agreements, and Conformance Criteria which provide the detailed technical decisions necessary to implement an application requirement in an interoperable manner. The NIUF Executive Steering Committee coordinates the activities of the two workshops.133 active applications for development of Application Profiles have been accepted;Application Profiles have been completed for 14 applications;12 Implementation Agreements have been completed; and8 Conformance Tests have been completed.Since its inception in 1988, the NIUF has achieved the following:CSL established the NIST Special Publication 823 series, Integrated Services Digital Network Technology Publications, to publish the approved Implementation Agreements, Conformance Tests, and other NIUF documents. Copies of these documents are available for sale by the Government Printing Office, (202) 783-3238 or the National Technical Information Service, (703) 487-4650.The October NIUF focused on finalizing plans for the Transcontinental ISDN Project 1992 (TRIP \u201892) on November 16\u201320, 1992, which marked the advent of National Integrated Services Digital Network . Cosponsored by the NIUF and the Corporation for Open Systems (COS), TRIP \u201892 involved 74 user organizations in 149 locations across North America as well as several international sites. National ISDN-1 is based on national and international standards and is consistent with Implementation Agreements developed by the NIUF.TRIP \u201892 Open Houses across the nation featured demonstrations of ISDN applications available to government and industry such as video/multimedia conferencing, desktop conferencing and screen sharing, LAN-to-LAN bridging, medical imaging, Group 4 facsimile, and image and large data file transfer. NIUF industry partners participating in the demonstrations at the NIST Open House site included AT&T Bell Laboratories, COMSAT, Bell Atlantic, and Northern Telecom. Also featured was a special session for about 170 government and industry executives. Speakers at this session included Robert M. White, Under Secretary for Technology, who presented a government view of national ISDN, and Irwin Dorros, Executive Vice President, Bellcore, who gave the industry perspective.A Catalog of National ISDN Solutions for Selected NIUF Applications and A Generic Model for ISDN Cost Analysis. Both documents resulted from a cross-industry team effort by NIUF members. The catalog focuses on demonstrating solutions for those applications identified as most important by an NIUF survey; most applications are satisfied with basic rate ISDN access and can be implemented using NI-1 solutions. The cost analysis document contains an ISDN checklist of both hard and soft costs and benefits. The document also includes a spreadsheet available in Microsoft Windows and MAC-based Excel, from which users can form the basis for their own customized spreadsheet for an ISDN cost analysis.Other highlights of the October meeting included a demonstration of Remote Message Retrieval Over ISDN by the Messaging and Answering Group and completion, subject to final approval at the NIUF February 1993 meeting, of two significant NIUF documents: For more information about the NIUF and its publications or to obtain conference proceedings, contact the NIUF Secretariat: Dawn Hoffman, Computer Systems Laboratory, National Institute of Standards and Technology, Building 223, Room B364, Gaithersburg, MD 20899-0001; telephone (301) 975-2937 or Fax (301) 926-9675."} +{"text": "Juvenile arthropathy it\u2019s a term combining heterogeneous group of joints diseases in children, which are characterized by structural, morphological and functional changes of inflammatory nature and non inflammatory disorders. Chronic inflammatory process may be \"driving\" mechanism that is determine the nature of the articular lesions with specific clinical, instrumental and laboratory picture or maybe just one of the features of another pathology. Similarity of clinical and radiological picture, chronic nature of the flow, various of pathogenetic therapy and outcomes of the disease do this group one of the difficult to diagnose.To study the masks of JIA and no rheumatology pathology joint in children of Russian Federation.Clinical, serological, x-ray manifestations, ultrasound, MRI, arthroscopy data were analyzed in more then 300 children which examined in hospital department with presumptive diagnosis JIA.All children were subjected to complete rheumatology examination, and remained under our observation for a long time in order to assess the dynamic of the articular lesion. Children with classic course of JIA were appointed basic anti-inflammatory drugs . In cases when clinically atypical duration or laboratory \"mute\" of arthritis, long persistence monoarthritis and also variants with fever or destructive bones change we were applied deeper imaging methods such as MRI, arthroscopy, 3-phase osteo scintigraphy and other. Over five years were diagnosed six cases of tuberculous lesion of the joints (specific destruction of bone + biopsy), two cases of tuberculous periarthicular soft tissue (cyst formation with tyromatosis), fourteen cases of vascular anomaly , five cases of atypical localization focus of osteoid-osteoma , six cases of pigmental villous and chronic hemorrhagic synovitis of the knee and ankle joint, several cases of the skeletal dysplasia, and in rare cases of histiocytosis, malignant B-cell lymphoma, osteomyelitis and other rare bones disorders. Not one cases of the CRMO. In many cases due to this methods, we were excluded such diagnosis like tumors of the joints, different forms osteochondropathy. Such typical changing of the bones in JIA are usually degenerative nature in chronic uncontrolled inflammation.In some cases in undifferentiated arthritis, time of the diagnosis may determine the success of treatment. Any arthritis after failure of anti-inflammatory and antibacterial therapy should be questioned of rheumatic nature. Application invasive and non-invasive additional imaging methods can reduce the risk of incorrect diagnosis.None declared."} +{"text": "Narrative approaches and storytelling are emerging as powerful health promotion tools that can spark interest, increase understanding of determinants of health, and translate complex science. A Story of Health, a multimedia e-book with continuing education credits was designed to harness the power of storytelling to increase environmental health literacy. Health professionals are a key audience. They recognize that patients may be suffering from preventable illnesses of environmental origin but often feel ill-equipped to educate individuals and families about risks associated with common exposures. A Story of Health seeks to fill this gap and help readers develop the competencies they need in order to help patients make informed choices, reduce health risks, improve quality of life, and protect the environment. Americans rate nurses and medical doctors as having the highest honesty and ethical standards of all professions. These medical professionals can play a key role in changing patterns of patient behavior and influencing public policies. The e-book provides an easily accessible method of developing environmental health competency. The multimedia format with graphical interpretations allows for quick reviews of topics or for more in-depth analysis via links to additional resources. The CE evaluations have been overwhelmingly positive. A Story of Health multimedia e-book with continuing education (CE) credits was designed to harness the power of storytelling to increase the environmental health literacy of health professionals, policy makers, and health advocates; encourage inclusion of anticipatory guidance in professional practice, and stimulate policy changes.Narrative approaches and storytelling are emerging as powerful health promotion tools that can increase understanding of determinants of health and translate complex science . Case-baA Story of Health capitalizes on the narrative approach to teaching by using fictional stories to convey how multiple environmental factors interact with genetics to affect health across the life span. The first installment of the 150-page peer-reviewed e-book, which includes chapters on asthma (Brett\u2019s story), developmental disabilities (Amelia\u2019s story), and childhood leukemia (Stephen\u2019s story), was released in 2015 and is available online without cost . Free CE credits are offered through the Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR). About two-thirds of the downloads are accompanied by CE registration suggesting that CE credits are an incentive for health professionals to read A Story of Health.The stories explore influences of the natural, built, chemical, food, economic, and social environments on health across the life span\u2014from conception to elder years. The individual stories reveal how these environments are further expressed through education, family structures, housing, nutrition, access to health care, social supports or stressors, and more. Collectively, these multi-level variables interact to create conditions conducive to health and wellness\u2014or vulnerability and disease. Health promoting interventions from the individual level to the policy level are highlighted to encourage action.A Story of Health\u2019s ecological approach is central to the concept of environmental health literacy, a relatively new subdiscipline that \u201ccombines key principles and procedural elements from the fields of risk communication, health literacy, environmental health sciences (EHS), communications\u2019 research and safety culture\u201d , \u201cParents of young children are intensely interested in the impact of the environment on their children\u2019s health. They may look to their pediatrician for guidance about how to evaluate news reports about potential hazards in the air, water, and food\u201d . PediatrA 2015 survey of more than 200 pediatric oncologists, fellows, and nurse practitioners also underscored the need for increased training about environmental health exposures related to cancer . AlthougA recent national online survey of more than 2,500 fellows of the American Congress of Obstetricians and Gynecologists (ACOG) also revealed that routine guidance to patients on the health effects of environmental exposures was not a high priority . AlthougA Story of Health provides an alternative method of developing environmental health competency for health care providers, as it can be easily accessed online and reviewed at the time and pace of one\u2019s choosing. The multimedia format with graphical interpretations allows for quick reviews of topics, or more in-depth analysis via links and references to additional resources. Web-based medical education matches the efficacy of more traditional forms of delivery such as face-to-face conferences and lectures Toxicity. During a 1-year period, A Story of Health CE course received more than double the registrations of one of the most popular ATSDR/CDC courses.Acquiring the knowledge and skills to counsel patients and families about the risks associated with exposure to environmental toxicants may be challenging for health care providers because of busy schedules, required continuing medical education in their specialties, and the relative scarcity of professional training about environmental health. lectures without A Story of Health describe the lives of people with different diseases, several common themes resonate throughout the e-book:Although the fictional narratives in Important environmental influences come from the natural, chemical, food, built, and social environments.Although there are exceptions, most diseases, as well as good health, are the result of complex interactions between genes and multiple environmental influences.Early-life experiences, particularly during critical windows of development, can have profound beneficial or detrimental lifelong effects, even into elder years.Preventing disease and promoting health require actions and commitments from the individual, family, community, and society, as they are all interconnected.A Story of Health team is currently developing the fourth story for the e-book on infertility and reproductive health\u2014Reiko and Toshio\u2019s Story\u2014that echo these common themes.A Story of Health is designed to convey complex concepts about multi-level influences on health through a family reunion scenario (scenario . A nesteThe fictional cases are communicated in text, illustrations, graphic images, videos, and links to additional resources and journal references. The stories include the following key concepts:Early origins of childhood and adult diseaseEpigeneticsMechanisms of actionAllostatic loadWindows of susceptibility and opportunityEffect modifiersEnvironmental justice and health disparitiesThe stories weave in relevant information about disease trends and demographics. They also include potential interventions, policy recommendations, and helpful tools, such as environmental exposure checklists, for practical application in the real world.The e-book draws content from the research of the top scientists in their fields and brings the collective expertise of the Pediatric Environmental Health Specialty Units network and the National Institute of Environmental Health Sciences Children\u2019s Environmental Health Centers into the e-book in a variety of ways.A Story of Health was developed through a cooperative effort of the ATSDR, the Collaborative on Health and the Environment, the California EPA Office of Environmental Health Hazard Assessment, the Science and Environmental Health Network, and the Western States Pediatric Environmental Health Specialty Unit. Leveraging the resources and networks of all the partners has also been an important outreach strategy.Promoting the availability of the e-book online via web sites, listservs, newsletters, YouTube presentations, and social media has been essential for reaching key audiences. A Story of Health filled a gap in their skills or knowledge, and > 89% reported they plan to apply the new knowledge to develop strategies and interventions in their practices (Currently, more than 3,300 health professionals, including physicians, nurses, and health educators, have registered for the online course. Evaluations have been overwhelmingly affirming. In an analysis of responses from users in the second quarter of 2015, > 95% indicated that ractices .With additional funding, and with new CE evaluation tools being developed by the CDC, the authors hope to conduct follow-up surveys of those who have taken the CE course to further evaluate the impact of the e-book. Use the following links:A Story of Health: http://wspehsu.ucsf.edu/for-clinical-professionals/training/a-story-of-health-a-multi-media-ebook/To download http://www.atsdr.cdc.gov/emes/health_professionals/index.htmlTo access CE registration:"} +{"text": "Promoting child wellbeing necessarily goes beyond the clinic as risks to child health and development are embedded in the social and physical environmental conditions in which children live. Pediatricians play a vital role in promoting the health of children in the communities they serve and can maximize their impact by advocating for and supporting efficacious, evidence-based strategies in their communities.To provide a succinct guide for community pediatric efforts to advance the wellbeing of all children and particularly disadvantaged children in a community, we conducted a theory-driven and structured narrative review to synthesize published systematic and meta-analytic reviews of policy-relevant, local-level strategies addressing potent and malleable influences on child health and development. An exhaustive list of policy-relevant, local-level strategies for improving child health was used to conduct a comprehensive search of recent (1990\u20132012), English language peer-reviewed published meta-analyses and systematic reviews in the 10 core databases of scientific literature. Our review of the literature encompassed six key conceptual domains of intervention foci, including distal influences of child health and proximal influences . We examined intervention effects on four key domains of child health and development: cognitive development, social and emotional competence, psychological and behavioral wellbeing, and physical health.Published reviews were identified for 98 distinct policy-relevant community interventions, evaluated across 288 outcomes. We classified 46 strategies as meeting scientific criteria for efficacy by having consistent, positive outcomes from high-quality trials . Another 21 strategies were classified as having consistent evidence of positive outcomes from high-quality observational studies only, while 28 strategies had insufficient evidence available to assess their effectiveness based on published reviews. We did not limit the review to studies conducted in the United States, but the vast majority of them were U.S.-based, and the results therefore are most applicable to the U.S. context.Based on our synthesis of published literature on community development strategies, we provide an illustration combining a comprehensive set of evidence-based strategies to promote child health and development across a wide-range of child health outcomes. A mounting body of research has documented the social gradient in child health . ChildreGiven the multiplicity of health risks associated with social disadvantage, strategies to promote child health and wellbeing necessarily go beyond the clinic and involve community-wide policy strategies that change the broader environments in which children live. There is a growing understanding that health disparity populations are overlapping populations suffering avoidable health inequities resulting from unequal distribution of health-damaging and health-protecting exposures in daily life ,11. PoliChild-focused community development initiatives offer great potential to prevent the numerous, potentially life-long and generationally transmitted, health inequities related to SES, race/ethnicity, and neighborhood. Recent efforts in the United States include the Promise Neighborhoods program modeled Despite sizeable investments in child-focused community development initiatives and the tremendous potential of such efforts to improve social and health inequities, extant enacted policies and programs often do not reflect effective practices based on scientific studies ,16,17. IThe Promise Neighborhoods Research Consortium (PNRC), a network of prevention scientists in the U.S., created a science-based framework to guide comprehensive, community-level efforts promoting development and health among socially disadvantaged children living in distressed neighborhoods . This frIn this paper, we present the results of a synthesis of published systematic reviews or meta-analyses of six intervention domains for protecting and promoting child health. We did not limit the review to studies conducted in the United States, but the vast majority of them were U.S.-based, and the results therefore are most applicable to U.S. context. Based on our synthesis of the published literature, we provide an assessment of the current state-of-the-science regarding community development strategies that influence child health. Finally, we present an illustration of a comprehensive set of evidence-based strategies for child health as guidance for pediatricians and other child health advocates advancing local community development efforts. Scientific evidence on health promotion and risk prevention strategies is diverse, complicated, inconsistent in quantity and quality, and often inaccessible to policymakers, health care providers and other community stakeholders . Our goaWe conducted a theory-driven and structured narrative review of systematic reviews of a comprehensive set of community development strategies for child health. We limited the scope of our narrative review to those strategies that have been assessed in peer-reviewed, published meta-analyses or systematic reviews for three reasons. First, the scope of the conceptual framework guiding our work precludes exhaustive review of individual studies or newly emerging reports on prevention strategies that have yet to warrant systematic review. Second, systematic reviews represent the pinnacle of the \u201clevels of evidence\u201d hierarchy and provide the best practical method for identifying effective interventions . Third, Guided by our conceptual framework Figure\u00a0, scholarWe include summaries of effects on both primary and intermediate child health outcomes. We define primary outcomes to include any measures of cognitive development, social/emotional competence, absence of psychological and behavioral problems, and physical health among children or adolescence. We define intermediate outcomes to include measures of any of the proximal and distal influences on primary child outcomes Figure\u00a0. For exalevel of evidence on a scale of 1 to 3 for each strategy following the standards of evidence for efficacious interventions laid out by the Society for Prevention Research . Gu. Gu15]. Published systematic reviews address 98 policy-relevant strategies with 288 studied outcomes ranging from primary indicators of child health to measures of important physical and social contextual influences on child health. Less than half (46 of 98) intervention strategies meet scientific criteria for efficacy, as defined by the Society of Prevention Research by havinhttp://promiseneighborhoods.org) displays all policy briefs in a searchable format organized by domain of influence on child health and development. The Consortium is also working actively to disseminate this information to the recent Promise Neighborhoods grantees and others planning community development initiatives.Our primary objective was to organize a very large and diverse literature into a conceptually logical framework that reflects the best of current science, and succinctly summarize large bodies of scientific literature that makes clear to end-users the strength of evidence and size of estimated effects across the whole range of community changes thought to improve child health and wellbeing. Additionally, for each intervention, we created policy briefs to provide pediatricians, local-level policymakers, and other stakeholders with accessible science-based summaries to help identify policies that may effectively address child health needs in their community and facilitate community action around those issues. The Promise Neighborhoods Research Consortium website of the quality of the reviews. However, narrative literature reviews with no systematic review or meta-analytic methods were excluded from our summary. We critically evaluated the studies included in each published review, classified the level of evidence, and provided a summary of findings. No individual study can definitively answer the question of a policy\u2019s effectiveness across populations and time. Therefore, the accumulation of evidence and meta-analysis of outcomes across studies provides a more accurate assessment of effectiveness than a single study. Finally, the vast majority of studies were U.S.-based, and the results therefore are most applicable to U.S. context. Therefore, one should generalize to other countries with care, especially when considering countries that are quite dissimilar to the U.S.We present a current state of the science in order to (1) inform pediatricians and other child health advocates about policy-relevant community strategies with the most evidence demonstrating efficacy at improving primary child health outcomes, proximal influences of child health and development , and distal influences ; as well as to (2) inform scientists of community interventions that require more empirical attention to determine their efficacy at improving child health and reducing health disparities. It is our hope that continued evaluation and systematic review of child health policies and policy-relevant strategies, in conjunction with translation of the most evidence-based strategies into effective polices and practices, will lead to optimal child outcomes and minimal health disparities.The authors declare that they have no competing interests.KK, AT and AW participated in the conceptualization of the study concept and design. AD and AT participated in the acquisition of data. AT, RO, AD, KK and AW participated in the analysis and interpretation of data. AT, RO, AD and KK drafted the manuscript. KK, AW, RO and AT participated in critical revision of the manuscript for important intellectual content. KK and AT supervised the study. All authors read and approved the final manuscript.Kelli A. Komro, MPH, PhD is Professor of Health Outcomes and Policy in the College of Medicine, Associate Director of the Institute for Child Health Policy, and University of Florida Research Foundation Professor.Amy L. Tobler, MPH, PhD is Assistant Professor of Health Outcomes and Policy in the College of Medicine and Institute for Child Health Policy at the University of Florida.Alexander C. Wagenaar, PhD, is Professor of Health Outcomes and Policy in the College of Medicine and Institute for Child Health Policy at the University of Florida and Associate Director of Public Health Law Research, a national program of the Robert Wood Johnson Foundation, housed at the Temple University Beasley School of Law.Alexis L. Delisle, MS, was an Institute for Child Health Policy predoctoral fellow at the time of this work.Ryan J. O\u2019Mara, MS, is an MD/PhD student at the University of Florida and was a Research Assistant in the Institute for Child Health Policy at the time of this work.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/13/172/prepubPolicy-relevant community strategies by level of evidence.Click here for filePolicy briefs for strategies by level of evidence.Click here for file"} +{"text": "The unfolded protein response (UPR) occurs in response to endoplasmic reticulum (ER) stress caused by the accumulation of unfolded or misfolded proteins in the ER. The UPR is comprised of three signaling pathways that promote cytoprotective functions to correct ER stress; however, if ER stress cannot be resolved the UPR results in apoptosis of affected cells. The UPR is an important feature of various human diseases, including multiple sclerosis (MS). Recent studies have shown several components of the UPR are upregulated in the multiple cell types in MS lesions, including oligodendrocytes, T cells, microglia/macrophages, and astrocytes. Data from animal model studies, particularly studies of experimental autoimmune encephalomyelitis (EAE) and the cuprizone model, imply an important role of the UPR activation in oligodendrocytes in the development of MS. In this review we will cover current literature on the UPR and the evidence for its role in the development of MS. The endoplasmic reticulum (ER) is one of the largest cellular organelles in eukaryotic cells, and consists of two types, rough ER and smooth ER Kaufman, . SecretoThe PERK protein contains an ER transmembrane domain, a cytosolic kinase domain, and a regulatory luminal domain by its endoribonuclease activity to produce the active transcription factor spliced XBP1 (sXBP1). sXBP1 enhances the expression of chaperones and certain cytoprotective genes, and promotes ER expansion is a T cell-mediated autoimmune demyelinating disease of the central nervous system (CNS) is the primary animal model used in MS research that displays many of the clinical, pathological, and immunological features of MS plays a critical role in the development of MS and EAE to young adult mice induces a synchronous consistent demyelination that allows for temporally controlled activation of PERK signaling specifically in oligodendrocytes has been generated 10, elevates the level of p-eIF2\u03b1 exclusively in oligodendrocytes, significantly ameliorates the severity of EAE clinical symptoms, and attenuates EAE-induced oligodendrocytes loss, demyelination, and axon degeneration in the CNS. Oligodendrocyte loss is one of the first signs of pathological changes in EAE and can occur before demyelinating lesions are identifiable. Importantly, the low dose of AP20187 treatment significantly reduces the number of apoptotic oligodendrocytes in the CNS of heterozygous PLP/Fv2E-PERK mice before the onset of clinical disease and the formation of demyelinating lesions (at PID12). Moreover, moderate PERK activation in mature oligodendrocytes does not significantly affect the immune responses in CNS or peripheral immune system during EAE against inflammatory attacks in immune-mediated demyelinating diseases suggesting activation of the ATF6 branch of the UPR in oligodendrocytes (Lin et al., PLP1 mutant mice and that CHOP deletion exacerbates the clinical symptom and oligodendrocyte apoptosis in PLP1 mutant mice. It has also been shown that upregulation of CHOP induced by moderate PERK activation in oligodendrocytes of heterozygous PLP/Fv2E-PERK mice does not have a detrimental effect on the cells under normal or disease conditions (Lin et al., PLP/Fv2E-PERK mice with a high dose of AP20187 strongly activates PERK signaling specifically in oligodendrocytes, resulting in strong inhibition of protein biosynthesis and upregulation of CHOP in the cells. Notably, strong PERK activation inhibits the myelinating function of oligodendrocytes in young developing mice by suppressing protein translation, but does not affect oligodendrocyte viability. Intriguingly, strong PERK activation in mature oligodendrocytes of fully-myelinated adult mice had minimal effects on the function and viability of the cells (Lin et al., A large number of studies have demonstrated that CHOP, an effector of the PERK-eIF2\u03b1 pathway, functions as a pro-apoptosis transcription factor in many cell types during ER stress (Tabas and Ron, It is well-documented that the UPR influences the development of a number of human diseases, including inflammatory diseases, neurodegenerating diseases, myelin disorders, and tumors (Zhang and Kaufman, in vitro model of myelination (Lin et al., Using genetic approaches, the studies described above well-documented the cytoprotective effects of the PERK-eIF2\u03b1 pathway on both mature and remyelinating oligodendrocytes in mouse models of MS (Lin et al., The ER is essential for the biosynthesis of myelin lipids and proteins. The volume of the ER increases dramatically in the cytoplasm of oligodendrocytes during the active phase of myelination (Wollmann et al., While the actions of PERK activation in oligodendrocytes in immune-mediated demyelinating diseases have been studied extensively, the underlying mechanisms through which PERK mediates protection remain unknown and deserve further investigation. Moreover, activation of the PERK pathway has been observed in other cell types in MS and EAE demyelinating lesions, including T cells, microglia/macrophages, and astrocytes (Chakrabarty et al., For many years, the focus of MS research has been on T cell-mediated demyelination of the white matter. Recent studies, however, have shown that neurodegeneration is not only an early event but also the primary cause of chronic disability in MS (Dutta and Trapp, In summary, previous studies have demonstrated the cytoprotective effects of the PERK branch of the UPR on oligodendrocytes in models of MS. Future studies will need to assess the role of other branches of the UPR in oligodendrocytes and the roles of individual branches of the UPR in other cell types involved in MS, particularly neurons, in this disease. The knowledge gained from these studies would provide a foundation to develop therapeutic strategies that protects both oligodendrocytes and neurons in patients with MS.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Cats have been transported as human commensals worldwide giving rise to many feral populations. In Australia, feral cats have caused decline and extinction of native mammals, but their time of introduction and origin is unclear. Here, we investigate hypotheses of cat arrival pre- or post-European settlement, and the potential for admixture between cats of different invasion events. We analyse the genetic structure and diversity of feral cats from six locations on mainland Australia, seven Australian islands and samples from Southeast Asia and Europe using microsatellite and mitochondrial DNA data.Our results based on phylogeographic model selection are consistent with a European origin of cats in Australia. We find genetic distinctiveness of Australian mainland samples compared with Dirk Hartog Island, Flinders Island, Tasman Island and Cocos (Keeling) Island samples, and genetic similarities between some of the island populations. Historical records suggest that introduction of cats to these islands occurred at the time of European exploration and/or in connection with the pearling, whaling and sealing trades early in the 19th century. On-going influx of domestic cats into the feral cat population is apparently causing the Australian mainland populations to be genetically differentiated from those island populations, which likely are remnants of the historically introduced cat genotypes.A mainly European origin of feral cats in Australia, with possible secondary introductions from Asia following the initial establishment of cats in Australia is reasonable. The islands surrounding Australia may represent founding populations and are of particular interest. The results of the study provide an important timeframe for the impact of feral cats on native species in Australia.The online version of this article (doi:10.1186/s12862-015-0542-7) contains supplementary material, which is available to authorized users. The deliberate or accidental translocation of species from their native habitat to new environments by humans , 2 may tVulpes vulpes) and the domestic cat (Felis silvestris catus) . All sequence data is available on GenBank, .The microsatellite data sets supporting the results of this article are available in the Dryad repository [Dryad doi:10.5061/dryad.6t066 ("} +{"text": "Cryptosporidium and Giardia (oo)cysts on environmentally relevant surfaces such as brushed stainless steel, formica, ceramic, fabric, and skin. Parallel experiments were conducted using clean and soiled coupons incubated under three temperatures. The die-off coefficient rates (K) were calculated using first-order exponential formula. For both parasites, the fastest die-off was recorded on fabric, followed by ceramic, formica, skin, and steel. Die-off rates were directly correlated to the incubation temperatures and surface porosity. The presence of organic matter enhanced the survivability of the resting stages of test parasites. The decay rates calculated in this study can be used in models for public health decision-making process and highlights the mitigation role of hand hygiene agents in their prevention and control.The objective of this study was to find out the impact of environmental conditions on the survival of intestinal parasites on environmental surfaces commonly implicated in the transmission of these parasites. The study was performed by incubating Enterobius vermicularis is more prevalent in temperate areas of parasites. Although with the present knowledge it is not possible to precisely define the role of environmental variables in the survival of parasites (oo)cysts, recovery of neglected enteric parasitic (oo)cysts/ova from naturally contaminated hands of children reported previously coupled"} +{"text": "Immune reconstitution inflammatory syndrome (IRIS) is originally described in association with antiretroviral therapy (ART) for HIV infected patients. IRIS consists of a broad spectrum of inflammatory diseases, such as infectious inflammatory, neoplastic, and autoimmune diseases, that present after starting an effective ART, leading to CD4+ cells increase and plasma HIV-RNA reduction. IRIS reflects either worsening of an already-diagnosed infection or presentation of previously subclinical infection. Opportunistic pathogens include cryptococcus, mycobacterium, herpesviruses, or also auto-antigens. The paradoxical worsening of clinical symptoms as observed in IRIS is also the phenomenon of drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS). In the course of DIHS/DRESS, cytomegalovirus diseases and herpes zoster are observed coincidently with the increase in lymphocytes or rapid reduction of systemic corticosteroids. Based on the similar manifestations between IRIS and DIHS/DRESS, DIHS/DRESS can be seen in a broad context as another manifestation of IRIS. Although the mechanisms of IRIS is complex and variable, depending on the latent pathogens and shift of immune status, use of the concept of IRIS can help our recognition of various manifestations that occur in the setting of DIHS/DRESS. The understanding of IRIS may improve the morbidity and mortality rates of DIHS/DRESS."} +{"text": "Engagement with social media, such as Facebook, Instagram, and Snapchat, may lead to negative outcomes for body dissatisfaction and disordered eating due to the appearance focused nature of the online interactions. The aim of this cross-sectional study was to examine relationships between social media photo-related activities and overvaluation of shape and weight, body dissatisfaction, and dietary restraint in adolescent girls. Participants were 101 year 7 girls who completed measures of social media use and body image and disordered eating via self-report. Significantly higher levels of overvaluation of shape and weight, body dissatisfaction, dietary restraint, and internalisation of the thin ideal were found for participants who regularly shared self-images on social media, compared with those who were not regular sharers. In addition, after controlling for media exposure and internalisation of the thin ideal, higher engagement in manipulation of self-images and greater investment in the self-images prior to sharing were associated with greater overvaluation of shape and weight, body dissatisfaction, and dietary restraint. Findings suggest that self-image related social media activities may contribute to body dissatisfaction and disordered eating and indicate important contemporary targets for social media based intervention for these problems."} +{"text": "To the Editor: Diphyllobothriosis, infection by tapeworms of the genus Diphyllobothrium (Cestoda: Diphyllobothriidea) in 2011 and increases continuously. More than 200,000 tons of fresh or chilled fish, which may serve as source of human fishborne diseases if eaten raw or undercooked, are imported to Spain every year. The fourth largest importer is Ecuador, the sixth is Chile, and the seventh is Peru; D. pacificum, in Europe, but it is highly probable that this species can be introduced anywhere through the importation of fresh or chilled fish from the Pacific coast of South America. This has implications for food safety rules and human health risk measures taken by national health and veterinary agencies. Regarding adequate processing of clinical samples and their preservation for morphologic and genetic evaluation, we strongly recommend fixation of positive fecal samples with eggs or segments (proglottids) immediately with 96%\u201399% molecular grade ethanol for future molecular diagnosis (In the present study, we confirmed human infections with the Pacific broad tapeworm, A summary of Diphyllobothrium and Diplogonoporus cases in Spain, photomicrographs of features of diphyllobothriids, and results of testing for human-infecting Diphyllobothrium spp."} +{"text": "Poor health systems and structures in countries affected by Ebola virus disease (EVD) have compounded difficulties in access to hospital care for Ebola patients. With this low healthcare access, individuals may be forced to seek alternative remedies for the management of EVD. One major study suggested that the transfusion of whole blood and serum from patients who had recovered from EVD reduces the risk of EVD-related fatality , with adIn the wake of the growing epidemic, it is possible that this alternative may bring new challenges such as the emergence of a black market trading of blood of EVD survivors . This maConcerns about transfusion-related transmission of HIV and hepatitis infection in the sub-Saharan African region are not unfounded. Afolabi et al. demonstrIn the face of an epidemic with a high fatality rate and low likelihood for access to quality medical care , the proMorenike O. Folayan Institute of Public Health Obafemi Awolowo University Ile-Ife, Nigeria Department of Child Dental Health Obafemi Awolowo University Ile-Ife, NigeriaBrandon Brown Department of Population Health & Disease Prevention University of California Irvine, CA, USA Email: brandon.brown@uci.eduAminu Yakubu Department of Health Planning and Research Federal Ministry of Health Abuja, Nigeria"} +{"text": "Knowledge translation researchers in the last decade have seen a torrent of publications arguing for the central importance of organizational context in influencing implementation success. The Translating Research in Elder Care (TREC) program investigates the role of organizational context on the use of best practices, provider and resident outcomes in residential long-term care facilities (nursing homes) in three western Canadian provinces. The purpose of this presentation is to present findings from our study examining the influence of organizational context on the use of best practices by healthcare aides.We collected survey data from 36 nursing homes, 103 units and 1262 healthcare aides and used Hierarchical Linear Modeling (HLM) to assess elements of organizational context that predicted best practice use by healthcare aides. Organizational context was measured using the Alberta Context Tool (ACT).In the final models, instrumental use of best practices was predicted by age, sex, shift worked, job efficacy, belief suspension, and the contextual variables social capital, organizational slack, informal interaction frequency, unit type, and profit status; 18% of the variance was explained in the final model. Conceptual use of best practices was predicted by: English language status, job efficacy, belief suspension, intent to use research, number of information sources uses, perception of adequate knowledge, and the contextual elements leadership, feedback processes, organizational slack, availability of resources, and province; 43% of the variance was explained in the final model.Our study identifies several individual and contextual factors that play an important role in healthcare aides' use of best practices in nursing homes. This has important practical implications for designing strategies for dissemination and implementation of best practices to increase healthcare professionals' ability to practice evidence informed care to improve health outcomes.Funded by Canadian Institutes of Health Research (CIHR)."} +{"text": "Several studies have presented morphological, biochemical and histopathological changes in the paraspinal skeletal muscle of patients with adolescent idiopathic scoliosis (AIS). Some abnormalities have been demonstrated such as an increased amount of type I fibers in the concavity and the decreased number of type II in the convexity, an increase in the intracellular concentration of glycogen and lipids, structural changes in the sarcolemma and myotendinous junction, changes in the activity muscle enzyme, an increase in intracellular calcium concentration.To evaluate the rotator muscle fibers at the apical vertebraof curves of patients with AIS by histological and immunohistochemical analysis.Cross-sectional study.Twenty-one patients with AIS submitted to surgical correction between 2,010 and 2,013 had the spinal rotator muscles biopsied in the concavity and convexity of the apical vertebra of the thoracic curve during the surgery. Serial cryosections were stained with Hematoxylin-Eosin (HE) and Sudan Red. We evaluated muscle atrophy and hypertrophy, fatty proliferation, presence of endomysial and perimysial fibrosis, presence of hyaline fibers, mitochondrial proliferation, muscle necrosis, nuclear centralization and inflammation. Two independent observers evaluated the sections.The average value of the angle of the main thoracic curve was 68\u00b0 Cobb. For analysis of non-parametric paired variables between the concave and convex side it was used the McNemar test with a significance level of 5%. The results of relative frequency and \u201cp\u201d values showed significant difference in both endomysial and perimysialfibrosis and fatty involution when compared to both sides of the apical vertebra.The paraspinal muscles at the apex of the deformity had higher involvement in the concavity when analyzing the fatty involution and fibrosis. However, both sides showed signs of myopathy, muscle atrophy through areas of necrosis and hyaline presence of fibers, mitochondrial proliferation."} +{"text": "David Stephens and colleagues describe their experience of treating patients with Ebola virus disease at Emory University in the United States. Ebola hemorrhagic fever, or Ebola virus disease (EVD), has emerged in the last year as a global threat and humanitarian disaster for the affected countries of West Africa and has also come to the United States (US) and Europe.The treatment of the first and three subsequent US patients outside of Africa at Emory University provided a number of challenges, as well as strategic and tactical lessons that included detailed planning and team work across multiple academic and health care units, emphasizing biosafety, the importance of institutional communications, addressing unanticipated challenges such as waste management, and the logistics of working closely with governmental agencies and outside collaborators.In providing effective care for individuals, the value of mobilizing a diverse health and academic community to work collaboratively to addressing a global threat is emphasized. This includes dissemination of best practice information; providing education and training about EVD; expansion of new knowledge about the clinical course, complications, and pathogenesis of EVD; the creation of new institutional forums, and engagement in the broader policy and equity issues of contagious health threats.Zaire ebolavirus), began in Meliandou, Guinea, West Africa and soon enveloped neighboring Sierra Leone and Liberia, with cases also in Nigeria, Senegal, and Mali [Ebola hemorrhagic fever, or Ebola virus disease (EVD), is caused by a highly contagious group of enveloped, single-stranded, negative-sense RNA viruses of the family Filoviridae. The disease has historically carried 53%\u201388% mortality \u20133. In Deand Mali \u20135. WHO hospital in Liberia were evacuated from Monrovia by a specially designed air ambulance to Emory University Hospital (EUH) . Until AThe strategic and tactical lessons and challenges presented by providing care for the first and subsequent US EVD patients at Emory University provide an opportunity to share lessons that may help others. Specific clinical and immunological features and diagnostic and detailed management issues of the patients at Emory are reported separately \u201311. It iEUH is the flagship clinical care facility for Emory Healthcare, staffed by 1,221 Emory School of Medicine faculty physicians, with over 3,600 employees, 25,300 admissions, and 157,000 outpatient visits annually. The hospital has one of the highest case-mix indexes (a measure of complexity of illness treated) among the University Healthsystem Consortium (UHC)-ranked facilities. Emory had established strong programs in health care delivery, quality, infectious diseases (ID), infection control and biosafety, immunology, vaccines, and public health that were important to its ability to respond to this series of events.The Serious Communicable Diseases Unit (SCDU) , Box 1 oThe SCDU was designed to proviThe SCDU was constructed within the EUH clinical research unit. The clinical research unit has been in existence for some 60 years and supports clinical research through the National Institutes of Health (NIH)-funded Clinical and Translational Science Awards (CTSA) program. The SCDU offers on-call, highly trained staff operating under standardized, ready-to-go protocols for providing care for patients infected with highly communicable contagious diseases.While not necessary for treatment of EVD, the isolation rooms feature negative pressure air handling, 20 air changes per hour, with laminar flow and high-efficiency particulate air (HEPA)-filtering completed before the air is 100% exhausted outside of the hospital (no recirculation). General and intensive care can be provided. The SCDU was activated on two previous occasions. The first was in 2003 for a CDC worker with concern for having been infected with severe acute respiratory syndrome (SARS) in Hong Kong, China. The second was in 2005 for a CDC employee in Angola with potential Marburg virus hemorrhagic fever. While unit activation has been infrequent, intensive training in this unit to maintain a state of readiness has been continuous for well over a decade, including detailed preparation for transport of patients and the training of nurses and physicians.www.emoryhealthcare.org/ebolaprep [A virtual tour of the SCDU and videos addressing many of the most frequently asked questions, together with access to all SCDU policies and standard operating procedures (SOPs), are available on the Emory education web site: bolaprep .The ID program at EUH was built to provide expertise in hospital epidemiology, antimicrobial management, transplant infectious diseases, and clinical microbiology. For over a decade, Emory University was an active member of the NIH Research Centers of Excellence (RCE) in Biodefense and was the site for the biosafety training program for select pathogens of the Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB) RCE. This particular program provided invaluable expertise, equipment, and support for the EVD effort. Emory ID and Emory Healthcare (EHC) also created the TravelWell clinic, an outpatient clinic available for assessment and evaluation of pre- and post-travelers and supporting major Atlanta corporations and the CDC. Emory\u2019s TravelWell is part of a 57-site worldwide travel network (GeoSentinel) with a 10-year database of 3,000 entries of those who either had returned ill following travel to Liberia, Sierra Leone, Guinea, or Nigeria or had just emigrated from one of those countries.The request for medical care for the initial patients came from the missionary organizations Samaritan\u2019s Purse and Serving in Mission (SIM) USA and from the patients themselves. The decision was coordinated through the US State Department and the CDC. EUH and EHC leadership made the decision to accept the patients\u2014a decision made quickly but not lightly. The decision was based on the need, confidence in the overall preparedness of EUH, and the more than a decade plus of training and preparation to address highly communicable diseases at EUH . ImportaThe SCDU medical team is led by the SCDU director, an ID trained physician who has spearheaded for over a decade efforts in establishing the protocols, training, education, and operations of the unit in conjunction with the CDC. Three other faculty members of the Department of Medicine, four additional ID physicians, two pathologists, five medical technologists, and 21 critical care nurses also support the unit.An SCDU unit director, clinical nurse specialist, and team coordinator handle logistics, organize training sessions, determine supply needs, and establish nursing schedules. Nurses provide care in 4-hour stretches to minimize donning and doffing of personal protective equipment. The overall effort has directly involved over 125 staff and support personnel.During the care and treatment of EVD patients, there were daily communications between the SCDU medical team and the CDC\u2019s Division of High-Consequence Pathogens and Pathology (DHCPP), the Division of Healthcare Quality Promotion, and the Emergency Operations Center for Ebola established at CDC, and with the US Food and Drug Administration (FDA) and other US federal agencies, as well as frequent communications with other academic units, industry, and providers in West Africa.The primary focus of training was on biosafety for all individuals who provided direct care or handled body fluids. All of these individuals received mandatory education and training, followed by strict competency verification before medical or nursing staffs were permitted to provide care for these patients.Effective and assertive communication was central to the safety of the SCDU team. Use of the buddy system was an essential element of the focus on individual and colleague safety. Because communication was so important, the team developed rules to govern direct patient care communication as well as within daily team huddles. These rules were reviewed each morning during the daily huddle and served as a platform to empower all members of the team, regardless of role, to facilitate communication and to maintain strict SOPs.The hospital support team was led by the CEO of EUH. The chief medical and nursing officers of EHC and EUH, and in particular the vice president of operations of EUH, were also heavily involved in leading the support efforts. During the care and treatment of the EVD patients, an operations team of key administrators and nursing and physician leadership met twice a day. Despite the extensive preplanning, opportunities to refine and improve both clinical and operations were noted, and all aspects of the hospital services were involved. Pharmacy, environmental services, engineering/facilities support, and pastoral care/counseling were especially important.Other ID faculty, including a pediatric ID specialist with experience in EVD, provided support for the frontline medical team. Periodic conference calls focused on support, therapeutic options in treating patients, and issues of postexposure prophylaxis, vaccines, surge planning, protocol development, and discussions of research as it related to EVD. To facilitate the necessary availability of SCDU dedicated ID providers, alternate faculty were recruited to cover the regular duties of the SCDU physicians. ID support also included contacting key national and international research leaders in EVD; evaluating, contacting, and obtaining, through outside groups, experimental vaccines and new drugs for Ebola; and communicating with the CDC, FDA, NIH, and other federal agencies, other university partners, and biotech/industry contacts, all of which were essential in the effort.The Emory Environmental Health and Safety Office (EHSO) was engaged immediately after the call for ongoing support. While clinical care settings are very different from those of labs, EHSO staff included individuals with expertise in training on Biosafety Level BSL 3 and 4 laboratory safety, which was helpful in translating to our clinical care situation. Conversations were conducted by EHSO with other national biosafety leaders in EVD. attending coverage for critical care management issues including airway management and line placement issues. Other subspecialties, such as renal medicine, were required on a case-by-case basis. The location of the SCDU away from other patient care units of EUH significantly reduced the impact on our other health care delivery and patient operations. DHCPP at CDC provided critical help to the unit for viral loads, specialized assays, and other support.10 RNA copies per ml of serum [Different outside perspectives and guidance were initially provided about the level of biosafety needed for EVD. Ebola viruses have a very low infectious dose, 1\u201310 aerosolized organisms, in nonhuman primate models and can of serum ), stool,To achieve the lowest risk to health care personnel, the highest level of biosafety was initially employed. This included MAXAIR powered air-purifying respirators (PAPRs), fluid-resistant body suits along with cover aprons, double gloves and shoe covers, and wiping down all surfaces with US Environmental Protection Agency (EPA)-registered disinfectants (no spraying) when doffing PPE. Other key biosafety SOPs developed were autoclaving within the unit for waste management, followed by disposal of regulated medical waste off-site after it had been autoclaved; decontamination; and handling of laboratory samples and waste. The consequences of transmission stressed the need for the highest level of biosafety.The importance of the EHSO office in reinforcing the prior training of personnel and monitoring the clinical staff for consistency and adherence to biosafety from training sessions to practices in real-time clinical care cannot be overemphasized. This included how to \u201cdon and doff\u201d impermeable fluid-resistant body suits, proper use of PAPRs, coordination of the disposal of waste, and the handling and transport of lab samples. EHSO also helped prepare and support the team psychologically, challenging them with spills and other incidents to practice remaining calm in the face of potential unexpected occurrences. Team engagement demonstrated the importance of melding the philosophies of clinical treatment/practice and biocontainment/biosafety. Feedback from frontline physicians, nurses, and hospital staff highlighted the contributions of EHSO to the effort and the value of the EHSO biodefense education and training expertise.Waste management for EVD is a significant hurdle. EVD results in copious amounts of vomit and diarrhea with up to 10 liters of fluid lost by patients each day. Up to 40 large \u201cbags\u201d per day of regulated medical waste were generated by our first two patients. A large-capacity autoclave was mobilized, with postautoclaved waste stored in 32-gallon leak-proof rubber waste containers in the SCDU until removal and incineration. All waste in toilets was disinfected with an EPA-registered disinfectant before flushing. Importantly, no traces of Ebola RNA on \"high-touch surfaces\" such as beds and bathrooms were detected during active care or after patient discharge prior to terminal decontamination with vaporized hydrogen peroxide.Guiding principles for communications included consistent messaging and protecting patient privacy while educating the public. Internal communications with a focus on transparency and education, within the bounds of confidentiality of medical information and protecting our patients\u2019 privacy, were vital. These included meetings with EUH hospital leadership and staff to address concerns, frequent emails and other communications with all faculty and staff at EHC and Emory, making sure instructions/checklists were in place, and facilitating the dissemination of protocols. To avoid unauthorized access to electronic medical records, a chart-warning flag was implemented. Confidentiality of medical information regulations were repeatedly stressed to all medical staff, residents, and fellows.www.emoryhealthcare.org/ebolaprep) [In external communications and interface with the media, the Emory communications teams tirelessly addressed media logistics, developed web and social media material, worked closely with governmental and nongovernmental external groups, developed talking points, and prepared the hospital and SCDU teams for communications venues. To maximize our preparedness and to address national concerns, press conferences and media interviews were conducted, and an EVD Questions and Answers document was developed and posted. The story exploded in broadcast print and social media. Over 84,000 media stories have been written linking Emory and Ebola. Emory communications created an Emory Healthcare Ebola Preparedness Protocols website (olaprep) to make The admissions heightened Ebola and other bio-threat concerns both locally and nationally. Questions about potential EVD patients began to occur immediately in our health care system and throughout the US. We developed and disseminated flow diagrams, algorithms, and SOPs for evalAs noted, a highly trained group of faculty, nurses, biosafety support, and other providers staff the EUH SCDU. While no trainees served on the direct care team, trainees benefitted from the experience of the unit and clinical experience with EVD through conferences and other education venues . An EVD \u201cMicro Vignette\u201d and other educational materials were developed for resident and fellow education. Further, ID and other specialty fellows have been integrated into the management planning for EVD patients, educated on the broader policies and procedures of the unit, are involved with the development of protocols for the management of Ebola patients who present to the Emergency Department (ED) or other clinical settings, and are educated about the collective experiences in treating the patients. In addition, a Massive Open Online Course (MOOC) \u201cEbola at Emory: Patients to Populations\u201d has been launched , an EBOLWork was initiated to better understand EVD pathogenesis and therapeutic options \u201311,15\u201319The event also led to broad faculty engagement across all parts of the institution through the creation of an Emory Ebola Task Force and Ebola Faculty and Community Discussion Forum . The TasEVD has arrived in North America and Europe and impacted us globally. Academic medical centers can be expected to be at the frontline to address EVD and other highly communicable infectious agents in the future. Our experience with EVDCommunicable infectious diseases will continue to be global threats to human health and have the potential to cause repeated humanitarian disasters.Coordination, detailed planning, and teamwork across governmental, nongovernmental, academic, and health care unitsEnvironmental Health and Safety as a key support team memberPreparedness in training, biosafety, surveillance, and communicationsDonning and doffing of PPEWaste management protocolsDecontamination and containment protocolsSpecimen handling for diagnostic testingEvaluation of provider competency in biosafetyAn organizational structure to solve unanticipated challenges and the logistics of working closely togetherThe rapid dissemination of best practice informationProviding education forums and frequent educational communications around disease transmission and riskConsistent messaging and protecting patient privacy while educating the publicExpanding new knowledge about the clinical course, complications and pathogenesis, diagnosis, treatment, and preventionEngagement in the broader policy issues of global health care inequitiesOur experience as an academic health center with EVD emphasized the importance of preparation, communications, and implementation:The institutional experience, while providing the opportunity to effectively care for these individuals, has led to best practice information and the education and training of others, created key academic, governmental, and community partnerships, expanded research programs in EVD, and resulted in the development and communication of new knowledge about this emerging disease. Mobilizing our diverse academic community to work collaboratively on this global problem is also an important long-term outcome."} +{"text": "Tropical diseases remain a major cause of morbidity and mortality in developing countries. Although combined health efforts brought about significant improvements over the past 20 years, communities in resource-constrained settings lack the means of strengthening their environment in directions that would provide less favourable conditions for pathogens. Still, the impact of infectious diseases is declining worldwide along with progress made regarding responses to basic health problems and improving health services delivery to the most vulnerable populations. The London Declaration on Neglected Tropical Diseases (NTDs), initiated by the World Health Organization\u2019s NTD roadmap, set out the path towards control and eventual elimination of several tropical diseases by 2020, providing an impetus for local and regional disease elimination programmes. Tropical diseases are often patchy and erratic, and there are differing priorities in resources-limited and endemic countries at various levels of their public health systems. In order to identify and prioritize strategic research on elimination of tropical diseases, the \u2018First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination\u2019 was convened in Shanghai in June 2012. Current strategies and the NTD roadmap were reviewed, followed by discussions on how to identify and critically examine prevailing challenges and opportunities, including inter-sectoral collaboration and approaches for elimination of several infectious, tropical diseases. A priority research agenda within a \u2018One Health-One World\u2019 frame of global health was developed, including (i) the establishment of a platform for resource-sharing and effective surveillance-response systems for Asia Pacific and Africa with an initial focus on elimination of lymphatic filariasis, malaria and schistosomiasis; (ii) development of new strategies, tools and approaches, such as improved diagnostics and antimalarial therapies; (iii) rigorous validation of surveillance-response systems; and (iv) designing pilot studies to transfer Chinese experiences of successful surveillance-response systems to endemic countries with limited resources. Please see Additional file Effective and timely surveillance and responses tailored to specific settings reflect the ability of a health system to provide reliable and judicious information for public health policy, pragmatic action in infectious disease control and elimination, and efficient sustainable development ,2. TropiDespite growing international funding and logistical support offered by the World Health Organization (WHO), multilateral agencies, philanthropic organisations and a host of new consortia to fight tropical diseases, the public health burden and the challenges facing programmes to achieve sustained control and ultimate elimination of the major NTDs are still enormous ,14. It hThe \u2018First Forum on Surveillance-Response System Leading to Tropical Disease Elimination\u2019 was held on June 16-18, 2012 in Shanghai. The Forum was jointly supported by the National Institute of Parasitic Diseases of the Chinese Center for Disease Control and Prevention (NIPD/China CDC), the Swiss Tropical and Public Health Institute (Swiss TPH) and the WHO. The purpose was to share knowledge and experiences pertaining to the control, prevention and elimination of major tropical diseases and to discuss novel approaches towards the establishment of integrated surveillance-response platforms and networks to assist these efforts. The Forum brought together scientists, public health experts and health policy specialists to explore and discuss promising surveillance-response systems with focus on, but not limited to, malaria, schistosomiasis, lymphatic filariasis and other NTDs. The participants in each session were engaged in in-depth discussion on current challenges, opportunities and measures to foster reliable effective surveillance-response systems as the strategic key for endemic countries moving towards disease elimination.It was felt that the establishment of a conceptual framework to design and implement surveillance-response systems is critical for the elimination of tropical diseases including NTDs. Surveillance-response systems with regard to infectious diseases of poverty have gained traction, particularly in settings where health systems provide an integrated data repository capable of characterising disease dynamics at multiple scales. Evaluating the impact of implemented programme(s) and intervention(s) in public health centres and health services on the population-level towards prevention or control of tropical diseases would benefit by a system for surveillance and response leading towards maximum positive health outcomes. To summarise, the two-fold objectives of this paper were: (i) to establish a platform for resource-sharing and effective surveillance-response systems for Asia Pacific and Africa with an initial focus on elimination of lymphatic filariasis, malaria and schistosomiasis; and (ii) to explore new strategies, with an emphasis on improved and more sensitive diagnostics and antimalarial therapies in elimination programmes.Schistosoma japonicum had declined to an all-time low with less than 300,000 infected people [Before 1955, just after the founding of the People\u2019s Republic of China, many infectious diseases were highly endemic, particularly in the southern parts of the country, similar to the epidemic and pandemic documented in Africa between 1980s and 2000 [d people ,24.Plasmodium falciparum malaria has been eliminated as a public health threat in all provinces except Yunnan. Among the 24 malaria-endemic provinces, annual incidence rates have dropped below 1 per 10,000 in 95% of the endemic counties, and only 87 counties have a rate above this threshold [With regard to malaria, it must be noted that sustained efforts have reined in the endemic areas, which are now considerably smaller with the number of cases in China decreasing from an estimated 30 million in the 1940s to less than 5,000 by the end of 2011 . Today, hreshold ,27. HencKnowledge on the unrelenting control of its many endemic tropical diseases and the growing expertise in other disease-endemic regions of the world has shown that China can harness evidence-based knowledge and information, create innovative approaches and implement large-scale, effective solution for both its own people and the global community. The low-level transmission patterns of infection and re-infection rates in China and other endemic countries underscore that continuing control activities are critical for ultimate success of schistosomiasis and malaria surveillance-response systems. For example, transmission features in schistosomiasis include environmental contamination by eggs excreted by a large number of domestic and wild animal species that contribute to transmission; indeed the proportion of eggs from water buffaloes might account for up to 90% of all eggs found in the endemic areas ,32. In aP. vivax transmission and mixed infections with P. falciparum and P. vivax are documented, respectively [It was documented that active mapping of disease transmission hotspots and molecular characterization of genetic diversity and population dynamics were effective for early detection, allowing prompt treatment using safe and efficacious drugs. Meanwhile, patient compliance and adherence to any effective prescribed regimen is vital for public health management in primary healthcare and minimising the evolution of resistant parasite strains resulting from sub-therapeutic doses and drug selective pressure indicators. There is a pressing need to develop new surveillance tools and strategic responses to shift the focus from control to elimination. With regard to local elimination of malaria in China, specific response packages must be tailored for different settings . For exaectively ,37.Anopheles vectors and transmission [Highly sensitive and specific diagnostic tools are urgently needed to target mass screening of asymptomatic gametocyte reservoirs in low/moderate endemic areas as well as sub-microscopic parasitaemia and intensive integrated management of hotspots linked to environmental, climatic and ecological appropriateness for smission ,38. Intesmission . Additiosmission ,18.New reliable tools and efficient strategies against other communicable diseases were discussed, such as development of highly sensitive diagnostic assays for early detection of low-transmission settings, MDA, development and validation of vaccines for prevention and drugs for management, improvement of preventive strategies and environmental sanitation, information, education and communication (IEC), community participation and ownership, mechanisation of agriculture, sewage drainage, building of public latrines, waste management and provision of clean water as well as modelling based on a minimal essential database approach Table\u00a0.Health system and health policy makers, and government will require development and implementation of new surveillance-response system policies in the context of infectious diseases elimination towards eradication (e.g. containment of private-sector workers importing parasitic diseases). New policies will include prevention and control, community-based mobilisation, IEC as well as participation and cooperation to re-enforce management, community ownership and development, such as mechanisation of agriculture and food production. For example, in malaria information system, remote sensing, web-based information, eHealth and mHealth for health services, information and communication) have proved useful in controlling malaria in remote areas and enhancing active surveillance as well as new and fast ways of gathering geographical, spatial, ecological and meteorological data relevant for the understanding of foci of vector transmission, dynamics mapping for patient follow-up, containment of infections or outbreaks and monitoring resistance -43.In schistosomiasis, veterinary public health and emphasis on the socioeconomic importance of zoonoses are needed along with health education with special reference to farming and the development of a new policy for surveillance-response systems to contain outbreaks and resurgence. In addition to prevention, control and spatio-temporal surveillance tools relevant to the understanding of schistosomiasis transmission dynamics, mapping of infectivity and close monitoring of outbreaks are important ,44-46.Surveillance and response represent the final, crucial steps in achieving effective elimination of a disease , as recognised in many of the ongoing malaria and NTD elimination programmes -49. Intrhttp://www.theglobalfund.org/en/) [P. falciparum, a dry-season, breeding-site mapping and an epidemiological survey were conducted, followed by diagnosis of malaria patients in the community and treatment in combination with integrated vector management and long-lasting insecticidal net (LLIN) campaigns). In addition, in their move towards elimination of the vicious cycle of poverty and infectious diseases, malaria consortia should continuously provide technical assistance for health system strengthening and the development of innovative tools to improve malaria surveillance and provide national and district staff with the information they need to respond to malaria outbreaks as well as to individual cases [Passive and active surveillance systems have been utilised for different purposes and at different stages of disease control and elimination Table\u00a0. Passiveorg/en/) ,51. Actial cases ,52-54.P. vivax and P. falciparum malaria addressed based on WHO\u2019s global roadmap.The Forum elaborated on a set of effective and essential features to achieve infectious disease elimination, such as (i) political stability and good governance; (ii) commitment to use local resources for elimination activities; (iii) worthy organisational and technical infrastructure coupled with qualified and committed personnel; (iv) adequate general health care services delivery; (v) making communities understand and support the control programmes; (vi) no major uncontrolled population movements; and (vii) The move from morbidity control to interruption of transmission and achievement of elimination requires novel, advanced technologies, either aimed at reducing the infection reservoir or at reducing the rate at which infections spread. This can be done by an innovative research portfolio that is expanded to include NTDs, zoonoses and other socioeconomic determinants in most endemic countries, particularly in sub-Saharan Africa. Important outcomes from the First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination include foremost important lessons from previous outbreaks and resurgences of parasitic diseases in China and elsewhere; second, new surveillance-response platforms capable of further strengthening existing health systems at all levels; third, long-term commitment, which is crucial to achieve sustainability of the elimination agenda; fourth, political will, i.e. commitment to use local resources and implementation of innovative multi-sectoral, integrated approaches; fifth, improved diagnostic tools for early detection of infection and disease; and finally, but not the least, capacity-building, new partnerships and use of innovative technology to render existing surveillance-response systems more effective ,50,52,55The following questions were raised: (i) Do we have, and are we using, the most effective surveillance tools (this is of particular relevance with regard to diagnostics)? (ii) Are we implementing the most effective surveillance-response packages tailored to a given transmission setting? (iii) Is it possible to innovate and incorporate additional surveillance measures to existent interventions? (iv) What are the contributions of private companies to health? (v) How can we be sure that we move in the right direction? The Forum promptly progressed to addressing these questions during different sessions.Participants felt that the Forum provided a stimulating environment for exchange of ideas and experiences giving an impetus for rapid progress towards surveillance and response systems in elimination of tropical diseases that impact on the health and well-being of disadvantaged and marginalised populations in the world. It was concluded that the Forum should be held every 2 years. Hence, at the time of writing the current report, planning for the June 2014 forum is intensifying. The following recommendations for strengthening research on surveillance-response systems for disease elimination were put forward.The Forum recognised that containing the emergence and spread of tropical diseases requires early alertness, active detection and diagnosis of its pathogenic cause. Concerted efforts and effective partnerships are needed to share the roles and responsibilities in defining powerful surveillance-response systems to mitigate the public health burden of tropical diseases thereby ensuring scalability and sustainability.Setting up a genuine coordination and collaboration between Asia Pacific and Africa with regard to public health and control/elimination of malaria and NTDs was encouraged, emphasising surveillance-response systems that rely on an integrated and dynamic approach to risk management with ongoing research, data collection and real-time analysis, thereby driving evidence-informed knowledge translation into policy decisions and action with a feedback process to facilitate continuous advancement and adaptation.Continuous scrutiny of all aspects of infectious diseases occurrence and spread, pertinent to effective control and elimination, requires systematic collection, collation, analysis, interpretation and dissemination of health data and the establishment of a resource-sharing platform for surveillance-response system between Asia Pacific and Africa. Reconvening the Forum every 2 years would provide an opportunity to discuss progress and challenges in implementing local, national or regional surveillance-response system for targeted infectious diseases, discoveries and developments among scientists, public health specialists, politicians and other stakeholders.Importantly, documented limitations call for dispersion of technological advances in most developing countries of Asia Pacific and Africa, so that surveillance-response strategies and rapid diagnostic methods, tools and approaches can be improved. This requires continued innovation, validation and application of efficient, low-cost diagnostic, affordable novel therapeutic agents and vaccines ,5.in vitro sensitivity limitations of currently deployed detection tools (e.g. microscopy and rapid diagnostic tests) have been documented, and hence, there is a need for improved tools in assessing susceptibility [Sensitive diagnostic tools based on molecular methods and advanced biotechnological assays need to be developed as surveillance tools for monitoring and verification of elimination of tropical diseases ,39,52,56tibility ,56.The Forum provided a unique opportunity to discuss surveillance-response systems as the final stage towards elimination of infectious diseases, especially NTDs, based on a \u201cOne World-One Health\u201d perspective. Five research priorities were recommended: (i) dynamic detection and mapping of transmission, particularly low-level transmission, also using eHealth and mHealth; (ii) near real-time monitoring of population dynamics; (iii) modelling to establish minimal essential databases and indicators to be collected in space and time; (iv) design of effective response packages tailored to different transmission settings and levels; and (v) rigorous validation of approaches and response packages with regards to effectiveness within elimination programmes.It was emphasised that regional strategies, innovative data management tools, inter-sectoral, multi-disease control approaches and research framework on control and elimination of infectious diseases of poverty must be strengthened . SurveilChina can provide expert support on the establishment of diagnostic tools and techniques, in providing capacity building and training on tropical diseases to laboratory technicians, medical staff and disease control managers in Africa. Moreover, support in monitoring techniques and conducting collaborative research on all aspects of effective surveillance-response mechanisms can be provided depending on context, nature of endemicity. Assistance can be provided to African countries to complement their own electronic reporting system for infectious diseases , including continuous monitoring and evaluation of disease transmission dynamics through innovative Sino-Africa partnership. China had developed effective surveillance and early warning systems (EWS) for malaria and schistosomiasis based on electronic-based reporting systems ,59 and tP. falciparum and P. vivax exist. Drug resistance is a very important consideration in malaria control demanding the application of approaches, such as real-time molecular genotyping of sexual and asexual resistant biomarkers from asymptomatic and symptomatic population. This activity is paramount in endemic areas for the monitoring of emerging trends of susceptibility and drug resistance, which are key components of malaria control towards elimination.It is worth noting that China has made significant contributions in the discovery and development of drugs against malaria (e.g. artemisinins), schistosomiasis (e.g. artemisinins and mefloquine) and soil-transmitted helminthiasis (e.g. tribendimidine) -63. The Future global health involvements include the establishment of comprehensive sites for M&E and impact assessment in sentinel sites, focussing on three areas of possible research-action programmes: (i) characterising how demographic, epidemiological and environmental factors influence disease transmission by comprehensive comparison of population prevalence, capacity building in diagnostic ability, effects of integrated vector management between demonstration areas and control areas; (ii) socioeconomic factors and the status of prevailing health systems; and (iii) strategy and measurement assessment, including evaluating intervention effects of a related policy and strategy applied in the interventional areas and further exploration of the external validity of the findings from these areas.The Forum reviewed the action plans of NTD control and elimination articulated in the WHO roadmap and China CDC, as well as the national schistosomiasis elimination programme for China (2009-2015), placing particular emphasis on surveillance-response systems. China\u2019s challenges and needs in tropical disease control, and its experiences and lessons learnt necessitate national governments to build and implement surveillance-response systems to deal with tropical diseases, including imported cases and new outbreaks.The first Forum provided a platform for exchange among participants from different countries and sectors who presented their principles and approaches from disease control to elimination. The reader should, however, be aware that the current report expresses the opinions of the individuals participating in the Forum and does not intend to be an exhaustive exploration of the subject matter or a representation of consensus.During the First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination, a priority research agenda within a \u2018One Health-One World\u2019 frame of global health was developed, including: (i) the establishment of a platform for resource-sharing and effective surveillance-response systems for Asia Pacific and Africa with an initial focus on elimination of lymphatic filariasis, malaria and schistosomiasis; (ii) development of new strategies, tools and approaches, such as improved diagnostics and antimalarial therapies; (iii) rigorous validation of surveillance-response systems; and (iv) designing pilot studies to transfer Chinese experiences of successful surveillance-response systems to endemic countries with limited resources.More than 100 scientists, disease control managers and other stakeholders participated in the First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination. It offered the opportunity for discussions and exchange of ideas and opinions with emphasis on disease elimination and the key role played by surveillance-response systems. Strengths and limitations of national and international strategies for elimination, prevailing strategies, and novel approaches required for elimination, rely on useful surveillance-response platforms. Funding channels should be explored to intensify research and development of new, innovative and effective platforms. Supporting Sino-Africa partnership for control of parasitic diseases will require taking initiatives for global health and the best experiences from China and the international community to Africa. New operational research should be devoted to identify risk factors and hotspots of transmission, monitoring emergence and spread of disease outbreak with enhanced geographical information systems (GIS), health systems, care management and an integrated approach in improving the efficiency of surveillance-response systems.Sustained control can only be made leading to elimination by accelerating breakthroughs in research, while fully understanding inputs, processes, outcomes and impact on transmission. The launch of the WHO roadmap perpetuates the need for effective surveillance-response systems tailored to local settings. Systems effectiveness depends on access to highly sensitive diagnostics, prompt treatment and follow-up as well as quality of care and patient trust. Sensitive tools for surveillance for xenobiotic monitoring and a deeper understanding of which tools and strategies are most suitable to achieve elimination of malaria, schistosomiasis and other NTDs are needed. Moving from classical M&E to surveillance as an intervention and interruption of transmission not only requires high standards in data collection and appropriate analysis, but also experiences in modelling and validation, verification of elimination and reliable forecasting. Finally, relevant effective intervention science is a must in order to improve the effectiveness of the policies recommended and the public health interventions undertaken.The authors declare that they have no competing interests.ET, XZ, RB, MT, XNZ conceived the review concept. ET, LA, XZ, JHC, XNZ carried out the literature search, developed the structure for the manuscript, and drafted the paper. ET, XZ, RB, JGG, MT, XNZ participated to organize the draft sections, co-wrote sections of the draft, and ET, RB, JU, MT, XNZ edited the overall manuscript. All authors read and approved the final version of the manuscript before submission to Infectious Diseases of Poverty.Multilingual abstracts in the six official working languages of the United Nations.Click here for file"} +{"text": "The Millennium Development Goals (MDGs) made a marked transformation for neglected and vulnerable communities in the developing countries from the start, but infectious diseases of poverty (IDoPs) continue to inflict a disproportionate global public health burden with associated consequences, thereby contributing to the vicious cycle of poverty and inequity. However, the effectiveness and large-scale coverage of artemisinin combination therapy (ACT) have revolutionized malaria treatment just as the control of lymphatic filariasis (LF) and onchocerciasis have benefitted from harnessing the broad-spectrum effect of avermectin-based derivatives. The paradigm shift in therapeutic approach, effected by these two drugs and their impact on community-based interventions of parasitic diseases plaguing the endemic low- and middle-income countries (LIMCs), led to the Nobel Prize in Physiology or Medicine in 2015. However, the story would not be complete without mentioning praziquantel. The huge contribution of this drug in modernizing the control of schistosomiasis and also some intestinal helminth infections had already shifted the focus from control to potential elimination of this disease. Together, these new drugs have provided humankind with powerful new tools for the alleviation of infectious diseases that humans have lived with since time immemorial. These drugs all have broad-spectrum effects, yet they are very safe and can even be packaged together in various combinations. The strong effect on so many of the great infectious scourges in the developing countries has not only had a remarkable influence on many endemic diseases, but also contributed to improving the cost structure of healthcare. Significant benefits include improved quality of preventive and curative medicine, promotion of community-based interventions, universal health coverage and the fostering of global partnerships. The laudable progress and benefits achieved are indispensable in championing, strengthening and moving forward elimination of the IDoPs. However, there is an urgent need for further innovative, contextual and integrated approaches along with the advent of the Sustainable Development Goals (SDGs), replacing the MDGs in ensuring global health security, well-being and economic prosperity for all. This year's Nobel Prize in Physiology or Medicine, awarded for the discovery of artemisinin and ivermectin, was divided between Youyou Tu \"for her discoveries concerning a novel therapy against malaria\" and William C. Campbell together with Satoshi \u014cmura \"for their discoveries concerning a novel therapy against roundworm infections\" Fig.\u00a0. These pThe burden of persisting and threatening infectious diseases in most developing countries is a complex affair, a fact recognized by The United Nations' Millennium Development Goals (MDGs) that repArtemisia - qinghaosu - has a long history in Chinese traditional medicine), are broad-spectrum drugs that can be used to cure many more infections than mentioned above; amazingly, the artemisinins have even effect against immature schistosomes, while ivermectin seems to limit the behaviour of the malaria vector. However, it was not evident that a new era had begun until the new drugs were in general use. Trying to pinpoint this historic shift exactly is of course futile, but it can be said that after the large-scale introduction of modern chemotherapy in the 1980s and 1990s, the first decade of the new millennium marks the time that world-wide implementation of mass drug administration (MDA) occurred [The root cause of the infectious diseases of poverty (IDoPs) is the ubiquitous presence of infectious agents. However, social and economic issues play a large role in their transmission and persistence, a fact recognized in both the MDGs and the follow-up SDGs. Still, the transformation of the endemic landscape is almost entirely due to large-scale distribution of the three novel 'wonder drugs' artemisinin, ivermectin and praziquantel, mainly used against malaria, lymphatic filariasis (LF)/river blindness and schistosomiasis, respectively. All three, discovered and developed in the 1970s , LF (Brugia and Wuchereria), hookworm infection and other soil-transmitted helminthic (STH) infections [The discovery of artemisinin and ivermectin have had, and will continue to have, a long-lasting, strong impact on the IDoPs, the former due to its effect on the parasites causing malaria; the latter because its effect on the different nematodes that cause river blindness against acute and severe malaria, intermittent preventive treatment and curative with respect also to the asexual plasmodium stages, has provided relief and hope for a large proportion of vulnerable populations in the endemic areas \u201311. Impote drugs , 11, 16 te drugs in strente drugs .Both acute and severe malaria continues to exert a deep-rooted impact in 109 countries and territories around the world and still constitute a leading risk factor for infant mortality and sub-optimal growth and development in spite of the global malaria elimination campaign programmes (GMECPs) that were in effect in the 1950s to the 1970s , 18\u201320.Artemisia plant extracts could kill P. berghei, a rodent malaria parasite laboratory model. The following year, she succeeded in isolating the active ingredient (qinghaosu), now part of ACT, the most important class of anti-malaria medications [In 1971, at the Pharmaceutical Institute of the Academy of Traditional Chinese Medicine, Youyou Tu showed that ications , 21. Artications , 22, 23.ications . Impressications , 24, 25.ications , 25, 26.The latest decades have witnessed substantial progress in raising awareness and increasing the production, adoption and distribution of existing effective interventions besides the use of ACTs, e.g. indoor residual spraying (IRS) and large-scale distribution of long-lasting insecticidal nets (LLINs) as prescribed by the RBM's universal coverage partnership , 27, 28.William C. Campbell and Satoshi \u014cmura discoveries proved to be a breakthrough in the tenacious fight against infections caused by roundworm parasites, mainly onchocerciasis and LF, dreaded health scourges of the most vulnerable groups of affected populations. The discovery, industrial development and implementation of the active avermectin derivative ivermectin (best known under the brand name Mectizan) led to a significant reduction of onchocerciasis in the endemic areas in central Africa and Latin America as well as of LF and scabies that are also endemic in India and Southeast Asia, thus improving the situation in vulnerable communities in low- and middle-income countries (LIMCs) , 3. In aO. volvulus, is transmitted to humans through bites of infected female blackflies (Simulium spp.). Adult worms can live up to 18\u00a0years in infected human hosts and release up to 1,000 microfilariae daily causing a variety of ailments including skin lesions due to chronic dermatitis, , rashes, intense itching, depigmentation as well as visual impairment due to eye inflammation causing corneal scars eventually leading to irreversible blindness [Onchocerciasis, transmitted by the filarial worm lindness , 32. Thelindness . The Onclindness and its lindness , 13 at alindness . Intervelindness . As of 2lindness .O. volvulus and reduction of the burden of visual impairment and blindness have been achieved [The Onchocerciasis Elimination Program of the Americas (OEPA) was launched in 1992 under the Pan American Health Organization (PAHO) with the goal of interrupting onchocerciasis transmission in six endemic Latin American countries by 2015 . The WHOachieved , 42. Howachieved , 35, 43.Schistosoma spp. species capable of infecting humans [Echinococcus spp. [Taenia spp. that can infect the brain and muscles with its eggs and larvae (cystocercosis) and food-borne trematodes (FBTs), such as Paragonimus spp., Opistorchis spp. and Clonorchis spp. [Though not recognized for this year's Nobel Prize, the story would not be complete without mentioning praziquantel. Praziquantel, a drug that has modernized the control of schistosomiasis and many other helminth infections in the same way the ACTs and ivermectin worked for malaria and LF/onchocerciasis, respectively , 45. Prag humans , 50\u201352 tcus spp. , whose lFasciola spp., a parasitic worm preferably treated with triclabendazole (sold under trade names Egaten and Fasinex) [FBT transmission is linked to traditional customs, e.g. consumption of dishes containing raw fish, crustaceans and plants in countries where these diseases are sustained by entrenched cultural practices, which are difficult to change. FBTs affect over 56 million people infected in over 70 countries ; this fiFasinex) .Schistosomiasis is acquired through contact with water infested with cercariae, the free-swimming larval forms emanating from the intermediate snail host when infected. The microscopic adult worms live in the veins of abdominal organs, where large amounts of eggs are produced for excretion via faces or urine aimed at hatching and infecting fresh-water snails thus closing the parasite's lifecycle. Large numbers of the eggs are, however, trapped in the tissues and where immune reactions cause damage that varies from subtle to serious. Millions of people suffer from severe schistosomiasis , 44, 53,The global IDoP elimination agenda will require strengthening community, national and regional leadership and commitment to rapidly increase funding and fostering integrated multidisciplinary and inter-sectorial policies. Furthermore, scaling-up of high-impact MDA coverage of available drugs, development and implementation of new, effective vaccines and other novel approaches and tools are needed in addressing the geographical complexity of the panoply of different diseases including malaria, river blindness, LF and schistosomiasis , 57. ThiThe pharmacological and therapeutic paradigm shift discussed here calls for further, strong investments in research and development in the field of drugs and vaccines creating pipelines of new products capable of tackling the challenge of rapid emergence and spread of vectors, parasites and drug resistance. Timely, evidence-based and cost-effective operational approaches and solutions for IDoPs and NTDs are required for dealing with the rise and spread of insecticide resistance, and the environmental impact of climate change. Likewise, development of diagnostics with improved sensitivity and specificity as well as preventive therapeutics and efficient information communication/dissemination mechanisms underscore the quest for novel and innovative approaches. Leveraging on lessons learnt, efficient and integrated intersectoral partnerships as well as collaboration in the development of needed, new diagnostics, drugs and vaccines are much needed. So are also proven and innovative community-based programmes with respect to ownership in health systems, surveillance and new opportunities in elimination interventions packages and eventually in moving forward eradication of IDoP worldwide."} +{"text": "Depression is a highly prevalent disorder that poses a significant social burden to society. Despite continued advances toward the understanding of the pathophysiology of this disease, its molecular/cellular underpinnings remain elusive, which may be at the basis of the lack of effective treatment strategies. Among the different lines of research, recent literature suggests that impaired neuron and glial plasticity may be a key underlying mechanism in the precipitation of the disorder. Surprisingly, glial cells appear to be involved both in the pathophysiology of major depression and in the action of antidepressants. In particular, several works refer to alterations in the morphology and numbers of astrocytes, microglia, and oligodendrocytes in the context of depression, in human patients, and animal models of depression. These observations are linked to functional evidences, such as impairments in the cross-talk between glia and neurons, changes in the level of neurotransmitter or immunoactive substances, myelination status, and synapse formation, maintenance or elimination.Polyakova et al. begin by suggesting the astrocytic S100B as a novel marker of minor depression, specifically in males, which could help to understand its pathophysiology. The study point outs the possible relevance of glial cells in the modulation of brain neuron-glia networks at least in some types of depression. Rial et al. explore the multiple interactions between glial and neuronal cells at the synaptic level, which may be impaired in depressive-like conditions. The authors address how purines may be used to restore synaptic efficacy by modulating glia-neuron bidirectional communication, possibly reverting depressive-like behaviors. Jo et al. discuss the importance of the glial-mediated immune modulation through cytokine signaling that may trigger depressive episodes, and Branchi et al. highlight that by participating actively in the modulation of the extracellular environment microglia are an integral part of brain plasticity and, therefore, appear to account directly for the precipitation of the depressive disorder. Brites and Fernandes point out that the disruption of secreted extracellular vesicles, an alternative form of neuro-glial signaling, may also underlie depressive behavior. Collectively the research indicates that these novel forms of neuro-glia communication may represent a novel approach for modulation of the brain networks and, thus, its manipulation may allow the development of autologous therapies for depression.This Research Topic highlights the roles played by neurons, astrocytes, and microglia in depressive disorder(s). Di Benedetto et al. suggest a link between fluoxetine modulation of aquaporin four levels in astrocytes with consequences for astrocyte morphology and re-establishment of a functional glia-vasculature interface, which may underlie its antidepressant effect. Interestingly, the decreased levels of astrocyte-specific connexin 43 (Cx43) appear to be related with antidepressant and anti-anxiolytic phenotypes as suggested by Quesseveur et al. Moreover, the authors suggest that the inactivation of Cx43 might induce beneficial effects through an attenuation of the stress response, \u201cavoiding\u201d depressive symptoms. In accordance, Jeanson et al. explored the effect of antidepressants on the functional status of astrocytic connexins, showing a complex pattern of responses that links astrocytes to the mode of action of these drugs. Exploring the use of deep brain stimulation (DBS) as an alternative for treatment-resistant depression patients, Eti\u00e9vant et al. discuss the beneficial role of astrocytes in the process based on the absence of a DBS-effect after pharmacological lesion of astrocytes.In addition to the implication of glia in the pathophysiology (and treatment) of depression, a number of studies associates glia-related pathways to classically accepted antidepressant mechanisms. Specifically, in this Research Topic, Overall, the excellent reflections and novel data sets that make up this Research Topic provide evidence for a role of glial cells, namely microglia and astrocytes, in the mechanisms underlying depression and the effect of antidepressants. Collectively, the data indicates that despite the rapid advancement of the field there is still a long way to go. The study of glial cells will continue to reveal novel and more effective therapeutic mechanisms for depression and its symptomatology.All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.JO and LP received fellowships from the Foundation for Science and Technology (FCT) and their work is funded by FCT (SFRH/BD/101298/2014 to JO and IF/01079/2014 to LP) and Bial Foundation (207/14 for JO and 427/14 for LP) projects. SV is supported by FCT (SFRH/BPD/81627/2011). CG is supported by FCT (SFRH/BPD/63013/2009). This work was co-funded by the Life and Health Sciences Research Institute (ICVS), and Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023). This work has been also funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the (FCT), under the scope of the project POCI-01-0145-FEDER-007038.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Magnetic resonance imaging (MRI) is an imaging modality widely used in clinical practice.The use of MRI for imaging of the thorax, however, has been historically considered oflimited value, despite the effort of physicists and radiologists to obtain positive andreproducible results in several studies. MRI plays a role in the assessment ofcardiovascular disease, mediastinal lesions and abnormalities of the brachial plexus andchest wall. However, clinical indications are restricted to specific conditions,generally as a problem-solving technique.,2. In more recent years, however, MRI hasevolved from a research tool to a useful modality in the assessment of thoracic disease.Technical advances such as very short echo times and ultrafast turbo-spin-echoacquisitions, that allow breath-hold imaging with full anatomic coverage and help toovercome cardiac pulsation,4, have improved the capability ofthoracic MRI. The use of contrast agents for perfusion MRI and gas imaging forassessment of pulmonary ventilation have further increased the applications of MRI inthe investigation of lung diseases-8.Continuous motion from cardiac and vascular pulsation and respiratory motion are one ofthe major challenges in MRI of the chest as they severely affect imaging quality. Asignificant limitation of thoracic MRI is imaging of the lung due to intrinsiccharacteristics of the pulmonary tissue and the presence of physiologic motion. The lowproton density of the lung parenchyma generates low signal intensity and lowsignal-to-noise ratio when compared to other parts of the body. Furthermore,susceptibility artifacts at tissue-air and liquid-air interfaces of the alveoli greatlyaffect signal intensityRadiologia Brasileira, Hochhegger et al. provide a concise yet comprehensivereview of MRI of the chest. The authors convey an instructive discussion of technicalaspects and challenges of thoracic MRI, including limitations of 3T MRI in the chest,and suggest strategies to overcome some of these obstacles.In the article \"Chest magnetic resonance imaging: a protocol suggestion\", published inthe current issue of ,11 as well as theadvantages of MRI in the staging of lung cancer when compared to CT and 18-FDG-PET/CT.Various studies have demonstrated the value of MRI in the detection and assessment ofdegree of tumor invasion in the mediastinum, pleura and chest wall, thus contributing tothe T descriptor of the TNM staging system-14. The present articlediscuss the role of whole-body diffusion-weighted MRI in the detection of distantmetastases (M staging) and remark the potential role of diffusion MRI in thecharacterization of irradiated lung tissue. The authors also describe the advantages of MRI in themorphological and functional assessment of patients with pulmonary hypertension,including estimation of cardiac function as well as surgical planning,17. Importantly, the use of MRI in the diagnosis of pulmonaryembolism and in the follow up of cystic fibrosis and pneumonia are discussed-20, highlighting the importance of MRI in populations at increasedrisk of ionizing radiation complications such as young patients and in pregnancy. Recentstudies assessing the use of thoracic MRI in cystic fibrosis in particular have shownpromising results, including depiction of morphological changes as well as evaluation ofpulmonary function and respiratory mechanics,21,22. The clinical impact of an accurate ionizingradiation-free modality for a young population requiring frequent imaging assessmentcannot be underestimated.In the first part of the manuscript, the main clinical indications of MRI of the chest ispresented, including recent data regarding the role of MRI in the distinction betweenmalignant and benign pulmonary nodulesThe authors finalize the article providing a basic MRI protocol applicable to most commonthoracic diseases while also suggesting additional sequences to be used in specificthoracic abnormalities. The proposed protocols are suitable to most state-of-art MRIscanners and can be easily implemented.I commend the authors for they effort to present MRI as a valuable modality in theassessment of pulmonary diseases, increasing awareness of the peculiarities andadvantages of this modality to the radiology community as well as for providingobjective tools that can move MRI from an underutilized technique to a modality with thepotential to substantially contribute to thoracic radiology."} +{"text": "Muscle weakness in corticosteroid myopathy is mainly the result of the destruction and atrophy of the myofibrillar compartment of fast-twitch muscle fibers. Decrease of titin and myosin, and the ratio of nebulin and MyHC in myopathic muscle, shows that these changes of contractile and elastic proteins are the result of increased catabolism of the abovementioned proteins in skeletal muscle. Slow regeneration of skeletal muscle is in good correlation with a decreased number of satellite cells under the basal lamina of muscle fibers. Aging causes a reduction of AMP-activated protein kinase (AMPK) activity as the result of the reduced function of the mitochondrial compartment. AMPK activity increases as a result of increased functional activity. Resistance exercise causes anabolic and anticatabolic effects in skeletal muscle: muscle fibers experience hypertrophy while higher myofibrillar proteins turn over. These changes are leading to the qualitative remodeling of muscle fibers. As a result of these changes, possible maximal muscle strength is increasing. Endurance exercise improves capillary blood supply, increases mitochondrial biogenesis and muscle oxidative capacity, and causes a faster turnover rate of sarcoplasmic proteins as well as qualitative remodeling of type I and IIA muscle fibers. The combination of resistance and endurance exercise may be the fastest way to prevent or decelerate muscle atrophy due to the anabolic and anticatabolic effects of exercise combined with an increase in oxidative capacity. The aim of the present short review is to assess the role of myofibrillar protein catabolism in the development of glucocorticoid-caused myopathy from aging and physical activity aspects. Glucocorticoids, well-known immunosuppressive and anti-inflammatory drugs, have unfortunate side effects upon long-term use and high doses: fast twitch (FT) muscle fiber atrophy and development of myopathy ,2. Glucoet al. [Glucocorticoids, chemically classed as steroids, are hormones that affect the metabolism of carbohydrates. These steroids have an anti-inflammatory effect, but there are also many side effects of catabolic action. The catabolic effect of glucocorticoids depends on individual tissues. In contrast to the loss of protein from skeletal muscle, bone, lymphoid tissue, and smooth muscle, there is an increase in the rate of cardiac, hepatic, and urogenital activities . The catet al. , who aboet al. are the et al. . A decreet al. and of tet al. , shows t\u03b1, increases adiponectin and IGF-1 concentrations, and reduces total and abdominal visceral fat [More than four decades ago it was shown that the catabolic action of corticosteroids depends on the state of functional activity of skeletal muscle . Moderateral fat . Increaseral fat via a maeral fat . The receral fat .Over a lifespan there is a decrease of skeletal muscle mass, primarily as a result of the reduction of FT fibers , accompaMuscle fibers and myofibrils of glucocorticoid-caused myopathic glycolytic muscle are thinner in comparison with the control group and disappeared completely from one fifth of the area of myofibrils of myopathic muscle myosin filaments . The intDuring ageing muscle strength decreases significantly; for example, the hindlimb grip strength in old rats decreases by about 50% due to sarcopenia . GlucocoProtein degradation, particularly myofibrillar protein degradation, is typical for glucocorticoid myopathy. Protein degradation in skeletal muscle fibers, particularly in FT fibers with low oxidative capacity, is mediated by the activity of the ubiquitin\u2013proteosomal and the lysosomal pathways . The actIn the case of corticosteroid myopathy, sarcopenia, and cachexia, the molecular mechanisms of regulation of muscle, metabolism, and induced wasting disorder-related skeletal muscle atrophy is almost similar. Cachexia is characterized by the loss of adipose tissue as a result of an imbalance in lipogenesis and lipolysis, with enhanced lipolysis supported by neuroendocrine activation and tumor-related lipolytic factors .The central question is how to prevent or decelerate skeletal muscle atrophy in the elderly and glucocorticoid myopathic patients. Aging causes a reduction of AMPK activity as the result of reduced function of the mitochondrial compartment . AMPK acMuscle weakness in corticosteroid myopathy is the result of destruction and atrophy of fast-twitch muscle fibers and their myofibrillar machinery. The disappearance of one fifth of myosin filaments from myofibrils and a decrease in MyHC IIb isoform relative content are the reasons for decreased muscle strength and motor activity in the case of corticosteroid myopathy. The higher the degree of muscle atrophy, the lower the muscle elasticity and the higher the tone. A decrease in titin and myosin, and in the ratio of nebulin and MyHC in myopathic muscle, shows that these changes of contractile and elastic proteins are the result of increased catabolism of these proteins in skeletal muscle. Both glucocorticoid-caused myopathic and aging-caused sarcopenic muscle wasting is mainly a result of the decrease and atrophy of fast-twitch muscle fibers. In both cases, the myofibrillar protein synthesis rate decreases. Slow regeneration of skeletal muscle is in good correlation with a decreased number of satellite cells under the basal lamina of muscle fibers. Aging causes a reduction of AMPK activity as the result of reduced function of the mitochondrial compartment. AMPK activity increases as a result of increased functional activity. Resistance-type muscle activity causes anabolic and anticatabolic effects in skeletal muscle: muscle fibers hypertrophy and myofibrillar proteins turn over faster. These changes are leading to the qualitative remodeling of fast-twitch muscle fibers. As a result of these changes, muscle strength is increasing. Endurance-type muscle activity improves capillary blood supply, increases mitochondrial biogenesis and muscle oxidative capacity, and causes a faster turnover rate of sarcoplasmic proteins as well as qualitative remodeling of type I and IIA muscle fibers. As both muscle strength and endurance decrease in the elderly, particularly during glucocorticoid administration, the combination of endurance and resistance training may have the best rehabilitative effect."} +{"text": "The Manchester Synthetic Biology Research Centre (SYNBIOCHEM) is a foundry for the biosynthesis and sustainable production of fine and speciality chemicals. The Centre's integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals production. An overview of these capabilities is described. By harnessing the power of predictive SynBio methods, SYNBIOCHEM is driving next-generation sustainable manufacturing processes that are appropriate and commercially relevant for scale-up across many industrial sectors .The Manchester University Synthetic Biology Research Centre (SBRC), SYNBIOCHEM (http://www.mib.ac.uk/) and builds on the MIB's core strategy of uniting teams of interdisciplinary scientists and industrial partners to deliver challenge-led innovation in bio-based chemicals and broader industrial biotechnology sectors. SYNBIOCHEM also builds on a long-term vision and commitment by the University of Manchester in sustainable Industrial Biotechnology, leveraging and integrating world-leading capabilities in MIB Centres of Excellence including: Biocatalysis, Biotransformation and Biocatalytic Manufacture (CoEBio3); Manchester Centre for Biophysics and Catalysis (MCBC); Manchester Centre for Integrative Systems Biology (MCISB) and the Michael Barber Collaborative Centre for MS (MBCMS). SYNBIOCHEM was established in 2014 funded jointly by the U.K. Biotechnology and Biological Sciences Research Council, the U.K. Engineering and Physical Sciences Research Council and The University of Manchester. Led by three directors the Centre unites a complementary team of SynBio researchers at Manchester in pursuit of SynBio solutions that will deliver wider access to chemical diversity and more rapid and predictable delivery of chemical targets for scalable production/manufacturing. The interdisciplinary team includes not only chemists, biologists and computer scientists, but also investigators from the Manchester Institute of Innovation Research and the School of Social Sciences contributing insight of RRI relevant to the Centre activities. A key challenge includes consideration of the societal impact of SYNBIOCHEM research activities to ensure that the Centre anticipates, prepares for and, if necessary, mitigates the impact of SynBio technology in the wider society, economy and environment [SYNBIOCHEM is located in the Manchester Institute of Biotechnology (MIB; SYNBIOCHEM has established state-of-the-art and fully integrated Design/Build/Test technology platforms for bio-based chemicals production . The plaSYNBIOCHEM has an open and collaborative culture with a strong emphasis on building academic and industry partnerships, both at the national and international levels. Industrial foresight and awareness coupled to translation of SYNBIOCHEM discovery science and technology towards commercial exploitation are at the core of the Centre's strategy. The Centre hosts regular open meetings in a variety of formats, enabling one-to-one discussions with industrial partners, the development of new collaborative projects with external stakeholders, and through an industry club for joint supervision of research studentships in projects that address scientific problems of interest to the club members. Early SYNBIOCHEM programmes have resulted in protection of new intellectual property for the development of tools and microbial factories/hosts relevant to the production of pravastatin , biosynthttp://synbiochem.co.uk.In summary, SYNBIOCHEM is addressing major challenges in SynBio through a foundry concept and an open collaborative ethos with external partners. The Centre's integrated technology platforms provide a unique capability to facilitate predictable engineering of microbial bio-factories for chemicals production. Further information about the Centre and routes to collaboration can be obtained from the SYNBIOCHEM website:"} +{"text": "This paper presents, from the perspective of technological development andproduction, the results of an investigation examining 61 clinical studies withvaccines conducted in Brazil between 1938-2013, with the participation of the OswaldoCruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies havebeen identified and reviewed according to criteria, such as the kind of vaccine, their rationale, design and methodological strategies.The results indicate that IOC and Fiocruz have accumulated along this timesignificant knowledge and experience for the performance of studies in all clinicalphases and are prepared for the development of new vaccines products and processes.We recommend national policy strategies to overcome existing regulatory and financingconstraints. Clinical studies are crucial for the development and registration of new products andconstitute today a structured process, mandated by strict legislation involving a growingnumber of participants, in a stepwise strategy.The Oswaldo Cruz Institute (IOC) and the other technical units which constitute the OswaldoCruz Foundation (Fiocruz) are recognised as very important institutions for basic scienceand biological and technological research on tropical diseases in Brazil. Theseinstitutions have a long tradition of clinical studies which have proven to be vitallyconnected to the prevention of infectious diseases of public health importance for Braziland other countries. In this paper, we review and analyse these studies, occurring over aperiod exceeding seven decades, from the perspective of technological development (TD). Theunderstanding, in a historical sense, of the evolutionary stages of these clinical studieswill hopefully provide a better understanding of the processes that were involved and mayhelp policy and decision-makers to conceive of new alternatives and create possibilitiesfor the design of new studies in the future.For the selection of the clinical studies we adopted the following criteria forinclusion: (i) studies conducted in human beings; (ii) prospective; (iii) vaccination asthe basic intervention; (iv) longitudinal and individual follow-up of participants; (v)published in scientific medical journals; (vi) conceived and conducted according toethical and legal criteria for clinical research in human beings, with tolerance to theabsence of formal ethical and regulatory evaluations regarding the older studies; (vii)conducted with participation of at least one unit or professional of Fiocruz/IOC.These restrictive criteria, besides being conceptually acceptable, met the requirementto limit the scope of the research within an acceptable range. Studies which did notmeet these criteria were excluded. These included retrospective studies,clinical-epidemiological studies, seroepidemiological studies, pharmacovigilance studiesand observational studies. Although the latter did not fit into the classical model ofclinical studies, some of them could be classified as clinical studies, in a broadersense definition.For studies conducted at the origin of IOC, which are outstanding and part of itshistory, these criteria were not strictly applied, which is justifiable, consideringthat the legislation on clinical studies came later. However, if they are not formallyperfect, they have been conducted ethically, with the best science and methodologyavailable at the time.The search for papers was done by databases, including PubMed, from the National Centerfor Biotechnology Information, National Institutes of Health, United States of America,and LILACS, the Latin-American database from BIREME-Regional Library of Medicine, fromPan American Health Organization (PAHO)/World Health Organization (WHO). However, mostpapers were found through personal archives, consultations with colleagues, somereference books on the history of vaccines and otheTo recover original papers, we used, besides PubMed and LILACS, the SciELO database,Capes Periodicals Gateway and the libraries of the National School of Public Health,Bio-Manguinhos/Fiocruz and Mourisco Castle. Photocopies were also obtained from theHinari Programme, from WHO and Oxford Journals.We use terms \"clinical trial\" and \"clinical study\" interchangeably.The period of study extended up to the year 2013 .The clinical studies with vaccines under the scope of IOC and Fiocruz, besides theirrelevance to the public health of Brazil and many other developing countries, havecontributed to the institutional TD.These technical advances built institutional knowledge and skills in vaccinethermostability, new freeze-drying formulation, use of certified inputs, improvement ofquality control methodologies and the skills to incorporate new products throughtechnology transfers, which resulted in scientific breakthroughs and have been landmarksof Fiocruz history.Haemophilus influenzaeType b (Hib) vaccine, measles/mumps/rubella (MMR) androtavirus vaccines [GlaxoSmithKline (GSK)] and shortly themeasles/mumps/rubella/varicella (MMRV) vaccine . Besides leading to theintroduction of new vaccines into the NIP, in a relatively short time, technologytransfers of these vaccines have made possible the creation, expansion and improvementof new platforms, production and laboratories and the creation of a qualified workforcethat is now a most valuable asset of Fiocruz. The positive consequences of theseinnovative processes have been outstanding and should not be minimised. Moreover,transfer of technologies has been feasible because of the intrinsic capacity of theinstitution for absorbing, in a relatively short span of time, the newly involvedtechnologies.Examples of tech transfer include the yellow fever (YF) vaccine (Rockefeller Institute),the polysaccharidic AC meningococcal vaccine (Institut M\u00e9rieux), the poliomyelitis andmeasles vaccines (BIKEN Institute), the The clinical studies of measles vaccines were conducted to evaluate the successfultechnology transfer and implement the regular use of a vaccine to counteract one of themain causes of child mortality in Brazil . The tecThe clinical studies with poliomyelitis vaccines and many additional seroepidemiologicalstudies resulted in changes and improvements in vaccine composition and eventuallyresulted in the elimination of this disease in Brazil and many other Latin Americancountries.oral polio vaccine (OPV) technologywas obtained under the umbrella of the Brazil-Japan Cooperation Agreement. Thetechnology transfer for this vaccine came through the Japanese Poliomyelitis ResearchInstitute. These actions included redesigns and upgrades of facilities, provision ofequipment, \"on the bench\" training within production laboratories, quality control andneurovirulence testing in nonhuman primates. The creation of this highly qualified groupin 1982 allowed Bio-Manguinhos to take the responsibility for the quality controltesting of the OPV vaccine used in the national routine immunisation program or in masscampaigns. Later, this responsibility was transferred to the National Institute forQuality Control. Another great contribution from Bio-Manguinhos was the formulationimprovements of OPV vaccine, including a doubling of the dose of type 3 OPV, required tocontrol poliomyelitis outbreaks in Northeast Brazil. This formulation change wasaccomplished in just two weeks after the decision was made. The highly satisfactoryresults led the PAHO to extend this recommendation to all Latin American countries and,afterwards, WHO recommended the use of the same formulation for all countries.As with the measles vaccine, the The clinical studies with diphtheria, tetanus and pertussis/Hib vaccine drove thetechnology transfer for the Hib portion of the vaccine. This resulted in theintroduction of this vaccine into the routine vaccination schedule, which, in a veryshort time, drastically reduced the incidence of Hib meningitis.Plasmodium falciparum , which needs better protection, and for pertussis and YF, which needimproved safety.Although some of the achievements have been remarkable, we should recognise thatinnovations at IOC and Fiocruz have been incremental and did not change paradigms . The innThe results presented here indicate that, over the last several years, there have beenconsiderable quantitative and qualitative advances in the development of clinicalstudies under the scope of IOC and Fiocruz. These demonstrate that clinical studies nolonger constitute a bottleneck for innovation, in terms of local capacity. However,regulatory and financial constraints still remain. There are also regulatory andoperational issues that need to be addressed, in order to streamline processes withoutloss of safety and quality. Slow decision-making and excessive centralisation ofregulatory and ethical processes may, in fact, decrease the quality of studies and mayresult in loss of opportunities in a competitive world.It should be noted that, although not reviewed here, several clinical studies withmeningococcal vaccines have been conducted at Bio-Manguinhos/Fiocruz, of which threehave been Phase I studies and published in congress annals , b,2010Although several new innovative vaccines are in development, their complexity isincreasing and will certainly require creativity and scientific and technologicalcapacity to achieve a final product.It should also be stressed that if we have been weak in technological innovation so farin Brazil, we have been innovators on the ethical concept that vaccines are a right ofcitizenship and that all people should have free access to them, as to basic sanitaryservices and education. The vaccine schedule of the Ministry of Health has significantlyexpanded and now includes all vaccines used by developed countries . MoreoveThe contribution of vaccines for the improvement of health conditions of the Brazilianpopulation is evident and outstanding. The infectious diseases targeted by vaccination(except TB) are under control. The Brazilian producers of vaccines made these conquestspossible and the clinical studies with vaccines have been an essential part of thisprocess.The review of clinical studies under the scope of IOC and Fiocruz within the period ofthis study indicates the strength and potential of IOC and Fiocruz to conduct all phasesof clinical studies with vaccines. However, the innovation component is still weak andshould be strengthened. To achieve this objective as well as to accelerate the TD of newand innovative vaccines, we suggest: (i) the urgent development of a new legal andinstitutional framework for Bio-Manguinhos/Fiocruz, allowing flexibility and capacity toproduce and to operate in the market. It is necessary to conciliate social commitmentwith speeding up of processes and entrepreneurial capacity, which are essential toindustrial activity and technological competitiveness; (ii) to stimulate intra and interinstitutional partnerships and the exchange of personnel, nationally andinternationally; (iii) to stimulate group and personal cooperation through meetings andcommon projects; (iv) to promote public-private partnerships, leading to technologytransfers, to search for common development of new products and processes; (v) tostimulate innovation and creativity; (vi) to attract new talent, creating an inspiringand receptive atmosphere and environment to innovation and creativity; (vii) to searchfor expertise, wherever it may reside, to solve the technological and organisationalproblems of Bio-Manguinhos/Fiocruz; (viii) to increase the governmental financing forclinical studies and to stimulate the non-governmental financing; (ix) to stimulateexcellence, at all levels."} +{"text": "Ultrasongraphy (US) is a powerful diagnostic imaging tool for evaluating musculo-skeletal disorders in children. US is relatively cheap, non invasive and does not require sedation thus it is generally well-tolerated. Lack of ionizing radiation and dynamic imaging capabilities are significant advantages compared to CT and MRI too.US is ideally suited to the evaluation of the bone, cartilage and soft-tissue structures, including tendons and ligaments, joints and muscles .The combined use of new generation high frequency transducers and of Power Doppler increases the diagnostic accuracy of US.US is widely used in the diagnosis of hip disorders in children . In deveBesides hip\u2019s disorders, US can be employed in many other pathological conditions of the pediatric musculoskeletal system, including congenital, infectious, neoplastic and inflammatory disorders . ParticuIn acute osteomyelitis US is able to identify early abnormalities in the soft tissues overlying the bone just few days after the onset of symptoms before the appearance of radiographic signs. As infection progresses, US can depict interruption of the cortical profile related to bone destruction and diffuse involvement of subcutaneous tissue with formation of abscesses.Due to the peculiarities of the growing skeleton, the knowledge of musculoskeletal pediatric anatomy and especially of growth-related changes in healthy children is extremely important in establishing whether the US findings reflect pathology or are part of normal development ."} +{"text": "Indirect contact transmission is considered as the most common mechanism of transmission of microorganisms in healthcare environments. Contaminated medical devices, equipment and surfaces in the environment of the dental surgeries are applied as a vehicle. Microbial contamination (bioburden) of medical devices from the category of critical, semicritical and non-critical was monitored in orthodontic surgeries in this project.The file included 11 dental chair units in Department of Orthodontic, Faculty of Medicine and Dentistry, Palack\u00fd University Olomouc and 11 dental chair units in private orthodontic surgeries. Dental chair units belongs to the category of non-critical medical devices and at the same time is defined as \"patient zone\" there is applicated \"My Five Moments for Hand Hygiene-Dental Care\".Swabs were taken from the following places: headrest, hand lights, armrest, spittoon, terminal of a rotary tool, control panel, and hand control of doctor's chair. orthodontic bands and wires belong to the category of critical medical devices. Orthodontic pliers belongs to the semicritical category of medical devices. Microbial contamination of the above mentioned medical devices was monitored by using of cotton swabs and cultivation in liquid and solid culture medium.Public orthodontic surgeries: Orthodontic bands and wires which included to the critical category of medical devices were contaminated in one case by coagulase-negative staphylococcus.Pseudomonas aeruginosa, from the group of gram-negative bacteria, was demonstrated the most often. Microscopic filamentous fungus Aspergillus sp. was demonstrated from spittoon in one case.Private orthodontic surgeries: Staphylococcus aureus was demonstrated in two cases in the private surgeries on the surface of semicritical medical devices (orthodontic pliers). It is very necessary to follow the recommendations for disinfection or sterilization of the above mentioned critical and semicritical category of medical devices.The public medical facility has a higher incidence of coagulase-negative staphylococcus in category of critical and semicritical medical devices. None declared."} +{"text": "Treatment system planning and resource allocation is hampered by the lack of systems-level data and planning frameworks. We developed and pilot-tested a needs-based planning model for substance use services and supports that aligns with the estimated needs of the population of local health regions, takes a broad systems approach beyond the specialized sector, and yields estimates of required treatment capacities for service categories along the continuum of care.Using national population survey data, we estimated, for 94 regional planning areas in Canada, the number of people in need of substance use treatment within a given year, based on five \u2018tiers\u2019 of problem severity. We then estimated the probable help-seeking population for each level of severity, based on a synthesis of the literature. Working with a national expert consensus panel, we estimated the optimal trajectory of clients across several defined categories of treatment services organized by level of care. Integrating steps 1\u20133 yielded the number of people to plan for in each service setting. We piloted the model in nine Canadian jurisdictions, conducting gap analyses that compared the projected and actual service utilization, and supplemented by stakeholder feedback and local indicators of need, such as wait lists and referral data.The model development process and gap analyses at the nine pilot sites yielded important results for local planners, but with national implications. Results indicated that the capacity of moderate-intensity services is adequate in many regions, but that larger gaps exist in low-threshold services and high-intensity services , providing opportunities for international knowledge exchange."} +{"text": "Over the past two decades, improved diagnosis, pharmaceutical therapies, and interventional strategies have impressively improved the armamentarium of modern cardiologists in the fight against the most incident and lethal diseases: heart failure, ischemic heart disease, and arrhythmia. The innovations in the field have mostly been enabled by inventions based on hypothesis-driven approaches. The invention and development of key cardiac biomarkers, such as natriuretic peptides and cardiac-specific troponins, may serve as examples. Based on few candidate molecules, the discovery of these markers requires neither high-throughput molecular screening, nor advanced computational methodologies for interpretation and refinement of results.e.g., age, body mass index, and kidney function) in such trials rather neglect the individuality of patients and their diseases. Hence, it is pivotal to enhance the characterization of prevalent and incident cardiovascular diseases, and either better select the appropriate therapy for the individual patient or define the personal drug target in a single patient.What has changed such that authors of this Special Issue on Computational Cardiology propose the requirement of a structured interaction of clinical, molecular, and bioinformatics experts? Evidence-based changes that have been implemented into current guidelines of cardiovascular medicine are mostly due to large-scale randomized clinical trials. Although this approach was hugely successful to improve prognosis of patients, in the future the treatment and outcome net-benefit expected from additional or refined treatments are predicted to become smaller and smaller. To further improve the management of heart disease, it is therefore important to increase personalization of new approaches. While the intricate power of statistics in randomized trials is obvious, the less than handful selection and phenotyping criteria for existing and upcoming pharmacotherapies and cardiac interventions;\u2022a real-time approach for data integration in the hospital setting and usage of big data on a population level;\u2022prevention of disease by early identification of health hazards;\u2022endorsement of health economic approaches in high-burden diseases, such as heart failure;\u2022improvement of point of care phenotyping and decentralized patient care to relieve the hospital setting;\u2022e.g., that are suited for gene repair;definition of new or personal drug-targets, \u2022automated monitoring of novel treatments for the early detection of treatment success and side effects.One could list the selected foreseen challenges and roles of computational cardiology including:Based on these fields of future innovations, the vision of the future of precision medicine demands for far more than rocket science, namely the simulation of molecular pathways, cells, tissues, organs, and whole organisms. The ignition will be set by advances in molecular and clinical phenotyping in conjunction with the recent developments in bioinformatics methods for integration of multi-level high-throughput and high-content datasets with clinical data. This will pave the way for integrative approaches for patient care in the real sense of personalized medicine.In this Special Issue on Computational Cardiology, we cover some of the exciting insights into new approaches toward a more personalized patient care using computational means. The authors highlight the importance of biobanks and comprehensive data resources, building the basis for future developments of diagnostics and potentially more targeted therapies The authors have declared no competing interests."} +{"text": "The following Acknowledgements statement is missing from the published article:The authors thank Mani Vembar, CT Clinical Science, Philips Healthcare, Cleveland, Ohio for his comments and suggestions in the preparation of this manuscript."} +{"text": "The standards of scholarly publications are evolving to meet the ever-growing demands of digital communications globally. Current authors, reviewers, editors, and publishers face numerous challenges, which can be overcome through Continuous Professional Development (CPD) aimed at advancing skills in research reporting and communicating with the global scientific community. The best scientific traditions nurtured by research and academic institutions in the Russian-speaking world over the past centuries may add to the quality of publications in the rest of the world. Conversely, the recent achievements in the systematization of scientific evidence and proper research reporting, made in Anglophone countries, are of great interest to the Russian counterpart, entering the global research competition.European Science Editing journal, and translated the EASE guidelines for authors, which is now the main reference for most Russian-speaking authors from Russia and other European and Asian countries.With that in mind, the Russian Regional Chapter of the European Association of Science Editors (EASE) organized its first seminar on science communication in Moscow on March 25, 2014 . It was chaired by Associate Professor, Dr Sergey V. Gorin and attended by a multidisciplinary group of researchers, journal editors, and experts in bibliographic databases from several leading Russian academic and research institutions in Moscow, Perm, Ryazan, and Yaroslavl. Dr Sergey Gorin opened the Seminar by presenting its aim and introducing lecturers. The aim was to improve research reporting and communication skills of Russian-speaking authors, reviewers, and editors and to facilitate their networking with collaborators from the English-language scientific journals and editorial associations such as EASE. The Russian chapter of EASE already arranged a regional meeting in 2013, published a paper in the The first lecturer, Member of The Russian Academy of Natural Sciences, President of The League of Professional Image Makers, Prof Viktor M. Shepel reflected on philosophy of culture of scientific publications and shared his life-long experience of evaluating style and structure of multidisciplinary research publications. Prof Shepel emphasized the importance of novelty, creativity, and courteous style of research writing. Easily understandable and logical flow of ideas, correctly elaborated hypotheses, as well as brevity and evidence-based writing are all indicative of high culture of the authors. The authors who do not properly use scientific terms and excessively rely on professional slang distract the non-expert readership. Unfortunately, not all researchers are skilled to present details of methodology applicable to the concrete circumstances and aims of their research, which complicates the evaluation of the papers, particularly those written by PhD candidates. The authors should analyze and report whether the materials used for their studies are representative enough for the generalization of the results. Finally, each paper should have a limited, logically justified number of references to link each statement with a relevant scientific evidence or fact. Overly citing literature sources or quoting words of wisdom of eminent scientists do not allow the readership to judge the style of the authors. Generally, Russian-speaking researchers are modest in expressing their own style of writing and expressing ideas, and are too often critical toward their own research work.http://elibrary.ru/), still do not have strict criteria for calculating research performance indicators. This is why the interpretation of the citation counts and related indicators is often prone to bias. The lecturer also touched upon some rampant cases of plagiarism in Russian papers and its detection by reviewers and science editors. The plagiarism-detection software currently employed by journal editors calculates quantitative indicators that do not reflect the real picture of scientific misconduct. Plagiarism in research grant applications still goes unnoticed by most research evaluators. Some Russian scholarly journals lack traditions of peer review, which leads to a wide variability of its models across periodicals. Strangely, there are journal editors who consider \u201coral peer review\u201d as viable as the written models.The second talk was given by Prof Oleg S. Sukharev from the Institute of Economics of the Russian Academy of Sciences. He discussed the current standards of scholarly journal and book publishing, and criticized the widespread \u201cobsession\u201d with the numbers of papers at the expense of their quality. Monographs and other types of books are becoming increasingly unpopular among the authors because of the inappropriate crediting system and unnecessary prioritization of the long lists of publications and large citation numbers. Prof Sukharev reminded the audience of the long-forgotten principle \u201cbetter fewer, but better.\u201d He was also critical of ranking journals based solely on citation indicators and distinguishing the so-called elite journals. Many ground-breaking research papers are not highly cited despite having true impact on science and bringing prestige and even Nobel prizes to their authors. Moreover, not all citations in research papers are correct and relevant. Citation databases, and particularly the Russian Index of Scientific Citations (http://www.ease.org.uk/publications/impact-factor-statement) and the San Francisco Declaration of Research Assessment (http://am.ascb.org/dora/). He stressed the importance of opening access to scholarly publications, which may increase their influence on the global scientific progress. At the same time, Dr Gasparyan referred to the increasing number of retractions in English-language journals, which is largely due to their accessibility through the free full-text digital libraries and repositories. The subscription to periodicals and the distribution through the regular postal services are no longer capable of meeting the increasing demands of updated scientific information worldwide. Digitization, which includes the assignment of Digital Object Identifiers (DOIs), XML encoding for permanent archiving and preservation of scientific literature, indexing and posting full-texts of journal articles on digital platforms, is the requirement of the \u201cbig science\u201d era. Many journals from non-Anglophone countries may improve their visibility and attractiveness for the global scientific community by following the best examples of online journals from Anglophone countries. That said, the authors should be also aware of the \u201cpredatory journals and publishers,\u201d which are listed by Jeffrey Beall on his blog (http://scholarlyoa.com/). The blog contains information on unacceptable practices, which corrupt the open access and waste the authors\u2019 efforts.The second session of the Seminar was run by Associate Professor, Dr Armen Yuri Gasparyan, who presented functional characteristics of bibliographic databases and search platforms, analyzed journal impact indicators, and introduced the EASE Statement on Inappropriate Use of Impact Factors . Prof Zhanna \u0410. \u041cingaleva , Prof Svetlana A. Gusar , Olga V. Kirillova (NEICON School in Moscow), and Elena V. Karpunina (Intereconom Publishing) shared their thoughts on the visibility of Russian journals in international bibliographic databases and reassured that most regional journals are now correcting format of references and upgrading standards of peer review and ethical publishing, which will be helpful for indexing in the future.All the lectures were thoroughly analyzed and commented on by the Seminar participants at the roundtable discussion. The participants were encouraged by Dr Gasparyan to submit their best papers to the journals with wide visibility and international outreach. Some exemplary journals were discussed in detail (eg, The Seminar participants were awarded with certificates credited with CPD credits in research methodology and communication. It was decided to arrange such seminars with international participation annually to discuss matters arising across multidisciplinary journals and to advance science communication skills of non-native English-speaking authors, reviewers, and editors of regional journals."} +{"text": "There is an urgent need to build Research and Development (R&D) capacity for leishmaniasis and other neglected tropical diseases (NTDs) in the Middle East and North Africa.The neglected tropical diseases are a group of 17 viral, bacterial, protozoan, and helminthic infections that often have high morbidity but low mortality, causing disabilities through their impact on child development and education, pregnancy outcomes, and worker productivity [Leishmania is the most important protozoan infection in the MENA region [NTDs promote poverty and interfere with economic development. Emerging information indicates that the Middle East and North Africa (MENA) region is highly endemic for several NTDs, with increasing levels of poverty and disease in the region . Today, A region . Rapid uA region . Among tA region .http://www.afro.who.int/), have been successful in MENA countries, many have not received such attention.Globally, compared to HIV/AIDS, malaria, and tuberculosis, which receive 42.1% of the funds allocated to overseas development assistance for health, NTDs have generally been ignored, receiving only 0.6% of the budget . StudiesA similar level of neglect for both mass treatment of and R&D for NTDs has been noted for MENA countries. The World Health Organization (WHO) reports that mass drug administration coverage for many NTDs in MENA is low. For instance, the coverage for soil-transmitted helminthic infections in the WHO Eastern Mediterranean Region is less than one-half the coverage in sub-Saharan Africa . In addiAs mentioned previously, leishmaniasis represents a good case study of the challenges facing control of NTDs in MENA. Today, MENA countries exhibit some of the highest incidences of cutaneous leishmaniasis globally , with woIn addition to conferences, by establishing regional R&D and training centers of excellence in the MENA region, we could promote and build long-lasting research skills and capacities and enhance the contribution of research to the control and elimination of NTDs. One such center was suggested recently for southern Europe , but a pLeishmania major), and the second-highest prevalence of anthroponotic cutaneous leishmaniasis (Leishmania tropica infection) [Iran is one of the MENA countries with the highest prevalence of zoonotic cutaneous leishmaniasis (fection) . With mofection) . There aIn the coming years, geopolitical events taking place in the MENA region could promote the emergence or re-emergence of widespread NTDs. Now, more than ever, we need to re-examine the necessity to strengthen and expand existing programs for the control of NTDs in MENA, through improvement of mass treatment coverage for these diseases and identification of innovative ways to enhance R&D capacity in the region."} +{"text": "The aim of tissue engineering is to promote the repair of functional tissues. For decades, the combined use of biomaterials, growth factors (GFs), and stem cells has been the base of several regeneration strategies. Among these, biomimicry emerged as a robust strategy to efficiently address this clinical challenge. Biomimetic materials, able to recapitulate the composition and architecture of the extracellular matrix, are the materials of choice, for their biocompatibility and higher rate of efficacy. In addition, it has become increasingly clear that restoring the complex biochemical environment of the target tissue is crucial for its regeneration. Toward this aim, the combination of scaffolds and GFs is required. The advent of nanotechnology significantly impacted the field of tissue engineering by providing new ways to reproduce the complex spatial and temporal biochemical patterns of tissues. This review will present the most recent approaches to finely control the spatiotemporal release of bioactive molecules for various tissue engineering applications. Although approved by the US Food and Drug Administration (FDA) in 2002, the high doses of rhBMP-2 used by this device resulted in major adverse side effects, including cancer, spinal cord compression from soft tissue swelling, spinal cord impingement from ectopic bone formation, elevated bone resorption from osteoclast activation, and preferential induction of adipogenesis over osteogenesis interactions between cells and the extracellular matrix (ECM) have been proven to be crucial to orchestrate tissue formation and regeneration in response to injury. Materials such as hydrogels and scaffolds engineered to emulate the ECM can support tissue healing Hoffman, .Three-dimensional patterning has been defined as the entrapment of biochemical (PLLA) scaffolds loaded with rhBMP-7 enhanced osteogenesis. Kim et al. (PLGA) for the controlled release of small bioactive molecules (Pandolfi et al., m et al. accompliInterface tissue engineering focuses on the development of tissue grafts capable of replacing defective interfaces, such as ligament-to-bone, tendon-to-bone, and cartilage-to-bone (Almod\u00f3var et al., in vitro 2D cell cultures, which fail to reproduce tissue complexity. Recently, 3D cultures on biomimetic materials mimicking the ECM microenvironment are becoming the in vitro models of choice to study the regenerative process of specific tissues. 3D biomimetic cultures are more physiologically relevant than those in 2D and simpler than in vivo models (Hoffmann and West, Most of the current understanding of the regenerative process is based on the use of simplified in vivo (Lee et al., in vitro and in vivo (Gelain et al., Recently, in a very elegant study, the Anseth research group proposed an RGD patterned hydrogel, synthesized through a versatile process of sequential bio-orthogonal click-chemistry reactions (DeForest et al., In vivo, the transient nature of GF signaling is combined with the slow, sustained signals received from the ECM (Lund et al., de novo matrix deposition (Kim et al., However, in the natural ECM, cells not only respond to signals presented on the surface of the ECM but also to soluble stimuli, especially in the regeneration process. Usually, these factors diffuse through the ECM and bind to their specific receptors on cells\u2019 surface, activating specific transduction cascades. in vivo. Altogether, the studies herein reviewed show the potential of 3D biomaterials spatiotemporally patterned with bioactive molecules to recapitulate the complex biochemical milieu of target tissues.In the past decade, significant advances have been accomplished in the design of biopatterned materials able to accomplish temporally and/or spatially controlled release of bioactive molecules. Despite these advances, methods should be further developed to prepare patterns and gradients with controlled shape and kinetics, in order to tune the desired cell mechanisms SM and FT conceived the idea of this review. SM wrote the Abstract, Introduction, and Conclusion sections. LP drafted the first paragraph, FT drafted the second paragraph, and SM and FT revised and finalized the mini-review with the help of ET.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "One of the major concepts of modern epidemiology and disinfectology is prevention and fighting with healthcare-associated infections (HAI).Prophylaxis of HAI in Russia.Epidemiological, statistical.It is one of the largest documented chronic outbreaks of Nosocomial Salmonellosis in the world which occurred (1994-1996) at the big multi-speciality hospital with more than 1,500 beds. The outbreak was active for approximately 3 years and more than 350 surgical and intensive care unit patients fell ill. At that point in time it was impossible to eliminate the outbreak by means of traditional antiseptics and antibiotics used for patients\u2019 treatment.2 of healthcare organization areas. Phagoprophylaxis schemes of patients found in NS effective disease area and undergoing treatment at in-patient hospital, and sanitation and phagoprophylaxis of stuff were developed and described by the author for the first time.For the first time ever in global practice adapted salmonella bacteriophage was used in a combined manner for treatment of NS patients (83 people), phagoprophylaxis of patients admitted to the in-patient hospitals and undergoing treatment there , sanitation and phagoprophylaxis of staff , and biological disinfection of more than 15,000 mThe method of Salmonella Bacteriophage combined use was highly effective, harmless, non-toxic while treating patients with salmonellosis at surgical and intensive care units, it allowed performing effective disease prevention in risk groups and sanitation of staff, it was cost-effective and highly effective in decontamination of surfaces and objects in medical organization. Combined use of adapted salmonella bacteriophage allowed isolating and eliminating of long-existing effective disease area of Nosocomial Salmonellosis for 3 months from the time of bacteriophage\u2019s application.None declared."} +{"text": "With contributions from USA, Taiwan, Japan, and Korea, this special issue holds great insight. This special issue offers comprehensive knowledge on chitosan and collagen as biomaterials, especially with respect to their basic biological and chemical properties, as well as clinical applications. Two review articles described the preparation and biological application of chitooligosaccharide and its derivatives and the relevance to clinical dentistry of distinct characteristics of mandibular bone collagen. Original articles reported seven experiments: 3 chitosan topics and 4 collagen topics. The former demonstrated the contributions for a proteomic view of chitosan nanoparticle to hepatic cells, the promotion of D-glucosamine to transfection efficiency, and chitin application as skin substitutes. The latter showed the contributions for hydroxyapatite-gelatin nanocomposite, genipin modification of dentin collagen, dentin phosphophoryn/collagen composite for dental biomaterial, and biological safety of fish collagen."} +{"text": "Human albumin is used for volume expansion and resuscitation and to correct hypoalbuminemia . HypoalbAlbumin mobilizes polyunsaturated fatty acids (PUFAs) from the liver and other tissues, and thus enhances the formation of cytoprotective bioactive lipids \u2013 lipoxins, resolvins and protectins \u2013 that, in turn, suppress production of proinflammatory prostaglandins, free radicals and cytokines. The beneficial actions of albumin thus depend on its ability to mobilize PUFAs and the formation of adequate amounts of lipoxins, resolvins and protectins. For those who have hepatic and tissue deficiency of PUFAs, albumin fails to mobilize PUFAs and formation of lipoxins, resolvins and protectins will be inadequate, which may explain failure of the beneficial actions of albumin in the critically ill.The cell membrane is rich in PUFAs that give rise to both proinflammatory prostaglandins, thromboxanes and leukotrienes and anti-inflammatory lipoxins, resolvins and protectins see Fig. BalancePlasma concentrations of TNF\u03b1, interleukin (IL)-6 and macrophage inflammatory protein-2 were significantly lower and the IL-10 concentration higher in the albumin-treated hemorrhagic shock model animals . HypoalbTNF\u03b1 administration to healthy well-nourished rabbits produced hypoalbuminemia and endoBased on the preceding discussion, I propose that PUFAs need to be administered along with albumin to enhance formation of lipoxins, resolvins and protectins to derive the benefit of albumin therapy in the critically ill ,17.Beneficial actions of albumin are limited by: availability of PUFAs in the liver and other tissues; formation of adequate amounts of lipoxins, resolvins and protectins from PUFAs; activity of cyclooxygenase and lipoxygenase enzymes; circulating levels of TNF\u03b1 and other cytokines that interfere with the formation of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid and induce hypoalbuminemia; enhanced formation of reactive oxygen species that peroxidize PUFAs and thus reduce their availability; and formation of proinflammatory prostaglandins that antagonize actions of lipoxins, resolvins and protectins ,17 (see Adipose-fatty acid binding protein (A-FABP), which induces insulin resistance and whose levels are increased in the critically ill , is a caA-FABP can be linked to the expression of Toll-like receptors, macrophage activation, synthesis and release of proinflammatory cytokines IL-6 and TNF\u03b1, activation of cyclooxygenase-2 expression and eicosanoid synthesis, events that cause insulin resistance and initiation and progression of inflammation and sepsis. PUFAs and lipoxins, resolvins and protectins suppress A-FABP expression, inhibit macrophage and cyclooxygenase-2 activation, and decrease production of proinflammatory cytokines, and thus decrease insulin resistance and resolve inflammation and augment recovery from sepsis ,19. Henc"} +{"text": "The gap between what is known and what is practiced results in patients not benefitting from advances in healthcare and unnecessary costs for clients and health systems. The Promoting Action on Research Implementation in Health Services (PARIHS) framework posits 1) strong evidence, (2) context in terms of coping with change, and (3) facilitation as elements influencing successful implementation of new knowledge [ strong eThe development of the Context Assessment for Community Health (COACH) tool departed from the PARIHS framework and was undertaken in Bangladesh, Vietnam, Uganda, South Africa and Nicaragua in six phases; (1) defining dimensions and draft tool development, (2) quantitative and qualitative content validity amongst in-country experts, (3) content validity amongst international experts, (4) response process, (5) translation and (6) evaluation of psychometric properties. The tool has been validated for use amongst physicians, nurse/midwives and community health workers in these five settings.This study indicates that dimensions of context identified to influence implementation in high-income healthcare settings are also relevant in LMICs. Having said this, there are additional aspects of context of relevance in LMICs. The final version of the tool includes 49 items measuring the following eight aspects of context: leadership, work culture, monitoring services for action, sources of information, resources, community engagement, commitment to work and informal payment.Application of the COACH tool will allow for systematic characterization of local healthcare context prior to or as part of the evaluation of implementing new interventions and allow for deepened insights into the black-box of implementation in LMICs."} +{"text": "Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique\u2019s application to the diagnosis and monitoring of RP. The light-sensing retinal tissue is composed of specially functionalized cell layers including the ganglion cell layer (GCL), the bipolar/horizontal cell layers, and the photoreceptor cell layer. The outer retinal layer, consisting of the outer plexiform layer (OPL), the outer nuclear layer (ONL), and the photoreceptor layer, detects, by means of numerous rods and cones, contrast and color, respectively. The photoreceptors for the initial sensing of light receive the light information of visual objects and transfer signals to retinal ganglion cells and optic nerves in the brain. Photoreceptor degeneration causes retinitis pigmentosa (RP), one of the most common inherited ophthalmologic diseases in vivo, can be useful for early diagnosis. Although there is no approved treatment for RP, vitamin A and docosahexaenoic acid have been reported to delay its progress in vivo, though imaging of rod cells remains a challenge Patients in the early stage of RP usually suffer from night blindness since primary RP incurs rod degeneration. Night blindness symptoms worsen as the disease progresses, followed by constriction of vision and, eventually, central vision loss Differential interference contrast (DIC) microscopy is designed to image unstained, transparent specimens, enhancing the contrast resulting from the optical path difference between two beams that are split from the Nomarski prism. In the present study, we set up a DIC microscopy system and observed photoreceptor cells with RP at the cell level.The DIC microscopy system used in our laboratory is comprised of a polarizer, Nomarski prisms, a condenser, an objective lens, and an analyzer . Light prd/rd) mice, both widely utilized animal models in RP research, were housed and provided with standard chow and water provided ad libitum. Male Sprague-Dawley rats and C57BL/6 (wild type) mice were reared separately as controls. Autosomal recessive RP occurs in the RCS retina due to malfunction of MERTK, a member of the Axl subfamily of receptor tyrosine kinase, which inhibits contact between photoreceptors and the RPE rd mice follows a pattern similar to that in human RP: apoptosis of rod photoreceptors, followed by death of cone photoreceptors rd mice, similarly to some human RP cases, results from a mutation in the \u03b2 subunit of cGMP-dependent phosphodiesterase rd mice aged 3 weeks and 3 months, were prepared . Samples were obtained from both eyes so as to compare, under DIC, retinal flat-mount and histological images of retinal sections stained with Hematoxylin and Eosin (H&E). Specifically, the retina of the right eye was extracted and flat-mounted with buffer solution on slides; the left eyeball was enucleated and fixed with 4% paraformaldehyde overnight and embedded in an optimum-cutting-temperature compound. Ten-micrometer-thick sections were obtained for H&E staining.The use of animals in this study was approved by the Animal Research Committee of Seoul National University Hospital, and complied with the regulations of the Association for Research in Vision and Ophthalmology\u2019s Statement for the Use of Animals in Ophthalmic and Vision Research. Royal College of Surgeons (RCS) rats, and C3H/HeJ retinal-degeneration . This RP-induced decrease agreed well with the closed-loop decremental tendency. Also, the tissue shrinkage could be confirmed by the cell decrement. A number of cells in the photoreceptor sample with RP at 8 weeks were even more decreased, since the RP had completely progressed. Thereby, the automated counting method which needs more validation in future research was demonstrated to be a possible diagnostic method for photoreceptor diseases that tend to manifest cell-number decrements.The DIC images were also analyzed by MATLAB for automatic diagnosis of RP based only on images rd mouse images obtained using the DIC technique well coincided with the measured histological morphologies of the photoreceptors. Also, the clear DIC images made possible the application of an automated counting program (designed using MATLAB) to image analysis and photoreceptor counting. Based on our results, we conclude that the DIC technique is a feasible and effective method of RP diagnosis. Indeed, more generally, the novel application of DIC microscopy to retinal imaging at the cell level potentially can be utilized as a simple and convenient retinal-disease-diagnostic technique. Future research should focus on the potential application of DIC microscopy to in vivo and real-time diagnostics and monitoring of human RP.The images obtained demonstrate that by the DIC technique, we can clearly distinguish RP-affected abnormal retinal tissue from normal retinal tissue. Also, DIC images can be used to estimate the elapsed time of RP. The RCS rat and"} +{"text": "Stem cells mainly include embryonic stem cells (ESC), pluripotent stem cells (iPS), Epiblast-derived stem cells (Epi-SC), and adult tissue stem cells. ESC are pluripotent, being able to differentiate into the ectoderm, mesoderm and endoderm (Evans and Kaufman, Stem cell treatments include new technologies and therapies that aim to replace damaged tissues and cells in order to treat disease or injury (Lindvall and Kokaia, The ability of stem cells to self-renew and their capacity for differentiation offers significant potential for the generation of tissues with minimal risk of rejection and side effects. A number of stem cell therapies are still in the experimental stages, and are controversial (Francis et al., Stem Cell Treatments is to publish all findings and experiences of stem cell treatments, experimentally and clinically, and to open up new possibilities for the treatment of various diseases such as Alzheimer's disease, traumatic brain injury, heart disease, diabetes, and cancer, etc., that we may promote health and extend the human life span.The goal of"} +{"text": "High risk behaviors (HRBs) can impact public health. HRB refers to any kind of behavior or reaction that can potentially harm psychological and biological aspects of an individual. These behaviors are hazardous to several areas of human development which include: health, performing duties or tasks commensurate with developmental stage, playing expected social roles, learning the skills, feeling competent and adequate, and preparation for doing tasks . PrevaleAlmost hundred years ago, ADHD was described as a childhood disorder called hyperactivity. Nearly six decades later, the \"minimal brain damage\" and \"minimal brain dysfunction\" were replaced with hyperactivity. With the introduction of attention deficit as the central feature of this disorder, a significant change occurred in the approaches of etiology and diagnosis of ADHD . CurrentPeople with ADHD, suffer from social and interpersonal problems. Inattention and hyperactive/impulsive behavior can cause social problems in this population , thus, PSymptoms of ADHD, in general, and its comorbidity with other disorders can increase probability of performing HRBs, but these are not the only determinants of high risk behaviors. Overall, ADHD patients have major problems in decision-making, executive functioning and social cognition. Their decision-making in ambiguous situations has the same features of \"intuitive-existential\" decision-making system . Also, tIn a review of the studies done over a period of 30 years by Uekermann et al. found that ADHD is associated with deficit in social cognition (e.g., face perception, emotional prosody perception . DeficitAlthough our understanding of ADHD and its association with HRBs has increased by the conducted research, there are still questions and issues regarding to hereditary, neuropsychological, developmental, environmental, psychological, social factors of ADHD which should be studied further. Some of the major issues in this regard are listed below.1- The interaction of genetic and environmental factors in the development of ADHD.2- The development of brain networks and circuits associated with ADHD symptoms, impaired executive functions and social cognition of people with ADHD.3- Deficits in executive function as a general capacity and also its components and how executive functions relate to HRBs in children and adults. 4- Studying the effectiveness of drug treatments and psycho-social interventions on executive functions and improving the deficit of social cognition depending on ADHD subtypes and developmental stage of the patients.5- Impact of parenting styles and cultural-social factors on development and maintenance of ADHD symptoms with HRBs, and the impact of ADHD on parental behaviors.6- The role and influence of different situations and emotional states in decision-making of people with ADHD."} +{"text": "Phase contrast magnetic resonance imaging (PC-MRI) is the current gold standard for blood flow quantification. Using this technique it is possible to quantify cardiac output, stroke volume, shunts and valve insufficiencies. The accuracy of flow quantification is highly dependent on the manual delineation of the vessels of interest. Therefore, the purpose of this study is to develop an automatic method for vessel segmentation in PC-MRI sequences.A total of 211 subjects from a previous study [The stroke volume from the automated method agreed well with manual delineations Figure , with a In conclusion, the proposed method for vessel segmentation results in bias and variability comparable to manual delineations.Swedish Research Council, Swedish Heart-Lung Foundation, Medical Faculty at Lund University."} +{"text": "Morphogens are secreted signaling molecules that play instructive roles to regulate tissue patterning and cell identity in a concentration-dependent fashion during early embryonic development. Four principal mammalian morphogens include retinoic acid, as well as members of the Wingless-int (Wnt) and transforming growth factor beta (TGF-\u03b2)/bone morphogenic protein (BMP) and sonic hedgehog (Shh) families. Morphogen gradients control a plethora of developmental events related to specification and differentiation, cell and tissue polarity, growth control and regeneration.In the nervous system, neuronal differentiation, the polarized outgrowth of neuronal projections, the pathfinding of axons toward their target cells, and the recognition of pre- and post-synaptic partner cells are fundamental requisites to allow the assembly of functional synapses. During the last decades, a growing body of evidence gathered from invertebrate and vertebrate model organisms has shown that the same morphogens classically known to orchestrate early embryonic development are also involved in the precise wiring of the nervous system.Aviles et al.; Bernis et al.; Berwick and Harvey; Dickins and Salinas; Pinto et al.; Rosso and Inestrosa; Silva-Alvarez et al.; Varela-Nallar and Inestrosa; Aviles et al.; Varela-Nallar et al.), BMP , and Shh signaling pathways. Research also covers the function of signaling cascades activated by other types of morphogens, including the fibroblast growth factors , the hepatocyte growth factor (HGF) , and netrin . In addition, researchers have contributed with the emerging roles of new molecules, such as the thyroid hormone , SCO-spondin , and vitamin C . Articles are focused on a wide variety of cellular processes involved in the establishment of neuronal connectivity, such as neurogenesis, neuronal specification, and maturation , axonal outgrowth, polarization, and guidance , and synapse formation , either in physiological contexts or in models of diseases affecting the normal function of the nervous system, including epilepsy , Alzheimer's disease , and amyotrophic lateral sclerosis .The aim of this research topic is to highlight the fundamental roles that morphogens play during the establishment of synaptic connectivity. Hence, we have brought together 12 original research articles and eight reviews. They are mainly focused on Wnt (We are confident that this integrative research topic emphasizes the central and pleiotropic roles played by morphogens during neural development. We therefore hope that the original articles and reviews presented here will inspire future directions of research focusing on the diversity of cell signaling mechanisms controlling the assembly, maintenance and regeneration of the nervous system.JH and NO wrote, edited and revised the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "There is an alarming increase in the number of cases of diabetes with the global prevalence rate at 9% for the year 2014 . DiabeteMesenchymal stromal cells are at a forefront of the cell-based therapies and Davey et al. elegantly summarized importance of MSCs for diabetic microvascular complications . The revDr. Rajashekhar further reiterated the importance of MSCs in diabetic microvascular complications in his review by summarizing the critical benefits of MSCs for the treatment of diabetic retinopathy . His artFurthermore, Mizukami and Yagihashi summarized the importance of ASCs in the treatment of diabetic neuropathy adding tin vivo home to ischemic retina and integrate into retinal vasculature in diabetic retinopathy . Their sculature .+ cell levels and restoration of NO helps in correcting CD34 dysfunction choice of an ideal stem cell type, (ii) rigorous characterization of stem cells, (iii) site of injection and route of delivery, (iv) limited survival, (v) risk of tumors, and (vi) impaired potency, before the cell therapy reaches to the clinic. However, with advancement in research, stem cells will provide effective treatments for diabetic microvascular complications.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Using different modalities of neuroimaging, both structural and functional brain connectivity can be mapped. The connectivity analysis has been widely applied into investigating the brain mechanisms of cognitive functions and neuropathology of different brain disorders. However, there are still some challenges when mapping, analyzing, and modeling the brain connectivity at different scales. This special issue aims at reflecting the advances in studies of brain connectivity, including both modeling methods and applications. In this special issue, different imaging techniques, such as structural MRI, diffusion MRI, and functional near-infrared spectroscopy (fNIRS), were employed in the studies of brain connectivity. The applications addressed hemispheric asymmetry, primary insomnia, and motor training. Also, the computational modeling methods and analysis toolbox of brain connectivity were introduced. The types of papers include review articles as well as original research.With the advent of brain imaging techniques, the study of human brain connectivityFor the modeling methods of brain connectivity, R. C. Sotero (2015) reviews computational models of phase-amplitude coupling (PAC) generation ranging from realistic networks of Hodgkin-Huxley neurons to neural mass models (NMMs) describing only the average activity of the neuronal populations involved and showed that NMMs are rich enough to provide a variety of PAC patterns. For the analysis toolbox of brain connectivity, J. Xu et al. (2015) developed a MATLAB software package that facilitates fNIRS-based human functional connectome data-analysis, which will be useful for the resting-state brain functional connectivity (FC) studies. For the application studies of brain connectivity, N. Shu et al. (2015) investigated the hemispheric asymmetry of brain white matter anatomical network which is constructed by diffusion MRI tractography and demonstrated that the topological asymmetries of the anatomical networks might reflect the functional lateralization of the human brain. L. Zhao et al. (2015) investigated the topological alterations of the structural covariance network for patient with primary insomnia, suggesting that insomnia might be related to underlying increase in brain network integration encompassing the sensory to motor networks, the default mode network, and the salience network and decrease in the integration between the sensory regions and the frontoparietal working memory network.The special issue also contains several review papers: B. Wong et al. (2015) review structural and functional connectivity studies of bilingualism and examined different issues such as whether the language neural network is different for first- (dominant) versus second- (nondominant) language processing; the effects of bilinguals' executive functioning on the structure and function of the \u201cuniversal\u201d language neural network; the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. T. D. Ben-Soussan et al. (2015) review the connectivity studies of quadrato motor training and proposed a general model tying cerebellar function to cognitive improvement, via neuronal synchronization as well as biochemical and anatomical changes.In summary, the papers collected in this special issue cover a wide range of topics that are on the frontier of the methods and applications of brain connectivity."} +{"text": "Evidence based policy-making has been promoted as a means of ensuring better outcomes but what counts as evidence in policy-making lies within a spectrum of expert knowledge through scientifically generated information. Different actors provide varying degrees of support for and use of different types of evidence in policy development. Since not all forms of evidence share an equal validity or weighting for policy-makers, it is important to understand the key factors that influence their choice of evidence.A retrospective cross-sectional study was carried out at the national level in Nigeria. A case-study approach was used and the Nigerian Integrated Maternal Newborn and Child Health (IMNCH) strategy was selected because it met the criteria of being: (i) recently developed (<10 years old); and (ii) of international prominence. Two frameworks were used for conceptualization and data analysis namely: (i) framework for analyzing the role of evidence in policy making developed by Mirzoev et al., in 2012, and (ii) the policy triangle. They were used to explore the key contextual and participatory influences on choice of evidence in developing the IMNCH strategy. Data was collected through review of relevant national documents and in-depth interviews of purposefully selected key policy and decision makers. Thematic analysis was applied.The breadth of evidence used was wide, ranging from expert opinions to systematic reviews. The choice of different types of evidence was found to overlap across actor categories. Key influences over actors\u2019 choice of evidence were: (i) perceived robustness of evidence - comprehensive, representative, recent, scientifically sound; (ii) roles in evidence process, i.e. their degree and level of participation in evidence generation and dissemination, vis-\u00e0-vis their role in the policy process; and (iii) contextual factors such as global agenda and influence, timeline for strategy development, availability of resources for evidence generation, and lessons from previously unsuccessful policies/plans.Actors\u2019 choice of evidence in policy making is influenced not only by the characteristics of evidence, but on the roles these actors play in the process, their power to influence the policy, and the context in which evidence is used."} +{"text": "In 1995, Dr.Parker developed the vacuum-assisted breast biopsy technique (using theMammotome\u00ae equipment), to improve the accuracy of biopsies ofmicrocalcifications in adipose breast tissue. Core and vacuum-assisted biopsies were initially greeted withskepticism and even rejected by some medical professionals. Image-guided percutaneousbiopsies, however, would bring changes to the field and gain broad acceptance for use inclinical assessments.In 1989, Dr. Parker started performing percutaneous biopsy, using a core needle and anautomatic deployment device, for the diagnosis of nonpalpable breast lesions, thedetection of which was becoming increasingly more frequent after the advent ofhigh-resolution mammography. In their first study of the topic, published in 1990,Parker et al. compared the performance of core biopsy with that of surgical biopsy,concluding that core biopsy represents a reliable, rapid, and affordable alternativethat is well-tolerated by patients with minimum complications and a low risk ofparenchymal scarring; b) failure to standardize practices after a benignhistopathological result, resulting in patients who should be merely observed undergoingsurgery, and vice-versa; c) lack of technique and tactics in carrying out the procedure,including the incorrect choice of access and faulty spatial reasoning; d) lack ofappropriate documentation of the procedure-the report, the record of the lesion beforeand after the biopsy, and X-rays of the biopsy fragments -leaving the radiologist vulnerable from a legal aspect; e) lack of auditing of the results,making it impossible to evaluate the performance and identify errors to becorrected-8. Items a), b) and c) are certainly the result of gapsin the education of the radiologist. It is extremely important that radiologists whowork with breast imaging procedures frequent institutions that specialize in and arededicated to specific training. Item d) illustrates the distortion in our model of care,in which low rates of pay by the medical insurance companies leads to an excessivenumber of exams per hour. That problem can be solved only by presenting a united frontwithin the Brazilian College of Radiology and Diagnostic Imaging, because individuallywe are impotent. Item e) illustrates the absence of an auditing culture. There is nointerest in the matter, and radiologists do not receive specific training in that. Inaddition, it is difficult to obtain and correlate results in day-to-day practice,because patients are lost in the system.Although the demand for percutaneous biopsies is currently increasing, many problemsarise, resulting in false-negatives, late or delayed diagnosis, and increases in cost.Among the most important problems are the following: a) unawareness of the technicalcriteria for indicating the procedure (on the part of the requesting physician), as wellas of the criteria for recommending and selecting the best type of biopsy (core orvacuum-assisted) and guidance for each lesion (on the part of the radiologist), given that an incorrectindication/choice generates technical difficulties and diagnostic errors, as well asresulting in inefficient allocation of resourcesIn conclusion, the considerations above are points for reflection. The ultimate goal isto improve the experience of patients subjected to breast biopsy."} +{"text": "In 2014 World Kidney Day (WKD) will focus on chronic kidney disease and aging. The mission of WKD is to raise awareness so that everyone cares for their kidneys and, if appropriate, check to assess if they are at risk for kidney disease. Prevention of kidney disease, early detection, and subsequent kidney protection are critical aims for WKD.Last year, the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF), focused the World Kidney Day (WKD) of 2013 on acute kidney injury . VariousGTH and HN contributed as authors of the manuscript.The author declared no competing interests.Ethical issues have been completely observed by the author.None."} +{"text": "Undoubtedly, residents play a very important role in the healthcare system of most countries. The process of admission of medical trainees into specialties, residency training and their assessment are key determinants of the future of healthcare.In Canada, according to the 2014\u201315 data, there were 13,439 residents (excluding Fellows) distributed in 42 specialties/sub-specialities.Philips and Barker who systematically examined the occurrence of fatal medication errors over 25 years in the US attribute a significant spike in medication errors in July to the entry of a new cohort of medical residents.4A recent study by Curtis and Dube looked at the characteristics of CMGs, IMGs and CSAs in an era where measures are being taken to alleviate physician shortage.In Canada, the Canadian Resident Matching Services (CARMs), a non-profit, fee-for-service organization, facilitates a fair and transparent process of resident admissions into programs.*The Royal College of Physicians and Surgeons and the College of Family Physicians of Canada play are regulatory bodies that oversee the quality of residency training in Canada. Research into the training process and application of educational principles helps promote training quality. In this edition, Guajardo and colleagues examine the effect of inclusion of patient name and image in virtual patient cases on knowledge acquisition.A large part of resident training involves role modeling by preceptors. In Canada, with its wide distribution of population in rural and remote areas, medical schools train students and residents in these areas under the supervision of preceptors. Piggott, Morris, and Lee-Poy examine the facilitators and barriers to engagement of preceptors in distributed medical campuses. There are several barriers that can be addressed by medical schools such as: provision of training of preceptors in being better teachers, ensuring that preceptors in these areas are aware of curricular objectives, among others. Lubitz, Lee, and Hillier look at the perception of residents to the longitudinal integrated curriculum, a form of training provided in mostly rural areas.With the introduction of the CanMEDs roles, residents are trained and assessed using the CanMEDs framework.A large volume of literature exists in relation to the transformation of trainees from novices to experts."} +{"text": "The axillary artery presents abnormalities in its origin and course and a variable branching.A rare case of axillary artery bifurcation and branching was observed in a 60-years-old European male cadaver of Greek origin. The right axillary artery at the second part was bifurcated into a superficial and a deep brachial artery. The superficial brachial artery anteromedial to the median nerve and lateral to the ulnar nerve gave off the acromio-thoracic artery and two lateral thoracic arteries. The deep brachial artery behind the median nerve, after giving rise to the anterior circumflex humeral artery trifurcated into a branch that coursed distally, the posterior circumflex humeral artery and the subscapular artery. The latter subdivided into the circumflex scapular artery, a muscular branch for the subscapularis and the thoracodorsal artery. The continuation of the deep brachial artery divided laterally into a humeral nutrient artery and medially into a trunk which trifurcated into the profunda brachii artery, a deep muscular branch and a branch to the posterior compartment of the arm. The profunda brachii artery ended as radial and middle collateral arteries.Deviations from the normal arterial pattern are of immense significance for anatomists, plastic, cardiovascular and orthopedic surgeons, vascular radiologists and interventional cardiologists. The pectoralis minor muscle divides the AA into three parts. The 1) Adachi . Althoug) Adachi . The varIn the present case, a unilateral high bifurcation of the AA into a superficial brachial artery (SBA) in front of the median nerve (MN) and a deep brachial artery (DBA) behind the MN is described. This abnormal division of the artery may have clinical application in hemorrhagic emergencies, where the accurate diagnosis and surgical repair or ligation of the vessels is crucial.During routine dissection of a 60-years-old Greek male donor who died after cardiac arrest, an unusual case of high bifurcation of the AA into two arterial stems supplying the right axilla and the upper limb was observed Figure\u00a0A. The prThe coexistence of abnormalities of the AA is unusual, while isolated aberrations of the arterial pattern follow a wide range among races and/or bilaterally (3rd part) (Natsis et al. st part and the 2nd part of the AA was also reported (Huelke rd part of the AA, although the PBA may be absent (Samuel et al. Twenty-three different arterial patterns of the AA have been recognized (De Garis and Swartley A Huelke . The LTA Patnaik or from Patnaik . The TDA Patnaik . Moreoved Huelke . In our d Huelke who obsend part of the AA into SBA and DBA occurred. Other authors (Cavdar et al. rd part, while a rare bifurcation at the 1st part, absence of the SSA and origin of the ATA from the DBA, was also referred (Jurjus et al. The AA high bifurcation into SBA and DBA (Cavdar et al. The variable pattern of the AA is of paramount importance for surgeons and interventional physicians. Although the superficial course of the SBA makes the arterial grafting and cardiac catheterization easier, the high bifurcation of the AA and its abnormal branching pattern may pose problems to clinician during angiographic procedures leading to diagnostic errors. The SBA due to its abnormal origin and position may be more prone to serious injury leading to hemorrhage (Jurjus et al. nd part. Documentation of such rare abnormalities in the axilla is highly significant for aneurysms and trauma surgery (Ortiz-Pomales et al. The present case provides additional information on the branching and distribution pattern of the AA since the high division of the artery occurs at the 2The body donor gave written informed consent before its death for the publication of this case report.K. Natsis - Professor, Director of the Department of Anatomy, Medical School, Aristotle University of Thessaloniki, Greece, natsis@med.auth.grM. Piagkou - Assistant Professor, Department of Anatomy, Medical School, National and Kapodistrian University of Athens, Greece, mapian@med.uoa.grNA. Panagiotopoulos - Research Fellow, Department of Anatomy, Medical School, National and Kapodistrian University of Athens, Greece, panagiotopoulos.nikitas@gmail.comS. Apostolidis - Associate Professor, Department of Anatomy, Medical School, Aristotle University of Thessaloniki, Greece, stlsa@med.auth.gr"} +{"text": "Caloric restriction (CR), the reduced intake of calories without malnutrition, extends lifespan of many organisms, from yeast to mammals, and delays the progression of age-related diseases. Evidence show that hypothalamus is a crucial brain region for the progress of whole-body aging and the"} +{"text": "Three hundred and twelve delegates from 73 cities in 16 countries took part in the conference. Actual problems of urogenital tract infection (UTI) including tuberculosis (TB) as a specific infection were discussed, including: nosocomial infections in urology, various aspects of prostate biopsy, epidemiology and diagnosis of urogenital tuberculosis, gender and age related characteristics of urinary tract infections, and male infertility, The meeting of the ESIU/EAU board at the annual EAU Congress in Paris in 2013 had decided to organize the Conference on Urogenital Tuberculosis (UGTB) in a region with a high prevalence of this disease. As the Novosibirsk Research TB Institute and the TB Department of Novosibirsk Medical University are well-known for their studies in this field, and Siberia is an epidemic region of TB, Novosibirsk was chosen as a place for this Conference. The meeting was organized as a joint event between several medical associations: The European Section of Infection in Urology (ESIU)/European Association of Urology (EAU), International Commission on UTI of the International Society of Chemotherapy for Infection and Cancer (ISC), Russian Society of Urology, Russian National Association of Phthysiologists, Asian Association of Urogenital Tract Infection and Sexually Transmitted Diseases (UTI&STI), Novosibirsk Research Institute for Tuberculosis and Novosibirsk Medical University, Russia. The Organizing Committee was chaired by Professor Truls E. Bjerklund Johansen, Chair of the ESIU, Professor Kurt G. Naber, Past-President of the ISC, and Honorary Chair of the ISC WG UTI, and Professor Ekaterina Kulchavenya, as President of the Conference. The International Conference \u201cUrogenital Infections and Tuberculosis\u201d was held in Novosibirsk, from 24 to 26 October 2013. Three hundred and twelve delegates from 73 cities in 16 countries took part in the conference, and 191 doctors attended via on-line translation. One of the conference highlights included the World Health Organization (WHO) report which indicated that 8.6 million people suffer from TB in 2012, including 1.1 million cases among people with HIV. In 2012, 1.3 million people died from TB. In 2012, an estimated 450,000 people developed multidrug-resistant TB (MDR-TB) globally and there were an estimated 170,000 deaths occurred from MDR-TB.M. tuberculosis may affect any organ of the human body, and next to the lungs the most common sites of the disease are the urogenital system, bones and joints. Unfortunately, because of delayed diagnosis, urogenital tuberculosis (UGTB) often has a complicated course. UGTB may mimic urogenital tract infection (UTI) with common bacteria, a fact that confuses many doctors who are not familiar with TB. The official opening ceremony was attended by the Minister of Public Health of the Novosibirsk region, Professor Leonid Shaplygin , and theFor three days there were parallel lectures, debates and discussions in two halls\u2014in English and Russian languages with simultaneous translation. The following problems were discussed: latent urogenital infections, their bacteriological diagnosis and therapy; complicated urogenital infections, their prevention and treatment; sexually transmitted infections; infectious diseases of the reproductive system as a cause of infertility and sexual dysfunction; interrelation of infections and tumors of the urogenital system: mistakes in diagnosis and features of combined therapy; standards of examination and treatment of patients with urogenital infections; epidemiology, organization of early detection and follow up of patients with urogenital tuberculosis; classification of urogenital tuberculosis; diagnosis, therapy and surgery of urogenital tuberculosis; multi-organ tuberculosis, and multi-drug resistance (MDR) with extrapulmonary tuberculosis.On the first day of the conference, participants were able to attend sections dedicated to the following topics: bladder leukoplakia, kidney stones, and the problem of non-specific cystitis, chronic prostatitis, and sexually transmitted infections. In the session on bladder leukoplakia, the etiology and pathogenesis of this disease were considered in addition to the role of sexually transmitted diseases. Also, the possibilities of minimally invasive procedures as well as the prospects for recovery of anatomy and physiology of the urothelium were demonstrated. A new method of less invasive intravesical laser therapy for bladder leukoplakia was presented with evidence of its superiority compared to transurethral resection. Problems of urolithiasis are by no means new to urology, but they are still quite relevant. The latest techniques and the \u201cgold standard\u201d lithotripsy and litholytic therapy were presented and prevention of infectious complications and preoperative preparation were thoroughly discussed . Although the topic of non-specific cystitis in urological practice has been repeatedly considered at various congresses and conferences, the contributions and discussions in this section were again very lively.On the second day of the Congress, the followings topics were discussed: current issues of nosocomial infections in urology, various aspects of prostate biopsy, epidemiology and diagnosis of urogenital tuberculosis, gender and age related characteristics of urinary tract infections, and male infertility. Possibilities of minimally invasive and endoscopic procedures in urology, as well as modern methods of drainage of the urinary tract and wounds were demonstrated to the audience.Ekaterina Kulchavenya emphasized in her presentation on the classification of UGTB that UGTB remains an important problem, especially in developing countries, because it is often an overlooked disease. Classification includes exact description of forms and stages of the UGTB, because each stage implies a different approach of management. Thus, accurate classification is the basis for good therapeutic results. Kidney tuberculosis (KTB) at stage 1\u20132 should be treated with chemotherapy, KTB at stage 3 requires partial nephrectomy, and KTB at stage 4 is indicated for nephrectomy. A stricture of ureter needs reconstructive surgery in KTB 1\u20133, but nephron-ureterectomy in KTB-4. Male genital tuberculosis (MGTB) should be treated with chemotherapy; fistulas are treated by surgery. Generalized UGTB, combining both kidney TB and male genital TB should be managed depending on the forms and stages of the kidney and male genital TB. UGTB is a tremendously diverse disease. A unified standard approach is therefore impossible. The common term \u201cUGTB\u201d gives insufficient information about therapy needed, e.g., surgery, and prognosis\u2014and makes evaluation of general epidemiology difficult. In contrast, a more detailed clinical classification will also improve the therapy of UGTB.Mete Cek from Trakya University (Turkey) reported the results of a 10-year, worldwide study on the prevalence, structure and characteristics of nosocomial infections in hospitalized urological patients. Besides prevalence and contemporary classifications, also a detailed analysis was presented concerning causes of nosocomial infections, antibiotic resistance patterns of uropathogens, and international practices of antibacterial therapy.Mycobacterium tuberculosis and drug susceptibility testing. According to the author\u2019s data, isothermal microcalorimetry could displace all other culturing methods, since the minimum detection time is only 25 h and the test easily identifies the drug sensitivity of the pathogen. With regards to UGTB, with this technique the growth rate and doubling time of 4 different mycobacteria could be determined in urine simultaneously.Florian Wagenlehner from the University of Giessen had two presentations, one on complications of prostate biopsy and the other on new antibiotics in urology. Every year in Europe more than 1 million prostate biopsies are performed, and the risk of infectious complications after this procedure is rising. The author proposed a strategy to minimize the risk of infectious complications and justified the need of targeted antibiotic prophylaxis. In his second presentation he analyzed the global bacterial antibiotic resistance in urology in relation to the antibacterial activity of different classes of existing and new antibiotics in the pipeline. Gernot Bonkat from the University of Basle (Switzerland) presented the isothermal micocalorimetry as a new method for identification of Topics of the third day of the conference were prevention of urogenital infections, chemotherapy and surgery of urogenital tuberculosis.Magnus Grabe discussed the prevention of infectious complications in urological surgery. He encouraged all participants to follow the recent recommendations of the EAU Guidelines.Bj\u00f6rn Wullt reviewed in his presentation the optimal management of uncomplicated UTI according to the 2013 updated EAU guidelines. Seung-Ju Lee described the methods of reconstructive surgery in UGTB. Denis Kholtobin presented his rather huge own surgical experience. He emphasized the necessity of simultaneous extirpation of bladder and prostate in male patients with bladder TB.M. tuberculosis with BACTEC 960 and GeneXpert. According to data of the Novosibirsk Research TB Institute, in 12.5% of patients with prostate tuberculosis that initially showed negative culture results, M. tuberculosis was finally found with these new methods.Anna Mordyk paid special attention to difficulties of bacteriological confirmation of UGTB. The main reasons are: (i) rare and scant mycobacteriuria and (ii) non-optimal previous antibacterial therapy for \u201curogenital tract infections\u201d, which in fact means overlooked UGTB. Olga Alhovik presented new techniques for rapid identification of On Wellcome Reception after first day of the Conference some participants who made biggest contribution in this event were awarded with Diplomas and Prizes, We do not know the real incidence and prevalence of UGTB as it includes KTB, MGTB, and female genital TB. All these forms of TB have their own clinical features and require their own approaches to the diagnosis and management. Before anti-TB drugs were created, the prevalence of UGTB was huge. Every fifth urological in-patient had UGTB, more than third of all pyonephrosis were due to TB . NowadayThis first conference brought together urologists and TB specialists not only from the Siberian region, but also from the whole of Russia and other countries as well. The outstanding quality of the presentations and the lively discussions during the congress underlined the high degree of relevance of this event. Participants were able not only to gain useful information, but also to find new partners for further joint research.There are many un-solved problems in TB urology. Unique terminology, classification, and approach to diagnosis, therapy and surgery for patients UGTB are needed. Heated discussions, hot debates and arguments between participants at this Conference resulted in agreement on key points.M. tuberculosis can be found in the ejaculate of half of the TB patients [The take home messages emphasized the need for more awareness regarding UGTB in many regions of the world, considering that UGTB is a sexually transmitted disease, as patients . A betteAfter Conference memory picture of the faculty was made in the hall of the Congress Center ."} +{"text": "Juvenile scleroderma (JS), represents a rarely seen group of connective tissue disease with multiple organ involvement. Although quite rare in childhood, cardio-vascular and pulmonary involvements are the most important mortality and morbidity factors. Pulmonary arterial hypertension (PAH), the most important sequelae of pulmonary involvement, could be determined by echocardiographic examinations. Early cardio-vascular and pulmonary involvement determination is extremely important in reducing mortality of patients.The aim of the study was to use non-invasive methods to examine cardio-pulmonary involvement of the disease in patients. Treatment of patients with positive findings in the early stage of the disease possibly reduces the morbidity and mortality.Totally of 35 patients with scleroderma, followed up at Cerrahpasa Medical Faculty, Pediatric Rheumatology Department with diagnosis of juvenile scleroderma were included in the study. Doppler echocardiography was performed at Cerrahpasa Medical Faculty, Pediatric Cardiology Department and pulmonary function tests were performed at Laboratory for pulmonary function tests at Cerrahpasa Medical Faculty. FVC and DLCO were measured in order to investigate pulmonary fibrosis. The assessment of PAP and risk factors for PAH was made by measurement of maximum tricuspid insufficiency (TI), end diastolic pulmonary insufficiency (PI), AT/ET, RAP and contraction of vena cava inferior during inspiration.The values of TI, PI, AT/ET and PAP were found to be normal and statistically sign\u0131ficant different from the pathological values. The results of FVC and DLCO were found to be statistically significant above normal values. In other words, no patient was found to have cardio-pulmonary involvement.Although quite rare in juvenile scleroderma, cardio-vascular and pulmonary involvement is the most important factor in the prognosis of the disease. Early diagnosis, regular follow up and appropriate treatment are important in reducing the cardio-vascular and pulmonary complications of the disease.None declared."} +{"text": "The authors would like to supply additional information in relation to the study.The characteristics of the sample population included in the study are outlined in the table supplied. The methods pertaining to this are as follows:Informed consent and inclusion into study: Each subject who qualified for the study was explained the purpose and procedures of the research and written informed consent obtained. Questionnaires were used to assess demographics, oral hygiene and diet. Oral hygiene habits were assessed by frequency of brushing, flossing, smoking history and visits to the dentist, while food habits were assessed by routine exposures to one of the four diet patterns: (i) Standard American , pasta and similar dishes, and desserts). (ii) Hispanic and Latino , avocado, olives, fruits, sweet breads, red meats), (iii) Asian or (iv) not fitting into any of the above categories.The legend for Table S1Ethnicity Table(JPG)Click here for additional data file."} +{"text": "Selection of appropriate outcome measures is crucial in clinical trials in order to minimize bias and allow for precise comparisons of effects between interventions -3.We aimed to assess the frequency and completeness of outcome measures in randomized controlled trials (RCTs) included in Cochrane systematic reviews (SRs), focusing on evaluations of the efficacy and safety of rehabilitation interventions for mechanical LBP.We performed a cross-sectional study of all RCTs included in all Cochrane SRs (full-text) published on The Cochrane Database of Systematic Reviews in February 2013. Two authors independently evaluated the type and frequency of each outcome measure reported in the full-text of RCTs, the methods used to measure outcomes, and the proportion of outcomes fully replicable based on the reported information 84.7% \u2013 93.7 %), disability , range of motion , and quality of life measured respectively by 70, 43, 41, 19 different measurement instruments (Figure A large number of outcome measures and a myriad of measurement instruments were used across all RCTs. The reporting was largely incomplete, suggesting better opportunities for the standardization of approaches and reporting."} +{"text": "The NMC portal allows users to access the experimental data used in the reconstruction process, download cellular and synaptic models, and analyze the predicted properties of the microcircuit: six layers, ~31,000 neurons, 55 morphological types, 11 electrical types, 207 morpho-electrical types, 1941 unique synaptic connection types between neurons of specific morphological types, predicted properties for the anatomy and physiology of ~40 million intrinsic synapses. It also provides data supporting comparison of the anatomy and physiology of the reconstructed microcircuit against results in the literature. The portal aims to catalyze consensus on the cellular and synaptic organization of neocortical microcircuitry . Community feedback will contribute to refined versions of the reconstruction to be released periodically. We consider that the reconstructions and the simulations they enable represent a major step in the development of in silico neuroscience.We have established a multi-constraint, data-driven process to digitally reconstruct, and simulate prototypical neocortical microcircuitry, using sparse experimental data. We applied this process to reconstruct the microcircuitry of the somatosensory cortex in juvenile rat at the cellular and synaptic levels. The resulting reconstruction is broadly consistent with current knowledge about the neocortical microcircuit and provides an array of predictions on its structure and function. To engage the community in exploring, challenging, and refining the reconstruction, we have developed a collaborative, internet-accessible facility\u2014the Neocortical Microcircuit Collaboration portal 13\u201316] somatosensory cortex from sparse data on its cellular and synaptic organization , 11 electrical types (e-types), and 207 morpho-electrical types (me-types); ~7.5 million connections belonging to 1941 unique m-type specific connection types; and ~40 million synapses belonging to six synapse types (s-types) . The synaptic level represents the anatomical and physiological properties of synaptic connections between specific pre-post combinations of m-types, and the complete map of intrinsic input and output synapses , from and to neurons of different types.An interactive browser across three levels: Comparisons between the morphological, molecular, electrical, synaptic, and physiology properties of the reconstruction and its overall circuit anatomy against the published literature.Experimental datasets used in the reconstruction process.Animations of simulated microcircuit activity under a variety of experimental conditions.Images illustrating key steps in the reconstruction process.Tools for analyzing, and simulating the reconstructed microcircuit.Models of neurons, ion channels, and synapses for the NEURON simulation environment.The microcircuit section of the portal contains data computed during the reconstruction process, using methods described in , electrical types (e-types), morpho-electrical types (me-types), and synapse types (s-types), numbers of intrinsic, and extrinsic synaptic connections and associated synapses, and the number of unique synaptic connection types between neurons of specific source and target m-types in a layer are given for each layer is given , calbindin (CB), and calretinin (CR)], and neuropeptides they express is given back-propagating from the axon , neurotransmitter release probability (U), time constant for recovery from depression , time constant for recovery from facilitation , and the predicted correction factor necessary to account for dendritic filtering (space-clamp artifacts). Physiological data at the connection level summarizes the kinetics and time course of post-synaptic potentials (PSPs). The data provided include onset latencies, peak amplitudes, 20\u201380% rise times, decay time constants, transmission failures, and the coefficient of variation of PSP amplitudes , a web link to the publication, the name of the contact author, and the names of the persons who undertook the literature search are also provided.The literature consistency contains papers considered in the validation process. For each paper we identified one possible evaluation criterion. Each paper is annotated to show the evaluation criterion, and the result of the validation . Where a paper was not actually used, it is marked as not implemented, or not applicable. Additional annotations describe the species and age of the animals used in the study, the brain region, cortical layer, and cell type concerned, the key finding, and other relevant results. The The evaluation criteria are based on the morphological, molecular, electrical, synaptic, circuit anatomical, and physiological properties of the reconstructed microcircuit. For ease of presentation, papers are grouped according to the class of properties considered in their evaluation criteria.This sub-section presents 64 papers used for the validation of experimentally reconstructed neuron morphologies. The papers provide data for Sholl statistics, dendritic and axonal lengths, dendritic and axonal volumes, soma diameters, and dendritic and axonal segment branch order and path distance statistics. Overall, the properties of the morphologies used in the reconstruction were consistent with the results reported in 17 papers, possibly consistent with 10 papers and inconsistent with nine papers. Six papers whose data were not comparable with the reconstruction were excluded from the validation process.in silico staining. This sub-section presents six papers providing the necessary data. The papers present data on the expression of the main calcium binding proteins and neuropeptides expressed by neurons of different types.During the validation process, gene expression data associated with specific neuron types was used to perform This sub-section presents 77 papers describing the electrical properties of different cortical neuron types. Data are provided for ion channel kinetics, electrical firing patterns, and passive membrane properties, including the resting membrane potential, membrane time constant, and input resistance. Other data describe electrophysiological features including AP amplitude, AP half-width, firing frequency, inter-spike interval, and dendritic properties including bAP and EPSP/IPSP attenuation.A, and GABAB receptor peak conductances, EPSC/IPSC properties , EPSP/IPSP properties , transmission failure rates, c.v. of EPSP/IPSP amplitudes, short term depression and facilitation, and tonic excitation and inhibition.This sub-section contains 81 publications used to validate the anatomical and physiological properties of synaptic connection types in the reconstruction. The data provided includes spine and bouton densities for different neuron types, as well as data for pairs of neurons belonging to specific m-types: synaptic innervation patterns, number of synaptic contacts per connection, connection probabilities, transmitter release probabilities, AMPA, NMDA, kainate, metabotropic glutamate, GABAThis sub-section presents 43 papers used to validate the anatomical properties of the reconstructed microcircuit. The properties considered include microcircuit thickness, individual layer thicknesses, layer-wise distributions and densities of neurons, total axon and dendritic lengths, total number of synapses and their densities, and layer-wise distributions of bouton densities from thalamocortical axons.This sub-section contains 47 papers used to assess the physiological properties of the reconstructed microcircuit. Relevant properties include the frequency of network oscillations, patterns of propagation of electrical activity across different cortical layers, the physiological properties of thalamocortical synapses, and the balance of excitatory and inhibitory synaptic conductances in different neuron types due to network activity.Over the past two decades, Markram and colleagues have experimentally characterized the cellular, and synaptic microcircuitry of developing (P13-16) rat neocortex, where the anatomical, physiological and synaptic properties are not completely mature stained coronal slices with annotations of individual layer extents, and spreadsheets summarizing measurements of layer heights.Measurements of individual layer heights.Data are given as microscopy images of NeuN stained slices with annotations of individual layer extents, and spreadsheets summarizing measurements of neuron counts across different layers.Layer-wise distributions and densities of neurons.Data can be obtained as text files containing the expression patterns of calcium binding proteins, and neuropeptides for morphologically identified neurons.Molecular characterization of single neurons based on the expression of calcium binding proteins , and neuropeptides .Data are provided as text files containing 3D representations of neuronal morphologies reconstructed using Neurolucida .More than 1000 morphological reconstructions of neurons of different m-types.Data are given for current stimuli (in pA), and voltage responses (in mV) from whole-cell patch clamp recordings in single neurons acquired using IGOR Pro .More than 1500 electrical recordings from neurons of different e-types.Data are provided for post-synaptic responses obtained from whole-cell patch clamp recordings in synaptically connected pairs of neurons.More than 5000 experiments from synaptically connected neurons.2+. Movies of evoked activity show electrical activity in response to the stimulation of thalamocortical fibers at different levels of extracellular Ca2+. Additional movies visualize the distribution of afferent synapses for a single exemplar neuron for each of the 55 different m-types, and predicted dendritic attenuation of EPSPs and bAPs for 5 exemplars for each of the 207 me-types.The videos section provides movies of simulated spontaneous and evoked activity in virtual cortical slices, obtained from the reconstructed microcircuit under a variety of simulated experimental conditions. Movies of spontaneous activity show electrical activity in the reconstructed microcircuit at different levels of depolarization and extracellular CaNeuroM provides a range of morphometric analyses that allow a user to quantify properties of the axonal and dendritic morphologies of neurons, and provides features that are used in the classification of different neurons into one of 55 m-types. NeuroR utilizes the results of NeuroM to identify and repair arbors that were severed during slice preparation. NeuroC produces clones of the neurons repaired by NeuroR, introducing statistical variations in the arbors of each cloned neuron. This procedure makes it possible to generate a limitless number of unique instances of neurons belonging to a given m-type.The tools section contains three tools used for the analysis, repair and cloning of neuronal morphologies. downloads section provides models of single neurons, synapses, and predicted maps of input-output synapses. Models are available either in the native format used in the reconstruction process, based on the NEURON simulation environment, or in the emerging NeuroML 2.0 , and LEMS . Models of individual neurons (in the NEURON simulation environment) can also be obtained from the me-type fact sheets [see Morpho-Electrical Types (me-types)]. Model packages for individual neurons contain a 3D reconstructed morphological model, models of ion channels and synapses, synaptic model parameter descriptions, and a template model of the electrical type. Additional helper scripts for the NEURON simulation environment are provided to instantiate a morphoelectrical neuron model, distribute ion channel mechanisms on axonal and dendritic arbors, and simulate electrophysiological and synaptic experiments.The in vitro. The shortfall can be overcome by in silico synthesis of axons, utilizing data from in vivo filled neurons and to enable community-driven refinement of the reconstruction. Newer versions of the reconstruction will be released periodically, consisting of data structures consistent with the current version. We consider that these reconstructions and the simulations they enable represent a major step in the development of in silico neuroscience.The NMC Portal is part of a broad trend toward the development of large repositories of anatomical and physiological data. Other examples include The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Idiopathic scoliosis induces change in coordination between body segments, spinal anatomy, left-right trunk symmetry and gait pattern. Various treatment methods have being used for scoliosis which includes: physical therapy, occupational therapy, osteopathic therapy, casting, bracing and surgery. However, using brace is a commonly used method in this regard. Although, the influence of brace to reduce the scoliosis curve has been investigated in lots of research studies, there is not enough research regarding the influence of brace on performance of scoliotic subjects while walking and standing. Therefore, the purpose of this study was to evaluate the immediate effect of brace on stability performance of scoliotic subjects and the symmetry of the ground reaction force applied on the right and left feet while walking.Then girls aged between 8 and 12 years were recruited in this study. The gait analysis was assessed using a three-dimensional motion analysis and a force plate (Kistler) in two conditions, with and without Boston brace. Moreover their stability was evaluated by use of force plate. The difference of kinetic and stability parameters between two conditions(with and without Boston brace)was checked by use of paired T-test.For scoliotic patients, comparison of in-brace and out-brace situations revealed a significant decrease in postural sway in brace associated with increase of patient stability. But very short-term bracing in AIS has no significant effect on the symmetry of force applied on right and left limbs during walking .Bracing aligned the vertebral column and improved the abilities of the subject to stand and walk."} +{"text": "A 36-year-old woman, with no remarkable medical or family history, was admitted to thehospital in cardiogenic shock. Transthoracic echocardiography (TTE) revealed severebiventricular dilation and dysfunction. Several mobile masses consistent with thrombi wereattached to the apex and protruding into the left ventricle (LV) beyond the mid-ventricularlevel (Any condition with severe LV systolic dysfunction increases the probability ofintraventricular thrombus formation. Incidence of systemic embolization is low;nevertheless, it increases in cases of large, protuberant and highly mobile thrombi.Therapeutic approach in this scenario is controversial. It is generally agreed thatanticoagulation should be the initial therapy in most of cases, but there are no specificrecommendations regarding thrombolysis or thrombectomy.TTE is the gold standard technique for diagnosis and stratification of embolic risk, sinceit allows accurate assessment of morphology, mobility and point of attachment of theclot.Conception and design of the research and Analysis and interpretation of the data: LorenzoN; Acquisition of data: Lorenzo N, Restrepo JA, Aguilera MC; Writing of the manuscript:Lorenzo N, Rodriguez D; Critical revision of the manuscript for intellectual content:Lorenzo N, Aguilar R."} +{"text": "C, the founder of the prion protein family, there has been a constant quest to dissect its biological function and that of its two homologs, Doppel and Shadoo. While clues were greatly anticipated from the generation of PrP null mice, alterations appeared quite imperceptible at first examination, beyond the clear-cut resistance to prion infection. Taking a closer look at these knockout mice, together with the generation of mice invalidated for Doppel and Shadoo has in the end yielded much information on the -sometimes overlapping- roles of these proteins. These in-depth investigations have also explored functions of the prion protein family beyond the central nervous system, which was obviously the first focus of interest since prion diseases are neurodegenerative disorders. This Frontiers Research topic on the promiscuous functions of the prion protein family incorporates contributions ranging from the field of developmental biology to that of structure-function, including aspects related to cell biology, signal transduction, and neuronal homeostasis.From the discovery nearly 30 years ago of the cellular prion protein PrPC deletion (Halliez et al., C expression after the brain, i.e., the placenta (Makzhami et al., C expression in human gestational diseases. The review by Allais-Bonnet and Pailhoux is dedicated to the gonads, a unique tissue where PrPC, Shadoo and Doppel are all expressed, raising the question of a potential redundancy between the three proteins, as well as their roles in reproductive functions (Allais-Bonnet and Pailhoux, C and the pathways involved in epithelial to mesenchymal transition, a process associated with major changes in cell adhesion properties and that physiologically takes place during embryonic development, while also involved in cancer metastasis (Mehrabian et al., C to stem cell biology and its recent association with tumor-initiating cells (Martin-Lanneree et al., C, with special emphasis on the protective role exerted by this protein (Sakudo and Onodera, Starting from the embryo, the contribution by Halliez et al. provides a comprehensive review of the impact of PrP invalidation on embryonic development, compiling data from both mice and zebrafish and highlighting the key cellular pathways affected by PrPC and cell signaling. The mini-review by Roucou elaborates on the connection between PrPC dimerization, proteolytic processing and the recruitment of cell signaling cascades (Roucou, C-related signaling and src family kinases, in contexts ranging from embryonic cell adhesion to regulation of NMDA activity (Ochs and Malaga-Trillo, C against NMDA-dependent excitotoxicity is the focus of the review by Black et al, which also discusses the pathophysiological implications of this regulation as to ischemic injury, neuroinflammation, and Alzheimer's disease (Black et al., C as a cell-surface receptor for Abeta oligomers, and follow-up investigations on the contribution of PrPC to Abeta toxicity, which is summarized in the review by Watt et al. (C to zinc homeostasis, and discusses how age-regulated deregulation of the interplay between PrPC, lipid rafts and zinc may contribute to Alzheimer's disease. The fate of PrPC during aging is further discussed in the review by Gasperini and Legname, which notably highlights the changes in the biochemical properties and lipid raft association of PrPC in aged animals (Gasperini and Legname, Several contributions go down to the molecular scale and focus on the relationship between PrP Roucou, . Ochs ant et al. . This reC, Doppel and Shadoo, as well as their specificities, in relation with their propensity to misfold (Rezaei, Further zooming on the molecule itself, the review by Rezaei provides a global view of the biochemical and structural similarities between PrP Rezaei, .Collectively, these works underscore the advance in our understanding of the functions exerted by the prion protein family and underlines their versatile roles according to the cellular context and interacting partners involved. Finally, they provide some future directions for further dissecting how the deregulation of these proteins functions can cause or contribute to pathological conditions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Building on momentum in five NIH-supported meetings, \"Advancing the Science of Dissemination and Implementation,\" the NIH convened three separate meetings during 2013-4, each addressing an overarching issue: \"Developing a field-based approach to D&I research training\"; \"Measurement & Standardized Reporting\"; and \"Fit between Investigation and Research design?\"Meeting themes were selected by the NIH D&I Workgroup, addressing pressing needs in the field and high-demand topics from prior meetings. Targeted groups of participants were invited to the meetings, each led by a team of researchers and NIH staff.The training meeting yielded a map of current training, a field wide training vision, and a set of tensions--notably training for a rapidly evolving field. The research design workgroup produced a common terminology that crosses diverse fields of medicine and public health as well as disciplines, and categorized 27 different designs that have been used for dissemination and implementation research. The reporting workgroup identified four broad areas, planning, delivery, evaluation, and long-term outcomes as well as cross-cutting issues to provide reporting consistency. The meetings further generated a set of issues that cross-cut the three topics, including how to reflect the evolution of measurement, design and reporting within training programs and how to train reviewers, editors, decision-makers, and practitioners?The three issue-focused meetings provided opportunity to take stock of the field ten years after the initial NIH D&I meeting and generated papers that both synthesize the stimulate important advances for the field.Reporting guidelines improve the overall depth and quality of manuscripts across specialties and journals. No reporting guidelines for Dissemination and Implementation (D&I) research yet exist. We sought to develop a framework from which D&I reporting guidelines can be derived and to identify ideal metrics.The National Institutes of Health held a series of invited state-of-the-science meetings to address key gaps and opportunities in D&I research in 2013. One of these focused on reporting and evaluation/measurement. This workgroup's objective was to identify key areas in need of better measurement and reporting at all stages of D&I research.The workgroup concluded that the existing plethora of reporting guidelines mandated additional exploration before deriving D&I-specific reporting guidelines, and decided that a D&I framework divided into the planning, delivery, evaluation, and long-term outcome phases of research was an essential first-step.The overriding objective of the D&I framework was to improve population health, health equity, social well-being, and health system efficiency. The workgroup identified the following stages to be essential: Planning: D&I intervention's evidence-basis and mechanism of change, setting characteristics like organizational capacity for change and resources, evaluability and scalability of the implementation strategy, key partnerships, and study design. Delivery: reach; adoption; implementation fidelity, dose, adaptation, and costs. Evaluation: primary outcome effectiveness including measured unintended consequences; explicit description of settings and intervention adaptation, including PRECIS criteria for pragmatism, and robustness of implementation effort. Long-term Outcomes: sustainability, evolvability, transportability; conditions under which the findings hold; and an economic evaluation. In addition, participants identified multiple cross-cutting elements extending across all stages, including: multilevel context; multiple stakeholder perspectives; and societal costs. The next step is to contrast existing reporting guidelines with this new D&I framework to highlight overlap or deficiencies relative to complete and consistent D&I research reporting, and to identify appropriate measurement instruments.The fields of medicine and public health have made great progress in determining whether an intervention is efficacious or effective by conducting carefully crafted randomized clinical trials. In contrast to these designs to evaluate an intervention's efficacy or effectiveness, the designs for dissemination and implementation (D&I) research are not yet well established, a factor that has no doubt has impeded developing our knowledge of effective D&I. By its very nature D&I research is intimately connected to understanding how programs, practices, or policies work in different contexts, so there is more attention in D&I research on external validity, as contrasted to the heavy emphasis on internal validity that many of the randomized efficacy and some effectiveness trials address.This presentation is a product of a workgroup meeting of 10 scientists and NIH staff, convened by NIH to facilitate D&I research. This committee addressed differences in terminology and provided a summary of the designs that have been used in D&I research, including both randomized and non-randomized studies. We identified 27 designs and found it useful to categorize these designs into several broad categories. One category of designs involves what can be termed the \"traditional translational pipeline\" of interventions that move step by step from efficacy, to effectiveness, to implementation research. A second major class of designs involves \"hybrid designs,\" which combine elements of effectiveness and implementation research in one single design. Thirdly, we describe designs that are focused on quality improvement as the primary goal, in contrast to producing generalizable knowledge.Several of these latter designs borrow from diverse areas of engineering.We provide illustrations of these alternative designs and discuss cross-cutting issues, including community engagement and ethics in conducting implementation research.Demand for training in the science of dissemination and implementation is high, reflected in oversubscribed registrations for the NIH meetings on Advancing the Science of D&I and applications to existing training programs. D&I training is provided in a small number of national programs, but given local university courses and degree programs and the growth of on-line webinars, a field-wide perspective on training is needed.NIH convened a meeting of representative U.S. and Canadian trainers and trainees to in September 2013 to assess the field, identify cross-cutting themes, and develop a field-based training vision.The training meeting yielded a map of current training, including NIH funded summer training institutes, a handful of Master's and PhD programs, individual graduate courses, CTSA Cores, and on line webinars. Program aims, participants and funding sources vary, as do training deliverables . Training gaps were identified, including programs at the doctoral level and those designed for decision-makers, and practitioners. Several serious challenges were identified, including: shaping and continually evolving training for a rapidly advancing field, establishing boundaries with related fields, targeting appropriate levels of training specificity versus generality, and sustaining high-intensity training. The meeting also generated issues that cross-cut with the measures/reporting and research design meetings. Participants underscored the importance of a regular national meeting to provide an intellectual home for those trained in D&I. Meeting products will include papers for publication reporting a field-based training vision.The meeting yielded a map of current training in dissemination and implementation research as well as gaps and needs to be met through new training initiatives and a repository of training resources."} +{"text": "The aim of this study was to analyze current scientific impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014).Affiliation search of the Scopus database was performed on November 23, 2014 in order to identify published papers from the Ss Cyril and Methodius University of Skopje (UC&M), Republic of Macedonia. A total number of 3960 articles were selected for analysis (1960-2014). SCImago Journal Rank (SJR), Source Normalized Impact per Paper (SNIP) and h-index were calculated from the Scopus database.The number of published papers was sharply increased with maximum of 379 papers in 2012 year. The largest number of papers has been published in Macedonian Journal of Medical Sciences, Journal of Molecular Structure, Lecture Notes in Computer Science, Acta Pharmecutica, and Macedonian Journal of Chemistry and Chemical Engineering. The biggest SJR and SNIP has journal Nephrology Dialysis Transplantation. First three places of the top ten authors belong to Dimirovski GM, Gavrilovska L, and Gusev M. Top three places based on Scopus h-index belong to Kocarev L, Stafilov T, and Polenakovic M. The majority of papers originate from UC&M, but significant numbers of papers are affiliated to Faculty of Medicine, Faculty of Pharmacy, and Institute of Chemistry as members of UC&M, as well as Macedonian Academy of Sciences and Arts. Articles are the most dominant type of documents followed by conference papers, and review articles. Medicine is the most represented subject.Officials of the Ss Cyril and Methodius University of Skopje should undertake more effective and proactive policies for journal publishers and their Editorial Boards in order to include more journals from UC&M in the Scopus database. Scopus is the world\u2019s largest abstract and citation database of peer-reviewed literature with smart tools that track, analyze and visualize research. Easy to use and comprehensive, Scopus is designed to quickly find the information researchers\u2019 need. Scopus indexes over 20,500 titles from 5,000 publishers worldwide; contains 49 million records, 78% with abstracts; includes over 5.3 million conference papers; and provides 100% Medline coverage and one in Trnava, Slovakia [AF-ID (\u201cUniversity of SS Cyril and Methodius Trnava\u201d 60021677)] which was excluded from analysis.A total number of 3960 articles, all from Ss Cyril and Methodius University , were selected for analysis (1960-2014). SCImago Journal Rank (SJR), Source Normalized Impact per Paper (SNIP) and h-index were calculated from the Scopus database [The number of publication in the period of 1960-1991 year was very small (1-29 papers per year). Starting of 1991 year, the number of published papers was sharply increased with maximum of 379 papers in 2012 year .The largest number of papers from Ss Cyril and Methodius University of Skopje have been published in Macedonian Journal of Medical Sciences (136 papers), followed by Journal of Molecular Structure (79 papers), Lecture Notes in Computer Science (46 papers), Acta Pharmecutica (38), and Macedonian Journal of Chemistry and Chemical Engineering (37 papers). The rest of journals published less than 36 papers top. TheThe number of papers published by top ten authors is shown in Scopus Hirsh index (h-index) for the top ten authors affiliated to Ss Cyril and Methodius University of Skopje was presented as calculated by Scopus. We can see from the The biggest number of papers belongs to Ss Cyril and Methodius University (3051 papers), but significant number of papers belongs to Faculty of Medicine, Ss Cyril and Methodius University (860 papers), Faculty of Pharmacy, Ss Cyril and Methodius University (145 papers), Institute of Chemistry, Cyril and Methodius University (138 papers), as well as Macedonian Academy of Sciences and Arts (105 papers) left. MoDocuments by type and documents by subject area are published by Ss Cyril and Methodius University of Skopje, shown in In this paper analysis of documents affiliated to Ss Cyril and Methodius University of Skopje deposited in the Scopus database (1960-2014) is presented. Starting of 1991 year, the number of published papers was sharply increased with maximum of 379 papers in 2012 year. The largest number of papers from Ss Cyril and Methodius University of Skopje has been published in Macedonian Journal of Medical Sciences, Journal of Molecular Structure, Lecture Notes in Computer Science, Acta Pharmecutica, and Macedonian Journal of Chemistry and Chemical Engineering. The biggest SCImago journal rank per year (SJR) and Source Normalized Impact per Paper (SNIP) has journal Nephrology Dialysis Transplantation. First three places of the top ten authors belongs to Dimirovski GM, Gavrilovska L, and Gusev M. Top three places based on Scopus h-index belongs to Kocarev L, Stafilov T, and Polenakovic M.The majority of papers originate from Ss Cyril and Methodius University of Skopje , but significant number of papers are affiliated to Faculty of Medicine, Faculty of Pharmacy, and Institute of Chemistry as a members of Ss Cyril and Methodius University of Skopje, as well as Macedonian Academy of Sciences and Arts. Most of the papers affiliated to Ss Cyril and Methodius University of Skopje originate from Macedonia, Yugoslavia, United States, and Germany. Articles are the most dominant type of documents followed by conference papers, and review articles. Medicine is the most represented subject. Engineering, computer science, chemistry, biochemistry, genetics and molecular biology, physics and astronomy are represented in more than 10%.From the top 10 journals participating in the Ss Cyril and Methodius University of Skopje publishing, only two of them are published in Republic of Macedonia . The biggest SCImago journal rank per year and the biggest Source Normalized Impact per Paper have the journal Nephrology Dialysis Transplantation, published outside the Republic of Macedonia. Thus, the impact of journals from the Ss Cyril and Methodius University of Skopje participating in Scopus database is very small. Other journals supported, attached or affiliated to mention UC&M as a publisher are not participating at all in the Scopus database. Officials of the UC&M should undertake more effective and proactive policies for journal publishers and their Editorial Boards in order to include more journals from UC&M in the Scopus database.http://www.researcherid.com/) [http://orcid.org/) [Analysis of author rank is very sensitive issue. In this analysis total number of published papers in Scopus database was bigger than the number of papers affiliated to Ss Cyril and Methodius University of Skopje in the same database. These differences are caused by affiliation changes of the top ten authors. For example, Dimirovski GM was affiliated with 121 papers to Ss Cyril and Methodius University of Skopje, and the rest of 139 papers are affiliated to Dogus Universitesi Istanbul, School of Engineering, Istanbul, Turkey. Similarly, Soptrajanov B, Polenakovic M, and Kocarev L have additional profiles as a result of their affiliation to Macedonian Academy of Sciences and Arts. Additional problems arise when author impact analysis search is used: i) some authors have used different names in different periods of time; ii) some authors transliterate their names in several different ways; iii) some authors add or do not add \u201cv\u201d; iv) some authors use only one of their two surnames; v) there are some identical names and surnames in the world for different researchers . All of id.com/) and in tid.org/) . IdentifFor the first time in Republic of Macedonia, current scientific impact of academic staff employed at the Institutes of the Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Republic of Macedonia, was analyzed and published. Based on different citation values and citation indexes, it was concluded that Institutes of the Faculty of Medicine are very heterogeneous with three groups of institutes: institutes with higher scientific impact; institutes with intermediate scientific impact, and institutes with low scientific impact . ScientiRecently we presented the results of SCImago Institutions Rankings for R. Macedonia (2009-2012) and show that only Ss Cyril and Methodius University of Skopje were included in the SIR with world rank of 1726 to 1821. Regional rank in Eastern Europe was gradually increased from 156th in 2009 to 127th in 2013 year [In summary, analysis of documents affiliated to Ss Cyril and Methodius University of Skopje deposited in the Scopus database (1960-2014) have shown that the number of published papers was sharply increased with maximum of 379 papers in 2012 year. The largest number of papers from Ss Cyril and Methodius University of Skopje has been published in Macedonian Journal of Medical Sciences. The biggest SCImago journal rank per year and Source Normalized Impact per Paper has journal Nephrology Dialysis Transplantation. First three places of the top ten authors belong to Dimirovski GM, Gavrilovska L, and Gusev M. Top three places based on Scopus h-index belong to Kocarev L, Stafilov T, and Polenakovic M. Officials of the UC&M should undertake more effective and proactive policies for journal publishers and their Editorial Boards in order to include more journals from UC&M in the Scopus database."} +{"text": "Development of normal hematopoietic cells is an ordered multi-step process, tightly regulated by a complex network of intrinsic factors and microenvironmental cues that control cell fate decisions within the bone marrow (BM) has been the most popular systems biology tool for the study of normal and leukemic hematopoiesis. This type of modeling is useful for the time evolving non-linear competition between normal and leukemic cell populations, considering multiple compartments to simulate different maturation stages or multiclonal behavior acting collectively within a dynamical complex context . By tracking HSC replication, the expansion of the hematopoietic system was apparent from birth to adolescence, when steady-state levels are reached. Stochastic modeling of replication kinetics has shown to be useful to predict cell rebounding upon hematopoietic transplantation or under emerging conditions proteins, and other molecules produced and expressed by niche cellular elements, may dictate the final fate decision , multi-compartment (differentiation stages), and agent-based modeling of leukemia pathobiology is a promising tool for the study of feedback pathways in the searching of auxiliary strategies for leukemia treatment, normal hematopoiesis rebounding, and relapse delay. The construction of novel \u201csystems within a system\u201d integrative theoretical models (Figure To this extent, the use of \u201cedge-technology\u201d s Figure that betJE: Analysis of published data, discussion of the topic-related information, drafting, and writing the paper. LM and RP: Conception and design of the Opinion Article, analysis of published data, discussion of the related information, drafting, and writing the paper. Critical review of the intellectual content.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Following the publication of our article , we notiAG performed the majority of experiments, analyzed the data, and drafted the manuscript. VH provided MDA231 and MDASrc ezrin KD and EZR/WT-expressing cell lines and contributed to the design of experiments. AS performed the TMA staining for Src/Ezrin, image analysis, clinical outcome correlations, and VEGF-A/-C western blots. DL supervised AS in establishing and optimizing the quantification of Src/ezrin in histopathological tissue samples by multi-channel immunofluorescence. MH assisted with the aortic rings experiment and analysis. NL assisted in quantification of angio/lymphangiogenic activity in tumour xenograft H&E sections. KN assisted in design and interpretation of aortic ring assay and analysis. YM collected the clinical outcome data for the in-house human breast cancer cohort and assisted in analysis and interpretation of clinical correlative studies. SS assessed the tumours in our breast cancer cohort and oversaw the construction, staining, and analysis of all TMA-related experiments. BEE conceived the project, supervised experiments & analysis, and contributed to writing of the final manuscript.All authors have made substantial contribution to the design of experiments, data analysis, and drafting of the manuscript. All authors have reviewed and approved the final version of this manuscript and agree to be accountable for all aspects of the work presented herein."} +{"text": "Introduction: The burden of cervical cancer is large and growing in developing countries, due in large part to limited access to screening services and lack of human papillomavirus (HPV) vaccination. In spite of modern advances in diagnostic and therapeutic modalities, outcomes from cervical cancer have not markedly improved in recent years. Novel clinical trials are urgently needed to improve outcomes from cervical cancer worldwide.Methods: The Cervix Cancer Research Network (CCRN), a subsidiary of the Gynecologic Cancer InterGroup, is a multi-national, multi-institutional consortium of physicians and scientists focused on improving cervical cancer outcomes worldwide by making cancer clinical trials available in low-, middle-, and high-income countries. Standard operating procedures for participation in CCRN include a pre-qualifying questionnaire to evaluate clinical activities and research infrastructure, followed by a site visit. Once a site is approved, they may choose to participate in one of four currently accruing clinical trials.Results: To date, 13 different CCRN site visits have been performed. Of these 13 sites visited, 10 have been approved as CCRN sites including Tata Memorial Hospital, India; Bangalore, India; Trivandrum, India; Ramathibodi, Thailand; Siriaj, Thailand; Pramongkutklao, Thailand; Ho Chi Minh, Vietnam; Blokhin Russian Cancer Research Center; the Hertzen Moscow Cancer Research Institute; and the Russian Scientific Center of Roentgenoradiology. The four currently accruing clinical trials are TACO, OUTBACK, INTERLACE, and SHAPE.Discussion: The CCRN has successfully enrolled eight sites in developing countries to participate in four randomized clinical trials. The primary objectives are to provide novel therapeutics to regions with the greatest need and to improve the validity and generalizability of clinical trial results by enrolling a diverse sample of patients. Cervical cancer is the fourth most common cancer in women worldwide with almost 530,000 cases diagnosed in 2012 , a subsidiary of the Gynecologic Cancer InterGroup (GCIG), is a multi-national, multi-institutional consortium of physicians and scientists focused on improving cervical cancer outcomes worldwide by making cancer clinical trials available in low-, middle-, and high-income countries. In this manuscript, we describe the early activities of the CCRN, with a focus on describing a model of collaborative capacity-building, with the overall goal of promoting cervical cancer research and improving access to novel therapies.The CCRN is a subsidiary of the GCIG, a non-profit network of appointed representatives from international cooperative research groups for clinical trials in gynecologic cancers. The GCIG was established in 1990s with the goal of promoting and conducting high quality clinical trials to improve outcomes for women with cancers of the ovary, uterus, and cervix. The GCIG has been highly successful in completing clinical trials, publishing results, and developing consensus conferences.The CCRN developed to address the lack of cervical cancer clinical trials, increase enrollment on existing trials, and improve the standards of cancer care in low- and middle-income countries. In light of the limited improvement in survival in locally advanced cervical cancer in the decades since chemoradiation became the standard of care, the vision of the CCRN was to provide infrastructure and support for cancer clinical trials in developing nations that have a significant burden of cervical cancer.The CCRN reports to and is guided by the Executive Board of Directors of the GCIG. This Board has regularly scheduled teleconferences and semi-annual meetings. The chair and co-chair of the CCRN are elected for 3-year terms by voting members. The chair of the CCRN serves on the Executive Board of the GCIG and a formal report of activities and progress is made to the membership at the General Assembly at each semi-annual meeting.The mission of the CCRN was formulated by the committee chair and participating members. The literature was evaluated for best practices for clinical trials within gynecologic cancers, with emphasis on methods for low- and middle-income countries in which clinical trial resources are often limited. The CCRN then developed standard operating procedures (SOP) to evaluate potential participating sites to ensure appropriate infrastructure prior to clinical trial enrollment. The principal investigators of the CCRN trials normally select potential sites. The SOP workflow is demonstrated in Figure The SOP includes a pre-qualifying questionnaire to evaluate clinical activity, site resources, clinical trials infrastructure, radiation therapy treatment records, radiotherapy quality assurance, and clinical management documentation Table . AdditioFor potential study sites deemed eligible after the pre-qualifying survey, a site visit must be performed by an audit team to evaluate the appropriateness and readiness to participate in CCRN trials. Infrastructure, the physical plant, and human resources are evaluated to ensure that clinical trial participation can succeed. The audit team typically includes one clinical specialist and one clinical trials manager. Various measures of quality assurance are performed, depending on the requirements of the available clinical trial. To date, the CCRN has received limited funding from the International Gynecologic Cancer Society (IGCS) and the GCIG, as well as support from the NCI.To date, 13 different CCRN site visits have been performed. Of these 13 sites visited, 10 have been approved as CCRN sites including Tata Memorial Hospital, India; Bangalore, India; Trivandrum, India; Ramathibodi, Thailand; Siriaj, Thailand; Pramongkutklao, Thailand; Ho Chi Minh, Vietnam; Blokhin Russian Cancer Research Center; the Hertzen Moscow Cancer Research Institute; and the Russian Scientific Center of Roentgenoradiology. Approval with contingencies has been granted to sites in Cluj, Romania, and Minsk, Belarus.Through significant efforts within the Cervix Cancer Committee at the GCIG, four multi-national cervical cancer clinical trials suitable for both developed and developing nations have successfully been opened.The Tri-weekly Administration of Cisplatin in LOcally Advanced Cervical Cancer Trial , developed by investigators from the Korean Gynecologic Oncology Group (KGOG) and the Thai Cooperative Group, is a randomized phase III study that compares weekly chemotherapy for advanced cervix cancer to every-3-week chemotherapy. Preliminary data from a phase II trial by the KGOG suggest that every-3-week chemotherapy may confer a survival benefit .The OUTBACK Trial is led by investigators from the Australia/NewZealand Gynecologic Oncology Group (ANZGOG). This study is a randomized phase III trial evaluating the efficacy of extended adjuvant chemotherapy in women with advanced cervix cancer compared to the standard of weekly cisplatin chemotherapy and definitive radiotherapy. The OUTBACK chemotherapy consists of four cycles of carboplatin and paclitaxel chemotherapy administered after standard concurrent chemoradiotherapy. The rationale for the study is a meta-analysis of several studies that showed adjuvant chemotherapy to be a promising approach .The INTERLACE Trial is headed by the National Cancer Research Institute (NCRI) from the United Kingdom. This is a randomized phase III study evaluating neoadjuvant chemotherapy prior to concurrent chemoradiotherapy for women with advanced cervix cancer compared to concurrent chemoradiotherapy alone. The goal of this study is to improve compliance with additional chemotherapy by giving it before standard chemoradiotherapy, as opposed to after standard chemoradiotherapy.The SHAPE Trial is spearheaded by investigators from the NCIC Clinical Trials Group in Canada. This randomized phase III trial is evaluating radical hysterectomy versus simple hysterectomy in women with early-stage cervix cancer. The primary endpoint is freedom from pelvic failure.Each approved CCRN site chooses to participate in one or more of the four available clinical trials. To date, 48 patients have been enrolled.The greatest burden of cervical cancer is in developing countries, particularly parts of Africa, Central and South America, Eastern Europe, India, and other parts of Asia . The outThere are many challenges in conducting multi-national clinical trials, particularly in low-resource settings , 15. HumIn spite of these real and complex challenges, there are tremendous opportunities to enhance clinical trials results and improve cervical cancer outcomes through collaboration, creativity, and persistence. Rapid improvements in technology, particularly internet-based approaches, have made communication and quality assurance checks more feasible, timely, and cost-effective. Investments in research training and infrastructure development have the potential to influence not only cervical cancer clinical trial involvement but also standard care and care for other types of cancers. While sophisticated translational trials involving complex imaging and biomarker measurement will be confined to core GCIG settings, pragmatic trials that are aimed at defining worldwide standard of care, as well as trials directed at practices in low- and middle-income countries, are within the capability of the CCRN.In summary, the CCRN has developed a methodology to evaluate potential clinical trial enrollment sites in low- and middle-income countries to make cervical cancer clinical trials available in countries with the highest burden of disease. The CCRN has successfully enrolled 10 sites in developing countries to participate in four randomized clinical trials. The primary objectives are to provide novel therapeutics to regions with the greatest need and to improve the validity and generalizability of clinical trial results by enrolling a diverse sample of patients, with the ultimate goal of improving outcomes from cervical cancer worldwide.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Despite major advances in the treatment of hematological diseases over the last decades, allogeneic hematopoietic stem cell transplantation still remains the only curative option for many of them. According to the recent survey of the European Society of Blood and Marrow Transplantation (EBMT), nearly 15\u2009000 alloHSCT are currently performed each year across Europe and EBMT-affiliated countries (Approximately 50% of these patients will develop a major late complication \u2013 chronic graft-vs-host disease (cGVHD), a multi-organ allo- and auto-immune disorder affecting the skin, lungs, mouth, liver, eyes, joints, and gastrointestinal and genital tracts -4. As a Chronic GVHD can last for many years causing severe medical, social, and quality of life problems, as well as significantly impacting health-related costs and health care management. A recently published report from the Center for International Blood and Marrow Transplant Research has identified a clear increase in the incidence of cGVHD from 1995 to 2007 due to the more frequent use of peripheral blood graft instead of bone marrow, unrelated donors, and older recipients Consensus classification was developed in 2005 and prospectively validated ,6-10. HoThe German-Austrian-Swiss cGVHD consortium assessed the usefulness of the NIH criteria in routine clinical practice and reported high rates of acceptance for definitions of cGVHD, as well as overall and organ-specific NIH cGVHD severity scoring among the vast majority of participants . An inteTherefore, there has been significant research activity and renewed interest in cGVHD in the world over the last decade. It is likely that the current better characterization of cGVHD, standardization of research tools, and numerous new treatment opportunities will lead to improved clinical outcomes, such as clinical symptoms, function status, quality of life, morbidity, and survival.However, not a single agent has yet been approved for cGVHD prevention or treatment, neither by the US Food and Drug Administration (FDA) nor by the European Medicines Agency (EMA). The current standard front-line steroid therapy has a 50% failure rate with significant toxicity, and there are no standards for second-line (and beyond) therapeutic options.Croatian Medical Journal presents several excellent articles that are a product of these enhanced international collaborations and efforts by teams across Europe to address cGVHD.The focus now in this field is on further in-depth study of the biology of cGVHD, developing and validating new biomarkers, and pursuing clinical trials of new agents that would eventually develop pathways to their FDA and EMA regulatory approvals. The aim is to develop more effective, less toxic, and more targeted treatments that will not interfere with the beneficial graft-vs-tumor effects. To advance this field and break the 30-year-old suboptimal treatment paradigms, the goal is that each cGVHD patient should be either treated in a clinical trial or at least should be documented within a registry capturing essential clinical data on the course of cGVHD. The tools and opportunities to harness cGVHD and create better and safer alloHSCT are in our hands right now. This issue of the Acknowledgment This work is supported by the Unity Through Knowledge Fund project entitled \u201cClinical and Biological Factors Determining Severity and Activity of Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.\u201d The opinions expressed here are those of the authors and do not represent the official position of the National Institutes of Health or the US Government."} +{"text": "In 2014, the World Health Organization (WHO) declared two \"public health emergencies of international concern\", in response to the worldwide polio situation and the Ebola epidemic in West Africa respectively. Both emergencies can be seen as testing moments, challenging the current model of epidemic governance, where two worldviews co-exist: global health security and humanitarian biomedicine.The resurgence of polio and the spread of Ebola in 2014 have not only exposed the weaknesses of national health systems, but also the shortcomings of the current global health regime in dealing with transnational epidemic threats. These shortcomings are of three sorts. Firstly, the global health regime is fragmented and dominated by the domestic security priorities of industrialised nations. Secondly, the WHO has been constrained by constitutional country allegiances, crippling reforms and the limited impact of the (2005) International Health Regulations (IHR) framework. Thirdly, the securitization of infectious diseases and the militarization of humanitarian aid undermine the establishment of credible public health surveillance networks and the capacity to control epidemic threats.th World Health Assembly address these fundamental issues.The securitization of communicable diseases has so far led foreign aid policies to sideline health systems. It has also been the source of ongoing misperceptions over the aims of global health initiatives. With its strict allegiance to Member States, the WHO mandate is problematic, particularly when it comes to controlling epidemic diseases. In this context, humanitarian medical organizations are expected to palliate the absence of public health services in the most destitute areas, particularly in conflict zones. The militarization of humanitarian aid itself threatens this fragile and imperfect equilibrium. None of the reforms announced by the WHO in the wake of the 68The online version of this article (doi:10.1186/s13031-015-0058-1) contains supplementary material, which is available to authorized users. Margaret Chan, Director General of the World Health Organization (WHO), declared a public health emergency of international concern after consultation with an Emergency Committee of experts convened under the provisions of the revised (2005) International Health Regulations (IHR) . F. Fth rev the BWC , while i the BWC . The pro the BWC , 31.TablThe case of Syria is illustrative of the limitations imposed by UN mandates on the capacity of the WHO to ensure adequate public health responses in areas of civil conflicts . UN agenArmed conflict that flies in the face of international humanitarian law. Civil unrest. Migrant populations. Weak border controls. Poor routine immunization coverage. Bans on vaccination by militant groups. And the targeted killing of polio workers\u201d [The setbacks of the Global Polio Eradication Initiative in its final stage could have been anticipated precisely in those conflict zones where access and trust are paramount. However, new counter-terrorism and foreign policies of Western coalitions are enmeshing humanitarian action into international security agendas, which can discredit the neutrality of all humanitarian actors, for example when relief and health care are provided to secure the acceptance of counter-insurgency operations , 40. Theworkers\u201d . Ironicaworkers\u201d .A consensus has emerged to say that the disastrous situation in Guinea, Liberia and Sierra Leone reflects the disarray of national health systems and a vacuum in global health governance , 44. Witth World Health Assembly consist in: (i) integrating WHO outbreak and emergency response units, (ii) the creation of a global health-emergency workforce, (iii) setting up an emergency contingency fund, and (iv) advancing the research and development of medical products for infectious diseases of epidemic potential, and (v) strengthening health systems. One could muse over the fact that such measures are belated, obvious or simply represent an attempt to resurrect similar assets dismantled by a recent round of crippling reforms. More than with circumstantial resolutions, global health would be served by genuine reforms of the current regime, emphasizing universal health values instead of security and diplomacy interests. This would entail a new constitutional mandate for the WHO. Reflecting on the future of global health governance, Lawrence Gostin has called for a new Framework Convention on Global Health [It is uncertain how the current global health security regime will evolve , particul Health . With a th World Health Assembly address these fundamental issues.The setbacks of the Global Polio Eradication Initiative and the delayed control of the Ebola epidemic in West Africa reflect a fragmented approach to outbreak preparedness. More broadly, they point to profound flaws in the current regime of global health governance, which is guided by foreign affairs and security policies. The securitization of communicable diseases has so far led foreign aid policies to sideline health systems. It has also been the source of ongoing misperceptions over the aims of global health initiatives. With its strict allegiance to Member States, the WHO mandate is problematic, particularly when it comes to controlling epidemic diseases. In this context, humanitarian medical organizations are expected to palliate the absence of public health services in the most destitute areas, particularly in conflict zones. The militarization of humanitarian aid itself threatens this fragile and imperfect equilibrium. None of the reforms announced by the WHO in the wake of the 68"} +{"text": "In this case, calcium-phosphorus index of animals\u2019 enamel, with high caries resistance, have no significant differences with the calcium-phosphorus index of human enamel rather, it is even lower.Investigation of the structure and morph-chemistry of enamel and dentin should ultimately lead to development of effective caries prevention strategies. Accordingly, we have studied the nanostructure and morph-chemistry of teeth utilizing X-ray microanalysis, scanning electron microscopy and atomic force microscopy and tunneling. The results suggest that the surface of primary and permanent teeth enamel is not as smooth as previously considered. Rather enamel surface has apertures which are conducive to realization of morphological and chemical processes. Detailed examination of the enamel surface reveals that most of anatomical defects/holes do not end blindly; rather, they penetrate the enamel surface (resembling \"tunnels\"), branch and intersect each other to form enamel \"bridges\" in dentin. Examination of enamel using atomic-powered and tunnel microscopy not only confirm the presence of these nanostructures, - but also help discern more refined characteristics. Consequently, it appears that the tunnels intersect one another at 90 degrees angle. The morph-chemical examination of enamel reveals differences in the structure of intact compared to carious enamel and dentin. Calcium and phosphorus - are the main structural elements of enamel and dentin. The amount of potassium, sulfur and chlorine increases respectively in caries pathology, while the concentration of sodium, silicon, and especially magnesium decreases. The same pattern is observed for dentin. These observations suggest that high concentration of magnesium increases, while chlorine and sulfur decrease the effectiveness of the protective properties of enamel thereby leading to alteration of caries resistance. Subsequently, we examined teeth obtained from animals. In beaver\u2019s enamel, the content of magnesium is higher (seven fold) compared to those of human. The concentration of chlorine and sulfur are higher in people\u2019s enamel that confirms our previous researches concerning the impact of these elements on the caries resistance level of enamel. Differences in microelements structure, the prevalence of magnesium in beaver\u2019s enamel, determined the differences in microhardness of the enamel. The content of the elements is 1.5 times higher in tooth enamel of beavers than humansIn conclusion, the novel discovery of structural formations and the morph-chemical structure of human and animal enamel may ultimately lead to identification of a new approach to caries prevention and development of new, more effective formulation of oral hygiene products."} +{"text": "This special issue of the International Journal of Environmental Research and Public Health includes peer-reviewed publications from investigators who participated in this conference.Health disparities have been defined as a particular type of health difference closely linked with social, economic and/or environmental disadvantage. The National Institute on Minority Health and Health Disparities (NIMHD) at the National Institutes of Health, has a comprehensive portfolio of grants that fund scientific research to improve racial/ethnic minority health and eliminate health disparities. The The scientific program included general, and concurrent sessions, panel discussions and poster sessions. The conference also included specialized technical workshops; workshops on collaboration, scientific leadership, grantsmanship, and mentoring; and meet the expert sessions focused on career development for early stage investigators planned in collaboration with NIH staff. The conference offered unparalleled opportunities for networking and exchanging ideas, forging new scientific collaborations, resource sharing and opportunities for specialized training.The 2014 Minority Health and Health Disparities Grantees\u2019 Conference was held 1\u20133 December, in National Harbor, Maryland. The theme of the symposium, State of the Science in Achieving Global Health Equity-Past and Present Advances and Future Directions-highlighting best practices in biomedical, behavioral, population and health policy research that contribute to improvements in US and global health equity among populations who carry the burden of health disparities. Collaborative, sustainable, replicable and culturally appropriate research promoting prevention, reduction and elimination of heath disparities were also discussed;Achieving Health Equity Through a Population Health Research Paradigm-highlighting effective population health interventions that are often multi-sectorial and community engaged; Transdisciplinary Social, Behavioral and Clinical Approaches for Understanding and Achieving Health Equity in Cardiovascular, Cerebrovascular, and Related Peripheral-Vascular Diseases-highlighting ethnic- and racial-specific variations and determinants underlying health disparities in cardiovascular, cerebrovascular and related peripheral-vascular diseases; andTransdisciplinary Collaborations: A Call to Action-highlighting evidenced-based transdisciplinary research approaches to reduce health disparities, and the strategies to promote diversity in the biomedical research workforce.Health disparities have been defined as a particular type of health difference closely linked with social, economic, and/or environmental disadvantage. Hence, health disparities adversely affect groups of people who have systematically experienced greater obstacles to health based on their ethnicity or race, gender or sex, age, religion, socioeconomic status, mental health, physical disability, or other relevant characteristics . Health In addition to keynote lectures and panels, 1364 abstracts were presented in thirty concurrent scientific sessions and three poster sessions. Research presented spanned a variety of disease areas-cardiovascular, diabetes, obesity, cancer, mental health, infectious disease, stroke and other diseases that disproportionately impact health disparity populations. Studies examined the etiology of disparities; the intersection of biological and behavioral risk factors, the physical environment, social determinants of health, and public health and health care system factors in addressing health disparities; and multi-level community interventions and other population-based studies to improve minority health and reduce health disparities. International Journal of Environmental Research and Public Health is dedicated to the publication of selected peer-reviewed manuscripts resulting from conference presentations. Highlights on a few of these research papers are as follows:This special issue of the Carriere and collaborators studied Ala54Thr) polymorphism of the fatty acid binding protein 2 (FABP) on HDL cholesterol in Mexican-Americans with type 2 diabetes (T2D). They found that the Thr54 allele carriers who were heterozygous or homozygous for the threonine-encoding allele had lower HDL cholesterol and higher triglyceride levels at baseline compared to the Ala54 homozygotes. They concluded that the Ala54Thr polymorphism of FABP2 modulates HDL cholesterol in Mexican-Americans with T2D and that Thr54 allele carriers may be responsive in interventions that include dietary changes.Salto and collaborators conductein-vitro study results that targeting the gain-of-function pathways may improve treatment efficacy when R248Q mtp53 proteins are expressed in TNBC.Shtraizent and collaborators performeMiranda-Diaz and collaborators investigIn a retrospective epidemiologic study, Holmes and collaborators investigUsing the Jackson Heart Study as a model, Addison and collaborators highlighUsing both GIS and regression analysis models, Mathis and collaborators conducteWe would like to thank the conference organizing committee, scientific review committee, other conference committees and staff, and the National Institute on Minority Health and Health Disparities leadership and staff for their contributions to making the conference a success and publication of this special issue possible."} +{"text": "The increase in body weight is a serious global public health problem, with high risk of associated diseases such as diabetes, cardiovascular disease, hypertension, and some forms of cancer. The option for foods with high energy value but poor in micronutrients increases the nutritional status and contributes to the deficiency of important minerals in human health. The use of minerals, among them calcium and magnesium, to control body weight has been the object of several studies.The purpose of this study was to investigate the effect of with the calcium and magnesium supplementation in diets offered to Wistar rats.A biological assay was conducted with 24 animals, distributed in four groups of six. The control group (GI) received feed prepared according to the AIN-93G standard ; the calcium-supplemented group (GII) received this diet containing approximately four times this mineral; the group supplemented with magnesium (GIII) received approximately four times this mineral; and the lipid-supplemented group (GIV) received it with a 14% addition of vegetable oil, but no mineral supplementation. The diets were isocaloric . The variables measured were weight, feed efficiency coefficient, liver and kidney histology, and the following laboratory parameters: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and serum calcium and magnesium levels.After 35 days, the GII animals showed the lowest level of feed efficiency, when compared with the other groups, and consequently exhibited lower body weight, with a significant increase in VLDL, TG and serum calcium levels and a decrease in serum magnesium. The morphological analysis of liver and kidney revealed tissue damage in all groups that received supplementation.The supplementation with calcium proved a possible resource for body weight control, in contrast with that observed in the animals that received magnesium supplementation, whose results were similar to those of controls."} +{"text": "Background.\u2003Following the 65th World Health Assembly (WHA) resolution on intensification of the Global Poliomyelitis Eradication Initiative (GPEI), the Nigerian government, with support from the World Health Organization (WHO) and other partners, implemented a number of innovative strategies to curb the transmission of wild poliovirus (WPV) in the country. One of the innovations successfully implemented since mid 2012 is the WHO's engagement of surge capacity personnel.Methods.\u2003The WHO reorganized its functional structure, adopted a transparent recruitment and deployment process, provided focused technical and management training, and applied systematic accountability framework to successfully manage the surge capacity project in close collaboration with the national counterparts and partners. The deployment of the surge capacity personnel was guided by operational and technical requirement analysis.Results.\u2003Over 2200 personnel were engaged, of whom 92% were strategically deployed in 11 states classified as high risk on the basis of epidemiological risk analysis and compromised security. These additional personnel were directly engaged in efforts aimed at improving the performance of polio surveillance, vaccination campaigns, increased routine immunization outreach sessions, and strengthening partnership with key stakeholders at the operational level, including community-based organizations.Discussion.\u2003Programmatic interventions were sustained in states in which security was compromised and the risk of polio was high, partly owing to the presence of the surge capacity personnel, who are engaged from the local community. Since mid-2012, significant programmatic progress was registered in the areas of polio supplementary immunization activities, acute flaccid paralysis surveillance, and routine immunization with the support of the surge capacity personnel. As of 19 June 2015, the last case of WPV was reported on 24 July 2014. The surge infrastructure has also been instrumental in building local capacity; supporting other public health emergencies, such as the Ebola outbreak response and measles and meningitis outbreaks; and strengthening the integrated disease surveillance and response. Due to weak health systems in the country, it is vital to maintain a reasonable level of the surge capacity for successful implementation of the 2013\u20132018 global polio endgame strategy and beyond. In May 2012, the 65th World Health Assembly (WHA) resolved to intensify the Global Polio Eradication Initiative (GPEI) and declared the completion of poliovirus eradication a programmatic emergency for global public health , 4.In October 2011, Nigeria announced the establishment of a Presidential Task Force on Polio Eradication to provide highest-level leadership to the national effort to guide the polio eradication initiative (PEI) back on track. The task force oversaw a number of initiatives aimed at rapidly achieving the goal of interrupting poliovirus transmission within the shortest time possible. However, an in-depth review of the performance of polio eradication activities in the highest-risk states and local government areas (LGAs) indicated that the high-level commitment at federal and state level did not always translate into improved program quality at the operational level . The 23rThe health system in Nigeria faces multiple challenges, including poor healthcare infrastructure, underfunding of programs, frequent strikes by health workers, and weak oversight at the lower levels \u201310. In rFurthermore, in January 2012, Nigerian high level government officials visited India to review factors that contributed to the successes in the polio eradication efforts in that country . One of The World Health Organization (WHO) team in Nigeria has a broad range of public health practitioners comprising physicians, epidemiologists, pharmacists, logisticians, laboratory experts, data managers, communication experts, program managers, and administrative support staff providing technical support for polio eradication, routine immunization (RI), and accelerated control of vaccine-preventable diseases at national and subnational levels. The WHO was uniquely positioned to implement the surge project as per the mandate from 41st WHA and its physical presence in all 36 states of the federation and the federal capital territory . Prior tTo this end, in March 2012, WHO-Nigeria developed a project to substantially increase its technical capacity to support planning, implementation, monitoring, and evaluation of critical PEI activities, particularly in the states, LGAs, and wards (districts) at highest risk for polio transmission, to ultimately achieve interruption of poliovirus transmission within the shortest time possible.In this article, we document the recruitment, deployment, and management processes and how implementation of the WHO's surge capacity project contributed to the improvement of PEI and RI performance indicators.We conducted a retrospective review of publications by global and local PEI partners and working groups, WHO internal documents, secondary sources, and unpublished reports to obtain data for this article.In early 2012, the WHO country office, with input from key stakeholders, submitted a proposal to the Bill and Melinda Gates Foundation to support the implementation of the surge capacity project. Between 2012 and 2015, the Bill and Melinda Gates Foundation allocated $84 million to support the surge capacity project.The surge capacity project focused on 11 states at high risk for polio transmission , selected on the basis of an epidemiological risk analysis. The states were Bauchi, Borno, Jigawa, Kaduna, Kano, Katsina, Kebbi, Niger, Sokoto, Yobe, and Zamfara. The project aimed to support the HR states to achieve and sustain quality supplemental immunization activities (SIAs) required to ensure poliovirus transmission is interrupted, to maintain certification standard acute flaccid paralysis (AFP) surveillance and to improve RI coverage . CriticaThe recruitment process commenced after developing elaborate terms of reference, key performance indicators, and qualification requirements for each position. The WHO communicated the vacancies through internal notices and existing health networks at all levels. Under its overall responsibility, the WHO formed an interagency panel comprising representatives from National Primary Health Care Development Agency, the Nigerian Ministry of Health, and the United Nations Children's Fund to conduct the selection process. The screening included short-listing the applications on the basis of standard scoring criteria, administration of pretraining and posttraining tests, and interviews. Each panel submitted a detailed report on the selection proceedings, along with a list of recommended candidates and their scores, to the WHO central office for approval.The WHO adopted various contract types to facilitate deployment of the surge capacity personnel in the prevailing epidemiological, operational, and security circumstances. Such contract types included staff contracts, characterized by short or fixed terms and mainly involved for central and zonal level staff; special services agreements, which involved nonstaff, were governed by United Nations security regulations, and were used mainly to engage cluster coordinators; and agreements for performance of work, which involved nonstaff , were not governed by UN security restrictions, and allowed flexibility in determining the payment rates and movement of the contract holder.In addition to the training conducted to administer selection tests during the recruitment process, the WHO and partners organized and cascaded trainings. The training package covered topics on the Expanded Program on Immunization and involved field visits to health facilities offering RI and surveillance services, to further perform hands-on practices using the approved RI and surveillance checklists.In 2012\u20132013, the WHO engaged an international consulting firm and conducted a series of management trainings for top- and middle-level managers, including surge capacity personnel with supervisory responsibilities. The training introduced the following concepts: understanding management styles, performance management and accountability, team building and maintenance, objective setting and monitoring performance, handling difficult conversations, coaching for development, and improving creativity and innovative problem solving skills.The WHO officers support efforts to enhance program ownership and oversight, improve immunization operations, and sustain high quality surveillance performance. It is important to provide them with a working environment conducive to providing objective technical and operational guidance to the PEI program. The WHO operational focus is drawn from the national immunization plan, which drives the allocation and deployment of technical assistance, particularly at the field levels. To this end, after close review of the WHO's staffing strength vis-\u00e0-vis the expected technical deliverables, the WHO implemented a series of in-country staff rotation.The WHO used the policy of placing high-quality personnel in the worst-performing LGAs. To this effect, based on a thorough risk analysis conducted in collaboration with national authorities and partners, coupled with the performance assessment results, state- and LGA-level personnel were reassigned biannually to deploy high performers in priority areas .Along with the substantial increase in the number of personnel, it was necessary to strengthen the monitoring and evaluation capability to systematically monitor staff performance. In 2014, the WHO introduced a systematic accountability framework and implemented it in all its field offices, using key performance indicators aided by geographical information systems and mobile device technologies, coupled with periodic supportive supervisory visits to the field . Additional monitoring and evaluation officers, as well as data management personnel, were hired at the central level and in priority zones and states.In March 2012, the WHO made a major adjustment to its functional organogram to establish that adequate technical, managerial, and administrative support systems at all levels to effectively support the enhanced WHO technical infrastructure. The revised structure reflected the WHO's extended presence down to LGA and ward levels after the introduction of the surge capacity. The adjustment further optimized the span of control and supervisory lines.In 2013, the WHO trained 532 cluster coordinators and LGA facilitators and 1 637 field volunteers. Each session took 4 days, using the Expanded Program on Immunization comprehensive package that included polio SIAs, nonpolio SIAs, surveillance, RI, and data management. Specific topics were drawn from the standard operating procedures developed for technical surge personnel . Furthermore, 214 participants received management training, of whom 45 were from government and partner agencies.Following the full implementation of the surge capacity, the human resource strength of the WHO increased by >400%. Table The WHO used agreements for performance of work for >80% of the overall personnel, while 11% and 7% of personnel were engaged under fixed-term and special service agreements, respectively. These cadres possessed a higher technical caliber and were placed in supervisory responsibilities at state, zonal, and central levels.Between August 2013 and July 2014, the WHO undertook various waves of mass rotations that resulted in rotation of 50 high-level technical officers, the majority of whom coordinated zonal and state level activities. The administrative focal points in all 37 field offices were also relocated or reprofiled between December 2014 and February 2015. These periodic movements contributed to enhanced managerial capabilities and fostered staff accountability.Guided by surge capacity deployment optimization analysis and the cumulative feedback during 2014 from the accountability framework, the WHO made necessary adjustments during the 2015 surge capacity deployment. States in northeast zone with persisting security challenges and programmatic priorities were assigned more personnel by shifting staff from states such as Jigawa that had relatively more resources. The current deployment of 2 210 human resources involved in the surge capacity in the 11 HR states is shown in Figure The majority of surge capacity personnel were deployed and became fully functional toward the end of 2012. As highlighted in Figures 3Figure Microplan development is one of the core process indicators for successful and quality immunization campaigns for which the surge capacity personnel are directly responsible. As Figure As of 19 June 2015, cases of WPV infection in the country decreased during 2012\u20132014, with 122 cases in 2012, 53 cases in 2013, and 6 cases in 2014, with the last case reported on 24 July 2014. End-process independent monitoring of polio SIAs showed that 86% of wards achieved 90% vaccine coverage by the end of 2012, which increased to 96% by the end of 2014.With respect to RI indicators, the surge capacity also contributed to the steady improvement in the implementation of fixed and outreach sessions to immunize children. Each state has a goal of conducting 80% of planned fixed and outreach RI sessions. As Figure The WHO reorganized its functional structure, adopted a transparent recruitment and deployment process, provided focused technical and management training, and applied systematic accountability framework to successfully manage the surge capacity project in close collaboration with the national counterparts and partners. The engagement of >2 200 surge capacity personnel has enhanced the WHO's technical capability to contribute to the achievements registered in the intensified PEI and RI activities in Nigeria. Guided by the epidemiological risk analysis and feedback from the accountability framework, the majority (92%) of the surge personnel were strategically deployed in the northern part of the country, which remains a priority from epidemiological, operational, and security perspectives. To facilitate acceptance by the community, the surge capacity personnel were hired from the communities where they resided, using suitable contractual arrangement. The personnel have built up personal relationships with key stakeholders in the community to obtain buy-in for successful implementation of several innovative interventions that have been introduced since 2012.The surge project gave the program an opportunity to use technically competent health professionals who understand the grassroots' cultural and operational context. As such, they are suited to address challenges unique for every local area in the context of the diverse political, social and economic landscape in Nigeria. Their extended presence at LGA and ward levels created the capacity to successfully translate the high-level commitments and strategies into operational levels.The surge capacity is well aligned with the updated WHO functional structure and integrated into the existing health systems in the country. The collaboration with the government and partners in recruitment, deployment of the surge personnel, and collective program reviews at ward, LGA, state, and national levels, coupled with application of WHO's rigorous accountability framework, contributed toward improved program performance. As outlined in the WHO's standard operating procedures, the surge personnel are directly involved in training, planning, implementation, monitoring, and review of the field-level polio campaign performance and timely outbreak investigation and response; active case based surveillance; and intensification of RI activities . Furthermore, the surge capacity personnel have been instrumental in sustaining the program in security-compromised areas, which were not accessible to regular staff.Owing to the weak health system in the country, the surge personnel are also called upon to support other activities, such as nonpolio immunization campaigns, integrated disease surveillance and response, and other disease outbreak investigations and responses .The surge project faces challenges of attrition, mainly because of the implementation of accountability framework and, to some degree, resignations. In 2014, 300 agreements for performance of work were not renewed, because of persistent poor performance [Despite the challenges in recruitment and maintenance of such a large workforce, the partnership coordination and management architecture put in place contributed to maximize efficiency and accountability from ward to national levels .In conclusion, as recommended in the 24th ERC report and the 2012\u20132013 global polio emergency plan, the WHO responded to the call for action and equipped its personnel, including those involved in the surge capacity, with the standardized tools and knowledge to optimize the substantial investment on the project . As statWe recommend the sustenance of the surge project to maintain the polio program's momentum and successful implementation of the polio endgame strategy in Nigeria , 20. As"} +{"text": "Abscisic acid (ABA) is the master hormone governing the intricate network of molecular switches and physiological responses of guard cells that determine the degree of stomatal aperture. Once plants sense water deficit, ABA is synthesized, and enters the guard cells triggering a series of signals that result in stomatal closure and preservation of the water status of the whole plant. ABA signaling in guard cells involves several mechanisms sustained by enzymes, small molecules, and second messengers that finally promote the inactivation of inward-rectifying K+ channels, activation of outward-rectifying K+ channel, and activation of slow and rapid-anion channels is required for ABA-dependent induction of stomatal closure and (B) negative effects leading to the attenuation of the ABA signaling through the inhibition of key effectors of stomatal closure (inhibition of NADPHox and OST1 by S-nitrosylation). A recently published article adds new in vitro and in vivo evidences showing that the family of ABA receptors PYR/PYL/RCAR is inactivated by nitration of tyrosine residues leading to the degradation of the receptor via proteasome. The non-reversible nitration of tyrosine residues is a post-translational modification of proteins that requires the formation of the strong oxidant peroxynitrite, a compound formed from the fast reaction between superoxide (OAs stated, OST1 is a serine/threonine protein kinase that acts as a positive regulator mediating the ABA-induced stomatal closure through the activation of downstream effectors (Wang et al., Overall, this opinion article tries to recall the already known two sides of the NO \u201ccoin\u201d as a ubiquitous, homeostatic, and synchronizer molecule in cell physiology. Thereby, we highlight here the rationale of NO acting both in promoting and arresting the ABA-induced/phospholipid-mediated signals triggering the stomatal closure, as a way to avoid the exacerbation of a hormonal stimulus. In future investigations, however, it remains to be deciphered if the multi targets of NO are reached simultaneously or through a temporal and spatial pattern of its actions.The analysis, revision of the bibliography and the discussion of the data were conducted by AL, CG, and LL. The manuscript was prepared and written, including round of corrections, by AL, CG, and LL. The design and general supervision was performed by LL.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Microorganisms are common colonizers of superficial (phylloplane) and internal tissues (endophyte) of a variety plant species . PhyllopFor isolation of yeasts, samples leaves, stems and flowers of B. dracunculifolia were colected; 10 g were macered in 90 mL of saline solution and dilutions of the suspension were spread in solid medium BDA and TSA. After purification and preservation, the isolates were characterized by colony morphology and grouped. Isolates representant of each group were subsequently identified by molecular techniques based on the amplification and sequence analysis of ITS1-5, 8S-ITS2 rDNA. For evaluation and screening of potential enzymes producers, enzymatic activity was performed in solid media . ProteolWere obtained 69 isolates, being 74% of these isolates of yeasts and yeast-like fungi. On the basis of on colony morphology the isolates were grouped into four morphotypes . The majority of the isolates was originating from samples of flowers and showed black colonies on PDA media. By analysis of ITS1-5,8S-ITS2 rDNA sequences in Genbank database, the isolates were identified as members of the species Starmerella bombicola, Aureobasidium leucospermi, A. pullulans, Rhodotorulla mucilaginosa and Occultifur externus. The isolates were promissing for enzyme production, specially for amylolytic and lipolytic activities which were predominant among the isolates. The most promising isolates were belonging to the genus Aureobasidium sp., which showed activities for the five enzymes tested. The isolates identified as promising for the production of enzymes, especially those of the genus Aureobasidium sp. were selected for more specific analyzes aimed at quantification and perfecting of culture conditions that allow greater production and can contribute to to the development of alternatives to enzymes already available in market."} +{"text": "Under current conditions of development of health care and generally mankind, prevention of healthcare-associated infections (HAI) is one of the global world problems.Prophylaxis of HAI in Russia.Epidemiological, statistical.HAI affect 5-10% of patients staying at in-patient departments and rank the tenth place among the causes of population mortality. Annually according to the data of official statistics in Russia approximately 30,000 of HAI cases are registered but the experts consider their actual quantity to be not less than 2-2,5 mln of people.Under current conditions in Russia \u201cNational Concept of Prevention of Health Care Associated Infections\u201d (2011) was enacted and is valid. The present concept was developed by specialists of Federal Service for Surveillance on Consumer Rights Protection and Human Well-being, famous scientists and health professionals, and it determines the purpose, principles, general architecture, major improvement concepts of national system of health care associated infections prevention, its functioning mechanisms and also expected social-and-economic effect.Taking into account absence of specific means and prevention issues solution methods one of the most important concepts of HAI control is improvement of disinfection and sterilization methods. This concept in Russia is particularly significant due to wide spread of microorganism with high resistance to the effect of majority of antibiotics and antiseptics groups, development of modern technologies , building and reconstruction of centralized sterilization in-patient departments with updated equipment for washing and disinfection of medical products and endoscopic devices.None declared."} +{"text": "Low levels of bilirubin exert antioxidant effects, but some neonates may develop very high levels of unconjugated bilirubin (UCB), with an increase of the unbound free fraction at the time of insult exposition is supposed to influence the location of selective brain damage, as well as the severity of consequences . The cliTo avoid neurological consequences, the Clinical Practice Guideline of the American Academy of Pediatrics recommend total bilirubin determination (TSB) on every jaundice infant, both during hospital stay and post discharge follow-up. To this goal, Bilistik , a new mEarly neuronal accumulation of bilirubin in damaged regions and its brain metabolism may have a role in the marked regional differences observed in kernicterus impairment. This hypothesis is supported by the role of brain cytochrome P-450 (Cyp), known to oxidize UCB. In the brain of Gunn rats, an early upregulation of Cyp mRNAs was observed in the unaffected brain regions, cortex and superior colliculus, in contrast to the delayed and slight upregulation observed in the affected regions, inferior colliculus and cerebellum , where Uin vitro and challenged with bilirubin in controlled (concentration/timing) manner, strictly modelling different histopathological aspects of neurological conditions.Clarification of pathophysiology of UCB neurotoxicity, that continues to be an important risk among newborns worldwide, may open new perspectives for therapeutic approaches, focused in protecting directly the brain, the final target of bilirubin toxicity. To this aim the development of new research models, appear of particular relevance. Among them the organotypic brain cultures, living slices of the CSN that can be cultured"} +{"text": "The clinicalstudies establish the absorbed doses in organs, by improving the compartimental models andallowing the prescription of the activities (amount of radiation) to be administered tohumans. Both in preclinical and in clinical studies, quality control ofradiopharmaceuticals labelling is one of the steps in the quality assurance system, whichis mandatory for registry in the Health Regulatory Agency . Thebiological effects of ionizing radiation in Medicine were identified by biodosimetry inroutine or in non-planned situations. In industrial applications, accidents have beenreported. Treatments of radiological victims in different contexts, includingreconstructive dosimetry for cutaneous radiation syndrome (CRS), should be obligatorydisciplines in the professional curricula of the multidisciplinary teams. The low-intensityred and infrared laser effects are increasing in Regenerative Medicine, nevertheless theassociated risks are unknown and there is a lack of safety requirements. Eight paperspresented in the SBBN Congress were selected to be published in the Brazilian Journal ofMedical and Biological Research, Volume 48(10), 2015.In the last two decades, the applications of ionizing and non-ionizing radiation in Biologyand Medicine have been improved considerably in Brazil. The 2014 SBBN Congress, entitled\"Framework, science and technology for preclinical and clinical studies with ionizing andnon-ionizing radiation\", was held in Caxambu, MG, during the XXIX FeSBE Annual Meeting.About 50 posters were presented in Radiobiology, Radiopharmaceuticals, Radiationprotection, Biophotonics and Photobiology. For new radiopharmaceutical developments, thepreclinical studies were essential because the \"2014 SBBN Congress President"} +{"text": "To analyze the relations between the meanings of working and the levels of doctors work well-being in the context of their working conditions. The research combined the qualitative methodology of textual analysis and the quantitative one of correspondence factor analysis. A convenience, intentional, and stratified sample composed of 305 Spanish and Latin American doctors completed an extensive questionnaire on the topics of the research. The general meaning of working for the group located in the quartile of malaise included perceptions of discomfort, frustration, and exhaustion. However, those showing higher levels of well-being, located on the opposite quartile, associated their working experience with good conditions and the development of their professional and personal competences. The study provides empirical evidence of the relationship between contextual factors and the meanings of working for participants with higher levels of malaise, and of the importance granted both to intrinsic and extrinsic factors by those who scored highest on well-being. The research focuses on the social, organizational, and psychological effects of new, unstable, and fragmented employment, especially in Latin-American countriesAs the labor world is a fundamental scenario of people\u2019s psychological experience, the social and organizational changes in working conditions similarly affect workers\u2019 labor subjectivity, social working relations, professional ethical values and meanings, occupational health, job satisfaction, and work well-being levels.,Research on the meaning of working, work values, and working life is heterogeneous,,,,,,,,,,The literature about the different types of work well-being is extensive and diverseContemporary work well-being theories are greatly influenced by the ideas of Warr and his ecological modelThese changes,The Brazilian Federal Constitution from 1988 created the foundations of a Unified Health System , which defined health as \u201ceveryone\u2019s right and duty of the State\u201d. However, access to health services is not as easy for every citizen, for multiple reasons, as significant social and economic inequalities, disparities between states, deficit of public investment in health infrastructure, public subsidies to the private sector, double coverage of health services for a privileged minority, and the asymmetric distribution of funding SUS between the public and private sectors. All these features greatly affect the quality of the health system and the conditions of medical workth century, among them the creation of the Ministry of Health, Welfare and Social Security in 1924 and of the National Health Service in 1952. The 1981 Reform condensed and summarized the difficult balance between two conflicting tendencies: the movement for the recovery of public health system eroded by the dictatorship and the neoliberal insistence on cutting public spending. At the beginning of this century, new reforms were implemented concerning social rights in health, reorganization of the hospital network, and universal mandatory health plans regulated by the State. In contrast, funding for the system drags large deficits that involve job insecurity, deteriorating working conditions and low quality of work life for the health professionalsThe Chilean health system has a long history marked with milestones along the 20The Colombian health system of the past decades is the heritage of the strengths and weaknesses of Law 100/1993 and its successive reforms of 2007 and 2011. Law 1,752/2015 introduced a new regulation of the fundamental right to health and a new general social security health system. The underlying problems that have been dragging Law 100 were caused by conflictive visions of health as a source of business and as a fundamental rightFor its part, the current Spanish health system reflects the tension between hardly compatible objectives and strategies: the goal of excellence in managing the health systemMisi\u00f3n Barrio Adentro, which includes modules and Comprehensive Diagnostics Centers (CDI). This policy tried to increase the coverage of health services for the poorest populations. However, it failed to focus on fundamental problems of the Venezuelan health systemThe Venezuelan health system consists of a network of hospitals and clinics financed by the State or by private systems. In the 2000s, the government created a network of health centers and outpatient clinics as part of the The background of the present study consists of the changes in Latin-American and Spanish health systems, the value transformations in health care professionalism, and the growing work overload and job insecurity in flexible jobs within current medical working conditions. In this context, the objective of this research was to analyze the relations between the meanings of working and the levels of doctors work well-being in the framework of their working conditions.This study combined two approaches: one qualitative, with keywords concerning the meanings of working; and one quantitative, using a self-report survey made up of a battery of scales measuring well-being at work and working conditions.Pragmatic and epistemological reasons led researchers to seek a compromise between random and convenience sampling. This study combines a long questionnaire, a target-group with little time available to complete it, and a remarkable diversity of contexts among countries regarding opportunities and restrictions in access to random samples. This set of circumstances would determine a very low response rate in random sampling, with consequent problems of statistical representativeness. Following the principles of Grounded TheoryWe conducted a homogeneous collective concerning type of service and professional sector (medicine) composed of 305 professionals employed in hospitals or other large and complex health centers in Brazil, Chile, Colombia, Venezuela, and Spain. The collective was also somewhat heterogeneous, as all the participants were recruited by convenience, intentional, and stratified sampling, according to six criteria: gender, generation, country, type of contract, seniority in the organization, and whether they had management responsibilities. About half of this group was male, mean age was 42 years, around 40.0% worked in Spain, and the others belonged to various participating Latin-American countries . Seventy-five percent of the participants had stable employment contracts, the juniors and seniors in the organization were equally distributed, and one third had experience in health care services management.The general tool to collect data was a self-report survey, which also included items concerning sociodemographic information. To analyze the meanings of working, this questionnaire included a free-word association item that invited people to write four keywords defining their current work experience. For the quantitative variables, a standardized battery of scales including the Working Conditions ScaleThe section concerning working conditions included 44 closed items. It was designed according to a theoretical model that configures working conditions around a three-way relationship of the organization with the method, the environment, and the person. A principal component analysis showed the existence of six factors, related to material and social environments, regulation and development methods, organizational adjustment to the person, and adaptation of the person to the organization. The six scales of the theoretical model represented by these factors were rated on an 11-point Likert scale ranging from 0 to 10 .The Questionnaire of General Labor Well-being included a series of 55 closed items organized according to a theoretical model of general work well-being. Factor analysis yielded two independent factors: the first one, called Psychosocial Well-being, comprised three scales measuring affections, skills, and expectations; and the second one, Collateral Effects, contained three scales evaluating somatization, exhaustion, and alienation. The affections and skills scales had a semantic differential format, ranging from 1 to 7; the expectations scale had a Likert format, ranging from 1 (low) to 7 (high). The three collateral effects scales ranged from 0 (never) to 6 .All scales showed high internal consistency, with Cronbach\u2019s alpha values ranging from 0.80 to 0.97. The psychometric study indicated that the overall instrument reproduced the structure of the proposed theoretical models, and that it was a measurement tool particularly sensitive to the psychosocial dimension of working conditions and of work well-being of health care professionals, and to evaluate the bipolar nature of their well-being experience.For the qualitative analysis, we used a dual pathway of textual and content analysis, and for the quantitative analysis, we combined descriptive statistics and factorial correspondence analysis, which shows relationships in a set of categorical variables from the contingency table data.,For the textual analysis of lexical forms associated with working experience, we performed thematic analysis of the corpus of data collected sequentially, combining two procedures: bottom-up data classification without adjusting to existing coding frames and top-down recoding, based on a theoretical framework. The result of this process was a dictionary drawn from all the original words of the questionnaire, which was based on a theoretical perspective, facilitating the analysis and discussion of its contents. This theoretical framework was grounded in the burnout and engagement modelsIn an initial coding level, general codes related to the malaise and well-being axes were constructed. The categories associated with the malaise pole were negative working conditions, discomfort, exhaustion, cynicism (negative attitude towards the organization), depersonalization (negative treatment of people), and (self-)inefficacy. The categories linked to the well-being pole were positive working conditions, well-being, vigor, commitment, good relationships, personalization, and efficacy., exhaustion, lack of commitment, depersonalization, and inefficacy. The remaining 11 codes have positive connotations: good (socioeconomic) conditions, opportunities, satisfaction, well-being, empowerment, commitment, ethics, good relations, plenitude, efficacy, and competences. We created an additional category that grouped a low percentage of non-specific responses.In a second level of categorization, specific codes were designed including words that condensed groups of meanings from the original terms. This list includes 25 codes, 14 of them with negative connotations: overwork, bad management, disorganization, bad environment, injustice, inappropriate work, lack of resources, instability, dissatisfaction, malaiseThe Ethics Committee of the Autonomous University of Barcelona approved this study. All participants signed an informed consent form. Moreover, in all cases, we applied the international rules on confidentiality of participants and institutions, safeguarding the anonymity of responses, commitment to returning results, and responsible use of information.All the participants tended to associate medical practice experience in their respective health center to a double type of factors: the valuation of their own working conditions ; and a set of semantic codes, value systems and beliefs rooted in local cultures of each country, but also very influenced by the respective socioeconomic and health policy joints of every place and time. In this regard, the data obtained show a picture characterized by the following major trends in assessment of working conditions: (a) general convergence between countries on scoring averages ranging between 5.5 and 7.5, depending on factors and scales; (b) no statistically significant differences between the various Latin-American groups; (c) almost statistically significant differences (p = 0.054) between the respective averages of Latin-American and Spanish professionals concerning working conditions in general (tending to show above the first collective); (d) significant differences between Latin-American and Spanish on the general factor \u201corganization and individuals\u201d . This means that the Latin-American group recognized more adaptation of individual professionals to their organization . In addition, they perceived a greater degree of accommodation of the organization to the person . The Chilean group showed a special configuration, evaluating their own working conditions close to those of other Latin-American countries scores, but considering their own work experience very close to the Spanish group terms .The corpus of the meaning of working variable consisted of 161 word forms generated by the participants, with frequencies ranging from 45 to 1 and a total of 769 lexical forms. The distribution quartiles obtained from the responses to the General Labor Well-Being Questionnaire formed the continuous variable well-being. We assigned each response to a category , according to the quartile corresponding to its score on the questionnaire.2 (75) = 148.820, p < 0.001) led to rejecting the null hypothesis of independence between the meaning of working and the malaise-well-being quartiles and to accepting the alternative hypothesis: the meaning of working and the malaise-well-being quartiles were significantly related.A Chi-square test and well-being (0.470).The highest relative contributions corresponded to malaise (0.903) and well-being (0.900), which showed that they were well placed in the axis. However, the other modalities of normal and risk were not so well placed. Lexical forms that defined the axis and that were found adequately placed corresponded to the variable meaning of working, but other variables that were also well placed did not contribute to its definition., inefficacy, and dissatisfaction. The pole representing the working experience for professionals positioned in well-being quartile included good conditions and plenitude.To facilitate interpretation of dimension 1, malaise-well-being and their lexical forms, the modalities of the two variables were located on an axis in accordance with their coordinates and absolute and relative contributions. The pole consisting of lexical forms that defined the meaning of working experience for those located in the malaise quartile included bad management, overwork, exhaustionThe axis risk and malaise and their lexical forms were characterized by the higher absolute contributions of the lexical forms dissatisfaction (0.149), overwork (0.128), strengthening (0.119), disorganization (0.106), and depersonalization (0.081). The examination of its coordinates showed that at the upper end of the axis were located lexical forms that defined the meaning of working experience as dissatisfaction (1.311), bad management (1.240), depersonalization (1.081), and strengthening (0.656), whereas at the lower end of the axis were mainly located disorganization (-1.236) and overwork (-0.580).Regarding the profile of the malaise-well-being quartiles, as observed in the column profile, the second axis was defined by the modalities risk (-0.337), normality (-0.179) at one extreme, and malaise (0.248) and well-being (0.236) at the other.At the malaise - well-being pole, the highest relative contribution is strengthening (0.474), and, at the normal-risk pole, disorganization (0.586). These scores indicate that these categories were not well placed on the second axis, and neither was the modality normal.To view the interpretation of dimension 2, risk-malaise and their lexical forms, the modalities of the two variables were placed on an axis according to their coordinates and absolute and relative contributions. On this axis, one pole includes the lexical forms that define the meaning of working experience as disorganization and overwork for those in the risk-normality quartiles. On the opposite pole, the meaning of working experience in the malaise-well-being quartiles was associated with dissatisfaction, strengthening, and depersonalization.The meanings of working for the medical group located in the malaise quartile were made up of lexical forms of job discomfort, showing strong evidence of frustration and exhaustion. The set of words included in this category showed that most aspects involve a negative assessment of working conditions and the management of health facilities. Specifically, work experience was described with the terms: bad management , work overload , exhaustion , inefficacy , and dissatisfaction (disappointment).In contrast, the job experience of medical professionals who were located in the well-being quartile, including extrinsic and intrinsic aspects, was described as working with good conditions and plenitude . Globally, results showed the clear and intense relations between the meanings of working experience and perceived work well-being in the context of specific working conditions.This study overviewed how Latin-American and Spanish doctors construct their experiences and meanings of the complex relationship between work, malaise, and well-being in a changing world of health care systems and services. The research provides information about two main points: (a) the close association between specific working conditions and meanings associated with job well-being and professional performance, and (b) the strong link between the meanings that doctors assign to their professional practice and the general environmental characteristics of the settings and contexts where they work. In this regard, situational diversity explains some differences in meaning, whereas shared contextual background tendencies allows better understanding of detected similarities of work, professional values, and ethical dilemmas.,,-,,The distribution of keywords on the malaise-well-being axis makes evident the relationship between meaning of working and job well-being experienced by medical professionals. On the malaise quartile, work meanings appear closely associated with worse objective and perceived organizational working conditions . In contrast, scores in the well-being quartile were related to perceived good working conditions and to the importance granted to intrinsic and extrinsic factors. The discourses on working and well-being from the surveyed physicians were consistent with data from previous empirical studies,,,,,Two single trends in working conditions were reported by most participants as especially problematic common concerns: emerging job insecurity from the temporal instability of job contracts, and the perceived intensification of work due to task overload, which in the health sector was expressed as attendance pressure, the main psychosocial risk factor of professional burnout,,,,,,,,,The results linking the meanings given to professional experience, job well-being, and working conditions are consistent with the strong association reported between the available material resources of hospitals and the mental health symptoms observed in health care professionals (doctors and nurses),,,,,,,,,,,From a sociological and cultural point of view, the data collected suggest an underlying paradoxical process: the historical tension between differentiation and homogenization megatrends. Literature indicates the structural and manifest differences between countries, concerning general economic, social, political, demographic, cultural and historical backgrounds, state and market structures, and health system administration modelsThe joint impact of these conflicting processes is visible in the meanings given by doctors to their professional practice, closely related to their perception of the quality of their own specific organizational environment. Spanish and Chilean participants shared their respective working experiences, commonly described as an overloaded and monotonous agenda, and bureaucratic, politicized, inflexible, and ineffective management. These professionals considered work overload as the worst of their working conditions and as a main psychosocial risk factor of burnout. Another perceived major cause of professional discontent in the daily routine was job insecurity. Spanish participants with unstable jobs (temporary contract) reported lack of career prospects in a public service systemThe professional practice of Colombian doctors also showed their discomfort with temporary contracts, low pay, difficulties of the public health care system, and frustration for failing to provide good service to the community. Thus, they conveyed a critical point of view about the negative working conditions of medical care, affected by some aspects of the reforms carried out during the past few years. They also expressed a shared belief in the need to seek greater coverage and equity in health services for most people.The meanings given by Venezuelan doctors to their work reflected a difficult experience of tension between vocation requirements and the limited resources to carry out their profession, strongly influenced by the progressive deterioration of the national public health system in recent decades, characterized by lack of supplies for diagnostic tests, lack of medicines, infrastructure problems, and precarious working conditions.,,Over the last few years, the Brazilian government invested in health personnel and infrastructures, developing public health policies. In this context, participants of this country showed a confuse representation of work, which some describe as an uncomfortable experience and others as an opportunity to put professional and ethical principles into practice-,Moreover, within this basic diversity, the various countries also share a more or less successful history of health system reforms. Despite their remarkable variety of achievements and strategies, they were oriented toward the similar main goal of increasing the health system efficiency and redesigning the management and direction of the public health system, health care centers, services, and working conditions of medical professionals. This historical innovation has generated new organizational subcultures and professional practices facing a challenging, difficult, and conflicting cultural combination of values, such as efficiency and empathy, cost-benefit analysis and the Hippocratic path, business and humanism, common good and private benefit, commercial and social demands, managerial and professional priorities, market laws and the personal quality of working lifeThis underlying historical background and cultural matrix is an important explanatory key to the similar meanings constructed by professionals living and working in such heterogeneous settings, crossed by conflicting megatrends. They described their experience of reforms as changes, bureaucratization, politization, or reorganization, and noted certain dominant values of the new model of managing health system, such as flexibility, efficiency, competitiveness, demand-resources, financing, profit, client, quality, or cost-benefit. The shared appraisal of the health system reforms by most respondents to the questionnaire provides evidence of an unbalanced process: perceived positive general advances concerning infrastructural and organizational investments and negative outcomes from the new management of an increasing number of patients and health care professionals.,,,-,,In this way, despite their contextual diversity, doctors from different countries tended to acknowledge certain good organizational, material, and technical working conditions, which allow them to work more and better with patients. However, they expressed also discomfort about work overload, time pressure, and certain ethical and professional strains and dilemmas posed by new organizational demands, economical restrictions, and working conditions. They also criticized reform strategies and practices for being insufficient to promote health and well-being policies for medical and other health care professionals. Thus, they showed the discrepancy between the official rhetoric about the need to develop human talent as a strategic resource in health care organizations and the practical inattention of the psychosocial dimension of medical professional risks and their quality of working lifeAnother link among the common cultural background of the surveyed workers was the manifest centrality of work in their personal and social life and of values of medical professionalism in the entire sample of participants in the study. Participants showed it independently of their present political context, working conditions, relative job satisfaction, or specific organizational circumstances of their professional practice.,,,-,,,,,,,,,,,Our data are consistent with the information provided by the literaturestricto sensu non-epidemiological research enhances our theoretical understanding of current relevant emerging professional experiences in this population. Moreover, the study performed a combination of qualitative and quantitative methodological strategies, using a design of text dictionary and adopting the bipolar malaise-well-being axis. The empirical work promoted the participation of professionals from five countries, focusing on a profession that involves important psychosocial risks. The results point out some aspects to consider in the preventive political agenda aimed at avoiding, eliminating, or minimizing risk factors as well as promoting healthy organizational conditions of the professional medical practice.The present research has limitations and strengths. The adopted theoretical sampling procedure does not allow statistical generalization of the obtained data to the reference population. However, this"} +{"text": "Those planning, managing and working in health systems worldwide routinely need to make decisions regarding strategies to improve health care and promote equity. Systematic reviews of different kinds can be of great help to these decision-makers, providing actionable evidence at every step in the decision-making process. Although there is growing recognition of the importance of systematic reviews to inform both policy decisions and produce guidance for health systems, a number of important methodological and evidence uptake challenges remain and better coordination of existing initiatives is needed. The Alliance for Health Policy and Systems Research, housed within the World Health Organization, convened an Advisory Group on Health Systems Research (HSR) Synthesis to bring together different stakeholders interested in HSR synthesis and its use in decision-making processes. We describe the rationale of the Advisory Group and the six areas of its work and reflects on its role in advancing the field of HSR synthesis. We argue in favour of greater cross-institutional collaborations, as well as capacity strengthening in low- and middle-income countries, to advance the science and practice of health systems research synthesis. We advocate for the integration of quasi-experimental study designs in reviews of effectiveness of health systems intervention and reforms. The Advisory Group also recommends adopting priority-setting approaches for HSR synthesis and increasing the use of findings from systematic reviews in health policy and decision-making. Health policymakers and managers (henceforth decision-makers), as well as other stakeholders involved in health systems worldwide, routinely face difficult decisions around improving health care and promoting equity. Ideally, decisions and recommendations should be informed by the best available research evidence, which typically comes from systematic reviews of research \u20133. SysteThe Alliance for Health Policy and Systems Research (\u201cAlliance\u201d), a partnership housed within the World Health Organization (WHO), is pioneering support for strengthening capacity for synthesis of health policy and systems research through the establishment of systematic review centres in low- and middle-income countries (LMICs). The need for such a resource is especially acute in these settings due to the limited capacity of individuals, teams, organisations and knowledge systems to support the production and use of systematic reviews . To dateThe work of the Alliance centres complements that of other recent global initiatives. The Evidence-Informed Policy Network (EVIPNet) has actively promoted partnerships at the country level between policymakers, researchers and civil society in order to facilitate both policy development and policy implementation informed by the best scientific evidence available . SimilarAlthough there is growing recognition of the importance of systematic reviews to both inform policy decisions and produce guidance for health systems, a number of important methodological challenges remain and there is a need to better understand the processes supporting the transparent use of review findings in complex health system decisions. In addition, there is a multiplicity of initiatives in the field and better coordination is needed. The Alliance therefore convened an Advisory Group on Health Systems Research Synthesis (\u201cAdvisory Group\u201d) to bring together different collaborations, groups and institutions interested in HSR synthesis and its use in decision-making processes .In this paper, we outline the rationale of the Advisory Group, the six areas of work steering its activities and the guidance it provides to the Alliance and beyond; the paper also reflects on challenges in producing complex HSR syntheses and fostering their use in health systems decision-making.Since 2009, a series of consultative meetings led to the development of recommendations to improve international collaboration on HSR synthesis, with a focus on LMIC needs and capacity building Table\u00a0.Table 2EThe consultative meetings also revealed a landscape of research synthesis in which the focus and activities of organisations varied in terms of the following: (1) content , (2) research questions , (3) geographical focus (high-income countries (HIC) or LMIC)), and (4) capacity building (for supply and/or demand for reviews). The Advisory Group was established to play a central role in advancing the science of HSR synthesis and knowledge translation by developing and strengthening networks among individuals, groups, institutions and collaborations that have an interest in this field. Participating organisations include Cochrane and The Campbell Collaboration, numerous academic institutions and governmental and nongovernmental organisations ).The Advisory Group has evolved to include participants from 17 organizations/networks who convene once every 3 to 4\u00a0months to discuss current challenges and advances related to both producing systematic reviews and drawing on them for guidance on strengthening health systems. The group shares information, identifies where further methodological work or training is needed and builds cross-institutional links, and thereby, with its anchoring at the Alliance and WHO, serves as a global focal point for coordination around the issues.The Advisory Group, together with the Alliance more broadly, has contributed to setting priorities for health systems research on a global scale , 18. TheLimited capacity and issues of financial sustainability of groups in LMICs that undertake systematic reviews are further important challenges identified by the Advisory Group. For example, how can these groups secure core funding, ensure the availability of specialised resources such as information scientist support and statistical tools, strengthen their capacity to undertake the wide range of reviews needed to inform health system decisions and improve their engagement with decision-makers in the review process? Discussions on these issues contributed to the development of the new Global Evidence Synthesis Initiative (GESI), led by an international collaborating group of organisationsAnother important challenge identified by the Advisory Group relates to strengthening the capacity of decision-makers and stakeholders to access, assess and apply HSR evidence in decision-making and to create a \u201cuser-pull\u201d for HSR evidence. The Advisory Group advocates for and supports the development of user-friendly summaries of HSR syntheses and recognises the importance of sensitization workshops for users of HSR syntheses, institutionalised mechanisms for researcher-user interactions and knowledge translation activities. The last involves using knowledge translation tools such as evidence briefs for policy and briefing notes and convening dialogue sessions with decision-makers and stakeholders.For a number of areas within the field of HSR, evidence from quasi-experimental studies forms a substantive component of the overall evidence base for questions on the impacts of interventions. Evidence from quasi-experimental studies may be particularly important for reviews of interventions or exposures whose effects are not, often for practical reasons, easily amenable to measurement using designs based on random assignment of participants or facilities to comparison groups under the direct control of researchers. Quasi-experimental studies, such as regression discontinuity designs, , 23 inteHowever, efforts to integrate quasi-experimental studies into effectiveness review frameworks in both HICs and LMICs are, in general, at an early stage of development \u201328. ThisWith the Harvard School of Public Health, the Alliance organized a workshop in 2013 focused on the following: (1) establishing a taxonomy of quasi-experimental study designs, (2) developing guidelines for systematic review authors on incorporating quasi-experimental studies in reviews, (3) devising strategies to build institutional capacity to support the wider inclusion of quasi-experimental studies in reviews, (4) establishing approaches to translate evidence from quasi-experimental studies for policymakers, and (5) strengthening partnerships between researchers in HICs and researchers in LMICs.One of the outputs of the workshop and the background work commissioned by the Alliance is the identification of five quasi-experimental study designs frequently employed in health systems research: natural experiments, instrumental variable analyses, regression discontinuity analyses, interrupted times series studies and difference studies including controlled before-and-after designs, difference-in-difference designs and fixed effects analyses of panel data .Systematic reviews addressing the full range of health system issues may be useful for decision-making Table\u00a0. HoweverThe EPPI Centre is leading a study, funded by the Alliance, on supporting policy-relevant systematic reviews for health systems. Interviews with policymakers and systematic reviewers have emphasised the importance of connecting these two groups and supporting their mutual engagement with formalised procedures and structures, so as to ensure that their motivations for producing and using systematic reviews are aligned in terms of the urgency and generalizability of products .In addition, members of the Advisory Group are conducting scoping reviews to assess the most appropriate knowledge synthesis methods to answer different types of research questions , 34. Thewww.healthsystemsevidence.org), a database for all types of systematic reviews of HSR. In this database, systematic reviews, and links to their included primary studies, are complemented by a range of other policy-relevant documents addressing health systems, including evidence briefs for policymakers, overviews of systematic reviews, systematic review protocols, economic evaluations and descriptions of health system reforms. The database is available in Arabic, Chinese, English, French, Portuguese, Russian and Spanish; it can be searched using country, region and LMIC filters; it includes links to user-friendly summaries written by other groups. These features make the database a particularly powerful resource for health system decision-makers, stakeholders and researchers. HSE also now includes the beta version for an Intergovernmental Organizations\u2019 Health Systems Documents Portal, developed as a complete inventory of all policy-relevant WHO documents about health systems. Another useful repository is PDQ-Evidence (http://www.pdq-evidence.org), which links systematic reviews of HSR and other health research, overviews of reviews and their included primary studies.The Advisory Group acknowledges the utility and promotes the use of repositories of evidence synthesis in this field, such as Health Systems Evidence (HSE) , was established for this purpose but initially included only reviews of effectiveness. The Advisory Group therefore initiated discussions with PROSPERO regarding how the full range of health systems systematic reviews , the international prospective register of systematic reviews the research domain, for instance human and financial resource constraints for conducting reviews and limited open access to and functionality of databases; (ii) the policy domain, including limited access to HSR systematic reviews and difficulties in assessing both how well evidence syntheses were conducted and how much confidence to have in their findings; and (iii) optimising the linkages between these domains to foster the uptake of findings into policy-making, for instance the alignment of review questions with policy needs and timeliness in the production and uptake of HSR synthesis.Further work of the Advisory Group aims to address these challenges, including capacity development and methods development across these domains. Ongoing work by members of the Advisory Group includes developing norms and standards for qualitative and mixed-methods reviews, building on existing resources , 37 and We argue that early engagement with decision-makers is critical for prioritizing, planning and conducting HSR systematic reviews and for enhancing the relevance and uptake of review findings. In engaging with decision-makers, special attention should be given to the challenge of translating priority policy issues into reviewable HSR questions. Funders of initiatives to strengthen health systems are also a key target audience of the Advisory Group. When designing and funding such initiatives in LMICs, we would suggest that funders take into consideration both available policy-relevant HSR syntheses and the need to build capacity for HSR synthesis.Those conducting reviews should give more consideration, when it is appropriate to do so, to evidence from quasi-experimental studies on the impacts of health systems interventions. Following from this, further development of the methods and standards for incorporating quasi-experimental evidence into reviews is needed. Complementary to developing standards for reviewing is the work of the EQUATOR initiative, which seeks to improve the reliability and value of health research by promoting transparent and accurate reporting of studies and reviews . Given tOverall, the focus on collaborative priority setting for research, judicious choice of study designs and relying on systematic reviews rather than single studies for making decisions about health systems set this work alongside the movement advocating less waste and greater value in biomedical research , 42. We These efforts need continued collaboration and coordination across different organizations, networks and actors. We believe a coordination mechanism like the Advisory Group can fulfil the need for aligning interests, methods and approaches and for securing interest and investments in the field of health systems research synthesis globally.http://www.who.int/alliance-hpsr/projects/hsrsynthesis/en/index.htmlMore information on the activities of the Advisory Group is available at"} +{"text": "The flow of fluids in complex geometries like porous media plays anNIST Tutorial/Workshop on Lattice Gas and Lattice Boltzmann Methods. The organizer was Dr. Nicos S. Martys of the Building Materials Division. The purpose of this workshop was to familiarize NIST scientists and members of industry with the basic ideas of lattice gas and lattice Boltzmann methods and to inform the audience of recent developments in such computational methods.In August 1995, the NIST Center for Theoretical and Computational Material Science and the NIST Building Materials Division [Building and Fire Research Laboratory (BFRL)] cosponsored a workshop titled The workshop was attended by over 50 participants of which approximately 40 % were from industry, 30 % from academia and 30 % from national laboratories.The Lattice Gas/Boltzmann workshop was held over 2 days and divided into two parts. The first part was a tutorial given by Dr. Hudong Chen of Exa Corporation, Cambridge, Massachusetts. Dr. Chen is a world expert on lattice gas and lattice Boltzmann methods having published over forty papers on this relatively new topic. In this tutorial the basic concepts of lattice gas and lattice Boltzmann methods were introduced. The second part of the workshop was devoted to recent developments in, and applications of, these methods. The following sections include representative sample highlights of the workshop.Dr. Xiaowen Shan of Los Alamos National Laboratory discussed a recently proposed lattice Boltzmann model for simulating multi-component, multi-phase flows by incorporating long-range interactions into the fluid dynamics. It was shown that the equation of state of the fluid could be altered from an ideal-gasto one that matches any specific functional form. When the equation of state is properly chosen, the fluid system will separate into multiple phases each of which still obeys the Navier Stokes equation. The coexistence curve, density profile across a liquid-gas interface, surface tension, and diffusivity in a multi-component system were obtained analytically for this model.Dr. Ray Kapral introduced a lattice gas model describing the mesoscale dynamics of spatially distributed, chemically reacting systems. Results were presented for two examples of such systems. First, chaotic front dynamics that arise from diffusively driven instabilities were described. Second, the dynamics of catalytic oxidation processes on metal surfaces was discussed. In this case, the metal-catalysed oxidation was preceded by the coupling of the reaction kinetics to surface phase reconstruction, and gave rise to a rich variety of pattern formation processes on micrometer to submicrometer length scales. Consequently one could begin to probe fluctuation effects and the breakdown of mean field theories in these systems.John F. Olson in collaboration with Dr. Daniel H. Rothman of the Massachusetts Institute of Technology presented results from lattice gas simulations of two-phase flow through Fontainebleau sandstone. The three-dimensional rock geometry, obtained by x-ray microtomography, was used to investigate complex flows through a natural medium. Results were compared with earlier studies of flow through artificial porous media, and with recent experimental measurements on the same media. These comparisons illuminated the potential and the limitations of these techniques.Dr. Norman Margolus of the MIT Lab for Computer Science discussed his group\u2019s involvement in research on large-scale cellular automata (CA) modeling of physical systems. This research has been part of a long term effort to better match computations to the constraints of physics, with the ultimate aim of effectively harnessing the potential of computer hardware that can take advantage of the uniformity, simplicity, and spatial locality of cellular automata computations. Recent developments in dedicated \u201cCellular Automata Machines\u201d have significantly advanced their ability to efficiently and flexibly model and analyze large-scale cellular automata systems.Bruce Boghosian of the Center for Computational Science at Boston University described a lattice gas model of the nonequilibrium dynamics of microemulsions. The model was based on the immiscible lattice gas of Rothman and Keller , which iThe NIST Tutorial/Workshop on Lattice Gas/Boltzmann Methods provided an opportunity for NIST scientists to learn about state-of-art techniques for the modeling of many complex flow problems. The workshop also provided an opportunity for interaction with many of the world leaders in the field of cellular automata modeling of fluids.There has been ongoing research in the application of lattice Boltzmann methods in the modeling of single and multi-component flow in porous media like bui"} +{"text": "After the MOEA-based model construction is finished, the system automatically generates appropriate scatter plots, quantifies the relationships, finds differences between the two populations of models, and calculates the statistical significance of those differences.Coregulation of ionic current levels, and specifically the changes that appear to take place in such relationships in response to deafferentation and pyloric dilator (PD), proposed in . In addi"} +{"text": "BrisSynBio is the Bristol-based Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC)-funded Synthetic Biology Research Centre. It is one of six such Centres in the U.K. BrisSynBio's emphasis is on rational and predictive bimolecular modelling, design and engineering in the context of synthetic biology. It trains the next generation of synthetic biologists in these approaches, to facilitate translation of fundamental synthetic biology research to industry and the clinic, and to do this within an innovative and responsible research framework. BrisSynBio is supported by \u00a313.6 million from Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC), which includes a \u00a33.3 million investment in new state-of-the-art equipment and computing, and significant additional University of Bristol support. BrisSynBio is led by the University of Bristol in partnership with the University of the West of England. It is a multidisciplinary Centre distributed across four Faculties, with an administrative hub in University of Bristol's new \u00a356 million Life Sciences Building . BrisSynBrisSynBio's Director, Professor Dek Woolfson, is one of the U.K.'s leading advocates for advancing and broadening synthetic biology approaches to include biomolecular design and engineering . He has BrisSynBio's scientific focus is on the rational design and engineering of nucleic acids, lipids, peptides and proteins as structural, enzymatic and regulatory components in new biological and bio-inspired systems. BrisSynBio is organized into three research Strands:Strand 1\u2013Enzyme Cascades and Cell Factories: This strand focuses on the isolation, characterization and scalable production of \u2018new-to-science\u2019 natural product-based therapeutics and agrochemicals. A major emphasis is polyketides, the most structurally and functionally diverse family of bioactive natural products known. These molecules represent challenging, frequently intractable targets for synthetic organic chemistry, and as such biosynthesis offers the only generally applicable route to efficient production. Exemplar projects include: engineering Trans-acyltransferase (AT) polyketide synthase (PKS) antibiotic gene clusters to deliver bioactive compounds, led by Willis [Escherichia coli, led by Race [y Willis ; scalabl by Race \u20138; and m by Race .Strand 2\u2013Self-assembled Systems and Minimal Cells: This strand explores using and combining stripped-down biological components and machinery to build virus- and cell-like micro-compartments. It involves the systematic inclusion and networking of engineered biomolecular and cellular components, and gene circuitry to establish biomimetic operations and modules. Achieving this vision depends critically on the construction and design of self-assembled systems, novel representations of synthetic cellularity and re-engineering of minimal cells. Exemplar projects include: developing hybrid peptide-virus nanoparticles for immunology and cell delivery, led by Woolfson [Woolfson \u20134; desigWoolfson ; and engWoolfson .Strand 3\u2013Programming Complexity in Natural Systems: Strand 3 integrates modelling, cell biology and imaging to address the predictable reprogramming and control of single cells, cell populations and cells in multicellular organisms. Applications are envisaged for whole-cell biosensors for the detection, analysis and remediation of aromatic pollutants; the use of engineered cells to control cell populations; and the development of wheat strains with the potential to revolutionize wheat breeding for agriculturally important traits. Exemplar projects include: design and implementation of orthogonal components for transcriptional logic gates, led by Savery [tools for the rational design of synthetic gene circuits [y Savery ; harnessy Savery ; and a sy Savery . The fircircuits .Design and Characterization of Biomolecular Components; Engineering and Modelling across Scales; and Public Engagement and Responsible Research and Innovation. For the second of these, three computational scientists are employed to cover theoretical aspects and computational modelling and simulation. Sophisticated models can help predict the outcome of experiments, and hence inform which experiments are most likely to provide useful outcomes. Additionally, they offer powerful methods for interpreting experimental results. BrisSynBio has built upon existing close relationships between modelling and experimental groups by providing an interface across the scales of modelling that are addressed by different research groups at Bristol so that experimental researchers can readily collaborate with the appropriate group for the scale of problem they are addressing: atomistic molecular modelling and simulation, led by Sessions and co-workers [The Strands are supported by three cross-cutting Themes in: -workers ,3,17; mo-workers ; and coa-workers .fundamental problems, ethics and responsible innovation in the design and engineering of synthetic-biological systems. A philosopher works alongside BrisSynBio researchers, examining what \u2018responsible innovation\u2019 and \u2018ethical science\u2019 mean in practice, as well as fundamental ethical and philosophical questions raised by BrisSynBio's research and synthetic biology activities more broadly. As part of this aspect of BrisSynBio, the Centre and its researchers are proactively involved in a range of public engagement, from traditional science cafes and visits to local schools, to innovations such as Question Time-style panel discussions and supporting a show at the 2015 Edinburgh Fringe [In Theme 3, Kent leads thh Fringe .All of these research activities are underpinned by major new facilities supported through the Centre grant for: high-throughput molecular biology; NMR spectroscopy and peptide synthesis; high-performance computing; microfluidics; FACS; and advanced microscopy and imaging. And to help pave the way to applications, BrisSynBio's current industrial partners include Bruker, GSK, Syngenta and UCB, through which BrisSynBio aims to realize translational outcomes in the areas of fine and specialty chemicals, medicines and healthcare, and wheat breading."} +{"text": "The national roll-outs of evidence-based psychotherapies in the Department of Veterans Affairs (VA) afford an unusual opportunity to study both implementation and sustainability. Although unique in some aspects of management and resources, the VA also serves as an excellent laboratory to understand the implementation of best practices as it is a more organized and controlled environment, free of the barriers faced in other more fragmented segments of the U.S. health care system. In a two-year NIMH grant, we utilized a theory-based model to collect baseline data regarding the adoption of two evidence-based treatments for Posttraumatic Stress Disorder (PTSD), Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT), in a national sample of 38 VA PTSD residential treatment programs with over 200 providers. In a subsequently funded NIMH R01, we are extending our investigation with the same population and model to see: (1) how well PE and CPT are sustained over time, (2) what organizational and individual factors influence sustainability, and (3) what effects implementation and sustained use of PE and CPT have on patient outcomes. Implications for implementation in and outside of the VA health care system will be discussed.Updates on measurement of a model of implementation for health care: advances toward a testable theoryOne comprehensive theoretical model for understanding implementation of innovations was initially developed by Rogers (1962) and elaborated on by others . This model construed implementation as a complex process influenced by five broad constructs: (a) perceived characteristics of innovation, (b) potential adopter characteristics, (c) communication and influence, (d) system antecedents and readiness, and (e) outer context. Although a considerable evidence-base was used to develop the model, the authors did not fully operationalize their model, making it difficult to test formally. Our group undertook a systematic review of the literature and, using an iterative process, we examined existing measures and utilized or adapted items. Where no one measure was deemed appropriate, we developed other items to measure the constructs through consensus. The review and iterative process of team consensus identified three types of data that could be used to operationalize the constructs in the model: survey items, interview questions and administrative data. Over three waves of data collection concerning the implementation of two evidence-based psychotherapies disseminated nationally within Department of Veterans Affairs, we have made changes to the quantitative measurement of aspects of this model including the exclusion of the measurement of some constructs as well as refinement of others . This presentation will review these changes as well as psychometric properties of other constructs and their items.Testing the model using quantitative data for implementation of two evidence-based psychotherapies for PTSD in VA residential treatment programs: outcomes for two yearly time pointsThis study examined the implementation of two evidence-based psychotherapies, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT), in the Department of Veterans Affairs (VA) residential Posttraumatic Stress Disorder treatment programs. The current analyses focused on continued implementation a year after an initial assessment of implementation and of provider and site variables thought to be related to implementation. Seventy-five providers from 38 programs provided complete quantitative data on both baseline and follow-up. At one year follow-up, there was continued effect of supportive organizational context on the implementation of both PE and CPT delivered in a group format.Unlike at baseline, effects of perceived characteristics of treatment on implementation of PE and of supportive organizational context on CPT delivered individually were no longer significant. Rather, social connections predicted a lower likelihood of implementation of CPT individually. These effects all remained, even after taking into account baseline levels of implementation.Implementation of two evidence-based psychotherapies for PTSD in VA residential treatment programs: patient-level outcomesThis presentation will discuss the effects of implementation of two EBTs for PTSD (PE and CPT) in the U.S. Department of Veterans Affairs (VA) residential treatment programs on patients' PTSD symptom severity, alcohol and drug use, and treatment satisfaction. The instruments were administered to patients upon admission and four months post-discharge. The short form of the Mississippi Scale for Combat-Related PTSD was used to measure PTSD and alcohol and drug abuse were measured using the composite indexes from the Addiction Severity Index. Controlling for length of stay and baseline symptoms, implementation of PE and CPT predicted improvement in PTSD symptom severity and alcohol use. The implications of these findings are that two EBTs for PTSD can be feasibly and effectively disseminated to routine clinical settings and implementation produces favorable patient outcomes."} +{"text": "Based on panel data of Chinese listed companies, this paper estimates the impact of low-carbon city policy (LCCP) on enterprise investment efficiency (EIE) by the heterogeneous timing difference in differences (HTDID) method and examines the heterogeneous effect of urban culture on the impact. The results show that LCCP improves EIE, and the research conclusion passes the robustness tests. Mechanism analysis reveals that LCCP mainly acts on EIE along two paths: promoting enterprise technological innovation and easing financing constraint. But the LCCP does not have a significant effect on resource allocation. On urban culture heterogeneity, the ecological wisdoms of green urban culture and Confucian culture, such as benevolence to all beings and the harmony between man and nature, help to enhance the promoting effect of LCCP on EIE. From the perspectives of the synergistic development between formal and informal institutions and of urban cultural governance, this research provides important reference and data support to EIE improvement. Notice on Launching the Pilot Program of Low-Carbon Provinces and Low-Carbon Cities in 2010, kicking off the piloting of low-carbon city development. In the meantime, the Chinese economy is moving from the high-speed growth stage to the high-quality development stage. The further decline of industrial production efficiency has severely bottlenecked the macroeconomic growth of China in recent years. The low-carbon city policy (LCCP) requires cities to clarify their development strategies, principles, and directions during the pursuit of low-carbon development; accelerate the research and development, promotion, and application of low-carbon technologies; build a low-carbon industrial system characterized by greenness, environmental friendliness, and high recyclability; and implement the industrial policies, fiscal and tax policies, and technology promotion policies for low-carbon development, aiming to strengthen the driving role of low-carbon technology innovation on economic development. Enterprises are the most important participant and contributor in the construction of low-carbon cities. Being major emitters of carbon dioxide, enterprises are the core organizers of low-carbon product research and development and need to improve investment efficiency, one of the most effective ways to reduce carbon emissions and lead the construction of low-carbon cities. In the context of China's economic transformation, culture lies at the core of the informal institution and significantly affects economic and social development. The implementation of the LCCP is inseparable from the cultural foundation at the city level. Therefore, it is particularly important to explore the impact of LCCP on enterprise investment efficiency (EIE) and consider the role of urban culture for the implementation of policies. Facing the realistic needs of ecological protection and high-quality development, this paper is aimed at answering the following questions: does China's LCCP help improve EIE? Under the influence of culture, an important informal institution, does the relationship between LCCP and EIE varies with the culture of specific cities?Global warming, a consequence of greenhouse gas emissions, exposes human beings to multiple risks, including sluggish economic growth and worsening living environment. To address these risks, the National Development and Reform Commission of China issued the Rich results have been drawn on the evaluation of the effect of LCCP. Many scholars used the data of Chinese listed companies to evaluate the impact of LCCP on the total factor productivity . For exaBased on the above analysis, this paper intends to reveal the impact mechanism of LCCP on EIE and to empirically test that impact. Taking the LCCP as a quasinatural experiment, the authors estimated the impact of LCCP on EIE, using the heterogeneous timing difference in differences (HTDID) method, and alleviate the endogenous bias through a series of robustness tests. In addition, urban green culture and Confucian culture were taken as examples; the heterogeneous impact of urban culture was examined, revealing the key role of cultural governance in the implementation of LCCP. This is another defining feature of this research. The research findings help to examine the achievements of low-carbon city construction, deepen the understanding of the factors affecting EIE, and provide reliable suggestions for promoting high-quality economic development while implementing low-carbon governance.The main contributions are as follows: firstly, scholars have not reached a consensus on how environmental regulation affects economic efficiency of enterprises \u201311. At tUnder the global trend of carbon reduction, China launched the first batch of low-carbon pilot projects in 2010. Each pilot region was required to explore a low-carbon development model according to its own conditions. Subsequently, the second and third batches of pilot projects were determined in 2012 and 2017, respectively. The pilot regions need to complete the following tasks: establishing a responsibility system for carbon control target, setting up a carbon emission data statistics and management system, formulating supporting policies for low-carbon development, constructing a low-carbon industrial system, and advocating the low-carbon green lifestyle. This paper intends to demonstrate the impact of LCCP on EIE from three aspects: technological innovation effect, financing constraint effect, and resource allocation effect.Specifically, the technological innovation effect refers to the influence of LCCP over EIE via technological innovation. LCCP is an environmental regulation policy proposed by China at the city level to reduce carbon emissions . The infThe financing constraint effect refers to the influence of LCCP over EIE via easing the financing constraint. To integrate the concept of low-carbon development into the production and operation of enterprises, the government has continuously stepped up its support for enterprises. Local governments have made bold explorations and attempts with the help of the autonomy granted by their superiors, such as tax relief, financial subsidies, loan discounts, special funds, and talent incentives, aiming to help enterprises to expand financing channels. Banks and other financial institutions regard the government support and subsidies as implicit guarantees and lower the credit threshold for the enterprises receiving such support and subsidies. For example, the low-carbon urban plans of the pilot regions all cover various financial policies, namely, the special funds for low-carbon development, subsidies for specific industries, preferential loan interest rates, and tax reductions and exemptions. Through capital allocation, these financial policies guide enterprises to reduce investment in polluting projects and invest more funds in green industries and environment-friendly production processes , therebyThe resource allocation effect refers to the influence of LCCP on EIE by affecting enterprise resource allocation. On the one hand, the implementation of LCCP, whether it is the formulation of emission reduction requirements, the collection of pollution taxes, or the trading of pollution rights, will generate new costs, which will cause enterprise production to deviate from the original optimal state. The reason is that environmental regulation will increase the corporate cost of pollution control and system compliance . Some enThrough the above analysis, the following hypotheses were presented.LCCP can promote EIE.LCCP can suppress EIE.LCCP influences EIE via technological innovation effect.LCCP influences EIE via financing constraint effect.LCCP influences EIE via resource allocation effect.Chinese and Foreign Urban Knowledge Dictionary. It is a rather complex and diversified issue. Urban culture, as a way of communication between people and cities, is rooted in the soil of urban historical development and is the characteristic gene of a city. Urban culture has strong regional characteristics, and its development is largely affected by administrative division. Therefore, different cities may vary significantly in terms of culture. As an informal system, culture has an important impact on the economy and enterprise behavior. Urban green development is impossible without the support and guidance of culture. The promotion and implementation of LCCP cannot be detached from the special \u201csoil\u201d of urban culture, especially the green gene in culture. Urban green culture is the value and philosophy of ecoenvironment protection and resource utilization with urban characteristics, both of which gradually form in the process of urban operation and management. As the main body of Chinese traditional culture, Confucian culture has a subtle influence on the behavior of Chinese people. Its ecological ethics and wisdom are highly consistent with modern concepts like ecological civilization and green development. Both urban green culture and Confucian culture carry the gene of green culture, exerting an important impact on the implementation of LCCP. Therefore, this paper takes urban green culture and Confucian culture as examples to explore the different roles of urban culture differences in the implementation of LCCP.Urban culture is mainly defined in two ways: deducing from the definition of culture and defining by the features of the city itself. Concerning the first way, urban culture is defined as the sum of material and spiritual wealth created by people in the city and is the overall form of their living conditions, behavior patterns, spiritual characteristics, and urban features. Concerning the second way, urban culture is defined as a cultural model with urban characteristics jointly created by citizens in the long-term life process and is the sum of urban living environment, lifestyle, and living habits, according to the The Outline of the Tenth Five Year Plan for National Economic and Social Development proposed to break the extensive \u201cblack\u201d development model with GDP growth as the fundamental goal, switching to a resource-saving, environment-friendly, and green path towards sustainable development. Since then, urban green culture has been gradually formed through urban green operation and management and imperceptibly affected the public's values and decision-making. Therefore, Confucian culture and urban green culture are the representatives of traditional culture and emerging culture, respectively, and carry the very gene of green culture. Meanwhile, the two cultures vary greatly from city to city.Confucian culture has a long history of development. After more than two thousand years, Confucian culture has gradually established the core values and moral norms of Chinese culture and has become the ethics of \u201cdaily use without knowing.\u201d With a low per capital ecological wealth, China faces a growing mismatch between the public's pursuit of high-quality life and the insufficient supply of urban development resources. Urban green culture refers to the values and philosophy of ecoenvironmental protection and resource utilization with urban features. These values and philosophy are formed gradually during urban operation and management. Firstly, urban green culture can promote enterprises to generate cohesive and centripetal forces, which are friendly to the environment. By giving play to the guiding role of culture, the awareness of environmental protection can be formed subtly, and employees are encouraged and instructed to care for the environment and make concerted efforts for environmental protection. Secondly, urban green culture will form a binding force in enterprises through institutional norms and responsibility requirements. The social and environmental responsibilities that enterprises should undertake in production and operation will be stressed, motivating enterprises to develop the relevant institutions. Hence, urban green culture will lay a good basis for the promotion and implementation of LCCP and actively shape the influence of LCCP over EIE.The behavior of enterprises is affected by the institutional environment . China iTo sum up, the following hypotheses were presented.The stronger the urban green culture, the more LCCP improves EIE.The stronger the Confucian culture, the more LCCP improves EIE.i and t are the serial numbers of enterprises and years, respectively; Investeffi,t+1 is EIE; LCCi,t is the low-carbon piloting state of the registered city of the enterprise; Xi,t is a series of control variables; \u03bci, \u2211Year, \u2211Industry, and \u2211Province are the fixed effects of individuals, years, industries, and provinces, respectively; \u03b5i,t is a random error; and \u03b2 is the estimate of HDID, the key index of this research.Taking the low-carbon city piloting policy of China as an example, this paper explores how LCCP affects EIE. Since the piloting program starts from different years in different cities, the HDID method was adopted to recognize the influence of LCCP over EIE. The benchmark econometric model can be designed asThe research samples are the nonfinancial Chinese enterprises listed in the A-share board of Shanghai and Shenzhen stock exchanges from 2007 to 2016. Financial enterprises were excluded from the samples, mainly for the following two reasons: firstly, the financial industry, especially the banking industry, is more special than general industries. For example, many banks earn profits from off-balance sheet businesses. Bias is unavoidable if listed banks are analyzed based on the three major financial statements. Secondly, the financial enterprises have different financial statement requirements different from nonfinancial enterprises, because of the difference in business model between the financial industry and other industries. The statement structure and main accounting items of the financial industry are also different from those of general industries. The following samples were also excluded: the samples receiving special treatment (ST) or facing delisting risk (\u2217ST), the enterprises issuing both A-shares and B-shares, and the enterprises with key variables missing. The relevant data were collected from China Stock Market & Accounting Research (CSMAR) database and WIND database.The low-carbon city piloting (LCC) is defined as follows: if the registered city of a listed enterprise implements low-carbon piloting, LCC = 1 in the current and following years; otherwise, LCC = 0. During the sample period, two batches of pilot cities were announced. Hence, the first and second batches of pilot cities were selected as the treatment group. Some cities belong to both batches. As a result, the start time of piloting of a province was taken as that of every city administered by that province.The EIE was measured mainly referring to the research of Biddle et al. and Choii,t is the investment level of the enterprise in year t, which is measured by the ratio of the cash paid for the purchase and construction of fixed assets, intangible assets, and other long-term investments to the total assets at the beginning of the period, and Growthi,t\u22121, Levi,t\u22121, Agei,t\u22121, Sizei,t\u22121, Cashi,t\u22121, Reti,t\u22121, and Invi,t\u22121 are the growth capacity, debt rate, listing period, company scale, cash holding ratio, stock return, and investment level of the enterprise in year t \u2212 1, respectively.The model can be expressed as follows:\u03b5i,t reflects the inefficient investment expenditure of the enterprise. If \u03b5i,t > 0, then the investment is excessive; if \u03b5i,t < 0, then the investment is insufficient. The absolute value of the residual \u03b5i,t was taken to measure the EIE (Investeff). This value reflects how much the enterprise investment deviates from the theoretical expectation. The greater the value, the larger the deviation and the lower the EIE.The regression residual price-earnings ratio has been used as a key variable to measure investor sentiment, which has been proved to bear on the investment behavior of enterprises through equity financing, catering, manager optimism, debt financing, and other channels. Thirdly, the local government would intervene in the economic operation of enterprises by means of government subsidies, guiding local investment, and changing the investment direction and level of enterprises. Fourthly, the duality of chairman and general manager, as an important allocation mechanism of decision-making power, directly affects EIE. Fifthly, market competition can improve information sharing. In a fully competitive market, owners will have reliable information of managers. Thus, the information asymmetry between shareholders and management is mitigated, so that executives will not expand blindly or get complacent, and the enterprises will invest more efficiently. Sixthly, the sustainable growth rate reflects the sustainability of enterprises. The sustainable growth rate can affect EIE through earnings retention and financial structure.The HDID model controls the key explanatory variables and solves the endogeneity induced by the correlation between time-invariable individual features. But the time-varying individual features should be controlled to reduce the estimation inconsistency arising from missing variables. Referring to the literature, this paper selects the following control variables: enterprise size (Size), price-earnings ratio (PE), government subsidy change (Subchange), holding concurrent positions of chairman and general manager , industry concentration (Hhi), and sustainable growth rate (Sgr). In addition, industrial and provincial dummy variables were included. Reasons for choosing the control variables are as follows: firstly, the existing research has shown that enterprises of different scales have different financing constraints, which affect EIE differently. Secondly, Investeff represents the deviation of enterprise investment from the theoretical expectation, the greater the deviation, the lower the EIE. Hence, the empirical results reveal that LCCP significantly enhances EIE. According to column (5) of Next, EIE was divided into excessive investment and insufficient investment and treated as the explained variable separately. On this basis, model was regrDki,t is a series of dummy variables, indicating the k-th year since the implementation of low-carbon city piloting . This paper mainly considers parameter \u03b2k . The other variables in formula between city attribute and time trend to the benchmark regression model, where Sc is the city attribute and f(t) is the first-order term of the time trend. The cross-term controls the time-varying influence of the intrinsic difference between city attributes over EIE. The regression results are recorded in column (1) of The first batch of low-carbon pilot cities in China was designated by the superior government. As for the second and third batches, application and expert review were added as necessary links of determining low-carbon pilot cities. Thus, the list of low-carbon pilot cities is not determined purely by random. To mitigate the negative effect of nonrandom selection on estimation results, this paper adds the cross-term Sc \u00b7 The approval time of low-carbon pilot cities was moved ahead by 3 years, and variable Before_3 was added to model . The regConsidering the effect of its abnormal value, the explained variable was censored at the 1% and 99% quantiles. The regression results are displayed in column (4) of Per capita gross domestic product (GDP) was added to the benchmark model. The regression results are shown in column (5) of Two cross-terms were designed: the cross-term between whether the city is a new energy demonstration city and the time of approval (Ncity) and the cross-term between the city environmental protection criticized by superiors and the time of criticized (HBYT). The two terms were introduced to model . The regTo increase the similarity between treatment group and control group, this paper further removes the provinces without any pilot cities. The regression results are displayed in column (8) of Regarding the measurement of urban green culture, this paper selects the actual year-end number public vehicles and trams/ to depict the green consumption concept of residents. The samples were grouped by the median of the variable and tested separately. The results are shown in columns (1) and (2) of To rule out the possibility that the above results are caused by government intervention, this paper uses the government-market relationship index compiled by Fan et al. to measuNational Sustainable Development Plan for Resource-Based Cities (2013-2020), this paper divides cities into resource-based cities and non-resource-based cities and performs regression on each group. The results are shown in columns (5) and (6) of Compared with non-resource-based cities, many resource-based cities in China lag behind in the construction of urban green culture, due to their long-term dependence on resources. According to the Referring to the research of Du , this paUnder the influence of green culture and Confucian culture, enterprises identify with different goals and pursue legitimacy to different degrees. This paper holds that LCCP has a more positive impact on the EIE in high-carbon emission industries than low-carbon emission industries. To test this hypothesis, the industries were divided into high-emission industry, medium-emission industry, and low-emission industry, according to the trisectional quantiles of carbon emissions of all industries in China, in reference of the carbon emission data in 2009. The relevant data come from Carbon Emission Accounts & Datasets (CEADs). The regression results are shown in The impact of LCCP on EIE mainly manifests as three effects, namely, technological innovation effect, financing constraint effect, and resource allocation effect. These effects are tested separately in this paper.The R&D expenditure reflects the willingness of enterprises to invest in technological innovation. Therefore, this paper selects R&D expenditure as a proxy variable for technological innovation and measures the variables with the ratio of R&D expenditure to operating income. The regression results are shown in column (1) of Scholars mainly use KZ, WW, and SA indices to measure the financing constraint of enterprises , 35. AmoThis paper uses capital allocation efficiency as a proxy variable of resource allocation efficiency and designs model followinThis paper measures the EIE with the Richardson enterprise expectation investment model. The research samples are the A-share listed nonfinancial enterprises in Shanghai and Shenzhen stock exchanges of China from 2007 to 2016. On this basis, the impact of LCCP on EIE was estimated by using HTDID, and the heterogeneous effect of urban culture was also investigated.The main conclusions are as follows:(1) Overall, LCCP improves EIE, and the research conclusion passes a series of robustness tests. (2) Mechanism analysis reveals that LCCP mainly acts on EIE along two paths: promoting enterprise technological innovation and easing financing constraint. But the LCCP does not have a significant effect on resource allocation. (3) The influence of LCCP over EIE varies with urban cultures. The ecological wisdoms of green urban culture and Confucian culture, such as benevolence to all beings and the harmony between man and nature, help to enhance the promoting effect of LCCP on EIEThe policy implications are as follows:First, the positive effect of LCCP on EIE was demonstrated through empirical research. The construction of low-carbon cities is an important means for European developed countries to improve residents' well-being and urban competitiveness. In developing countries, the legal system is relatively weak, and the relevant pilot policies may be difficult to implement. The research results prove that LCCP has the same ideal effect in developing countries like China and can be used as an important means to promote high-quality economic development.Second, strengthening urban cultural governance is of great significance to LCCP promotion. Urban cultural governance focuses on improving the cultural connotation and quality of urban governance. This is particularly true as China witnesses increasing urban scale, rapid construction, the lack of urban culture, and cultural imbalances. Then, it is necessary to highlight the construction of cultural soft power in governance goals and contents. Special attention should be paid to urban cultural governance from the perspective of green development, making cultural governance a powerful guarantee for promoting the progress of urban civilization and green development."} +{"text": "Health Related Quality of Life (HRQoL) is a cornerstone in the evaluation of modern medicines, healthcare practice and other medical interventions . It is oIn health economics, it is useful to perform cost-effectiveness and cost-utility studies by considering the preferences of patients , 9. The Li et al. have evaluated the global, sex, age, region, and country-specific cardiovascular disease (CVD) burden, along with the trends, risk factors, and implications for the prevention of CVD. This study would help explain the characteristics of the global CVD burden in order to set up more effective and targeted prevention strategies. Lobo et al. have studied the need to address potential caregiver-affecting issues at many stages of health planning, recovery, and policymaking in order to generate the evidence to enable stroke caring engagement. In addition, a thorough understanding of the processes involved in stroke care, available services and individual needs and experiences to develop a more realistic approach toward engagement with whom. Cheng and Jin have investigated the association between smoking and HRQoL among Chinese individuals aged 40 years and older using an instrumental variable probit model. Their findings showed that smoking leads to a smaller probability of having a better quality of life, thereby anti-smoking campaigns are then needed to highlight the negative effect of tobacco use on HRQoL. In a multinational study, Ghazy et al. have also assessed the quality of life and its determinants among healthcare workers living and working in the Arab world. The findings of this study indicate that more attention should be administered to this key group in order to ensure their productivity and service provision. Besides, AlKuwaiti et al. have also explored the physical, social, psychological, spiritual, and lifestyle impact of a positive COVID-19 diagnosis on a sample of the UAE population. The study shows that patients with COVID-19 have perceived very good support in terms of their physical health from the government and health authorities, but need social, psychological, and educational support during the infection period and after immediate recovery and post-recovery.To date, plenty of research is conducted in this field and relates, for example, to the choice of the instrument, methodological development, ability to capture specific health dimensions, and lots more. Our Research Topic was open to the subject area of health-related quality of life in healthcare and in clinical practice. Articles included instrument development, new technologies, application, evaluations and outcomes. For example, Shi et al. have assessed the cost-effectiveness of the same-day discharge (SDD) in comparison to that of regular care for primary total hip arthroplasty patients. This is achieved by analyzing the effect using the Oxford hip score (OHS), medical costs (both out-of-pocket and reimbursed), mean incremental cost-effectiveness ratio (ICER), and quality-adjusted life years (QALYs) at 6-month follow up. By a standard cost-effectiveness analysis (CEA), this study would help physicians, government and health authorities to look at SDD in a more precise and efficient approach. Additionally, Shao et al. have also evaluated the cost-effectiveness of camrelizumab plus chemotherapy to treat sq-NSCLC from the Chinese healthcare system perspective. The findings of this economic evaluation approach would provide evidence for clinicians, government and health authorities in making optimal decisions in general clinical practice.With regards to cost-effectiveness analyses, Kharroubi and Kelleher have developed a novel Bayesian non-parametric model for estimating the utility values of health states defined by a generic descriptive system, to generate quality-adjusted life years and hence to conduct cost utility analysis of healthcare interventions. The new Bayesian statistical model also permits the utilization of evidence from one country as potential prior information for a study in another. The results of this study suggest that existing countries' valuations could be used as informative priors to generate better utility estimates than modeling the data from each country separately. This sort of analysis (borrowing strength from existing countries) could be particularly promising in terms of reducing the need for conducting large surveys in every country, which would in turn reduce the cost of cross-country valuation. This will be hugely important for countries where large-scale evaluation exercises are expensive and hard to conduct, particularly for countries with small population size or low- and middle-income countries.To this end, our Research Topic was sealed with a methodological paper where So as a final word, Health Related Quality of Life in Healthcare has become the focus of health related research and practice especially after the COVID-19 crisis which have unveiled systems weaknesses and the need for future preparedness with more evidence based oriented actions and polices which this topic has aimed for.SK participated in the conceptualization of the idea, the design of the Research Topic, editorial drafting, and the final review of the editorial. IB reviewed and finalized the editorial and participated in the conceptualization of the study. All authors have read and approved the final editorial."} +{"text": "The COVID-19 pandemic remains a public health problem threatening national and global health security. The socio-economic impact of COVID-19 was more severe on developing countries including Lebanon, especially due to the fragile healthcare system, weak surveillance infrastructure and lack of comprehensive emergency preparedness and response plans. Lebanon has been struggling with plethora of challenges at the social, economic, financial, political and healthcare levels prior to the COVID-19 pandemic. The COVID-19 pandemic in Lebanon revealed gaps and challenges across the spectrum of preparedness and response to emergencies. Despite these challenges, the Lebanese response was successful in delaying the steep surge of COVID-19 cases and hospitalisations through imposing strict public health and social measures. The deployment of the national vaccination plan in Lebanon in February 2021 coincided with the reduction in the number of cases and hospitalisation rates. The aim of this manuscript is to advance the epidemiologic evolution of COVID-19 in Lebanon pre- and post-vaccination, the challenges affecting the response and recovery, and the lessons learned. Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has been a global public health problem. SARS-CoV-2 has rapidly spread worldwide and accounted for more than 649\u00a0711\u00a0690 cases and 6\u00a0654\u00a0580 deaths until the write-up of this manuscript . Ba. Ba26]. The lifting of PHSMs prior to the availability of COVID-19 vaccines, and specifically during the 2020 holiday season, had a significant impact on the already fragile healthcare system suffering from shortage of medical equipment and medication as well as incentives and livelihood subsidies. This coincided with the detection of the first SARS-CoV-2 variant of concern (VOC), alpha (B.1.1.7) . A sharpThe day 27 January 2021 marked the announcement of the national COVID-19 vaccination plan as well as the launching of an online registration platform, IMPACT, for COVID-19 vaccine registration and reporting of adverse events . The COVThe BNT162b2 vaccine was the first to be delivered to Lebanon followed by the ChAdOx1 vaccine , 37. By Despite all the challenges, the national vaccine campaign was successfully launched and was coupled with a gradual decline in the number of reported cases and incidence rates. The lowest number of reported cases was reported in the period extending between 1 May and 31 July 2021 with an average daily case of 378 and average daily positivity rate of 2.3% and 2. SWith the emergence of SARS-CoV-2 variants and vaccine escape mutants, several studies reported breakthrough infections among fully vaccinated individuals \u201352. HoweAt the beginning of the pandemic in Lebanon, there was limited capacity in detecting, tracing and isolating confirmed COVID-19 cases. The RHUH was the only hospital designated for testing, quarantining and treating confirmed cases . This reSARS-CoV-2 seroprevalence studies are important to estimate the burden of COVID-19 in a population and to understand the dynamics of disease transmission, risk of infection as well as the evolution of the pandemic . While sMoreover, the lack of concerted efforts between academics and national stakeholders as well as lack of information-sharing system resulted in poor engagement of the scientific community in supporting decision-making. Modelling studies, for examples, are important to inform and help policy makers to implement appropriate public health measures and mitigate virus spread. Few modelling studies were conducted in Lebanon to predict the spread of SARS-CoV-2 as well as the impact of COVID-19 vaccination , 70, 71.unpublished data).Importantly, limited genomic data on circulating SARS-CoV-2 variants have been available in Lebanon due to the lack of national genomic surveillance programmes and the lack of concerted efforts between research institutions and the MoPH to support the latter. SARS-CoV-2 genomic surveillance is important to continuously monitor the circulation and emergence of variants in order to guide national public health policies. Scattered reports on limited number of samples revealed the detection of B.1 lineage (20A clade), B.4 lineage (19A clade) and the B.1.1 lineage (20B clade) in 11 samples collected from hospitalised patients between February and March 2020 . Later aThe structure of the national healthcare system had a major impact on the national response to COVID-19. Approximately, 84% of healthcare facilities are located in large cities and most of them are private healthcare facilities . The numDespite all these challenges, Lebanon was able to delay the exponential rise in COVID-19 cases until January 2021 through intermittent lockdowns and community mobilisation. The latter was translated by the engagement of municipalities in sharing information with the MoPH, albeit later during the course of the pandemic, as well as monitoring home isolation for confirmed and suspected cases under their jurisdiction. Few months into the pandemic, the concerted efforts and collaboration between the MoPH, the Ministry of Interior, the Lebanese Red Cross, the United Nations agencies, the WHO and the Disaster Risk Management Unit resulted in better implementation of the national response against the spread of SARS-CoV-2. Moreover, volunteers were trained for contact tracing nationwide, testing and data collection specifically at points of entry (airport and land borders). The ability of the RHUH to care for COVID-19 patients early during the pandemic, the compliance of the Lebanese community to the implemented national strategies and safety measures, and the deployment of the COVID-19 vaccines contributed significantly to the success of the national response.The COVID-19 pandemic revealed global gaps and brought to the surface the need to reimagine the pillars of global health security. Lebanon, similar to other countries, grappled with a variety of challenges that unravelled the dire need for a national strategy cutting across emergency preparedness, response and recovery from crises. This strategy should be applied and sustainable for any type of threat including agents of potential epidemic threats as well as biological, chemical, radiologic and natural disasters. A prioritised plan of action supporting the development of the national health sector strategy on health security as well as strengthening the existing infrastructure is needed. These efforts require rethinking and reimagining the healthcare system and its components in order to manage crises. The COVID-19 pandemic unravelled many structural obstacles and barriers spanning the entire spectrum of emergency preparedness in Lebanon. The need to enhance surveillance and shift from disease-based surveillance into comprehensive surveillance programmes was clear for timely response to disease outbreaks. While this might seem generic, however, Lebanon has been suffering from political instability for the past five decades; the former hampered the institutionalisation of systemic programmes for disease prevention and care. Consequently, political commitment is needed to invest in sustainable capacity building and strengthening and updating the infrastructure of Lebanon's surveillance system and its healthcare infrastructure through: establishing an organic and sustainable link between the public and private sectors, the development of laboratory networks and decentralised yet linked genomic surveillance programme, robust health bioinformatic system for transparent data sharing while linking epidemiologic data to clinical data and genomics; importantly, the coordination between policy makers and research institutions is critical to advance contextual data that will feed into national needs of national stock supplies and supply chain . While researchers are well represented on national, regional and international committees and task forces on prevention and control of infectious diseases and disaster management and while the former had a positive impact on guiding national policies to control COVID-19 in Lebanon, an inherent lack of trust between policy makers and the community was obvious through lack of compliance of the community and lack of catch-up on vaccination depicted through the current low coverage rates. The development of a strong risk communication and community strategy is instrumental in times of emergencies and allows the engagement of communities in policymaking. This is more critical in Lebanon in order to build trust and engage the public in decision-making.Importantly, the recovery from an emergency must begin during the response and consequently, we recommend the development of a national policy for safe return to work, the establishment of a multisectoral recovery task force to coordinate and implement recovery arrangements , and supporting the MoPH to expand resources to strengthen the medical and public health sectors.Enormous efforts and actions were put in place to respond to the COVID-19 pandemic in Lebanon during a progressively worsening economic and financial situation; however, the COVID-19 pandemic revealed the vulnerability, gaps and needs of the healthcare system in Lebanon including epidemiologic surveillance, genomic surveillance, integrated and concerted data sharing, diagnostic capacity, community mobilisation and risk communication. The national commitment to these important inherent components of a rapid response requires resources and investment in human and technical expertise to reduce inequality in access to information and care."} +{"text": "According to the American Psychological Association APA, , Health Several issues and factors are still understudied in Health Psychology. Psychological effects of the COVID-19 outbreak, caregiving experiences, work-related stress and life-work balance, quality of life of sexual minorities, health-related orientations and motivations among younger generations, and the impact of the new media on people's mental health are just a few examples of Health Psychology phenomena that need further investigation. A critical issue in Health Psychology is measurement. A variety of crucial psychological constructs, health-related behaviors, and responses to health, illness, and healthcare need to be addressed and measured in Health Psychology research and practice. Intervention programs designed to foster good health by changing negative health behavior, promoting positive health behavior, and enhancing the management of chronic conditions have been of particular interest to Health Psychology since its beginnings as a distinctive discipline. The availability of psychometrically sound measures is crucial to assessing the effectiveness of such interventions and deepening our understanding of the social and psychological processes of health and illness Apple, .We launched the Research Topic \u201cMeasurement in Health Psychology\u201d in this context. Because measures are a critical part of research and practice in Health Psychology, we were interested in providing an overview of up-to-date measurement principles and methods, which could help improve the process of developing valid, reliable, and sensitive instruments to be used in the fields of Health Psychology.Within this Research Topic, we brought together research studies developing new tools or advancing the psychometric study of existing measures relevant to Health Psychology. Twenty-three articles authored by 105 contributors from different countries and continents were accepted. The research contributions published in this Research Topic relate to self-report measures of socio-environmental and psychological/behavioral influences on health and disease, as framed within the biopsychosocial model Engel, , which hZhan and Wang) presented the development of a new measure to assess the subjective evaluation of harmonious family relations as a resource for physical and mental health. Three independent samples of Chinese university students were enrolled, respectively, for item analysis and exploratory factor analysis (EFA) of the initial item pool; confirmatory factor analysis (CFA) and assessment of internal consistency; and relationships to other variables and test-retest reliability over a two-month interval. Results supported a nine-factor model of family harmony, with adequate reliability and validity as evidenced by positive correlations with criterion measures of subjective well-being and family function, cohesion, and adaptability, and negative correlations with loneliness scores.Six articles in this Research Topic addressed constructs belonging to the social domain of the biopsychosocial model. Three papers dealt with the assessment of family relationships. One of them evaluated the psychometric properties of a Chinese version of the 10-item Family Communication Scale (FCS) to measure positive family communication. EFA and CFA supported a one-factor structure, which showed adequate internal consistency and test-retest reliability and correlated in the expected direction with wellbeing indicators and frequency of communications with family members via Information and Communication Technologies.Another paper proposed a new short measure to assess the bonding between parents and children under 1 year of age, namely the \u201cMe and My Baby\u201d (MaMB) questionnaire. Factor analyses and Rasch calibration performed on data from 434 mothers provided initial evidence that the MaMB reliably measures infant bonding.Finally, UK researchers . Applying CFA and Rasch analysis, the authors found evidence of a unidimensional structure with adequate reliability. Evidence of validity was provided by relationships with a measure of the risk of physical and psychosocial abuse and neglect by primary caregivers. As for formal caregiving, Italian researchers developed a 20-item scale to assess emotional, informational, appraisal, and instrumental social support by healthcare providers in the oncology setting (Tomai and Lauriola). Scale dimensionality and reliability were tested using exploratory structural equation modeling (ESEM) and Mokken scaling analysis. Evidence of validity and reliability and expected associations with doctor communication skills and trust in the physician supported the use of this new measure of healthcare social support as multidimensional a construct.In the context of caregiving, one paper tested the psychometric characteristics of the Zarit Burden Interview in Peruvian informal primary caregivers of persons diagnosed with intellectual disabilities tested the validity and reliability of the School Burnout Inventory among Chilean high school students. CFAs on the 8-item Chilean version supported two statistically equivalent first- and second-order three-factor models of school burnout as composed of exhaustion, cynicism, and inadequacy, which showed gender invariance. Internal consistency and test-retest reliability were acceptable, and school burnout scores correlated as expected with study-related emotions, academic psychological capital, and academic engagement.Finally, as for the school environment, one article tested the psychometric properties of the Farsi version of Perth Alexithymia Questionnaire (PAQ). Based on CFA results, the 5-factor model of the original PAQ replicated well on data from college students, with adequate internal consistency and test-retest reliability. Evidence of associations with other variables was collected for the Farsi PAQ.Nine papers addressed the assessment of individual characteristics and behaviors relevant to health and illness. Within the field of psychosomatic disorders, Iranian researchers . An 11-item Spanish version with three factors was obtained using CFA and ESEM and proved to be invariant across gender and age within and between five different study samples. Reliability coefficients were satisfactory, and correlations with relevant criterion measures provided evidence of convergent and divergent validity.The Work-Related Rumination Scale was tested on a sample of Puerto Rican workers (Lang and Ye) presented a Chinese adaptation of the Self-Objectification Beliefs and Behaviors Scale (C-SOBBS). As a result of exposure to sexual objectification in interpersonal situations and visual media, self-objectification entails viewing one's own body from a third person's perspective and has been linked to poorer women's mental health. The authors found evidence of structural (CFA), convergent, discriminant, and incremental validity, and adequate internal consistency and test-retest reliability for the C-SOBBS. In another paper, Chinese researchers proposed the development and validation of the Psychological Needs of Cancer Patients Scale to identify the psychological care demands of cancer patients . Results of EFA and CFA supported a six-factor model of value and esteem, independence and control, mental care, disease care, belonging and companionship, and security, with acceptable reliability and expected associations with anxiety and depression.As to individual beliefs and expectations, one article . Data from Italian university students were analyzed via EFA and CFA, followed by Rasch analysis. A four-factor model of despair, adjustment, proactivity, and aversion was supported, which was invariant across gender and age and showed adequate reliability. Discriminant and criterion-related validity based on correlations with personality characteristics helpful in coping with disasters and predictive validity on levels of enjoyment and anger 2 months later were also supported. To assess coping strategies to deal with cancer, researchers from Portugal performed a cross-cultural adaptation and psychometric evaluation of the Perceived Ability to Cope with Trauma Scale (PACT). Results of CFA on data from patients recently diagnosed with early breast cancer supported the original PACT two-factor model of coping flexibility as composed of forward and trauma focus domains, which showed adequate internal consistency and associations in the expected direction with self-efficacy to cope with cancer, quality of life and psychological distress.Two articles addressed situation-specific coping. The Robust Pandemic Coping Scale (R-PCS) was developed to assess coping strategies related to pandemic situations at all stages of the epidemic management cycle developed a brief scale to assess the affective, cognitive, and behavioral attitudes of youth and young adults toward condom use. Using EFA and ESEM, the authors found support for the hypothesized three-factor model. The scale showed strong invariance across gender, adequate reliability, and expected relationships with sexual risk behaviors and condom use.In the area of health-related attitudes, Chilean researchers tested the psychometric performance of a very brief measure of problematic internet use, namely the Compulsive Internet Use Scale (CIUS), when used with Lithuanian medical students and resident doctors. Results indicated that the brief, 5-, 7-, and 9-item versions of the CIUS were reliable and valid screening tools to assess the severity of symptoms of problematic internet use in the medical population. Another brief, 6-item scale of excessive use of social networks was adapted for use with Mexican adolescents and young adults . Altogether, the structural properties of the response options fitted the partial-credit model. CFA supported a single domain of addiction to social networks, with measurement invariance across sex, age, and educational campus, good internal consistency, and theoretically consistent associations with sensation seeking and depression.Among health-related behaviors, one study presented the traditional Chinese version of the Recovering Quality of Life (ReQoL) outcome measure. The ReQoL measures mental health recovery, defined as a self-directed process of healing and transformation, which has received increasing attention in evaluating the outcomes of mental care. The Chinese ReQoL showed good psychometric properties in terms of internal consistency, test-retest reliability, factor structure (CFA), known-group validity, and associations with relevant variables in the general population.A total of eight papers focused on assessing outcomes of the interactive relationships between biological, environmental, and psychological/behavioral factors. Two papers focused on health-related quality of life (HRQoL), which is a primary outcome in the evaluation of interventions' effectiveness on people's health. One article examined the validity and reliability of the Minnesota Living with Heart Failure Questionnaire in individuals with coronary artery disease. EFA and CFAs supported a three-factor model of physical, social, and emotional disease-specific HRQoL. The Lithuanian version was reliable and showed evidence of convergent validity based on correlations with another measure of HRQoL (SF-36) and with exercise capacity assessed using a standardized computer-driven bicycle ergometer.Lithuanian researchers . CFA confirmed a bifactor model, which was invariant across gender and age in a sample of university students. Based on reliability analyses, the authors advised against the interpretation of specific-factor scores and recommended the computation of a general wellbeing score.Six papers addressed the assessment of indicators of mental health or adjustment to health problems. One of them presented the validation of a Kazakhstani version of the Mental Health Continuum\u2013Short Form to assess emotional, social, and psychological wellbeing presented the validation study of a multidimensional inventory for the assessment of mental pain after traumatic experiences (FESSTE30) in the German speaking general population. CFA showed a satisfactory fit of a five-factors measuring somatization, depression, intrusive memories, dissociation, and anxiety. The scale showed evidence of reliability and strong correlations with measures of psychological distress, PTSD symptoms, and the extent of traumatic experiences.Another article . Based on the results of PCA and CFA, the authors proposed a revised model (MI-RSWB-R) with general religiosity and connectedness domains reflecting religious and spiritual wellbeing, respectively, and suggested using the remaining subscales to gain insight into specific, separate facets of wellbeing. All MI-RSWB-R domains showed adequate reliability and relationships with the centrality of religiosity.The Swedish version of the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB) was psychometrically tested to assess the spiritual wellbeing of a large sample of university students tested a Brazilian-Portuguese version of the 12-item Infertility-Related Stress Scale (IRSS-BP) to assess adjustment to the infertile condition. ESEM showed a bifactor model with one general and two specific intrapersonal and interpersonal stress factors, which was invariant across Brazilian and Italian infertile individuals. All three IRSS-BP factors showed adequate composite reliability and theoretically meaningful associations with gender, infertility duration, and depression scores.Brazilian and Italian researchers tested the psychometric properties of the Starkstein Apathy Scale (SAS) to assess apathy in a sample of English speaking people having experienced a stroke. A revised 9-item version of the SAS targeting impairment of apathy/motivation was obtained, which was unidimensional and reasonably reliable, with no substantial item differential functioning across time, age, sex, and education.Using Rasch's partial-credit model, correlation, and regression, one study . Ego integrity in older people is crucial to help them achieving successful aging and a better quality of life. Through a three-step process involving expert validity and piloting, item analysis and principal component analysis, CFA, and assessment of reliability and relations to criterion measures, the authors found acceptable validity and reliability evidence, supporting the use of the Chinese IPB.Chinese researchers developed and tested a 40-item short form of the Inventory of Psychosocial Balance (CIPB-SF) to assess ego development based on Erikson's theory in Chinese older adults (In this Research Topic, we invited researchers from around the world to contribute to measuring key constructs in Health Psychology by sharing the development and improvement of measures to be used by Health Psychology researchers and clinicians.Two-thirds of the accepted papers presented further development and validation of existing instruments for use in different cultural contexts or populations with specific characteristics. This emphasizes that the validation process is never complete but is instead an ongoing process, which involves collecting multiple types of evidence to support the appropriateness and meaningfulness of inferences and decisions made from measurement scores Messick, . Most paAltogether, 23 measures with promising psychometric characteristics are made available to researchers and clinicians to ensure a valid and reliable assessment of psychosocial variables and behaviors that may influence health and illness, as well as to evaluate health outcomes and monitor the effectiveness of Health Psychology interventions. This Research Topic certainly does not exhaust the issue of measurement in Health Psychology. Still, we hope that other colleagues will take new initiatives to further share the development and testing of valid, reliable, and sensitive instruments to be used in Health Psychology research and practice.All authors listed have a substantial and equal contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Measurement-Based Care (MBC) is an emerging healthcare model with a number of potential advantages over traditional approaches for the treatment of substance use disorder (SUD). Despite SUD treatment programs being theoretically well suited for the implementation of MBC, its uptake has been minimal, which in turn limits further research, knowledge synthesis, and translation into clinical practice.The goal of this knowledge synthesis project is to stimulate greater consideration of MBC models in addictions programs, with three interrelated objectives: 1. To summarize the existing evidence from research literature 2. To complement the literature findings with the data from our clinical research and quality improvement projects 3. To explore potential risks and difficulties of MBC implementation in the SUD treatment programsNarrative review. Knowledge synthesis.To date, only two published randomized controlled trials, which along with the data from our pragmatic clinical research, support the wider implementation of MBC in the substance abuse treatment settings, but also indicate the high need for larger-scale clinical trials and quality improvement programs. Potential barriers to the implementation of MBC for SUD are outlined at the patient, provider, organization, and system levels, as well as challenges associated with the use of MBC programs for clinical research. Critical thinking considerations and risk mitigation strategies are offered toward advancing MBC for SUD beyond the current nascent state.The state-of-the-art of MBC in SUD care settings reviewed and the strategies for further development from adminsitrative, clinical, and research prospectives outlined.No significant relationships."} +{"text": "QEEG is a modern electroencephalography (EEG) analysis that records digital EEG signals, which are processed, transformed, and analyzed using complex mathematical algorithms. When Hans Berger recorded the first EEG of a human brain in 1924, his observations were limited to the time domain. Still, he suggested that frequency analysis would improve the interpretation of EEG signals in the future. QEEG has brought new EEG signal feature extraction techniques: analysis of specific frequency band and signal complexity, analysis of connectivity, and network analysis. The role of QEEG is not necessarily to pinpoint an immediate diagnosis but to provide additional insight in conjunction with other diagnostic assessments for obtaining a precise result and disease severity stage or specific treatment response evaluation. The clinical application of QEEG is extensive, including neuropsychiatric disorders, epilepsy, stroke, dementia, traumatic brain injury, and many others.Neurotechnology establishes strategic connections between various disciplines, from neuroscience and medicine to engineering and artificial intelligence, tackling the more profound understanding of fundamental brain principles and enhancing the advancement of new technological methods in experimental and clinical settings.EUNeurotech, the European University of Brain and Technology, brings together eight leading European universities, partner research institutions, companies, societal stakeholders, cities, and (non) governmental organizations to build a trans-European network of excellence in brain research and technologies to increase the competitiveness of European education, research, economy, and society. In this context, the University of Medicine and Pharmacy Iuliu Ha\u021bieganu (UMFIH), through the Erasmus+ department, developed the first Blended Intensive Program (BIP) within the NeurotechEU Alliance, organizing the QEEG Summer School (QEEGSS). BIP aims to open more opportunities for learners to participate in blended mobilities, supporting the development of transnational and transdisciplinary curricula and innovative teaching methods such as research-based learning and challenge-based approaches.th and 15th, 2022, to promote a basic understanding of QEEG analysis and its applications in a multidisciplinary environment. This innovative event was the first BIP of the NeurotechEU alliance, developed with its academic partners: UMFIH through Erasmus+ department and RoNeuro Institute for Neurological Research and Diagnostic.The first edition of the QEEGSS educational program was conducted in Cluj-Napoca, Romania, between July 11e.g., medical school students, psychologists, neuroscience or PhD students) from six European countries , facilitating multidisciplinary interaction and exchange of skills.The five-day training followed a simple-to-complex approach, from the source and principles of EEG to the most complex types of QEEG analysis. It provided early-stage researchers with a basic yet modern understanding of where QEEG has arrived today and potential avenues for its development. QEEGSS brought together junior researchers with a common interest in QEEG and distinctive backgrounds and the Society for the Study of Neuroprotection and Neuroplasticity (SSNN) .This educational and practical event was set up to unfold over 5 days in two locations: UMFIH on the first two days and RoNeuro on the following days for the hands-on sessions. Furthermore, as part of the BIP recommendations, the final lecture was developed as a virtual course with innovative interactive resources. A total of 23 delegates from different countries participated in the intensive program: Germany \u2013 Bonn University (6 delegates), Bulgaria \u2013 Medical University of Sofia (4 delegates), the Netherlands \u2013 Radboud University (3 delegates), Slovenia \u2013 Maribor University (2 delegates), Hungary \u2013 Debrecen University (1 delegate), Romania \u2013 UMFIH (6 delegates), Carol Davila University of Medicine and Pharmacy, Bucure\u0219ti (1 delegate).Participants were given the opportunity to share their knowledge and experience on conventional EEG, discuss and question basic concepts, and analysis of QEEG. Ultimately, the delegates were divided into five teams, and the goal of each team was to develop a project idea that involved the QEEG assessment of subjects with specific pathology. Then, being provided with a potential methodological approach, they were invited to build up a research proposal and an elevator pitch as they were applying for a grant, convincing the evaluation board that their ideas were relevant and feasible.All participants were early-stage researchers with distinctive backgrounds from medical sciences up to psychology, with an interest in the QEEG assessment of neuropsychiatric physiology and pathology.Prof. Dafin Fior Mure\u015fanu opened the QEEGSS with an overview of the new paradigms in neurophysiology research and the importance of extending the knowledge about neuroscience inside an ever-increasing technology in this field.After the introduction, the participants were divided into five teams and encouraged to propose a research hypothesis aligned with their shared interests, which could be tested through QEEG. Each team came up with creative project proposals, such as:The effects of antidepressants on sleep architecture in offspring rodents with a history of prenatal stress;The benefits of mindfulness meditation in young ADHD subjects;The effects of imagination of motor action on mu waves.In the second part of the day, Dr. Livia Popa lectured on the fundamentals of EEG, describing the sources of the electric scalp activity and recording principles . ThroughThe following presentations focused on spectral analysis, time-frequency decomposition, and various connectivity analyses. First, Dr. Victor D\u0103bal\u0103 presented how a Fourier transformation (FT) works, emphasizing the Fast Fourier Transform (FFT) and the convolution theorem. Next, Dr. Diana Chertic introduced the most used methods for obtaining time-resolved frequency representations of EEG data and for assessing the connectivity in the time domain. Finally, Dr. Hanna Drago\u0219 covered the basics of several connectivity methods such as coherence, phase-locking value, and the Granger causality. By being asked to fixate on a central flashing dot while ignoring the dots existing anywhere else in the visual field, the participants were introduced to the concepts of selective attention and motion-induced blindness as changes in communication structure between brain areas. QEEG applications in daily neurological practice were highlighted through clinical cases that entertained the participants in debates on differential diagnoses from neurodevelopmental to neurodegenerative disorders.The third day occurred at the RoNeuro Institute for Neurological Research and Diagnostic. The institute has a multidisciplinary clinical activity and a research branch driving innovation in neuroscience across sectors. The day started with Dr. Livia Popa offering an interactive and comprehensive presentation about EEG patterns, types of activity, and artifacts. The participants were also instructed on the features of EEG in neurological disorders, comprising a full dive into the complex concept of EEG.Dr. \u0218tefan Strilciuc then coordinated a hands-on experience targeting the Independent Component Analysis (ICA) technique, used for two fundamental QEEG steps: cleansing the data prior to the analysis and identifying the brain sources of specific signal patterns.The hands-on session continued on the fourth day, when the participants could record the EEG of a randomly assigned participant. Afterwards, they were instructed on the preprocessing and analysis of the recorded signal, both activities led by Dr. Livia Popa. Using the EEGLAB software, the time series data was first referenced, filtered, cleared from artifacts and bad segments, and analyzed using FFT and time-frequency decomposition. Some source reconstruction techniques were also employed, and the participants were introduced to the forward and inverse problems.The last day of QEEGSS started with an online lecture, which offered a basic overview of several technologies that can be used in conjunction with QEEG, covering their development, functions, mechanisms, and research applications. Therefore, concepts like transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), eye tracking (ET), magnetoencephalography (MEG), transcranial direct-curent stimulation (tDCS) and transcranial alternating current stimulation (tACS) were developed through innovative interactive virtual resources by Dr. Irina Vlad.QEEG participants had the opportunity to enrich their local experiences by attending various leisure and cultural activities, such as familiarizing with the Romanian culture and language, exploring the Turda Salt Mine (recently considered for UNESCO heritage inclusion), sharing a multicultural dinner, experiencing a deep dive into the history and architectural landmarks of Cluj-Napoca through a guided visit to the city's historical center, and, lastly, exploring the Alexandru Borza Botanical Garden.The QEEGSS lectors and participants contribuEU. As quantitative electroencephalography is becoming a reliable tool for experts in the interconnected fields of neurosciences and biotechnology, the event cleared a possible pathway regarding the interest of future generations in exploring the boundaries of their field of expertise.The first edition of QEEGSS marked the beginning of BIP educational events within the alliance of NeurotechConsidering the critical significance of international collaboration and the continuous need for multidimensional and multidisciplinary approaches for neurotechnology applications in research settings, the QEEGSS offered a peak into QEEG and its potential to drive developments in clinical neuroscience and beyond."} +{"text": "Dear Editor,Along with the increasing administration of COVID-19 vaccines, in the last months, the detection of potential adverse skin reactions has increased, highlighting the possibility that not only SARS-CoV-2 infection but also COVID-19 vaccines can induce cutaneous manifestations.A 61-year-old Caucasian woman presented to our department with a 3-month history of ten, symmetrical, whitish, xerotic and sclerotic plaques, with a diameter ranging between 5\u202fcm and 12\u202fcm localized in the abdominal area, lower limbs, back and upper limbs A. Her faGM is identified by more than four plaques, at least 3\u202fcm, that involves two or more anatomical regions and differs from scleroderma by the absence of Raynaud phenomenon, sclerodactyly, facial involvement, nail fold involvement, and specific autoantibodies.None declared.Giovanni Paolino: Study concept and design; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; writing of the manuscript or critical review of important intellectual content; final approval of the final version of the manuscript.Matteo Ricardo Di Nicola: Writing of the manuscript or critical review of important intellectual content; final approval of the final version of the manuscript.Nathalie Rizzo: Study concept and design; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; final approval of the final version of the manuscript.Santo Raffaele Mercuri: Study concept and design; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; final approval of the final version of the manuscript.Nathalie Rizzo and Santo Raffaele Mercuri share the co-last authorship.None declared."} +{"text": "Exosomes are a class of extracellular vesicles (EVs) comprising a heterogenous population of biological nano-vesicles enclosed by a lipid bilayer . All eukShpigelman et al., at the University of California, San Diego, CA, United States, are reporting a pioneering study developing a reporter cell line for quantitative measurement of EV release from antigen-presenting cells (APCs) in a phenotypic high-throughput screening format. They show that the new, dual-reporter cell line exhibits robust responses and has the potential to become an excellent research tool for the screening of compounds that induce or inhibit EV release by APCs. An article by Shukla et al., at the University of California, San Diego, CA, United States, aimed at identifying small molecules that could induce EV release in a human monocytic leukemia THP-1 reporter cell line. They described a process of screening the EV release that could add a new dimension to structure-activity relationship studies of vaccine adjuvant activity. A study by Olivero et al., at the University of Genoa, Italy, addresses the important question of whether exosomes are actively released from presynaptic nerve terminals. Their findings provide strong evidence supporting the release of EVs from presynaptic structures and indicate an increased EV release upon exposure of synaptosomes to a depolarizing stimulus.Alsop et al., from the group of one of our Research Topic Editors, Dr. Kendall Van Keuren-Jensen at the Translational Genomics Research Institute, Phoenix, AZ, United States, together with multiple collaborators, have generated an atlas of small RNAs from 30 different tissues and three different blood cell types. They analyzed various tissues for the enrichment of small RNA sequences, assessed their expression in different human biofluids in cell-free circulation as well as from EVs on the miRNA cargo in cerebrospinal fluid-derived EVs and to determine if AD risk factors have an impact on EV-associated miRNA expression patterns. Their study showed that APOE-\u03b54 and female sex, two known risk factors for the disease, influence EV-associated different miRNA levels in the CSF of patients with AD. Bilousova et al., at UCLA, CA, United States, led a multi-omics study analyzing putatively microglia-originating small EVs from cryopreserved human brain tissue in search of novel biomarkers for Alzheimer\u2019s Disease. The analysis included lipids, proteins, and miRNAs in microglia-originating small EVs from human brain tissue and indicated the release of neuronal and myelin materials via EVs. Another important finding was a significant decrease in docosahexaenoic acid levels in AD, which potentially could be used as a biomarker. A review article by Ghosh and Ghosh from the Indian Institute of Technology Jodhpur, India, described in detail the role of small EVs as pathogenic agents transmitting toxic protein forms that propagate neurodegenerative disorders throughout the CNS. It is becoming increasingly evident how small EVs can be harnessed in identifying neurodegenerative disease biomarkers , Milan, Italy, demonstrated that EVs isolated from the plasma of patients with COVID-19 harbor SARS-CoV-2-related protein materials. They observed that EVs recovered from patients with mild symptoms effectively modulated antigen-specific CD4-positive T-cell responses. The study also suggested that the patient-derived EV-associated proteins not only induced an immune response, but also the EV cargo could help identify the pathological state of patients in the acute phase of the disease.A timely study by Moros et al., at the Universidad de Zaragoza, Zaragoza, Spain, and Istituto di Scienze Applicate e Sistemi Intelligenti, Pozzuoli, Italy, isolated EVs from the freshwater cnidarian polyp Hydra Vulgaris and investigated their biochemical, morphological, and functional characteristics. The analysis showed that EVs released by this species transfer protein and major components of axial patterning, modulating foot and head regeneration. A review article by Fang et al., China Agricultural University, Beijing, China, and Dr. Brett M. Tyler Oregon State University, Corvallis, OR, United States compiles information regarding recent research on the biogenesis of EVs and their pathobiological functions in organismal communication of microbes. The authors highlighted key questions related to the transfer of genetic materials between species which requires further exploration in this direction.Kutchy et al., at the University of Nebraska Medical Center, Omaha, NE, United States, and collaborators in Grenada and China showed that EVs could be used as a vehicle for the effective delivery of drugs to the brain. The authors investigated the biodistribution of ultra-small, iron oxide-labeled, mouse astrocyte-originating EVs after intranasal perfusion in mice and suggested that engineered EVs could be utilized for targeted delivery of therapeutics into several organs including the brain. In another review article, Zheng et al., from Fudan University, Shanghai, China, summarized the current research advances on the involvement of EVs in the pathogenesis, diagnosis, and treatment of the autoimmune disease, systemic lupus erythematosus (SLE) and lupus nephritis (LN). In this article, the authors have discussed the role of several immune cell-originating EVs in the regulation of the innate immune responses and highlighted the necessity of further research to fully understand the involvement of EVs in the pathophysiological mechanisms of SLE and LN.The delivery of therapeutics across the blood-brain barrier for brain disorders has remained challenging despite recent progress . A studyKang et al., at the University of Illinois, Chicago, IL, United States, studied the effects of the inflammatory cytokines on mesenchymal stem cell-derived EV-mediated immunomodulation. They concluded that TNF\u03b1 preconditioning of human mesenchymal stem cells results in the generation and release of EVs that can alter the phenotype of macrophages, both in vitro and in vivo. Corsello et al., at the University of Texas Medical Branch at Galveston, TX, United States, investigated the presence of innate immune mediators, including interferons in EVs, released from airway epithelial cells infected with the respiratory syncytial virus. The study found significant levels of soluble and EV-associated interferon \u03bb in nasopharyngeal secretions (NPS) and NPS-derived EVs from children with respiratory syncytial virus infections.While EVs have been extensively studied in the field of cancer and someOverall, this Research Topic covers broad aspects of extracellular vesicle biogenesis, their isolation and characterization strategies, involvement in intercellular communication, and the roles EVs play in different human diseases. The topic also includes articles that investigated and discussed the possibilities of using small EVs as potential disease biomarkers and opportunities for therapeutic applications. These basic, translational, and clinical studies demonstrate the importance and high potential of EVs in human health and diseases including neurodegenerative disorders and cancer, as well as in understanding intercellular communication in low organisms, including microbes and polyps. Future scientific efforts to fully understand the mechanisms of EV-mediated cell-cell communication in health and different disease states are expected to provide critical insights into basic biological processes, development of biomarkers, identification of therapeutic targets, and harnessing EVs as a vehicle for drug delivery."} +{"text": "From ancient times to the present, mankind has experienced many infectious diseases, which have mutually affected the development of society and medicine. In this paper, we review various historical and current infectious diseases in a five-period scheme of medical history newly proposed in this paper: (1) Classical Western medicine pioneered by Hippocrates and Galen without the concept of infectious diseases (ancient times to 15th century); (2) traditional Western medicine expanded by the publication of printed medical books and organized medical education (16th to 18th century); (3) early modern medicine transformed by scientific research, including the discovery of pathogenic bacteria (19th century); (4) late modern medicine, suppressing bacterial infectious diseases by antibiotics and elucidating DNA structure as a basis of genetics and molecular biology ; and (5) exact medicine saving human life by in vivo visualization and scientifically verified measures (after the 1990s). The historical perspectives that these five periods provide help us to appreciate ongoing medical issues, such as the present COVID-19 pandemic in particular, and remind us of the tremendous development that medicine and medical treatment have undergone over the years. From ancient times to the present day, the most important mission of medicine and medical care has been to diagnose and treat illnesses. It is well known that medicine before the 18th century was fundamentally different both in medical perception and medical scientific technology from what followed . Until tAfter recent studies on the history of medical education ,4, we neSince the beginning of the year 2020, the COVID-19 pandemic caused by SARS-CoV-2 has not only inflicted severe damage on the world economy but also caused indescribable suffering to people around the world. Although this experience has been a very disastrous one, it has also provided us with an opportunity to once again reaffirm the relevant roles of medicine and medical care for the world. At the same time, it is also relevant to recall the emergence of these great infectious diseases that have occurred one after another in history as part of the common experience of humankind.The Western medical tradition began in ancient Greek and Rome since 5th century BC, long before the discovery of infectious pathogens and without the concept of infectious diseases. The medical documents of Hippocrates and Galen were handed down and compiled into medical textbooks in the Middle Ages. From the records they contain of several devastating plagues, their causative pathogens have been investigated and interpreted by modern researchers from the symptoms and the modes of progression described therein.Corpus Hippocraticum) . Phy. PhyTheopeatedly .Box 1Theoria (theory of medicine), the theoretical foundations of medicine in five subdivisions, including Physiologia, Pathologia, Semeiotica, Hygiena, and Therapeutica(A) Practica (practice of medicine), the individual illnesses(B) Anatomia et Chirurgia (anatomy and surgery), the structure of the human body as a basis of medicine, and its application to surgical operations(C) Botanica et Pharmatica (botanics and pharmaceutics), botanical remedies, utilizing botanical or herb gardens for education and research(D) Practica books dealt with the diagnosis, therapy, and prognosis of individual illnesses, including both the regional illnesses a capite ad calcem (from head to toe) and systemic illnesses such as fevers [Practica books, indicating there was no collective concept of infectious disease at that time , gastrointestinal symptoms (diarrhea and vomiting), respiratory symptoms (cough and dyspnea), and so on, were confused with the diseases and represented the illness. In the 19th century, the pathological changes of organs found by postmortem autopsy were regarded to be the cause of diseases, or the illness itself. There are several diagnostic innovations observed during this time Box 2)..Box 2).Box 2Jean-Nicolas Corvisart: Discovery of the diseases of the heart and great arteries conducted in vivo diagnosis using the chest percussion maneuver (1806).Ren\u00e9 Th\u00e9ophile Hyacinthe La\u00ebnnec: Development of indirect auscultation and discovered pulmonary diseases supported by observations made during autopsy (1819).Richard Bright: Discovery of the kidney diseases by autopsy of dropsy patients after scarlet fever (1827), which came to be known as Bright\u2019s disease.Rudolf Ludwig Carl Virchow: Cellular pathology (1858) and recommended histopathological diagnosis, which improved the accuracy of pathological diagnosis.Surgery up to the 18th century had high risks of developing bacterial infections peri- and post-operationally, and its application was limited to the treatment of wounds and tumors on the body surface. The British surgical scientist Joseph Lister proposed a disinfection method using carbolic acid in the 1870s and later developed a surgical sterilization method. In the mid-19th century, ether anesthesia was performed in a public surgery in the United States (1846), and the anesthesia method spread rapidly to Europe and the United States. These innovations enabled surgical operations of visceral organs deep in the body, such as the digestive, respiratory, and reproductive organs .Box 3Joseph Lister: A disinfection method using carbolic acidin the 1870s and later developed a surgical sterilization method.TheodorBillroth: Pyloric resection (1881) and gastrectomy (1885)William Halsted:Development of radical mastectomy for breast cancer (1889)Harvey Cushing: Apioneer of brain surgery (from 1912)With the Industrial Revolution and urbanization in the 19th century, the water-borne diseases of dysentery and cholera became common causes of death in many countries see Sup.contagio\u201d (contact) had been used since the 16th century [In the mid-19th century, the causes of plagues and epidemics were still obscure, and miasma (contaminated air) and contagion (disease seeds) were discussed as possible causes of diseases. The German anatomist Jakob Henle (1840) classified the causes of diseases into miasmas, contagions, and miasmatic-contagions . The con century .Bacillus anthracis [Mycobacterium tuberculosis (M. tuberculosis) (1882) [Vibrio cholerae (V. cholerae) (1884) [Yersinia pestis (Y. pestis), the pathogen of the plague (1894). Bacteriology was the mainstream state-of-the-art science, leading to the discovery of numerous pathogens during this period and reventhracis , Mycobac) (1882) , and Vib) (1884) , all thrs period .specielle Pathologie\u201d in German, and \u201cpathologie interne\u201d in French. In these textbooks, the diseases of organs were arranged according to individual organ systems in addition to systemic diseases. As the most popular textbook in this period, Niemeyer\u2019s Lehrbuch der speciellen Pathologie und Therapie (1858) [In the 19th century Europe, medical textbooks dealing with the diagnosis, therapy, and prognosis of individual diseases were published under various titles such as \u201cpractice of medicine\u201d in English, \u201ce (1858) recognizIn the 20th century, the increased international mobility and the worldwide wars spread serious airborne infectious diseases, such as influenza and tuberculosis. On the other hand, medical science succeeded in overcoming the infectious diseases by antibiotics against bacterial pathogens and by identifying specific pathogenic viruses.The investigation of antimicrobial agents began with the discovery of pathogenic bacteria at the end of the 19th century. Salvarsan and sulfonamides were produced by chemical synthesis in 1911 and 1935, respectively . AlexandStaphylococcus aureus (S. aureus) was, however, reported in 1942, the same year of the introduction of Penicillin G [S. aureus (MRSA) was first reported in 1961 [Bacterial infectious diseases were significantly suppressed by antibiotics, and deaths from infectious diseases such as tuberculosis and gastroenteritis decreased sharply after World War II . Penicilcillin G . This le in 1961 , and rap in 1961 [At the end of the 19th century, while bacteria were discovered, viruses such as influenza and smallpox were not yet known. Tobacco mosaic virus was the first virus to be discovered in 1892 by Dmitri Ivanovsky . Dutch ms fluid) . At the s fluid) .The electron microscope, invented in 1938 by German scientists Max Knoll and Ernst Ruska, enabled the observation of virus morphology . During By the mid-19th century, the records of six influenza pandemics remained ,42, and Principles and Practice of Medicine [In the early 20th century, infectious diseases increasingly attracted the attention of researchers after the discovery of pathogenic bacteria at the end of the 19th century. The contents of medical textbooks in this period generally listed the infectious diseases at the top, followed by diseases of organs in various organ systems, as exemplified by the most notable textbook of the time, Osler\u2019s n, 1920) , initially introduced in 1977 for the treatment of herpes simplex virus infections caused by HSV-1 (herpes simplex virus type 1) ,47. SoonSeen from the perspective of the history of medical science, current medicine obtained robustness in the diagnosis and treatment of infectious diseases. Even though human society faces emerging issues such as the ongoing pandemic, the global burden of antimicrobial resistance remains one of the most urgent health threats. AIDS is still the leading cause of death across Sub-Saharan Africa, although antiviral drugs have been developed. Since the beginning of the 21st century, three coronavirus pandemics have emerged, the present one of which is still ongoing see Sup.The outbreaks occurring prominently during the period of exact medicine are associated with interactions between humans and domestic and wild animals. In fact, approximately 75% of emerging human diseases in the period of late modern medicine and exact medicine have been zoonotic ,51. One Harrison\u2019s Principles of Internal Medicine, 20th edition (2018) [Since the end of the 20th century, various novel categories of diseases were recognized in addition to infectious diseases and diseases of the organs, including malignant tumors, autoimmune diseases, endocrine and metabolic disorders, and diseases caused by environmental factors. These topics were included in the medical textbooks in this period as exemplified by the widely adopted, best-selling American textbook n (2018) (see SupBy following the history of medicine since the ancient Greek and Roman period and the severe experiences with various infectious diseases, we can better appreciate the current state of medical scientific achievement. When seen through the historical viewpoint on infectious diseases, advanced \u201cexact medicine\u201d has greatly minimized the impact of COVID-19, which has caused significant damage to society and humanity. The fear of COVID-19 has been remarkably reduced thanks to exact medicine, and human civilization must continue to co-exist with SARS-CoV-2. The world in the post-COVID era may never be the same as before, as the historical infectious diseases changed society, economy, and human life in each epoch. It is evident that novel world health issues will continue to emerge. In 2022, as the COVID-19 pandemic continues, monkeypox outbreaks have been reported from non-endemic and endemic countries in widely disparate geographical areas . Further"} +{"text": "Cultural competence and related terms began to appear in the 1960s in the context of the development of civil rights movements in many countries. The importance of research of cultural competence among mental health professionals is raised with the globalization trends of the modern world, when the growth of ethno-cultural diversity, internal and external migration, temporary movement of people lead to intensification of intercultural interaction.The current study aims to reveal contemporary tendencies in cultural competence understanding and development.Theoretical analysis and systematization of research publications in order to clarify concepts, models and applications of cultural competence.The following tendencies were revealed. Cultural competence continues to attract significant attention of researchers and practitioners, especially among the mental health specialists who work with representatives of different cultures. A number of similar concepts and their components have been proposed: cultural competence, intercultural communicative competence, cross-cultural competence, cultural intelligence, cultural awareness, cultural acceptance, intercultural sensitivity, intercultural adaptation, multicultural competence, multicultural orientation. The difficulties and limitations of existing models noted: a shift of attention to a specialist, but not to a client; borrowing static and absolutistic ideas about cultures, without consideration of cultures development and interaction.There is a trend in contemporary global world for broad research and development of cultural competence that improve professional qualities of healthcare professionals and provide psychological assistance to representatives of different ethnic and culture groups, confessions and minorities. The reported study was funded by the Russian Foundation for Basic Research, project number 17-29-02506.No significant relationships."} +{"text": "The current research examined how the associations between the level and changes in the Big Five personality traits and different types of health outcomes differ across ages over the lifespan and during the aging process in particular. Using data from the two large longitudinal studies, we observed three important patterns based on the results. First, levels and changes in personality traits demonstrated substantial effects on health across different life phases, with the effects observed even in very old ages. Second, overall, the prospective relations between personality traits/changes in personality traits and health outcomes increased in strength in mid adulthood and/or early stages of late adulthood; however, the strength of their connections diminished in very old ages. Finally, there were some trait-specific and health outcome-specific patterns in the age-differential associations between personality and health."} +{"text": "The paper uses the analytic hierarchy process (AHP), spatial autocorrelation analysis, and geographic detectors to reveal the spatial pattern of agricultural production space suitability in China, explores the impact mechanism of agricultural production development, and explores the optimization and promotion strategies for the development of regional agricultural production in various regions in the future. The results show that the resource and environmental carrying capacity, and the agricultural production space suitability under the direction of China\u2019s agricultural production function, show a \u2018polarization\u2019 development trend in space, with high levels in the southeast and low levels in the northwest, with significant spatial agglomeration. The factors influencing the suitability of agricultural production have significant spatial differentiation laws in the Nine Agricultural Areas of China. Climate change factors are the dominant factors affecting the areas with poor resource endowment and traditional agricultural areas in the northwest. Factors that reflect the level of urbanization are the main factors that affect the agricultural production space suitability in the middle and lower reaches of the Yangtze River and South China. China\u2019s agricultural production spatial suitability areas can be divided into nine types of suitable geographical areas. In the future, the impacts of climate change and urbanization on agricultural production space should be considered, and strategies should be taken, according to local conditions, in different regions to improve their suitability. For a long time, the one-sided pursuit of economic growth in urban development, the extensive development mode of urban construction land expansion and the one-way unbalanced flow of urban and rural factors have greatly squeezed the production space of agriculture . At the Agricultural production space is a complex system, affected by social, economic, cultural, institutional and other dimensions, as well as the interaction of national and local top-down multi-scales ,11. The China is the world\u2019s largest food producer and also the country with the fastest urbanization rate. In the context of climate change and urbanization, studying the suitability of China\u2019s agricultural production space has important enlightenment significance for agricultural production and layout of other developing countries in the world, and can provide useful experience for coordinating urbanization and agricultural development. This paper attempts to identify the dynamic evolution process of agricultural production space suitability in China by constructing a comprehensive index evaluation system for agricultural production space suitability evaluation, and analyzing the impact mechanisms and optimization strategies of different scales, locations and types of agricultural production space. This paper seeks to fill the gap in the existing research on the suitability of agricultural production space, which has neglected the impact of climate change and urbanization. By filling this gap, this paper helps in explaining and understanding the evolution trend and law of agricultural production space in China, and provides a reference for the optimization and adjustment of agricultural space and sustainable agricultural development in the future.The main structure of this paper is as follows: In order to analyze the agricultural production space, this paper first constructs the evaluation index of agricultural production space suitability. Based on the conceptual definition and understanding of the spatial suitability of agricultural production ,35,36, tIn order to analyze the relationship between the suitability of agricultural production space and urbanization and climate change, this paper starts from the connotation of urbanization and climate change, and combines the relevant research on the impact of urbanization and climate change on the suitability of agricultural production space . Six indq-statistic. The calculation formula is as follows:In this paper, geodetectors are used to analyze the factors affecting the spatial suitability of agricultural production. Geodetection is a quantitative research method that detects spatial differentiation characteristics and reveals the driving factors and influencing factors behind spatial differentiation ,40, and h = 1, \u2026, L is the number of secondary regions. In the formula, q is . When q = 0, it indicates that the spatial distribution of agricultural production space suitability in China is in a random distribution state. An increase of q shows that the influence factors of independent variables have a greater impact on agricultural production space suitability in China. This paper selected five indicators, population density, night light index, added value of secondary production, water and heat balance index, and annual average temperature, to detect the impact of urbanization and climate change on the spatial pattern of agricultural spatial suitability in China.The threshold range of According to the regional conditions, development orientation, resource and environment carrying capacity, suitability degree of agricultural production space and other factors of different agricultural production spaces, and referring to the traditional naming method of regional types , this paChina Statistical Yearbook (County-Level). The mean elevation was derived from the SRTM 90 m DEM Digital Elevation Database. The soil erosion degree and the spatial distribution index data of China\u2019s annual 1 km vegetation index (NDVI) were obtained from the website of the Resources and Environment Science Data Center, Chinese Academy of Sciences . The Chinese water system vector shp data came from the National Geomatics Center of China . Meteorological data, such as precipitation, accumulated temperature, and temperature, were derived from the China Regional Surface Meteorological Element-Driven Dataset of the National Tibetan Plateau/Third Pole Environment Data Center . The land use data were derived from the China Multi-period Land Use Land Cover Remote Sensing Monitoring Dataset (CNLUCC). The traffic data came from the geographic data sharing service platform of the College of Urban and Environment Sciences, Peking University. The vegetation net primary productivity data came from the Google Earth Engine platform .The social and economic data, such as the fertilizer application amount and the total power of agricultural mechanization, in the comprehensive evaluation system of agricultural production space suitability were mainly acquired from the The Nine Agricultural Areas of China reflect agricultural development conditions, agricultural production conditions and agricultural spatial patterns in a certain period, and are the result of a planning and implementation process that integrates elements of nature, society, economy and ecology ,43. Its The spatial distribution characteristics of the suitability of agricultural production space were obtained by overlaying and processing the grid data of the indicators of the spatial suitability of agricultural production from 1), night light index (X2), land-average secondary industry added value (X3), water\u2013heat imbalance index (X4), average annual temperature (X5), and crop water demand (X6), were detected. The matching degree of spatial characteristics was analyzed for four first-level suitability indicators, including resource environmental bearing capacity (Y1), spatial form (Y2), location conditions (Y3), and production conditions (Y4). In addition, based on the detection of influencing factors, this paper selected the three most powerful factors for each first-level index of suitability for spatial matching , the average secondary production value added (0.407), population density (0.373), night light index (0.177), crop water requirements (0.018) and water\u2013heat imbalance index (0.014). The agricultural production space suitability in China was mainly affected by factors such as the average annual temperature, the average industrial added value of the land, and the population density , land-average secondary production added value (0.407), population density (0.373), night light index (0.177), crops\u2019 water demand (0.018) and hydrothermal imbalance index (0.014). The agricultural production space suitability was mainly affected by factors such as the average annual temperature, the average industrial added value of the land, and the population density.The agricultural production space suitability is subject to the comprehensive disturbance of multi-dimensional factors, such as climate change and urbanization. This paper selected three indicators, population density, night light index and land-average added value of secondary production, which reflect the development level of urbanization, and reflect the degree of climate change. The water\u2013heat imbalance index, the average annual temperature and the crop water demand, and a total of 6 indicators, were used to conduct in-depth exploration and research on the formation mechanism of the spatial pattern of agricultural production space suitability in China. Using the classification of the agricultural production space suitability in China and the classification results of each influencing factor, coupling matching analysis was carried out, and the distribution results of the agricultural production space suitability in China, and the spatial matching of elements in 2018, were obtained . The q sq statistic for each influencing factor and the first-level indicators of resource and environmental carrying capacity, spatial form, location conditions and production capacity. The spatial matching degree between the top 3 influencing factors of the force and the 4 first-level indicators was analyzed ; Lower suitability zone, dominated by severe cold temperatures in Qinghai Tibet Plateau (II); Higher suitability zone, dominated by the optimization of water\u2013heat matching degree in the Northeast China Plain (III); Higher suitability zone, dominated by warming and drying in Loess Plateau (IV); Higher suitability zone, dominated by industrialization in Huang-Huai-Hai Plain (V); Medium suitability zone, dominated by topography in Sichuan Basin and surrounding regions (VI); High suitability zone, dominated by comprehensive factors in the Middle\u2013lower Yangtze Plain (VII); High suitability zone, dominated by the altitude difference in Yunnan-Guizhou Plateau (VIII); High suitability zone, dominated by population agglomeration in Southern China (IX) . An optiThe differences in resource endowment, socio-economic conditions, location conditions, and government policies, of the different types of agricultural areas resulted in different suitability characteristics and development paths among the various types of agricultural areas. There were also significant differences in the mathematical characteristics of resource and environmental carrying capacity conditions, spatial form conditions, location conditions, production conditions, and suitability characteristics . Based oLand resources, water resources, climate conditions and environmental conditions are the basic factors that affect agricultural production and play a decisive role in the suitability of agricultural production space. First of all, climate change leads to changes in planting systems and crop production layout. Global warming has led to an increase in the temperature in middle and high latitudes of China, leading to an earlier crop sowing date, a later winter season, an overall extension of the growing season, and an increase in the accumulated temperature during the winter, which may lead to changes in planting systems. More northern and high-altitude regions can carry out multi-cropping production and planting, and the planting areas expand northwards. The multiple cropping index increased, and the suitable planting area was further expanded . SecondlThe rapid progress of urbanization and industrialization has brought China many conveniences, such as economic development, social progress and industrial upgrading, as well as positive and negative effects on the suitability of agricultural production space. First of all, the urbanization process has brought a lot of agricultural transfer population, and the modern non-agricultural sector has absorbed a large amount of labor from rural areas, which has brought about the non-agricultural transfer of agricultural production subjects and optimized the allocation of urban and rural resource elements. Secondly, the rapid progress of urbanization has led to extensive and disorderly expansion of construction land, which has had a far-reaching impact on agricultural production subjects and space, leading to reduction of the quantity and quality of cultivated land, the occupation of high-quality cultivated land and permanent basic farmland, and great reduction in the suitability of agricultural production space. For example, in the middle and lower reaches of the Yangtze River, where there is a high degree of economic and social development, and, likewise, in the southeast coastal areas, agricultural production space has become fragmented and decentralized due to the interference of high intensity human activities; thus, affecting the suitability of agricultural production space. Finally, urbanization has driven the development of urban industry and technological progress, and has had multiple effects on agricultural production space. On the one hand, the development of urban industry drives the innovation of agricultural technology. Industrialization provides more advanced and convenient mechanized production tools for agricultural production, effectively saves the labor input cost of agricultural production , improveIn addition, price mechanism, livelihood mode, policy guarantee and technology input are also auxiliary factors that affect the suitability of agricultural production space in China. First, the market price mechanism affects farmers\u2019 willingness to plant, and the fluctuation of market price affects the income of agricultural producers engaged in agricultural production activities, thus, affecting the enthusiasm of agricultural producers engaged in agricultural production activities. This then affects the way agricultural production entities engage in agricultural production and operation activities, causing changes in the quality of agricultural production space, and, ultimately, leading to changes in the suitability of agricultural production space. Second, the shift of the main agricultural production body\u2019s part-time livelihood mode is also an important factor affecting the suitability of agricultural production space. Areas such as the middle and lower reaches of the Yangtze River and South China have conditions conducive to production, such as high matching of water and heat resources, flat terrain for farming, and abundant labor force. However, these areas often have a high level of economic development, and the labor income of central cities is significantly higher than that of rural areas. Farmers, based on the consideration of rational economic people, tend to move to cities and the surrounding areas to engage in other occupations with higher returns. As a result, a large number of agricultural production subjects, mainly young and middle-aged people, have turned to non-agricultural production modes, which has caused problems, such as aging and feminization of agricultural production subjects , and, thBased on the background of the era of urbanization, industrialization and climate change. and the major strategic needs of rural revitalization, sustainable agricultural development and food security, this paper integrated multidisciplinary theories and research methods, and deeply developed the spatial and temporal pattern, evolution process, influencing factors, type of differentiation and coping strategies of agricultural production space suitability in China. The specific conclusions are as follows:First, the proportion of each region in each suitability degree did not change much and was relatively stable in 2000, 2009 and 2018. The areas with poor suitability are mainly located in the Qinghai-Tibet Plateau and the northern arid and semi-arid regions, which have improved a lot in the past 10 years, mainly due to the increase in precipitation in the middle and high latitudes, which has improved the suitability of agricultural planting in this region. From the perspective of the spatial differentiation pattern, the agricultural production space suitability in 2000, 2009 and 2018 showed a polarized distribution, with high levels in the southeast and low levels in the northwest. The agricultural production space suitability in each county in China is significantly affected by the suitability of neighboring counties, showing a significant positive correlation.Second, the factors influencing the agricultural production space suitability in China have significant spatial differentiation laws in the nine agricultural areas in China. Climate change factors, such as annual average temperature and the water\u2013heat imbalance index, are the dominant factors affecting areas with poor resource endowment and traditional agricultural areas in the northwest. Factors that reflect the level of urbanization, such as population density and nighttime light index, are the main factors that affect the agricultural production space suitability in the middle and lower reaches of the Yangtze River and South China with relatively high levels of economic development, good water and heat matching, and favorable location conditions.Third, based on geographical location, the dominant influencing factors of the agricultural production space suitability, the degree of agricultural production space suitability in 2018, and the types of agricultural production space suitability in China can be divided into the following zones: Medium suitability zone, dominated by water\u2013heat imbalance in Northern arid and semi-arid region; Lower suitability zone, dominated by severe cold temperatures in Qinghai Tibet Plateau; Higher suitability zone, dominated by the optimization of water\u2013heat matching degree in the Northeast China Plain; Higher suitability zone, dominated by warming and drying in Loess Plateau; Higher suitability zone, dominated by industrialization in Huang-Huai-Hai Plain; Medium suitability zone, dominated by topography in Sichuan Basin and surrounding regions; High suitability zone, dominated by comprehensive factors in Middle-lower Yangtze Plain; High suitability zone, dominated by the altitude difference in Yunnan-Guizhou Plateau; High suitability zone, dominated by population agglomeration in Southern China.Fourth, agricultural production is a production process that is highly dependent on climatic resources, and, at the same time, is subject to comprehensive disturbances by its production subject and other related subjects. Differences in resource endowment, socio-economic conditions, location conditions, and government policies have resulted in different suitability characteristics and development paths among various types of agricultural areas. The natural conditions, environmental conditions and location conditions of regional agriculture reflect the macro background value of agricultural development in the region. The scientific application of strategies, such as the rational development and utilization of regional agricultural resources, the improvement of acquired technologies and policy guidance, are \u201clate remedy\u201d measures and important approaches for the rational utilization of regional agricultural resource conditions and sustainable agricultural development. In the future, optimization and improvement strategies should be given for the agricultural production space in different regions according to local conditions.This paper enriches the empirical research on spatial adaptability of agricultural production and agricultural sustainable development. It also provides important reference for agricultural regional planning and high-quality agricultural development in other developing countries. Limited by the availability of data, the frequency of natural disasters, farmers\u2019 livelihood choices and market food prices have not been considered, which is also the shortcoming of the paper. As climate change and human activities disturb the agricultural production space more and more intensely, more and more experts and scholars have begun to consider how agricultural production can reduce the frequency of external disturbances and improve the system resilience of agricultural production to actively respond to disturbances. On the one hand, the indiscriminate use of agricultural chemicals worldwide in the last century has increased crop yields to a certain extent, but, at the same time, has brought great damage to terrestrial and aquatic ecosystems. Nanomaterials, biomass charcoal and nitrogen fertilizer, and other new materials, could reduce the disturbance of agricultural production to the outside world. They could also improve the diversification of crops, organic agricultural production, large-scale planting and irrigation in water-deficient arid and semi-arid areas. The resilience of agricultural production could be improved by means of technological upgrading and other means. Therefore, it is urgent to classify the agricultural production space caused by different influencing factors, and to explore the future agricultural development path of each regional type."} +{"text": "Mental health literacy (MHL) could be defined as a knowledge of mental health, comprehension of its importance, adequate attitude to information about mental health, possession of skills and abilities to provide assistance and self-help to maintain and promote mental health.The aim of the present study is to identify possible relationships between the components of mental health literacy and the manifestations of the emotional sphere of the respondents.The sample consisted of 220 young people from 16 to 23. Emotional Empathy Questionnaire , self-assessment of mental states (G. Eysenck), questionnaire from the study of Reavley et al., and the custom MHL questionnaire were used.Most significant of relationships revealed by Pearson\u2019s Product-moment correlation analysis: Adequate actions of respondents in a mental health-threatening situation inversely correlates with anxiety , aggressiveness , frustration , rigidity . Comprehension of the importance of specialized care inversely correlates with frustration . Helping others in difficult situations correlates with empathy .A low level of the behavioral component of MHL is often manifested with high anxiety, aggressiveness, rigidity, frustration. Correlation between the cognitive component and frustration may indicate that sufficient level of this component does not allow the individual to fall into a state of deep frustration in mental health-threatening situations. Individuals with low level of anxiety, rigidity, aggression are more inclined to understand the importance of seeking professional help. An individual with lower frustration and aggressiveness will less likely choose destructive behaviors .No significant relationships."} +{"text": "In addition, at least a quarter of the total direct cost impact of healthcare interventions affects other economic sectors. International methods and tools are lacking for the rigorous and comparable assessment of the costs and outcomes of (public) health care from a societal perspective. The H2020 PECUNIA project (grant No 779292) brought together ten partners from six countries (AT/DE/ES/HU/NL/UK) between 2018 and 2021 aiming to improve the comparability and feasibility of multi-sectoral, multi-national health economic evaluations in Europe. A multi-step, mixed methods approach was used following a new harmonized costing concept to develop new methods and tools for the standardised identification, definition, measurement and valuation of costs in multiple sectors justice, education, employment and productivity, and patient, family and informal care), and for the broader, harmonised, supra-national assessment of outcomes using selected mental disorders as illustrative examples. This presentation will summarise the relevant advances in costing methods, give an overview of the developed tools that are now publicly available ("} +{"text": "Emerging and reemerging plant diseases can be defined as those diseases caused by new or reappearing pathogens which, due to their intrinsic characteristics, have the ability to spread rapidly and cause epidemics in certain agro-climatic contexts. In recent years, both DNA and RNA viruses have been implicated in important disease outbreaks in plants. The different forms of mutation, recombination and other types of genetic exchange, considered as the basis of the evolutionary forces of viruses, have undoubtedly given rise tothe genetic diversity found in plant virus populations. In this context, environmental factors play an important role in driving virus evolution. In addition, the rapid expansion of human activity in the world of commerce, agriculture, anthropization of natural ecosystems and climate change have further contributed to the instability between hosts and virus populations, favouring the emergence of viruses with mutant and/or recombinant forms, with potentially negative impacts on plants, vectors and ecosystems.Lal et\u00a0al.), an important group of emerging viruses with a destructive potential on many crops; capable of causing serious social and economic losses , currently causing major losses in rice production mainly in sub-Saharan Africa (SSA). This review deals with the molecular characteristics of RYMV: the genomic structure, function and gene diversity, and RYMV-host interactions. In particular, the review sheds light on mechanisms related to the qualitative resistances, controlled by three recessive genes RYMV1, RYMV2 and RYMV3, and quantitative resistances, with the description of several QTLs found in Oryza germplasm. Finally, since RYMV shows high genetic variability and some Oryza germplasm has low or non-durable resistance, the review suggests possible genetic improvement strategies for a significant enhancement of rice protection through the use of assisted selection with molecular markers and by employing genome editing to impair susceptibility.The second review addresses the problem of yellow mottle rice virus (YMRV) , with particular reference to the contribution provided by high-throughput sequencing (HTS). The work takes into consideration the period 2011-2020, during which 45 new viruses have been described in tomato, 14 of these identified by HTS. Based on the data present in the literature and in the databases, the authors list 312 viruses, satellite viruses, or viroid species (in 22 families and 39 genera) identified in tomato. This represents the highest number of viral and viral-like agents described in a single botanical species. The work also underlines the importance of the application of HTS for epidemiological studies, in particular for the identification of the virome of weeds and other wild plants, or for the identification of viruses in vectors, irrigation water or wastewater and soil. The HTS analysis of environmental samples helps to greatly improve the understanding of epidemiology and ecology of tomato-infecting viruses and can facilitate virus disease forecasting in order to prevent virus disease outbreaks in tomato. Finally, the review outlines the main tomato viruses, highlighting their potential threat and impact. Newly emerged viruses, such as tomato brown rugose fruit virus (ToBRFV), are capable of overcoming the Tm-22 resistance gene used to contain tobacco mosaic virus (TMV) and tomato mosaic virus (ToMV) infections in greenhouse tomatoes. Tomato spotted wilt virus (TSWV) easily overcomes the resistance mediated by the Tsw hypersensitivity gene in pepper with increasing temperatures. A group of emerging geminiviruses, of subtropical and tropical origins, including tomato leaf curl New Delhi virus (ToLCNDV) and tomato leaf curl virus (TYLCV), mostly are virulent at high temperatures. Their vector, Bemisia tabaci, is notoriously thermophilic and a highly invasive species.The final review concerns the progress on tomato virome research . The work also highlights progress in the detection of ToBRFV, mainly regarding sensitivity, compared to previous methods. This paper also emphasizes the practical advantages deriving from the use of LAMP, since it can be applied by poorly equipped laboratories and unskilled persons at official country points of entry, providing a new diagnostic tool for phytosanitary investigations and management of ToBRFV. The second work describes an RT-qPCR assay for the diagnosis of parietaria mottle virus (PMoV), based on a specific TaqMan\u00ae probe ,. PMoV is considered an emerging pathogen in the Mediterranean basin on tomatoes and peppers. This virus has recently expanded its natural host range assays, both real time and visual, for the diagnosis of ToBRFV on leaf samples and seeds of tomato and bell pepper and desmodium leaf distortion virus (DesLDD) and two deltasatellite. This is the first report of (i) a monopartite New World begomovirus found in a host other than tomato and (ii) deltasatellites found in C. siliquosus, thus extending the host and helper virus ranges of this recently recognized class of DNA satellites.The paper of Crinivirus, family Closteroviridae) (ToCV) is expanding its geographical and host ranges associated with the emergence of whiteflies of the Bemisia tabaci complex (genus Fabavirus in the family Comoviridae), an emerging virus in economically important crops worldwide. They investigated the BBWV2-pepper (Capsicum annuum L.) pathosystem, using two distinct BBWV2 strains, PAP1 (a severe strain) and RP1 (a mild strain). Upregulation of several genes associated with pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and ethylene signaling were associated only with the severe PAP1 strain, with high ethylene emission detected. Authors conclude that the activation of PTI-associated defense responses increase symptom development during BBWV2 infection in a virus strain-specific manner.Tomato chlorosis virus (genus complex . Fortes Phaseolus vulgaris L.) in the North-Western Himalayan region of India by Rashid et\u00a0al. Three viruses were identified: bean common mosaic virus (BCMV), bean common mosaic necrosis virus (BCMNV), and clover yellow vein virus (ClYVV), with BCMV more widespread and BCMNV and ClYVV new records from India. In another paper , applied HTS to characterize the virome of Pseudostellaria heterophylla, generated data on three novel carlaviruses and one novel amalgavirus.HTS analysis has been applied to study the diversity of virus(es) associated with common bean and papaya ringspot virus (PRSV) in cucurbits with a novel recombination pattern detected in the HC-pro. Despite the origin from interspecific recombination, they proposed that these viruses still belong to ZTMV according to their genome characteristics; their results provide insights into the prevalence and evolution of ZTMV and PRSV in cucurbits.Vo et\u00a0al.). ToLCNDV-ES hardly infects tomato and some isolates would not at all. Nonetheless, ToLCNDV-ES in the presence of TYLCV proves to be able to multiply and infect tomatoes. In addition to the known risk of formation of recombinants between geminiviruses, this work highlights the risks of a possible expansion of the natural hosts for this group of emerging viruses thanks to the phenomena of assistance and complementation between viruses.The last paper concerns a complementation phenomenon between TYLCV and ToLCNDV-ES, first observed in the field and then demonstrated in the laboratory with agro-inoculations of infectious clones (Emerging and Reemerging Viruses in the Context of Global Change. We are deeply grateful to all the authors and reviewers who with their exceptional work have made possible the realization of this special issue. We believe that this collection will increase knowledge and awareness about the importance of emerging and reemerging viral diseases in order to improve the monitoring and the possible control that derives from them, with the aim to prevent epidemics in agricultural crops.In summary, this Research Topic provides cutting-edge methodologies, research, observations and knowledge on the current scenario of All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "Risk levels of spring pollen allergy for tourists in different assessment units were revealed by combining the green zone allergenicity index model and three-dimensional risk assessment matrix. The results showed that: (1) There were seven primary pollen-allergenic plants in the Summer Palace, including Platycladus orientalis, Sabina chinensis, Salix babylonica, Pinus tabulaeformis, Populus tomentosa Carr, Morus alba L. and Fraxinus chinesis, among which Platycladus orientalis and Salix babylonica were the highest allergenic. (2) Among 18 spots, tourists faced the highest risk level of pollen allergy in spring at three spots, namely the Hall of Serenity, Hall of Benevolence and Longevity, and Gallery of Literary and Prosperity. (3) The two routes of the Long Corridor and Longevity Hill scored high on the risk level. (4) Among four areas, risk levels of the Front-hill and Rear-hill areas were high. Given the increasing spatial-temporal uncertainty of pollen allergy and tourist behaviors under global warming and urbanization, the related monitoring should be strengthened in the future. Furthermore, the dynamic and improved assessment of pollen-allergy risk should be institutionalized and be integrated into the evaluation of tourism experience quality. Tourism administration should make full use of relevant assessment results and conduct more effective risk communication.Pollen allergy has already been an increasingly prominent ecosystem disservice in tourism attractions. However, few studies have assessed the tourist risk of pollen allergy through integrating multidisciplinary knowledge of ecology, medicine, phenology, and risk management. Basing on the conceptual framework of risk assessment proposed by UNISDR, we first established an index system of pollen-allergy risk for tourists in attractions and outlined assessment methods 18 available indexes were put forward to cover three aspects: hazard of plant allergen, tourist vulnerability, and resilience of assessment units. Subsequently, taking the Summer Palace as the case study area, we conducted a tourist risk assessment of pollen allergy. Values of nine available indexes were obtained Pollinosis is a \u201cnational disease\u201d around the world. It can cause allergic rhinitis, conjunctivitis, hay fever or asthma, urticaria, and allergic dermatitis, etc. Patients may suffer from shock and have a risk of sudden death, when correlated symptoms are severe. In developed countries, 20\u201330% of the population is allergic to pollen , while tStudies on pollen allergy came from medicine, ecology, phenology, and some other disciplines. Among them, medicine focused on the difference in the allergenicity and emissions of various pollens, the association between its incidence and the demographic characteristics of patients, and seasonality changes of airborne pollen . EcologySabina chinensis, Populus tomentosa, Fraxinus chinensis, Rhus Typhina, Syringa reticulata, and the latter includes Chrysanthemum morifolium and Brassica rapa. Despite their undeniably benefits of the adaptability to local climatic conditions, the ease of management, and the ability to enhance the landscape, allergenic plants make tourism attractions uncomfortable seasonally for the human respiratory system. Under the background of nature tourism and outdoor education becoming more and more popular, people' exposure to the allergenic environment is increasing.Tourism attractions play a key role in tourism and have become more and more important with the continuous enhancement of Chinese travel desire and payment capability. In 2021, the number of National A\u22125A level tourism attractions in China reached 14196, and their tourism revenue increased to 2.92 trillion yuan, up 31.0% over 2020 . CompareMorus, Robinia and Cerasus yedoensis across many regions have already advanced , factor (B), category index (C) and bottom index (D). The pollen-allergy risk of tourists in attractions was defined as the target (A). According to the risk conception and the pollen-allergy formation mechanism, the target was determined by three factors on the B layer, including the hazard of plant allergen, tourist vulnerability, and resilience of assessment units. As for the hazard of plant allergen, its category indexes and bottom indexes were selected considering both the biological and ecological characteristics of allergenic species. With reference to the meanings of risk exposure and the resistibility of human body in the assessment theory of natural disaster risks , 30, catvia phenological observations and airborne allergen monitoring. Concerning the third category index of tourist exposure, we selected two basic indexes (tourist amounts and dwell time) used in most studies on tourist behaviors. More tourist amounts and dwell time mean greater tourist exposure. According to previous studies, tourist amounts can be obtained via the sampling survey, GPS tracking survey model model , 31 , S = vertical crown projection area covered (m2), H = canopy height (m), ST = total surface area of the assessment unit (m2).Where k = number of pollen allergenic species, NRisk level matrix is another convenient fundamental tool used to assess risk , 30, 38.2, in which 357.20 km2 are parks , canopy breadth and canopy height of every allergenic plant were measured by DBH ruler, tape measure, and laser rangefinder, respectively. During the investigation course, The DBH was measured at the height of 1.3 m, and the canopy breadth was calculated as described by Liu et al. .Platycladus orientalis, Sabina chinensis, Salix babylonica, Pinus tabulaeformis, Populus tomentosa Carr, Morus alba L, and Fraxinus chinesis. Their phenological observation data were obtained from the Chinese Phenological Observation Network . Records of first flowering dates (FFD), full blooming dates (FBD) and end of flowering dates (EFD) of them in 2021 were extracted from the dataset, whose observation process conformed to the traditional criteria in China . By use of a search engine developed by Sichuan University was revealed by combining the data mining of visitors' check-in on Sina Weibo and the dwell-time analysis. Among the 18 scenic spots, the Hall of Benevolence and Longevity, East Palace Gate, Gallery of Literary Prosperity and North Palace Gate were most visited in the spring of 2021. Therefore, tourist vulnerabilities of them were the highest. In contrast, the scenic spots of the Marble Boat, Chamber of Cultivation, Hall of Happiness and Longevity, Chamber of Clearness, and West Palace Gate had low tourist vulnerabilities. Among the five scenic routes, the tourist vulnerabilities of the Long Corridor route and the Longevity Hill route were very high and high, respectively, while those of the West and East Causeway routes were both low. As for the scenic areas, the tourist vulnerability of the Front-hill area was very high, while that of the East-lake area was the lowest . OverallBecause all the six medical centers are located near the gates of the park, the distances from the assessment unit to the nearest gate have great influence on their resilience. Among the 18 scenic spots, four scenic spots had the poorest resilience, namely the Garden of Farming and Weaving, Chamber of Clearness, Marble Boat, and Hall of Serenity . AccordiAccording to the assessment results of the three-dimensional risk matrix, tourists in three scenic spots had a very high risk of pollen allergy, whose governance should be given the top priority . In the 2 would increase the likelihood of seasonal allergies throughout the continental USA, with end-of-century emissions being increased up to 200% shows that heat waves will significantly increase the risk of morbidity and mortality, and have a profound impact on population behavior patterns and transportation choices for travel . David M2.5 concentration model and three-dimensional risk assessment matrix to assess and map the risk levels of spring pollen allergy in 18 scenic spots, five scenic routes and four scenic areas. The results showed that: (1) There were 7 primary pollen-allergenic plants in the park, among which Platycladus orientalis and Salix babylonica had the highest allergenic hazard. (2) Among 18 spots, tourists faced the highest risk level of spring pollen allergy in three spots, namely the Hall of Serenity, Hall of Benevolence and Longevity, and Gallery of Literary Prosperity. (3) The two routes of the Long Corridor and Longevity Hill scored high on the pollen-allergenic risk level. (4) Among four areas, the Front-hill and Rear-hill areas were high risky for tourists.Climate change has already affected human health directly and indirectly in China. From the perspective of tourism management, it is imperative to assess the pollen-allergy risk of tourists and visualize it by risk mapping. For this purpose, we established an assessment index system consisting of 18 available bottom indexes, which covered three aspects of allergen hazard, tourist vulnerability and resilience of assessment units. The quantification and coupling of assessment indexes were also outlined. Taking the Summer Palace as the case study area, we obtained the values of nine representative indexes 2 concentration, and extreme events. Urbanization will also affect the local climate, thermal environment and PM2.5 concentration. As a result of these two driving forces, greater uncertainty of pollen allergy risk may occur subsequently in the future. Therefore, under the policy background that Chinese government has placed increasing emphasis on the construction of ecological civilization and the improvement of human wellbeing and public health, the high-quality development of tourism attractions should attach importance to the risk impact of local thermal environment, climate comfort and air pollution and the National Key Research and Development Program (Grant No. 2018YFA0606102).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In low- and middle-income countries, facility-based neonatal care practices can be improved using a collaborative cross-learning quality improvement approach incorporating remote mentoring, coaching, and supportive supervision. Combining a training package to improve the knowledge and skills of health care workers in managing sick and preterm neonates with point-of-care quality improvement skills successfully reduced the unindicated use of oxygen, antibiotics, and phototherapy while increasing the use of enteral feeds.Despite a significant reduction in the use of 2 lifesaving medical interventions\u2014oxygen and antibiotics\u2014no increase in mortality or short-term adverse outcome was observed, indicating an overuse of these interventions in the preintervention period.A strategy of combining professional training activities and coaching in continuous quality improvement methods can successfully improve the health care of sick and preterm neonates. With the rapid expansion of access to facility-based neonatal care, it is important to monitor for both overuse and underuse of evidence-based interventions. We evaluated the efficacy of training health care workers (HCWs) in point-of-care quality improvement (POCQI) and a preterm newborn health care package (PHCP), followed by remote mentoring and supportive supervision in improving health care practices, neonatal survival, and morbidities in special neonatal care units (SNCUs).This pre- and postintervention quality improvement study was conducted at 3 SNCUs in Madhya Pradesh, India from February 2017 to February 2019. Clinical care teams comprising doctors and nurses from the study sites were trained in POCQI and the PHCP. The teams identified, prioritized, and analyzed problems and designed quality improvement initiatives at their respective health facilities. Change ideas were tested by the local teams using sequential plan-do-study-act cycles. Facilitators maintained contact with the teams through quarterly review meetings, fortnightly videoconferencing, on-demand phone calls, and group chat service. State SNCU coordinators made follow-up visits to supplement coaching. Study research staff independently collected data on admissions, health care practices, and outcomes of neonates.A total of 156 HCWs were trained in the POCQI methodology and PHCP. Sixteen quality improvement projects were formulated and implemented. Among 13,821 enrolled neonates , improvement was seen in reduction of use of oxygen , antibiotics , and dairy milk . Enteral feeds were started within 24 hours of admission in a larger number of neonates, resulting in fewer days to reach full feeds. There was no effect on survival at discharge from the hospital .A collaborative cross-learning quality improvement approach with remote mentoring, coaching, and supportive supervision was successful in improving the quality of care at SNCUs. Special newborn care units (SNCUs) at district hospitals provide FBNC to about 0.9 million neonates every year, on approximately 16,000 beds across India.\u2013Although the SNCUs have adequate infrastructure and supplies, concerns have been raised about suboptimal knowledge and poor skills of the health care workers (HCWs) that staff them.Can combining knowledge and skills augmentation activities with problem-solving skills improve HCWs\u2019 ability to adapt and adopt evidence-based practices and improve health outcomes in SNCUs?\u2013Our study evaluated whether the implementation of an intervention package to improve the knowledge and skills of the HCWs in providing clinical care as well as undertaking QI activities would improve health care practices, neonatal survival, and morbidities in the SNCUs. To test this hypothesis, we developed a theory of change that formed the basis of the package of interventions .14 The tThis before-and-after study was conducted from February 2017 to February 2019 in the SNCUs of 3 district hospitals and a medical college in the state of Madhya Pradesh, India . All livThe study was coordinated by the All India Institute of Medical Sciences, New Delhi, the Postgraduate Institute of Medical Education and Research, Chandigarh, and the Government Medical College Hospital, Chandigarh. Institutional ethics committees at the 3 coordinating sites and the Indian Institute of Public Health, Hyderabad approved the study protocol. National Health Mission, Madhya Pradesh also approved the study protocol. Written informed consent was obtained from parents of the enrolled neonates, HCWs at the study sites, state SNCU coordinators, and state child health consultants.The study intervention was guided by a theory of change and the work plan was divided into preintervention and intervention phases.\u2013The preintervention phase had 2 components\u2014formative assessment and baseline neonatal data collection. The formative component started with the development of a theory of change based onBOXImprove oxygen administration methodsMonitor and promote the use of continuous positive airway pressure and surfactantOptimize oxygen use:Minimize amount of blood samplingRestrict use of blood productsEffective use of phototherapyReduce exposure to blood products:Early initiation and rapid advancement of enteral feeding with breast milkImprove nutritional status:Improve aseptic techniques at birth and during hospital admissionReduce sepsis:Hypothermia preventionKangaroo mother carePain controlReduce noise and light exposureIncrease parental involvement in careImprove developmental care:www.pretermcare-eliminatingrop.com) were developed and reviewed by 35 neonatologists and nurses from across the country. The Point of Care Quality Improvement (POCQI) tool, developed in collaboration with the World Health Organization South-East Asia Regional Office (WHO-SEARO), guided the training for conducting QI projects.In parallel, we assessed the baseline levels of knowledge, skills, attitudes, and practices of SNCU health care personnel, state SNCU coordinators, and child health consultants. This preassessment focused on the clinical care pathways including the drivers of improvement identified in the theory of change. We also assessed the problem-solving and QI skills of the HCWs. Results of this formative part of the study are being reported separately. Based on this formative phase, we designed, pilot-tested, and finalized a collection of interventions with 2 components: (1) improvement in knowledge and skills of the HCWs in neonatal care and (2) improvement in the ability of staff to practice the knowledge and skills gained by conducting QI activities at their respective SNCUs. The content for training HCWs on best practices in preterm care was called the preterm newborn health care package (PHCP) and included 10 modules composed of brief webinars, videos, case studies, posters, job aids, and key messages. The content of each module was divided into specific learning objectives, with a self-assessment in the form of multiple-choice questions following each objective. The evidence-based content and materials in the PHCP . Activities for knowledge and skill augmentation included small group discussions, skill practice, and simulated clinical scenarios. The second part consisted of clinical data presentation from each SNCU, choosing target areas of improvement, forming QI teams, analyzing the root causes of the problem, and outlining the QI project activities. Each SNCU team not only worked on the development of its own QI project but also reviewed and gave feedback on the QI projects of other SNCUs. During the study, selected HCWs from each SNCU underwent a total of 5 in-person sessions that covered all the modules developed under the PHCP.Ongoing support: In addition to the training in the remaining modules during successive in-person workshops, all the training materials were available online for ongoing training and review. Skill training corners were also established in each SNCU, and a skill lab was established in the mentoring medical college.QI projects and mentoring: The theory of change guided the selection of QI projects. Doctors and nurses working in each SNCU selected specific problems to be addressed by a QI project and decided the goal and outcome measures for each project based on the 4 criteria outlined in the POCQI guide\u2014importance to patient outcomes, affordability in terms of time and resources, ease of measurement of outcome, and whether the identified problem was under the control of team members. Following the workshop, the SNCU teams returned to their units and started working on their respective QI projects. We held web meetings every two weeks to review progress and provide guidance for any bottlenecks encountered. Team members presented their completed projects in subsequent on-site workshops after which they developed and conducted new QI projects. The intervention period continued from September 2017 to February 2019 and over this period each SNCU conducted 3\u20135 QI projects .A study research nurse at each of the 3 SNCUs collected the health outcome data of the admitted neonates. The primary outcome of the study was the proportion of neonates who survived without developing severe ROP. Secondary outcomes included death before discharge, adverse outcomes , hypothermia at admission, neonatal hyperbilirubinemia needing phototherapy or exchange transfusion, and duration of hospital stay. Various care processes reported include enteral feeding practices, use of oxygen and antibiotics, and screening for ROP.The primary outcome of the study was the proportion of neonates who survived without developing severe ROP.We defined the composite primary outcome as neonates discharged alive from SNCU and not found to have severe ROP on screening examination before discharge or during follow-up. We defined severe ROP as ROP needing laser ablation or surgery to prevent loss of vision. Although estimates of mortality among SNCU admissions are available, no such information is available about the incidence of severe ROP, the second component of the composite primary outcome. Therefore, the sample size was calculated for the incidence of mortality among SNCU admissions. With an estimated enrollment of 3,000 neonates in the preintervention period and 10,000 neonates during the intervention period, the study had 90% power to detect an absolute reduction of 2% in mortality (from 10% to 8%) with a 2-sided alpha of 0.05.P value of less than .05 was considered statistically significant and no adjustment was made for multiple comparisons.Study nurses prospectively collected data from the bedside clinical records and entered it into a custom-built Android application. We then analyzed the data using Stata 16.1. Categorical data are presented as numbers and percentages. Normally distributed numerical data are presented as mean and standard deviation, and skewed numerical data are presented as median with interquartile range. We used a mixed-effects regression model to estimate the effect of the intervention, with SNCU site as random effects and other covariates as fixed effects. The covariates included in the model were based on biological plausibility and significant differences between the preintervention and intervention periods. We conducted a post-hoc secondary analysis to account for the possible effect of a secular trend in the preintervention and intervention periods. For this, we aggregated the data for each month and then analyzed the data using the interrupted time-series regression method which separates the effect of intervention from the preintervention trend. A Supplement, Table S1 and Table S3). All the doctors and >90% of nurses in the study SNCUs received training over the period of intervention. All the learning modules were covered over the 5 in-person sessions and the continuous online training and mentoring. The flow of online modules on the web portal ensured that the participants were able to proceed to the subsequent module only after successfully completing the knowledge assessment of the current module. The skill check activities were directly observed. Due to the midway change in the mentoring medical college, preintervention data were not available from the SNCU in Bhopal and so data from this site were not included in our primary analysis. Throughout the study, the 3 SNCUs were mentored by investigators from outside the state of Madhya Pradesh.Over the study period, a total of 5 in-person sessions were held and 156 HCWs were trained. A total of 16 QI projects were completed at the 3 study SNCUs of the district hospitals and 1 SNCU of a medical college . Antenatal care was almost universal, with 87% of mothers having had at least 3 antenatal check-ups and 11.2% having had cesarean delivery. A high proportion (43.6%) of neonates were preterm (<37 weeks of gestation). Over the study period, the profile of enrolled neonates remained similar , althougA total of 343 (10.2%) neonates died during the preintervention period and 1,106 (10.6%) during the intervention period . As gravely sick neonates may be referred for tertiary care or taken home by parents for compassionate care, we also calculated the rate of adverse outcomes including death, referral to a higher center, or left the hospital against medical advice. No difference was observed in the incidence of adverse outcomes .P<.01), and very preterm gestation. The duration of oxygen therapy also decreased .Several health care practices improved during the intervention period . These iecreased . A signiecreased . The proThe use of many interventions, including oxygen and antibiotics, declined, indicating overuse in the preintervention period.Supplement, Figures S1 and S3). The trend-adjusted analysis showed no significant change in other health care practices, death, or adverse outcomes .The interrupted time-series analysis adjusting for the preintervention trend showed a significant reduction of 2.2% per intervention month in the proportion of neonates who were started on oxygen at admission and a significant reduction of 5.1% per intervention month in the proportion of neonates who received antibiotics . An additional challenge was the state government practice of measuring performance evaluation of the SNCUs by the number of admissions and use of various medical interventions. In our formative evaluation, this was associated with unnecessary admissions, delayed discharge, and overuse of medical interventions. During the intervention period, the SNCU teams identified and ran QI cycles to address these issues. Combined with the PHCP to improve the knowledge and skills of HCWs in managing sick and preterm neonates, the QI cycles successfully reduced the use of oxygen, antibiotics, and phototherapy while enteral feeds were initiated earlier resulting in a shorter time to reach full enteral feeds. Significant reduction in the use of 2 lifesaving but double-edged interventions like oxygen and antibiotics without a concomitant increase in the incidence of death or referral to a higher center supports our preintervention assessment of overuse. Alternatively, the profile of admitted infants may have changed over time, resulting in a lower use of oxygen and antibiotics. However, this alternate explanation is refuted by the similarity of baseline variables and significant effect size obtained even after adjusting for biologically plausible prognostic factors. Rather, the case mix in the intervention period had a higher proportion of preterm and male neonates and lower use of antenatal steroids, all of which are risk factors for increased sickness and mortality.,We evaluated the efficacy of a novel package of interventions in improving the health care practices and outcomes in district level-2 neonatal care units. We observed significant improvement in the health care provided to sick or preterm neonates at admission and during the hospital stay. However, we did not observe any improvement in neonatal survival. Our study intervention was based on the assumption that unexplained variation in the care provided to neonates admitted to the SNCUs is related to the quality of care. During the baseline period of observations, we found that many health care interventions were often being used without clear indications. These included administration of oxygen, intravenous fluids, antibiotics, and phototherapy. The root causes of injudicious use of these interventions were lack of standard operating procedures and fear of adverse outcomes in absence of use , it is not able to address the gaps in the structure of the health system .The study has certain limitations. The first major limitation is that due to the lack of consistent availability of ophthalmologists at the district hospitals, only a subset of eligible preterm neonates could be screened for the development of ROP. Therefore, the study was not able to report any change in the incidence of severe ROP, a component of the composite primary outcome of the study. Second, being an uncontrolled study, the role of secular trends and external influences cannot be ruled out. We used an interrupted time-series regression analysis to control for the preintervention trend. Although this reduced the number of practices that were found to have improved significantly, this can be explained by reduced power as aggregated data were used in the analysis instead of individual patient data. Third, working on 1 QI project could have led to improvement in another clinical domain and the confounding effect of QI projects on each other cannot be removed. However, the QI teams at each SNCU worked on only 1 QI project at a time and only after completing the project took up the next QI project using the new baseline level of performance at that time. Fourth, the QI activities in the study focused only on the health care processes within the SNCUs. Obstetric practices, resuscitation, and, if outborn, care during transport, have a major influence on neonatal mortality and morbidity. This limitation may be a major reason for the study intervention not resulting in improved neonatal survival. Fifth, the study did not formally evaluate the sustainability of the effects of the intervention package. It is possible that the withdrawal of the external collaborators could result in reverting to previous health care practices. Lastly, we have not evaluated the cost-effectiveness of the intervention.Focusing only on health care processes within the SNCUs may be a major reason that the study intervention did not result in improved neonatal survival.An intervention package based on a situational analysis, consisting of a novel combined training and problem-solving approach and driven by HCWs, was able to significantly improve neonatal health care practices and reduce the injudicious use of many potentially harmful therapies. Future studies should target QI efforts at the full continuum of fetal-neonatal care including childbirth, resuscitation, transport, and postdischarge follow-up.Authors in the Retinopathy of Prematurity-Quality Improvement India Study Group: All India Institute of Medical Sciences, New Delhi, India, Department of Pediatrics: Ashok K. Deorari and Anu Thukral; Postgraduate Institute of Medical Education and Research, Chandigarh, India, Department of Pediatrics: Praveen Kumar, Sourabh Dutta, Sundaram Venkataseshan, and Shiv Sajan Saini; Postgraduate Institute of Medical Education and Research, Chandigarh, India, Department of Ophthalmology: Mangat Dogra and Deeksha Katoch; Government Medical College and Hospital, Chandigarh, India, Department of Neonatology: Deepak Chawla, Suksham Jain, and Meenakshi Sharma; Government Medical College and Hospital, Chandigarh, India, Department of Ophthalmology: Subina Narang; Indian Institute of Public Health, Hyderabad, India: Rajan Shukla, G.V.S. Murthy, Snigdha Das, and Ammaji Ch; National Health Mission, Bhopal, India: Rajashree Bajaj and Manish Singh; and London School Hygiene & Tropical Medicine, London, United Kingdom, Department of Clinical Research: Clare Gilbert, International Centre for Eye Health."} +{"text": "Among various regenerative cues, including chemical, biological, optical, magnetic and mechanical factors, the implementation of advanced pharmacological approaches, electrical and mechanical stimuli have long been underestimated in regard to their potential for the development and improvement of bioengineered and biological tissues, such as the bone, cartilage, muscle, heart, and nerve.The primary mission of tissue engineering and regenerative medicine (TERM) is to mimic the architectural and functional nature of impaired tissues . TERM hain vitro studies. Long-term evaluation on the reparative potential of mechanically and electrically conductive biomaterials is the key to identifying a translational approach to advance the field of mechano- and electro-active tissue regeneration therapies.Mechanical and electrical activities play a crucial role in a series of physiological phenomena in the living body and are important for the functionality of mechano- and electro-active tissues, such as bone, cartilage, muscle, heart, brain, spinal cord, and peripheral nerve. Therefore, it is vital to focus on the application of conductive scaffolds and their regulation on endogenous electrical activities in the process of tissue regeneration, with or without exogenous mechanical and electrical stimuli of different paradigms . Positive outcomes have been reported in previous literature, but it is poorly understood how electrical phenomena affect cell physiological function-behavior, metabolism, signaling transduction, and gene expression, or how the combination of engineered conductive scaffolds with the specific delivery of therapeutic drugs boosts the regenerative capacity of tissues. For instance, the inter-cellular communication between neurons or glial cells influenced by electrically conductive scaffolds is not well elucidated in nerve tissue engineering. Some preliminary findings were obtained from In this Research Topic, we have covered the latest advances in the modulation of electrophysiological activities of cells, tissues, and organs by conductive biomaterials and their regenerative signaling mechanisms. This has ultimately led to a comprehensive display of papers .Liu et al. stressed the involvement of osteoclasts and osteoblasts in the activation of various mechanical transduction pathways and discussed changes in the differentiation, formation, and functional mechanisms under multiple forms of mechanical stress to bone tissues. Mei et al. designed a mesoporous bioactive glass biomimetic scaffold to enhance cellular adhesion and to improve osteogenic/cementogenic differentiation in human periodontal ligament cells.Some papers focused on physiological and metabolic response of excitable and non-excitable cells and tissues on electrically active substrates under mechanical and electrical stimuli in normal and tissue injury environments. Wang F et al. proposed a conductive adhesive and anti-bacterial Zwitterionic hydrogel dressing to repair full-thickness skin wounds. In their study, modulation of electrical paradigms facilitated intercellular communication and transcriptional signaling, mechanical stimulation for angiogenesis and skin development and function supported by conductive scaffolds. Tian Y et al. claimed pro-healing effects of mechanically conductive tissue engineering strategy with bardoxolone methyl on nucleus pulposus cells and tissues by inhibiting extracellular matrix (ECM) catabolism and promoting ECM anabolism. In addition to traditional electrical stimuli, in vitro and in vivo evaluation of wound healing and tissue regeneration technologies of combined electrical stimulation and smart materials also yielded some promising results, including novel electroactive scaffold design and user-friendly application .Jiang Y et al. reported the Netrin-1 modified adipose-derived stem cells and the combined application of such in vitro and in vivo tissue engineering strategies to accelerate or improve the development and function of bioengineered endovascular tissues. In addition, there are some research papers concerning novel biomaterial design, fabrication and application for mechanobiology/electrobiology and interfacial characterization of these biomedical materials in bone and nerve regeneration .The improvement in tissue regeneration, either in functionality or morphology, largely depends on the increasing knowledge of the properties of mechano- and electro conductive tissues and organs. The purpose of physical stimulation is generally to simulate the nature of the living tissue and organ itself. For instance, microenvironmental remodeling in nerve repair is essential and influenced by the spatial and temporal changes after nerve injury. This also greatly affects the scaffold design and physiochemical factors of the nano- and micro-scale biomaterials . The rec"} +{"text": "In contemporary context the difficulties of making sense of social ambiguity becomes one of the most important appeals for seeking the psychological help. This grounds the importance of studying the mechanism underlying the quality of mentalization and its individual variations.The objective of the study was to find empirical relations between the quality of mentalization and its cognitive, emotional and expressive mediating factors.(1) The Adult Attachment Interview, scored using Social Cognition and Object Relations-Global rating method for mentalization ability. (2) Group embedded figures test. (3) New Tolerance-Intolerance to ambiguity and (4) Toronto alexithymia scale questionnaires. Twenty participants, aged 18-38, looking for psychological consultation, took part in the study.Correlation analysis suggests positive relation between field-independency and tolerance to ambiguity . The complexity of representations of the mind positively correlates with the understanding of social causality . The affective quality of relationships\u2019 representations positively correlates with the ability to emotionally invest into relationships , and with the understanding of social causality . The ability of emotional investment into relationships also positively correlates with the understanding of social causality . There is a negative link between the severity of alexithymia and the presence of long-term relationships with a partner .Mentalization should be understood as a system, with underplaying cognitive, expressive and emotional factors.No significant relationships."} +{"text": "The sudden changes in daily routine due to the containment measures adopted for facing the COVID-19 pandemic have had an impact on the mental health of the general population. In particular, young adults are exposed to a higher risk compared to the general population to suffer from the consequences of the pandemic, in terms of anger and irritability, depressive symptoms and somatic complaints, insomnia, lack of motivation and loneliness. In particular, loneliness can be particularly pronounced during young adulthood.This study aimed to describe the levels of loneliness in a sample of Italian young people during the national lockdown in 2020, evaluating clinical and socio-demographic differences and the role of coping strategies and levels of resilience.A sub-analysis of a sample of adults aged 18-34 years has been drawn on a larger cross-sectional observational national trial in which, among other psychopathological dimensions, the levels of loneliness have been assessed by the UCLA scale short version.Levels of loneliness were particularly severe in a third of cases , in association with depression, anxiety, stress, OCD symptoms, higher rates of suicidal ideation, sleep disturbance and excessive use of Internet. Levels of loneliness tended to increase over time.Overall, during the Italian COVID-19 lockdown young people have experienced quite high levels of loneliness: this dimension could represent a useful domain to assess in routine clinical practice.No significant relationships."} +{"text": "Cannabidiol (CBD) has been gaining increased attention in contemporary society but seems to have been little explored in dentistry. This scoping review mapped the scientific and technological scenarios related to the use of CBD in dentistry. Peer-reviewed publications were searched in five international databases, patents were searched in five technological platforms. In total, 11 articles and 13 patents involving CBD in dentistry-related applications were included. The countries contributing to most articles were Brazil (27.3%) and USA (18.2%). The studies involved experiments on animals (63.6%) and/or using bacteria or cells (36.4%), and no clinical study was found. Three different applications of CBD were observed: periodontal therapy (45.4%), aid for bone regeneration (27.3%), and general use in oral therapies (27.3%). Patent inventors were based in China (53.8%) or USA (46.2%). The patent claims were mainly compositions for oral care, tooth whitening, injury repair, antifungal, anti-inflammatory, and analgesic effects. A total of 76.9% of the patents were filed in association with a company. In general, research suggests that CBD has promising biological properties for applications in dentistry, whereas patents indicate that the current interest of industry relies on compositions for oral care. There appears to be extensive room available for research and technological applications of CBD in dentistry. Endocannabinoids are naturally occurring molecules in mammals produced in the endocannabinoid system ,2, whichCannabidiol (CBD) is a compound without psychoactive activity derived from Cannabis sativa plant . CBD hasIncreasing research and development of CBD and its medical applications have been undertaken due to financial support by various private and governmental organizations in the past years. The global CBD market is expected to reach approximately USD 30 billion by 2025 . CBD hashttps://osf.io/yk65c/ (accessed on 10 October 2022). For the mapping, the following parameters were selected: (i) Population\u2014articles and technological products; (ii) intervention\u2014use of CBD or its synthetic analogs; (iii) comparison: other substances or treatments that may have been tested (if applicable); (iv) dental and oral medicine applications, (v): articles or patents. One general question guided the review: What scientific applications and technological products based on CBD or its synthetic analogs are being used in dentistry at present?This scoping review has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guideline . The stuThe inclusion criteria consisted of in vitro or in vivo studies and patents that have evaluated or reported the use of CBD for dental applications or subjects . Studies that evaluated the use of CBD alone or associated with other substances or biomaterials in dentistry were included. In addition, studies that evaluated other synthetic analogs were also included. The search was restricted to documents published in English without restriction on date. Case reports, case series, pilot studies, opinion articles, letters, and conference abstracts were excluded due to the high risk of bias associated to these articles. Reviews were excluded to concentrate the analysis to original articles. Studies on the use or smoke of cannabis plants and other cannabinoids also were excluded. Patents including CBD were excluded when its application or scope of patents was not related to dentistry or oral medicine.The searches in literature databases were performed by two independent reviewers (CD and AE-H) and patent tools (CD and AB), with no starting date and continuing through to December 2021. The research for articles was carried out in five international databases: PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library. The search strategy was based on the MeSH terms of PubMed and the specific terms of the other databases, using the search strategies presented in All records identified were imported into the EndNote program . The independent researchers identified articles and patents by first analyzing titles and abstracts for relevance and eligibility criteria using the online system Rayyan QCRI . Retrieved records were classified as included, excluded, or uncertain. Full-text versions of the included and uncertain records were selected for further eligibility screening. Discrepancies in a screening of titles/abstracts and full texts were resolved by discussion. In case of disagreement, the opinion of a third reviewer (RRM) was sought.We created two spreadsheets in the Microsoft Office Excel 2013 software for data extraction from articles and patents. The spreadsheets were pilot tested by three reviewers to reach a consensus on which data to collect and how. Two independent reviewers extracted the main relevant data, specifically focusing on the outcomes in dentistry, and influence of CBD on the dental applications. The following items of data were collected for articles: year, first author, journal, study design, country of the corresponding author, CBD dosage, route of administration, CBD presentation, manufacturers, applications , and sponsors of the studies. From patents, the following data were collected: patent numbers, year, title, inventors, country of inventors, main claims, and company. The mapping of research findings and patents was carried out considering the application of CBD in different dental subjects.A total of 2312 unique articles and 989 patents were identified with 229Characteristics of the 11 original studies included are presented in Characteristics of the 13 patents included are shown in The main applications of CBD and its synthetic analogs in dentistry are illustrated in The anti-inflammatory properties of CBD also made it a suitable alternative for the prevention and treatment of oral mucositis, by reducing the inflammatory process and the severity of lesions ,19. CBD This scoping review mapped the available literature and patents on the use of CBD for dentistry-related applications. Most of the peer-reviewed literature suggested that the positive effects of CBD could be attributed to its anti-inflammatory, analgesic, antimicrobial, biological, and osteoinductive properties. The patents also seemed to rely on these properties to offer technological applications of CBD in dentistry. The dental subjects mainly involved in the literature and patents reviewed were periodontology, oral medicine, and oral surgery. These subjects, the potential technological applications of CBD, and future research challenges on the topic are discussed as follows.CBD has anti-inflammatory properties and was shown to be capable of reducing alveolar bone loss in induced periodontitis ,25. PharThese anti-inflammatory and analgesic properties of CBD have been reported to be dose-responsive, without ideal doses having been established for a possible antioxidant and anti-inflammatory action ,21,26. TIn an in vivo study , the synPorphyromonas gingivalis and Filifactor alocis, which are key components of subgingival microbiota [CBD showed effective antimicrobial properties in the reduction of colonies of bacterial strains against oral bacteria and two biofilms . High docrobiota . Dental crobiota . Howevercrobiota .CBD has shown favorable biological and osteoinductive properties. When used alone or in combination with other substances, CBD was sufficiently effective and reliable to produce cell migration and bone differentiation ,7,26 andIn line with the recent literature on the use of CBD in dentistry, our findings also revealed an increasing interest in technology and appropriation relative to dental applications of CBD in recent years. Despite the increasing progress in filing these patents, only one patent dating bA number of limitations relative to research and technological applications of CBD in dentistry can be cited. One limitation is the absence of clear regulations governing the supervision of the quality of CBD , which cStudying of the behavior, dosage, and mechanisms of action of CDB used in dentistry-related clinical conditions;Acceptability of CBD-based treatments among dental patients;Standardization of the methods used for extraction of CBD and standardization of in vitro and in vivo tests with this compound ;Evaluation of the cytocompatibility of CBD in order to develop safe products;More basic studies are needed to increase safety of CBD for use in dental patients;Since CBD has been approved for use in patients in many countries, clinical studies with patients are also needed in dentistry, which means that the available evidence is of low quality, low certainty, and prone to risk of bias.The scientific articles reviewed indicated challenges to the current clinical use of CBD in dentistry and a potentially extensive field for research and products using CBD and its synthetic analogs, including:Cannabidiol has been gaining increasing attention in contemporary science and society but seems to have been little explored in dentistry-related research and patents to date. Dental research evidence suggests that CBD has anti-inflammatory, analgesic, antimicrobial, biological, and osteoinductive properties for potential periodontal, oral surgery, and oral medicine applications. Patents available indicate that at present, the interest of industry relies on compositions for oral care products including toothpaste, mouthwash, and dental floss. There appears to be extensive room available for research and technological applications of CBD in dentistry, especially as far as the lack of clinical trials is concerned."} +{"text": "Dear editor,Melkersson-Rosenthal syndrome (MRS)/orofacial granulomatosis is characterized by the triad of recurrent orofacial edema, recurrent peripheral facial palsy, and fissured tongue.The cause of MRS is unknown. The authors of the present study demonstrated an increase in the expression of HLA A*02, HLA DRB1*11 to HLA DQB1*03 and a decrease in the levels of HLA A*01, HLA DRB1*04, HLA DRB1*07, and HLADQB1*02 in patients with MRS when compared to the control group, indicating genes that may predispose to or protect against the disease.The histopathological findings of MRS include non-caseating granulomas similar to CD, which may suggest that MRS and CD might be part of the same clinicopathological spectrum.4The present report describes seven cases of MRS in children and adolescents, drawing attention to a possible association with CD.The analyzed data from the cases diagnosed with granulomatous cheilitis/MRS/orofacial granulomatosis were: sex, age, lesion location, neurological impairment, and colonoscopy exams . The diaThis sample represents the largest case series of children with MRS in Latin America.There was a predominance of male patients; the only female patient noticed symptoms at age 15. The cases reviewed by Savasta et al. showed a prevalence of female patients.Only patient 6 reported a previous bout of facial palsy, having also had an episode observed by the authors. Facial palsy affected 61/116 (52.6%) of the previously reported pediatric cases.Cases 4, 5, 6 and 7 had fissured tongue; cases 4 and 6 had geographic tongue and FUNADERSP \u2012 (29/2016).Camila F\u00e1tima Biancardi Gavioli: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Yasmin da Silva Amorim City: Statistical analysis; approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; critical review of the literature.Giovanna Piacenza Florezi: Design and planning of the study; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Silvia Vanessa Louren\u00e7o: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Marcello Menta Simonsen Nico: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Plant-derived antioxidants are a large group of chemical compounds that include the secondary metabolites of plants and the substances formed in food during processing . These compounds are widely distributed in fruits and vegetables, as well as their derived products. Natural antioxidants have been gaining increasing interest, mainly due to the association between their consumption and the prevention of cardiovascular disease, cancer, neurodegenerative disorders, diabetes, and some other illnesses. Many research studies on plant-derived antioxidants have shown that these compounds exhibit a wide range of biological effects, including anti-aging, anti-inflammatory, anti-atherosclerotic, and anti-cancer. The bioavailability and bioefficacy of plant-derived antioxidants, including polyphenols, carotenoids, and tocopherols, are dependent on their molecular structure, food matrix, the occurrence of other substances, and their digestion pathways. Recent evidence suggests that the pharmacokinetics and metabolism of bioactive compounds are crucial to understanding their role and function in human health. However, the exact mechanisms of action, effects, and bioavailability of plant antioxidants are still not fully recognized.This Special Issue consists of 18 articles focusing on the field of fortified and functional foods, the impact of technological processes on the content and transformation of bioactive components and the antioxidant activity of food, as well as in vitro and in vivo studies of the bioavailability, bioaccessibility, and bioactivity of plant-derived antioxidants, and explaining the effect of metabolism and pharmacokinetics on the efficacy of plant antioxidants and other potentially health-promoting mechanisms.Lactobacillus casei, and pork sausages [The scientific literature provides many examples of the use of plant raw materials rich in antioxidants and by-products of their processing to obtain fortified or functional foods, especially products that are poor in antioxidants in traditional formulations. A rich source of many active substances with health-promoting properties is sea buckthorn. Among them, antioxidants, phytosterols, essential fatty acids, amino acids, and vitamins C, K, and E should be mentioned. Sea buckthorn shows antimicrobial and antiviral properties and is a potential nutraceutical or cosmeceutical. Moreover, it has been proven to help treat cardiovascular diseases, cancer, and diabetes, as well as gastrointestinal and skin problems. Sea buckthorn is the most often used in the production of foods such as juices, jams, wines, pies, and liquors. There are also known examples of the addition of this fruit or its preparations for the enrichment of frozen yoghurt, soy drinks fermented by sausages . Anothersausages determinsausages . Waste osausages used appsausages .Polyphenolic extracts, which could be used as functional food ingredients and whose qualitative\u2013quantitative composition and properties depend on the extractant used, can be obtained from grape pomace. A study by Caponio et al. showed tBrassica oleracea var. gongylodes) were used as research material. The study indicated that UVB irradiation could induce an overall alteration in metabolite composition. Increased levels of secondary metabolites, such as anthocyanins and phenolic acids and ABTS free radical scavenging ability were observed during UVB irradiation [The cultivation conditions and the type and parameters of the production processes used affect the chemical composition and properties of raw materials as well as semi-finished and finished products. Research into the effect of UVB radiation on changes in the composition of primary and secondary metabolites in plants was conducted by Yeo et al. . Purple adiation .Thermal processes can cause changes in the chemical composition, structure of compounds, and the bioactive properties of food. For example, roasting affects the qualitative and quantitative composition of polyphenols, the formation of Maillard reaction products and, consequently, the antioxidant potential of carob kibbles . ThermalO-glucoside (C3G) showed a low bioavailability of this compound and confirmed its significant instability under intestinal conditions [O-glucoside binds in the vicinity of the catalytic site of \u03b1-amylase and lipase. In contrast, in the case of \u03b1-glucosidase and lipoxygenase, no direct contact with catalytic amino acids was found. However, further research involving biological assays is needed to confirm the possibility of using this extract as a natural agent to treat and reduce the incidence of MS [The bioavailability, bioaccessibility, and bioactivity and, consequently, pro-health potency of plant bioactive compounds depend on their molecular mass, chemical structures, concentration in food, as well as food matrix and digestion pathways. Studies provided by Fraisse\u2019s team using a simulated gastrointestinal tract model on the bioavailability of cyanidin-3-nditions . The decnditions . Other hnditions . The anace of MS .Humulus lupulus L.), their bioavailability and their biological activity. It reports the most important results obtained so far in the primary and secondary prevention of several non-communicable diseases, such as cancer and MS, understood as a cluster of risk factors for diabetes mellitus and cardiovascular diseases in the presence of central obesity [A review article authored by Zugravu et al. describe obesity .Triticum spelta L. cv. Ostro), the highest relative bioavailability of p-coumaric acid and trans-ferulic acid showed seeds subjected to enzymatic treatment and then fermentation. These processes also allowed for the improvement of the antioxidant activity of the tested material [Talaromyces amestolkiae [The bioavailability of phenolic compounds contained in food matrices can be enhanced by the prior application of various bioprocessing techniques. In the case of spelt seeds -epicatechin and only in stem bark extract: (+)-catechin) and nine phenolic acids were identified in the extracts). All of the tested extracts showed antioxidant and DNA-protective potential, most visible in the case of extracts from flower parts and leaves [Andonova et al. conducted leaves .Carotenoids are colored compounds with lipophilic properties and poor solubility during digestion, resulting in low and variable bioavailability. On the other hand, they are characterized by high antioxidant activity affecting several health benefits. The effect of frequently consumed proteins , gelatin, GEL; turkey and cod) on carotenoid bioavailability and cellular uptake was studied. The food content after joint digestion in the gastrointestinal tract of these proteins with food matrices rich in carotenoids (tomato and carrot juice and spinach) was studied in Caco-2 cell models. The matrices containing higher amounts of non-polar carotenes after protein addition were characterized by better fractional bioavailability during simulated digestion in the gastrointestinal tract than analogous systems of matrices rich in more polar xanthophylls. The digestion of matrices in the presence of protein promoted the cellular uptake of carotenes and counteracted the negative effect of proteins on the bioaccessibility of xanthophylls by improving the cellular uptake of lutein + zeaxanthin (up to 12%), especially in the presence of WPI and SC proteins .n = 16) conducted by \u00c1vila-G\u00e1lvez [Flavanones are consumed in our diet almost exclusively with citrus fruits and, to a lesser extent, with some herbs or tomatoes. Hesperidin is the main flavanone present in oranges, and eriocitrin in lemons. The available scientific evidence shows that the intake of flavonoid-rich citrus fruits is associated with a lower risk of stroke and the occurrence of certain types of cancer. However, the low solubility of hesperidin hinders its bioavailability. A randomized human crossover pharmacokinetic study n = conducteThe LC-ESI-LTQ-Orbitrap-MS was used to study the distribution of oleaceins (OLEA), oleocanthalu (OLC), and their metabolite derivatives in rat plasma and organs/tissues after the acute intake of refined olive oil. Unmetabolized OLEA was detected in the stomach, small intestine, liver, plasma and, above all, in the heart. OLEA metabolites, in turn, were mostly distributed in the liver, heart, spleen and lungs. OLC was detected only in gastrointestinal samples, while its metabolites were widely distributed in rat tissues, with the small intestine and liver being the most important metabolizing organs. The obtained results may partially explain the mechanism of the beneficial effect of extra virgin olive oil consumption. However, further detailed pharmacodynamic studies are needed to link the ingested concentrations of OLEA and OLC and the composition of their metabolites with the frequency of the intake and the effect on the human body ,18."} +{"text": "Background: The impacts of health inequities on healthcare access, utilization, and outcomes have been highlighted by the COVID-19 pandemic, but these issues have been ongoing, yet understudied, in infectious disease epidemiology. Health inequities affect access to care, quality of care, and health outcomes in all healthcare settings. One healthcare setting that has yet to be fully studied in the context of health inequities is nursing homes. Nursing homes have a host of facility and population-specific issues that differ from other healthcare settings, making the impacts of health inequities likely unique and imperative to understand. The impacts of health inequities on nursing homes are unclear, and they likely have downstream effects on trends in morbidity, mortality, and transmission of multidrug-resistant organisms (MDROs) and other pathogens. Method: Here, we present a descriptive analysis, integrating multiple datasets relating to nursing home facility factors (data from the CMS Provider of Services and the CDC NHSN), nursing-home staffing trends , and social vulnerability . We conducted a spatial analysis of nursing-home locations and the social vulnerability of the area. Results: Investigations of facilities and health inequities are best conducted in small spatial geographies. Analyses with less detailed spatial geographies miss high levels of heterogeneity in social vulnerability. Figure Conclusions: These findings highlight that health inequities affect the quality and quantity of care of in nursing homes and that research conducted at larger geographical scales may overlook important mechanistic factors. This work will inform epidemiological models for disease transmission in nursing homes, accounting for the impacts of health inequities on transmission. Abating health inequities in all healthcare settings is a necessity to improve public health for the entire United States.Funding: NoneDisclosures: None"} +{"text": "Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with the etiology and progression of neurodegeneration and other neurological pathologies. Hence, brain lipids are emerging as important potential targets for the early diagnosis and prognosis of neurological diseases. This review aims to highlight the significance and usefulness of lipidomics in diagnosing and treating brain diseases. We explored lipid alterations associated with brain diseases, paying attention to organ-specific characteristics and the functions of brain lipids. As the recent advances in brain lipidomics would have been impossible without advances in analytical techniques, we provide up-to-date information on mass spectrometric approaches and integrative analysis with other omic approaches. Last, we present the potential applications of lipidomics combined with artificial intelligence techniques and interdisciplinary collaborative research for treating brain diseases with clinical heterogeneities. This review article explores lipid alterations in brain diseases and provides insight for future brain lipidomic research. With an increase in the aging population worldwide, brain diseases such as neurodegenerative diseases, psychiatric diseases, and brain tumors are being increasingly recognized as leading causes of morbidity and death . NoBrain cholesterol accounts for 25% of the total cholesterol found throughout the body. Cholesterols, which are mostly generated from astrocytes, are transferred to neurons through the formation of cholesterol-rich lipoproteins, including apolipoprotein E (APOE) (fig. S1) (N-acetyl-\u03b1-neuraminidase 3 (Neu3) and phospholipase D (PLD) , a neuronal protein that affects the regulation of synaptic vesicles and neurotransmitter release, the subsequent production of Lewy bodies , and the loss of dopaminergic neurons (HTT) gene is a well-known cause of HD is an inherited progressive brain disease characterized by abnormal motor functions (chorea and dystonia), psychiatric complications (anxiety and depression), and cognitive functions (dementia) spectrometry, fluorescence assay, and MS and software tools have been developed for monitoring large-scale datasets, for performing the compositional and structural profiling of numerous lipids, and for analysis of their molecular networks . LIPID MAll these developments in MS-based analytical platforms and software tools for data interpretation have led to the availability of increasing reference data for lipidomic research, thereby facilitating large-scale studies. In recent years, these analytical tools and DBs have been used for brain lipidomics. However, many brain lipids are still unknown, increasing the need for their global and in-depth characterization.Brain diseases, such as neurodegenerative diseases and psychiatric diseases, commonly exhibit molecular and clinical heterogeneities, which makes the development of diagnosis and treatment strategies quite difficult. Multi-omics is a powerful and useful approach to unravel the molecular mechanisms of diseases gene GBA (one of the genetic risk factors for PD), and lipid substrates of GCase, such as glucosylceramides, ceramides, and sphingosines, is explored using the CSF of patients with or without gene mutations . IThe fundamental agenda in brain research involves understanding the structural and functional characteristics of molecular organization in the brain, starting from the genes to the whole organ, and the development of treatment approaches for brain diseases and psychiatric diseases. To achieve this goal, the use of human resources is inevitable because animal models used often demonstrate limitations in reflecting the physiological state of humans owing to the differences in the genotype and life cycle. In addition, interdisciplinary collaborative research between different fields such as neuroscience, mathematics, physics, computer science, engineering, and medicine is required for the systematic investigation of brain functioning and the practical application of research results . Unlike"} +{"text": "Building on the importance of family and friends as sources of social connectedness in later years of life, we conducted a contextual examination of their independent and interactive roles in predicting mental health, using a compensatory social convoy model. In a sample of older Korean Americans, we anticipated that friend networks would be a more important predictor of mental distress when strong family relationships were absent. Data were from 2,140 participants in the Study of Older Korean Americans, a multi-state survey of Korean immigrants age 60 and older . To identify family types, latent profile analysis (LPA) was performed with 17 variables assessing family networks, positive and negative interactions with family members, and incidence of mistreatment by family. Linear regression models of mental distress then examined the direct effects of family type and networks of friends, as well as their interactions. LPA on family-related items identified three family types: close-knit, mixed, and dysfunctional. Membership in the close-knit group and a larger network of friends were associated with lower levels of mental distress. In addition, a significant interaction was found between dysfunctional family type and friend network , where the positive effect of friend networks was most pronounced in the context of dysfunctional family relationships. These findings support the use of a compensatory social convoy model. Substituting for family resources, friend networks yielded compensatory mental health protection for those with dysfunctional family relations."} +{"text": "Approximately 30 years after the publication of the first Sicilian checklist of macrofungi, a new updated version is presented here. The census of macromycetes was carried out through periodic observations in different agricultural and forest ecosystems, in urban areas, in public and private gardens, and in botanical gardens. The 1919 infraspecific taxa included in 508 genera belonging to 152 families were collected in the Sicilian territory. Ectomycorrhizal fungi are the most represented ecological category, followed by saprotrophs on wood, saprotrophs on litter, and terricolous saprotrophs. The interest in this rich group of organisms is evidenced by the nutritional and therapeutic value of a high percentage of species. The actions linked to the National Recovery and Resilience Plan and The Network for the Study of Mycological Diversity will further increase the number of macrofungi for Sicily in the future. The checklists are modern tools for evaluation of fungal diversity and valuable papers to highlight ecological data, and tips for management and exploitation of protected areas, agro- and forest ecosystems. Relevant studies were published around the world\u2014in Europe and in Italy ,5,6,7,8.The assessment of fungal diversity in the Italian regions is still incomplete and needs further investigation. In most Italian regions, it is difficult to document the exact number of mushrooms due to lack of mycologists. Even greater difficulty is faced in the evaluation of the presence of hypogeous macrofungi as few research groups have dogs trained to harvest.The territories included in the Med-Checklist consider the Italian peninsula as a separate region from a floristic point of view, and its two major islands, Sicily and Sardinia, are separately coded . The envOn the basis of literature data reported from 1814 to 1991, a preliminary survey on fungal diversity in Sicily was carried out by Venturella , with anFrom 1991 to present, the study of macromycete diversity has continued unabated through an intensive exploration of forest ecosystems, natural parks, nature reserves, public and private gardens, botanical gardens, cultivated and uncultivated lands.Based on data collected during 30 years of long-term observation, an up-to-date assessment of fungal diversity of Sicily is reported in this paper.The physiographic uniqueness of Sicily coupled with the paleogeographic vicissitudes, over time have determined the progressive evolution of a rich vascular flora (ca. 3000 species) and the presence of a number of rare species or in any case of considerable taxonomic significance . In agreQuercus ilex L. subsp. ilex, Q. coccifera L., and Q. suber L. as well as semi-evergreen oaks Quercus pubescens Willd. s.l. and Q. virgiliana (Ten.) Ten. In the warmer areas near the sea, forests can be replaced by aspects of Mediterranean maquis such as those characterized by Juniperus turbinata Guss., J. oxycedrus L. subsp. oxycedrus, J. macrocarpa Sm., Pistacia lentiscus L. and other sclerophyllous shrubs such as Cistus creticus L., C. salvifolius L. and C. monspeliensis L.The forest area of Sicily corresponds to 512,121 hectares and includes 58 types of forest vegetation . The coaAmpelodesmos mauritanicus (Poir.) T. Durand & Schinz and other types of grassland and shrub communities. Even rarer are the natural forests of Mediterranean conifers such as Pinus halepensis Mill., P. pinea L. and P. pinaster Aiton, which are considered pioneer plants. In the hills, the natural forest vegetation, in the hottest and driest conditions, consists of mixed forests of deciduous oaks with dominance of Q. pubescens, while in cooler climatic conditions, with a marked oceanic climate, are more diffused Q. cerris L., Q. petraea (Matt.) Liebl and the endemic Q. gussonei (Borz\u00ed) Brullo. These species have in some cases been replaced for agricultural purposes or for the use of wood by Corylus avellana L., Fraxinus ornus L., and Castanea sativa Mill. The degradation aspects are represented by mesophilic shrubs dominated by different taxa belonging to the family of Rosaceae such as Pyrus pyraster. (L.) Burgsd. and P. amygdaliformis Vill. The forest vegetation of the mountain area is characterized by forests of Fagus sylvatica L. sometimes mixed with Acer pseudoplatanus L., Quercus petraea (Mattuschka) Liebl., Taxus baccata L. and llex aquifolium L. An exclusive characteristic of Sicily is the presence of forests of Q. ilex that reach an altitude of 1500 m well above the maximum elevation found in other parts of Italy. Of considerable interest is also the presence of different endemic trees and shrubs and evidence of relict forest vegetation such as Abies nebrodensis (Lojac.) Mattei, Betula aetnensis Raf., Celtis aetnensis (Tornab.) Strobl, Populus tremula L., Pinus laricio Poir., Quercus gussonei (Borz\u00ec) Brullo, Zelkova sicula Di Pasquale, Garfi & Qu\u00e9zel, and Genista aetnensis (Raf. ex Biv.) DC. Upland shrubs such as Sorbus graeca (Spach) Schauer and Berberis aetnensis C. Presl. are found in some areas lacking tree forest vegetation. Woody species that vegetate above the edge of the forest are found only on Mount Etna, but also in the Madonie. This vegetation is dominated by the shrubs of Astragalus nebrodensis on the Madonie and by A. siculum on Mount Etna.In the areas most subject to disturbance, the vegetation is currently represented by Fagus sylvatica L. in Sicily can therefore be considered a remnant of the glaciations, when conditions had to be favorable even at lower altitudes.The presence of Salix pedicellata Desf., S. alba L. and S. purpurea L., associated with Populus nigra L., P. alba L., Laurus nobilis L., Sambucus ebulus L., Cornus sanguinea L., Prunus mahaleb L. and Alnus cordata (Loisel.) Desf. , cupules of Castanea sativa Miller [Lanzia echinophila (Bull.) Korf], and cladodes of Opuntia ficus-indica [Pleurotus opuntiae (Durieu & L\u00e9v.) Sacc.] complete the list.Ectomycorrhizal fungi (637 taxa) are the most represented ecological category , followeFungi are recognized worldwide as fundamental components in every type of ecosystem . After aThe climatic features of Sicily are favorable to the development of basidiomata and ascomata of different fungal species. The observations carried out during the present study showed a constant presence throughout the year of macrofungi in ecosystems. Most species are collected in fall, although the presence of macrofungi appears to be strongly affected in some years by prolonged periods of drought. In the woods of the hinterland, it is possible to have optimal conditions of temperature and humidity able to favor the appearance of macrofungi even in the summer. In Sicily, spring is not a season of abundance for fungal fruiting and ascomycetes predominate among species. In winter and summer, pathogenic basidiomycetes and wood saprotrophs can be predominantly observed.Due to the presence of the three major regional parks in these territories, the largest number of infraspecific taxa is found in the provinces of Palermo, Messina and Catania. In the other provinces, reafforestations are prevalent and thus the composition of fungal coenoses is reduced in quality and quantity.Marasmius bulliardii while it is very common to observe Fistulina hepatica at the base of chestnut trees. In Quercus ilex forests, fungi responsible for wood decay are observed on stumps and trunks. Compared with other oak forests, fewer macrofungi are reported Quercus suber forests and in the maquis. This is due to the greater state of degradation of the forest coenosis due to frequent fires that cause a significant reduction in the number of mycorrhizal species and saprotrophs, the latter negatively affected by the drastic reduction in plant residues. In pastures, grasslands, and garrigues, the number of mycorrhizal species is limited to those of shrubs of the genus Cistus (Lactarius cistophilus and Leccinellum corsicum). Saprotrophs on litter and lignicolous species are widespread in riparian vegetation.The greatest number of species is found within beech forests. The low night temperatures, the summer storms and the presence of occult precipitations determine, starting from the second decade of August, the early appearance of macrofungi that are generally found, at lower altitudes, in autumn within the forest ecosystems. A rich number of lignicolous species, mostly pathogenic and to a lesser extent saprotrophic, has also been surveyed within beech forests, growing on trees, branches of different sizes that have fallen to the ground and stumps. A similar condition of prevalence of mycorrhizal species is found in oak and holly forests and in chestnut groves. In the latter type of forest, an important role in the decomposition of the abundant litter layer is provided by The high percentage of mycorrhizal species within the natural forests and reforestations of Sicily allows to exclude at the moment a decline in forest ecosystems. In some forested areas, frequent fires cause a reduction in mycorrhizal species and saprotrophs on litter due to the drastic reduction in plant residues. Conversely, silvicultural practices and the resulting failure to remove woody debris of different sizes promote the appearance of crusty, shelf-like, or gelatinous lignicolous macrofungi.Pleurotus ssp.) represent a valuable example for the economic enhancement of fungal diversity in Sicily. Of great interest is the presence on the Sicilian territory of rare species classified according to IUCN criteria as Vulnerable (Alessioporus ichnusanus) [Poronia punctata) [Pleurotus nebrodensis) [Grifola frondosa, Ganoderma lucidum, and Ericium erinaceus, with proven pharmacological activities including antibacterial, antifungal, antiviral, cytotoxic, immunomodulating, anti-inflammatory, antioxidative, antiallergic, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities.The presence of prized and edible truffles, especially within the holm oak and pine woods, is of relevant interest especially for the areas of the Sicilian hinterland characterized by a depressed economy . These pnusanus) , Least Cunctata) , and Endodensis) . MushrooPleurotus and Tuber species, can provide an important income in agroecosystems, especially in rural or marginal areas.Although the number of fungal species is still in constant flux, Sicily is among the Italian regions with the highest diversity of fungal species, many of which are of potential applicative interest and economic interest. Therefore, it is necessary to raise the level of knowledge and attention on the part of local communities towards this group of organisms. The data reported in this survey strongly increase the knowledge on distribution and ecology of macromycetes in Sicily and may help better valorize such non-timber products. The outcome of the checklist carried out in Sicily could provide the Regional Administration with useful information for the conservation and exploitation of fungi in natural habitats, with particular reference to forest ecosystems. Legislation should limit the level of danger existing for the conservation of fungal diversity and support such strategies with more rigorous limits against wild edible mushroom overharvesting. The cultivation of some prized edible mushrooms, i.e., The National Recovery and Resilience Plan (NRRP) and The Network for the Study of Mycological Diversity (NSMD), recently launched, will contribute to implement the monitoring of mycological biodiversity within national terrestrial habitats.These actions will be carried out with the contribution of institutions such as the Higher Institute for Environmental Protection and Research (ISPRA) of the Italian Ministry of Ecological Transition and the Working Group for Mycology of the Italian Botanical Society through an Open Science initiative."} +{"text": "Next, the microstructure and properties after the selective laser melting fabricating process which act as an emerging technology compared to conventional manufacturing techniques are also enlightened. Thereafter, the development of multi-scale simulation and machine learning (ML) in material design is illustrated with typical examples and the great concerns in PHSS research are presented, with a focus on the precipitation techniques, effect of composition, and microstructure. Finally, promising directions for future precipitation hardening stainless steel development combined with multi-scale simulation and ML methods are prospected, offering extensive insight into the innovation of novel precipitation hardening stainless steels.Precipitation hardening stainless steels have attracted extensive interest due to their distinguished mechanical properties. However, it is necessary to further uncover the internal quantitative relationship from the traditional standpoint based on the statistical perspective. In this review, we summarize the latest research progress on the relationships among the composition, microstructure, and properties of precipitation hardened stainless steels. First, the influence of general chemical composition and its fluctuation on the microstructure and properties of PHSS are elaborated. Then, the microstructure and properties under a typical heat treatment regime are discussed, including the precipitation of B2-NiAl particles, Cu-rich clusters, Ni Precipitation hardening stainless steel (PHSS) has a long history and is widely employed in aerospace industries, marine environment applications, and nuclear reactor fields due to its ultra-high strength, satisfactory ductility, and excellent anti-corrosion properties ,2,3,4,5.The microstructure and distinguished properties of ultra-high strength stainless steels have been characterized through experimental techniques in the past decades ,9,10. ThVarious martensite variant microstructures with significant anisotropy features were demonstrated based on first principles calculation and phase-field simulation methods, which is in acceptable agreement with experimental results ,25. The In this review, we concentrate on recent progress in the advancement of PHSS, including the ultra-high strength steel not limited to the precipitation hardening steel (PHS) and PHSS, in regard to the modeling of composition-microstructure-properties relationships, especially in the hot working process, as well as the effects of compositions on the microstructure and properties of PHSS steels. Although the PHSS has a relatively long history, we would like to present how to establish a quantitative model of composition-structure-property to quickly discover novel high-performance PHSS. We start by summarizing the composition development and property features of PHSS, the microstructures and properties under representative heat treatments, and then discussing the microstructures and properties of the PHSS prepared by the selective laser melting (SLM) method. Finally, the strategies of alloy design and tailored property optimization of PHSS are prospected. This work is devoted to providing useful insight into the design strategies that are used to develop novel high-performance PHSS, specifically for engineering applications.Many investigations on PHSS have been carried out, and most of them focus on mechanical and corrosion behavior ,30,31,32The first-generation precipitation hardening martensitic stainless steel was designed in the 1840s . PHSS haPHSS is mainly strengthened by the precipitation of various nanoprecipitates during the aging treatment ,48, whicThe alloying elements in ultra-high strength stainless steel are mostly concentrated in transition metallic elements, and the corresponding frequency of alloying elements is displayed in 3Ti phases; Ni acts as a stabilizer of the austenitizing element, which promotes alloys with enhanced properties , a, a150], Generally, the traditional material design method based on trial and error is very cumbersome; therefore, it is urgent to carry out the modeling optimization. In recent years, the multi-scale calculation and simulation methods of materials have been developed rapidly and widely harnessed in the material design and mechanism research of new materials, which provides an efficient way for the development of new PHSS. The obtained FDM is determined through a numerical strategy. Physical characteristics of fluid flow, temperature, entropy optimization, and concentration have been illustrated. Variations of parameters are graphically investigated . The micAs shown in There are many types of alloying elements, and the additional content of alloying elements as well as the interaction between various elements would increase the complexity of the experiment. The traditional trial and error approaches are simple in facing the dilemma of low efficiency. C.E. Campbell et al. establisWith the vigorous development of computational science, it is a new trend to examine the influence of alloying elements on the properties of materials by leveraging algorithms to model rationally. Additionally, common ML algorithms were adopted to investigate the intrinsic relations of materials especially in steels, including random forest (RF), linear regression (LR), support vector regression (SVR), multi-layer perceptron (MLP), convolutional neural network (CNN), and K-nearest neighbor (KNN) ,185,186.3Ti nanoprecipitates coupled with thermodynamic calculations and PM theories [Physical metallurgical (PM) method has been employed as an efficient strategy to develop distinguished mechanical properties and illustrate the mechanisms of strength increment. Furthermore, Chunguang Shen et al. introductheories . Meanwhitheories . Therefotheories ,189. 3Ti phase, Cu-rich clusters, and other strengthening phases. A novel material with multiple co-existing particles was indicated to achieve comprehensive performance. In the present work, we focus on the establishment of the composition-microstructure-properties model of PHSS to urgently develop novel precipitation hardening stainless steels with superior mechanical properties. We over-reviewed the development history of representative PHSS. The influence of the composition fluctuation of general alloying elements on the microstructure and properties is discussed, and the research progress of the microstructure and properties of PHSS after the heat treatment process is summarized and illustrated, especially in the aspects of mechanical properties to guide the optimization of the heat treatment process. The relationships between precipitation strengthening nanoparticles and the microstructure and properties of steel were revealed, including typical B2-NiAl precipitates, NiCompared to traditional fabrication techniques, the advancement of AM in terms of machine capabilities and process parameters has resulted in the development of parts. The emergence of AM techniques provides strong support for the manufacturing and application of PHSS parts, especially for improving the microstructure and performance of PHSS steel prepared by SLM. At present, the AM technology of alloys is still in the immature stage. The parallel development of AM technology based on the traditional method of fabricating alloys provides convenience for the application of PHSS. There is still an enormous space for SLM to fabricate steel parts due to the drawbacks of PHSS, such as anisotropy, macro and micro defects, and residual stress after the existing processes.The development of new techniques and new approaches ensures the future exploration of PHSS with application potential. Moreover, it is necessary to employ ML strategies in materials science to extract the data from the results of experimental physical metallurgy and multi-scale simulation approaches, rather than trial-and-error methods, to comprehensively and efficiently design tailored PHSS with excellent mechanical properties. Additionally, future investigations will focus on developing reliable and robust databases and modeling the assessable correlations of chemical composition, hot work processes, microstructure, and properties. Machine learning and multi-scale simulation methods are used to reveal the relationship among the fraction and features of precipitates, processes, and properties to achieve accurate regulation of the precipitates. Meanwhile, attention should be paid to the precision heat treatment parameter control that takes into account fluctuations in composition by combining intelligent algorithms.Therefore, ML coupled with multi-scale simulation approaches and experimental methods undoubtedly exhibits a high-efficiency direction toward the development of novel PHSS with high performance, since ML has a strong capability to solve the intrinsic quantitative relationship between the microstructure of composition/process properties in the PHSS system. The prosperity of ML applications in PHSS design is poised to provide the perspective for a novel paradigm in integrated multi-scale computational materials science as a whole."} +{"text": "Polycystic Ovarian Syndrome (PCOS) is the most frequent hormonal/endocrine disorder in women of reproductive age and is one of the most common causes of infertility. Approximately 20% of Danish women of reproductive age are diagnosed with PCOS, and yet only a little attention has been paid to the psychological symptoms appearing in women with PCOS. The present study investigated anxiety, depression, and lower quality of life among Danish women of reproductive age who are diagnosed with PCOS.This was a cross-sectional survey study among 326 Danish women who self-reported as being diagnosed with PCOS. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression, and the PCOS-QOL scale was used to measure the quality of life. Chi-square tests and logistic regression analyses were used for analyzing data.Sixty-six percent of women were found to have anxiety (n = 216), 41% of women had depression and 70% of women had low quality of life The most frequently reported symptoms were irregular menstrual cycle (86%), overweight (73%), and mood swings (65%), and irregular menstrual cycle, overweight and infertility were the were perceived of having higher severity. After adjusting for age, ethnicity, education, and income, the severity of symptoms, namely irregular menstrual cycle, infertility, overweight, and hirsutism, were independently and positively associated with depression, and severity of symptoms, namely irregular menstrual cycle, mood swings, and hirsutism, was independently and positively associated with anxiety. Lower quality of life was independently associated with both anxiety and depression.Women with PCOS are at higher risk of anxiety, depression, and consequently, lower quality of life. Clinicians and other healthcare professionals should pay attention to the importance of mental health support in women with PCOS and work towards promoting it.\u2022\u2002Women with PCOS are at higher risk of anxiety and depression, and lower quality of life.\u2022\u2002Health care professionals working with women with PCOS should be aware of this and be prepared to offer necessary support."} +{"text": "The interest in membranes and membrane bioreactors for health and life sciences is rapidly growing thanks to their wide applications in advanced therapies and biotechnologies. Therapeutic approaches include the integration of membranes and membrane bioreactors for tissue regeneration and repair, for drug testing and drug delivery, and for cell therapy. Innovative biotechnologies employ membranes and membrane bioreactors for the production and selective separation of biological and bioactive molecules, for the design of diagnostic systems, and for the development of new drugs and pharmaceutical compounds.This Special Issue collects six original research articles by renowned experts, highlighting the current advances and new trends in membrane preparation, the membrane separation process, membrane bioreactors, and membrane applications in tissue engineering and biotechnologies. A new sequential fabrication route of wet spinning combined with UV curing has been presented by Yin et al. for the z-axis and forming a multi-layered epidermis. This strategy represents an attractive tissue engineering approach for the creation of specific human epidermal strata to test the effects and toxicity of drugs, cosmetics, and pollutants.The use of membranes is of key interest in the development of engineered tissues. Membranes provide adaptable biomimetic microenvironments that can emulate the essential characteristics of the physiological ones, including tissue-specific extracellular matrix interactions. Surface properties trigger specific cell responses dictating the cell fate in terms of cell growth, migration, proliferation, differentiation and functional activation. Salerno et al. developeDesign optimization of membrane bioreactors for tissue engineering applications and upscaling analyses requires an in-depth knowledge and understanding of the mass transport of nutrients to ensure uniform distribution and to solve critical limitation issues. Wang et al. investigThe global biopharmaceutical market for therapeutic proteins, vaccines, and gene vector manufacturing requires reliable and efficient separation processes to ensure the safety, potency, and efficacy of the therapeutics. Membrane ion-exchange chromatography promises several advantages over column chromatography, including low operating pressure and fast flow rates, ease of use, and elimination of cleaning and validation costs in single-use applications. To this end, Lemma et al. developeMembrane emulsification is a promising methodology in cosmetic and pharmaceutical biotechnology, with unique properties in terms of precise manufacturing of emulsion droplets under mild operating conditions, suitable to preserve the stability of bioactive labile components. Piacentini et al. used memNovel approaches in membrane technology aim to overcome the main drawback of filtration and separation processes, i.e., membrane fouling. This phenomenon, caused by the accumulation of solutes on the membrane surface or within the membrane pore structure, irreversibly affects the performance of the membranes and increases the overall operational cost due to the need for regular membrane-cleaning procedures. Among the different antifouling strategies that have been employed, magnetic responsive membranes allow for the control of solute-membrane interactions through a reversible adjustment and modification of physicochemical properties of the membrane surface, which translate into tuneable permeate fluxes and superior antifouling characteristics. Upadhyaya et al. developeIn conclusion, the different contributions collected in this Special Issue highlight the multifunctional role of membranes and membrane bioreactors in health and life science applications, addressing critical issues and aspects of the field. Membranes for their help and support during the review process.As guest editors, we would like to thank all the authors for their outstanding contributions. We sincerely feel that overall these papers offer innovative approaches and new trends that could stimulate future research in membrane science applied to the biomedical and pharmaceutical field. We would also like to thank the reviewers for their valuable contributions and the editorial staff of"} +{"text": "Viral hepatitis is a major global public health problem that affects hundreds of millions of people and is associated with significant morbidity and mortality. Five biologically unrelated hepatotropic viruses account for the majority of the global burden of viral hepatitis, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Omics is defined as the comprehensive study of the functions, relationships and roles of various types of molecules in biological cells. The multi-omics analysis has been proposed and considered key to advancing clinical precision medicine, mainly including genomics, transcriptomics and proteomics, metabolomics. Overall, the applications of multi-omics can show the origin of hepatitis viruses, explore the diagnostic and prognostics biomarkers and screen out the therapeutic targets for viral hepatitis and related diseases. To better understand the pathogenesis of viral hepatitis and related diseases, comprehensive multi-omics analysis has been widely carried out. This review mainly summarizes the applications of multi-omics in different types of viral hepatitis and related diseases, aiming to provide new insight into these diseases. Viral hepatitis is a major global public health problem that affects hundreds of millions of people and is associated with significant morbidity and mortality. Five biologically unrelated hepatotropic viruses account for the majority of the global burden of viral hepatitis, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). Despite that HAV does not develop into a chronic infection, HBV, HCV, HDV and occasionally HEV may cause chronic infections, of which HBV and HCV have a significant association with chronic incidence. Most deaths from viral hepatitis are due to HBV and HCV infections. According to the statistics, it was estimated that 296 million people were infected with hepatitis B, 58 million people were infected with hepatitis C and 1.1 million people died as a consequence of viral hepatitis infections in 2019 . In 2015The advances in technology have created a variety of new fields of study, commonly referred to as omics. Omics is defined as the comprehensive study of the functions, relationships and roles of various types of molecules in biological cells. The multi-omics analysis has been proposed and considered key to advancing clinical precision medicine, including genomics, transcriptomics and proteomics, metabolomics and so on . GenomicTo better understand the pathogenesis of viral hepatitis and related diseases, comprehensive multi-omics analysis has been widely carried out. Hence, this review summarizes the applications of multi-omics in different types of viral hepatitis and related diseases, aiming to throw light on the development of these diseases.Hepatitis A virus is a positive-strand RNA virus, which is transmitted through the fecal oral route. HAV outbreaks are often associated with poor sanitation, overcrowding or contamination of food and water . HAV infUsing genomics, To better understand the biogenesis of quasi-enveloped HAV (eHAV) virions, Hepatitis B virus is the most common cause of acute and chronic liver diseases worldwide, and approximately 4 million people are infected with HBV every year, especially in Asia and Africa . About 1By comparing the genomes of ancient African strains and HBV, As the DNA virus, HBV is different from other RNA hepatitis viruses since its viral genome can be integrated into the host liver cell genome. HBV integration is considered to lead to the occurrence of HCC, and the study of its structure is of great significance to the occurrence and development of HBV-related HCC. Advances in genomics have deepened the understanding of the diagnosis, prognosis of HBV-related HCC. The detailed genetic analysis of liver tissue provides important information for tumorigenesis and progression . The finThe applications of proteomics are of great significance in hepatitis B and related diseases . ProteomThe applications of proteomics provide new strategies for the occurrence, progression and replication of HBV. Based on yeast proteomics, In addition to the traditional HBV markers HBsAg and anti-HBs, the applications of proteomics have also expanded the development of diagnostic markers. Two differential proteins, VWF and C8B were considered to have the potential to distinguish HBV infection genotypes B and C and could provide precise guidance for HBV genotyping . The pepIn CHB patients, fibronectin levels in plasma have been demonstrated to be a predictor of HBsAg clearance . Long-teIn recent years, the applications of proteomics in HBV-related cirrhosis have also been reported. Autoantibodies recognized aminoacylase-1 (ACY1) were considered biomarkers to differentiate HBV-related cirrhosis and CHB patients by serum proteomic detection . ProteomProteomics also plays an important role in HBV-related liver failure. As HBV is a risk factor for the development of HCC, the applications of HBV-related HCC proteomics have also been paid more and more attention. O-glucoside was confirmed to inhibit HBsAg and HBV replication through mechanisms involving mitochondria infection . CHC infE-cadherin is a mediator of HCV entry into host cells and is closely related to HCV-induced epithelial-mesenchymal transition. Through functional genomics, Proteomics matters in hepatitis C and related diseases . ProteomDiagnostic and prognostic biomarkers of HCV-related HCC can be discovered by proteomics. Through the comprehensive metabolomics analysis, Through the genome-wide miRNA functional screening and transcriptomic analysis, Hepatitis D virus is only found in humans currently. It is a satellite virus, which is assembled, released and entered by the envelope protein of HBV. It is the smallest known RNA virus, encoding a single protein.Using meta-transcriptomics, Hepatitis E virus (HEV) is an important zoonotic virus that can infect various hosts. It has 7 main genotypes. Patients with HEV infection are mostly asymptomatic, some patients will present jaundice and symptoms of acute hepatitis . Besidesin vitro HEV exposure, which was beneficial for the study of the interaction between HEV and host cells. Three different strains of porcine HEV were identified by The study by In conclusion, the applications of multi-omics have shown the origin and development of the hepatitis virus and provided new strategies for the diagnosis, prognosis and treatment of viral hepatitis and related diseases . There aBesides, multi-omics applications are not limited to genomics, proteomics, metabolomics and transcriptomics, and other omics are also developing, including radiomics, viromics, and so on. The joint application of these omics is believed to provide new insight into viral hepatitis and related diseases.ZX and JL had the idea for the manuscript. ZX and DL performed the literature search and data analysis. XX and XW drafted and critically revised the work. All authors contributed to the article and approved the submitted version."} +{"text": "The uncertainty of COVID-pandemia, vital danger and disruptions in the habitual social contacts can be paralleled to the experiences of severe emotional stress and violence, usually found in the people with Borderline Personality Disorder. Both can be regarded as hampering the ability to categorize and express thoughts, feelings and experiences. The implementation of distant forms of psychological counseling may accentuate the mentalization deficiency.To develop a theoretical framework for an empirical typology of impairments of mentalization.The model of consciousness proposed by L.S. Vygotsky was used for theoretical generalization of the levels of categorical structures of mentalization observed in previous empirical studies.The following structures were identified: (1) the syncretic type of mentalization with low differentiation and complexity of object representations, their negative affective tone, autistic, chaotically mutable motivation and low emotional investment in relationships were described in patients with schizotypal disorders; (2) the \u201ccomplex\u201d type, with literal, non-generalized, field-dependent and rigid, or unstable, representation of the self, others and relationships as a result of the \u201cfusion\u201d of cognitive representations with the current emotional states. Similar types of mentalization were previously described in people with BPD and self-harming behavior .The \u2019syncretic\u2019 and \u2019complex\u2019 types of mentalization produce affective-cognitive distortions of the image of a psychotherapist, hamper the understanding of the conditional and metaphorical character of the therapeutic process, render difficult the de-traumatization of the unbearable experiences, and lessen the effectiveness of consultations of people with BPD.No significant relationships."} +{"text": "Systematic research efforts have been focused on the development of low-dimensional structures, such as nanotubes (NTs), because of the potential of their use in nanodevices and in applications in nanoelectronics and biomedicine. After intense investigation on carbon nanotubes (CNTs), nanotubes made up of elements other than carbon, called non-carbon nanotubes (N-CNTs), have also attracted research attention, as they can be more suitable for electronic and optical engineering applications than their carbon counterparts. Success in assembling CNTs and N-CNTs together has opened the perspective of integrating these innovative complex structures into advanced NT-based systems. As experimental studies on the mechanical behaviour of CNTs and N-CNTs are limited by experimental difficulties in characterizing nanomaterials at the atomic scale, theoretical, analytical and numerical studies to predict the mechanical properties of NTs are of great importance.This Special Issue, comprised of a total of five research articles, is dedicated to recent developments in the modelling and numerical simulation of the mechanical properties of graphene sheets ; CNTs anThe next two research articles ,3 of theThe research article of Pereira et al. is dedicThe last article by Sakharova et al. providesThe works of this Special Issue promote research for the evaluation of the mechanical properties of carbon and non-carbon nanotubes and CNT-based structures by mostly numerical approaches. As a Guest Editor, I believe that the overall quality of the methodologies and achievements presented in this Special Issue contributes to the progression in our understanding of the mechanical behaviour of carbon and non-carbon nanotubes, aiding the future design and optimization of advanced nanotube-based structures."} +{"text": "Due to volatile, uncertain, complex, and ambiguous (VUCA) project context, human decision-making behaviors can affect the performance of engineering project. Therefore, understanding the process of perception, cognition, and decision caters to minimizing the risks that attribute to behaviors . Peng et al. focused on safety behaviors in transportation systems. They introduced theories of electroencephalogram (EEG) and the utilization of EEG in scenarios of fatigued driving, distracted driving, and emotional driving. Lastly, Wang et al. utilized bibliometric methods to summarize the interdisciplinary applications of neuroscience tools in building construction. The results show that EEG and eye-tracking techniques are the predominant neuroscience tools in building construction studies, while functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and trigeminal nerve stimulation (TNS) are still at the adoption stage .Amongst the non-original research articles, Fan C. et al. regard EEG signals as the gold standard of cognitive status and proposed an end-to-end brain-computer interface framework named EEG-TNet for mental workload estimation of workers. The event-related potential (ERP) is a kind of real-time EEG signal related to the stimuli events , etc.] to promote management efficiency in the engineering industry. EEG, for instance, has been used in five of all thirteen original research articles. Among them, Qu et al. proposed a method to identify human-computer interaction intention and cognitive state based on eye movement and EEG parameters to solve the unsmooth and inefficient problems in human-computer interaction. Equipment teleoperation is a powerful solution for hazardous construction environments and attracted researchers' attention. Fan J. et al. investigated the effect of eye movement on teleoperation performance in excavating tasks. They built eye-tracking heatmaps with virtual annotations, representing operators' visual attention allocation. Based on these heatmaps, they concluded that visual attention is influenced by the excavating tasks and the shape of virtual annotations plays a critical role in visual attention allocation.Two studies using eye-movement parameters were presented in the Research Topic. Hu and Shealy used fNIRS to measure the neuro-cognition changes of the engineers when they were asked to evaluate the implementation of conventional stormwater and green stormwater design options. So as to test whether design engineers think about the environmental and social sustainability benefits of green infrastructure can influence what attributes engineers consider and how they weigh these attributes during the design decision-making process. Ding et al. focused on the problem of the increasing hazards caused by construction and demolition (C&D) waste in the construction industry. In order to explore measures that could mitigate the problem, fNIRS has been used to investigate whether the media can influence consumers' willingness to pay for C&D waste recycling products and thus increase consumers' choices.The association between engineering decision-making and neuro-cognition was examined in two studies using fNIRS. Yang et al. attempted to explore the role of the right temporoparietal junction in the effects of the CEO-to-employee pay ratio on potential investors' perceived investment potential in the construction industry. The mechanisms underlying these effects of tDCS in the right temporoparietal junction on the perceived investment potential are also explored in the study.Zhao, Ao, et al. found that the experience of home-based learning significantly influenced the attitudes of university students of civil engineering, which in turn had a positive influence on their intention to continue online education. Chen et al. developed a whole-process digital management system platform and used a variety of advanced digital construction hardware and three-dimensional model software to coordinate the measurement, design, construction, and inspection work in the process of highway engineering construction. Zhao, Wang, et al. explored the key influencing factors of urban intelligent transportation construction and proposed a root cause analysis method based on a fuzzy cognitive map to model the construction process.Lastly, three papers in this Research Topic use different tools to explore the measures to increase the efficiency of engineering education and the construction industry. We appreciate the contributions of all the authors, the reviewers, and the editorial board members for contributing to this Research Topic. We hope that this Frontiers Research Topic can enrich the body of knowledge and encourage the utilization of cognitive neuroscience theories, methods, and tools in the Architecture, Engineering, and Construction Industries.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Multiple hospitalisations towards the end of life is an indicator of poor-quality care. Understanding the characteristics of patients who experience hospitalisations at the end-of-life and how they vary is important for improved care planning.To describe socio-demographic and clinical characteristics of patients diagnosed with serious mental illness who experienced multiple hospitalisations in the last 90 days of life.Data for all adult patients with a diagnosis of serious mental illness who died in 2018-2019 in England, UK were extracted from the National Mental Health Services Data Set linked with Hospital Episode Statistics and death registry data. Variables of interest included age, gender, marital status, underlying and contributory cause of death, ethnicity, place of death, deprivation status, urban-rural indicator, and patient\u2019s region of residence. The number of hospitalisations and patient\u2019s sociodemographic & clinical were described using descriptive statistics and percentages, respectively.Of the 45924 patients, 38.1% had at least one hospitalisation in the last 90 days of life. The median number of hospitalisations was 2. Most of those hospitalised , died in a health care establishment . There were marked geographic differences in the proportions of hospitalisations.The North West region of England recorded the most hospitalisations , compared to other regions.Further analysis is needed to understand factors independently associated with hospitalisations in people with serious mental illness. Funding: This project is supported by the National Institute for Health Research (NIHR) Applied Research Collaborations (ARC) South London."} +{"text": "Gliomas are the most common and aggressive intra-axial primary tumours of the central nervous system (CNS), arising from glial cells. The poor prognosis of these tumours partly results from a lack of significant advances in early diagnosis and treatments prolonging life .Most of the available local treatment options, including radiotherapy and neurosurgery, heavily depend on precise knowledge of the type, location, and extent of the tumour. Visual assessments of medical imaging represent a unique possibility for the detection, characterization, and monitoring of diseases. Qualitative evaluations still represent the modality for intraoperative assessments using ultrasound (ioUS) and/or optical coherence tomography (OCT) to identify lesions and potential residue, analyse the vascularization pattern, and characterise the nature of the mass. Technological advances in both structural and functional imaging (MR and PET imaging) also enables defining several images features, through multiparametric and quantitative evaluations of gliomas ,3.In the field of quantitative imaging, the main issues regard the acquisition/reconstruction parameters, tissue segmentation, feature extraction/selection, and the appropriate statistical analysis of data .Radiomics analysis, considered to be the most advanced development inimage quantification, may provide valuable diagnostic, prognostic, and predictive information of tumours. However, its role in gliomas is still undefined. Numerous studies have demonstrated the correlation between the heterogeneity of the tissues and the radiomics features, which can obtain relevant information not conventionally assessable in medical imaging ,6. FuturThere is still a need to validate the advanced use of MR and PET techniques, as the diagnostic methods increasingly utilized in clinical and research settings ,8,9,10. Diagnoses, disease extensions, vascularization patterns, differential diagnoses between low-grade and high-grade gliomas, and definitions of disease status after treatment remains the main issues of medical imaging in gliomas. This Special Issue will focus on developing in vivo quantitative and qualitative imaging , also considering the novel application of radiomics-based analysis to improve the current role of imaging in the management of gliomas.We invite authors to submit contributions of novel findings or reviews that comprehensively highlight the latest discoveries in the field."} +{"text": "The Second International Conference on Rail Transportation (ICRT), initiated and hosted by Southwest Jiaotong University, completed its agenda after two days of academic reports and seminars, and came to a successful end on 6 July 2021, in Chengdu, China. The conference chairman was\u00a0Professor Wanming Zhai from Southwest Jiaotong University.\u00a0The conference received tremendous support from multiple co-sponsors including National Natural Science Foundation of China, Transportation & Development Institute of ASCE, National Innovation Center of High Speed Train of China, University of Illinois at Urbana-Champaign, Tongji University, Delft University of Technology, China Academy of Railway Sciences, Royal Institute of Technology (KTH), Central South University, Politecnico di Milano, Central Queensland University, Beijing Jiaotong University and University of Technology Sydney.The 2nd ICRT covered a variety of railway research fields such as rail vehicles, infrastructures, traction power, operation and maintenance, environment impacts, sustainable development, etc. Affected by the COVID-19 epidemic, the conference was held in a combination of online and live ways. As one of the largest gatherings of railway researchers, engineers, and technicians, this conference has attracted more than 70 well-known experts to join the conference committees, over 300 Chinese representatives to meet in Chengdu, and thousands of scholars from 22 countries to participate online. After a rigorous peer review process, the conference has accepted 120 full-length papers from 18 countries, and 96 oral presentations have been selected in the conference program.Railway Engineering Science is published for the extended versions of six plenary presentations, which are related to design of locomotive, wheel-rail interaction, train-bridge interaction, railway track structure and subgrade. The following are brief introductions of the six articles:Prof. Maksym Spiryagin from Central Queensland University, Australia, systematically presented the problems, assumptions and solutions in locomotive design, traction and operational studies and summarized the existing major challenges in the future developments of locomotive traction science and digital twins.The research team led by Professors Yunmin Chen and Xuecheng Bian of Zhejiang University, China, focused on the mud pumping problem in high-speed railway. On the basis of the numerical simulation, in-situ soil core test, and full-scale physical model of ballastless track, the formation of mud pumping in roadbed of ballastless track was revealed, and the effectiveness and engineering application of the polyurethane injection on mud pumping remediation was verified.Prof. Buddhima Indraratna from University of Technology Sydney, Australia, presented the mechanical behaviors of four recycled rubber products applied in railways and developed a rheological track model to reveal the energy dissipation capacity of the track with these applications, which may promote environmental sustainability and more affordable ballasted tracks.Prof. Ant\u00f3nio Gomes Correia from University of Minho, Portugal, proposed a geomechanics classification for subgrade coupling the stiffness (resilient modulus) and permanent deformation behaviour, which could be a potentially useful tool in the evaluation and modelling of the foundation of railway structures.The research team led by Prof. Zili Li of Delft University of Technology, the Netherlands, presented new insights into the friction modifiers (FMs) by experimentally investigating the effects of two types of top-of-rail FMs, and their application dosages on wheel\u2013rail dynamic interactions with various angles of attack.Prof. Yongle Li from Southwest Jiaotong University, China, presented a comprehensive literature review of research works on train\u2013bridge systems under external excitations including crosswinds, waves, collision loads, and seismic loads, and provided some valuable suggestions for further research on train\u2013bridge coupling vibrations under external excitations.Particularly, nine distinguished railway experts from different research fields were invited to deliver plenary presentations, who shared the state-of-the-art academic research and engineering practices. This Special Issue of These papers collectively present the recent progress, new insights and in-depth discussions in the aspect of essential challenging issues from rail transportation industry, which are expected to provide useful guidance and inspiration for the above research subjects.We would like to sincerely appreciate all contributing authors, involved peer reviewers, management and technical teams for their effort, time and collaboration to guarantee the high-quality publications of this Special Issue."} +{"text": "Genomics, transcriptomics and metabolomics are increasingly generating key insights for the development of precision approaches in heath and disease. Omics technologies have unlocked the high-throughput discovery of diagnostic biomarker and the systems-level evaluation of the efficacy and toxicity of novel therapies.In the subfield of sport medicine and sport science, the application of -omics methods is relatively recent; yet, the number of peer-reviewed original research articles has seen a steady rise over the last years.Athletic performance can be affected by a combination of endogenous and exogenous factors, including genomic and metabolomic profiles, as well as diet, medicament/drug intake, training regimen, and exercise. In this respect, the application of omics approaches encompassed, for instance, the multi-parametric assessment of training efficacy, injury predisposition, and the identification of robust biomarkers for the indirect detection of potentially \u201cinvisible\u201d forms of doping. In addition, multi-omics integration approaches in sport medicine and doping sciences hold a clear promise for better understanding of the molecular/system levels of athlete\u2019s pathophysiology.What we believe should be indispensable to maximize the potential benefit that such approaches promise, is the promotion of cross-disciplinary and collaborative science, beyond the individual laboratories and research institutions.If we wish to ensure that evidence-based, multi-omics studies, will be complementing efficiently, omics data and the associated meta-data should be available without delay in curated repositories. The availability of omics data generated in independent studies, will enable results validation in the context of distinct populations of subjects/athletes , and allow to gauge unprecedented insight from genome-wide association studies (GWAS) to identify associations between genotypes and phenotypes and how this reflects on performance and drug testing. Meta analyses of literature data would indeed allow to assess and possibly validate any cause-effect relationships emerged from new studies, also, but not only, allow replication and confirmation of the results.In this first volume of the special research topic \u201cOMICS-Based Approaches in Sports Research\u201d, we welcomed submissions tackling 1) integrated omics in sport physiology and pathophysiology, 2) predictive biomarkers associated with improved athletic performance and on sport related risks on athlete\u2019 heath and injuries, 3) investigation of hormones and growth factors for improved anti-doping tests, 4) identification of novel biomarkers for the detection of sport doping, 5) novel statistical/modelling approaches for omics data integration, interpretation and doping detection. The feedback we received was beyond our most optimistic expectations: 57 scientists responded to our call with eight full length, high quality original articles. All published contributions are now available \u201copen access.\u201dThese studies covered different subfields of sport medicine and physiology of exercise, ranging from the interaction between mitochondrial function and the microbiome, to novel, indirect methods for the detection of doping.Khoramipour et al. applied metabolomics to compare metabolic profiles and movement patterns between different male basketball player positions, with focus on relationships between indicators of internal and external loads during elite basketball games. The integration of video-based time motion analysis (VBTMA) with metabolomics of saliva samples and multivariate data analysis demonstrated distinct metabolic profiles of backcourt and frontcourt players, with significant changes involving aerobic/anaerobic pathways.Mach et al. addressed the impact of endurance exercise on the functionality of mitochondria and on the composition of the gut microbiome in elite horses. The authors used transcriptomics, metabolomics and fecal microbiome analysis before and after hose endurance race. Their results show the association between energy metabolism, oxidative stress and inflammation with butyrate-producing bacteria, suggesting the possibility of enhancing/improving athletic performance by targeting the gut-mitochondria axis.Narduzzi et al. used steroidomics and complete blood count analysis to tackle one among the most debated topics in doping testing, that is the detection of the intake of low doses of human growth hormone (GH) in association with recombinant erythropoietin. GH intake affects human hematopoiesis and steroidogenesis. Thus, the authors analyzed the complete blood count and the steroidomics profile in healthy, physically active young males and demonstrated that leukopoyetic and steroidal biomarkers in conjunction with classical endocrine biomarkers allow the accurate detection of the intake of micro-doses of recombinant GH.Al-Muraikhy et al. dissected the influence of age and high intensity endurance on the effect of aerobic exercise on the complement system. Using peripheral blood, they show that high endurance elite athletes exhibit lower levels of complement components C2, C3b/iC3b and adipsin, and this observation is age-independent.Al-Menhali et al. studied the proteomic responses of the heart to exercise training in mice by high resolution mass spectrometry. Proteomics analysis revealed specific changes in proteins involved in the respiratory electron transport chain and implicated in glutathione conjugation. These results represent a further step towards the full understanding of the molecular mechanisms underlying the beneficial effects of exercise on the heart.Al-Muraikhy et al. addressed the issue of biological aging and its correlation to alterations in the metabolic pathways, specifically characterizing the metabolic activity in relation to telomere length in elite soccer players.Lima et al. investigated whether whole blood in long-term storage and whole blood left over from standard hematological testing in short-term storage could be used for transcriptomic analysis, despite lacking RNA preservation; their result show that quantity, purity, and integrity were not significantly compromised from short- or long-term storage in blood storage tubes lacking RNA stabilization, indicating that transcriptomic analysis could be conducted using anti-doping samples collected or biobanked in absence of RNA preservation.Sellami et al. outlining the state of the art and the expected forthcoming developments of molecular big data and omics-disciplines in sports sciences.Finally, the first volume of this special research topic was closed by a perspective article by We thank all the Authors for the time and energy dedicated to the preparation and submission of the articles published in \u201cOMICS-based Approaches in Sport Research\u201d, and we look forward to welcome submissions of new articles for the second volume."} +{"text": "The \"Law on Doctors of the People's Republic of China,\" which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance.We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk\u2013benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009).We developed the first guideline for the management of pediatric off-label use of drugs in China.The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.The online version contains supplementary material available at 10.1186/s12887-022-03457-1. Off-label use refers to the use of drugs beyond the scope of the drug instructions and labels provided by the manufacturer and approved by the National Medical Products Administration of China . DiffereThis guideline was developed by the Chinese Society of Pediatric Clinical Pharmacology, the Chinese Medical Association, the National Clinical Medical Research Center for Child Health and Disease , and the Chinese GRADE Center. Methodological support was provided by the Chinese GRADE Center, the World Health Organization (WHO) Collaborating Center for Guideline Implementation and Knowledge Translation, and the Institute of Health Data Science, Lanzhou University. The guideline was launched on April 12, 2021, and finalized on December 24, 2021. The guideline followed the methodology proposed by WHO and the Experts from a broad range of disciplines including pediatrics, pharmacy, management and health policy, and evidence-based medicine, as well as parents of children participated in the development of the guidelines. The participants were divided into the steering committee, a secretarial team, an evidence team, a consensus team, and an external review team. A full list of members is provided at the end of this article. All members completed a declaration of interest form and stated that they had no economic conflicts of interest directly relevant to this guideline.This guideline is registered at the International Practice Guideline Registry Platform (Registration no. IPGRP- 2021CN088). The guideline protocol is available on request from the registration platform.The target audience of this guideline includes pediatricians, pharmacists, medical managers, policymakers, and primary care physicians. The management population of the guideline is children and their guardians.The themes of this guideline were determined during one round of a questionnaire-based survey and two rounds of expert interviews. At the beginning, the working group identified 11 themes by analyzing published guidelines relevant to the topic and interviewing pharmaceutical specialists. Subsequently, we developed a questionnaire to evaluate the importance of these themes and ask suggestions for additional themes. Sixty-six themes were obtained through the feedback from the survey. After de-duplication, merging, and discussion with the consensus team meeting, eight themes were finally selected to be included.We performed a systematic literature search for each question through PubMed, Web of Science, Embase, China Biomedical Literature Database (CBM), WanFang Data, and China Knowledge Network database (CNKI) to identify literature published from inception to August 13, 2021. We used the search terms \"pediatric*\", \"paediatric*\", \"child*\", \"infant*\", \"adolescent*\", \"neonat*\", \"newborn*\", \"teen*\", \"off-label\", \"off label use*\", \"unlabeled use*\" and \"unlicensed medicines\" combinedBased on the summary table of the available evidence for each theme and consideration of patients' preferences and values, fairness, and the implementation ability of the management measures, we drafted initial recommendations on off-label drug use for children. Two rounds of Delphi surveys on recommendations were then conducted on November 4, 2021, and November 8, 2021, respectively, and a total of 19 suggestions from experts were collected. Recommendations were considered to have reached a consensus when 80% of the voters agreed to the recommendation.The secretariat prepared the first version of the guideline in accordance with the RIGHT checklist and sent the full text to the external review committee. All opinions and recommendations of the review committee were taken into consideration in the revision and creation of the final draft of the guideline.This guideline is planned to be updated within three to five years based on emerging relevant evidence, following the Reporting Items for Updated Clinical Guidelines: Checklist for the Reporting of Updated Guidelines (CheckUp ) checkliThe guideline entitled \"Management Guideline for the Off-label Use of Drugs in China 2021)\" focuses on the definition of off-label use of drugs, evidence grading standards, management of informed consent, monitoring of adverse drug reactions and adverse events, main responsibilities of hospitals and manufacturers, conditions for reimbursement by social health insurance, and the national approval system, resulting in recommendations in nine thematic areas of health care workers did not follow the \u201cExpert Consensus on Off-label drugs in pediatrics in China\u201d guidance document, with 52.6% of the reasons being \"no expert group on off-label use\" .To ensure the rationality of off-label use of drugs to treat children, the process of protocol development and safety monitoring requires the discussion and collaboration of experts from various disciplines, including pediatricians, pharmacists, and nurses \u201317. In aGuidelines and consensus statements on the management of off-label use of drugs for children from China and abroad emphasize that off-label drug use should be evidence-based. Most clinicians, however, lack the necessary skills and time to conduct systematic reviews of existing evidence . EvaluatClinical experts in the corresponding diseases.Non-clinical experts in medical technology, such as professionals in clinical testing, pathology, imaging, or ultrasound.Experts in the field of essential medicine, such as biologists and pharmacologists. In complex clinical cases involving, the expert committee can be expanded if the expertise of the regular committee does not cover all aspects related to the actual situation of the patient. Under the principles of individualized medical model and precision medicine, we suggest that the expert groups should be expanded on a case-by-case basis to include non-clinical medical technologists and basic medicine specialists when discussing off-label treatment of children who have comorbidities or need to take multiple drugs off-label at the same time. For example, we suggest including microbiologists for questions regarding the off-label use of drugs to treat infectious diseases; and radiologists for questions related to ultrasound and MRI contrast agents in children.Formulating and regularly updating the list of drugs commonly used off-label for children in their respective medical institution;Participate in consultations for off-label drug use in children;Promptly release data on serious adverse events or adverse reactions(ADRs) related to off-label drug use. Evidence from adults can be used as indirect evidence;In the lack of high-quality pediatric clinical evidence, an extrapolation of evidence from adult trials can help mitigate the impact of limitations caused by insufficient sample size, disruption of equilibrium, and heterogeneity in pediatric clinical trials . Both thWe suggest assessing the evidence by systematic reviews in cases when there are not yet any approved indications for children, but there is evidence for both adults (in China) and children (anywhere).When there exists evidence only from Chinese adults evidence and no high-quality evidence is available for the pediatric population, we suggest using these findings with caution. A comprehensive analysis of all available information and data is required prior to use, including differences in organ function in specific age groups, the impact on pharmacological characteristics, knowledge of the disease, epidemiological conditions, non-clinical trial data, pharmacokinetics (PK), pharmacodynamics (PD), clinical effectiveness, and safety differences between adult and pediatric populations for drugs with the same or similar mechanism.Evidence from similar diseases in children can be used as indirect evidence;Evidence from pharmacokinetic or pharmacodynamic equivalency modeling studies on pediatric populations can be used as indirect evidence.Evidence from similar diseases may need to be considered for some specific types of disease, such as rare diseases in children , 30 or pIt is not suitable to adopt the adult dose directly for children based on the child's age and weight alone . InsteadBenefit and risk assessment is an appropriate method to judge the rationality of off-label drug use , 5. In rThe severe shortage of drugs for neonates is a worldwide problem , 40, maiCompared with adults, assessing the benefit-risk of off-label use of drugs in children is more complicated . BecauseInformed consent is a crucial tool for doctors and patients to defend their legitimate rights and interests. Although children have a limited ability to estimate risks, signing informed permission is vital for children's mental health and treatment participation. Article 19 of the Civil Code of the People's Republic of China stipulatEvidence-based drug databases and drug directories, such as the Micromedex Pharmaceutical Database, the British National Formulary for Children (BNF-c) , the DutCurrently, awareness on the principles of adequate off-label drug use is poor among clinicians . For halThe World Health Organization categoriCurrently, adverse drug response events are being monitored and reported through the National Adverse Drug Reaction Database of the State Drug Administration in China . HoweverWhile clinicians, pharmacists, and nurses should individually assess the risk of children taking off-label drugs during the process of monitoring adverse drug reactions, we suggest seeking help from parents or guardians of children, especially of children who are incapable of autonomous behavior , 72.Pediatricians should consider whether or not their child patients have the ability to be independent during drug education. 83.5% of medical working groups believed that the family members or guardians of children should be informed when they use off-label drugs . As a reComprehensive drug education is essential to the safety of off-label use of drugs for children. For example, for children and adolescents who use psychotropic drugs beyond the label, a list of information on overdose drug instructions is required . The druEffective drug education enhances doctor-patient communication, promotes public knowledge of safe drug use, and reduces misunderstanding-related doctor-patient confrontations , 81. BecAlthough the guideline is the first Chinese evidence-based guideline for the management of pediatric off-label use of drugs, there were certain difficulties in the application of evidence-based methodology in the area of health care. Because of the diversity and heterogeneity of the types of research on each topic, we were unable to produce systematic reviews of evidence.Off-label use of drugs in children is common globally, also in China. This guideline provides 21 recommendations grouped into 8 themes and a list of evidence on the common types of off-label use of drugs in children, in order to assist the management of pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on off-label use of drugs in pediatrics, as well as provide recommendations for future healthcare policies in China.Additional file 1: Supplementary 1. Management Guideline for the Off-label Use of Drugs in China (2021).\u00a0Supplementary\u00a02.\u00a0A list of common types pediatric off-label use of drugs, evidence levels, and recommendations."} +{"text": "Empoasca onukii and Trialeurodes vaporariorum. Ecological shading significantly affected the composition of soil microbial communities in tea plantations, in which WS significantly reduced the diversity of soil microorganisms.Ecological shading fueled by maize intercropping in tea plantations can improve tea quality and flavor, and efficiently control the population occurrence of main insect pests. In this study, tea plants were intercropped with maize in two planting directions from east to west ) and from north to south and west shading (WS)) to form ecological shading, and the effects on tea quality, and the population occurrence and community diversity of insect pests and soil microbes were studied. When compared with the non-shading control, the tea foliar nutrition contents of free fatty acids have been significantly affected by the ecological shading. SS, ES, and WS all significantly increased the foliar content of theanine and caffeine and the catechin quality index in the leaves of tea plants, simultaneously significantly reducing the foliar content of total polyphenols and the phenol/ammonia ratio. Moreover, ES and WS both significantly reduced the population occurrences of Camellia sinensis (L.), is a subtropical perennial evergreen crop, and it is one of the main cash crops in China /EGC (%) \u00d7 100 . The pheEmpoasca onukii and Trialeurodes vaporariorum, as being the main insect pests in the tea plantation, were selected to assess the effects of ecological shading by intercropping maize on the population occurrences of insect pests. Moreover, the Shannon\u2013Wiener index (H), Pielou evenness index (E), Margalef richness index (D) and Simpson dominance index (C) of the insect community were calculated based on the species and numbers of sampled insects on tea plants. The formulas are as follows:The field investigation was conducted every 10 days after the intercropped maize plants were taller in height than tea plants, i.e., from the last ten days of July to the last ten days of October in 2019 and 2020, respectively. Three tea plants were randomly selected for each treatment of the ecological shading and its respective control (WECK for ES and WS and SSCK for SS) to count the number of insects, and the species of collected insects were also identified and classified. Cameras, insect nets, and suction-implements were used as methods of insect collection and statistics. In this experiment, two key insect pests, Shannon\u2013Wiener diversity index:Pielou evenness index:Margalef richness index: Simpson dominance index:iP: relative abundance of insect species i; iN: number of individuals for species i; N: the total number of individuals of all species in the community; S: the number of species in the community; Hmax: Maximum species diversity index.Chao1 index, Shannon\u2013Wiener diversity index (H), Pielou evenness index (E), and Simpson dominance index (C). The latter three formulas were same as in Chao1 = S + F12/2F2), F1 and F2 are the count of singletons and doubletons, respectively.On 2 October 2020, three sampling sites were randomly selected in each treatment of ES, WS, SS, WECK and SSCK, and the surface soil (depth: 0\u201320 cm) near the tea tree plants was collected. The collected soil samples were sent to Shanghai Personal Biotechnology Co., Ltd. for the 16S rRNA gene sequencing study. Initial screening was performed on the original off-board data of high-throughput sequencing based on sequence quality and retested the problem samples. The library and samples were divided according to the index and barcode information of the original sequence of an initial quality screening, and then the barcode sequence was removed. We performed sequence denoising or operational taxonomic units (OTUs) clustering, according to the QIIME2 DADA2 analysis process or V-search software analysis process. The specific composition of each sample (group) at different taxonomic levels was displayed to understand the overall situation. In order to compare the differences in microbial composition among the samples and display the distribution trend of species abundance of each sample, a heat map was used for species\u2019 composition analysis. The heat map was drawn using abundance data from the top 20 genera with an average abundance. The horizontal and vertical coordinates of the heat map plotted the clustering tree ordering according to the correlation between the samples, i.e., plotted the clustering heat map. The diversity indices of soil microbial communities for different samples were counted, including the E. onukii and T. vaporariorum, and the dynamic values of the community diversity indexes for the insects in the tea plantations. Additionally, one-way ANOVAs were used to analyze the effects of ecological shading treatment on the diversity indices of soil microbial communities in the tea plantation. Furthermore, the significant differences between/among treatments were analyzed by the LSD test or t-test at p < 0.05.SPSS 25.0 and GraphPad Prism 7 were used for the statistical analysis. The latter was used for making line and column charts. A two-way repeated measures ANOVA was used to analyze the effects of sampling year (2019 vs. 2020), ecological shading treatment and their interaction (with sampling time as repeated measures) on the measured indexes of foliar soluble nutrients, functional components and quality indexes of the tea leaves, the population dynamics of the key species of The ecological shading treatment and sampling year both had significant effects on the foliar contents of soluble sugars and free fatty acids, while it had no significant effect on the foliar content of the soluble protein in tea plants . When coThere were no significant differences in the contents of the foliar soluble nutrients of the tea plants among the three ecological shading treatments of SS, ES and WS . AdditioEcological shading treatment, sampling year and their interaction had significant effects on the foliar contents of the functional components of tea plants. When compared with the respective control no-shading treatment , the ecological shading treatments of SS, ES and WS significantly reduced the foliar content of polyphenols, and significantly enhanced the foliar contents of caffeine and theanine in the tea plants .The foliar polyphenol content of the tea plants in the control no-shading treatment of EWCK was significantly higher than that in the control no-shading treatment of SSCK, and the trend was just opposite for the foliar theanine content, while there was no significant difference in the foliar caffeine content of tea plants between the two control no-shading treatments of SSCK and EWCK . MoreoveEcological shading treatment, sampling year and their interactions had significant effects on the leaf quality indexes of tea plants, except for the effect of sampling years on the phenol/ammonia ratio of tea leaves. When compared with the respective control no-shading treatment (SSCK or EWCK), the ecological shading treatments of SS, ES and WS significantly increased the catechin quality index, and significantly decreased the phenol/ammonia ratio in the leaves of the tea plants . MoreoveT. vaporariorum and E. onukii on tea plants, except for the effect of sampling year on the population dynamics of E. onukii fed on tea plants. When compared with their respective control no-shading treatment (SSCK or EWCK), the ecological shading treatments of ES and WS significantly reduced the population dynamics of T. vaporariorum and E. onukii on tea plants, while the ecological shading treatment of SS significantly increased the population dynamics of T. vaporariorum on tea plants . Additionally, the ecological shading treatment significantly influenced the values of the Margalef richness index (D), and the sampling year significantly impacted the values of the Simpson dominance index (C), describing the insect community in tea plantation , and the ecological shading treatments of ES and WS both significantly increased the value of the Margalef richness index (D) of the insect community in the tea plantation (H), describing the insect community in the ecological shading treatment of ES, was significantly higher than that in the ecological shading treatment of SS (When compared with their respective control no-shading treatment (SSCK or EWCK), the ecological shading treatments of ES significantly enhanced the value of the Shannon\u2013Wiener index , and Acidothermus, Acidibacter, AD3, Subgroup_2, WPS-2 and IMCC26256 were the six dominant bacterial genera , Pielou evenness index (E) and Simpson dominance index (C)) in the tea plantation , Pielou evenness index (E) and Simpson dominance index (C) of the soil microbial microorganisms, while the ecological shading treatments of SS and ES did not significantly affect the community diversity indexes of the soil microbial microorganisms in the tea plantation (H), Pielou evenness index (E) and Simpson dominance index (C) of the soil microbial microorganisms in the control no-shading treatment of EWCK were significantly higher than those in the control no-shading treatment of SSCK , Pielou evenness index (E) and Simpson dominance index (C) of the soil microbial microorganisms in the ecological shading treatment of ES were significantly higher than those in the ecological shading treatments of SS and WS, and these three community diversity indexes of soil microbial microorganisms in the ecological shading treatment of SS were significantly higher than those in the ecological shading treatment of WS in the shade treatments (ES and WS) decreased and the insect diversity index increased. It is speculated that the shading effect of maize might have caused the changes of the content of secondary metabolites in tea leaves, and indirectly affected the occurrence of pests. Studies have shown that secondary metabolites affect insects\u2019 food selection, feeding and utilization, and thus affect insects\u2019 growth, behavior, and population biology [A large number of studies have found that the incidence of plant diseases and insect pests in the compound cultivation mode of tea plantation was relatively mild . When cobaccarum . Our fin biology . Prior s biology ,40,41. OSoil microbes decompose organic matter, participate in soil nutrient cycling and plant nutrient supply, and the composition of their community structure is a major indicator for assessing soil quality and fertility . Some scProteobacteria, Acidobacteria, and Actinobacteria were the relatively large microflora in farmland soil, and intercropping had an effect on their proportion in the community. In this experiment, the ecological shading of maize affected the composition and distribution of the soil microbial community.The results of this experiment showed that the Chao1 index, Shannon\u2013Wiener index, Pielou evenness index and Simpson dominance index of soil microbial community were decreased by the western shading of maize, i.e., the richness, diversity, evenness and dominance of the soil microbial community were decreased. It must be mentioned that the shade was the most intuitive feeling for people when intercropping with corn in tea plantation. However, the causes for the changes of tea detection indexes and quality were closely related to the changes in the soil microbial structure and field temperature, the occurrence of plant diseases and insect pests, and the changes of tea garden biodiversity after the shade formation. The changes in tea quality were the combined result of shading, pest reduction and changes in soil structure. This is an important point in pastoral landscape design: it is not a separate existence but a mutual influence. Agroforestry combines the use of trees with annual crops or fodder plants on the same piece of land that build up synergies, which leads to a higher resilience and allows crops to maintain long-term productivity .The effects of the ecological shading formed by intercropping maize on tea foliar soluble nutrients, foliar functional components, quality indicators, insect occurrence in tea plantation, and soil microbial diversity were summarized from different planting directions \u00a0Table A2"} +{"text": "Data was collected using a structured questionnaire and analyzed with Microsoft Excel software.one hundred and fifty-one (151) health facilities with a total bed capacity of 3089 were enrolled into the study. Overall, the least prepared infection prevention and control, water and sanitation core components in ascending order were the coordination committee structure (13.19%), guidelines and SOPs (21.85%), vector control (22.02%), staff management (30.63%), and training received (33.64%). The best prepared components in descending order were integrated disease surveillance and response capacity (69.83%), medical waste management system (57.12%) and infrastructure compliance (54.69%).the findings of this study which is comparable to those of other studies in similar settings validates the perception that Infection Prevention and Control/Water, Sanitation, and Hygiene (IPC/WASH) capacity and readiness is inadequate in South Sudan. To scale up these core components, we recommend development and implementation of a comprehensive and long-term infection prevention and control strategic plan as part of the country\u2019s broader health sector recovery planning. Infection Prevention and Control (IPC) is aimed at preventing avoidable infection of patients and healthcare workers at health facility and community levels . It is aWater, Sanitation, and Hygiene (WASH) plays an essential role in IPC, particularly in healthcare settings. Infection prevention and control and WASH are two sides of the same coin; thus, safe WASH contributes to enhanced IPC, patient, and health workers\u00b4 safety, and vice versa . A robusSouth Sudan experiences recurrent incidents of emergencies regularly; a significant number of these emergencies are outbreaks of infectious diseases which often results in high morbidity and mortality. The country\u2019s southern parts sit in the ecological zone of the EVD and yellow fever, which is contiguous with the same zone in neighboring Democratic Republic of Congo (DRC) and Uganda . The couSouth Sudan scaled up IPC/WASH interventions due to the increasing threats of disease outbreaks, however, there is a paucity of reliable data on the status of IPC/WASH interventions in the country. This is a major constraint to evidence-based prioritization, planning, implementation and monitoring of IPC/WASH interventions. Thus, IPC interventions are often ad-hoc rather than proactive and systematic. Furthermore, the technical knowledge and capacities of national and international agencies involved in implementing IPC/WASH interventions in the country are often weak, affecting both the quantity and quality of interventions. Given the exposure of South Sudan to threats of cross border importation of EVD, recurrent outbreaks of infectious diseases and the ongoing COVID-19 outbreak, which require effective IPC/WASH interventions for prevention and control, the importance of having reliable data for evidence-based planning, implementation and monitoring of interventions cannot be overemphasized. An IPC/WASH study was thus conducted in selected health care facilities in the country.The objective of the study were to assess the readiness and capacity of the core components of IPC/WASH in health facilities to effectively respond to and contain potential outbreaks of EVD and control the ongoing COVID-19 outbreak in the country and to establish baseline information for planning, implementation, supervision, monitoring, and evaluation of short- and long-term IPC/WASH interventions. The study also sought to raise awareness about and provide evidence for advocating for more investments in IPC/WASH in the country. In this research article, we present and discuss the key findings, conclusions, and recommendations of the study.Study design and sampling method: a descriptive cross-sectional study on the capacity and readiness of the core components of IPC/WASH to respond to infectious disease outbreaks was conducted in health facilities in six high-risk States of South Sudan from February 2020 to December 2021. The three Equatoria States were initially enrolled into the study in 2020. With the report of the first case of COVID-19 in the country on April 5, 2021 and subsequent declaration of an outbreak, three more States, namely, Western Bahr el Ghazal, Lakes and Jonglei, classified as high risk for both EVD and COVID-19 transmission, were enrolled into the study. A purposive sampling method was used to identify between 14 to 16 health facilities per State. Inclusion criteria were any operational health facility with permanent structures and at least two or more healthcare workers.Study setting: South Sudan, a country experiencing a chronic humanitarian crisis, is bordered by Uganda in the South, DRC in the South West, Central Africa Republic in the West, Sudan in the North, Ethiopia in the East and Kenya in the Southeast. These borders are porous with free population movements between the neighboring countries for economic and sociocultural reasons. The country has a 2021 population of 11.4 million and landmass of 619,745 km2 [(Annex 1) adapted from the WHO guidelines on core components of IPC programmes at the national and acute health care facility levels [Data collection: quantitative data was collected using a structured questionnaire y levels and Watey levels both of Data analyses: the data was cleaned, entered and analyzed with Microsoft Excel software. Twelve indicators identified based on expert consensus were analyzed . The aveEthical clearance and approval: administrative clearance for this study was provided by the Ministry of Health of South Sudan. World Health Organization provided the ethical clearance (WHO e-Pub no: ePub-IP-00331783-EC).One hundred and fifty-one (151) health facilities with a total bed capacity of 3089 in six States were enrolled into the study. Almost half (49%) of the surveyed health facilities were PHCCs while the rest were PHCUs (25%) and hospitals (14.51%) . WesternThis study sought to establish the capacity and readiness of the core components of IPC/WASH in health facilities to prepare for and respond to disease outbreaks and enhance the safety of patients and health workers in South Sudan. To the best of our knowledge which is based on an exhaustive literature review, it is the first documented study that comprehensively assessed the status of IPC/WASH in health facilities in the country thus, its findings will form the baseline for planning, supervision, monitoring, and evaluation of IPC/WASH interventions moving forward. The findings showed a lack of readiness of most IPC/WASH components to prevent disease outbreaks except for IDSR capacity, infrastructure compliance and medical waste management system. There was a generally poor readiness of IPC/WASH committee structure, vector control and IPC/WASH supplies components across most of the study area. The study showed weak IPC readiness in the three Equatoria States which had the highest risk for EVD transmission.et al. in their study of IPC in eight conflict-affected countries [et al. and Fofanah et al. in Sierra Leone [et al. in Liberia [The general lack of readiness of most IPC/WASH components that were observed in this study is similar to the findings of Lowe ountries and thosra Leone ,24. Thisra Leone . Likewis Liberia .et al. and Forrester et al. in their assessment of IPC in Liberia [The high scores observed in the IDSR capacity, infrastructure compliance and medical waste management system components may be associated with ongoing health interventions before and during the study period. As part of efforts to respond to the chronic humanitarian crisis in the country, humanitarian partners led by WHO made massive investments in an Early Warning Alert and Response System (EWARS) to address the need for good quality and real-time data for timely detection and response to epidemics. The EWARS built a foundation for improving disease surveillance which resulted in significant improvements in IDSR capacity all over the country . Similar Liberia ,29.et al. which showed that low income countries were less likely to have functional IPC/WASH programmes [et al. in Sierra Leone [The IPC/WASH committee structure which requires minimum funding and efforts to implement was the weakest among all the IPC/WASH components which is corroborated by the findings of Tartari ogrammes . This fira Leone . Inadequet al. [The below average score observed in the vector control component across all the States points to gaps in the malaria control programme, which is primarily responsible for this component hence the need for strengthening the national malaria prevention and control programmes and ensuring greater coordination and collaboration between it and the the IPC/WASH programme at all levels. Although similar to the findings of another study conducted in Uganda , the belet al. .Limitations: the above findings should be interpreted within the context of three key limitations. Only six and seven health facilities were sampled in Jonglei and Lakes States due to access constraint. Given this small sample size, the findings in both States may not be a true reflection of the IPC/WASH readiness. The purposive sampling method used may have resulted in selection bias in which the more readily accessible and possibly the most functional and good performing health facilities were selected. Lastly, the involvement of some Ministry of Health IPC/WASH officials in the data collection process may have introduced interviewer bias. The data collectors may have focused on their predetermined perceptions which may affect their assessment of the various components of IPC/WASH. This bias was addressed by rigorous screening, selection, training and supervision of the data collectors and physical verification of the responses.The findings of this study which is comparable to those of other studies in similar settings validates the perception that IPC/WASH capacity and readiness is inadequate in South Sudan. This observation is confounded by the fact that the massive IPC/WASH investments made during the EVD preparedness programme of 2018 to 2020 and the ongoing COVID-19 response programme seem not to have yielded the anticipated outcomes. The inadequate capacity and readiness of the IPC/WASH programme observed in this study are mainly due to the chronically weak health system, lack of a comprehensive national IPC/WASH strategy and inadequate knowledge and funding of IPC/WASH interventions in the country. Other factors include weak capacity for IPC/WASH planning, implementation, supervision, monitoring and evaluation in the country. Furthermore, most of the international IPC/WASH norms and standards may not be realistic in view of the peculiar context of South Sudan.Moving forward, we propose four main recommendations based on our findings. First, the results of this study should be used to develop and implement a long-term IPC/WASH strategic plan for the country as part of the broader health sector strategic, health system recovery and annual humanitarian response planning. This strategic plan should have a clear monitoring and evaluation framework based on the baseline established by this study and should be actualized through annual IPC/WASH operational plans. Second, the study results should be used to scale up advocacy and resources mobilization for IPC/WASH in the country. Third, international IPC/WASH norms, standards and guidelines should be adapted to suit the South Sudan context. For instance, it may be practically impossible to constitute IPC/WASH committees in every health facilities due to inadequate staffing hence the need to innovate. Fourth, establishment of national and State level platforms for IPC/WASH coordination is critical to coordinate and monitor progress.Infection prevention and control/water, sanitation, and hygiene (IPC/WASH) is a critical component of outbreak preparedness, response, prevention and control in humanitarian settings such as South Sudan;There is inadequate evidence-based information for the planning, implementation, supervision, monitoring and evaluation of IPC/WASH interventions in the country;Despite the exposure of the country to threats of disease outbreaks, the readiness of the IPC/WASH programme to adequately respond to these outbreaks is unknown.This study identifies the key gaps in the readiness and capacity of IPC/WASH programme in the country to prevent and control diseases outbreaks;The study further provides baseline information for future planning, supervision, monitoring and evaluation of IPC/WASH interventions at health facility level."} +{"text": "The current ecosystem services of karst protected areas cannot fully enhance human well-being, and the value of eco-products cannot be effectively realized. Research on eco-products and ecological civilization is conducive to the regional sustainability. The results of a statistical analysis of 258 related articles indicate: (1) the number of published articles has increased rapidly after slow growth, indicating that this research field has become a research hotspot and has broad research prospects; (2) the research content mainly involves five aspects, such as eco-product supply, eco-product value realization, eco-industry, ecological civilization, and monitoring and evaluation; (3) the articles research area is mainly distributed in the karst areas with a fragile ecological environment in China and the eco-product value realization and ecological civilization pilot areas; (4) the research frontiers are revealed from four aspects of eco-product supply ability, eco-product value realization, the driving force of eco-product value realization on the formation of eco-industry, model and effectiveness of ecological civilization; (5) it is necessary to deepen the research on the improvement mechanism of eco-product supply capacity, the classification systems and value accounting standards of eco-products, the formation mechanism of eco-industries under ecological threshold constraints and the driving mechanism of eco-industry to ecological civilization. The 2030 Agenda for Sustainable Development, adopted at the 70th session of the United Nations General Assembly, marks the beginning of a new era for humanity to move toward a sustainable society . Ecologi2, accounting for about 15% of the land area [The distribution area of modern carbonate rocks in the world reaches 22 million kmand area , affectiand area ,14. Karsand area .In March 2022, the Convention on Biological Diversity (CBD) proposed to expand the coverage of protected areas under the global biodiversity framework, and it is planned that the total area of protected areas will reach 30% of the global land area by 2030 . The proThe construction of ecological civilization in karst protected areas is an important measure to protect the eco-environment of karst protected areas and enhance the well-being of karst communities. How to effectively realize the value of eco-products has become a hot issue of common concern for governments and scholars. The purpose of research on eco-product value realization is to solve the externality problem in supply and protect the functionality and integrity of ecosystems , and theScholars have three main understandings on the connotation of ecological products. The first view equates eco-products with ecosystem services, and believes that they are the well-being that natural ecosystems provide to humans ,21. The https://www.webofscience.com), Foreign Journal Resource Service System (http://fpd.juhe.com.cn/) and China National Knowledge Infrastructure (CNKI) (https://www.cnki.net/). The searching date was on 12 November 2021. To identify relevant studies, a search was conducted based on the platforms including Web of Science (WOS) , Linbo Zhang (5), Yihong Zhou (5), Weiming Li (5), Shuilin Qiu (4), Hongxing Zhang (4), Zhiyun Ouyang (4), Huiyi Yu (4), Shuzhong Gu (4) and Jinnan Wang (3). When calculating the number of published articles by authors, all authors in the articles were accounted regardless of the author\u2019s order.In 1990, ecological civilization was first systematically proposed in Ecological Awareness and Ecological Civilization . In 2005The contents of the articles are shown in We conducted an interpretation and analysis of the distribution of organizations by using the occurrence frequency of each institution of related articles as the basis, and then sorted them from high to low. The statistical results show that the studies are mainly distributed in the following three types of research institutions. (1) Institutions that have long been engaged in the related research on ecological civilization and sustainable economic development, and have good relevant research foundation and experience, such as: the Chinese Academy of Natural Resources Economics, Environmental Planning Institute of the Ministry of Ecology and Environment and Development Research Center of the State Council. (2) Institutions in finance and resources directly related to the subject of the research, such as Lanzhou University of Finance and Economics, Central University of Finance and Economics and Hebei University of Economics and Business. (3) Institutions in the areas where the national eco-product value realization mechanism pilots are located, such as: Shandong University, Zhejiang University and Lishui College. Moreover, senior colleges and universities with majors related to agriculture and forestry are also the main camp of research institution articles with related studies, such as China Agricultural University and Beijing Forestry University, Renmin University of China. In general, research foundation and experience, professional connection and geographical advantages are the main factors affecting the distribution of articles research institutions.The \u201cmeta-rule\u201d of territorial spatial planning is the preservation and appreciation of natural resources . At the Ecological design and product full-cycle environmental management have become important links in the research and development of eco-products. To quantitatively evaluate eco-product design, Ng proposedThe environmental cost in the process of economic development has caused a prominent contradiction between the supply and demand of eco-products. It is urgent for us to improve the ecological environment, increase the total supply of eco-products and enhance the supply capacity . The supThe core of expanding consumption demand of eco-products is to coordinately promote the whole of society to form ecological values, green lifestyles and green consumption models . The useThe calculation method of eco-product value usually adopts the calculation method of ecosystem service value, which is divided into two stages of functional volume accounting and monetary value volume accounting according to the studies by Daily et al. and Ouyang et al. ,38,39. UEcological banks such as forest banks, wetland banks and water banks are new platforms for value realization. These ecological banks can promote the capitalization and make eco-products become productive forces. So, they can change resources into assets. The operation process of ecological banks includes resource investigation, project planning, value evaluation, circulation reserve and operation . These eEco-products have diverse and complex characteristics, so the value realization paths are also different. The property rights of purely public eco-products (such as clean water) are common. The economic value of them, which is difficult to realize through market transactions, mainly relies on governmental paths. Value payments of them are in the form of transfer payments, ecological compensation and specEntering the era of ecological civilization, the classical division of labor among the three industries can no longer meet the needs of industrial development in the era of ecological civilization. Ye and Han proposedEco-resources must be fully relied on to realize ecological industrialization, and regional characteristics must be found to promote industrial ecologicalization . Both ecThe eco-industry chain of protected areas is the input\u2013output relationship of material, value and information. Based on the input\u2013output perspective of eco-products, the eco-industry chain structure model includes four links: the eco-product industry chain, the derivative industry chain, the product demand market and the supporting industry chain . The heaDue to the differences in natural and socio-economic resource endowments, the specific models and paths for ecological civilization vary from place to place. Bao believesThe development level of ecological civilization is usually measured by eco-efficiency , ecologiThe contradiction between the supply shortage of eco-products and the demand for high-quality eco-products has become increasingly prominent . It is uFrom the perspective of eco-product value formation, the biological and physical structure of the ecosystem and the process of material, energy and information flow form the ecosystem functional units. Each functional unit ensures the supply of ecological material products and ecological service products. Under certain conditions, when material products and service products of the ecosystem meet human needs, the monetization value assessment can be conducted. Coupled with the design of a reasonable transaction mechanism, the value of eco-products can be realized . TherefoKarst protected areas should analyze the particularity of consumers\u2019 demand for eco-products under the influence of karst culture on the premise of understanding the impact of karst fragmented landscape pattern and dual structure on ecosystem functions, and then clarify the mechanism for improving the supply capacity of karst eco-protection products.Scholars have different views on the concept and classification of eco-products. Due to the differences in the concept of eco-products, the classification systems and value accounting standards of eco-products are also different, which directly affects the accuracy and comparability of the value accounting, and hinders the process of value realization. Many scholars directly use Gross Ecosystem Product (GEP) to calculate the value of eco-products, and include agricultural products, forestry products, animal husbandry products and fishery products into eco-products ,56. GEP With rapid economic and social development, many protected areas are facing the dual pressure of eco-protection and economic development. Eco-industries give full play to the advantages of natural resources and economic resources have strong survival, expansion and competitiveness. It is necessary to establish a coupling model between ecological carrying capacity and eco-industries, and clarify the interaction between the two. The ecological control mechanism for the formation and optimization of eco-industries is also important. The first is to analyze the unique attributes of karst protected areas, improve the accounting indicators and methods of GEP and calculate the functional and monetary value of karst eco-products. The second is to collect and optimize the fragmented management rights and use rights of eco-resources, expand the paths for value realization and explore the value-added mechanism of eco-products. The third is to build trading systems including eco-products certification system, clarify the driving factors for the formation of eco-industries, optimize the industrial structure and clarify the formation mechanism of the eco-industries.In the critical period when human society is entering the ecological epoch and realizing the improvement of ecological environment quality from quantitative change to qualitative change, the important position of eco-industries in strongly promoting ecological civilization is becoming increasingly more prominent . Due to For example, based on ecological industrialization of karst reserves and industry ecologicalization of buffer zones, the driving mechanism for ecological industries extension on the eco-economic system is to be explored. Based on eco-cultural gene mapping, eco-brand culture shaping and ecological value enhancement, the driving mechanism for ecological culture inheritance on the eco-cultural system is to be elucidated. The driving mechanism for the multi-subject participation of eco-industry management on the eco-responsibility system is to be revealed. The driving mechanism for trade-offs, synergies and compensation of eco-industrial benefit distribution to the eco-system is to be clarified. The inner logic for the five systems of ecological civilization is to be analyzed, the driving framework for eco-industries to the eco-security system can be conducted and the driving mechanism for eco-pattern formation to the eco-security system can be proposed.In this paper, we conducted a systematic literature review by analyzing 258 articles retrieved from the Web of Science, CNKI and Foreign Journal Resource Service System of Guizhou Normal University Library. The main conclusions are as follows: (1) studies on eco-protection product value realization and ecological civilization are increasing rapidly, showing a broad research prospect; (2) among the studies on eco-product supply, value realization, eco-industry, ecological civilization and monitoring and evaluation, the studies on eco-product value realization are most common, mainly focusing on mechanisms and paths for value realization; (3) the related research has mainly been conducted in China. After analyzing the main developments and landmark achievements, the paper proposed four scientific issues to be addressed.The reasons for more literature written in the Chinese language than in English may be as follows: (1) the concept of ecological products has been put forward in China by the Chinese, and some pilot projects in China have formed models that are worth learning from; (2) international scholars use the concept of ecosystem services more than ecological products. The eco-products related academic research is still in the exploratory stage. Some scholars even confuse the concepts of eco-products and ecosystem service, believing that the two are the same.In fact, the two concepts are different. Ecosystem service has been widely studied internationally. The concept of eco-products was proposed based on ecosystem service, but is an extension to it. Ecosystem services emphasize the benefits of natural ecosystems to humans, while eco-products emphasize the human\u2013nature life community. Ecosystem service value emphasizes the value of ecology and arouses the awareness of human beings to protect nature and protect ecology. The value of eco-products emphasizes the value of products and services jointly created by man and nature, and emphasizes the value created by the behavior of human beings to protect and restore ecology.The future directions of eco-products and ecological civilization can be conducted based on the following aspects: (1) the mechanism of improving the supply capacity of eco-products based on eco-products (ecosystem structure and process) and the ecological market (consumer demand); (2) the classification systems and value accounting standards of eco-products; (3) the formation mechanism for ecological industries under the constraints of ecological thresholds based on the carrying capacity of ecosystems; (4) the driving mechanism for eco-industries on ecological civilization. These future research topics are especially suitable for protected areas, such as natural world heritage, geoparks, nature reserves and scenic spots, due to the high-grade eco-products in these areas.Through the study of the characteristics and supply of the ecosystem, the attributes of eco-products, the mechanism for improving supply capacity and the mechanism for value realization are clarified. The industrialization of eco-products produces eco-industries, which directly drives the construction of the eco-economic system and eco-cultural system, and then promotes the construction of the eco-institutional system and eco-responsibility system, thereby building the eco-security system and realizing the goal of ecological civilization.Ecological civilization acts on ecosystem supply through ecological protection and ecological restoration, and acts on ecosystem demand through ecological demand expansion. Through research on the formation mechanism for the eco-industry and the driving mechanism for eco-industry to ecological civilization, the model and paths of ecological civilization based on ecological protection can be conducted to provide the basis for the construction of ecological civilization and sustainability in karst protected areas."} +{"text": "This editorial sets the scene for our Special Issue on the growing problem of sedentary behavior and physical inactivity in the Asia-Pacific region. In many societies, more than 40% of the adult population and growing numbers of children are insufficiently physically active to safeguard their health. This is contributing to high rates of cardiovascular disease, obesity, and other deleterious health outcomes across the region. The Asia-Pacific is heterogeneous and complex, with diverse social, cultural, and environmental barriers that affect intentions and opportunities for regular physical activity. Recently, the problem has been compounded by the acceleration of population aging, the worsening effects of anthropogenic climate change, and the ongoing COVID-19 pandemic. Without strong leadership, enduring funding support, and innovative interventions that cut across policy and society, we may yet be facing a century of unmitigated expansion of morbidity across the Asia-Pacific. Many adults and children across the Asia-Pacific region are not sufficiently physically active to support their health ,2. This Diverse factors are conspiring to reduce opportunity, time, and motivation for physical activity across the Asia-Pacific region. These include lack of appropriate and consistent infrastructure, inequities in access to sports facilities, poor work-life balance, changing modes of learning and leisure, COVID-19 pandemic restrictions, increasing risk aversion, and others ,12. At tThis Special Issue of the International Journal of Environmental Research and Public Health brings together cutting-edge research that explores a diversity of topics related to inactivity in the Asia-Pacific. The carefully curated selection includes manuscripts concerning reductions in children\u2019s play, later life activity declines, the rise of metabolic disease risk factors, unequal distribution of behavioral impacts associated with the ongoing COVID-19 pandemic, and other thought-provoking contributions. It is hoped that this Special Issue will inform ongoing debate and stimulate new research, policy, and interventions to promote higher levels of activity across the life course in this rapidly changing region.The Asia-Pacific region has several geographical definitions, which typically comprise over 50 nations across Oceania and the Pacific, South and South-east Asia, North-east Asia, and Central Asia. This region is arguably the most populous, rapidly aging, culturally diverse, and economically disparate area of the globe . This exConsiderable discrepancies have been reported in the measurement of physical activity across the Asia-Pacific region. This may be due to a lack of standardized measurement, which has been well documented in largescale review studies of regional data . Indeed,Mortality and morbidity data across the region also provide indirect evidence of deleterious lifestyle behaviors. For example, despite being highly preventable cardiovascular diseases (CVD) remain the leading cause of death across the region . PacificThe regional problem of inactivity is potentially influenced by the mega-trends of population aging and anthropogenic climate change, which will define health and behavioral outcomes in many societies over the 21st century. Population aging refers to a demographic transition from a younger to an older age structure whereby growth in older adult cohorts significantly outpaces changes among cohorts of children and younger adults due to long-term reductions in fertility and increases in longevity . Across Beyond population changes, the progression of anthropogenic climate change is also likely to affect opportunities for physical activity at a population level. Anthropogenic climate change refers to long-term changes in temperature and weather patterns linked to human industrial activities and the burning of fossil fuels . The resThe ongoing COVID-19 pandemic has added to the challenge of regional inactivity in several ways. Enforced lockdowns, quarantine and self-isolation, home-based and online modes of work and learning, social distancing, cancellation of sport and group exercise, and the permanent closure of businesses serving recreational physical activity needs are some of the ways in which the pandemic has altered the regular behavior of children and adults across the region. At the time of writing, the world is entering the third year of the pandemic and a seventh wave of infection with no signs of abatement despite the wide availability of relatively effective vaccines and booster shots. The historic and lingering nature of this pandemic is leading to long-term changes in physical activity patterns at a population level. This has been shown in cross-national studies using objective activity (step count) data collected from smartphone accelerometry and GPS data . Such stPersistently high levels of physical inactivity in the Asia-Pacific region portend poorly for the management of obesity, cardiovascular disease, and other deleterious health conditions in the coming decades. Population aging, climate change, and the ongoing COVID-19 pandemic are adding to the current crisis of inactivity with no near-term solutions in sight for these emerging problems. In order to tackle this complex issue, interventions at multiple levels will be required, along with strong government leadership and enduring funding commitments. International and national guidelines for physical activity have been clearly established for decades based on a robust evidence base , and theThree areas for potential action that hold some promise for arresting activity declines include a renewed focus on school-based physical education, community interventions led by health professionals, and urban environmental remediation strategies. Across the Asia-Pacific, physical education programs that were once a staple of school and university life are being reduced or replaced with academic subjects at an alarming rate . The val"} +{"text": "As an early warning strategy for coronavirus disease 2019 (COVID-19), environmental detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater was integrated into pandemic responses in Australia, Germany, New Zealand, the United Kingdom of Great Britain and Northern Ireland, and the United States of America. is a pervasive global health concern, complicating treatment of infectious diseases and routine medical procedures. The Philippines has experienced increasing numbers of infections resistant to specific antibiotic combinations, for example, carbapenem resistance in New molecular diagnostic laboratories established for the detection of SARS-CoV-2 in the Philippines could be used for other emerging infectious diseases and, thus, contribute to improved resilience during future epidemics. This article discusses how the strengthened monitoring and surveillance capacity developed for SARS-CoV-2 in the Philippines provides opportunities for environmental surveillance of emerging infectious diseases and AMR.Environmental surveillance, specifically WWS, could be used as an adjunct to clinical and laboratory diagnosis of individuals for the detection of local outbreaks. Similar to clinical testing, WWS utilizes reverse transcription-quantitative polymerase chain reaction (RT-qPCR). .It is possible for WWS to detect and analyse chemical or biological compounds to understand the health status of communities. (The Philippines has recently increased its molecular laboratory testing capacity for SARS-CoV-2. The number of public and private sector laboratories with the ability to detect SARS-CoV-2 using polymerase chain reaction (PCR) increased from one in the first quarter of 2020 to 247 by the end of April 2022. , with RITM, can develop, implement and study the cost\u2013effectiveness of multidisciplinary WWS in the response to emerging infectious diseases.Bringing Filipino institutions and multidisciplinary professionals together with experience in environmental and clinical surveillance could be a starting point for a national One Health integrated surveillance system where clinical and environmental samples from human health systems, animal health systems, food systems and the environment can be analysed and correlated. This system could inform hygiene, sanitation and infection prevention strategies to reduce the risk of spreading AMR and infectious disease outbreaks of pandemic potential. A One Health integrated surveillance system could increase its reach by building on the growing capacity of Filipino medical technologists in the use of RT-qPCR as they handle more samples due to the surge of COVID-19 cases. Capacity building could also be supplemented by online training from experienced global researchers through today\u2019s communication technology. The Philippine Interagency Committee on Antimicrobial Resistance (ICAMR), established in 2014 and comprising the DOH, Department of Agriculture, Department of Science and Technology, Department of Interior and Local Government, and Department of Trade and Industry, could oversee the One Health integrated surveillance system, as the committee is already strengthening surveillance and laboratory capacity for AMR. (As epidemics continue to affect the Philippines, improved preparedness, response and resilience to emerging infectious diseases including AMR could be supplemented by a One Health integrated surveillance system. To implement such a system, the country would need to develop capacity in environmental surveillance, including WWS, making use of existing infrastructure and expertise while exploring possibilities for collaboration with global experts and international partners. National agencies and committees, such as the DOH, RITM and ICAMR, would have to take on responsibility for overseeing and leading this initiative. A multidisciplinary approach and the identification of relevant Philippine institutional partners would be needed to sustain this initiative and prepare for emerging infectious diseases and chronic health-system challenges."} +{"text": "The utilization of crop straw biomass resources is highly emphasized by governments and academia in recent decades. Based on the core databases of the literature in China National Knowledge Infrastructure (CNKI) academic journals, CiteSpace software is used to analyze and process the hotspots, and this study proposed the primary coverage and evolutionary trends of research on the utilization of crop straw resources. The thesis proposes the research development trend for improving the institutional mechanism of the utilization of crop straw resources, strengthening technology research and development, exploring the economic model of green cycle agriculture, accelerating the construction of the industrial system, and designing new paths of resource utilization in multiple ways, which helps estimate the development trend of the utilization of crop straw resources and provide inspiration and direction for future research and practices. Straw feed processing methods mainly include straw bulking, ammonification, pellet feed, straw silage, straw compaction, and straw microstorage. The integration and optimization of the aforementioned technologies are effective means to promote the utilization of straw for feed. Technological progress is mainly achieved through the optimization of the main body, process, facilities, and auxiliary parts. .3) The SAt present, straw energy utilization modes mainly include straw to biogas, straw centralized gas supply, straw power generation, and straw solidification molding .The utilization of biomass to generate energy is an important source of energy in the future. There are various ways of energy utilization, but the utilization technology needs to be further explored. At present, the main modes of straw energy utilization include biogas production, straw-fired cogeneration, and densified corn stover briquetting fuel .4) Straw Raw Materialization and Base Materialization UtilizationPractice shows that the efficiency of straw-fired cogeneration is low while the cost is high . Current2 emissions and saving energy The systems and mechanisms should be improved for using crop straw as resources. Under the leadership of the government, professional teams were organized to conduct in-depth research; the policy obstacles in the utilization of crop straw as resources were clarified, and targeted policies about financial support, technical assistance, incentive system, and performance assessment for the utilization of crop straw as resources were formulated.2) Research on the resourcization technique of crop straw should be strengthened. The backward technology of straw recycling results in high production costs and small scale of straw-consuming enterprises. Strengthening the technical level of straw industrial utilization is the most important task at present.3) It is necessary to adhere to the concept of carbon peak and carbon neutrality to explore the green circular agricultural economic model. Governments should promote the recycling of crop straws, especially the economical and intensive utilization of straw resources, and explore the suitable mode of green agriculture and recycling agriculture.4) The construction of an industrial system should be accelerated for the utilization of crop straw resources. Countries all over the world, especially developed countries, should guide the exploration of diversified industrial utilization of crop straw, such as fertilizer, energy, feed, and raw material. The straw resource utilization industrial system should be constructed to get rid of crop straw resource utilization of small scale and low benefit predicament.5) The utilization paths of crop straw are designed in diverse ways. In view of the needs of rural revitalization, beautiful countryside construction, and territorial space planning in the new era, a diversified design of the crop straw resource utilization path is carried out so as to explore a low-carbon and high-efficient regional straw resource utilization path tailored to local conditions.The implementation of a series of national strategies such as new countryside construction, beautiful countryside construction, territorial space planning and rural revitalization, efficient utilization of resources, ecological environment protection, and high-quality economic development has become the theme of China\u2019s development. Based on the analysis of the current predicament and research progress of crop straw resource utilization, the authors assume that more attention should be paid to the following area:The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher."} +{"text": "Semiconductor heterostructures form the basis of modern electronics and optoelectronics, and the study of physical phenomena in them, along with the development of technological methods for their manufacture, is actively carried out all over the world to ensure progress in the output parameters of devices. The most important trends in the development of semiconductor heterostructures are both the development of new systems of materials and the continuous decrease in the size of active regions of various types of heterostructures, including superlattices, quantum wells, and quantum dots, down to the nanometer level, corresponding to the thickness of few monolayers and even less . Technological methods for growing heterostructures are constantly being improved, and along with the study of self-organized heterostructures (such as quantum dots), methods are being developed for obtaining structures with an ordered complex surface topology. An important role in achieving the desired properties of heterostructures and developing new technological methods is played by the development of various analytical methods for studying the structural, optical, and electrophysical properties of quantum-sized heterostructures. Seven articles of this Special Issue reflect almost all of the above areas of research on semiconductor heterostructures.In this Special Issue, Davydov et al. describe0.52Al0.48As/In0.53Ga0.47N quantum well structure with two quantum-confined electron states and two hole sub-bands. The properties of this structure were studied by measuring photoluminescence spectra in a wide temperature range (10\u2013300 K). The authors determined the energy position of localized states in such quantum wells using phenomenological analysis based on experimental measurements of the Fermi edge singularity and its analysis in terms of the line shape model with key physical parameters, such as the Fermi energy, the hole localization energy, and the band-to-band transition amplitude.In the next article, Ahn et al. consider2 islands were used by Mintairov et al. [Measurements of the magneto-photoluminescence spectra of single-electron quasi two-dimensional InP/GaInPv et al. to find The following articles of the Special Issue are devoted to solving various technological problems in the implementation of various semiconductor heterostructures for light-emitting devices and transistors.Novikov et al. describeThe problems of selective growth of InGaAs quantum wells on GaAs substrates by metalorganic chemical vapor deposition were analyzed by Shamakhov et al. . They co18 cm\u22123 can be achieved in the p-GaN/AlN-IL/AlGaN structure.Dai et al. describeIn the last article of this Special Issue , the autIn general, the Special Issue includes seven articles from different groups devoted to the study of the basic properties and technological peculiarities of various semiconductor heterostructures, including quantum wells, quantum dots, and superlattices, grown by metal\u2013organic vapor deposition or molecular beam epitaxy. These structures are designed to implement various devices, such as InGaAs semiconductor lasers, quantum electronics devices, high-power UVC emitters with electron beam pumping, Ge(Si) infra-red emitters, and various types of HEMT."} +{"text": "For more than 40 years, under the leadership of four editors and two publishers, The International Journal of Aging and Human Development (IJAHD) has featured multidisciplinary scholarship related to aging processes and older adults. With the publication of eight issues a year, with over 800 pages of scientific content, the IJAHD places emphasis upon psychological and social studies of aging and the aged. However, the Journal also publishes research that integrates observations from other disciplines that illuminate the \"human\" side of gerontology. A more recent focus includes midlife development, as well. About half (47%) of the publications in the IJAHD are from international colleagues. This presentation will discuss tips for both international and US-based scholars for ensuring timely reviews and positive decisions for manuscript submissions, including such areas as key words, suggesting unbiased reviewers, formatting, writing mechanics, clearly-articulated methods, and a sound theoretical basis."} +{"text": "Entering the twenty-first century, the centenary neurosurgery has entered the era of network neurosurgery, along with the development of brain research \u20133, the dNetwork neurosurgery is based on the topological characteristics of the brain networks, using multimodal intelligent neurological imaging and minimally invasive surgical techniques. In the process of diagnosing and treating neurological diseases, network neurosurgery can protect and remodel the patient\u2019s functional brain networks and thus improve the level of diagnosis and treatment of refractory neurological disorders. Network neurosurgery will be the nexus for translational research in the field of human brain science.In the early twentieth century, neurosurgery gradually became an independent clinical specialty by a deep understanding of brain neurophysiology and functional localization. The centenary history of neurosurgery can be divided into three stages: classical neurosurgery, microneurosurgery, and minimally invasive neurosurgery. The three dimensions of brain anatomy and cognitive discovery, leap development of biomedical imaging, and the update of surgical instruments are the driving force of the continuous development of neurosurgery.In the late nineteenth century, surgeons began to engage in the surgical treatment of intracranial tumors, brain abscesses, epilepsy, spinal cord compression, and trigeminal neuralgia. In 1870, Fritsch and Hitzig firstly proved the functional localization of the parietal cortex. Subsequently, Flechsig mapped the functional areas of movement, sensation, and vision in human brains and established the examination methods of the nervous system. The diagnostic techniques of pneumoencephalography (1917), cerebral angiography (1927), electroencephalogram (EEG) (1929), and other specialized methods detecting the location of intracranial lesions have laid the foundation for neurosurgery. In 1919, Cushing (1869\u20131939), a neurosurgeon, proposed and established the neurosurgery. During this stage, the neurosurgery solved the patients\u2019 increased intracranial pressure and neurological deficits caused by intracranial lesions.From the 1950s to the late twentieth century, the successive appearance of computerized tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) provided reliable imaging evidence for early detection and accurate localization of intracranial lesions. The surgical microscope and microsurgical instruments, such as high-speed cranial drill, controllable operating table and skull frame, automatic retractor, ultrasonic suction, and bipolar coagulation, solved the problems of lighting, narrow field, and hemostasis that interfered with the process of neurosurgery. The new procedure of microsurgery, especially the transcranial approach, can accurately remove the brain lesions while effectively protecting the normal brain structure.The minimally invasive neurosurgery was capable of early and accurate diagnosing neurological disorders and locating the functional areas based on modern diagnostics imaging. The neurosurgical equipment of navigation systems, neuro-endoscopy, cerebral blood flow, and electrophysiological monitoring have provided more reliable guarantees for the accurate detection of lesions and avoidance of neurological impairment during surgery. Endovascular interventional techniques and stereotactic radiosurgery have become new modalities for minimally invasive neurosurgery.Entering the twenty-first century, the research boom of brain science, the digitization of medical imaging, and the emergence of modern technology in hybrid surgery have promoted neurosurgery to the era of networks neurosurgery.The human brain is the most complex object in the known universe. Understanding the structure and function of the brain is the most challenging frontier scientific problem in the twenty-first century. Brain research has important clinical significance for the effective diagnosis and treatment of brain disorders. Brain science research reveals the theory of cerebral networks and promotes neurosurgery in the era of networks neurosurgery.Modern digital neuroimaging, such as functional MRI (fMRI), DSA, single photon emission computed tomography (SPECT), positron emission tomography (PET), and other multimodal neuroimaging technologies, has achieved the leap from anatomical neuroimaging to functional neuroimaging. The structural brain imaging and functional networks have laid a solid foundation for networks neurosurgery.The modern neurosurgical hybrid operating room is equipped with intraoperative MRI and cerebral angiography equipment, which provides real-time imaging data and thereby guides the operation. Intraoperative waken-up anesthesia, frameless stereotaxic robots, intraoperative neurophysiological monitoring (IONM), and other technologies have established a technological platform for networks neurosurgery.In the procedure of networks neurosurgery, the neural network and its relay station can be precisely positioned. The intraoperative resection of intracranial lesions and implantation of electrodes are accomplished with neuroengineering, nanotechnology, brain-computer interface, and other technologies. Networks neurosurgery not only treats brain tumors and neurovascular diseases but also opens new avenues for chronic pain , movement disorders , epilepsy, mental disorders, hearing impairment, vision loss, and other refractory neurological disorders.The vast majority of brain hubs in the human brain functional networks have only a few connectivities, while a few hubs have a great many connectivities, known as the key hubs of the brain networks. The structure and function of the networks will be seriously affected if the key hubs were damaged . ExploraThe blood supply and the structure of brain networks are strongly linked to functional connectivity \u201310. AlthRevascularization contributes to the recovery of brain functional networks in patients with ischemic stroke. Chronic cerebral hypoperfusion affects the structure and function of fiber tracts in adult patients with moyamoya disease (MMD) , and theThe prediction of recovery in brain network connectivity is available after the revascularization by brain network analysis, which may contribute to predicting the selection of surgical management. Prospectively, the preoperative evaluation will no longer be limited to the degree of ischemia in the management of cerebrovascular diseases. The surgical indications and prediction of surgical outcomes are determined regarding the status of brain network connectivity.The generation and regulation of consciousness and cognition exist at the level of neural circuit. The cerebral cortex plays a central role in consciousness and cognitive functions. There may be complex neuronal subsets in the single brain region. Central circuit is the core circuit that generates, maintains, and regulates the consciousness. The core structure of central thalamus is a key target for deep brain stimulation (DBS) in consciousness disorders. The functional connectivity and neural oscillatory characteristics of the central thalamocortical circuit are strongly associated with loss and recovery of consciousness. Different frequencies of electrical stimulation can awaken the state of loss of consciousness. Therefore, it is a key way to resolve individual differences, increase the rate of awakening, and shorten the awakening duration, by developing an adaptive approach of closed-loop neuromodulation based on the regulatory mechanisms and theories and forming an effective clinical practice for DBS awakening in consciousness disorders. Besides, it provides novel ideas for analyzing the \u201cPrinciples of Brain Cognition and Neural Mechanisms of Consciousness.\u201dBy directly measuring the pathological brain activity and providing adjustable stimulation, DBS is feasible to treat neurological and psychiatric disorders related to abnormal circuit function. The brain electrodes and pacemaker , 16, whiBrain-computer interface (BCI) establishes a new communication and control channel between the brain and the external environment that is independent of peripheral nerves and muscles. Thus, it is practicable to accomplish the direct interaction of the brain and external devices. BCI can be used as an auxiliary communication and control method for patients with severe movement disorders. By utilizing the signals of the motor cortex, patients can precisely control the external robotic arm and manipulator and restore motor dysfunction. Obtaining and analyzing the EEG signals of patients with chronic consciousness disorders through BCI equipment, the diagnosis and assessment, prognosis evaluation, and even communication of consciousness disorders can be achieved. Further clinical research on neurodegenerative diseases is warranted.In the twenty-first century, brain research has advanced by leaps and bounds, targeting the network neurosurgery. Therefore, actively and rationally constructing the new discipline is an arduous task for the neurosurgery community ."} +{"text": "The National Institutes of Health\u2019s Asian American, Native Hawaiian and Pacific Islander Health Scientific Interest Group (NIH AANHPI-HSIG) provides a viewpoint on developing approaches to enhance research on health and wellbeing for Asian American, Native Hawaiian, and Pacific Islander ethnic populations, in order to advance racial equity amongst such populations. Asian American (AA), Native Hawaiian and Pacific Islander (NHPI) populations are highly heterogeneous racial/ethnic groups with diverse health disparity concerns including hepatitis B and chronic liver disease, diabetes without obesity, various types of cancer, and stroke etc. , 2. AA aAsian American, Native Hawaiian, Pacific Islander (AA and NHPI)\u201d to describe the populations in an Executive Order (14031) on May 28, 2021, which reinstated and reinvigorated the White House Initiative (WHIAANHPI) on improving the quality of life and opportunities to participate in federal programs for AAPI proclaimed in an earlier Executive Order (13125) on June 7, 1999 [The National Institutes of Health Asian American Pacific Islander Health Scientific Interest Group (NIH AAPI-HSIG) was established in April 2021 with approval from Dr. Michael M. Gottesman, the NIH Deputy Director for Intramural Research . The groe Order 1031 on Marder 1312 on June In just over 1 year, the NIH AANHPI-HSIG has initiated several projects to integrate NIH-wide efforts to enhance knowledge and awareness of health disparity and assess the research needs for AA and NHPI populations , 6. We hMental health issue facing the AA and NHPI community is another important topic that was discussed at the 1st NIH AANHPI Mental Health and Well-Being Seminar Series hosted by the NIH AANHPI-HSIG . As partThrough these initiatives we have recognized that in order to advance health equity, more research on health disparities specific for the AA and NHPI racial/ethnic subgroup is needed. To address this need, a NIH-wide AANHPI Research Priority Recommendation Working Group has been formed. The Working Group led the effort to publish the first NIH Request for Information (RFI) (NOT-CA-22-047) specifically focusing on actionable priority recommendations to improve research on health and well-being of AA and NHPI populations in line with the White House [To celebrate the AANHPI-Heritage Month, AANHPI-HSIG successfully organized its inaugural AA and NHPI Health Research Conference on May 4\u20135th, 2022, with a central theme of \u201cFrom Mechanism to Translational Research: Improving the Health and Therapeutic Outcome for AA and NHPI Populations\u201d . Dr. LawAll of Us research project using intentional community engagement efforts and the multilevel AANHPI engagement strategy, and the New York Genome Center\u2019s Polyethnic-1000 program that enrolls ethnically diverse and underserved cancer populations in New York City were highlighted. Participants of the conference also stressed the need of data disaggregation for AA and NHPI subgroups, discussed the language accessibility problem for AA and NHPI populations in seeking medical care or involving in clinical research, and addressed the effect of anti-Asian hate/discrimination on health. The conference not only enhanced the awareness of AA and NHPI heritage and highlighted scientific achievements in AA and NHPI health-related research, but also informed NIH leadership of the current research needs and priorities.The two-day conference, which included participants from across the HHS, had for scientific sessions on Cancer; Diabetes and Other Diseases; Other Health Conditions; Mental Health, Community Health Care, Caregiver and Indigenous Medicine, respectively; each followed by a Panel Discussion and Summary session . Many isIn summary, advancing AA and NHPI health research is an integral part of the NIH\u2018s charge on minority health and health disparities research. The NIH AANHPI-HSIG can contribute to the WHIAANHPI on advancing equity, justice, and opportunity for AA and NHPI communities in the United States in many areas, including data disaggregation for AA and NHPI subgroups, language access, promoting inclusion, capacity building and community engagement, through enhancing research focusing on the health and well-being of AA and NHPI populations . The res"} +{"text": "This presentation highlights the development of Age-Friendly care interactive modules to prepare the future healthcare workforce to care for older adults in Age-Friendly Health Systems. To date, there is a gap in the educational preparation of nurses, advanced practice nurses, and other health professionals to work in Age-Friendly Health Systems upon entry into practice. This project, funded by a faculty innovation grant at Seton Hall University, provides undergraduate and graduate nursing and interprofessional students with the background knowledge to care for older adults in Age-Friendly Health Systems. The aim of this project was to develop five interactive modules to embed in undergraduate and graduate nursing and interprofessional curricula focusing on the provision of care to older adults using the evidence-based 4Ms Framework: What Matters, Medication, Mentation, and Mobility. Faculty collaborated with instructional designers in development of the modules using Articulate 360 to embed them in curricula. The first module focuses on the background of the Age-Friendly Health Systems movement, how health systems may become an Age-Friendly Health System, and the evidence for the 4Ms Framework. The second module focuses on assessment and act on strategies related to What Matters to older adults including advance care planning strategies. The third module covers crucial information related to Medication such as avoiding potentially inappropriate medications, deprescribing, and antibiotic stewardship. The fourth module focuses on Mentation and covers assessment and act on strategies for depression, delirium, and dementia. The fifth module focuses on Mobility such as promoting mobility and decreasing fall risk."} +{"text": "Yao et al.) Emerging diseases and health issues, lifestyle and diet changes urge us in seeking novel bioactive substances and formulations from plant sources (The investigation on plants that are both medicinal and edible is rooted in different ethno-medicinal systems ( sources . RelatedAlong with the strong increase in the publication of medicine food homology study , researcIn this Research Topic, we have provided a discussion forum for the community, and received 47 full length article submissions, with 17 papers published, which covers cultivation and pharmacognosy of medicinal and food plants, ethno-pharmacological practices and pharmacological investigation, food function and safety evaluation of selected plants; identification of novel pharmacological and biological effects of plants, strategy on the development of pharmaceutical, nutraceuticals and functional products, reviews as well as general methodology and research advancement , 2.This Research Topic provides a platform and community space for sharing and enlightening the state-of-art discovery and scientific understanding in edible and medicinal plants . Efforts"} +{"text": "A sustainable approach in asphalt pavement engineering should focus on materials, design methods, and technologies that can contribute to minimizing environmental impacts through a reduction in energy consumption and natural resources, while ensuring that all performance standards and requirements are met.The decision-making process should be appropriately updated by adopting suitable tools and methodologies, such as LCCA and LCA, to measure the potential economic and environmental impacts associated with the adoption of sustainable solutions.This Special Issue includes recent and original studies that address the design and construction of sustainable asphalt pavements performed by several researchers belonging to different universities. The scope of the presented studies is extensive and multidisciplinary, covering many aspects related to (i) recycled and renewable materials for the production of asphalt concrete, (ii) low-energy and low-emission technologies, (iii) long-life design solutions, and (iv) green urban development.(i) Recycled and renewable materials in asphalt pavements may be employed for the modification of asphalt binders and/or for the full or partial replacement of natural aggregates and mineral filler in asphalt mixtures ,2. In th(ii) Cold-mix asphalt technologies, including water-foamed asphalt and emulsion-based mixtures, have been extensively used for their energy-saving and emission-reducing features. The study of focused (iii) Durability and performance life are recognized to be critical factors in the sustainability of road pavements . The SpeComposite admixtures of lignin and glass fibers have been successfully used as additives to improve the performance of asphalt mixtures, in terms of moisture susceptibility and thermal cracking resistance . The env(iv) The construction of a sponge city is a major green innovation that can be used implement the concept of sustainable development. The study of addresseThe editors give special thanks to the authors and the editorial team of Materials for the collaborative and peer-review process. We hope you enjoy reading this Special Issue and find new concepts for future and present research."} +{"text": "Sexual and reproductive health (SRH) among young people, aged 10\u201324 years, in Sub-Saharan Africa (SSA) remains a major public health challenge, with evident gaps in access to SRH services and increased risk of poor SRH , 4. HoweTemin et al. open this collection by exploring HIV-related risk determinants from the perspective of foreign migrant adolescent girls and young women in South Africa who participated in an evidence-based female-focused intervention\u2013\u201cGirls Club Project.\u201d They provide recommendations for more inclusive HIV prevention programming that reaches foreign migrant adolescent girls and young women. With a similar focus on risk factors, Envuladu et al. assessed the covariates of sexual activity and consistent condom use among adolescents in Plateau State, Nigeria. Their results suggest a need for gender-tailored interventions. Taking a broader perspective, tailored interventions that are contextually appropriate can enhance the acceptability and adoption of SRH interventions.Yuya et al. assessed the level and predictors of knowledge of reproductive rights among Haramaya University students in Ethiopia. The study revealed that lack of awareness/information on reproductive health issues and absence of reproductive health services utilization were important predictors of participants' knowledge of reproductive rights. This warrants further investigations on whether knowledge of reproductive rights can promote uptake of sexual and reproductive health services. Lawrence et al. shared the work undertaken by the team as part of the Public Health Adolescent Services Evaluation, which is a national evaluation of adolescent HIV services in Kenya. The evaluation revealed a preference for adolescent autonomy in seeking sexual and reproductive health services and contacting healthcare workers for sexual and reproductive health information. This study confirms the value of adolescent and youth-friendly health services and the need for contextually appropriate strategies to enhance uptake and adoption.Two authors highlight knowledge and uptake of Youth Sexual and Reproductive Health services with helpful insights. Bridging the Research-to-Practice gap, three articles highlight the application of implementation science in young people's sexual and reproductive health. Mgoli Mwale et al. evaluate the sustainability of the Community Score Card to improve Adolescent Sexual and Reproductive Health in Ntcheu, Malawi. Their work provides compelling evidence of the importance of agents and context in the sustainability of interventions. They specify real-world facilitators, barriers, and opportunities in promoting sustainability within resource-constrained settings. Libous et al. offer a new generalizable approach to guide intervention adaptation that builds on existing infrastructure, culture, and resources to inform implementation strategies. Their work focused on the adaptation of a trauma-informed cognitive behavioral therapy intervention addressing mental and sexual health for adolescents and young adults living with HIV guided by the ADAPT-ITT framework. Obiezu-Umeh et al. presented compelling findings from a systematic review of 23 articles on the implementation outcomes and implementation strategies of youth-friendly sexual and reproductive health services in sub-Saharan Africa. The authors underlined the need to develop rigorous studies further to understand better which and what combination of implementation strategies would lead to more gain in promoting the uptake and sustainment of youth-friendly sexual and reproductive health services. These articles provide concrete suggestions for community and young people's engagement in intervention development, adaptation, and implementation processes, to foster co-creation and ownership within communities. These are critical for the adoption, scale-up, and sustainability of interventions as we seek to bridge the research-to-practice gap.Echoing the call for Individually, these contributions address an array of critical issues. Collectively, they provide momentum on the importance of contextually appropriate, youth-friendly, and youth-engaged approaches to enhance the uptake, scale-up, and sustainability of young people's SRH interventions in SSA. We acknowledge that articles presented in this collection are not exhaustive of the work in the field. Nevertheless, the findings, insights, and perspectives discussed in each paper could inspire new research and interventions.This special issue continues to highlight substantial structural, social, and individual barriers that limit the uptake of SRH services. Nonetheless, a few articles highlight the importance of active community engagement and active youth participation to circumvent these barriers. Community engagement and youth participation can enhance the uptake, appropriateness, and sustainability of SRH intervention and can help move us closer to the goal of bridging the research-to-practice gap in promoting SRH among young people in SSA. Participatory approaches such as crowdsourcing that involve community members in solving a problem and then publicly sharing innovative solutions could provide an opportunity to co-create with young people and community members , 7. ThisAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Original Research, one Hypothesis and Theory, and one Perspective have addressed this issue by studying possible microbiota involvement and modulation in the case of psoriasis, epilepsy, depression, and a possible correlation with environmental exposure to glyphosate and glyphosate-based herbicides with neuropsychiatric conditions. In all these publications, diet, probiotics, and lifestyle changes represent also valid support for ameliorating health conditions.In the last decade, the gut-skin-brain axis has emerged as a research field offering more and more evidence on the way foods and intestinal microbiota can affect the development of intestinal/skin diseases , and neuSun et al. considered two physiological body barriers, i.e. skin and gut, and investigated the relationship between intestinal microbiota and psoriasis development with an epidemiologic analysis and an experimental approach. In psoriatic patients, the incidence of gastrointestinal discomfort symptoms was significantly higher than in healthy subjects and the gut microbiota was improved when patients received therapy of oral acitretin and narrow-band ultraviolet B, with an evident decrease in their psoriasis area and severity index (PASI) score compared to untreated subjects. The transplantation of fecal microbiota from psoriatic patients or healthy controls into mice after the application of imiquimod cream confirmed that psoriatic microbes delayed recovery of psoriasiform dermatitis and induced a lesser decrease of IL-17A, a key proinflammatory psoriatic cytokine, thus validating the epidemiologic data. This study represents an excellent example of the translational integration of preclinical and clinical investigations and helps in better defining the complex association between dysbiosis and psoriasis with the final aim of developing microbiome-based therapeutic options for dermatologists.The original research by Wang et al. for epilepsy, a disease imposing low quality of life for millions of people. The hypothesis of a possible gut dysbiosis has been considered by the authors based on the published studies about the regulating role of bacteria in neuroinflammation and oxidative stress. Under this perspective, the administration of probiotics, Bifidobacterium and Lactobacillus strains, prebiotics, inulin, and synbiotics, the combination of bacteria and inulin, were administered to kainic acid-induced epileptic rats, and both clinical manifestations and biochemical markers of the supposed involved mechanisms were collected. This pre-clinical results obtained show a decreased frequency and duration of seizures, an extended latency period with a major effect due to synbiotics, together with an improvement in cognitive impairment. The biochemical markers of lipid peroxidation, DNA damage, diminished total antioxidant ability, inflammation, and the release of IL-1\u03b2, IL-6, and TNF-\u03b1, confirm the authors' hypothesis and pave the way for finding new therapeutic agents.The connection between the gut and brain has been investigated by Ghannoum et al. provide a Hypothesis and Theory contribution shedding light on the potential link between the gut microbiome and depression, exacerbated by the COVID-19 pandemic. The authors provided clinical evidence suggesting that integrative management of depression may also include microbiome modulation. Despite this issue deserves further data to be fully comprised, the possibility to help people to understand the causes of their mental problems and to avoid the use of antidepressant drugs, often without real positive effect or coupled with strong side effects and costs, is worth to be investigated.Perspective opinion made by Barnett et al., the reader enlightens by the descriptive evidence of how glyphosate, which was designed to combat threatening weeds competing for nutrients and resources for crops production, induces alterations of the gut microbiota diversity, associating with neuropsychiatric conditions like anxiety, depression, autism, and important maladies like Parkinson and Alzheimer's disease. The discussion of the topic walks through a narrative describing how sub-toxic exposure to glyphosate and glyphosate-based herbicides is reported to perturb the abundance of important species in the microbial intestinal biome, which include commensals like Lactobacillus spp., Bacteroides spp, Bifidobacterium spp., Butyricoccus spp., Clostridium spp., and members of the family Ruminococcaceae, among others. The changes in the abundance of these bacterial species are the results of their susceptibility to the antimicrobial properties of glyphosate and result in the reduction of important microbial metabolites many of which are neurotransmitters, necessary for mental health and wellbeing acting through the gut-brain-microbiome axis. On the other hand, there is a selection of glyphosate-resistant microbes with the potential to increase the production of pro-inflammatory cytokines and reactive oxygen species which may result in dysfunctional hypothalamic-pituitary-adrenal axis activation, with deleterious consequences in neuronal homeostasis. The authors finish with a discussion of the benefits that the use of glyphosate and glyphosate-resistant plants brought to crop production in the world, which permits us to understand the need for the development of alternative methods for weed control.In the In conclusion, the published works evidence that perturbations of the gut microbiota uncouple the function of the Gut-Skin-Brain Axis which is evidenced by the development of diseases in humans or its preclinical models. A full comprehension of the involved mechanism, like high oxidative stress, DNA damage, impaired cell signaling, and associated dysbiosis, will open the way to offer alternative healing methods to drugs but above all, the possibility to prevent the onset of the associated diseases through a correct lifestyle and diet; all in all with the ultimate goal to promote patient's health.AF wrote the introduction and the conclusion. All authors summarized the contributions and added comments to the cited papers. All authors approved the submitted version."} +{"text": "Many existing and newly constructed bridges are made of reinforced and prestressed concrete. Advanced concrete materials play an increasingly important role in concrete bridges, facilitating the strengthening and repair of existing bridges, fast replacement solutions for parts of existing bridges, and for the design of novel challenging bridge projects. The development of advanced concrete materials and their structural applications is, thus, an important topic in the built environment.The articles presented in this Special Issue bring together research insights, practical applications, and discussions on how to develop better structural concrete materials for bridge engineering practices. Since articles were written both by materials scientists and bridge engineers, a wide view on the topic is presented.One example of an advanced structural concrete material is ultra-high-performance fiber-reinforced concrete (UHPFRC). With research on this topic having reached a high level of maturity, practical applications of this material are becoming increasingly more common. A key practical issue is related to the resulting fiber content, fiber orientation, and efficiency factor of the structural elements, particularly relevant for thin elements. This property determines the post-cracking tensile strength of the UHPFRC. In , the autAdvances in steel-fiber-reinforced concrete include the development of steel-fiber-reinforced expanded-shale lightweight concrete (SFRELC) . In partAnother example of an advanced structural concrete material is concrete with an MgO expansive agent and steel fibers added to the mix. This improved concrete mix was applFor the prefabrication industry, a better understanding of the structural behavior can result in the optimization of the resulting prefabricated elements. A topic of particular interest is the interface bond strength and anchorage performance of the steel reinforcement (ribbed and plain bars) in the prefabricated concrete. The experimental study of resultedFor existing bridges, the first challenge is often the proper assessment of the structure; the information is important for the evaluation of various possible solutions, such as for the strengthening of the structure. In , the autOn the topic of strengthening existing bridges, various advanced structural concrete materials are proposed. Experiments on reinforced concrete beams strengthened with textile-reinforced concrete (TRC) and fiber\u2013textile-reinforced concrete (F/TRC) showed the beneficial effects of this strengthening technique at the ultimate limit state, as well as in the serviceability limit state . A seconUHPFRC is also proposed for the strengthening of existing bridges . ExperimPolyvinyl alcohol fiber-reinforced engineering cementitious composites (PVA-ECCs) are proposed in another paper , where tAnother novel method for strengthening was proposed in , in whicUltimately, proposesMaterials, who helped handle the manuscripts of this Special Issue, as well as the journal staff, who provided expert assistance to the development of this Special Issue at every step of the way.These presented papers provide insight into the current state-of-the-art of advanced structural concrete materials in bridge applications, and show the way towards the practical application of these materials. I appreciate all author contributions and sincerely value the time and effort spent in preparing these articles. I would also like to thank all reviewers who contributed to this Special Issue for their time, effort, and valuable remarks to the articles. Finally, I would like to thank the academic editors of"} +{"text": "A 28-year-old male farmer from the rural zone of Alagoas, seropositive for HIV and not adhering to antiretroviral therapy, was admitted to an infectious disease service in northeast Brazil with continuous fever, asthenia, cough with bloody expectoration, and loss of 20 kg in 30 days.2 93%, and whitish plaques on the tongue. Complementary tests revealed upper gastrointestinal bleeding on endoscopy; interstitial infiltrate, lymph node enlargement, and bronchial thickening on chest radiography; and visceromegaly on abdominal ultrasound. The laboratory profile revealed severe anemia and thrombocytopenia and mild leukocytosis , besides intracellular structures in neutrophils suggestive of Histoplasma capsulatum in the blood smear , with a high rate of morbidity and mortalityAs definitive diagnosis of histoplasmosis can be difficult and time-consuming, the need to expand access to other tests becomes relevant and may be useful in deciding the initiation of empirical therapy for histoplasmosis. Thus, in the present case description, we highlight the relevance of performing microscopic examination of peripheral blood smear, allowing direct viewing of the fungus and the final diagnosis of histoplasmosis."} +{"text": "Chronic kidney disease (CKD) is a leading public health problem that affects a significant proportion of the population worldwide. It is a complex multifactorial disease and approximately 13% of the world population are affected by this disease . The numThe use of experimental models represents a valuable tool to understand the underlying pathophysiological mechanisms of kidney diseases and exploring novel therapeutic targets. Model organisms, in particular rats and mice, represent an invaluable resource for both fundamental and applied research, allowing prediction studies, modeling, and the identification of action mechanisms. Drug development requires tests on model organisms before the clinical trials and this makes these organisms essential for progress within the field.This Research Topic encompasses two research articles and two review articles. These articles introduced cutting-edge research on diabetic nephropathy (DN) and the role of cellular senescence in CKD. In addition, the role of extracellular vesicles (EVs) in acute kidney injury (AKI), CKD, DN and renal tumors has been discussed. However, drug/chemical-induced nephrotoxicity and other models of AKI were not discussed in these articles. The guest editors are pleased to present a compendium of these articles as follows:Hou et al., the investigators utilized the connectivity map (CMap) with renal tubulointerstitial transcriptomic profiles of biopsy-proven early- and late-stage DN, a leading cause of CKD, to identify novel treatment candidates. The therapeutic potential of the suggested candidate drugs was evaluated in vivo in streptozotocin-induced CD-1 mice, and in vitro utilizing HK-2 cells and immortalized bone marrow-derived macrophages (iBMDMs). CAY10603, a specific inhibitor of histone deacetylase 6 (HDAC6), was defined as a potential drug and the experimental findings showed its ameliorative effect on renal dysfunction, inflammatory cell infiltration, tubular injury and tubulointerstitial fibrosis in diabetic mice. These effects were associated with the inhibition of NLRP3 and pyroptosis as revealed by the studies on HK-2 cells and iBMDMs.In the research article by Wang et al. summarized and discussed the findings of the studies showing the effects of the active constituents of Rheum ribes on key signaling pathways implicated in the pathogenesis of renal fibrosis. The conducted analysis revealed the beneficial effects of Rheum ribes constituents against the development of renal fibrosis and their value as drug candidates.In another article, Zhao et al. summarized the common features and the interaction between CKD and renal senescence, and the therapeutic approaches, including senolytics, senomorphics, and immunomodulation. This review article highlighted the value of renal senescence as a promising target for therapeutic intervention of CKD.Etiology, pathological changes, phenotype, and outcome are among the similarities that renal senescence shares with CKD. Given these numerous similarities, is not clear whether renal senescence is a trigger or a consequence of CKD. In this review article, Xiang et al. summarized the latest studies showing the role of EVs in renal diseases and highlighted their value as therapeutic targets. EVs are cell-derived membrane structures released by most cells and play a role in cell-cell communication and as vehicles for information transmission. The association between EVs and renal diseases has been acknowledged. This review highlighted the updated progress in understanding the role of EVs in the progression of renal diseases and the possible therapeutic application of stem cell-derived EVs.The editors anticipate the published articles in this Research Topic to be of interest to the readers and expect researchers to benefit from achieving further progress in understanding the mechanisms underlying renal diseases and the development of novel therapeutics."} +{"text": "In this paper, we propose a method to identify different varieties of raisins by combining near-infrared (NIR) spectroscopy and machine learning algorithms. The direct averaging of the spectra taken for each sample may reduce the experimental data and affect the extraction of spectral features, thus limiting the classification results, due to the different substances of grape skins and flesh. Therefore, this experiment proposes a method to fuse the spectral features of pulp and peel. In this experiment, principal component analysis (PCA) was used to extract baseline corrected features, and linear models of k-nearest neighbor (KNN) and linear discriminant analysis (LDA) and nonlinear models of back propagation (BP), support vector machine with genetic algorithm (GA-SVM), grid search-support vector machine (GS-SVM) and particle swarm optimization with support vector machine (PSO- SVM) coupling were used to classify. This paper compared the results of four experiments using only skin spectrum, only flesh spectrum, average spectrum of skin and flesh, and their spectral feature fusion. The experimental results showed that the accuracy and Macro-F1 score after spectral feature fusion were higher than the other three experiments, and GS-SVM had the highest accuracy and Macro-F1 score of 94.44%. The results showed that feature fusion can improve the performance of both linear and nonlinear models. This may provide a new strategy for acquiring spectral data and improving model performance in the future. The code is available at Raisins are rich in dietary fiber, vitamins, carotenoids and polyphenols . StudiesIn the existing studies, Mostafa et al. used raisins images combined with support vector machine (SVM) and linear discriminant analysis (LDA) to identify fifteen kinds of raisins, with the highest average accuracy of 69.78% and , respectively. In the GA algorithm, the ranges of C and g were within in skin spectra of the different varieties of raisins were more obvious than that of flesh spectra; the differences of characteristic peaks of fatty acids, amino acids and carbohydrates in flesh spectra were more obvious than that of skin spectra. Studies have shown that skin and flesh are more susceptible to climate and content of water in the external environment, and only recording spectral data on the skin will limit the model classification performance [In the experiment, the spectrum shows that the differences of characteristic peaks of lipids and phenols Click here for additional data file.S1 File(ZIP)Click here for additional data file."} +{"text": "Dear Editor,A six-year-old female patient presented with hyperchromic confluent papules on the trunk and face , followiOn dermoscopy, the lesions were non-specific with a homogeneous brownish color and with structures similar to follicular crypts or openings .Figure 2Histopathological examination showed aBasaloid follicular hamartoma (BFH) consists of the proliferation of multifocal basaloid cells, with frequent connection to the epidermis.The main differential diagnosis of BFH is basal cell carcinoma (BCC). Both consist histopathologically of basaloid strands of cells in a fibrous stroma, but the BCC is not folliculocentric and can be seen in the interfollicular dermis.3Acquired BFH can show a linear pattern, following the lines of Blaschko - occurring due to mosaicism - or in a generalized form - commonly associated with autoimmune diseases.In the case described herein, BFH clones were distributed along the Blaschko lines, representing ectodermal development patterns, which is a rare distribution. When a somatic mutation or chromosomal nondisjunction occurs during embryogenesis, affecting an epidermal progenitor cell, the affected offspring cells proliferate and migrate along the lines of Blaschko.Currently, there is no standard treatment for BFH. Correct identification prevents patients from undergoing unnecessary surgery and also allows periodic monitoring to detect malignant transformations. Lesions that increase in size or change in appearance should be biopsied whenever detected. If associated with an autoimmune disease, treatment of the comorbidity may lead to the regression of the associated skin lesions.In summary, BFH is a rare type of benign skin tumor, with different presentations, which can be congenital or acquired. Its main differential diagnosis is basal cell carcinoma, and histopathology should be performed for differentiation. There is yet no standard treatment for this condition and, in most cases, it is not necessary.None declared.Gabriela Martins de Queiroz: Collection, analysis, and interpretation of data; design, planning, drafting and writing of the manuscript; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.Tayla Cristina Lopes: Collection, analysis, and interpretation of data; design, planning, drafting and writing of the manuscript; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.Maria Clara Dantas Valle Soares: Analysis and interpretation of data; drafting and writing of the manuscript; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.Carlos Bruno Fernandes Lima: Analysis and interpretation of data, design and planning of the manuscript; critical review of the literature; critical review of the manuscript; approval of the final version of the manuscript.None declared."} +{"text": "Alcohol withdrawal delirium is severe complication of alcohol withdrawal leading to high mortality. Early identification of severe course of psychosis and complications threatening the patient\u2019s life is the most important problem in the treatment of these patients.Under supervision were 690 men, dependent on alcohol, in the state of withdrawal with acute psychotic disorder ; the average age - , the average age of alcohol abuse - . The patients were examined in a dynamics after a re-hospitalization after 5-7 years. This allowed us to verify the differential diagnostic approach to acute psychotic disorders in a state of abandonment, to investigate the impact of chronic acute psychotic disorders on the course of alcohol dependence, including the formation of deficits.clinical, clinical and psychopathological, methods of quantified scales and mathematical statistics.There were estimated factors influencing the severity of alcohol withdrawal with delirium: total amount of alcohol consumed per week, drunken alcoholics, persistent alcohol abuse, social disadaptation, cognitive impairment, psychological disorders, reducing the quality of alcohol consumed, food pattern characterized total calorie mostly due to alcohol, life trajectory, severe or chronic somatic diseases, rate of progression of alcohol dependence.The severity of acute psychotic disorder in the state of alcohol withdrawal mostly depended situational factors such as the number of days of severe drinking before a psychotic disorder, the pattern of nutrition, the quality and quantity of alcohol consumed, the presence of acute somatic diseases.No significant relationships."} +{"text": "Rhipicephalus appendiculatus Subolesin, and a cross-species-effective vaccine formulation. As the next step, a controlled vaccine field trial has been approved by Ugandan state regulatory authorities, the Uganda National Council for Science and Technology (UNCST) and the National Drug Authority (NDA), to evaluate the efficacy and effectiveness of the vaccine formulation for the control of cattle tick infestations under field conditions. The results of this trial may lead to the approval of the vaccine for application in Uganda to improve cattle health and production while reducing the use of acaricides.A collaboration program was established between the group of Health and Biotechnology (SaBio) of the IREC Institute of Game and Wildlife Research and the National Agricultural Research Organization of Uganda (NARO) for the development of vaccines for the control of cattle ticks in Uganda. Controlled pen trials identified a tick protective antigen, Ticks parasitize livestock and wild animals with a higher prevalence in the warm tropics and sub-tropics while humans are accidental hosts, with all at risk for tick-borne diseases . EconomiRhipicephalus appendiculatus), blue ticks (R. decoloratus), bont ticks (Amblyomma variegatum), and red ticks (R. evertsi) , where NTV is the number of adult female ticks in the vaccine-treated group, and NTC is the number of adult female ticks in the control (adjuvant-only-treated) group.The candidate vaccine effect on the tick weight (DW) = 100[1 \u2212 (WTV/WTC)], where WTV is the average adult female tick weight in the vaccinated group, and WTC is the average adult female tick weight in the control (adjuvant-only-treated) group.The candidate vaccine effect on oviposition (DO) = 100[1 \u2212 (PATV/PATC)], where PATV is the average weight of the eggs per survived tick in the vaccine-treated group, and PATC is the average weight of the eggs per survived tick in the control (adjuvant-only-treated) group.The candidate vaccine effect on egg fertility (DF) = 100[1 \u2212 (PPLOV/PPLOC)], where PPLOV is the average weight of the larvae per gram of eggs in the vaccinated group, and PPLOC is the average weight of the larvae per gram of eggs in the control group.Finally, calculate the vaccine efficacy (E) = 100[1 \u2212 (CRT \u00d7 CRO \u00d7 CRF)], where CRT = NTV/NTC, CRO = PATV/PATC, and CRF = PPLOV/PPLOC, which is a representation of the reduction in the number of adult female ticks, oviposition, and egg fertility as compared to the control group, respectively.In conclusion, if vaccine efficacy and effectiveness are supported by the results of the trial, Ugandan state regulatory authorities will consider the approval of the vaccine for prospectus licensure for vaccine commercialization. These results will represent a key step for the Ugandan cattle industry with a positive impact on society and the economy."} +{"text": "Cancer is increasingly recognized as an extraordinarily heterogeneous disease featuring an intricate mutational landscape and vast intra- and intertumor variability on both genetic and phenotypic levels. Prostate cancer (PCa) is the second most prevalent malignant disease among men worldwide. A single metabolic program cannot epitomize the perplexing reprogramming of tumor metabolism needed to sustain the stemness of neoplastic cells and their prominent energy-consuming functional properties, such as intensive proliferation, uncontrolled growth, migration, and invasion. In cancerous tissue, lipids provide the structural integrity of biological membranes, supply energy, influence the regulation of redox homeostasis, contribute to plasticity, angiogenesis and microenvironment reshaping, mediate the modulation of the inflammatory response, and operate as signaling messengers, i.e., lipid mediators affecting myriad processes relevant for the development of the neoplasia. Comprehensive elucidation of the lipid metabolism alterations in PCa, the underlying regulatory mechanisms, and their implications in tumorigenesis and the progression of the disease are gaining growing research interest in the contemporary urologic oncology. Delineation of the unique metabolic signature of the PCa featuring major aberrant pathways including de novo lipogenesis, lipid uptake, storage and compositional reprogramming may provide novel, exciting, and promising avenues for improving diagnosis, risk stratification, and clinical management of such a complex and heterogeneous pathology. Cancer is increasingly recognized as an extraordinarily heterogeneous disease featuring an intricate mutational landscape and vast intra- and intertumor variability on both genetic and phenotypic levels. The complexity of cancer is reflected in a high level of diversity in terms of the underlying mechanisms and drivers of carcinogenesis, manifestation and progression of the disease, spectrum of metabolic and functional modifications of the affected tissue, variety of cellular processes and involved molecular actors, an array of disrupted regulatory circuits, and, finally, clinical outcomes. Furthermore, cancer represents a dynamic system that evolves over the course of qualitatively distinct states regulated by a wide range of entities operating on multiple spatial and temporal scales ,2,3.Under physiological conditions within intricate hierarchical systems, cells receive, send, and process sets of signals that condition the precise coordination of their behavior with the aim of preserving the stability and integrity of a complex structure such as a multicellular organism. Following comprehensive communication and control mechanisms, cells differentiate, grow, divide, and, finally, die when that serves the organism\u2019s well-being. The formation of a malignant phenotype is due to changes that affect the control systems of cell proliferation, senescence and longevity, relationships with other cells, and capacities to evade the surveillance and defense activities of the immune system. The interplay between genetic alterations and environmental factors modulates the expression of both oncogenes and tumor-suppressors, thus orchestrating the nonlinear progression of the neoplastic disease . With unConceptualization of the set of shared biological attributes of malignantly altered cells represents a theoretical framework for distilling the complexity of neoplasia as well asa heuristic tool for research and a better understanding of cancer biology. Key hallmarks of cancer cells are the maintenance of proliferative signaling, avoidance of exogenous growth suppressors, resistance to mechanisms of programmed cell death, replicative immortality, induction of angiogenesis, ability to invade and colonize distant sites reserved for other cells, alteration of cellular bioenergetics, i.e., metabolism reprogramming, and evasion of immune system-mediated destruction . These aThere is a mounting body of evidence underpinning the significance of malignancy type and tissue-specific metabolic alterations, fluctuations in bioenergetic sources, and oxidative stress modulation in supporting the anabolic requirements of tumor biomass production and cancer progression. It is evident that a single metabolic program cannot epitomize the perplexing reprogramming of tumor metabolism needed to sustain the stemness of neoplastic cells and their prominent energy-consuming functional properties, such as intensive proliferation, uncontrolled growth, migration, and invasion . Each ceMost solid tumors exert the so-called Warburg Effect, a phenomenon described in the mid-19th century with the pioneering works by Otto Warburg, the Nobel Prize winner, whereby cancer cells take up glucose at substantially higher rates than the surrounding non-transformed normal tissue and shift their dominant adenosine triphosphate (ATP)-producing pathway towards aerobic glycolysis. In such circumstances, even under normoxia and with completely functioning mitochondria, the glucose-derived carbon is preferentially converted to lactate rather than being oxidized as pyruvate within the tricarboxylic acid cycle (TCA) . It has Nevertheless, aerobic glycolysis is only one element of the cancer-related metabolic reprogramming puzzle. To engage in limitless replicative division, cancer cells require a continuous supply of both glucose and glutamine, representing the principal and most abundant extracellular nutrients, for the metabolic pathways governing the synthesis of the three major macromolecule classes .GlutaminFunctionally interdependent with cancer-specific glucose and glutamine catabolic pathways, reprogramming of the lipid- and cholesterol-associated metabolisms encountered in malignancy are of exceptional importance for the pathogenesis of cancer. Although their relevance was disregarded in the past, they now represent a topic of burgeoning scientific interest. Cancer cells exert pronounced avidity for lipids, which are derived endogenously from citrate or taken up from exogenous sources. In normal adult mammalian tissues, de novo lipogenesis is rather low with the exception of lipogenic tissues such as liver, adipocytes, and mammary epithelium during lactation. Conversely, tumorigenesis is associated with a remarkable amplification of lipid production . ExcessiContrary to their normal counterparts, whose survival and proliferation are dependent on specific signaling prerequisites based on adhesion and growth factors, cancer cells foster oncogenic alterations to circumvent dependence on these external inputs. Several aberrant oncoproteins and tumor suppressors, such as phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)signaling pathway, hypoxia-inducible factor-1 alpha (HIF-1A), MYC, and p53, have been associated with the regulation of the metabolic adaptation that favors tumorigenesis by facilitating cellular proliferation, access to vasculature, and stress resistance . The modProstate cancer (PCa) is the second-most prevalent malignant disease among men worldwide . The incPCa treatment requires an individual approach to each patient, and the decision is made depending on the stage of the disease while respecting the wishes and preferences of the patient. Active surveillance, surgery, and radiotherapy are reserved for localized PCa, with hormone therapy, chemotherapy, and target therapy being used in locally-advanced, advanced, or metastatic PCa.18F-fluorodeoxyglucose (FDG) cannot provide accurate differentiation between healthy and cancerous prostates [Benign prostatic tissue exerts a specific metabolic profile in baseline circumstances. Conventionally, mammalian cells energetically depend on aerobic respiration and, therefore, rely on citrate oxidation as a crucial step in the TCA cycle. Nevertheless, one of the major biochemical functional features of the glandular epithelium in the peripheral zone of the prostate is its exceptionally high citrate production and its subsequent secretion into the prostatic fluid. The unique metabolic programming of benign prostate cells to produce rather than oxidize citrate is biologically determined by another extraordinary feature: their capability to accumulate large intracellular concentrations of zinc. Increased zinc levels exhibit an inhibitory effect on the activity of m-aconitase, the mitochondrial enzyme catalyzing the stereospecific citrate conversion to isocitrate within the Krebs cycle. In other cell types, such inhibition is lethal, but in healthy prostate tissue, it enables secretion of citrate into the semen, where it serves as the buffering agent and energy source for spermatozoa as well as afree radical scavenger and chelating agent for zinc and calcium ions ,37. By crostates .In order to support proliferation concomitantly with the shift toward citrate-oxidizing metabolism, malignant prostate cells display the lipogenic phenotype. As opposed to most normal somatic cells, which predominantly utilize the lipids from exogenous sources, de novo fatty acid biosynthesis is reported to be exacerbated in various cancer cells irrespective of the abundance of the extracellular lipid content and circulating fatty acids . The sigThere is a complex interplay between the androgens and the modulation of the lipogenic program. In neoplastic prostate cells, androgen-regulated gene expression operates via common transcription factors of several genes significant for fatty acid synthesis and the cholesterol biosynthetic pathway. SREBPs have the central role in the synchronized cascade mechanism of highly coordinated androgen-mediated control of lipid metabolism in this oncopathology. It has been demonstrated that SREBP cleavage-activating protein (SCAP), compulsory for the nuclear translocation and activation of SREBP, FASN, and several lipid-modifying enzymes, including those implicated in the mevalonate-pathway, are upregulated in an androgen-dependent manner . FurtherSignaling pathways that elicit cancer lipogenesis culminate with the formation and accumulation of LDs. Accurate, controlled, and precise synchronization between factors of lipogenesis and lipolysis defines the net amount of lipids stored intracellularly. De novo synthetized or acquired lipids in the malignant tissue are commonly incorporated in triacylglycerols and cholesterol esters, and are then deposited within LDs. Anelevated abundance of LDs is the representative characteristic of various aggressive cancers, including PCa. The final step in the biosynthesis of triacylglycerols is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes; the overexpression of DGAT1 was found in PCa neoplastic cells compared to normal epithelium . FurtherAlthough the endogenous de novo lipogenesis is considered to be the dominant source of fatty acids in neoplastic cells, it has been acknowledged that, under metabolic stress, cancers may adopt additional means to obtain lipids, including scavenging from the extracellular milieu. Such aberrant metabolic routs, coupled with the proficient de novoformation machinery, fuel the pervasive upregulation of lipid abundance and accommodate the increased demand of the progressing neoplasia . FurtherIn addition to lipogenesis, reprogramming of the fatty acid composition patterns was acknowledged in the cellular pool and membrane phospholipid profile. Fatty acid desaturation, catalyzed by the family of stearoyl-CoA desaturases (SCDs), and elongation, depending on the activity of elongases, may have a significant role in PCa progression. SCD1 overexpression was demonstrated on both mRNA and protein levels in specific PCa cell lines and human tissue specimens, where it correlated with a higher Gleason grade and worse clinicopathological features . FurtherDeregulation of cholesterol metabolism is another hallmark of the PCa pathogenesis. Featuring an amphiphilic and virtually planar structure, cholesterol molecules represent major constituents of the cellular membrane, supporting its integrity and regulating itsfluidity and permeability. In the TME, both intrinsic and extrinsic cues trigger cholesterol metabolism alternation, thus supporting carcinogenesis and suppressing the antitumoral activity of the immunological landscape . PCa celThe lipidomics approach, involving comprehensive identification, structural characterization, and quantitation of the complex networks and pathways of cellular lipids and their interactions with other moieties in vivo, represents a platform of exceptional potential in PCa research. As a metabolome subset, ubiquitously present lipid species display multifaceted and diverse roles in both the etiology and sequelae of various pathologies. Exploration of lipid alterations in translational contexts and clinical settings serves not only to advance the fundamental comprehension of the biological processes underlying disease onset and trajectory, but also to assist in developing personalized risk-assessment models that may guide curative interventions . ProvidiIn summary, comprehensive elucidation of the lipid metabolism alteration in the PCa, the underlying regulatory mechanisms, and their implications in tumorigenesis and the progression of the disease are gaining growing research interest in contemporary urologic oncology. A better understanding of the unique metabolic signature of PCa, featuring major aberrant pathways including de novo lipogenesis, lipid uptake, storage and compositional reprogramming, may provide novel, exciting, and promising avenues for improving diagnosis, risk stratification, and clinical management of such a complex and heterogeneous pathology."} +{"text": "Additive Manufacturing of Polymer\u2013Fiber Composites is a newly open Special Issue of Materials, which aims to publish original and review papers on new scientific and applied research, and make great contributions to the finding and understanding of the fabrication of fiber-reinforced polymer composites using current advanced additive manufacturing techniques. This Special Issue also covers fundamentals, characterization, and applications of fiber-reinforced polymer composites.The technology of the additive manufacturing (AM) process has significantly piqued the interest of researchers and industrial players from various areas ,2,3,4,5.Studies on fiber-reinforced polymer composites for the additive manufacturing process have been carried out by many researchers and become an interesting topic to be explored in the additive manufacturing industry. The aims of the inclusion of fiber in the polymer-based feed stock materials are to reduce the percentage of polymers and consequently reduce the harmful substances that may emit during the fabrication process in AM. Moreover, fiber-reinforced polymer composites could improve the properties of the dominant materials and exhibit good performance in the final products. Employment of the fibers in the AM process should consider the type of fiber, fiber treatment, fiber size, fiber loading, and fiber characteristics. It is important to understand the composition of fibers to ensure their compatibility with the polymer, and how they could produce good resultant composites for AM.The AM process starts from the preparation of the feed stock until the disposal of the fabricated parts . The impIn this Special Issue, we aim to capture the cutting edge of the state-of-the-art research pertaining to advancing additive manufacturing of fiber-reinforced polymeric materials. The topic themes include advanced fiber-reinforced polymeric material development, processing parameter optimization, characterization techniques, structure\u2013property relationships, process modelling, etc., specifically for AM."} +{"text": "In contemporary Poland, Universities of the Third Age are the most visible institutional forms of active aging. These lifelong-learning institutions that are specifically for retirees often cultivate ideals of independence through workshops and classes that teach new, and potentially transformative, skills and hobbies . Universities of the Third Age in Poland emerged out of the fields of andragogy, pedagogy, and social work, fields that have regional intellectual roots in the late 19th/early 20th-century presocialist era, and are based on radically different ideals of personhood, relationality, and care than those of the contemporary postsocialist neoliberal era . This paper analyzes 1) historical data from institutional archives of two Universities of the Third Age in Poland, and 2) secondary sources on histories of andragogy, pedagogy, and social work, to create a locally grounded intellectual history of active aging in central and eastern Europe. The Polish case offers an opportunity to think across divergent political-economic eras, in which assumptions about the value of a person to society have shifted. By tracing how the fields of andragogy, pedagogy, and social work have shaped active aging in Poland, this paper finds that 1) dichotomies of East/West, socialist/capitalist, and individual/collective are insufficient to explain the history of contemporary practices of active aging, and 2) intellectual history can reveal complex relations between political-economic change, and ideals and practices of aging. These findings have implications for advancing gerontological theories of 1) active aging in cross-cultural contexts, and 2) how active aging relates to sociopolitical change."} +{"text": "Defined as, \u201cstereotype, prejudice, and discrimination directly towards people because of their age\u201d, ageism may contribute to adverse health outcomes, accelerate aging process, and increase the burden on health and social services. Little is known about the ageism impact on biological aging. Secondary analysis of the American Health and Retirement Study (2012 and 2016 waves) was carried out. Participants were asked: the self-perception of aging (SPA), the causes of receiving discrimination, including ageism as one of the causes, and the frequency of receiving such discrimination. The aging rate was measured using two distinct measurements: homeostatic dysregulation and epigenetic aging clocks . The influence of perceived ageism (current or previous waves) on the aging rate was modelled with linear models using biological aging (aka. homeostatic dysregulation and epigenetic age) as the dependent variable (outcome), ageism as the exposure, with considering confounders: sex, depressive symptom. The results show that more negative SPA, either from the previous (2012) or the same wave (2016), is associated with elevated homeostatic dysregulation and increasing epigenetic age . The association between the ageism receiving frequency and biological aging is similar but less significant. The results demonstrate that ageism is associated with accelerated biological aging. More interventions are called to combat ageism and foster the health and wellbeing of the older adults."} +{"text": "The coronavirus disease of 2019 (COVID-19) pandemic has led to increases in intimate partner violence (IPV), a leading cause of women's homelessness. Although the Canadian Government provided emergency funding to the violence against women and housing and homelessness sectors in response to COVID-19, Canada lacks a national legislative and funding framework to support coordinated prevention efforts. We review the context of IPV and homelessness among women and international policy exemplars. We then propose several starting points for developing a Canadian strategic framework, including adopting inclusive definitions of IPV and homelessness as well as evaluating a broad continuum of IPV-housing options and intersectoral partnership models. The intersections of intimate partner violence (IPV), homelessness, and the coronavirus disease of 2019 (COVID-19) pandemic necessitate a coordinated public health response strategy. As in prior infectious outbreaks, the COVID-19 pandemic has been associated with higher risks of violence against women, including IPV . In addiIn this activist/advocate note, we outline the context of gender-based violence and homelessness in Canada prior to COVID-19 and how the pandemic has exacerbated structural vulnerabilities for women. We propose that Canada needs a national legislative and funding framework that supports intersectoral coordination to maximize prevention efforts for women's homelessness and IPV during and beyond the pandemic. We discuss several starting points for building this framework based on successful local examples and international approaches, including adopting inclusive definitions of IPV and homelessness and evaluating a broad continuum of structural solutions. The COVID-19 pandemic has highlighted the gaps in public health policy for marginalized communities and presents a critical opportunity to restructure for a more equitable future of public health. Doing so requires countries to not only reflect inwards, but to consider successful policy and practice internationally, including areas of implementation that can be further improved.Although people of all genders experience IPV, women and gender-diverse populations tend to experience more severe IPV and more physical, psychological, and socioeconomic impacts . IPV is Most specialized housing supports available to women experiencing IPV in Canada are mandated for short-term stays . Few optEmerging evidence from the COVID-19 pandemic indicates that IPV has increased over the last year due to stressors like income loss or precarious employment, service disruptions, and lockdown measures . In CanaChanges in the risk and severity of IPV are exacerbated by a collision of structural vulnerabilities disproportionately impacting women during this pandemic, as in prior public health emergencies . These gDespite the gender-based and intersectional impacts of the COVID-19 pandemic, Canada paused development of its National Action Plans on gender-based violence and Missing and Murdered Indigenous Women and Girls as well as the National Indigenous Housing Strategy during the first 6 months of the pandemic. The Federal Government committed financial support in response to women's experiences of homelessness and violence in May 2020: $76 million for violence against women shelters (including off-reserve Indigenous shelters), sexual assault centers, and nonprofit gender-based violence organizations; and $10 million for shelters supporting Indigenous women and children fleeing violence on reserves . The houAs the Canadian Government recommits to developing its National Action Plan on gender-based violence , as well as New Zealand, which likewise implemented national legislation and is in the process of designing its National Action Plan to prevent family and sexual violence . As a reDespite a lack of large-scale investment in coordinated responses to IPV-related homelessness in Canada, locally practitioners have successfully committed to delivering longer-term options. For instance, a small-scale evaluation of Housing First adapted for women's homelessness needs in the province of Ontario found that six of 10 participants who had experienced complex histories of homelessness, violence, and trauma were housed at the end of the 2-year funding period, although the evaluators highlighted the need for a stronger integration with community services . EvaluatTo advance a coordinated intersectoral approach to preventing gender-based homelessness and violence in Canada, inclusive and standardized definitions of IPV and homelessness should be applied across (and within) jurisdictions, including in national funding streams. Legal definitions of IPV currently vary across Canada, often barring survivors from critical supportive services if they have not experienced specific definitions of physical or sexual violence . RegardiMoving forward, policies and programs related to homelessness should explicitly adopt an intersectional gender-based definition of homelessness that understands women's unique experiences, based on multiple and intersecting social locations: gender, sexual identity, race/ethnicity, Indigeneity, class, disability, and age . This muCanada's national strategies on housing and gender-based violence should be coordinated to provide the necessary legislative and funding infrastructure for key sectors to collaborate in developing, implementing, and innovating across the full continuum of intersectoral interventions. For instance, Canada's National Action Plan on gender-based violence should be developed with linkage points to the National Housing Strategy, including investment in long-term supportive housing solutions that account for the unique needs of IPV survivors . This muStrengthening intersectoral action to prevent gender-based homelessness and violence against women in Canada must address the disproportionate burdens faced by Indigenous women and girls due to historic and ongoing structural harms at the intersections of colonization, misogyny, and racism . This inThe COVID-19 crisis has demonstrated the consequences of siloed and chronically underfunded social care systems worldwide. Now more than ever, policymakers must mobilize the coordination of Canada's national infrastructure to address the structural causes and outcomes of gender-based violence and homelessness. This is a critical time to draw lessons from local and international examples of coordinated intersectoral action to strengthen Canada's systems-level response to gender-based violence and homelessness\u2014especially as the national government restarts the development of its National Action Plan for gender-based violence. Intersectoral action is essential for addressing the structural determinants of gender-based health inequities and strengthening the response to IPV during and beyond the COVID-19 pandemic."} +{"text": "Dear Editor,Betacoronavirus genus), responsible for the COVID-19 pandemic, can potentially cause severe acute respiratory syndrome (SARS), affect other organs, and trigger autoimmune events as a result of the cytokine storm.Infection caused by Coronavirus 2 , followed by UVB (narrow band). Two weeks after household contact with COVID-19, she developed a maculopapular rash . After 1The role of environmental factors and infectious agents as triggers or promoters of the development of CTCL is not yet fully established. Moreover, autoimmune disorders can generate a favorable environment for the risk of CTCL. Theories about the pathogenesis of MF and SS include increased Th2 activity, and reduced Th1 activity, the antitumor cytotoxic response of CD8 lymphocytes, the dendritic cell population, and the production of interleukin-12 and interferon-alpha.4The immunological dysregulation present in COVID-19 favors the reduction of the functional activity of regulatory T lymphocytes and an imbalance in the production of cytokines, in addition to the elevation of C-reactive protein and D-dimer serum levels.Although most patients with indolent or controlled CTCLs are not predisposed to viral infections, conditions at risk for infection and severe symptoms of COVID-19 are considered: aggressive or advanced CTCLs, ongoing immunosuppressive therapy, lymphopenia, chronic organ failure, coexisting comorbidities, advanced age.This unprecedented report of previously controlled MF, with exuberant and sudden cutaneous recurrence after SARS-CoV-2 infection, indicates viral immunogenic mechanisms as potential triggers of immune dysregulation in CTCLs.None declared.\u00c9derson Valei Lopes de Oliveira: design and planning of the case study; data collection, or analysis and interpretation of data; writing of the article or critical review of the intellectual content; collection, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case; critical review of the literature; approval of the final version of the manuscript.Ligia Magnani Landell: collection, analysis and interpretation of data; intellectual participation in the propaedeutic conduct of the studied case; approval of the final version of the manuscript.Cacilda da Silva Souza: design and planning of the study; analysis and interpretation of data; writing of the article or critical review of the intellectual content; collection, analysis and interpretation of data; critical review of the literature; approval of the final version of the manuscript.None declared."} +{"text": "The COVID-19 pandemic has had unprecedented and potentially irreversible impacts on health and health care globally. Many complex issues and factors therefore need to be accounted for as we look at the long-term impact of COVID-19 on humanity and society and how this ongoing crisis continues to affect health and health care outcomes for different populations. There are significant health disparities and sex inequalities associated with the COVID-19 pandemic. Sex-responsive interventions are imperative to address widening sex gaps resulting from the pandemic. Although many researchers have studied the impact of the COVID-19 pandemic on health disparities, there is a lack of research on the sole and joint association of the pandemic or sex differences and their specific impact on health and health care. The study examined the association of the COVID-19 pandemic, the association of sex, and the joint association of sex and the COVID-19 pandemic with health communication, physical activity, mental health, and behavioral health. We also highlighted the application of Bonferroni corrections when conducting multiple hypotheses testing simultaneously.To examine the association of the COVID-19 pandemic, the association of sex, and the joint association of sex and the COVID-19 pandemic with health communication, physical activity, mental health, and behavioral health.We drew data from the National Cancer Institute's 2020 Health Information National Trends Survey (HINTS). We described and compared the characteristics of social determinants of health, physical activity, mental health, alcohol use, patterns of social networking service use, and health information data sharing. Analyses were weighted to provide nationally representative estimates. Multivariate models were used to assess the sole and joint association with sex and pandemic. In addition, we applied the Bonferroni correction to adjust p-values to decrease the risks of type I errors when making multiple statistical tests.Females were more likely to use mobile health and health communication technologies than males, and the difference increased after the pandemic. The association between sex and mental health was significant after the COVID-19 pandemic. Females were more likely to experience depression or anxiety disorders. Both males and females had a slight decrease in terms of the quantity and intensity of physical activity and females were less likely to perform moderate exercise and strength training regularly. Males were likely to drink more alcohol than females.The COVID-19 pandemic amplifies the differences between males and females in health communication, physical activity, mental health, and behavioral health. Intersectional analyses of sex are integral to addressing issues that arise and mitigating the exacerbation of inequities. Responses to the pandemic should consider diverse perspectives, including sex."} +{"text": "Drowning and near-drowning are the consequences of recreational activities and natural disasters. The purpose of this study was to review the microbiology literature on drowning and near-drowning and to understand its applications in the diagnosis and treatment of these injuries and diseases.This study is the result of a short review on publications extracted by searching in scientific databases including Google Scholar, PubMed and Semantic Scholar in the period from 1961 to 2021, using the keywords \"Microbiology\" and \"Drowning\" or \"Near-Drowning\".A search in scientific databases revealed 184 articles related to \"drowning\" and \"microbiology\" and 84 articles related to \"near-drowning\" and \"microbiology\", of which 65 and 28 articles have been published in the last twenty years, respectively. Of these, 43 articles were used for this study. Regarding the microbiology of drowning and near-drowning, no study was conducted in the Islamic Republic of Iran in this field. The findings of the present study showed that:\u2022 Near-drowning in its victims causes physical and mental injuries, and invasive polymicrobial and fungal pneumonia, brain abscesses, and sepsis.\u2022 They are mainly associated with numerous bacterial agents e.g. Aeromonas spp., Nocardia spp., Vibrio spp., Photobacterium spp., Burkholderiapseudomallei, Pseudomonas spp., Plesiomonas shigelloides, and Shewanella spp. and Fungal and Protozoan pathogens are limited to Aspergillus spp., Scedosporium apiospermum, and Rhizopus spp., and Cryptosporidium parvum (rare), respectively.\u2022 If bacterial, fungal, and protozoa infections are not properly diagnosed and treated in drowning victims, they can lead to death in intensive care units and even long after discharge from the hospital.\u2022 Deaths from drowning and near-drowning are candidates for organ transplants, especially lung, bone, liver, and heart.\u2022 Clinical, environmental, forensic, and eco-microbio-epidemilogy studies in pre-and post-mortem drowning victims are being developed using cultured-based and molecular methods such as PCR, LAMP, NGS, and Metagenomics, etc. to determine the drowning microbiome pattern.Several cases of infections and diseases caused by drowning and near-drowning have been reported among the victims of recreational activities and natural disasters in different countries. Therefore, eco-microbio-epidemiological study of drownings in our country, where there is an average of 1,200 annual drownings on the north and south coasts and inland waters is essential. Even predicting tsunami and destructive storms on the shores of the Caspian Sea and the Oman Sea are very important in determining the microbiome pattern of natural aquatic areas and the role of microbes in diseases and complications caused by drowning. Finally, a national protocol should be developed for microbial monitoring of drowning victims from the scene of water accidents to the hospital bed and on the autopsy table.Microbiology, Microbiome, Drowning, Near-Drowning, Natural Disasters"} +{"text": "Gliomas are invasive brain tumors characterized by high rates of recurrence and mortality. Glioblastoma (GBM), a grade IV brain tumor, is known for its heterogenicity and its resistance to the current treatment regimen. MicroRNA (miRNAs) are small non-coding sequences of RNA that regulate and influence the expression of multiple genes. The detection of certain types of micro-RNA in tissues and blood serum can be used for diagnosis and prognosis, including the response of a particular patient to therapy. The purpose of this review is to analyze studies and experimental results concerning changes in microRNA expression profiles characteristic of gliomas. Furthermore, miRNAs also contribute to autophagy at multiple stages. In this review, we summarize the functions of miRNAs in GBM pathways linked to dysregulation of cell cycle control, apoptosis and resistance to treatment, and the possible use of miRNAs in clinical settings as treatment and prediction biomarkers. The posThis review considers the possibility of using miRNAs as prognostic markers and therapeutic targets in gliomas.2Many recently published works have confirmed the association of microRNA with chemotherapy and radiation resistance of patients' tumors 13].Fig.Fig13].FCSF allows to differentiate glioblastomas and brain metastases with high accuracy (91\u201399%) on the test dataset. Nevertheless, the authors note that the search for additional microRNA biomarkers and subsequent analysis of large cohorts of patients will help to increase the accuracy of the approach [Radiation resistance, often caused by the spread of CSCs in gliomas, remains one of the main difficulties in the treatment of glioblastoma. In the context of radiation resistance of gliomas, miR-21 is one of the most actively discussed microRNAs. Blocking this microRNA with anti-miR-21 promotes the formation of phosphorylated histone g-H2AX (an indicator of double-stranded DNA breaks) and suppression of phospho-Akt expression, activation of autophagy and apoptosis (including by inhibition of Cdc25A expression) after irradiation in cell lines gliomas ,14. MiR-3The principle of therapeutic targeting of micro-RNAs is based, on the one hand, on increasing their expression due to the introduction of synthetic micro-RNAs (micro-RNA mimetics) to inhibit oncogenes; on the other hand, on the inactivation of endogenous micro-RNAs using inhibitors (antagomiRs or anti-micro-RNA) in order to increase the expression of tumor suppressors . Effecti4Expression profiles of certain types of microRNA in gliomas repeat the changes characteristic of other types of malignant neoplasms. Similarly, to genes proper, subdivided according to their effect on tumor pathogenesis on tumor suppressors and oncogenes, by now it is already possible to distinguish classes of microRNAs that also play opposite roles in the pathogenesis and progression of gliomas - oncogenes and tumor suppressors . Studies of microRNA expression profiles have expanded our understanding of the mechanisms of progression of gliomas/glioblastomas, providing valuable information on the pathogenesis of these tumors and potential therapeutic targets . DetectiNone.Albert Sufianov and Sema Begliarzade conceptualized and designed the study. All authors participated in the acquisition, analysis and interpretation of the data. Tatiana Ilyasova and Yanchao Liang drafted the manuscript. Ozal Beylerli contributed to critical revisions of the manuscript. All authors agreed on the journal to which the article would be submitted, gave final approval for the version to be published, and agreed to be accountable for all aspects of the work.The authors declare that no conflicts of interest exist."} +{"text": "Hysterical disorders were considered separately in the context of the dynamics of the course of either endogenous affective diseases or schizophrenia, without attention to the conjugation and interaction of issues of hysterical symptoms and affective or psychotic syndromes.To test the psychopathological structure and provide a typology of the conjugation of hysterical symptoms with other psychopathological syndromes.120 patients (82 women and 38 men) with schizophrenic and affective disorders with associated hysterical symptoms were examined by a clinical psychopathological method.Three variants of conjugation were identified. In the group of hysterical disorders associated with affective diseases the structure and dynamics of hysterical symptoms directly influenced the developing affective phase: the low intensity of hysterical symptoms contributed to the development of an apatho-adynamic type of depression, and bright and spontaneous hysterical manifestations formed an anxious-hypochondriac type of depression. Hysterical disorders formed in the structure of the psychotic state influenced the nature, structure, dynamics and content of delusional, hallucinatory and paranoid disorders. \u201cCaste\u201d hysterical symptoms revealed a lack of connection with affective and psychotic states. Hysterical symptoms were characterized by persistence, stability, invariability of manifestations, long-term psychotherapeutic and psychopharmacological resistance.Clinical and psychopathological analysis of endogenous mental diseases of the affective and schizophrenic spectrum, occurring with hysterical symptoms, showed that the parameter of the conjugation of hysterical symptoms with other psychopathological syndromes is prognostically significant.No significant relationships."} +{"text": "The International Classification of Functioning, Disability and Health (ICF) provides a framework rooted in patient-centered care and the biopsychosocial model that facilitates a comprehensive description of a person\u2019s health and their level of societal participation. The importance of the ICF for assessing the needs of individuals with mental health problems (MHP) and intellectual disabilities (ID) is growing, especially in the social medicine.To describe the benefits and limitations of the ICF in clinical practice, pertaining to the assessment of healthcare needs and societal participation in persons with MHP and ID.Comprehensive literature search in medical databases using the Keywords: ICF, mental health, intellectual disabilities, social and occupational participation.ICF-based instruments such as the Mini-ICF-APP, with which impairments and competencies in social and occupational participation can be described, are playing an increasingly important role in healthcare and rehabilitation. In Germany, for example, in accordance with the Federal Participation Act, the entitlement to disability support benefits is assessed using ICF-based instruments, which therefore play a decisive role in social medical care.The functional descriptions of the ICF provide the opportunity for a standardized, yet individualized assessment of medical needs, general health and societal participation, thus facilitating the provision of a comprehensive package of care and support for people with disabilities. ICF-Core Sets and the Mini-ICF-APP are effective tools to describe level of function. It would be clinically valuable to further develop these instruments for use in persons with ID and MHP in the field of social medicine.No significant relationships."} +{"text": "There are about 1.5 million internally displaced persons (IDPs) in Ukraine, which requires an assessment of their mental health.To develop a psychoeducational program aimed at informing about the clinical manifestations (markers of symptoms) of mental disorders, the possibilities of preventing their formation and options for action in conditions of the formation or exacerbation of a mental state.270 IDPs were examined. Methods: clinical-psychopathological, psychometric, statistical.Evaluation of the mental state of IDPs with symptoms of mental disorders (risk group (31.92%)) indicates the presence of various emotional disorders that formed individual syndromes \u2013 asthenic (41.18%), agrypnic (45.59%), somato-vegetative (30.88%), anxiety-depressive . The risk factors for the development of mental disorders in IDPs were identified - the older age is from 50 to 59 and the average age is from 40 to 49 years; lack of a complete family, lack of work, low level of social employment, lack of satisfactory living conditions, a significant decrease in the level of well-being, the preservation of the significance of factors of mental trauma, the presence of certain prenosological syndromes. The proposed psychoeducational program is built on the principle of thematic seminars with elements of social and psychological training.The implementation of the program provides a comprehensive impact on the cognitive, emotional, psychophysiological, behavioral and social aspects of personality functioning."} +{"text": "The inter-organelle interactions, including the cytomembrane, endoplasmic reticulum, mitochondrion, lysosome, dictyosome, and nucleus, play the important roles in maintaining the normal function and homeostasis of cells. Organelle dysfunction can lead to a range of diseases , Parkinson\u2019s disease (PD), and cancer), and provide a new perspective for drug discovery. With the development of imaging techniques and functional fluorescent probes, a variety of algorithms and strategies have been developed for the ever-improving estimation of subcellular structures, organelle interaction, and organelle-related drug discovery with accounting for the dynamic structures of organelles, such as the nanoscopy technology and molecular dynamics (MD) simulations. Accordingly, this work summarizes a series of state-of-the-art examples of the recent progress in this rapidly changing field and uncovering the drug screening based on the structures and interactions of organelles. Finally, we propose the future outlook for exciting applications of organelle-related drug discovery, with the cooperation of nanoscopy and MD simulations. Cellular organelles with specific morphology and functions are highly dynamic in maintaining the normal operation of eukaryotic cell life activities , and theOrganelle bioimaging can aid our understanding of the organelle functions and the development of organelle-targeting therapy for various diseases. Conventional fluorescence microscopy (FM) opens the door to fine structural details of cellular architectures and dynamics, while the resolution is limited to approximately 200\u00a0nm because of the light diffraction . As the With the status of interactions between organelles in the improvements of pathogenesis and therapeutics, related articles are emerging as an endless stream. Recent advances in organelle-targeted fluorescent probes (FPs) provide us with a more suitable selection and high resolution scale under SRM . MeanwhiPrecise imaging of intracellular and subcellular structures and their dynamic processes are crucial to fundamental research in biology and medicine . Super-rWith the technical advancements in SRM, in practice, however, many factors can influence the achievable resolution, including the excitation and detection schemes, the properties of fluorescent probes (FPs), as well as the labeling and sampling density of FPs. SRM technologies have also enhanced the requirements of FPs, which need especially low cytotoxicity, high photostability, photobleaching resistance , and spevia STED method.The search for new therapies is a tedious process with long cycles and high risks . In the A receptor) Figure can obseeceptor) . The esteceptor) ] and deteceptor) ]. The tweceptor) (Nakane eceptor) and 2) ceceptor) (Ng and eceptor) . In cryoeceptor) . The cryeceptor) is a receceptor) . HoweverVia IPET and FETR, the adverse effect caused by the inclination error can be effectively limited, and the macromolecular center can be found more accurately, thus greatly improving the resolution of reconstruction results is the most common malignant primary brain tumor in adults. However, existing treatments, such as surgery and chemotherapy, have little effect on glioblastoma stem cells (GSCs) . After hAlthough the dynamic process of organelle interactions can be obtained by nanoscopy, it is still necessary to analyze the evolution behavior at the all-atom level. Molecular dynamics (MD) simulations could obtain structural and dynamical insight into organelle interactions at the all-atom level . MD simuin vitro. The rebalancing MD simulation force fields, based on experimental data on LLPS and without limiting specific coarse-particle sizes, not only perfect the interaction between proteins, but also correct the potential energy surface, improving the reliability of modeling interactions between membraneless organelles techniques enable the observation of fluorescence images of subcellular organelles beyond the diffraction limit and arouse the discovery of mitochondrial lysosome contact (MLC), providing a new perspective on the drug screening and the treatment of diseases . HoweverThe ideal of organelle interaction research is to capture a series of atomic resolution images in active state in chronological order, construct the dynamic structures during the interaction processes, and deeply understand the details of conformational transitions and \u201cenergy motion\u201d transformation mechanism. Due to the limitation of current nanoscopy techniques, SRM and cryo-EM analyses cannot reach the atomic resolution or look at how a particular change over time trends. The two deficiencies could be partially compensated by molecular dynamics (MD) simulation. Although the computational power of MD simulation is far from being able to replace the experiments, through careful design, especially constrained by the key dynamic spatial and temporal data provided by nanoscopy (SRM and cryo-EM), it can provide sufficient information for the construction of the initial model. Combined with Coarse-Grained MD and all-atom MD simulations, it is expected to not only connect the dynamic evolution process of organelle interaction on a large scale (the application of CG models sacrifices degrees of freedom), but also analyze the evolution behavior of key dynamic nodes at the all-atom level , then summarize the physical characteristics and laws of the structure-activity changes of the system, and establish the correlation between the dynamic structure and function of organelles .With the continued advances in SRM, cryo-EM, and MD simulation, the combination of the three techniques and the cooperation of super-resolution time series and cryo-EM structure information will be an effective solution for the in-depth investigation of large-scale dynamic structural evolution and will provide new insight for the organelle interaction and drug discovery. It is promising to see the breakthroughs with this approach in the field of organelle-related drug discovery."} +{"text": "Dementia is a neurodegenerative condition characterized by cognitive decline and increased functional dependency. With most persons living with dementia (PLWDs) residing at home, home-based interventions provide a convenient and individualized alternative for person-centered care. Most of the evidence focused on specific interventions or exercise-based activities; there remains a gap in understanding the impacts of a broader range of non-exercise interventions on PLWDs and their caregivers. This review aimed to understand the impacts of home-based, non-exercise interventions on the behavioral, functional, cognitive, and mood outcomes of PLWDs, and their caregiver's quality of life (QoL), burden and mood.Search for studies published up to June 2020 was conducted on CINAHL, PsycArticles, PubMed, SAGE Journals, Science Direct, and Web of Science. A search was also done manually based on the bibliographies of selected articles. The inclusion criteria for the systematic review were: (i) participants with a medical diagnosis of dementia, (ii) participants who resided at own home, (iii) intervention in the home setting, (iv) investigate interventions other than physical exercise, (v) randomized controlled trials (RCTs) or quasi-experimental studies, and (vi) full-text study published in English and in a peer-reviewed journal.Eighteen studies consisting of 14 RCTs and 4 quasi-experimental studies were included. Interventions included were occupational therapy, cognitive rehabilitation, tailored activity program, cognitive stimulation therapy, personalized reminiscence, music therapy, reality orientation, biobehavioral and multicomponent interventions. Results were mixed, but important intervention features were highlighted. Personalized activities for PLWDs that are aligned to their interest and ability appeared to contribute to intervention effectiveness especially in reducing behavioral symptoms and improving functional status. Involvement of caregivers in interventions is another feature of effective interventions for both the PLWDs and the caregivers' QoL, provided it is not deemed demanding or challenging to the caregivers. The inclusion of caregiver's education was effective in reducing caregivers' burden, particularly when the interventions improved the PLWD's functional status. Dementia is a neurodegenerative condition marked by cognitive decline that interferes with activities of daily living leads to a decreased functional ability to live independently overtime is PLWDs and their caregivers. The target intervention type is home-based, non-exercise interventions for dementia. N comparator factor (C) is being considered. The outcome variables (O) are PLWDs' behavioral symptoms, functional status, cognition and mood, as well as the impact on their caregivers in terms of caregivers' quality of life, their burden and mood. The study designs (S) included are randomized controlled trials and quasi-experiments.The reporting follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMA) guideline for systematic reviews and meta-analyses were used to identify potential articles within the databases. In addition, the reference lists of all relevant full-texts and review articles were hand-searched for eligible articles.Studies were identified and retrieved from the beginning of time up to 30 June 2021 from the following electronic databases: CINAHL, PsycArticles, PubMed, SAGE Journals, Science Direct and Web of Science. A combination of Search terms with truncation and Boolean operators . Next, the full-text articles were screened for final inclusion in the systematic review by the same three reviewers. If no consensus was reached among the three reviewers, the plan was to discuss the case with the fourth author (DGH) until a final consensus was reached; but this option was not required.The inclusion criteria for the systematic review were: (i) participants with a medical diagnosis of dementia, (ii) participants who resided at home in the community, (iii) use of individualized intervention in the home setting for participants, (iv) investigate interventions with treatment components other than physical exercise, (v) randomized controlled trials (RCTs) or quasi-experimental studies, and (vi) full-text study published in English and in a peer-reviewed journal.Studies were excluded if (i) the intervention was conducted in group setting, (ii) the intervention was conducted in institutionalized settings, and (iii) the study focused solely on exercise-related intervention.The quality of each included study was examined independently by two reviewers among BMB, CS, and MML using the Joanna Briggs Institute (JBI) Critical Appraisal Tool Checklist for randomized controlled trials . The characteristics extracted were experimental design, participants' demographics, intervention protocol and components, outcome measures, and findings. After independent data extraction, the accuracy of the data was verified by one other reviewer. The data was analyzed and synthesized on the qualitative directionality of the effects reported in the included studies. The effects on the PLWDs were grouped into: (i) behavioral disturbance, (ii) cognition, (iii) mood, (iv) functional status. The effect on the caregivers of PLWDs in terms of (i) quality of life, (ii) mood, and (iii) burden were also analyzed.A total of 3,882 studies were identified through the screening of the different databases, with 2,444 studies remaining after duplicates were removed. After the advanced search filter (abstract and/or title) was used, 148 studies were screened, with 97 full-text studies obtained and assessed for eligibility. Eighty-five studies were excluded, with reasons such as the type of study design, ongoing studies, settings of the studies and interventions that were unrelated to the research topic. This resulted in a total of 18 studies being included. The PRISMA flow diagram for the current review is illustrated in Fourteen studies were RCTs and four studies were quasi-experimental studies. Among the 18 studies included n = 3), tailored activity programme or TAP (n = 3), cognitive stimulation, (n = 2), occupational therapy (n = 2), reminiscence (n = 1), music therapy (n = 1), reality orientation (n = 1), biobehavioral intervention (n = 1), and multi-component intervention (n = 4).The studies covered interventions that include cognitive rehabilitation , music therapy, ICST, reality orientation, cognitive rehabilitation and multicomponent interventions. Outcome measures consisted of Neuropsychiatric Inventory, Revised Memory and Behavior Problem Checklist, and Agitated Behavior in Dementia Scale.Studies using TAP reported significant reduction of behavioral disturbance when compared to the control groups , Caregiver Assessment of Function and Upset Scale (CAFU), Bristol Activities of Daily Living Scale (BADLS), Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL), Functional Independence Measure (FIM), Direct Measure of Training (DMT), Disability Assessment for Dementia (DAD), Independent Living Scale (ILS), Instrumental Activity of Daily Living Scale (IADLS), Barthel Index (BI), Assessment of Motor and Process Skills (AMPS), Interview of Deterioration of Daily Activities in Dementia (IDDD) and a 3-point scale on competence, questionable and ineffective steps and deficits.The interventions included in these studies were TAP , cognitive rehabilitation, reality orientation, memory rehabilitation with caregiver psychoeducation, and a multicomponent intervention. Outcome measures used across studies were the Rivermead Behavioral Memory Test, Alzheimer's Disease Assessment Scale\u2014Cognition, MMSE, Weschler Memory Scale-Revised, Behavioral Assessment of the Dysexecutive Syndrome, Dementia Rating Scale-2, Test of Everyday Attention, 8-Words Test and Memory Awareness Rating Scale.Significant benefit to cognition were reported in two studies albeit the direction of change was counterintuitive.With a growing need to provide interventions for home-dwelling PLWDs, this review is the first of its kind to investigate the impact of home-based, non-exercise interventions on the behavioral disturbance, functional status, cognition and mood of PLWDs as well as caregivers' QoL, burden and mood.Tailored activities for PLWDs that are aligned to their interests and abilities appeared to contribute to intervention effectiveness especially in reducing behavioral disturbance and improving functional status. Involvement of caregivers in interventions is another feature of effective interventions for both the PLWDs and the caregivers' QoL and burden, particularly when the interventions are improving the PLWDs' functional status and provided the involvement is not deemed demanding or challenging to the caregivers. Longer duration of intervention and measurement are also critical in observing effectiveness.A reduced number and frequency of behavioral symptoms were reported in studies where the interventions were tailored toward the interests and abilities of the PLWDs benefits cognition by delaying deterioration in cognitive reserves of PLWDs through intellectual and social stimulation (Duan et al., The current review also did not find evidence of home-based cognitive rehabilitation benefitting cognition as a secondary outcome despite improvement in functional abilities (Clare et al., All included studies were based in the Western context, hence the transferability of the findings to Asian contexts may be affected given the presence of different sociocultural factors in dementia care. The inclusion criterion of only using studies published in English could have further limited Asian studies published in different languages from being reviewed.The studies had used varied outcome measures for specific outcomes. For example, caregiver burden was measured using various outcome measures such as the Zarit Burden Scale and the Caregiver Burden Inventory. Hence the lack of standardization might have affected the accuracy of analyzed results.There are mixed findings on the evidence of home-based, non-exercise interventions in alleviating PLWD's behavioral symptoms, functional status and cognitive decline as well as their caregivers' QoL. Evidence for improving the PLWDs' mood and their caregivers' burden and mood is limited.Interventions that were tailored to the interest and abilities of the PLWDs alleviated their behavioral disturbance and functional decline. Longer interventions that incorporated reinforcement of strategies and involvement of caregivers in interventions benefits the PLWDs' cognition.When interventions actively involved caregivers and included caregiver education and concurrently yielded a positive impact on the functional abilities of the PLWDs, benefits to the caregivers' QoL and burden were observed. However, the caregivers' involvement must not be overly intensive or causing inconvenience lest increasing their burden.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.DT, BB, CC, and MT conceptualized the presented work. BB, CC, and MT conducted the systematic search, the title and abstract screening, the full text screening, extracted the data, conducted the reporting quality assessment, and drafted the first version of the manuscript as a report. DT supervised the project during each stage of the work. DT and B-SW drafted the manuscript for submission. All authors revised the manuscript for intellectual content and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Complex neuro-immune-vascular interactions play key roles in the development of both neuroinflammation (an inflammatory response within the nervous system) and neurogenic inflammation (sensory nerve-released neuropeptides inducing inflammation in different tissues). Both phenomena have a substantial importance in the pathogenesis of several diseases and might be targets for pharmacological interventions.Therefore, the present Research Topic was designed to collect papers on the molecular mechanisms and pharmacology of pathological processes affecting neuro-immune-vascular interfaces, focusing on neurodegeneration, stroke, headache, neuropathic and other types of pain, as well as peripheral inflammatory diseases, such as arthritis or dermatitis. In addition, interactions between the peripheral and central nervous systems have also been explored.Neuroinflammation is usually accompanied by vascular reactions, including opening of the blood-brain barrier. In the present Research Topic, Inflammasomes were in the focus of the work of Inflammatory reactions may affect the peripheral nervous system as well. Inflammatory neuropathies are characterized by leukocyte infiltration of peripheral nerves, demyelination and axonal degeneration. Therefore, inflammation and pain control in chronic neuropathies is essential to improve the outcomes of the disease. Somatostatin released from capsaicin-sensitive peptidergic sensory nerve endings leads to anti-inflammatory and anti-hyperalgesic actions at distant parts of the body, through activation of the somatostatin receptor subtype 4 (SST4). Based on this knowledge, A specific subgroup of neuropathies, immune axonal neuropathies are described in the review of Finally, the paper of Altogether, as a result of the common effort of the Frontiers in Pharmacology team and the five guest editors, a balanced collection of original and review papers have been included in the Research Topic. Nine articles originating from six different countries cover a wide thematic range focused around inflammatory processes affecting the central and peripheral nervous systems."} +{"text": "Over the last few decades, various adsorption functions of polymer hydrogels for the removal of hazardous pollutants have been developed. The performance of hydrogel adsorbents depends on the constituents of the gels and the functions produced by the polymer networks of the gels. Research on hydrogels utilizing the characteristic functions of polymer networks has increased over the last decade. The functions of polymer networks are key to the development of advanced adsorbents for the removal of various pollutants. No review has discussed hydrogel adsorbents from the perspective of the roles and functions of polymer networks in hydrogels. This paper briefly reviews the basic requirements of adsorbents and the general characteristics of hydrogels as adsorbents. Thereafter, hydrogels are reviewed on the basis of the roles and functions of the polymer networks in them for the removal of hazardous pollutants by introducing studies published over the last decade. The application of hydrogels as adsorbents for the removal of hazardous pollutants is discussed as well. Conservation of water environments and water resources is a critical issue of this century. Efficient purification technology to reduce water pollution is essential, along with the promotion of reduced emission of pollutants. In the treatment and remediation of large water bodies, adsorption is an effective method for the separation of low-concentration pollutants. In the treatment of wastewater containing hazardous substances, the adsorption method is also a candidate process owing to its simplicity and cost-effectiveness. Various cost-effective solid adsorbents such as zeolites, activated carbon, modified clays, and ion-exchange resins have been developed for water treatment. Inevitably, the efficiency of the adsorption process relies on the performance of the adsorbent. Organic polymer hydrogels comprising a three-dimensional polymer network and a solvent have been shown to act as adsorbents for heavy-metal ions, dyes, and other organic hazardous pollutants because of their high performance, simplicity of use, and diversity in adsorbent design. Over the last few decades, the development of hydrogel adsorbents that effectively utilize the functions of polymer networks has increased ,4,5,6,7.In this short review, the basic requirements for adsorbents and the general advantages and challenges in the application of hydrogels as adsorbents are first reviewed. Then, the characteristics, advantages, and subjects of hydrogels as adsorbents are reviewed based on the roles and functions of the polymer network of gels, with an overview of studies published in the last decade. This review offers engineers and researchers an opportunity to gain more knowledge on hydrogels as adsorbent candidates.The design and use of adsorbents in the adsorption separation process are essential for adsorption separation technologies. Adsorbents that meet requirements like material cost, minimal environmental impact, stability, uptake rate, reusability, and adsorption capacity for target adsorbates will be selected in practice. In the modern design of adsorbents, the physicochemical structure of the adsorbent can be tailored to target pollutants. In the design of the adsorption separation process, the parameters of both the adsorption equilibrium and the mass transfer in adsorbents are crucial ,9. The aThe typical approach for improving the adsorption capacity is micronization and increasing the specific surface area of the adsorbents. Fibrization of adsorbents, as observed in non-woven fabrics, has also been used in recent years ,11. A coFrom an adsorption engineering point of view, the adsorption performance depends on operational conditions such as the adsorber reactor type, solid\u2013liquid ratio, and solution\u2013adsorbent contact time ,9. When Some adsorbents include a local gel phase. In most cases, only an adsorbent in which the entire adsorbent consists of a gel phase is called a gel adsorbent. Polymer hydrogels have several advantages in their application as adsorbents. The polymer networks create percolation pores with the desired solvent content and pore size. The specific surface area of polymer hydrogels is not typically discussed because of their network structure with a large amount of solvent. Open pores created by the polymer networks in the gels enable adsorbates to percolate deep inside the gels quickly, thus facilitating the adsorption capacity of the gels. Gels with high solvent content exhibit excellent diffusional permeability toward a range of substances. The diffusivity of solutes in gels has been extensively studied, both experimentally and theoretically. Various mathematical models used to determine the diffusion coefficient in gels have been developed and summarized in studies published in the 1990s ,17. NeveHowever, hydrogels have some drawbacks. Mechanical strength is a significant issue in many applications of the gels. The mechanical strength is an essential factor for the practical use of hydrogels. Thus, the strength of hydrogels has been improved by polymer selection and the structural design of polymer networks, such as the use of stiff polymers, an increase in the degree of polymerization, and the crosslinking method. Composites have successfully resolved the subject of strength through immobilization in a stiff porous matrix, the introduction of fiber materials such as nano-cellulose ,37,38, pApplications in which these functions are suited have been explored in many fields. Studies reviewing gel adsorbents in the last decade are introduced as follows.Naseem et al. (2018) reviewed microgels as adsorbents for the removal of aqueous pollutants such as heavy metals, nitroarenes, organic matter, and toxic dyes . The micMany studies on natural polymer gels as adsorbents have been reported. Various adsorbents using natural polymers and biomass, such as alginate ,43, chitLim et al. (2019) reviewed molecular gels as adsorbents for environmental remediation and water treatment and indicated the advantages of molecular gels with large selective capacities for pollutant sorption and recovery . MoleculHande et al. (2015) reviewed ion-imprinted polymer gels (IIPs) . MethodoSamiey et al. (2014) reviewed organic\u2013inorganic composite adsorbents for heavy-metal ions based on the composite structure of the adsorbents . The merPolymer gels as adsorbents were classified based on the roles and functions of the polymer networks in their applications as follows. The simple use of hydrogels is for the immobilization of supports and carriers. Even in this simple application of hydrogels, they have various advantages. The incorporation of diverse materials, simple solid\u2013liquid separation, stabilization of the immobilized substances maintaining high dispersion, accumulation and enrichment of target substances inside the gels, and the size control of stable solvent droplets with the size of gels are distinct advantages of the gels. The difference between hydrogels and emulsions or liquid immobilizing capsules is that water is immobilized in the polymer network with percolating open pores, and mass transfer across the surface of the gels is not restricted. The size of gels and pores are controllable, and mass transfer in the gels is not reduced, owing to the large amount of water and the percolating open pores in the hydrogels, which are also effective for the immobilized microorganisms and macromolecules, such as antibodies and enzymes, to maintain their activity over a long time. Furthermore, gels can produce a hierarchical reaction field because zoning of embedded substances can be achieved owing to the immobilization property of the polymer network.co-acrylonitrile) composite gel immobilizing magnetic CoFe nanoparticles for the removal of Cr3+, Cd2+, and dyes acrylamide) copolymer hydrogels [N-[3-(dimethylamino)propyl]methacrylamide (DMAPM)-co-N-tert-butyl acrylamide (TBAM) nanogels and applied them for the separation of carbon dioxide [N-isopropylacrylamide-N-tert-buthyacrylamide) copolymer gel slurry system [Ka shift is expected to yield a high-performance gel. To use this property, the mechanical strength of the gels to withstand repeated swelling operations is required. In addition, the gels must be micronized for a rapid response and adsorption. This process is energy-consuming when thermoresponsive gels are used because of the temperature-swing operation of the entire system. Therefore, it is crucial to devise methods to reduce energy consumption in practical applications. Effective utilization of the heat generated in chemical factories, steel mills, incinerators, etc. would increase the feasibility of these processes. Thin membranes fabricated on porous supports with nanosized particles of TBAM gels successfully achieved the energy-saving separation of carbon dioxide [Changes in the dissociation of ionic groups on the polymer networks occur depending on the volumetric change in the crosslinked polymer hydrogels. Weak acid-type or weak base-type ionic groups on the polymer chains undergo a shift in their dissociation equilibrium p the gel . This phydrogels . Honda e dioxide . Nagasawy system . A molec dioxide .3O4 nanoparticle-immobilized poly(3-acrylamidopropyl trimethylammonium chloride) microgels for the removal of AsO43\u2212 [3O4 nanoparticles effectively absorb oil spreading on the water surface, and the gels can be easily collected from the surface by the application of a magnetic field [Composite or conjugated forms of hydrogel adsorbents can increase the performance of the gel and the availability of the gels as adsorbents, considering the advantages of their use, cost, and material sharing from an ecological point of view. Adsorbents that exhibit advanced functions have been developed based on composite design. An example is the hydrogel embedding of magnetic nanoparticles . Solid\u2013lf AsO43\u2212 . The magic field . 2O), acrylamide\u2013acrylic acid sodium copolymer, and CuS for the storage of solar heat energy by light-to-thermal conversion developed light-to-thermal conversion phase-change composite hydrogels consisting of sodium acetate trihydrate matrix for immobilization of nano- and microsubstances, (2) scaffold for the strategic immobilization of functional groups, (3) stimuli-responsiveness of the polymer network, (4) contaminant uptake by self-assembly and gelation processes, (5) ionic and molecular imprinting, (6) integrated reaction field, and (7) dissociation control of ionic groups via volumetric control of the gel. Hydrogels have the diversity of creating various adsorbents suitable for capturing potential pollutants using the available functions as indicated in this review. Hydrogel adsorbents have the potential to create a functional adsorption process with a small environmental impact by integrating multiple functions into the gels. The variety of structural designs and functions of gel adsorbents would continue to expand their application. This is an era of comprehensive design of adsorbents and adsorption processes. In the life cycle of an adsorbent, green technology based on both adsorbent design and the optimum adsorption process is required. However, this effort is still in its infancy."} +{"text": "The human microbiota is equivalent to the major organs of the adult human body like the brain and liver, in terms of weight ~1.5 kg) and functionality. The gut, oral cavity, skin, and vagina are major residing homes of the human microbiota. The human microbiota comprises bacteria, viruses, archaea, fungi, and protozoans. Recent studies have revealed the presence of functional microbiota in blood, atherosclerotic plaques, adipose tissues, and other organs. Microbiota and their metabolites play a key role in insulin resistance, atherosclerotic plaque formation, inflammation, oxidative stress, and the metabolism of drugs and chemicals is becoming predominant among heart failure conditions. Hence, Shen et al. review its relationship with gut microbiota. A wide range of data on different microbial metabolites such as short-chain fatty acids, trimethylamine-N-oxide, and their molecular pathway leading to thrombus formation are discussed. In addition, the future therapeutic perspectives based on intervention in microbiota are elaborately presented.Atherosclerosis is the thickening of the blood vessel that aids different cardiovascular diseases. Aside from the different molecular pathways proposed for the formation of atherosclerotic plaques, recent research also suggests the role of microbial metabolites in this process . The bloYang et al. employed the in vitro and mice models to investigate the impact of Chinese rice wine metabolites on gut microbiota and subsequent impacts on diabetic cardiomyopathy. The mice treated with rice wine polyphenols and polypeptides led to a proliferation of Akkermansia and depletion of Desulfovibrio genera. A significant correlation was observed between the cardiac markers and microbiota profile, indicating the microbiota-mediated therapeutic impact.Dietary exposure, environment, and host genetics are the key players in shaping the microbiota of a human . The impIonescu et al. provide a comprehensive review of the studies related to microbiota and miRNAs and propose the mechanisms for the synergism between gut microbiota and host miRNAs during cardiovascular diseases.The gut microbiota interacts with numerous host factors and thereby influences host physiology and pathology. Numerous studies have revealed the role of microRNAs (miRNAs), the small, non-coding RNAs of mammalian origin that negatively regulate gene expression at the post-transcriptional stage. During the past decade, several studies have revealed the role of gut microbiota and miRNAs in different cardiovascular diseases . IonescuShanmuganathan et al. investigate the variation in the microbiota of human intervertebral disc tissue of healthy donors and patients with cardiovascular diseases undergoing surgery. The study reveals the abundance of proteobacteria (particularly the Pseudomonas genus) and firmicutes phyla in the degenerated disks. There is a significant loss in microbial diversity with an abundance of pathogenic bacteria in the degenerated disks.Recent studies explored the presence of microbiota in traditionally considered sterile tissues such as the liver, pancreas, breast tissue, and bone in both healthy and cancer tissues . In contOverall, this Research Topic provides different dimensions on the role of human microbiota during cardiovascular and other metabolic diseases. The major drawback in microbiota and disease studies is the non-exploration of the chicken and egg hypothesis, i.e., the cause and effect. At this moment, further studies are needed to explore the etiology of changes in the microbiota. We are hopeful that microbiota-based therapeutic approaches discussed here including fecal microbiota transplantation, probiotics, and prebiotic intervention with plant-derived metabolites will evolve into routine clinical practice in the near future.All of the contributors contributed to the Editorial process and approved this Editorial article."} +{"text": "A mental health (MH) assertive community treatment (ACT) is always designed expecting for a decrease in the pressure (visits and readmissions) in inpatient services and to increase care quality. An appropriate management of ACT provision can be crucial to develop a balanced community-based MH ecosystems.To assess the impact of the ACT on the performance of the MH ecosystem of Bizkaia .The ecosystem is structured by 19 MH areas, supported by 5 ACT teams. Here ACT provides high intensity mobile outpatient care to people suffering from severe mental disorders. The impact of these teams on the ecosystem performance was assessed by Monte-Carlo simulation, the Data Envelopment Analysis (DEA) and fuzzy inference. The input variables were the availability, number of psychiatrics, nurses and total of professionals of ACT services in each area. The outputs were: frequentation, incidence and prevalence of ACT services in each MH area. Performance indicators were: relative technical efficiency (RTE), statistical stability and entropy.The global ecosystem performance was high , the stability was medium-low and the entropy was medium-high .Results highlighted a positive impact of ACT in Bizkaia. Nevertheless, stability and entropy levels showed the existence of a high structural variability in ACT services due to the necessity of adjusting them to the user\u2019s specific needs.No significant relationships."} +{"text": "GNAS and TP53 mutations, and the diagnosis of OS arising from FD was strongly supported. This case highlights the characteristic images and molecular features of the malignant transformation of FD.Fibrous dysplasia (FD) is a benign fibro-osseous lesion that frequently involves the craniofacial bones and femur. Malignant transformation of FD is a rare occurrence. We report a 38-year-old woman with osteosarcoma (OS) arising from FD of the femur. Magnetic resonance imaging revealed a well-defined lesion in the medulla of the femur, with cortical thinning and local bone destruction. Wide excision of the femur was performed. Grossly, the inner part of the mass was hard and tan-gray in color, and the outer part of the mass adjacent to the cortex showed myxoid discoloration with infiltrative borders. Microscopically, most of the tumor consisted of curvilinear woven bone and fibrous stroma with bland spindle cells, which transitioned to the outer portion of the tumor, showing cellular proliferation of pleomorphic cells with frequent mitotic activity. Next-generation sequencing revealed"} +{"text": "In conclusion, the presence of OSA does not increase the need for glaucoma management.We try to evaluate glaucoma management numbers in patients with both glaucoma and obstructive sleep apnea (OSA) using the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was conducted and patients with glaucoma were enrolled and divided into the OSA and non-OSA populations. A total of 11,778 participants were selected in both the OSA and non-OSA groups. The primary outcomes were the number of anti-glaucomatous medications each year and the total number of glaucoma laser and glaucoma surgeries. The Cox proportional hazard regression was utilized to produce the adjusted hazard ratios (AHR) with corresponding 95% confidence intervals (CI) between the two groups. After a study period of 18 years, 286 and 352 events of laser and surgeries for glaucoma were found in the OSA and non-OSA groups, respectively. After considering the effect of potential confounders, no significant difference concerning the numbers of laser trabeculoplasty, trabeculectomy and tube shunt surgery, cyclodestructive procedure and eyeball removal were found between the two groups . In addition, the multiple anti-glaucomatous medication usages were similar between the two groups (all Glaucoma is a prevalent ocular disease that causes large numbers of visual impairments and legal blindness worldwide ,2. AccorRegarding the risk factors of glaucoma, old age is a well-established predisposing factor for glaucoma, and individuals aged older than 40 years are under a higher risk of glaucoma development and the prevalence of glaucoma reached 3.3% percent in those aged more than 70 years old ,7,8. RefObstructive sleep apnea (OSA) is a disease resulting from impaired ventilation , which cThe purpose of the current study is to survey the management numbers of glaucoma between OSA and non-OSA patients using the National Health Insurance Research Database (NHIRD) of Taiwan. The management of glaucoma is based on the number of anti-glaucomatous medications, arrangement of laser treatment and performance of glaucoma surgery.The NHIRD contains claims data of the National Health Insurance of nearly all inhabitants in Taiwan between 1 January 2000 and 31 December 2018. Our study obtained these data from the Longitudinal Health Insurance Database 2005 (LHID 2005), which is a sub-database of NHIRD and contains the records of nearly 2 million patients, which were randomly sampled from the NHIRD registry in the year 2005, and their data were connected from 2000 to 2018. Both the Ninth and Tenth Revisions of International Classification of Diseases were used for disease diagnosis in the NHIRD/LHID 2005. The accuracy of diagnosis is dependent on the physicians who enter the codes, and the system also provides the demography, time of medical visit, department codes, insurance codes of examination and codes of medications.We defined individuals as having glaucoma if their medical documents revealed (1) the presence of a glaucoma diagnosis; (2) the arrangement of intraocular pressure (IOP) measurement before glaucoma diagnosis; (3) the arrangement of visual field test, optical coherence tomography or fundoscopy before or on the same day of glaucoma diagnosis; and (4) the receipt of glaucoma diagnosis in ophthalmic outpatient department (OPD) and received treatment by an ophthalmologist. The index date was the date that the glaucoma diagnosis was entered into the NHIRD/LHID 2005. The exclusion criteria in this study were illustrated as follows: (1) receipt of legal blindness diagnosis before the index date; (2) receipt of an ocular tumors diagnosis at any time; (3) receipt of endophthalmitis or severe ocular trauma diagnoses at any time; and (4) outcome develops before the index date. Then, the patients with OSA were selected from the whole glaucoma population based on these criteria: (1) the presence of an OSA diagnosis, (2) the arrangement of polysomnography before the OSA diagnosis, and (3) the OSA diagnosis was entered by a thoracologist, otorhinolaryngologist or neurologist. After that, each individual with both OSA and glaucoma was matched to one glaucoma patient without OSA via the propensity score-matching (PSM) method according to demographic data, co-morbidities and medications listed in the following sections, and the non-OSA population constructed the control group. Subjects in the OSA group that could not be matched to one non-OSA patient were excluded from this study. A total of 11,778 patients were enrolled in both the OSA and non-OSA groups after the selection process. In addition, participants in the study population were categorized into OAG, NTG and ACG subgroups according to the diagnostic codes and differences in outcomes of these subgroups between OSA and non-OSA populations were analyzed. The flow chart of subject selection is revealed in The performance of glaucoma treatments, which were the primary outcome of our study, was defined as the following: (1) the number of topical anti-glaucomatous medications used, which included beta-blockers, alpha agonists, carbonic anhydrase inhibitors, prostaglandin, and miotic agents; (2) the arrangement of laser trabeculoplasty; (3) the arrangement of trabeculectomy and tube shunt surgery; (4) the arrangement of cyclodestructive procedure; and (5) the arrangement of eyeball removal. To prevent the overestimation of the primary outcome, the primary outcome was considered to develop only in patients who received introductory diagnostic codes, medical prescriptions and surgical treatments from an ophthalmologist.To make secure that the health status and the potential risk factors of advanced glaucoma between the OSA group and non-OSA group are sufficiently comparable, we investigated the influence of enrollment years, age, sex, urbanization, education level, and the following morbidities and medications in the multivariate model: hypertension, DM, ischemic heart diseases, hemodialysis, cerebrovascular disease, uveitis, cataract, refractive error, and steroid application including topical and systemic prednisolone, methylprednisolone, hydrocortisone, triamcinolone and dexamethasone. We longitudinally followed the data from the index date until the date of each outcome achievement, subject withdrawal from the National Health Insurance program, or till the end date of NHIRD/LHID 2005, which is 31 December 2018.p < 0.05, and p values less than 0.0001 were presented as p < 0.0001.The SAS version 9.4 was applied for all the analyses. After PSM of the OSA and non-OSA groups at a 1:1 ratio, descriptive analyses were used to show the difference of basic characters between the two groups, and the absolute standardized difference (ASD) between the two groups was also calculated and an ASD < 0.1 was regarded as a similar value. Then, the incidence rate and the adjusted hazard ratios (AHR) with corresponding 95% confidence intervals (CI) of primary laser and surgical outcome between the two groups were yielded through Poisson regression and Cox proportional hazard regression. The Cox proportional hazard regression incorporated the demographic data, systemic comorbidities, ocular comorbidities and steroid utilization. In the subgroup analyses, we stratified the OSA and non-OSA groups via age, gender, glaucoma subtypes , the duration of OSA, and the presence of OSA-related surgery . We then compared the incidence of laser trabeculoplasty, trabeculectomy and tube shunt surgery, and cyclodestructive procedure via the Cox proportional hazard regression again. Of note, the eyeball removal was not compared at this stage due to insufficient patient numbers. We produced the Kaplan\u2013Meier curve to illustrate the cumulative incidence of laser and surgical management between the two groups, and used log-rank test to determine the significance between two survival curves. For the anti-glaucoma medications, the percentage of any anti-glaucomatous medication usage and the percentage of more than one type of anti-glaucomatous medication applications between the two groups in every year was analyzed via independent T test and presented as a line chart. The statistical significance was regarded as The baseline characteristics between the OSA and non-OSA groups are shown in p > 0.05). Regarding the numbers of anti-glaucomatous medications, both the percentage of any anti-glaucomatous medication usage and the percentage of multiple anti-glaucomatous medications application showed similar values between the OSA and non-OSA groups .In the subgroup analyses, the glaucoma patients aged more than 60 years and with OSA received significantly fewer trabeculectomy and tube shunt surgery compared to the glaucoma patients aged more than 60 years without OSA . However, the incidence of glaucoma laser and surgical managements demonstrated similar values in all other subgroups stratified via age, gender, glaucoma subtype including the OAG, NTG and ACG, OSA duration, or presence of OSA-related surgeries .In our study, we found that co-existing OSA in glaucoma patients does not increase the incidence of advanced glaucoma management such as laser treatment and glaucoma surgery. Moreover, the percentage of patients with more than one anti-glaucomatous medication usage is similar between the OSA and non-OSA populations. On the other hand, the ratio of trabeculectomy and tube shunt surgery is lower in those glaucoma individuals with OSA and aged more than 60 years old.The association between OSA and glaucoma has been evaluated for decades . GeneralThe current study illustrated that the percentage of multiple anti-glaucomatous medication applications, the incidence of glaucoma laser therapy, and the ratio of glaucoma-related surgeries are similar between the OSA and non-OSA groups after adjusting multiple potential risk factors including steroids. To our knowledge, few studies have surveyed this issue concerning glaucoma severity and concurrent OSA before. Although some studies have proposed that glaucoma severity was associated with OSA ,21,22, tIn the subgroup analyses of this study, the impact of OSA on glaucoma management did not alter with different conditions. The only significant finding is the lower incidence of trabeculectomy and tube shunt surgery in the OSA population older than 60 years old than in the non-OSA population with the same age interval. The possible explanation is that the OSA-induced ocular surface irritation and retinal diseases meant that the patients came to the ophthalmic department more frequently ,32, and Regarding the demography between the OSA and non-OSA groups, the majority of covariates revealed similar distribution between the two groups even though OSA was diagnosed more commonly in males and those with metabolic disorders ,35,39. TThere are several limitations presented in the current study. Firstly, the claimed database nature of our data source meant that many important indexes could not be accessed, which included the polysomnography results throughout the OSA management, the application of continuous positive airway pressure device, the arrangement of weight-loss therapy, the details of the OSA treatment course, the results of glaucoma-related examination including the visual field optical coherence tomography, the fluctuating of IOP after treatment in both the OSA and non-OSA groups, the controlling of IOP and glaucoma damage progression after glaucoma management, and the exact severity of glaucoma and other ocular diseases. Because the IOP value was unknown in the NHIRD/LHID 2005 and the main mechanism of OSA-related glaucoma could be hypoxia and ischemia ,13,19, wIn conclusion, the presence of OSA does not affect the management numbers of glaucoma concerning anti-glaucomatous medications, laser treatments and glaucoma-related surgeries. Furthermore, the insignificant effect of OSA on glaucoma management is universal in different types of glaucoma including OAG, NTG and ACG. Consequently, the therapeutic program of newly diagnosed glaucoma should not be altered in those with OSA. A further large-scale prospective study to evaluate the effect of continuous positive airway pressure devices on the severity and management of glaucoma in OSA individuals is mandatory."} +{"text": "Globally, cancer ranks among the most common causes of death, especially among people under 70 years of age . With thAfrica is considered the most vulnerable continent in the world with regards to the availability of resources for optimal health care provision and comprises about 85.2% of countries that belong to the low-income/lower-middle-income economies . Also, mWe examine the implementation status of AI platforms for cancer outcomes in Africa and provide pointers that could maximize their utilization.The uptake of technology-driven systems available in developed regions is slower in Africa than in other parts of the world, as these platforms are often generated from integrative variables that may not be available for external validation and clinical application in many African settings. For oncology, this may be further challenged by the variation in molecular or etiological subtypes, as well as infrastructural and ethnocultural peculiarities of cancer management in the African region ,8. A preGenerally, the development of AI tools for assisted decision-making among patients with cancer in Africa can be considered a recent endeavour, with many models being reported from 2018 (Relative to the different subregions in Africa, the pattern of AI penetrance mirrors the ongoing economic and infrastructural development in the continent ,27. As sMoreover, oncological AI-based models in Africa were being considered for outcome determination among patients with breast, cervical, and colorectal carcinomas (The technical aspects of the development and validation of cancer-related AI models in Africa is generally satisfactory (The performances of the set of models proposed for use in African oncological settings so far were satisfactory to excellent upon validation -12,14,18Applying AI in developing credible tools for the prediction of cancer outcomes in Africa is a relatively recent endeavour. Model construction in the continent reflected the degree of technological advancement among the nations, as well as the availability of electronic health records and digitized clinical investigations. None of the models developed locally and internationally have been assessed for their impact and efficiency in automated assistive clinical decision-making and risk stratification. Hence, this should represent the phase of AI implementation to be addressed soon, especially in numerous remote areas of the low- and lower-middle-income areas. Likewise, for these settings, it is expected that the future will see the integration of AI-based prediction and other digital health technologies to mitigate the challenges of reduced manpower, substandard facilities, and lack of access to care currently experienced in cancer diagnosis and management in Africa."} +{"text": "Even though numerous studies on the systemic administration of antimicrobial drugs can be found in the literature, they still have many shortcomings related to the site-specific drug delivery, unwanted side effects and even potential toxicity. To overcome the above limitations, it is necessary to explore new approaches for the administration of active principles with antimicrobial properties.In this Special Issue, original papers have been published that bring new perspectives in the development of novel pharmaceutical formulations for antimicrobial applications. Active principles with antimicrobial properties, such as antibiotics ,2,3,4,5,A first study, in which the Chapman University School of Pharmacy, Chapman University Irvine, USA and the Department of Ophthalmology School of Medicine, University of Pittsburgh School of Medicine, USA collaborated, was designed to evaluate the stability of vancomycin eye drops in normal saline solution, phosphate-buffered saline (PBS) and balanced salt solution (BSS), while being stored for 7, 14 and 28 days at room temperature or refrigerated [Two other research teams from the Interdisciplinary Excellence Centre, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Hungary and the School of Engineering, Institute for Materials and Processes, University of Edinburgh, UK studied the preformulation of poly(vinylpyrrolidone)-based nanofiber mats loaded with ciprofloxacin (CIP) for oral administration . The aimAnother study involving researchers from Turkey, UK and Romania presents the fabrication of bacterial cellulose (BC)/polycaprolactone (PCL) patches loaded with different antibiotics (amoxicillin (AMX), ampicillin (AMP) and kanamycin (KAN)) for transdermal delivery . The obtC. trachomatis serovar D laboratory strain and the clinical isolate C. trachomatis serovar F. All tested liposomes efficiently delivered AZT to HeLa 229 cells infected with the laboratory Chlamydia strain, showing minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of AZT even 4\u20138 times lower than those obtained with free AZT. Also, AZT-loaded liposomes were effective against the clinical Chlamydia strain by decreasing the MIC values by two-fold compared to free AZT.A multidisciplinary research team from Hungary and Croatia managed to prepare and test several new formulations based on elastic liposomes loaded with azithromycin (AZT), which differ in surface charge . Their aThree Research Institutes from M\u0103gurele, Romania and three other Departments from the Faculty of Biology, University of Bucharest, Romania developed composite materials based on bioglass/ciprofloxacin/poly(methyl methacrylate) as multifunctional thin films for hard tissue implants . BrieflyCandida albicans infection.A stable and highly skin-permeable topical delivery system for itraconazole (ITZ) was obtained and tested by a multidisciplinary research team in Korea . This toAnother study that sought to obtain pharmaceutical formulations based on antifungal drugs was published following collaboration between researchers from Saudi Arabia and Ethiopia. Butenafine hydrochloride nano lipid carrier (NLC) formulations were obtained and optimized . The optLactobacillus acidophilus, Bifidobacterium animalis) combined with actives from Helianthus tuberosus and Plantago ovate as herbal prebiotics. The results obtained are encouraging and attest to the great potential of the obtained nutraceutical formulations for their designated purposes, recommending them for further in vivo studies.As is known, modulation of the immune system refers to a certain alteration in the immune response in the form of stimulation, amplification, expression or inactivation of some stage of the immune response. A material which exhibits a modifying immune system response to a threat is an immunomodulatory and this concept currently underlies the development of functional foods. The study of a group of researchers from Romania aimed toS. aureus and K. pneumonia, but low activity for P. aeruginosa and E. coli, and may be considered non-cytotoxic. The swelling behavior, the mechanical properties, and the antimicrobial activity recommend the use of this biocomposite in biomedical applications as wound or oral dressings.Another group of Romanian researchers proposes a new type of full-IPN hydrogel, based on chitosan and poly, obtained by combining two cross-linking methods: covalent and physical. In fact, the authors obtained a biocomposite consisting of silver nanoparticles dispersed in the matrix of IPN, designed to exert a synergistic antimicrobial activity through the action of both chitosan and silver . The bioS. aureus, E. coli, and K. pneumonia.The same type of matrix (with hydrogel character), but covalently cross-linked with glutaric aldehyde, was used to disperse ZnO particles in order to obtain a biocomposite proposed for the treatment of bacterial infections . The incA review discusses the possibility of using plant materials in the management of many inflammatory diseases, including periodontitis\u2014one of the most serious oral diseases which affects tissues, being caused by pathogenic bacteria and environmental factors . It is wStaphylococcus aureus and Escherichia coli, and high selective antiviral activity against the H1N1 influenza virus, with minimum host toxic effects.In another paper of this issue, harmala alkaloid-rich fraction (HARF) (which is hydrophobic) was included in 2-hydroxy propyl-\u03b2-cyclodextrin to obtain a host\u2013guest complex; by doing so, the water solubility and bioavailability of HARF was improved . The com2 and grafted with poly [Escherichia coli was eradicated at pH 6\u20137 and humidity 45\u2013100%, conditions in which most bacterial and fungal strains thrive.The last paper of the issue concerns the preparation of ligand brush nanocapsules, based on poly(vinyl pyrrolidone), coated with SiOum salt) . The ligPharmaceutics, titled Pharmaceutical Formulations with Antimicrobial Properties, are researchers with decades of experience in the field of controlled drug release, and they consider these articles reporting recent results concerning the obtaining of polymer\u2013drug systems, their properties and their biomedical applications justified and useful.The editors of this Special Issue of Pharmaceutics with the results of their recent research.The editors express their gratitude for the kindness and cooperation of the contributors, who are reputable researchers in the field and have responded to our call to contribute to this Special Issue of"} +{"text": "Sensitive indicators of nursing quality focus on the core elements of nursing quality management. Nursing-sensitive quality indicators will play an increasingly important role in the macro and micro management of nursing quality in my country. This study were aimed at formulating the sensitive index management of orthopedic nursing quality based on individual nurses for improvement of the quality of orthopedic nursing. Based on the previous literature, the existing challenges in the early application of the orthopedic nursing quality evaluation index were summarized. Moreover, the management system of the orthopedic nursing quality-sensitive index based on individual nurses was devised and implemented, including monitoring the structure and result indices of individual nurses on duty and sampling the process indicators of patients managed by individual nurses. At the quarter-end, the data analysis was performed and fed back to determine the key points of the changes in the quality of specialized nursing affecting the individual, and the PDCA method was utilized for persistent improvement. The changes of sensitive indices of orthopedic nursing quality before (July-December 2018) and 6 months after implementation (July-December 2019) were compared. P < 0.05). There were significant differences in other indices ( The formulation of an individual-based orthopedic nursing quality-sensitive index management system modifies the traditional quality management model, improves the specialized nursing level, contributes to the accurate core competence training of specialized nursing, and improves the quality of specialized nursing of individual nurses. Consequently, there is an overall improvement in the specialized nursing quality of the department, and fine management is attained. The sensitive indicators of nursing quality are nursing guidelines, regulations, procedures and methods formulated according to the content, characteristics, processes, management requirements of nursing work, and the characteristics and needs of nursing staff. Sensitive indicators of nursing quality are also yardsticks for measuring nursing work. The establishment of a systematic, scientific, and advanced nursing standardization system is conducive to improving the quality of nursing and nursing management and promoting the development of nursing disciplines and the training of nursing talents. On the basis of the above standards, each hospital formulates basic nursing quality standards, critically ill patient nursing quality standards, nursing documentation quality standards, and other standards but lacks specialist nursing quality standards. In the field of orthopedic nursing, domestic and foreign countries only focus on the evaluation of certain orthopedic diseases or individual nursing problems and lack comprehensive and overall orthopedic nursing quality standards. Sensitive indicators of nursing quality focus on the core elements of nursing quality management, and nursing-sensitive quality indicators will play an increasingly important role in the macro- and micromanagement of nursing quality in my country. Quantitatively identify nursing practices that are most relevant to patient outcomes in an effort to improve patient safety and quality of care , 2. The Previously, indicator management was based on the integrity level of wards, departments, and hospitals \u20138; howevThe Department of Orthopedics of our hospital is a national key construction discipline, integrating trauma, joint, and spine surgeries, bone oncology, microsurgery, sports medicine, and other specialized disease treatment disciplines. Seventy-seven orthopedic nurses were included as the study participants, with the age ranging from 22 to 42 years; title: one deputy chief nurse (1.30%), 13 chief nurses (16.88%), 51 nurse practitioner (66.23%), and 12 nurses (15.58%); working years: 29 (37.66%) with <5 years, 30 (38.96%) with 5\u2013 10 years, seven (9.09%) with 11\u2013 15 years, and 11 (14.29%) with >15 years; and posts: 19 nursing team leaders or specialized nurses (24.68%), 22 senior nurses (28.57%), and 36 junior nurses (46.75%).The following are the inclusion criteria: (i) clinical practical nurses registered with the Provincial Health Commission, (ii) clinical practical nurses registered with the Provincial Health Commission, (iii) clinical practical nurses registered with the Provincial Health Commission, with at least orthopaedic nursing work (1 year). The following are the exclusion criteria: (i) nursing managers (head nurses), nurses without a nursing practice certificate were excluded; (ii) working in orthopaedics for <1 year, with long-term leave; and (iii) sick leave, maternity leave; or studying abroad for more than 15 days (nurse).P < 0.05). Structural indicators Establishment of a Specialist Nursing Quality Control Group. In January 2019, a specialist nursing quality control group was established. The group members comprised the department nursing director, district nursing director, and specialist nurses, with a total of 10 members. The inclusion criteria for team members were bachelor degree or above; rigorous scientific fact-finding attitude; rich nursing expertise, strong thinking, and judgment; experience in nursing quality evaluation; 10 or more years of experience in orthopedic nursing or management; and intermediate level or above. The responsibilities of the team members include organizing core competency training based on sensitive indicators and performing individual nursing quality personalized management for individual nurses based on sensitive indicators.(2) Core Competency Training Based on Sensitive Indicators. The core competency training of orthopedic nurses includes the theoretical knowledge and practical skills related to sensitive indicators which are included as important elements of clinical practice competency. From January to March 2019, pretraining on personalized management of nursing quality of orthopedic nurses is organized and implemented. Content of the training included overview and interpretation of orthopedic nursing quality sensitive indicators, the connotation of indicators theoretical knowledge, nursing processes, and standards and application of orthopedic nursing quality sensitive indicators for nursing quality management; methods of training and assessment: theoretical lectures, case teaching, operation demonstrations, business visits, objective structured clinical examinations, skill training, and assessment; training hours: 120\u2009h/person.(3) The Specialist Nursing Quality Control Team Performing Individualized Monitoring and Improvement of Indicators. Individualized monitoring of structural indicators (nurse-patient ratio) and some outcome indicators are conducted, that is, monitoring the nurse-patient ratio and outcome indicators during the shift of the responsible nurse. Patients who were under the charge nurse's supervision throughout the hospital stay were monitored for outcome indicators (patient satisfaction at discharge). To investigate satisfaction, the hospital's revised \u201cPatient Satisfaction Questionnaire\u201d was distributed at the time of discharge, which included patient satisfaction with the medical environment, quality of care, professional skills of nurses, and service attitude of nurses. The survey forms were placed in the satisfaction survey box by patients or family members to reduce human interference factors. The process indicators including accuracy of blood circulation assessment in limbs, the accuracy of neurological function assessment, the accuracy of pain assessment, the passing rate of postural care, and accuracy of rehabilitation behavior training of the patients under the charge of this responsible nurse were sampled, and record forms were filled out. Moreover, members of the quality control team served as quality inspectors, and each nurse was continuously sampled for each indicator five times/quarter, and the total number of times each nurse sampled for the five indicators was 25 per quarter. The quality of the nurses' process of implementing specialized care was assessed to determine if the content was comprehensive, the method was correct, and the results were consistent with the quality inspector's evaluation. When the two evaluation results were inconsistent, another quality inspector made a judgment, and if necessary, the competent professor of the patient was asked to implement the evaluation and provide guidance.Quarterly data entry of quality evaluation was performed to establish a database of sensitive indicators of orthopedic nursing quality based on individual nurses. At the end of each quarter, the quality management team analyzed the above data by calculating each nurse's indicator value, comparing the growth rate of each nurse's indicator value to the previous quarter, comparing the difference in indicator values between nurses at the same level of position, comparing the difference between each nurse's indicator value and the indicator target value for nurses in the same level of position, and providing feedback to the individual nurse on the results of the analysis and the individual finding the impact of individual specialty nursing The results of the analysis are fed back to the individual nurse, and the individual identifies priorities for continuous improvement that affect individual specialty care changes. Simultaneously, targeted training is provided at the ward and unit level for nurses with large differences in indicator values and fluctuating indicator values, and specialty nursing core competency training is implemented based on individual nurses. For example, the pain assessment accuracy of a nurse's patients was the lowest among the process indicators and lower than the pain assessment accuracy of nurses in the same level of positions. The individual detected that the reasons affecting his low pain assessment accuracy were his lack of mastery of the use of different pain assessment scales, subjective judgment during pain assessment, and lack of timely assessment after implementing pain interventions. The individual proposed improvement measures, including changing the concept of pain, believing in the patient's chief complaint, learning relevant knowledge, and writing a case report on pain assessment in conjunction with the case; asking the district nurse manager or pain specialist nurse for bedside guidance; and self-evaluating the accuracy of pain assessment and comparing it with the evaluation results of the QI officer.\u03c72 test was used to compare the differences between the two groups with a test level of \u03b1 = 0.05. The types of diseases in which nurses performed care before and after implementation included extremity fractures, multiple injuries, pelvic fractures, brachial plexus injuries, hand trauma, osteoarthritis of the knee, femoral head necrosis, femoral neck fractures, femoral trochanter fractures, knee ligament injuries, knee meniscal injuries, lumbar disc herniation, cervical spondylosis, scoliosis, spinal cord injury, spinal fracture, extremity bone tumor, and sacral tumor. The differences in patients' sex, age, diagnosis, surgery, and condition classification were comparable and not statistically significant (P > 0.05). The results of the discharge patient satisfaction survey were selected for statistical analysis from the questionnaires completed by patients who had implemented the process index evaluation.Statistical analysis was performed using SPSS 20.0 software to compare changes in orthopedic nursing quality sensitivity indicators before implementation (July-December 2018) and 6 months after implementation (July-December 2019). Percentages were used for descriptive analysis and the P > 0.05). The incidence of external fixation complications in high-risk patients was 0.65%, the incidence of deep vein thrombosis was 0.52%, and the incidence of respiratory obstruction was 0.13%. In high-risk patients, the incidence of deep vein thrombosis was 0.13% and the incidence of respiratory obstruction was 0. Comparing the process indicators of nurse management at different levels with the results of patient discharge satisfaction, all indicators except the accuracy rate of neurological function assessment of patients in the nursing management of level 3 and the satisfaction rate of discharged patients from nursing group leaders or specialist nurses have statistics difference in science (P < 0.05). See Tables 2There was no significant difference in the nurse-patient ratio of nurses in charge of the same post before and after the intervention (With the gradual formation of a consensus on the concept of \u201cevidence-led improvement to replace evidence-based management,\u201d nursing-sensitive quality indicators will play an increasingly important role in the macro- and micromanagement of nursing quality in my country . In receOur study found no statistically significant difference in the proportion of nurses and patients in the same post before and after the intervention. The incidence of external fixation complications in high-risk patients was 0.65%, the incidence of deep vein thrombosis was 0.52%, and the incidence of respiratory obstruction was 0.13%. In high-risk patients, the incidence of deep vein thrombosis was 0.13% and the incidence of respiratory obstruction was 0. The reason for the analysis is as follows: Because of the relatively stable nurse-to-patient ratio, the level of professional care in the department is reflected in the difference between the quality of the process and the outcome . The evaOur study found that when comparing the process indicators of nurse management at different levels with patient discharge satisfaction outcomes, all patients except for the accuracy of neurological function assessment and patient satisfaction at discharge from nursing group leaders or specialist nurses in level 3 nursing management All indicators were statistically different. The reasons for the analysis are as follows: the assessment and management of nursing quality should be based on professional standards of nursing . NursingBased on individual nurses, this study implemented the management of sensitive indicators of orthopaedic nursing quality, and further explored the application value of sensitive indicators of specialized nursing quality. Facts have proved that both managers and individual nurses can accurately find the weak links in nursing according to the changes in the indicator data, thereby improving the professional nursing quality of individual nurses, thereby improving the overall professional nursing quality of the department, and achieving refinement. This study was limited to the orthopaedic ward in our hospital, and future research may include a multicenter study to further improve the management of sensitive indicators of orthopaedic care quality based on individual nurse practice."} +{"text": "The main components in the machine complexes responsible for generation and functions of these epi-markers have been characterized in recent years. These components display tissue-specific and delicate spatiotemporal patterns, and their fine-tuned orchestration contributes to the precise and dynamic regulation of the epigenomic and the epitranscriptomic landscapes, ensuring the normal growth, development, and reproduction. More importantly, the emerging evidence links the aberrant regulation of these epi-markers to pathogenesis of multiple diseases, potentially translatable to clinical applications for therapy.Dynamic and precise regulation of gene expression is orchestrated genetically and epigenetically in accordance with developmental stages and in response to environment stimuli. Aberrant genetic or epigenetic events could devastate gene expression, contributing to pathogenesis of disease. Epigenetic markers of base modifications such as 5-cytosine (5-mC), 5-hydroxycytosine (5-hmC) and adenosine methylation mThis Research Topic mainly focuses on the epigenomic and epitranscriptomic basis of human diseases. The aim of the topic is to provide a broad overview of current research on epigenetic aspect of development and pathogenesis of human diseases.Xu et al., found that deficiency in TET1, one of the erasers for base demethylation impairs learning and memory. In addition to neurological disorder, methylation status is also linked to cancers. One research article addresses the critical role of histone methyltransferase KMT5B on initiation of glioblastoma (GBM) via epigenetically regulating a subset of GBM-related genes associated with hypermethylation and 5-hmC loss of genomic DNA Lopez et al.Total 13 of articles published in this Research Topic focus on epigenetic regulation of learning and memory, immunological functions, and tumorigenesis. Two of them are related to base modification and human disease. Wang et al. found that dynamic histone modifications could activate a subset of genes involved in lipogenesis, energy metabolism and inflammation under the high-fat diet (HFD) conditions, addressing the contribution of the eating habits to the related pathology via histone modification.Histone modifications are associated with lipogenesis and obesity by repression or activation of gene expression. Two research articles are related to the link of histone modifications with metabolic disorders and autophagy involved in pulpitis. Yin et al., screened several groups of writers and erasers for histone methylations under TNF\u03b1 treatment, providing important information on the epigenetic regulation of autophagy genes during pulpitis, and more importantly this study could be translated to a novel clinical therapy.Autophagy is regulated epigenetically as well during development. epigenomic and epitranscriptomic basis of development and human diseases.As a summary, the research and review articles published in this Research Topic provide important scientific information in a convenient manner that is targeted toward readers with interest in the"} +{"text": "This Frontiers in Veterinary Science Women in Veterinary Neurology and Neurosurgery collection of scientific articles presents the innovative work of female neurologists working in the UK, Europe, and North America. The series comprises 13 articles showcasing original research and case reports in various fields of Veterinary Neurology and Neurosurgery, including advances in diagnostic imaging techniques and novel neurosurgical procedures.Boudreau et al. describes DWI MRI findings of spontaneous canine CVA in relation to the time of clinical onset, the DWI type (EPI vs. non-EPI), and the presence or absence of a haemorrhagic component of the lesion. The results of this study help to inform the appropriate clinical interpretation of these sequences by veterinary neurologists and neuroradiologists.Diffusion MRI is a specific sequence that detects and quantifies water diffusivity, which is the molecular motion (Brownian movement) of water and represents an intrinsic feature of tissues. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) are MRI sequences routinely used in the diagnostic investigation of suspected cerebrovascular accidents (CVA) in people . There iRemelli et al. highlights the usefulness of low and high-field MRI in complementing clinical and laboratory findings in the diagnosis of SRMA. In this retrospective study, including 70 dogs with SRMA, the MRI showed abnormalities in 98.6% of dogs, with the majority (87.1%) being MRI features suggestive of meningeal inflammation. T1W FAT-SAT sequences were particularly useful in detecting meningeal enhancement. In addition, the contrast enhancement of the synovium of the cervical articular facets and the epaxial muscles was detected in 48.6% of dogs.Steroid-responsive meningitis-arteritis (SRMA) is an inflammatory disorder of probable immune mediated origin, commonly recognized in dogs . It typiLaws et al. describes the clinical and diagnostic findings, treatment , and outcomes of dogs with SEE that were presented to five referral hospitals in the UK. This study provides detailed information on the presenting clinical signs, MRI findings, laboratory investigation results, treatment, and long-term outcomes. The results of this study inform client communication and clinical decisions on canine SSE management.Spinal epidural empyema (SEE) is characterized by the \u201caccumulation of purulent material in the epidural space of the vertebral canal\u201d . It can Goffart et al. shows that end-on fluoroscopy, with or without inversion, is a highly accurate technique for the intraoperative evaluation of bicortically placed Steinmann pins' position in the canine thoracolumbar vertebral column. Three-dimensionally printed patient-specific drill guides have been used to improve the accuracy of implant placement in the canine spine of the central and peripheral nervous system.The author confirms being the sole contributor of this work and has approved it for publication."} +{"text": "Using the technique of Force Field Analysis, the co-developer of CAPABLE examined drivers and restrainers of dissemination for the CAPABLE program. This generated 19 distinct drivers including robust research findings, demonstrated clinical and economic utility, and high value to older adults. The environmental shift toward value-based approaches in Medicare and Medicaid also increased the perceived value of CAPABLE. In addition, there were 8 restrainers, including component complexity, siloed health and housing sectors, and the operational lift needed to build the program. Lessons are offered from this case study to move from research to embedded practice."} +{"text": "In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dynamics. Another promising feature is the modulation of the synaptic transmission as synaptic plasticity and the intrinsic excitability of neurons as non-synaptic plasticity. Those modulations of physiological properties of neurons are considered induced by both transient and chronic exposures to inflammatory mediators, which cause behavioral disorders seen in mental illness. It is plausible for astrocytes and pericytes other than microglia and macrophage to induce the immune-triggered plasticity of neurons. However, current understanding has yet achieved to unveil what inflammatory mediators from what immune cells or glia induce a form of plasticity modulating pre-, post-synaptic functions and intrinsic excitability of neurons. It is still unclear what ion channels and intracellular signaling of what types of neurons in which brain regions of the CNS are involved. In this review, we introduce the ubiquitous modulation of the synaptic efficacy and the intrinsic excitability across the brain by immune cells and related inflammatory cytokines with the mechanism for induction. Specifically, we compare neuro-modulation mechanisms by microglia of the intrinsic excitability of cerebellar Purkinje neurons with cerebral pyramidal neurons, stressing the inverted directionality of the plasticity. We also discuss the suppression and augmentation of the extent of plasticity by inflammatory mediators, as the meta-plasticity by immunity. Lastly, we sum up forms of immune-triggered plasticity in the different brain regions with disease relevance. Together, brain immunity influences our cognition, sense, memory, and behavior Cyclostomatas). On the other hand, innate immunity existed long before the advent of vertebrates. The complement system has been found in ascidians and sea urchins, and Toll-like receptors are already present in cnidarians , pathogen-associated molecular patterns (PAMPs), and neurodegeneration-associated molecular patterns (NAMPs), and the mediators play distinct roles in both physiology and pathology in the CNS , activates microglia through Toll-like receptor 4 (TLR4), a pattern recognition receptor. Exposure to LPS facilitates the vesicular release at hippocampal excitatory presynaptic terminals , which intensifies the intrinsic excitability of Purkinje cells of intrinsic excitability, as the increase in the firing frequency of action potentials, and facilitate synaptic transmission in Purkinje neurons of juvenile rodents . In contrast, spontaneous events are recorded without TTX. When the amplitude of miniature EPSC and IPSC changes, it indicates changes in postsynaptic responsiveness.It is noteworthy that, generally, in synapses, there are two sites for modulation: pre- and post-synapses. The modulation of presynaptic release is identified by the increase and decrease in the frequency of miniature EPSC and inhibitory postsynaptic current (IPSC) of the excitatory and inhibitory synapses, respectively. Miniature EPSC and IPSC are the synaptic events recorded under voltage-clamp in the presence of a blocker of voltage-sensitive Navia downregulation of SK channels and the microglia activation reduces the intrinsic excitability of layer 5 (L5) and L2/3 pyramidal neurons mediated by TrkB signaling, associated with the neural pain , transient receptor potential cation channel subfamily A member 1 (TRPA1), interleukin-1 receptor 1(IL-1R1), and presynaptic ionotropic glutamate receptor [N-methyl-D-aspartate receptor (NMDA receptor)] released from microglia induces depolarization of anion reversal potential and modulates the driving force of inhibitory GABAergic channels via innate immune responses. The related inflammatory cytokines and the mechanism for induction have numerous variations. In the following sections, we discuss the roles of inflammatory mediators, cytokines, in synaptic and non-synaptic plasticity (Roles of Inflammatory Cytokines and Lipid Mediators in Synaptic and Non-synaptic Plasticity). And we describe modulations by chemokines . Lastly, we discuss the possible involvement of the immune-triggered plasticity in psychiatric diseases (Plasticity Triggered by Inflammatory Cytokines and Relevance to Psychiatric Diseases).The modulation of synaptic transmission and intrinsic excitability by immunity is expected to exist in CNS regions other than the cerebellum and cerebral cortex. Here, we show summary tables of the immune-triggered modulation of the synaptic efficacy and intrinsic excitability of neurons in different brain regions , 2. TablA receptors was identified in 1975 as a factor causing hemorrhagic necrosis in tumors planted in mice , which binds to the same receptor but does not convey a signal. IL-1 signal induces the expression of IL-8 and IL-6 by activating NF\u03baB and AP-1 In vivo, administration of LPS to the fourth ventricle impaired hippocampal memory tasks are synthesized by many cell types, including macrophages, as pre-pro-TGF\u03b2 (pre-propeptide), and the pre-propeptide is cleaved in the endoplasmic reticulum and secreted as an inactive dimer bound as a latent complex, tethered by the extracellular matrix. Serum proteinases and matrix metalloproteinases (MMPs) liberate the latent form, and TGF\u03b2-binding to transforming growth factor beta receptors (TGFBRs) transduce the signaling in the SMAD-dependent and SMAD-independent manners and LTP in hippocampal perforant path-dentate gyrus synapses are the physically active lipid mediators, which are produced in almost all tissues and involved in the induction of plasticity in the brain ligand 1 suppressed the induction of the LTD of parallel fiber-Purkinje cell synapses or HCN channels, would be another potential target for the drug administration, while we should note that inflammatory mediators could be modulators of not only fast synaptic transmissions and the intrinsic excitability but also metabotropic receptors of monoamine, mGluRs, GABABR, and other G protein-coupled receptors, which are also involved in the plasticity induction.Despite the difficulty in interpreting the biological significance of behaviors, learning, and cognition, the interaction of immune cells with neurons is a quite important feature of brain functioning. The immune-triggered plasticity and related meta-plasticity are expected to be involved in psychiatric disorders evoked by aberrant immunity, specifically at the stage of neurodevelopment and maturation of brain vasculatures . The funders had no role in the study design, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In 2013, about 60% of the urban sample economic growth and carbon emissions showed signs of tapping into potentials and increasing efficiency (absolute decoupling) and intensive expansion (relative decoupling). In old industrial cities, the proportion of relative decoupling shows a fluctuating upward trend. In the future, the government should accurately select its own development orientation and actively seek the \u201cbest balance\u201d between economic growth and a green and low-carbon path.Based on a literature review and theoretical mechanism, this paper takes the implementation point of the adjustment and transformation policy for old industrial cities as the breakthrough point, and uses a regression model to explore the impact of the adjustment and transformation policy of these old industrial cities on urban carbon emissions. This paper also robustly tests the effective mechanisms and environmental hypotheses. Overall, the implementation of the adjustment and renovation policy has significantly reduced the carbon emissions of old industrial cities by about 0.068 units. Compared with the control group cities, the pilot cities reduced carbon emissions by an average of about 310,000 tons after the implementation of the policy. Based on a summary of the excellent Chinese case experience and an empirical analysis, it can be concluded that improvements in the green innovation capacity of old industrial cities, the agglomeration of high-end service industries, and the strengthening of ecological restoration are important mechanisms that lead to reduced carbon emissions. There is no subsequent exacerbation of the carbon intensity of neighboring cities, and there is insufficient evidence to prove pollution via neighboring transfers and use of the beggar-thy-neighbor policy. The extended analysis shows that the \u201cinverted U-shaped\u201d CO General Secretary Xi Jinping has repeatedly emphasized that China\u2019s carbon dioxide emissions will peak before 2030, and the country will strive to achieve carbon neutrality before 2060. Activities related to industrial production and energy consumption are the main sources of carbon dioxide production. Vigorous promotion of carbon emission reduction in the industrial and energy fields is key to the successful implementation of new environmentally friendly development concepts, and to accelerate the construction of a modern industrial system, which in turn will help achieve carbon peaking, and then carbon neutrality. The old industrial cities have made historical and significant contributions to the formation and improvement of an independent and complete industrial system and national economic system in China, and have been indispensable in the post opening-up reform era, and during the current wave of modernization.The old industrial city, as a basic unit, still faces many difficulties and challenges with the existing institutional mechanisms, policy systems, and governance methods. The past problems remain prominent and cause difficulties for the old industries to adapt to the requirements of the industrial green and low-carbon transformation. Through an in-depth study of the adjustment and transformation of old industrial cities, in the face of today\u2019s good conditions, this paper aims to help accelerate the reform of high-quality economic development and promotion of green and sustainable development of the industrial economy. Promoting regional coordination and complementarity in order to reduce carbon emissions and pollution, are important to the success of building a beautiful, more affluent, healthier society. The policy of adjustment and reconstruction of old industrial bases across the country can be considered a starting point to achieving the environmentally friendly targets. This paper can provide operational, replicable, and scalable experience and practices for the low-carbon development of other industrial cities, and explore new ways for the green and low-carbon transformation of industrial cities across the country.Old industrial cities were once the engines that drove rapid economic development in Europe and the USA. \u201cDe-industrialization\u201d in the developed countries led to a severe recession. Similarly, due to market system changes, or the over-specialization of industries, old industrial cities will become prominent in developing countries, which will cause serious ecological and environmental problems . How to Due to the characteristics of the industrial development cycle, it is harder to achieve green transformation in old industrial cities . They maThe process of urbanization and industrialization in China differs from that of Western countries. The analysis of evolution elasticity theory shows that the economic growth rate and industrial structure of old industrial cities can be differentiated . Based oThe existing literature mainly comprises a factual elaboration and theoretical summary of the old industrial cities, and discusses their implementation path and future direction from the perspective of case analyses. However, less empirical attention has been given to the net impact of the adjustment and comprehensive transformation of old industrial cities on regional green and low-carbon development.(1)Evaluate the low-carbon effects and spatial spillover effects with the adjustment and renovation policies of old industrial cities.(2)Effectively identify the transmission mechanism by which the adjustment and transformation of old industrial cities can help reduce carbon and pollution.(3)Test whether a curve is significantly established in the old industrial city sample based on the Kuznets inverted U-curve theory of carbon dioxide.(4)To analyze the degree of decoupling of old industrial cities.Given this, the possible contributions of this paper are:We give a flow chart of the research framework of the article. The flow chart of the research framework is shown in Achieving carbon peaking and carbon neutrality are necessary to solve the outstanding problems of resource and environmental constraints, and to ensure sustainable development, in turn nurturing China\u2019s lucid waters and lush mountains. China\u2019s \u201cNotice of the State Council on Printing and Distributing the Action Plan for Carbon Peaking Before 2030\u201d identified the need to establish an economic system of green, low-carbon, and circular development by 2025. The Notice also specifies that carbon dioxide emissions per unit of GDP will drop by 18% compared to 2020, and that substantial progress will have been made in the comprehensive green transformation of economic and social development, with carbon dioxide emissions reaching a peak and achieving stable and moderate declines by 2030. The government encourage key fields such as energy, industry, transportation, and construction to formulate special plans for peaking, and promote key industries such as steel, building materials, nonferrous metals, chemicals, petrochemicals, electric power, and coal to put forward clear peaking goals and formulate peaking action plans. By 2060, the goal of carbon neutrality will be successfully achieved, and a green, low-carbon, and cyclical economic system and a clean, low-carbon, safe, and efficient energy system will be fully established, creating a new realm of harmonious coexistence between man and nature.Old industrial cities face dual pressures in the process of carbon reduction due to their own unique realities. The proportion of traditional industries is still relatively high, and it is increasingly difficult to tap the potential of energy conservation. The coal-biased energy structure, inefficient energy utilization, and low utilization of clean energy remain apparent. The lack of advanced technology reserves, the shortcomings of energy-saving and efficiency-enhancing technological innovation, the tight time window for carbon peaking and carbon neutralization, and the arduous task of realizing the green and low-carbon transformation of old industrial cities, are the unwanted features that still dominate old industrial cities.In order to promote energy conservation, emission reduction, and the sustainable development of old industrial cities, the reform plan for renovating these cities should focus on transforming the mode of economic growth and promoting sustainable development. The government focusing on transforming the mode of economic growth and promoting sustainable development, focusing on the new competitive advantage of re-engineering the industry, taking promoting green and low-carbon development, and enhancing innovation support capabilities as an important focus, promote the comprehensive, coordinated, and sustainable development of old industrial bases, building it into an important new low-carbon industrial base for the country and a key growth pole for the high-quality development of the regional economy.By considering the success rate of the measures taken by 94 old industrial cities after the implementation of the adjustment and renovation policy, their transmission path is proposed. Representative cities in the eastern region , central region , and western region were then selected for case analysis.Industrial green innovation. The continuous innovation of urban intelligent green manufacturing technology can help transport an industry to the high end of the value chain, change the existing unsustainable technology and production system, and improve the level of informatization and automation of the manufacturing industry. The government can deepen the degree of coupling between the innovation chain and the industrial chain; increase the transformation of innovation achievements and the research and development, as well as the application of green and low-carbon cutting-edge technologies; accelerate the upgrading of low-carbon products and technologies; and form new manufacturing processes and equipment that are efficient, energy-saving, environmentally friendly, and recyclable, building a green zero-carbon manufacturing system, thereby greatly reducing carbon emission intensity. Industrial technological innovation can broaden the depth and breadth of the development and utilization of renewable clean energy and promote a revolution in energy consumption. Industrial green innovation also reduces excessive dependence on fossil fuels, optimizes energy industry structure and energy use ways, and improves the efficiency of the optimal allocation of energy industrial cities. The government accelerate the conversion of old and new kinetic energy in cities, and continuously overcome key energy-saving technologies in major energy-consuming fields of industry, so as to reduce total carbon emissions from the source .Environment for innovation activities. An environment conducive to innovative scientific research and the construction of innovative service networks plays an increasingly important role in carbon emission reduction. Scientific research includes technological projects in the fields of energy conservation and environmental protection, low-carbon production, and clean energy, and forces and/or motivates enterprises to develop advanced production technology. The people in old industrial cities participate in and popularize the practice of green production and life, actively advocating green, low-carbon, and simple lifestyles in the whole society, and indirectly reduce the scale of carbon emissions .Efficient division of labor. Emerging high-end industrial clusters can reduce production and trade costs through the specialized division of labor and advantageous resource endowments, in turn effectively promoting business exchanges between enterprises. This will help reduce the volatility of demand for green and low-carbon products, deepen the division of labor in the industrial chain, and promote the extension of the industrial chain towards high added value .Element sharing. The agglomeration of high-end industries is conducive to promoting the effective allocation of production factor resources and recycling urban infrastructure. Element sharing helps to reduce the transportation distance, expenditure cost, and time search cost in old industrial cities. Element sharing can improve the government\u2019s treatment and utilization efficiency of pollutants, reduce the decentralized consumption of energy, improve the utilization efficiency of energy and elements, and thus promote the rapid reduction of urban carbon emissions.Spillover effect. The complementary effect of the modern low-carbon industry and its related industries will produce increasing returns to scale, resulting in the multiple effects of urban collaborative innovation, cutting-edge ideas, and spillover enhancement effects. The spillover effect will help to enhance the rooting and cohesion of the low-carbon industry, and increase the communication, interaction, and cooperation between enterprises and other related industries. The diffusion of urban clean technology will accelerate, and upstream and downstream enterprises will be promoted through exchanges and interaction along the industrial chain. In addition, other companies will benefit from the agglomeration of high-end low-carbon industries .2 emissions [Firstly, ecosystem protection and restoration can significantly increase the coverage of natural vegetation, prevent soil erosion and dust storms, increase soil fertility, expand the total amount of forest and grass resources, maintain biodiversity, and effectively improve regional air quality. Ecological governance can change local albedo, turbulent energy, and mitigate natural disaster losses. Ecological governance can promote the enhancement of the carbon sequestration and carbon absorption capacity of forests and wetlands, and effectively reduce the total carbon emissions of cities. Afforestation programs that promote increased terrestrial carbon storage are an important means of helping to gradually reduce atmospheric COmissions .The research on forest carbon sinks of Peking University also shows that for every cubic meter of forest growth, it absorbs about 1.8 tons of carbon dioxide on average, especially in the peak season of tree growth, the forest can absorb 1.6 kg of carbon dioxide per square meter per day. The United Nations Intergovernmental Panel on Climate Change estimates that the global forest carbon storage will exceed 11,000 tons. In order to achieve carbon neutrality, cities require conservation as well as sustainable management to increase carbon sink. Therefore, old industrial cities must formulate policies against deforestation and deforestation, promote scientific research on carbon sinks, actively build forest parks, and promote afforestation activities . ResearcSecondly, the expansion of the regional green area can optimize the urban ecological space pattern, enrich the urban connotation and functional quality, and continue to attract new workers. Profiting from their industrial heritage resources, cities can provide a high-quality creative environment and atmosphere through exhibitions and projects, creating green and low-carbon development ecological places, tourist attractions, and idyllic scenery complexes. Ecosystem protection will help cities fundamentally transform their original industrial structure of high energy consumption, high pollution, and high emission industries, realizing the integrated and diversified development of primary, secondary, and tertiary industries, continuously improving the \u201cgreen content\u201d of emerging industries, and accelerating the realization of low carbonization .DID model. The difference-in-differences method is an important scientific research tool for evaluating the effect of a project or policy implementation. This method can not only exclude unobservable individual heterogeneity among samples, but also account for the influence of unknown factors that change over time. The difference-in-differences method ensures unbiased estimation of policy effects and effectively controls the effect of the interaction between the explained variable and the explanatory variable. Based on the pilot list of old industrial cities, the benchmark regression model is constructed as follows:by Athey is used Panel quantile regression model. The basic idea of this model is to minimize the distance between the dependent variable and the fitted value, which can effectively eliminate the assumption of a normal distribution for the unobserved residuals based on the minimum residual squared and panel model, and better measure the independent variables in the variation trends and distribution shapes at multiple quantiles, which reflect the rich information of all samples.The parameter estimation method of the panel quantile regression model is as follows:Lnco2). Referring to the calculation method of Wu Jianxin [Perco2 and land average carbon emissions Aerco2 are both estimated as dependent variables.Explained variable: total urban carbon emissions . The carbon emission of urban transportation is based on the methods of Zhang Yan [4 kg/TJ (as CO2). The net calorific value of gasoline is 44.3 TJ/Gg, which is 44.3 \u00d7 10\u22126 TJ/kg. The diesel emission factor is 7.41 \u00d7 104 kg/TJ (as CO2). The net calorific value of diesel is 43 TJ/Gg, which is 43 \u00d7 10\u22126 TJ/kg. The emission coefficient of raw coal is 9.46 \u00d7 104 kg/TJ , and the net calorific value is 25.8 TJ/Gg, which is 25.8 \u00d7 10\u22126 TJ/kg. The urban public transportation uses diesel as the main fuel, and the density of diesel is 0.835 kg/L. Taxis use gasoline as fuel, and the density of gasoline is 0.725 kg/L. The urban thermal energy data were not taken into account due to the large area of missing values in the total urban heating supply and heating area.Direct energy carbon emissions are obtained by multiplying the total urban natural gas and LPG supply by the relevant conversion factors provided by IPCC2006. The COhang Yan and Zhaohang Yan . It is aCore explanatory variables. Pergdp), as measured by the ratio of urban real GDP to total urban population. GDP is an important factor affecting CO2 emissions in old industrial cities. With the continuous increase in the total economic volume and output scale, the new emission of pollutants has become prominent, which has brought great pressure on the emission reduction of old industrial cities. Investment level (Oinvest), as expressed by the ratio of the whole society\u2019s fixed asset investment and real GDP. The impact of investment levels on the green and low-carbon development of old industrial cities is uncertain. On the one hand, old industrial cities have increased investment to attract \u201chigh energy consumption, high pollution, high emissions, low added value\u201d enterprises to enter, and constantly reduce the quality of the city\u2019s green development. On the other hand, the increasing investment in environmental protection has provided effective financial support for eliminating the pollution stock and reducing the pollution increment. The government\u2019s efficient environmental protection investment can promote the reduction of the county\u2019s pollution emission intensity. Education scale (Oeduc), which is represented by the ratio of the number of students in regular high schools in the city to the urban population. The scale of education can significantly reduce the scale of carbon emissions in old industrial cities and increase the carbon sequestration of regional vegetation. Education has a reinforcing effect on public environmental protection behavior in old industrial cities. Education carries the universal function of social values and can increase knowledge about ecological and environmental protection. Industrial structure (Upais), as represented by the advanced index of urban industrial structure, that is, Dmarket), as represented by the ratio of the number of private and individual employees in the city to the total number of employees in the city. The improvement of market demand is conducive to the public consciously transforming green concepts into actual consumption actions and building a social action system for low-carbon consumption. To a certain extent, it is conducive to industrial structure adjustment and independent innovation, and guides enterprises to actively adapt to the requirements of green and low-carbon development. Communication facilities (Teleinst), as represented by urban fixed telephone users and mobile users. The rapid increase in the coverage of communication facilities can prompt the public to spontaneously monitor the environmental pollution around living areas, exert high pressure on local governments, and increase the quality and scope of government environmental pollution information disclosure. The multicollinearity test found that the largest covariate VIF was 2.56, 1/VIF was 0.91, and the mean VIF was 1.83. There was no serious multicollinearity problem.Other explanatory variables: Economic development statistical yearbooks over the years. If there was a problem of missing data, the CSMAR database and EPS database were used as alternatives. The descriptive statistics of the variables are shown in By selecting the time series data from 2006 to 2019, the annual change trend in urban carbon emissions in the treatment group and the control group was analyzed before and after the implementation of the policy. According to This paper considers the impact of the adjustment and renovation policies of old industrial cities on regional carbon emissions. The benchmark regression estimation results in Before the implementation of the old industrial city adjustment and renovation policy, the old industrial city exceeded the threshold of the carrying capacity of the social environment through the excessive consumption of energy resources, and substantial investment in related factors of production, which all reduced the stability and service functions of the regional ecosystem. Following policy implementation, the original economic development model of the old industrial city has been gradually broken. The old industrial cities, according to the resource endowment conditions and the main function positioning, anchors the green and low-carbon development plan, leading to deeply adjusting the industrial structure and making every effort to promote industrial energy conservation and emission reduction. The old industrial cities can accelerate industrial innovation and low-carbon construction projects, strengthen the hard constraints of the ecological environment, and promote the elimination of backward and excess production capacity. Old industrial cities actively explore new models of low-carbon industrial development and vigorously develop low-carbon modern service industries. Additionally, old industrial cities are accelerating the continuous reduction of energy consumption per unit of product, strengthening their recycling capacities and comprehensive utilization of resources, and promoting manufacturing and supply of green products. Old industrial cities can strictly abide by the red line of urban ecological protection, increase the carbon sinks in the ecosystem, resolutely curb the blind development of high energy consumption, and optimize the layout of land and space development and protection areas. To sum up, the implementation of the policy can effectively reduce the emission intensity of carbon dioxide pollutants in cities and promote the green and low-carbon development of cities.According to The implementation of the new development concept has enabled old industrial cities to gradually incorporate ecological civilization education into the national education system, which has strengthened innovation capacity building and talent training, incited green and low-carbon social actions, and popularized basic knowledge of carbon peaking and carbon neutrality. With the implementation of the new development concept, old industrial cities have gradually incorporated ecological civilization education into the national education system, strengthened innovation capacity building and talent training, and led to green and low-carbon social actions. People\u2019s consumption habits, ecological awareness, and market demand are constantly changing, resource conservation is increasing, and the degree of public participation is orderly. The coverage network of regional communication infrastructure can significantly enhance public participation in environmental governance, and enhance the environmental protection demands of informal forces. The advancement of communication facilities has significantly improved people\u2019s ideas and ways of thinking and boosted the rapid flow and efficient dissemination of diverse information. The coverage network of regional communication infrastructure can improve the availability of products and services in the region and help enterprises to make optimal production and sales decisions, thereby improving industrial production efficiency and reducing urban carbon emissions. In addition, the extensive way of economic development in old industrial cities negatively increases the pollution of the ecological environment and significantly increases the total regional carbon dioxide emissions. With the continuous increase in the total economic volume and output scale, the lagging industrial structure and the increasing risk of spatial layout, the synergy of the development of modern low-carbon industries needs to be improved, and the pressure of new pollutant emissions is prominent. With the weakening of environmental protection, the overall coordination of ecological protection has increased, and the comprehensive deepening of the reform has not yet formed a system integration effect.According to Overall, at the lower quantiles, the old industrial cities lack protection from mountains, rivers, forests, fields, and lakes, and the ecological space is instead constantly being eroded and occupied. High development intensity comprises the expansion of urban construction land, increased traffic density, continuous population growth, and intensification of the area of natural vegetation. Per capita consumption of energy-intensive products continues to rise, increasing the city\u2019s carbon emission levels. With the continuous increase in quantiles, the old industrial cities should start from improving the overall competitiveness of the region, clarify their own ecological function positioning, and strengthen the dual control of carbon emission intensity and total amount. The old industrial cities can adhere to the combination of industrial transfer and sustainable development, innovate the way and platform for undertaking industrial transfer, and improve the layout management of low-carbon industrial development and the ecological space within the region. Old industrial cities can optimize the carrying capacity of resources and environment, implement integrated protection and restoration, and consolidate the role of ecosystem carbon sequestration, thereby producing a positive green and low-carbon effect. At the highest quantile, the old industrial cities have heavy work tasks to reduce production capacity, adjust their structure, and change their methods, as there are serious historical problems, and the process of industrial transformation, upgrading, and optimization is relatively slow. The land use, energy consumption, water consumption, factor allocation, and pollutant discharge standards undertaken by the industry are relatively weakened, and it is easy to \u201cturn one eye and close one eye\u201d in order to continue to \u201cgive the green light\u201d for pollution-transfer enterprises. Old industrial cities neglecting the quantity and quality of investment promotion will lead to the misallocation of production factor resources and bring about regional ecological and environmental crises.Following the omitted variable test, the replacement variable test , the beAs old industrial cities differ with regards to geographical location, administrative level, social endowment, and regional attributes, the impact of policy implementation on urban carbon emissions will also differ. Therefore, in terms of geographical location, the cities were divided up into the eastern region, central region, and western region; in terms of administrative levels, they were grouped by size as large cities, medium-sized cities, and small cities; in terms of convenience, they were divided into cities with high-speed rail and cities without high-speed rail. The estimated results are shown in Compared with cities in the eastern and western regions, the adjustment and renovation policies of old industrial cities in the central region have not produced significantly positive regional green and low-carbon effects. Due to the complexity and particularity of the old industrial cities in the central region in terms of geographical location and social environment, it is easy to undertake the transfer of polluting industries and increase the level of carbon emissions. Overcapacity and low-efficiency in central cities still plague the process of industrialization reform. Influenced by interestism, the central region government relaxes environmental control and lowers the regional requirements for environmental quality, thereby ignoring ecological and environmental planning and protection in the region.The challenge of ecological environmental protection is thus increasing; hence, there is no evidence of positive pollution and carbon reductions. The old industrial cities in the eastern region actively exert their own resource endowment advantages, strengthen industrial environmental protection awareness and low-carbon concepts, and accelerate their industrial innovation capabilities and the training of high-quality talents. Old industrial cities in the eastern region are strengthening the research, promotion, and application of major low-carbon technologies to overcome the commonalities and key core technologies. In addition, the estimated effect coefficient generated by the implementation of the old industrial city policy in the western region is the largest. The old industrial cities in the western region are striving to promote the green, circular, and low-carbon development of the industry, actively exploring the environmental supervision, regulation mechanism, and innovative transformation path of the industrial wasteland, and steadily promoting the formation of a new model of green, low-carbon, and sustainable development. The western region is generally establishing a resource-saving and environmentally friendly development mode to further strengthen the main functions of the different regions.For large old industrial cities, the implementation of adjustment and renovation policies can have a very significant effect on reducing pollution and carbon in the region. Therefore, large-scale city governments are using \u201ccarbon peaking and carbon neutrality\u201d as the guide, and green and low-carbon industrial clusters as the carrier. In taking this approach, large cities will continue to adjust and optimize the regional layout of industrial productivity, guide a rational and orderly transfer of industries, have efficient and clean agglomeration, improve the coordination and supporting system of the industrial chain, create a circular industrial entity, and improve the level of industrial informatization. Large cities are accelerating the research, development, and promotion of industrial low-carbon technologies, exploring and innovating low-carbon industrial development models, enhancing independent innovation capabilities, improving industrial technology innovation mechanisms, promoting in-depth implementation of industrial green manufacturing, and developing an innovative green economy. Large cities are turning \u201cgreen\u201d in the \u201cbackground\u201d of industrial production, taking the lead in achieving carbon peaks with a more proactive attitude.Compared to old industrial cities without high-speed rail, those with high-speed rail have a significantly \u201cnegative shadow\u201d impact on their urban carbon emissions, which is conducive to reducing carbon levels and pollution, reducing costs, and increasing efficiency in the region. The reason is that the opening of high-speed rail can improve the accessibility level and location advantages of a city. Transportation times and efficiency increase the potential of agglomeration and economies of scale in the central area, and change the spatial distribution pattern of the urban industrial economy. High-speed rail cities continue to effectively promote the optimization of the industrial division of labor, and the complementation of comparative advantages in the region promote the continuous conversion of new and old kinetic energy, thereby greatly reducing the intensity and total amount of carbon emissions.Grinnov). Patents have become a popular way for researchers to measure green and low-carbon innovation. Therefore, with reference to Zhang [Green innovation quality , drawing on the practice of Xuan [Agglomeration of modern industries ( of Xuan to buildEcolores). This indicator is measured by the degree of urban green vegetation coverage [Ecological restoration and reconstruction refers to the fact that with the growth of the regional economy, there is a specific extreme point in the emission of carbon dioxide, which is an \u201cinverted U-shaped\u201d curve relationship that first increases and then decreases.2 environmental Kuznets curve (EKC) in old industrial cities, and the \u201cinverted U-shaped\u201d hypothesis is clearly established. When the cubic term of per capita income is added to the continuous increase in per capita income in old industrial cities, carbon dioxide emissions still show a clear \u201cinverted U-shaped\u201d relationship, which initially increases slowly, and then continuously decreases; the \u201cN-shaped\u201d curve hypothesis does not hold. In reference to the general framework test of Lind [Pgdp is found to be significantly larger than the threshold, and the extreme value point tested is within the range of the sample data. The null hypothesis is rejected at the 10% significance level Overall, the adjustment and renovation policies can produce a positive low-carbon and carbon-reduction effect, with an average reduction of about 0.068 units of carbon emissions. Compared with the average value, the implementation of the policy can reduce the urban carbon emissions by an average of about 310,670 tons. The policy implementation can effectively promote carbon reduction and pollution reduction in the middle quantile. There is no significant evidence that policy implementation leads to the transfer of pollution from old industrial cities to neighboring cities. The phenomenon of \u201cblaming the neighbors\u201d for serious pollution has not occurred, and thus the implementation of the policy can realize low-carbon regional development.(2)The adjustment and renovation policies of old industrial cities have had a distinct and negative effect on pollution reduction and carbon reduction for sample cities in the eastern and western regions, large cities, and cities connected to high-speed rail.(3)On the basis of summarizing excellent Chinese cases and conducting empirical estimates, it is found that after policy implementation, the innovation and improvement of urban green quality, the expansion of high-end industrial agglomeration scale, and the increase in ecological environment reconstruction are important mechanisms to reduce urban carbon emissions.(4)2 EKC in old industrial cities, but the \u201cN-shaped\u201d curve hypothesis does not hold. There are quite a few old industrial cities that have yet to cross the turning point of the EKC.There is a significant \u201cinverted U-shaped\u201d CO(5)During the implementation of the policy, in 2013, about 62% of the old industrial cities showed a state of relative decoupling and absolute decoupling. As the years pass, the trend of an increasing fluctuation of this ratio becomes more prominent, thus reversing the rapid growth of carbon dioxide in old industrial cities.The following conclusions are drawn:Based on the empirical results and conclusion analysis, the following policy recommendations are put forward:First, the city government should rationally design a dynamic path for carbon emission reduction to achieve absolute decoupling between economic growth and carbon emissions. City governments should fully integrate carbon peaking and carbon neutrality goals into medium- and long-term planning for economic and social development, and clarify the goals and outcomes of carbon reduction and carbon reduction tasks. City governments should cross the inflection point of the CKC curve as soon as possible; vigorously support cities with endowment conditions, key industries, and key enterprises to take the lead in peaking carbon emissions; and should not implement campaign-style carbon reduction. The government of the old industrial city should strengthen the top-level system design and promote the participation of diversified subjects, such as the government, society, and public, to realize the linkage of carbon emission reduction from top to bottom.Second, the government should take various measures to achieve green and low-carbon development. The government should strengthen the leadership of cutting-edge innovation in the industrial base, cultivate compound green and low-carbon talents, implement key core technology innovations, cultivate green and low-carbon emerging industries, promote cross-sector and cross-industry collaborative innovation, and accelerate industrial low-carbon transformation and digital transformation. The government should further increase the proportion of renewable energy production and consumption, and provide an important guarantee for the construction of a zero-carbon green energy system. The government should cultivate advantageous high-end industrial clusters; improve the coverage of regional communication infrastructure; strengthen regional division of labor and efficient cooperation; broaden the rational flow of production factors and channels; strengthen the coupling and linkage of green and low-carbon industries; and promote the advanced industrial foundation of industrial cities, the specialization of industrial division of labor, and the modernization of industrial chains. The government should speed up the transformation of the original extensive and high-carbon development mode; strengthen the restoration and management of the geological environment and vegetation coverage; enhance the ability to conserve water sources and soil; and realize the coordination and unity of the economic, ecological, and social benefits of resource development.Third, the government should build a cross-regional environmental coordination mechanism. The government should compile and apply a negative list for environmental access; implement an implementation plan for coordinating joint prevention, joint governance, and comprehensive governance; promote the simultaneous coordination of environmental regulations in adjacent areas; and strengthen the industrial division of labor and complementary advantages. The government should break the administrative level restrictions; build a cross-regional pollution-reduction and carbon-reduction coordination mechanism, and a cooperation platform; and achieve regional high-efficiency and integrated governance. The government should focus on the environmental effects of policy reforms in the central region cities, cities without high-speed rail, small cities, and medium-sized cities."} +{"text": "This evidence synthesis aimed at assessing the effectiveness of Faith-Based Organisations (FBOs) on Maternal and Child Health (MCH) outcomes; and explore the perceptions and experiences of the users and providers of MCH services delivered by FBOs in Africa. This review considered studies from African countries only. Both reviews and primary studies focusing on MCH services provided by FBOs were considered. Quantitative, qualitative, and mixed methods reviews were included with no restriction on the date and language. Primary outcomes included maternal mortality ratio, neonatal mortality, infant mortality, child mortality, quality of care, views, experiences, and perceptions of users of FBOs. We searched up to November 2020 in the Joanna Briggs Institute (JBI) Database of Systematic Reviews and Implementation Reports, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PROSPERO register, PDQ-evidence, Health Systems Evidence, CINAHL, EMBASE, and PubMed. We searched references cited by similar studies that may be potentially eligible for inclusion. We then updated the search for primary studies from December 2009 - October 2020. One systematic review and six primary studies met the eligibility criteria for inclusion. Methodological quality varied. These observational and qualitative studies found that FBOs offered the following MCH services - training of healthcare workers, obstetric services, health promotion, sexual education, immunization services, and intermittent preventive therapy for malaria. Maternal and Child Health (MCH) services provided by FBO suggest a reduction in maternal morbidity and mortality. Increased uptake of maternal healthcare services, and increased satisfaction were reported by users of care. However, costs of providing these services varied across the studies and users. This review shows that FBOs play an important role in improving access and delivery of MCH services and have the potential of strengthening the health system at large. Rigorous research is needed to ascertain the effectiveness of FBO-based interventions in strengthening the health systems in Africa. The Worve visit . To achive visit .et al. [The complex social, political, environmental and economic determinants of health calls on health systems to look beyond the provision of care by a single entity such as the public healthcare services . A privaet al. argue thet al. -10.An FBO is defined as an \u201corganization, with or without non-profit status that provides social services and is either motivated by religious faith or belief or have affiliations with religious groups\u201d . More reA number of published studies on the role and contribution of FBOs on maternal, newborn, and child health (MNCH), HIV/AIDS and other health issues have focused on understanding the different roles of FBOs in healthcare delivery, their reach, costs, and satisfaction from beneficiaries ,12,14. CThe protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD 42020153300 [Criteria used to consider studies for inclusion: we included systematic reviews and primary studies on MCH services provided by FBOs. We considered any level of care and facilities providing either maternal or child services or both by any health provider regardless of cadres. The comparison was of other types of organizations or health care services providers that are not faith-based such as government-owned healthcare facilities and non-governmental organizations. We defined maternal health as the health of women during pregnancy, childbirth, and postpartum (the first 42 days after delivery) [elivery) . Child helivery) . MCH seret al. 2015 [Secondary outcomes included utilization of MCH services, the proportion of live births, percentage of births attended by skilled health personnel, uptake of intermittent preventive treatment (IPT) for malaria, the proportion of HIV pregnant women on prevention of mother to child transmission (PMTCT), immunization coverage, maternal and child morbidity, stunted children, the proportion of children receiving treatment of childhood infectious diseases, like pneumonia, cost-effectiveness, access to care, client\u00b4s satisfaction, quality of care and continuity of care as reported in the studies. Systematic reviews are defined as reviews with the following characteristics as described by Moher al. 2015 : clear dSearch methods for identification of studies: the first search used a comprehensive search strategy to identify systematic reviews. It was developed for PubMed and adapted for other databases, with the assistance of an information specialist (Annex 1). We did not apply any date or language restrictions. The following key words were used with key terms such as 'systematic' or 'meta-analysis' in the title or abstract fields: 'delivery of care/economics', 'organization and administration', 'community health centres', \u2018faith-based organizations', 'faith-inspired interventions', 'hospitals/religious', 'quality of care', 'public-private partnerships', 'SDG3' and 'health services/research', 'faith-based facilities', 'religious programmes\u00b4, \u2018local faith communities', 'humanitarian care', 'faith-based aid'. We searched up to November 2020 in the JBI Database of Systematic Reviews and Implementation Reports, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PROSPERO register, PDQ-evidence, Health Systems Evidence [Annex 1). We searched in the JBI Database of Systematic Reviews and Implementation Reports, CINAHL, EMBASE, and PubMed.Evidence , CurrentSelection of studies, data extraction, and management: two authors (Chinwe Juliana Iwu-Jaja and Jeannine Uwimana Nicol) independently screened titles and abstracts of the records from the first search on CovidenceR software. The records were rated as 'or exclusion', 'for inclusion', or 'potentially eligible' accordingly.The full text of systematic reviews judged as 'for inclusion' or 'potentially eligible' were then assessed against the inclusion criteria independently by the two authors. Disagreements were resolved be through discussions and when consensus was not reached, a third author (Taryn Young) was consulted for arbitration. In the second round of screening to identify recent primary studies (from 2009-2020) five reviewers independently screened titles and abstracts of the records in Covidence. The full text eligibility assessment was independently done by the same four reviewers. Disagreements were resolved through discussions and when consensus was not reached, two of the reviewers (Jeannine Uwimana Nicol and Chinwe Juliana Iwu-Jaja) resolved the conflicts. Data were extracted using a pre-defined form which included key characteristics of included studies such as first author name, year of publication; objectives, number of included studies; countries, characteristics of participants, study type, types of interventions, intervention intensities, setting, and context where the study was conducted, outcome assessed, instruments used to assess outcomes ; comparisons of performed and results. Additionally, extracted data included the phenomenon of interest .Assessment of methodological quality, data analysis, and synthesis: two authors (Chinwe Juliana Iwu-Jaja and Jeannine Uwimana Nicol) independently, and in duplicate, assessed the quality of systematic reviews using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tool [ws) tool , qualitaws) tool . For priws) tool and the ws) tool for qualws) tool and guidResults of the search: a total of 13,810 article citations were identified through both stages of database searching, of which 12,844 were screened for titles and abstracts after de-duplication. These articles were a combination of primary studies and systematic reviews. After titles and abstracts screening, 64 studies (59 primary studies and three systematic review) were considered potentially eligible. We included one systematic review and eight primary studies ( studies .Characteristics of included studies: the systematic review included six primary studies conducted in eight countries in Africa (1987-2007), while the eight additional primary studies were conducted from 2012-2020. The systematic review conducted by Widmer et al. [r et al. assessedr et al. -31; thesr et al. ,29,31-33r et al. and two r et al. ,28. The The FBOs included Baptist Church, Christ Apostolic Church, Presbyterian Church, Catholic Church, Protestant Church, Catholic Church, Muslim organizations, Catholic Medical Services, Uganda Protestant Medical Bureau, Uganda Muslim Medical Bureau, the Christian Health Association of Malawi which includes Malawi Council of Churches and the Episcopal Conference of Malawi, the Kenya Conference of Catholic Bishops, Lutheran Church, and the Seventh-day Adventist Church. The services that were offered by these FBOs covered: capacity building: training of healthcare workers, community health workers, and volunteers in the community such as church/faith leaders, women leaders and others; health education and promotion; immunization services; obstetric and neonatal care services: births, management of neonates related complications, births and managing complications in newborns; sexual reproductive health and antenatal care: family planning services, antenatal care services including HIV testing for pregnant women, caesarian section and vaginal delivery, birth related complication and post-natal care up to 6 weeks after delivery; health education and promotion: hygiene, breastfeeding and immunization, family planning, counseling on family planning and HIV, malaria prevention including IPT, and Education on HIV prevention strategies; other primary health care services such as treatment of minor ailments, home-based care, community outreach programmes, among others; the reproductive services offered include safe motherhood (SMH) which comprise antenatal care (ANC) attendance, caesarian section and vaginal delivery, birth related complication and post-natal care up-to 6 weeks after delivery.The methodological quality of included studies: the methodological quality of the systematic review by Widmer et al. [apriori; there was no duplicate study selection and data extraction; no list of excluded studies; no risk of bias assessment; and no source of funding declared . The key methodological aspects that were not described include the identification of potential confounders and how these confounders were controlled in the analyses. The quality of two qualitative studies [Annex 2). The methodological areas of concern included the lack of reflectivity of the researcher(s) and whether the data reached saturation. Vossius et al. [Annex 3 and Annex 4.Four cross-sectional studies met six of the eight JBI criteria for quality -33 whileet al. met all studies ,28 was fs et al. study coEffects on FBOs on maternal and child health outcomes: the key findings on MCH services provided by FBOs are presented in When comparing government, FBOs, and private health facilities in terms of MCH services frequently rendered in the community, most government and FBO facilities provided obstetric services and prenatal care. The majority of FBOs (88.6%) and the government facilities (98.7%) offered prenatal care. There were higher immunization levels among women and children in the FBO facilities than government facilities offering similar services. Faith-Based Organizations (FBOs) had more supplies of health commodities than government facilities . In addiOne of the included studies in the review assessedA descriptive report includedet al. [From the qualitative studies, Aristide et al. highlighet al. highlighIn this study, we synthesized research evidence on FBOs providing MCH programs including HIV in Africa. The findings provide important insights into the contribution and potential impact of FBOs in the delivery of MCH services in Africa. Improving the utilization of antenatal care services, such as getting more mothers to attend professional healthcare visits while pregnant, is critical to improving maternal and child health . During High cost of health services has been described as a major limitation to accessing care . The cosWomen preferred the services run by the FBOs to those by the government facilities . These wet al. [et al. patient satisfaction is so critical that it has been used to assess the quality of care and health-related outcomes and behaviors [A study by Mwarey et al. conducteet al. . Apart fet al. . Accordiehaviors . These pet al. [One systematic review and six additional primary studies met the inclusion criteria - consisting of cross-sectional, qualitative, economic evaluation and pilot studies. Methodological quality appraisal of these studies raised some concerns such non-reporting confounding factors and how these confounding factors were controlled ; non reporting of the reflexivity of the authors/researchers ; and lack of clarity on incremental costs and only the provider point of view was considered in the economic evaluation. It\u00b4s important to note that the scarcity of reviews and poor methodological quality of the included studies is not an isolated situation for the African continent, but it has been highlighted in other systematic reviews conducted among Latinos and Black Americans ,48 Kagawet al. , in theiWe followed a pre-specified protocol, conducted a comprehensive search, without language restrictions, covering various electronic databases, and we searched for on-going and unpublished systematic reviews. Two reviewers independently applied pre-defined eligibility criteria to select studies for inclusion, extracted data and evaluated the methodological quality of each included study. PRISMA 2020 reporting guidelines were followed . Only obet al. (2004) in their review assessing the effectiveness of FBO based health programs indicate that there is an urgent need for collaboration between FBOs and researchers to facilitate capacity building of FBOs in conducting research and routine health information systems to improve the quality of scientific papers produced. Additionally, Derose and Rodriguez [With regards to policy and public health implications, strengthening health systems in Africa through public private partnerships (PPP) such as FBOs, further research is needed to ascertain the effectiveness and impact of FBO based interventions on MCH outcomes and other global health programs. This will require capacity building of FBOs, partnerships of FBOs and academia/research agencies and increased funding to support a pipeline of evidence generation that will enhance informed decision making and the attainment of SDGs at large in developing countries. DeHaven odriguez argue thFaith-Based Organisations (FBOs) play an important role in health systems strengthening and their presence could contribute to MCH through the reduction in maternal mortality and morbidity, increased uptake of maternal health care services, increased satisfaction by users of care, provision of HIV/AIDS services and an overall improvement in health outcomes. Future research need to carefully consider the questions to be addressed and refine these, based on existing evidence to avoid unnecessary duplication ,50. AdheFunding statement: this systematic review was supported by the funding from Stellenbosch University, Faculty of Medicine and Health Sciences-Early Career Research funding 2018. Award/grant number is not applicable. The funder did not have any role in the review process.There is high burden of maternal deaths in the African region which is common amongst the poorest and most disadvantaged population groups;Faith based organizations (FBOs) deliver between 30-70% of health services in low- and middle-income countries in Africa, including maternal and child health services;The role of the FBOs and their impact on maternal health outcomes in Africa need to be clearly understood.Faith-Based Organisations (FBOs) play an important role in improving access and delivery of maternal and child health care services;Experiences of participants using services provided by FBO are variable;Further research is needed to ascertain the effectiveness of FBO-based interventions in improving maternal and child health outcomes and ultimately strengthening health systems in Africa."} +{"text": "Dear Editor,A seven-month-old female patient presented with a history of a congenital, violaceous, fast-growing lesion located on the right plantar surface. Dermatological examination disclosed the presence of a firm spherical tumor, with dilated vessels on the surface, and central ulceration with friable, bleeding tissue, and hematic crusts A. The chMagnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) disclosed a well-vascularized solid mass, with the involvement of the underlying muscles and extending to the anterior aspect of the foot. Diffuse contrast enhancement was observed throughout the lesion, with no signs of arteriovenous shunts or a cluster of tortuous vessels (nidus), thus ruling out the diagnosis of a vascular tumor, including kaposiform hemangioendothelioma A and 2B.The patient was submitted to neoadjuvant chemotherapy to reduce tumor size C, followCIF is a rare malignant tumor of childhood; however, it is the most common soft tissue sarcoma in children under one year of age.Fibrosarcomas are malignant neoplasias composed of mesenchymal fibroblasts. The infantile variant shares histopathological characteristics with adult fibrosarcoma but has a better prognosis. Although local recurrences are common, the rate of CIF metastasis is less than 10% and the ten-year survival rate is up to 90%.5The histopathological findings of CIF include the proliferation of dense fusiform cells and vascularized areas. Immunohistochemistry is positive for vimentin and, in some cases, for desmin, smooth muscle actin, and cytokeratin.5The diagnosis of CIF should always be considered in the presence of a congenital, spherical, bleeding extremity tumor in children, aiming to avoid treatment delays.None declared.Luciana Baptista Pereira: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript; approval of the final version of the manuscript.Jo\u00e3o Renato Vianna Gontijo: Critical review of the manuscript; drafting and editing of the manuscript; approval of the final version of the manuscript.Marcelo de Mattos Garcia: Critical review of the manuscript; drafting and editing of the manuscript; approval of the final version of the manuscript.Karine Corr\u00eaa Fonseca: Critical review of the manuscript; drafting and editing of the manuscript; approval of the final version of the manuscript.None declared."} +{"text": "The approach to evaluating the effectiveness of psychosocial rehabilitation (PSR) of mentally ill patients implies a multidimensional, hierarchical consideration of mental pathology with the inclusion of clinical and psychopathological, socio-environmental and personal indicators when setting goals and objectives of PSRDevelopment of algorithms and models for evaluating the effectiveness of PSR taking into account: clinical, socio-demographic, psychological characteristics of the patient and the characteristics of the family environment, as well as factors of psychiatric care.Clinical, statistical, algorithms of the analytical hierarchy process (AHP) [1].Numerical estimates of changes (before and after the PSR program) in the main areas of patient\u2019s functioning disorders, such as motivation, cognition, compliance, coping strategies, family, skills, immediate environment, and others, are proposed as particular criteria for evaluating the effectiveness of PSR. Quantitative estimates for particular criteria are obtained on the basis of rank estimates, which are converted into numerical ones based on AHP algorithms [1]. Quantitative integral estimates of the effectiveness of PSR are obtained on the basis of partial estimates, taking into account the weight of the corresponding areas of impaired functioning of patients.S.S. Korsakov Journal of Neurology and Psychiatry. 2019; 119(2): 49-54The developed approach opens up prospects for obtaining numerical, partial and integral estimates based on various rank scales, which are of interest from the point of view of forming criteria-indicators (markers) of the effectiveness of psychosocial, rehabilitation, psychoeducational and psychotherapeutic measures. References: 1. Mitikhin, V.G., Solokhina, T.A. No significant relationships."} +{"text": "A 73-year-old male patient developed a poorly differentiated squamous cell carcinoma in the anal canal nine months ago. He was treated with two cycles of 5-fluorouracil and cisplatin and concomitant radiotherapy , with complete remission. Since forty-five days he presentes a painful perianal and intergluteal erosion with circinate pustular borders. Light microscopy showed pseudoepitheliomatous hyperplasia of the epidermis with microabscesses of inflammatory cells (neutrophils and eosinophils) and acantholytic keratinocytes . Indirect immunofluorescence was positive for IgG, with an intercellular pattern, 1:80 titer. The diagnosis of radiotherapy-induced pemphigus vegetans was established and there was significant regression with oral prednisone (40 mg) and topical betamethasone. A 73-year-old male patient developed a vegetating lesion in the anal canal nine months ago; the histopathology showed a non-keratinizing poorly differentiated squamous cell carcinoma. He was treated with two cycles of 5-fluorouracil and cisplatin and concomitant radiotherapy , with complete remission. The control colonoscopy and endoscopy after six months of treatment were normal. Forty-five days before coming to the clinic again, he had a painful perianal and intergluteal erosion with circinate pustular borders and some isolated pustules, with surrounding erythema . He was a)Ulcerated herpes simplex associated with immunosuppressionb)Ulcerated radiodermatitisc)Pemphigus vegetansd)Tinea associated with immunosuppressionThe histopathological findings were suggestive of pemphigus vegetans, which may present with acantholytic clefts associated with polymorphonuclear microabscesses,There was no therapeutic response to systemic antibiotics and antivirals initiated before the results of the investigation, and there was significant regression with oral prednisone (40\u2009mg) and topical betamethasone. After seven days, the pustular border disappeared, and there was total symptom regression, with the appearance of some hyperkeratotic and verrucous central areas . Later, There are several reports of radiotherapy-induced pemphigus vulgaris, but not of the vegetans variant. Reported cases are restricted to the irradiated area,The mechanism of induction of autoimmune acantholytic diseases by radiotherapy must be complex. One possibility is the antigenic alteration by radiation;This case demonstrates the possibility that pemphigus vegetans lesions may occur locally on a previously irradiated area.None declared.Hiram Larangeira de Almeida Jr.: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Ant\u00f4nia Larangeira de Almeida: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Pedro Henrique Evangelista Martinez: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Ana Let\u00edcia Boff: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Trypanosoma brucei. Despite important advances in the reduction or disappearance of HAT cases, AAT represents a risky reservoir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.Human African Trypanosomiasis and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei (T. b.) gambiense, present in Western and Central African countries, and the zoonotic T. b. rhodesiense, found in over 13 countries of Eastern and Southern Africa regions , with implications for both livestock and wildlife, and Human African Trypanosomiasis (HAT), also known as \u201csleeping sickness\u201d. HAT is caused by the etiological agent regions . AAT is Glossina sp.) in tsetse-inhabited areas. On the other hand, socio-economic instability, and geopolitical disputes compromise the fragile disease surveillance systems , , and the disubstituted compound . Isomethamidium can bind the kDNA with high affinity with an unconventional sideways geometry. The drug is preferentially accumulated in the mitochondrion (gamma-subunit of ATPase). Mutation of the ATP synthase subunit is sufficient to cause a substantial level of resistance. It is mainly prescribed to treat early infections caused by oma spp. . It is aoma spp. . It is poma spp. . IsometaT. b. evansi in camels and horses . Po. PoT. b.st T. b. . This wo and NMT . An addi and NMT . The mos and NMT profile, and very good selectivity [3 was able to cure the 60% of mice in a systemic model of HAT, and it can successfully cross the BBB. However, it was unable to clear parasitemia in a CNS model of the disease. Following the same approach, diaminopurines were also identified as compounds with antitrypanosomal activity. Optimization of hit-compounds led to a new promising entity with improved absorption, distribution, metabolism and excretion (ADME) properties and the efforts of international partners to engage other ministries and the community in the implementation of control strategies. The success of this strategy is largely attributed to the engagement of stakeholders and strategies including the use of insecticides to treat cattle as live bait for tsetse, therefore breaking the transmission of trypanosomes to both humans and animals [T. b. gambiense is still a problem [An effective and sustainable control of African Trypanosomiasis will be directly reflected on agricultural development and veterinary and public health, therefore contributing to poverty alleviation and population wellbeing. Animal health, public health, and economic needs sustain the urge to control Trypanosomiasis in sub-Saharan Africa. Since treatment of AAT reduces the animal reservoirs of zoonotic vector-borne programs . As a cldesiense . Controld to HAT . The ina animals . This fi problem .Trypanosoma spp. between animals and humans must be carefully monitored [Resistance to trypanocidals is becoming common, cross-resistance between classes has been identified, and resistant trypanosomes may pass from animals to humans. Since human\u2013animal proximity increases the risk of spill over and crossing species barriers, the interchange of onitored . Part ofTrypanosome species, for which the underlying mechanisms are yet to be discovered. Genetic combinations among different breeds and the introduction of trypanotolerant phenotypes may result in a balance between productivity and resistance to Trypanosomiasis, leading to a sustainable production and economical benefit [Trypanosoma spp. life cycle must prioritize collaboration and coordination of efforts at national, provincial, and district levels to integrate human health and veterinary and agricultural sectors together with wildlife and natural resources advocates, epidemiologists, policy makers, researchers, the pharmaceutical industry, and all those involved in epidemic preparedness. A framework must be designed in order to achieve: (i) depletion of parasite reservoirs through active case detection and treatment of the infected humans and domestic animals; (ii) ensure the best available treatment is employed and is adequate for the disease stage; (iii) reduction in the tsetse fly population and human and animal contact with tsetse flies by protecting population health vulnerabilities; (iv) reduction in human\u2013wildlife and livestock\u2013wildlife contact; (v) detection of both human and animal cases; (vi) development of effective communication strategies between all intervenors and implementation of guidelines and training opportunities for health workers; (vii) translation of research findings to solutions in order to support the development of new safer drugs for HAT and AAT prevention, more advanced treatments, and field-friendly techniques for an early diagnosis [Regarding vector control measures, both chemical and biological interventions and genetic control of these flies (releasing sterile insects into the wild) have been attempted. The interventions did not give effective results, and caused severe environmental consequences, besides the selection of insecticide-resistant tsetse flies . At the benefit . From thiagnosis ; and an effective surveillance of infection among wildlife, domestic animals, and humans; (ii) implementation of a vector surveillance system and control measures; (iii) implementation of an effective system for disease notification in both animals and humans; (iv) implementation of effective, sensitive, and fast diagnostic tools applicable to field conditions; (v) creation of an effective network linking communication between stakeholders, medical and veterinary departments, and government and policy makers; and, finally, investment in the development of safer and more easily available HAT and AAT therapies and prophylactics. Cooperation among different actors will make this approach feasible and sustainable."} +{"text": "The aforementioned educational event together with the 5th Teaching Course on Rare Neurological Diseases brought together a lively audience of over 1400 participants in a hybrid format, both online and on-site.The first day of the Summer School included presentations on the latest and most exciting or pressing issues in Neurology.The event started with a welcome address by Dafin Muresanu (Romania), Natan Bornstein (Israel), Volker Homberg (Germany), and Wolfgang Grisold (Austria).Wolfgang Grisold held a short presentation on the World Federation of Neurology (WFN) institution and activities. The World Federation of Neurology encompasses 6 regions and 123 member societies worldwide. As the World Health Organization approved the Global Action Plan to address epilepsy and other neurological disorders, the 10 years intersectoral action plan of the WFN was addressed, which is set to target:Followingly, Policy;Diagnosis and treatment;The implementation of strategies for promotion and prevention;Fostering research and innovation;Strengthening of public health approaches.The WFN activities include communication with regional and member societies, increasing the impact of international cooperation, education programs, development of publications, and international adaptation.Volker Homberg (Germany) and Dafin Muresanu (Romania) introduced the first session and covered topics such as neurorehabilitation, post-stroke deficits and post-stroke recovery.Volker Homberg (Germany), President-Elect of the World Federation of Neurorehabilitation (WFNR), presented a future perspective for neurorehabilitation, also highlighting the pillars of WFNR, namely (1) improvement of science, (2) improvement of services, and (3) improvement of education in neurorehabilitation. In the context of the global situation, where over 1 billion people live with some form of disability (and the number is increasing), prof. Homberg highlighted the differences in the availability of trained staff among different income countries and discussed high-tech and low-tech options for neurorehabilitation. Prof. Homberg pinpointed the strategies for neurological rehabilitation (restoration vs. compensation): replacement of dead tissue, \u201cwake up\u201d alternative structures, teaching bypass strategies, replacing functions by aiding devices, and adapting the environment to patients. He presented exciting avenues of technology for rehabilitation, such as rehabilitation robots, VR/AR technology, and brain-computer interfaces, putting an emphasis on the role of motivation in neurorehabilitation and the prospect of serious games, which can have a decisive role in therapeutic strategies. In contrast, the importance of more available low-tech options and the role of enriched environments were also marked, and the limitations and opportunities for both high-tech and low-tech undertakings were discussed. Pharmacological options for recovery and the latest achievements in neurorehabilitation were also addressed.Dafin Muresanu (Romania), Chairman at the Department of Neurosciences, Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca (Romania), presented advances and updates in neurorecovery after stroke, pinpointing the need for better evidence-based approaches in stroke, supported by the following 3 pillars:Theory and basic research;Evidence-based parameters;External validity.According to Prof. Muresanu, the whole science and practice of neurorecovery are based on the pillars above. The burden of neurological disorders in Europe was also discussed, with stroke being a significant component of the disease burden. Prof. Muresanu showcased the AHA/ASA guidelines, the role and advantages of the GRADE system, as well as the similarities with EAN guidelines. The role of multimodal agents in contrast to neuroprotectants for neurorehabilitation was also approached.Michel Brainin (Austria), Emeritus Professor of Neurology and Chair at the Department of Clinical Neurosciences and Preventive Medicine of Danube University in Krems (Austria), centered on cognitive deficits after stroke. Prof. Brainin's first message was that the most common manifestation of vascular diseases is not reflected in stroke but in cognitive impairment and dementia. Furthermore, he took a more focused glance at vascular cognitive impairment and what cognitive domains it affects. He discussed the risk and protective factors for dementia and stroke, presenting a case study. He also approached several topics, such as small vessel disease, strategic infarct, preexisting vascular damage, and preexisting Alzheimer's disease.The last presentation of the session was held by The second session was introduced and coordinated by Michael Brainin (Austria) and Natan Bornstein (Israel).Wolfgang Grisold (Austria), President of WFN, who discussed the educational activities of the World Federation of Neurology (WFN). Prof. Grisold discussed the IGAP , which centers around developing education training, structures for training, making research attractive, and promoting a public health perspective. He then presented the mission and current WFN educational activities, including accredited training centers, department visit programs, junior travelling fellowships, WFN grants, eLearningHub, and Young Neurologist programs.The first to present was Johannes Vester (Germany), Head of Biometry & Clinical Research at the Institute for Data Analysis and Study Planning (IDV) in Gauting (Germany) then presented \u201cA new gold standard to improve TBI clinical research \u2013 the multidimensional approach\u201d. The gaps in traditional trial designs and the need for multidimensional approaches were highlighted to capture the global status of TBI patients as accurately and comprehensively as possible. He outlined current approaches and different scales used in research, pinpointing the more accurate picture of outcomes that the multidimensional analysis offers in contrast to the often employed one-criterion paradigm, which has been the standard in the research of neuroprotective treatments over the past decade. To support his point, he discussed the meta-analysis of the CAPTAIN trials, trials based on multidimensional approaches.David Vodusek (Slovenia), Emeritus Professor of Neurology at the Faculty of Medicine from the University of Ljubljana (Slovenia), presented \u201cNeurological and neurophysiological evaluation of the lower sacral segments\u201d. Prof. Vodusek discussed steps in the diagnostics, the difficulty of assessing lesions affecting the peripheral nervous system in contrast to central nervous system (CNS) evaluation, methods, the testing of the motor function along with some issues in reflex testing, diagnosis of neurological lesions in sacral segments through different tools (including electromyography) and many other inspiring subjects.rd session of the day was introduced by Antonio Federico and Tudor Lupescu (Romania), addressing neuropathies and neurosciences in migrant populations.The 3Antonio Federico , Emeritus Professor of Neurology at the Department of Medicine, Surgery and Neurosciences from the University of Siena in Siena firstly discussed aspects of neurology and neurosciences in migrants and refugees, describing the global situation and the effects of immigration, both positive and negative, and pinpointed the phenomenon of \u201cbrain drain\u201d \u2013 the migration of highly educated individuals- in certain territories. Furthermore, Prof. Federico outlined the relationship between refugee status and migration with the health system and the aspects which link migration and neurosciences . He discussed the specific brain diseases in immigrants and refugees, showcased the influence of migration on brain development, and outlined some protective factors encountered in migrants which mediate cognitive disturbances. Finally, the needs and limitations of approaching the neurological health of migrants and the impact of migration on children were also topics touched upon.Max Hilz (Germany), from the Icahn School of Medicine at Mount Sinai, New York (USA) and University Erlangen-Nuremberg (Germany) offered an insightful presentation on \u201cDiabetic autonomic neuropathy\u201d, discussing the complications of diabetes and the relationship of diabetes with neuropathies, highlighting the importance of making an early diagnosis to prevent fatal outcomes. In addition, he discussed the fluctuation of heart rate and blood pressure with age, how to diagnose cardiac diabetic neuropathy and offered recommendations for assessment and diagnostic criteria.Tudor Lupescu (Romania), the Head of the Neurology Department from Agrippa Ionescu Hospital in Bucharest (Romania), presented diagnostic approaches to neuropathies. Differential diagnostics, profiling, timing assessment, types of neuropathies and their symptoms were the topics covered and presented in an inspiring case study.th session was introduced by Marc Fisher (USA) and Urs Fischer (Switzerland).The 4Marc Fisher (USA), Professor of Neurology at Harvard Medical School (USA) showcased his presentation \u201cRepurposing neuroprotection (Cyto) and recovery enhancing drugs in the thrombectomy era\u201d, where he discussed the ischemic penumbra as the target of acute stroke therapy, the relevance of combining cytoprotection with reperfusion, and the need for multi-targeted interventions, as well as the factors for multi-targeted approach. Decompressive surgery was also addressed as a topic. Further on, Urs Fischer (Switzerland), the Chairman of the Department of Neurology at the University Hospital in Basel (Switzerland) presented the \u201cManagement of spontaneous intracerebral haemorrhage\u201d. Prof. Fischer underlined the need for more recent evidence-based guidance in the global burden of stroke, discussed therapeutic approaches and the importance of lowering blood pressure, and showcased international randomized control trials, presenting their outcomes.Natan Bornstein (Israel), Professor of Neurology at Tel-Aviv University, Sackler Faculty of Medicine (Israel) discussed \u201cDiabetes and Stroke\u201d. One hundred years after the discovery of insulin, his insightful presentation began with a mention of diabetes as the leading risk factor for stroke and a short reminder of the increasing global burden of stroke (12/2 million new stroke cases per year with a significant proportion of DALYs). It repeatedly highlighted the critical role of primary and tertiary prevention for stroke. Type 2 diabetes will increase the risk of stroke and double the risk of stroke occurrence, stroke outcomes being significantly worse in patients with diabetes. Prof. Bornstein highlighted that diabetic patients have a risk of stroke similar to people without diabetes who are 25 years younger. Furthermore, Prof. Bornstein discussed the role of gut hormones and incretin-based therapies, presenting randomized control studies, and presented the role of new therapies that demonstrated protective effects in patients with type 2 diabetes and higher risk of cardiovascular complications or with established cardiovascular disease (SGLT 2 inhibitors: GLP \u2013 1 RAs). Moreover, he talked about the importance of neurologists in managing patients with type-2 diabetes mellitus, controlling diabetes and other risk factors to prevent initial stroke and stroke occurrence, and the importance of preventing atherosclerosis both for stroke and dementia prevention. He mentioned that controlling risk factors through medication and lifestyle modification can reduce the risk of stroke by 90%. Following his presentation, Laszlo Csiba (Hungary), Professor of the Department of Neurology at the Debrecen University in Debrecen (Hungary) discussed interesting cases from daily practice.th International Summer School of Neurology, the \u201cPsychiatry Perspectives in Neurocognitive Disorders\u201d parallel session, and the 5th Teaching Course on Rare Neurological Diseases will be highlighted in future materials.Other information and further details on the 17"} +{"text": "Under circumstances of pervasive global aging combined with weakened traditional family elder care, an incremental demand for institutional elder care is generated. This has led to a surge in research regarding institutional elder care. Rural residents\u2019 institutional elder care is receiving more attention as a major theme in social sciences and humanities research. Based on 94 articles related to rural institutional elder care, this study identified the most influential articles, journals and countries in rural institutional elder care research since 1995. This was done using science mapping methods through a three-step workflow consisting of bibliometric retrieval, scoping analysis and qualitative discussion. Keywords revealed five research mainstreams in this field: (1) the cognition and mental state of aged populations, (2) the nursing quality and service supply of aged care institutions, (3) the aged care management systems\u2019 establishment and improvements, (4) the risk factors of admission and discharge of aged care institutions, and (5) deathbed matters regarding the aged population. A qualitative discussion is also provided for 39 urban and rural comparative research papers and 55 pure rural research papers, summarizing the current research progress status regarding institutional elder care systems in rural areas. Gaps within existing research are also identified to indicate future research trends , which provides a multi-disciplinary guide for future research. The rapidly aging population combined with the weakening of traditional family aged care support ,2,3,4 haThe contribution of this study to the research field of rural institutional elder care is as follows: (1) The selection method of the literature samples covered in this paper is relatively comprehensive, and the high-frequency keywords related to rural institutional elder care extracted from the literature samples can reflect current research topics; (2) This paper presents high-impact articles, journals, countries, and authors related to rural institutional elder care; (3) This research explores the research evolution in the field of rural institutional elder care by using a scoping analysis method, and discusses the gaps within existing research, to identify future research topics. It should be noted that this review is a summary of the global research on rural institutional elder care, and in order to ensure the comprehensiveness of the review, it is not based on any country\u2019s definition standard of \u201crural\u201d and \u201curban\u201d. The division of \u201crural\u201d and \u201curban\u201d in this review follows the division criteria in the original literature samples. In other words, this review distinguishes between \u201crural\u201d and \u201curban\u201d based on the results of the search formula TS = and the specific content of the literature sample. Meanwhile, among the 94 literature samples, 39 comparative studies of urban and rural institutional elder care were retained, assuring enough relevant rural sample for conclusions.The remainder of this paper is organized as follows. The following section describes the overall research methods of science mapping and qualitative discussion. The third section shows the visualized scientific atlas and the results of the scoping analysis. The fourth section expands on the above analysis results and discusses the research gaps and trends in this field. The final section summarizes current research as identified and described in this review.Introduced by Pritchard , bibliomPain deterioration within 1 year predicts future decline of walking ability: A 7-year prospective observational study of elderly female patients with knee osteoarthritis living in a rural district; Multidrug-resistant organism infections in US nursing homes: A national study of prevalence, onset, and transmission across care settings and 1 October 2010\u201331 December 2011, Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in patients in long-term care in hospitals, rehabilitation centers and nursing homes of a rural district in Germany [Telerehabilitation for older people using off-the-shelf applications: Acceptability and feasibility and Assessing end-of-life preferences for advanced dementia in rural patients using an educational video: A randomized controlled trial [The Web of Science combines a traditional citation index with advanced Web technology and multiple and unique functions that accurately retrieve targeted literature. Moreover, it contains comprehensive literature information . As such Germany ; Other eed trial ,14. FurtVOSviewer, a text-mining tool developed by Van Eck and Waltman , was adoQualitative discussion is the final step required following a bibliometric search and scoping analysis. Qualitative research is always helpful to provide readers with more in-depth and useful insights ,19. An iGenerally speaking, scholars pay limited attention to rural institutional elder care. From This study systematically analyzes the source journals of 94 research articles on rural institutional elder care. The results are shown in Journal of Rural Health is found with the highest literature output, followed by Journal of the American Geriatrics Society, with both the second highest literature output and average citation times. From the perspective of average normalized citation, journals such as Collegian and JAMA Network Open are rated with the highest annual average influence.In The minimum number of documents of an author and the minimum number of citations of an author set in VOSviewer are 2 and 15, respectively. Of the total 357 authors in the literature sample, 22 met the selection criteria. Literature influence was assessed using Norm. Citations. As shown in Chinese researchers indicated by the red clusters in the co-authorship map contributed the highest value of Norm. These citations focused on exploring the relationship between social support and mental health and health-related quality of life in rural nursing homes in China and the gender differences in institutional care choices. For example, Zhang, et al. construcThis study identified those countries active in rural institutional elder care research, with the United States, Australia, and China standing out. Using VOSviewer, these countries\u2019 contribution to rural institutional elder care research is identified and evaluated. When drawing the map of countries conducting research in rural institutional elder care research, the minimum number of documents of a country and the minimum number of citations of a country were both set to 1. Finally, 23 out of 25 countries met the conditions. Keywords spotlight the main topic content of studies and depict the themes that have been focused on within a given domain . A netwoBased on the connection strength between keywords, VOSviewer divides 35 keywords into five clusters with different colors for distinction: red, green, blue, purple, and yellow see . It can Of the 94 identified research studies on rural institutional elder care, 39 offer relevant research conclusions based on comparative analyses between urban and rural institutional elder care, while the remaining 55 provide a more in-depth investigation specific to rural institutional elder care. According to the five mainstream research topics presented in the map of co-occurrence of keywords, studies on rural institutional elder care are classified.When exploring the present situation of institutional elder care in rural areas from urban\u2013rural comparative studies, a series of similarities and differences between rural and urban institutional elder care are identified. To provide clarity for readers, the primary trend of urban\u2013rural comparative studies is also discussed individually from the five research mainstreams identified from the keyword analysis, including (1) the cognition and mental state of the aged population, (2) the nursing quality and service supply of aged care institutions, (3) aged care management systems\u2019 establishment and improvement, (4) the risk factors of admission and discharge of aged care institutions, and (5) healthy institutional elder care and deathbed matters of the aged population.In the comparative studies of rural and urban institutional elder care on the cognition and mental state of the aged population, the happiness, satisfaction, depression, and cognitive level of residents and related personnel in rural old-age care institutions are the main research objects. Generally speaking, the happiness of the elderly in rural old-age care institutions is lower than that found in urban old-age care institutions . The satIn the meantime, from the comparative studies of rural and urban institutional elder care on the nursing quality and service supply of aged care institutions, it is generally believed that the level of nursing quality and service supply in old-age care institutions in urban areas is higher than in rural areas . This faLikewise, for rural and urban institutional elder care comparison concerning the elderly care management systems\u2019 establishment and improvement, the main research focus lies in the characteristics and recruitment paths of certified nursing assistants. Although both the staff of nursing homes in urban and rural areas rely heavily on relatives and friends in order to obtain recruitment opportunities, rural nursing staff are more likely to receive training in nursing institutions than those in urban nursing homes that might be trained by community colleges or websites .Furthermore, the differences between admission and discharge status of urban and rural residents and the exploration of related influencing factors remain a main focus. In the research on the status quo of admission to nursing homes, in general, the rural elderly tend to care for nursing homes better than the urban elderly ,62,63,64In the comparative studies of rural and urban institutional elder care on the healthy institutional elder care and deathbed matters of the aged population. There are two main emphases, one health and disease, and the other end-of-life decisions and care. In addition, in the contrastive research of health and diseases of the elderly between urban and rural institutional elder care, on the one hand, the significant regional differences in the level and quality of health services of residents in nursing homes between urban and rural areas are confirmed across many quality indicators . On the Studies on rural institutional elder care are more specific in scope than comparative studies. Certain characteristics unique to the rural setting can be found. To provide readers with structured and systematic insights, the discussion is also unfolded from the five research mainstreams identified from the keyword analysis, namely (1) the cognition and mental state of the aged population, (2) the nursing quality and service supply of aged care institutions, (3) the aged care management systems\u2019 establishment and improvement, (4) the risk factors of admission and discharge of aged care institutions, and (5) the healthy institutional elder care and deathbed matters of the aged population.In rural institutional elder care studies on the cognition and mental state of the aged population, scholars have described the cognition and mental state of rural institutional elder care-related groups, such as residents, family members and staff ,79,80. FFor the nursing quality and service supply of aged care institutions, the influence of facilities and service conditions of rural nursing homes on the quality of life, physical health, mental health, and social relations of the elderly has been confirmed . For theFor the rural aged care management systems\u2019 establishment and improvement, research topics can be roughly divided into two streams, staff management and institution management. In terms of staff management, there are a range of problems leading to the ineffective implementation of management systems. Some of these shortcomings are as follows: inadequate consideration of family members\u2019 opinions by management and staff , lack ofIn studies of rural institutional elder care on the risk factors of admission and discharge of aged care institutions, related factor analysis has always been a research priority. A high social capital level influences family members\u2019 familiarity with nursing homes in rural communities . In turnRegarding healthy rural institutional elder care and deathbed matters regarding the aged population, two main themes are identified: health and disease and end-of-life decision and care. In the field of health and diseases, the main concerns are adverse drug reactions in old-age care institutions , microbiAlthough the number of published research studies on institutional elder care in rural areas is relatively small, significant research gaps can be summarized by analyzing the existing literature to inform related stakeholders of future research directions. Based on the discussion of mainstream research topics and gaps, the framework of near-future directions in rural nursing homes is proposed and shown in Nowadays, comparative studies between urban and rural institutional elder care are an evident priority, where differences between urban and rural depressed and demented elderly are among the most commonly adopted research themes ,78,116. Compared with urban institutional elder care, the resource allocation of rural institutional elder care shows great room for improvement. Thus, scientific and rational resource allocation is needed for rural institutional elder care. Future research on staffing and capital investment is recommended. Furthermore, the rural institutional elder care system should be standardized, so that the innovation research of rural institutional elder care models is required for accumulation. In recent years, intelligent nursing homes , telemedThe essence of the nursing home is an institution, and its management mode is the core. According to the present research situation, the management mode of rural nursing homes is backward, so further research on management mode innovation is needed to promote the development of rural elder care.Descriptive and empirical research on influence factors of the admission and discharge of nursing homes pave the way for countermeasure research. The significance of countermeasure research lies in the accumulation of policy planning. With a global trend of an aging population, many countries have attached great importance to planning and developing old-age care policies , suggestOverall, the health level, illness condition, and end-of-life status of the elderly in rural old-age care institutions are worse than those in urban old-age care institutions. Furthermore, the improvement of healthy institutional elder care and end-of-life status is called for by society.Journal of Rural Health, Journal of the American Geriatrics Society, Collegian and JAMA Network Open. (2) Keywords are determined by co-occurrence keyword analysis, and the mainstream research keywords of institutional elder care in rural areas can be classified into five aspects: the cognition and mental state of the aged population; the nursing quality and service supply of aged care institutions; aged care management systems; risk factors of admission and discharge of aged care institutions, and healthy institutional elder care and deathbed matters of the aged population. (3) Co-authorship analysis reflects the most frequently cited articles from Yang et al. who have the highest Norm. Citations, with their work mainly exploring the relationship between social support and mental health, and health-related quality of life in rural nursing homes in China, as well as the gender differences in institutional care choices. (4) The countries active in carrying out research on rural institutional elder care include the United States, Australia, and China, significantly contributing to this research field.This study of rural institutional elder care follows a bibliometric research paradigm, employing scoping and qualitative analysis to find the current research scope and future directions. A total of 94 related articles are selected as samples for analysis with results listed as follows: (1) The influential journals that publish papers on rural institutional elder care include According to the outcomes of scoping analysis, this study further identifies gaps within this research field. Consequently, a systematic framework for further research is proposed: (1) There are only a few multi-dimensional comparative studies, and in the future, more attention should be paid to rural institutional elder care comparisons between developed countries and developing countries, comparison of various indicators of institutional old-age care in urban and rural areas, and comparison between ordinary old-age groups and special old-age groups; (2) Compared with urban institutional elder care systems, rural institutional elder care models and technology have greater room for improvement, and both the market and the government should actively encourage innovative research on rural institutional elder care; (3) Studies on urban institutional elder care have offered many notable recommendations, but those addressing rural areas and their circumstances are limited, and the sustainable development of rural institutional elder care model remains absent. In order to identify developmental pathways and provide practical policy recommendations, further efforts to upgrade and revitalize rural institutional elder care are needed.This study focuses on the research progress of rural institutional elder care, with the research results limited by the scope of the research literature samples but not specifically listed and selected the definition of urban and rural research. Furthermore, this research sample is derived from Web of Science Core Collection only, which may limit the scope of the review. In defining the literature sample, the completeness is constrained by the keyword indicators on which the sample selection is predicated so future research could expand the search query. Moreover, only journal papers were selected, excluding minutes, letters, etc., which ordinarily offers limited insight, but this remains an assumption. This study only contains English literature, and does not analyze the research output published in other languages, which also may result in the omission of important references in related fields."} +{"text": "Advances in Perovskite Quantum Dots and Their Devices\u2019 is a new open Special Issue of Materials in which original and review papers on the novel findings of synthesis, deep understandings of properties, and advanced potentials of applications in perovskite quantum dots are reported and published.\u2018Owing to their prominent properties including tunable bandgaps, strong absorption, efficient emission, and long carrier diffusion lengths, perovskites composed of metal-halide have rapidly emerged as materials with great potential in the last decade. Thus, their wide applications in solar cells, light-emitting diodes, lasers, photodetectors, X-ray scintillators, and catalysis have attracted the attention of researchers and captivated the broad scientific community.Furthermore, with the adaption of bulk perovskites to nanoscale ones, quantum dots exhibit a vast size-dependent optoelectronic performance, suggesting promising commercialization ability . For insThe research interests of this Special Issue include, but are not limited to, the following: the exploration of preparation methods; the scientific understanding of structures and optoelectronic mechanisms; the optimization of properties; wide-ranging applications; and the fabrication and performance enhancement of devices based on perovskite quantum dots."} +{"text": "Dear Editor,Acute localized exanthematous pustulosis (ALEP) is an atypical variant of acute generalized exanthematous pustulosis (AGEP), a rare drug reaction.3) and serum C-reactive protein. The pustule secretion culture was negative. The skin biopsy revealed intraepidermal subcorneal pustules and a superficial perivascular lymphocytic infiltrate is a particular form of AGEP. Approximately 25 reports have been published in the literature, confirming that it is a rare drug reaction.5As ALEP is a self-limited disease, the mainstay of treatment is the withdrawal of the suspected drug, promoting symptom improvement within a few days. Support therapy with topical or oral corticosteroids may be appropriate for the treatment of pruritus and inflammation in prolonged cases.In conclusion, ALEP is an unusual drug-induced skin reaction, and the majority of published cases were secondary to the use of antibiotics. However, it is important to emphasize that chemotherapeutic agents of the taxane class may also be responsible for this skin reaction.None declared.Ana Carolina Tardin Rodrigues de Medeiros: Statistical analysis; design and planning of the study; drafting and editing of the manuscript; intellectual participation in the propaedeutic and therapeutic conduct of the studied cases; critical review of the literature.Juliana Lopes Correa: Collection, analysis, and interpretation of data; drafting and editing of the manuscript; critical review of the literature.Ademar Schultz Junior: Collection, analysis, and interpretation of data; design and planning of the study; drafting and editing of the manuscript.Karina Demoner de Abreu Sarmenghi: Approval of the final version of the manuscript; effective participation in research orientation; intellectual participation in the propaedeutic and therapeutic conduct of the studied cases; critical review of the manuscript.None declared."} +{"text": "The biogeochemical roles of microbes in the Earth system are relatively well known , but theMagnetospirillum of Alphaproteobacteria: M. magneticum AMB-1 and M. gryphiswaldense MSR-1 [MTB are a group of morphologically, phylogenetically and metabolically diverse prokaryotes , affiliase MSR-1 ,8. Consiet al. [To solve this problem, Jinhua Li and co-workers developed a general strategy for identifying and characterizing uncultured MTB from natural environments at the single-cell level . In receet al. , they fuThis study links, apparently for the first time, the production of magnetic minerals to specific genes in MTB at the species/strain level, building on earlier observations that the genes associated with magnetosome formation vary among different MTB clades . This inmamABEIKMPQ) and the phylum-specific genes related to magnetosome formation. Interestingly, the genes mamL and mamO, which were previously thought to be core genes [mad and man genes may be involved in the growth of bullet-shaped magnetosome magnetite. These findings provide genetic evidence for the phylum-specific morphology of magnetosomes, which indicates that magnetofossil crystal morphology from the ancient geological record has the potential to be a reliable proxy for the taxonomic lineage of ancient MTB and their paleoecology.First, confirmation of the core genes are responsible for diverse chain configurations among MTB clades. For instance, the copy number, arrangement and homology of the mamK gene may influence the magnetosome chain structures in magnetotactic Pseudomonadota, and the Mad24 and Man5 genes may be involved in the assembly of multiple magnetosome chains in MTB of the Desulfobacterota and Nitrospirota phyla, respectively. This study further proposes a general model for the gene networks that control/regulate magnetosome biomineralization, including magnetosome membrane formation, protein sorting, iron transportation and magnetite nucleation, crystal mineralization, and chain assembly, in diverse MTB clades. This finding will further our understanding of magnetosome biomineralization in multiple bacterial clades and could pave the way for use of magnetofossils in paleoecology, paleoenvironment and evolution research.Second, demonstration of the key role of assembly ,9, suggeYet, the general model proposed here remains incomplete and will require refinement. Further investigation of more phylogenetically diverse MTB is needed in order to achieve a deep understanding of magnetosome biomineralization at the molecular level. Nonetheless, the new results of Jinhua Li and co-workers significantly expand our knowledge of the genetic basis for magnetosome biomineralization and will likely serve as a guiding framework for future molecular-scale studies of biogenesis and chain assembly of magnetosomes. The linkage of minerals to genes in MTB systems achieved in this study offers an excellent example for other fields of geomicrobial research."} +{"text": "The COVID-19 pandemic is having an unprecedented detrimental impact on mental health in people around the world. It is therefore important to examine factors that may buffer or heighten the risk of mental health problems in this context.This study explores the buffering effects of different flows of compassion and the magnifying effects of fears of compassion on the impact of perceived threat of COVID-19 on depression, anxiety and stress, and social safeness.4057 adult participants collected from the general community population across 21 countries from Europe, Middle East, North America, South America, Asia and Oceania, completed self-report measures of perceived threat of COVID-19, compassion, fears of compassion, depression, anxiety, stress, and social safeness.Self-compassion moderated the impact of perceived threat of COVID-19 on depression, anxiety and stress, whereas compassion from others moderated the effects of fears of COVID-19 on social safeness. Fears of compassion moderated the impact of perceived threat of COVID-19 on psychological distress. Only fears of compassion from others moderated the effects of fears of COVID-19 on social safeness. These effects were consistent across countries.Our findings highlight the universal protective role of compassion, in particular self-compassion and compassion from others, in promoting resilience by buffering against the harmful effects of the COVID-19 pandemic on mental health and social safeness. Furthermore, our results reveal that fears of compassion have a magnifying effect on the damaging impact of the COVID-19 pandemic on mental health and social safeness.I wasn\u2019t able to add the full list of authors above. Please add the full list as described below."} +{"text": "The relationship and mechanism between agricultural low-carbon technology application and farm household returns are not yet clear, especially the lack of evidence from developing countries. This paper takes large-scale farming households in Jiangxi Province, China, from 2019 to 2020 as the research object, and obtains relevant data from field research to explore the intrinsic impact of agricultural low-carbon technology application on the returns of large-scale farming households. Based on the relevant theoretical analysis, the division dimensions of agricultural low-carbon technologies were proposed, and agricultural low-carbon technologies were subdivided into ten specific low-carbon technologies according to six dimensions: tillage system, breeding, fertilization, irrigation, medicine application, and waste treatment. Relevant questions were designed and researched to obtain data on the application status of low-carbon technologies in agriculture and the income cost status of large-scale farmers. Based on the theoretical analysis, the research hypotheses were proposed, and an empirical analysis was conducted based on the obtained data from large-scale farmers. The application of seven low-carbon technologies in agriculture: conservation tillage system, direct sowing technology, selection of compound fertilizer/organic fertilizer/controlled-release fertilizer, soil formula fertilization technology, deep fertilization/irrigation fertilization, sprinkler/drip irrigation/wet irrigation/intermittent irrigation, and straw resourceization significantly improved the income level of large-scale farmers. Furthermore, the application of biodegradable agricultural membranes, biopesticides, and new pesticide-controlled release technologies did not have significant effects on the income level of large-scale farmers, due to their low application and penetration rate. Based on the findings of the paper, the government should strengthen the promotion and subsidies of agricultural low-carbon technologies, especially those technologies that have no significant impact on large-scale farmers\u2019 income, such as biodegradable agricultural membranes, biopesticides, and new pesticide controlled-release technologies, so as to achieve a win-win situation of reducing carbon emissions and increasing farmers\u2019 income. The history and current status of economic development show that economic development is a function of the dual-factor of technological progress and input factor addition . CompareThe existing literature focuses on the carbon reduction effect and driving factors of specific agricultural low-carbon technologies, and pays less attention to the economic consequences of the application of agricultural low-carbon technologies, which limits the popularization and application of agricultural low-carbon technologies to a certain extent ,11,12,13This paper has the following three contributions relative to the previous literature: (1) the existing literature on low carbon technologies in agriculture mainly focuses on the drivers of low carbon technologies in agriculture, but less on the economic consequences of low carbon technologies in agriculture. This paper explores the impact of agricultural low-carbon technologies on the returns of large-scale farmers and provides theoretical support for the long-term sustainable diffusion of agricultural low-carbon technologies. (2) The existing literature on low-carbon technologies in agriculture focuses on specific technologies, such as drip irrigation and soil testing and fertilization, and there is less literature on low-carbon technologies in agriculture in a holistic manner. This paper constructs an agricultural low-carbon technology index based on the characteristics and application of agricultural low-carbon technologies as a standard to measure the degree of application of agricultural low-carbon technologies. The construction of the agricultural low-carbon technology index can help solve the problem that agricultural low-carbon technologies are complex and difficult to measure. (3) This paper adds evidence with Chinese characteristics to the study of agricultural low-carbon technologies by taking the field surveyed large-scale farmers in Jiangxi Province, China, as the research object. Jiangxi Province is a representative agricultural province in central China. Jiangxi has a high forest coverage and a relatively low level of economic development, which represents the situation of major underdeveloped regions in China. Therefore, it is highly representative to carry out agricultural low-carbon technology research in Jiangxi Province. Conducting a study on the impact of its agricultural low-carbon technology application on returns is conducive to revealing bottlenecks in the diffusion of agricultural low-carbon technologies in developing countries, as well as promoting the application of agricultural low-carbon technologies.Based on the discussion and analysis of existing literature, this paper puts forward the research hypothesis of agricultural low-carbon technology driving the income of large-scale farmers. Combined with the survey data of large-scale farmers in Jiangxi Province, China, empirical research and draws corresponding conclusions and policy suggestions are carried out. This paper is structured as follows: Part II is a literature review and the formulation of research hypotheses; Part III is a dimensional classification of low-carbon technologies in agriculture; Part IV is an empirical study, including descriptive statistics of the sample and research hypotheses.2 emissions [Numerous scholars have worked on specific agricultural low-carbon technologies and their impacts. Agricultural low-carbon technologies are a collection of technologies that can reduce agricultural carbon emissions in the production stage of agricultural products (cradle-to-farm gate), such as biochar technology, the in-use of agricultural waste, and cropping systems ,15,16. Bmissions . Low carmissions . Agriculmissions . Meanwhimissions ,23. Thermissions ,25.Some other scholars have conducted in-depth studies on the drivers of low-carbon technologies in agriculture. Farm household characteristics, such as size, age, and gender, have important effects on low-carbon technology adoption . For exaIncreased energy consumption due to economic growth is an important cause of carbon emissions, and thus carbon reduction targets may severely reduce agricultural output ,37,38. AAccording to the theory of technological progress, innovation and application of technology are the core drivers of economic development. Agricultural low-carbon technologies are different from traditional high-carbon technologies, which can not only reduce the level of agricultural carbon emissions, but also increase the output and quality of agricultural products. From the perspective of specific agricultural low-carbon technologies, conservation tillage systems, soil testing and formula fertilization, sprinkler irrigation and drip irrigation and other agricultural low-carbon technologies not only reduce the cost of fertilizer and irrigation water for farmers, but also help to improve the yield and quality of crops. At the same time, ecological and low-carbon agricultural products are more likely to be welcomed by consumers, which helps to improve farmers\u2019 income. The economic benefits generated by the organic combination of various production factors need to be based on a certain scale, that is, economies of scale. Therefore, when studying the economic benefits of agricultural low-carbon technology, we investigate and use farmers with a scale of more than 100 mu, so as to improve the credibility of the research. Therefore, the basic hypothesis of this paper is that the application of agricultural low-carbon technologies has a positive impact on the returns of large-scale farmers, which is analyzed as follows.Tillage systems include no-till, minimum-till, and conventional tillage, among which no-till and minimum-till are conservation tillage systems. The conservation tillage system has significant economic and ecological benefits compared with the traditional conventional tillage system, which can achieve high quality, high efficiency, and high yield in agricultural production . FirstlyHypothesis\u00a01.The conservation tillage system can reduce production costs and help to improve the returns of large-scale farmers.Direct sowing and transplanting are the two main methods of rice cultivation in China at present. Direct sowing refers to the direct sowing of dry seeds or seeds that have been soaked and germinated; transplanting includes the basic processes of germination, seedling raising, and transplanting. As a new rice planting technology in recent years, direct sowing saves labor and energy compared with traditional transplanting, and the yield is not much different from that of transplanting, which can reduce the cost and obtain better economic benefits. Based on the above analysis, Hypothesis 2 is proposed.Hypothesis\u00a02.The application of direct sowing technology can reduce costs and promote the income of large-scale farmers.The agricultural membranes are one of the important carbon sources in the agricultural production process, and crops are often covered with agricultural membranes at the beginning of planting for drought and frost resistance. As a new low-carbon technology in agriculture, the use of biodegradable agricultural membranes can effectively reduce the carbon emissions of agricultural membranes. However, the cost of biodegradable agricultural membranes is relatively high compared to traditional agricultural membranes, and the difference in efficacy between traditional agricultural membranes and biodegradable agricultural membranes is not significant, which increases the cost and is not conducive to economic efficiency. Therefore, the promotion and application of biodegradable agricultural membranes should rely on the government to provide corresponding subsidies to make the use cost of large-scale farmers lower than that of traditional agricultural membranes, in order to effectively improve the utilization degree and realize low-carbon agriculture. Based on the above analysis, Hypothesis 3 is proposed.Hypothesis\u00a03.The application of biodegradable agricultural membranes will increase the cost and reduce the income level of large-scale farmers.The choice of fertilizer type can have a large impact on crop production. Reducing the application of nitrogen fertilizers and increasing the application of organic fertilizers and compound and controlled-release fertilizers can effectively reduce the greenhouse gas emissions of chemical fertilizers. Studies have shown that the application of compound fertilizers and controlled release fertilizers has a longer and more balanced nutritional effect than the application of nitrogen alone, and can increase yields. In addition, when determining the amount of fertilizer to be applied, the use of soil testing and fertilizer application technology can effectively reduce the waste of ineffective fertilizers, reduce costs and reduce the source of fertilizer carbon. In terms of fertilizer application method, deep application and irrigation fertilization can deliver effective fertilizer nutrients to the lower layer of soil and crop roots, and improve the utilization rate of fertilizer. Based on the above analysis, Hypotheses 4 to 6 are proposed.Hypothesis\u00a04.The application of compound fertilizer, controlled-release fertilizer, and organic fertilizer can enhance the profit level of large-scale farmers.Hypothesis\u00a05.The adoption of soil testing and fertilizer application technology can reduce costs and increase the returns of large-scale farmers.Hypothesis\u00a06.Deep fertilization and watering fertilization can improve the utilization rate of chemical fertilizers and enhance the profit level of large-scale farmers.Irrigation methods include conventional irrigation as well as the new sprinkler, drip, wet irrigation, and intermittent irrigation. Sprinkler irrigation is the use of decentralized nozzles for rotary water spraying irrigation; drip irrigation is the irrigation method through fine pipes to irrigation water to the roots of the crop; wet irrigation is to make the field near saturation of water, but does not establish a water layer of irrigation; intermittent irrigation is a certain interval of time, using intermittent water supply to the furrow or border in successive water supply, the use of wave surge flow in the furrow border to advance to wet the soil Irrigation method. Too much water in the soil may lead to problems such as low ground temperature, which may affect the normal growth and development of crops. Compared with the traditional large water irrigation the above four irrigation methods can achieve significant water saving, reduce irrigation water, improve irrigation efficiency, maximize the crop growth water demand and increase yield. In addition, the above four irrigation methods consume less power than traditional pumping flood irrigation, thus reducing carbon emissions. Based on the above analysis, Hypothesis 7 is proposed.Hypothesis\u00a07.The scale farmers using sprinklers, drip, wet irrigation as well as intermittent irrigation can achieve better economic benefits.The use of pesticides is another important source of carbon in agricultural production. Excessive pesticide application not only increases carbon emissions and agricultural production costs, but also threatens food safety and causes environmental pollution. Biopesticide is a general term for a series of new modern pesticides, mainly including biomass pesticides and biochemical pesticides. Compared with traditional pesticides, biopesticides are derived from animals, plants, or microorganisms and can repel pests without increasing the burden on crops, improving the quality and yield of agricultural products. The adoption of new pesticide-controlled release technologies can slow down the volatile process of pesticides, increase efficacy, reduce the use of pesticides, and lower the cost of agricultural production. Based on the above analysis, Hypothesis 8 and Hypothesis 9 are proposed.Hypothesis\u00a08.The adoption of biopesticides can enhance the level of returns of large-scale farmers.Hypothesis\u00a09.The adoption of new pesticide-controlled release technologies can reduce the cost of agricultural production and increase the level of returns of large-scale farmers.The treatment of agricultural waste is a key aspect of low-carbon technology application in agriculture, the most important of which is the fertilizer/feed utilization of straw. Returning straw resourceization can improve soil fertility, maintain soil temperature, inhibit water evaporation and increase crop yields. Burning straw not only leads to air pollution and a large increase in carbon emissions, but also reduces soil fertility and is not conducive to increasing crop yields. Based on the above analysis, Hypothesis 10 is proposed.Hypothesis\u00a010.Straw composting/overstocking can improve soil fertility, increase yields, and raise the level of returns for large-scale farmers.After the questionnaire design, questionnaire surveys were conducted successively: first, the subject group members went to Fuzhou city and Ganzhou city from 15 July to 15 August 2019, and with the assistance of the agricultural bureaus of Fuzhou city and Ganzhou city, they selected key townships in the counties where large-scale farmers were concentrated to conduct field interviews in the countryside; second, with the help of Jiangxi Province\u2019s Second, with the help of the \u201cOne Village, One Product\u201d college student project carried out in Jiangxi Province, members of the research team selected large-scale farmers who came to study at the College of Continuing Education of Jiangxi Agricultural University to conduct interviews from 20 December to 25 December 2020; Third, they went to the Jiangxi Provincial General Survey Team and Jiangxi Provincial Bureau of Statistics to access the information needed for the study. The total number of questionnaires obtained was 350, of which 322 were valid, as shown in As can be seen from y); the independent variables are the 10 agricultural low-carbon technology variables set above; and five additional control variables are set as population.\u03b11 to \u03b115 are variable coefficients, and \u03b8 denotes residuals.In Equation (1), y represents the net profit per mu for large-scale farmers. The average age of household heads in the research area was 47 years old. Only three households were under 30 years old, accounting for 0.9%; 63 households were under 40 years old, accounting for 19.62%; and 87 households were between 40 and 45 years old, accounting for 27.1%. This indicates that the farmworkers of large-scale farming households are generally older, mainly distributed over 40 years old, and these people have greater difficulties in accessing new knowledge and generating new ideas. In addition, 138 of the household heads are party members and cadres, accounting for 43%, a high proportion, indicating that party members and cadres play a pioneering and exemplary role in carrying out large-scale agricultural operations, or it may be that there is a shortage of young and strong rural laborers, and the older generation of laborers who remain in rural areas take up the main administrative work in rural areas. In terms of education level, the education level of heads of large-scale farm households is mainly distributed in high school and below, accounting for 87% of the total, with only 13% share of the university and above, and the largest number of heads of households with junior high school education level. This indicates that the education level of large-scale farm household heads is generally not high, and even university education has many informal full-time graduates, and the overall cultural level is low, which is not conducive to the acceptance and application of new agricultural low-carbon technologies. In terms of household size, the total household size of the studied large-scale farming households is five persons on average, and the labor force is 2.7 persons on average, and the agricultural labor force is 2.2 persons on average. It can be seen that the agricultural labor force is less than half of the total household size, and part of the labor force has been diverted to non-agricultural jobs.An important aspect of the production characteristics is the scale of planting. The object of this paper is the scale of farmers, defined as farmers with a planting area of 100 mu and above, and in the research process we focused on the selection of local large grain growers, as shown in As can be seen from The sample size farmers are mainly large grain farmers, and rice sales are their main source of income. In order to ensure the comparability of data, we only counted the sales income and production cost of rice. The relationship between income cost and land size is shown in It can be seen from Based on the complexity and systematic nature of low carbon technologies in agriculture, identifying and quantifying low carbon technologies in agriculture is the core problem to be addressed in this paper. The academic research on agricultural low-carbon technologies generally follows the traditional technology research paradigm, which simply classifies agricultural low-carbon technologies into binary variables of adoption/non-adoption, on the basis of which the influencing factors of agricultural low-carbon technologies are studied. Pathak and Aggarwal (2012) systematically studied the cost, classification, and improvement directions of agricultural low-carbon technologies, taking wheat and rice as an example in the Indus-Ganges plain of India, which provides an important reference for China . The 10 Low-carbon technologies in agriculture are applied throughout the whole process of agricultural production, and they are reflected in different cropping patterns and crops. Therefore, there is no unified academic standard for the classification of low-carbon technologies in agriculture, but some core classifications are mostly the same. In the process of agricultural production, fertilizers and pesticides are used as the main carbon sources, and the technologies for fertilizer and pesticide application are also used as the core agricultural low-carbon technologies, in addition to breeding, irrigation, and transportation. Scholars have put forward different classifications of agricultural low-carbon technologies. Although they are referred to in different ways, the basic connotations are similar, mainly around breeding, fertilizer, pesticide, irrigation, waste, cropping systems, and machinery, covering the whole process of agricultural production. Based on the basis and consideration of scholars\u2019 research, this paper divides agricultural low-carbon technologies into the following seven dimensions according to the agricultural production chain, as shown in The quantification of agricultural low carbon technologies is the basis for conducting a study on the drivers of agricultural low carbon technology applications on the returns of large-scale farmers. After the dimensional division and explicit classification of low carbon technologies in agriculture, 10 nominal variables for low carbon technologies in agriculture are set based on the design problem. After obtaining data on the application of low carbon technologies in agriculture, the level of application of agricultural low-carbon technologies is reflected by the mean value of each agricultural low-carbon technology application, as shown in Equation (2).ith agricultural low-carbon technology, i-th agricultural low-carbon technology (expressed as 0/1) of the j-th scale farm household, and N represents the number of sample scale farm households. The mean value of each agricultural low-carbon technology was calculated by this formula, and the specific application levels are shown in In Equation (2), As can be seen in The adoption of low-carbon technologies in agriculture not only reduces the level of agricultural carbon emissions, but also improves the efficiency of agricultural operations and increases income. Conservation tillage systems can increase soil moisture retention and nutrients, and improve yields. The application of organic fertilizers, compound fertilizers, and controlled-release fertilizers can improve the utilization efficiency of chemical fertilizers and increase soil fertility; soil testing and fertilizer application can maximize yields according to local conditions; deep fertilizer application and irrigation application can improve the utilization efficiency of fertilizers. New irrigation technologies such as sprinkler and drip irrigation can improve irrigation efficiency and increase yields. New pesticide-controlled release technology and bio-pesticides can control pests and diseases more environmentally friendly and improve the growing environment of crops. Straw resourceization can improve soil fertility, moisturize and increase temperature, and increase yield. Based on the questionnaire data, a linear regression of the model was conducted and the results are shown in As can be seen in As can be seen in 2O, the majority of the P2O5, and a portion of the N in chemical fertilizers. Promoting the return of straw to field has a great potential to reduce the use of chemical fertilizer, air pollutant emission, and environmental burden [The survey data from large-scale farmers in Jiangxi Province, China show that the application of agricultural low-carbon technologies such as conservation tillage system, direct sowing technology, the use of controlled-release fertilizer, deep fertilization, soil testing, and formula fertilization, drip irrigation, sprinkler irrigation, and straw resourceization have a significant positive impact on the income of large-scale farmers. (1) Consistent with Afshar and Dekamin (2022), the results show that conservation tillage systems can reduce the cost of agricultural production, improve income, and increase the returns of large-scale farmers . The conl burden .However, the adoption of new pesticide-controlled release technologies and biopesticides has no significant impact on the returns of large-scale farmers, mainly because the adoption of biopesticides and new pesticide-controlled release technologies in the actual production process is very small and difficult to form a scale. Most large-scale farmers do not know about biopesticides, and the practical application is more difficult. New pesticide-controlled release technology is also relatively small, scale farmers in the use of pesticides generally do not consider the use of controlled release agents, mainly on the function and role of pesticide controlled release agents and cost-effective understanding is not in place. In addition, new pesticide-controlled release technologies and biopesticides are still immature, which also limits their low-cost promotion and application ,54.Furthermore, the increase in household size can raise the income level, and the expansion of the planting scale reduces the unit income level. The increase of labor force can enhance the fine management of unit farmland and increase the unit output, while the expansion of planting scale reduces the level of fine cultivation of unit farmland and lowers the unit output. The effects of increasing household size and expanding planting scale on the level of returns of large-scale farmers are logically consistent intrinsically.The impact of low-carbon technologies in agriculture on the returns of large-scale farmers is systematically explored in this work. Based on the characteristics and application of low carbon technologies in agriculture, an agricultural low carbon technology index is constructed to measure the application of these technologies. Then the impact of low-carbon technologies on the returns of large-scale farmers in Jiangxi Province, China, was investigated through a field survey.The application of seven low-carbon technologies in agriculture: conservation tillage system, direct sowing technology, selection of compound fertilizer/organic fertilizer/controlled-release fertilizer, soil formula fertilization technology, deep fertilization/irrigation fertilization, sprinkler/drip irrigation/wet irrigation/intermittent irrigation, and straw resourceization could significantly improve the income level of large-scale farmers. However, the application of biodegradable agricultural membranes, biopesticides, and new pesticide-controlled release technologies did not have significant effects on the income level of large-scale farmers, probably because the application of the above three agricultural low-carbon technologies in the actual agricultural production process was relatively small and the penetration rate was not high, and the effects on income were not significant. Based on the findings of the paper, some suggestions are proposed.(1)Promote conservation tillage systems. Conservation tillage systems include no-till and minimum tillage, which can enhance soil carbon storage and significantly reduce the carbon emission level of farmland compared to traditional conventional tillage systems, and are key agricultural low-carbon technologies that return farmland from a carbon source to a carbon sink. In addition, a conservation tillage system increases soil organic matter content, regulates soil temperature, enhances soil moisture retention capacity, and improves yield, while reducing tillage costs and increasing economic benefits. Therefore, conservation tillage systems have significant synergistic effects between achieving low carbon agriculture and modernizing agriculture. In the actual production process, most farmers do not have a high awareness of the conservation tillage system, and they are still stuck in the traditional farming mindset that \u201cyou get what you put in, you get what you harvest\u201d, and that more tillage is necessary for high yield. To promote the conservation tillage system, on the one hand, we should strengthen the technical training of farmers, through technology in the countryside, centralized lectures, and other ways to make farmers aware of the advantages of the conservation tillage system; on the other hand, through the agricultural cooperatives, family farms and other local agricultural organizations of scale, so that the majority of farmers see the conservation tillage system can generate real income, driving the implementation of the conservation tillage system.(2)Promote direct sowing technology and encourage the use of biodegradable agricultural membranes. Although there is some decrease in yield compared to the traditional transplanting method, the overall benefit of rice cultivation is significantly increased. In addition, direct sowing technology eliminates the tedious process of traditional seed breeding and reduces the carbon emissions of the breeding process. The adoption rate of direct sowing technology in rice cultivation is gradually expanding, but there is still a significant proportion of large-scale farmers who have not yet used direct sowing technology. The reason for this may be that there are some problems with direct seeded rice technology, such as the increase in weeds, the climatic risk of inversion, and the high mechanization requirements for sowing and harvesting, so the acceptance is not yet high enough. The promotion and application of direct sowing technology should, on the one hand, strengthen the education and training efforts and the application of large households to drive the efforts, and on the other hand, actively solve the problems arising from the application of direct sowing technology, and improve the applicability of direct sowing technology. The popularity of biodegradable agricultural membranes is low mainly because the application of biodegradable agricultural membranes has little effect on improving economic efficiency, and the cost is high compared with traditional agricultural membranes. To promote the application of biodegradable agricultural membranes, it is necessary to strengthen the policy subsidies, improve the tax preferences and subsidies in production and use, reduce the production and use costs of biodegradable agricultural membranes, and make large-scale farmers take the initiative to adopt biodegradable agricultural membranes through government regulation and market-oriented approach.(3)Improve the science and efficiency of fertilizer application. Fertilizer is the first major source of carbon emissions from agriculture, to reduce agricultural carbon emissions, mainly from the use of chemical fertilizers to think of ways. But the growth of crops cannot be separated from chemical fertilizers, which have a great impact on the production results of crops. China is the largest fertilizer user in the world, and for every ton of fertilizer applied, the agricultural output value will increase by 1,245,910,000 RMB. Therefore, improving the science and efficiency of fertilizer application is the only way to achieve low carbon fertilizer use and high-efficiency income. First of all, in fertilizer selection, the use of compound and controlled release fertilizers, as well as organic fertilizers in the selection of fertilizers reduces the application of traditional nitrogen fertilizer. The use of compound fertilizer and organic fertilizer can balance soil nutrients, improve soil fertility and increase yield, while reducing carbon emissions, and the application of controlled-release fertilizer can prolong fertility and reduce the application of chemical fertilizers. Secondly, in the application method, deep fertilization or watering fertilization is used instead of the traditional spreading of fertilizer. Deep fertilizer application and irrigation fertilization can improve the efficiency of fertilizer utilization and reduce the amount of fertilizer, while increasing the yield. Finally, soil testing and fertilizer application techniques are used to determine the amount and type of fertilizer to be applied. Traditional fertilizer application is based on the amount of fertilizer applied in previous years or the amount of fertilizer applied by other local farmers, ignoring the nutrient demand of the soil. Soil formula fertilization can meet the individual needs of the soil, while reducing the waste of useless chemical fertilizers, lowering the soil burden, increasing yields, and improving economic benefits. In the actual production process, large-scale farmers have low awareness of the scientific nature of fertilizer application, and the lack of science in the amount of fertilizer used, the type of fertilizer applied, and the way of fertilizer application has made chemical fertilizer the number one source of carbon in agriculture, and also reduced economic benefits. To improve the science and efficiency of fertilizer application, we should strengthen the training of farmers on fertilizer application and raise their awareness of environmental protection. At the same time, agricultural extension personnel should also go deep into the farmers, go into the fields to give scientific guidance to large-scale farmers, and lead them to apply fertilizer scientifically to realize the synergy of agricultural economic benefits and environmental benefits.(4)Promote the use of new irrigation technology. Compared with the traditional large water irrigation, sprinkler irrigation, drip irrigation, moist irrigation, and intermittent irrigation can improve water use efficiency, reduce water use costs and improve economic benefits. In the sample study area, it is not common for large-scale farmers to adopt new irrigation technologies, and almost no farmers use sprinkler and drip irrigation, while some farmers use wet irrigation and intermittent irrigation. The cost of sprinkler and drip irrigation is higher than that of wet irrigation and intermittent irrigation, and the cost of water saved is not enough to compensate for the equipment cost of sprinkler and drip irrigation, thus the popularity rate is low. To promote new irrigation technologies, we should increase policy support and provide greater subsidies for sprinkler and drip irrigation equipment, so that farmers can afford to buy and use them. At the same time, strengthen the irrigation technology training for large-scale farmers, deepen the concept of new irrigation, and gradually reverse the backward irrigation situation in rural areas.(5)Promote the application of biopesticides and pesticide-controlled release formulations. Pesticide application is one of the important aspects of the agricultural production process and one of the important elements in the transformation of traditional agriculture to modern agriculture. The massive use of modern chemical pesticides on the one hand has greatly reduced crop pests and diseases, ensuring high agricultural yields and providing us with abundant agricultural products; on the other hand, it has also brought about serious environmental pollution, including a large increase in agricultural carbon emissions. As early as 1962, the American scholar Rachel Carson shockingly revealed in Silent Spring the great threat posed by the excessive use of pesticides to the human living environment in modern society. Controlling the excessive application of pesticides can not only reduce the cost of pesticide application for large-scale farmers, but also reduce agricultural pollution and carbon emissions, which is conducive to achieving a deep synergy between the economic and ecological benefits of agriculture. The promotion and application of biopesticides can significantly improve the current situation of pesticide pollution, and the elimination of pests and diseases through biological laws and mechanisms is the future development direction of agriculture. The new pesticide-controlled release technology can extend the efficacy of traditional pesticides, reduce the overuse of pesticides, and reduce the environmental risks brought by pesticides. In the actual agricultural production process, the application of biopesticides is very little, and the adoption of emerging pesticide controlled release technology is also less, mainly because the technology of biopesticides is still in the formative stage, is not mature, the application cost is very high, emerging pesticide controlled release technology also has a high application cost, the scale of farmers on emerging pesticide controlled release technology has not been really recognized. Promote the application of biopesticides can be emerging pesticide control release technology, on the one hand, the drug to strengthen basic research, improve the applicability of biopesticides, and pesticide control release technology to reduce costs; on the other hand, to strengthen the publicity and education of large-scale farmers, so that biopesticides and new pesticide control technology in the vast rural areas to gain recognition; and finally to strengthen policy subsidies to improve the application of large-scale farmers biopesticides and emerging pesticide The enthusiasm of controlled release technologies.(6)Improve the application rate of straw resourceization. The traditional way to deal with straw is to burn or abandon it regardless, which not only wastes the nutrients of the straw itself, but also greatly increases agricultural carbon emissions. Straw resourceization can improve the soil organic matter content, while regulating soil temperature, enhancing moisture storage capacity, and can increase yields without raising costs, improving economic efficiency. Eighty percent of the survey respondents have returned straw resourceizations, indicating that straw is commonly returned to the fields in the actual agricultural production process. For the application of straw resourceization of large-scale farmers, on the one hand, enhance the technical training of straw resourceization, improve the scientific nature of straw resourceization of large-scale farmers, improve the efficiency of straw utilization, and maximize the utility of returning to the field; on the other hand, further promote the application of straw resourceization, improve the popularity of straw resourceization, and strive to achieve the popularization of straw resourceization.(7)Improve the research and development innovation of agricultural low-carbon technologies, and provide a number of agricultural low-carbon technologies with low cost and good benefit. The promotion and application of low-carbon technologies in agriculture are not only conducive to enhancing the economic benefits of large-scale farmers, but also can achieve agricultural carbon emission reduction, which is the only way to achieve sustainable development of modernized high-carbon agriculture. To promote the application of low-carbon technologies in agriculture, farmers are the main body, the government is the leading, and technology is the key. The government should play a leading role in promoting the application of low-carbon technologies in agriculture and provide support for the promotion and application of various low-carbon technologies in agriculture. First, promote the research and development innovation of agricultural low-carbon technologies, and provide a number of agricultural low-carbon technologies with low cost and good benefit. Second, promote the construction of agricultural carbon sink market, and at the same time provide measurement support for farmers\u2019 carbon emission reduction, provide a carbon trading platform for large-scale farmers to achieve carbon emission reduction, and enhance the enthusiasm for large-scale farmers\u2019 carbon emission reduction. Third, drive the application of agricultural low-carbon technologies with new agricultural business entities . Fourth, strengthen the publicity and education for farmers to raise the low-carbon awareness of large-scale farmers. Fifth, propose a national development plan for low-carbon agriculture to provide legal support for the promotion and application of low-carbon agricultural technologies. Sixth, strengthen the construction of rural financial markets, encourage the development of new agricultural financial organizations, and provide financial support for the promotion and application of low-carbon agricultural technologies."} +{"text": "Editorial on the Research TopicHighlights in diagnostic and therapeutic devices 2021/22Developing flexible systems that monitor human health and deliver feedback therapy are the unmet medical needs for applications of personalized medicine and digital healthcare , 2. Sevei.e., United States, United Kingdom, Germany, Canada, France, Italy, Spain, Israel, Turkey, and Thailand) and nominated universities/institutions , University of California, Los Angeles (UCLA), University of Pennsylvania (UP), Tufts University, and Weill-Cornell Medicine,). Herein, we provide a brief introduction of these published articles and welcome readers to refer to these publications and their associated references for more details on this Research Topic.We are pleased to see the quality of the research submitted to our topic in diagnostic and therapeutic devices. This Research Topic finally contains six research and two review articles that address the recent advances and insights in diagnostic and therapeutic devices from scholars in a variety of countries from sole pressure and flow waveforms by using SYNCSMART software and that the results are within the inter-rater variability, providing a reliable assessment of patient-ventilator asynchrony. Afra et al. offer a comprehensive evaluation of the Vagus nerve stimulation (VNS) therapy system technology for drug-resistant epilepsy, including the technological evolution of the VNS with device approval milestones and a comparison of conventional open-loop and closed-loop generator models. This review could potentially serve as a valuable resource as this anti-epileptic neuromodulation technology continues to evolve. Basnet et al. report examining the field of energy-based medical therapies based on the analysis of patents, indicating an increasingly important role for energy-based therapies in the future of medicine. Prezelski et al. propose a novel multi-point injection cannula for achieving broader volume distribution than current single-needle designs and validate this system in benchtop studies of trypan blue convention enhance delivery in agarose brain phantoms, demonstrating a significant increase in volume distribution compared to single-needle delivery, while significantly reducing the total duration of the procedure. Schumayer et al. present an interesting three-dimensional masking process and demonstrate its successful application for the partial coating of a scleral contact lens electrode. Such techniques could open up more applications, including the mass production of brain electrodes or the structuring of microfluidic systems. Sringean et al. demonstrate the technical feasibility of using multisite wearable sensors to quantitatively assess early objective outcome measures of the ability of patients with Parkinson's disease to get out of bed, which significantly correlates with axial severity scores, indicating that axial impairment could be a contributing factor in difficulty getting out of bed.The articles published on this Research Topic cover a broad spectrum of research in wearable/implantable diagnostic and therapeutic devices that will bring new solutions and perspectives for the next-generation medical devices. We sincerely thank all the authors for their contributions to this Research Topic. It is also essential to acknowledge all the reviewers' time and assistance in ensuring the scientific validity and quality of the work submitted to this Research Topic."} +{"text": "Terminologies can seem very abstract to end-users. While most health professionals will be familiar with some terminologies , the controlled vocabulary thesaurus used for indexing articles for PubMed or ICD-10, WHO's terminology for disease coding), fewer will be aware of the depth and range of terminologies used in healthcare, nor of the central importance of multilingual standard terminologies in health care interoperability. Following a brief introduction to the use of terminologies, the integration of the International Classification for Nursing Practice (ICNP) the Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) will be presented, as an example of the use of terminologies, and their ongoing curation, maintenance and development."} +{"text": "Social isolation and loneliness are related but distinct constructs. A number of studies have examined these two constructs separately; however, the combined and interactive effects of social isolation and loneliness on health outcomes have rarely been studied. Using the most recent data of the Health and Retirement Study (HRS 2020) collected during the pandemic, this study aimed to explore the latent classes of social isolation and loneliness among adults aged 60 and older and to examine the associated psychological well-being. Social isolation was measured by five indicators, including living alone, no membership in any organizations, and less than once a month contact with children, relatives, and friends. Loneliness was measured by the 3-item UCLA scale. Four classes were identified by the Latent Class Analysis (LCA): neither isolated nor lonely , living alone and lonely , no social participation and lonely , and highly isolated and lonely . The results of multivariate regression indicated that compared to respondents who were neither isolated nor lonely, those who were in the class of living alone and lonely and the class of highly isolated and lonely had more depressive symptoms, stress, anxiety, worry, loneliness during the pandemic. The latent class of no social participation and lonely was associated with more depressive symptoms and covid-related stress. This study emphasizes the importance of specialized intervention strategies targeting the unique needs of older adults with different experiences of social isolation and loneliness."} +{"text": "The massive production and use of organohalides resulted in their worldwide contamination in soil, sediment and other environmental matrices . In addition, the debromination extent and rate of BDE183 could be enhanced by amendment of the BDE47. This study provides knowledge on new capabilities of Dehalococcoides and its potential in bioremediation of sites contaminated by both DBE47 and BDE183.In a Cimmino et al. deciphered the stoichiometry of pceABCT individual gene products in OHRB of Firmicutes. Notably, in contrast to a previously proposed model, results showed the formation of a membrane-bound PceA2B that could be devoid of PceC. These results provide unprecedented insight into the electron-accepting complex in PCE-dechlorinating OHRB of the phylum of Firmicutes.Reductive dehalogenase is the key enzyme to catalyze halogen removal from organohalides. Based on both transcription and translation analyses, Matturro et al. employed both 16S rRNA gene amplicon sequencing and metagenomic analyses to elucidate the microbial interactions among Dehalococcoides, Methanobrevibacter and Methanobacterium for the efficient dechlorination of trichloroethene (TCE) and reduction of Cr(VI) in a BES. In addition, at sites contaminated with chlorinated ethenes, abiotic factors could determine the fate of chloroethenes by affecting organohalide respiration of OHRB. Li et al. reported that FeS enhanced Dehalococcoides-mediated reductive dechlorination of TCE by formation of FeS nanoparticles and up-regulation of tceA transcription. These results could guide efficient bioremediation of sites contaminated by chlorinated ethenes and other contaminants.Bioelectrochemical systems (BES) hold great potential for bioremediation of sites co-contaminated by organohalides and heavy metals. With the success of the two volumes of this Research Topic, we would like to thank all the authors and reviewers for their valuable contributions. These papers significantly improve our understanding in organohalide-respiring bacteria and their electron transport chains, as well as in dehalogenating microbiome and bioremediation implications. Notably, several research gaps were also highlighted in this Research Topic, and awaited future studies: (1) contribution of microbial reductive dehalogenation to attenuation of organohalides in natural environments; (2) cycling of organohalides in varied environmental matrices and associated functional microorganisms and enzymes; (3) reciprocal interactions of the commonly co-existing abiotic processes with the OHRB-mediated reductive dehalogenation process. We hope that this collection of reviews and original research articles will be helpful for researchers and engineers seeking information on organohalide respiration and bioremediation applications.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "On the basis of complex clinical anamnestic, clinical psychopatological, pathopsychological research, data were obtained about reasons and conditions of formation, abnormal clinical psychopathological structure, syndrome peculiarities of emotional disfunctions for patients with episodic paroxismal disorders, generalized anxiety disorders and mixed anxiously depressed disorders.To realize the aim and tasks of the research, 145 patients were examined with anxiety disorders, that passed the stationary course of treatment.The purpose of the research was to discover emotional disturbance peculiarities for anxiety disorder patients with different origins of pathological syndromes.The basic method was a group psychotherapy with the elements of rational, positive, suggestive and family psychotherapy. In relation to disfunctions of emotional sphere, cognitive-behavioral therapy (CBT) was used for the phobic-depressive and anxious-depressed disorders.Decrease in general level of anxiety and internal anxiety was obtained for most patients. No spontaneous emergence of fear was practically observed. While active interviewing, patients stated that their former worries and fears have lost actuality and apparent emotional colouring, somatic-vegetative correlates of anxious states disappeared. Up to the end of the therapy course, a sense of calmness was attained as a base-line for the background emotional state. Considerable reduction of symptomatic of the depressed circle also took place. Patients\u2019 mood increased, their interests broadened, patients started to feel joy and optimism.To correct emotional disfunction of patients with episodic paroxismal disorders, generalized anxiety disorders and mixed anxiously depressed disorders, psychotherapeutic correction system is optimal to use, which is built based on stepwise and multimodal principles."} +{"text": "Among non-communicable diseases, cardiovascular disease (CVD) is the leading cause of mortality worldwide, which is associated with increased morbidity and hospitalization . To dateMa et al. creatively conduct an overview of EV research in CVD via a bibliometric analysis. The authors systematically collect the last 20 years of research on Web of Science Core Collection and perform a bibliometric analysis with visual tools (Citespace and Vosviewer). The results demonstrate that increasing attention was significantly paid to the capacity of EV in CVD from 2017 onwards, indicating the increasing popularity of the subject in this field. Furthermore, the authors conclude most of these studies focused on EV as biomarkers for CVD diagnosis, delivery vehicles, and a potential strategy for treating myocardial infarction.In this issue, Yao et al. prospectively performs atrial fibrillation (AF) modeling in Canines and investigates the function of EV in AF development. The authors reveal that blocking the release of small EV by GW4869 could alleviate AF by reducing atrial fibrosis. Mechanistically, EV-enclosed miR-21-5p targets the downstream TIMP3/TGF-\u03b21 pathway and induced fibrosis. Inhibiting the release of EV may be a potential strategy for AF treatment, which may help accelerate new clinical trials of AF treatment. Chen et al. systematically review the role of EV and EV-enclosed non-coding RNAs (NcRNAs) in the diagnosis and treatment of AF in more detail. Notably, EV-enclosed NcRNAs may also play a crucial role in the progression of AF.The study of Liu et al. and Yang et al. explore the role of adipose-derived EV in lipid metabolism, which is closely associated with vascular homeostasis. Epicardial adipose tissue (EAT)-derived EV-enclosed miR-3064-5p is identified as a key molecule in regulating lipogenic differentiation.The EV-mediated interaction between adipose tissue and blood vessels may play an important role in CVD. In this Research Topic, Hu et al. investigate the crosstalk between macrophages and cardiomyocytes. The authors reveal that ambient particulate matter could promote the release of EV and subsequently activate macrophages. EV-enclosed TGF-\u03b2 derived from macrophages promotes the fibrotic alteration of cardiomyocytes, ultimately leading to cardiac dysfunction. This study sheds light on the underlying mechanism and potential therapeutical strategy for air pollution-associated cardiovascular disorders.Interestingly, EV is proven to be involved in air-pollution-associated cardiac injury. Wei et al. summarize the role of platelet-derived EV in mediating intercellular communication, which contributes to arterial thrombosis. This review provides a new horizon as platelet-derived EV could provide promising biomarkers for the diagnosis of CVD.Notably, increasing evidence shows that platelet-derived EV are a crucial component of circulating nanoparticles in blood, indicating that platelet-derived EV play important roles in multiple pathological processes. In this Research Topic, Overall, this Research Topic provides a relatively comprehensive understanding of the role and potential application of EV in CVD, including a bibliometric analysis, overviews, and some surprising experimental articles. These studies identify a novel cargo and signaling axis in the development of CVD and provide a novel way of using different sources of EV and EV-enclosed cargo in diagnosing CVD. Nevertheless, EV-associated basic, translational, and clinical studies are still on the way. Here we sincerely hope that this Research Topic can provide readers with different viewpoints and new horizons in EV & CVD diagnosis and treatment, inspiring future studies on the therapeutical application of EV. In addition, we also hope the work can help to stimulate novel ideas in associated fields and improve the research progression of CVD.HW, YH, and JX are the topic editors of this issue and they have contributed to the writing and revising of the article. XZ, MZ, and YL contributed to drafting the Editorial. All authors approved it for publication.This work was supported by grants from the National Key Research and Development Project (2018YFE0113500 to JX), the National Natural Science Foundation of China (82020108002 and 81911540486 to JX and 82000253 to HW), the grant from Science and Technology Commission of Shanghai Municipality (20DZ2255400 and 21XD1421300 to JX), the Dawn Program of Shanghai Education Commission (19SG34 to JX), the Sailing Program from Science and Technology Commission of Shanghai (20YF1414000 to HW), Chenguang Program of Shanghai Education Development Foundation, and Shanghai Municipal Education Commission (20CG46 to HW).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "About 29\u201381% of post-stroke survivors suffer from dysphagia, which is characterized by varying degrees of eating disorders, choking cough, salivation, and abnormal pronunciation. Dysphagia is associated with increased risk of malnutrition and pneumonia and leads to prolonged hospital stay, poor prognosis, and mortality . For PAS, some studies used both liquid and semi-solid measurements and further produced two different PAS results and Dysphagia Grade (DD) in the meta-analysis. The reasons are unclear. DD is mainly assessed using questionnaires, whereas PAS requires the collection of video images for assessment by the Fiber Endoscopic Evaluation of Swallowing (FEES) or the Video Fluoroscopic Swallowing Study (VFSS). The Standardized Swallowing Assessment (SSA), Functional Dysphagia Scale (FDS), and Mann Assessment of Swallowing Ability (MASA) are commonly used as measurements of swallowing function, and some trials using these outcome indicators have been missed. Moreover, a trial instead of standard deviation (SD). We note that Khedr et al. and KhedWe added a randomized controlled trial , p = 0.04]. Heterogeneity also greatly reduced compared with Yang et al. . Subgroup analysis was conducted according to different frequencies. The efficacy of high-frequency stimulation and low-frequency stimulation in the treatment of dysphagia after stroke was greater than conventional rehabilitation, which was completely different from Yang's results. The results showed that rTMS was superior to conventional rehabilitation in the treatment of post-stroke dysphagia regardless of stimulation frequency. We emphasize the importance of carefully examining the data extraction and reviewing the results of the meta-analysis.As shown in In conclusion, we urge readers to be cautious about the quality and validity of the review analyzed by Yang et al. The study omitted several important trials and produced extraction/synthesis errors in the meta-analysis, leading the authors to underestimate the efficacy of rTMS in patients with post-stroke dysphagia.Y-lX, SW, and Y-hX conceived the idea and wrote the manuscript. QW and YW analyzed the data. All authors reviewed the final manuscript.YW was supported by Sichuan Medical Research Project Plan (Q18038). QW was supported by Development Project of Affiliated Hospital of North Sichuan Medical College (2021ZD014). Y-lX was supported by the North Sichuan Medical College of Medical Sciences Postgraduate Research Scholarship.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The COVID-19 pandemic has highlighted the need for resilient health systems with the capacity to effectively detect and respond to disease outbreaks and ensure continuity of health service delivery. The pandemic has disproportionately affected resource-limited settings with inadequate health capacity, resulting in disruptions in health service delivery and worsened outcomes for key health indicators. As part of the US government\u2019s goal of ensuring health security, the US Centers for Disease Control and Prevention has used its scientific and technical expertise to build health capacity and address health threats globally. We describe how capacity developed through global health programs of the US Centers for Disease Control and Prevention in Cameroon was leveraged to respond to coronavirus disease and maintain health service delivery. The health system strengthening efforts in Cameroon can be applied in similar settings to ensure preparedness for future global public health threats and improve health outcomes. The ongoing COVID-19 pandemic was declared a public health emergency of international concern by the World Health Organization (WHO) on January 30, 2020 began work in Cameroon during 1998 by establishing an HIV laboratory and research program. The presence of CDC in Cameroon evolved to an established country office in 2004, providing technical expertise and support to the Ministry of Health (MOH) to strengthen disease control efforts and develop sustainable public health capacity. In 2007, an agreement was signed between the US and Cameroon governments, establishing a partnership to prevent and control HIV/AIDS, avian influenza, and other infectious diseases. Consistent with the International Health Regulations (2005) that states WHO member states should develop, strengthen, and maintain their capacity to respond promptly and effectively to public health emergencies of international concern was activated for the response. The PHEOC is a state-of-the-art facility constructed and established with support from the US Defense Threat Reduction Agency and CDC and handed over to the government of Cameroon in June 2019 to ensure coordination and management of health emergencies , an established command structure to manage emergency responses . CoordinThe CDC-established Field Epidemiology Training Program supportehttps://anab.ansi.org), meeting international standards for quality management systems and competence for medical laboratories . Rapid tThe COVID-19 pandemic overwhelmed health systems globally and adversely affected health programs because available resources were focused on responding to the pandemic and tuberculosis treatment dispensation, and HIV viral load sample collection in the community. Clinical implementing partners collaborated with community-based organizations and satellite health facilities for HIV testing, linkage, and treatment dispensation. CDC conducted weekly virtual clinical program and data reviews with implementing partners and health facilities and held quarterly virtual sessions to review program performance and share best practices. Establishing virtual trainings and weekly granular site management (HIV service provision and program performance decreased in many President\u2019s Emergency Plan for AIDS Relief\u2012supported sub-Saharan African countries during the COVID-19 pandemic (The COVID-19 pandemic called attention to health system gaps and underscored the need for resilient health systems to effectively respond to health threats while ensuring continued health service delivery. The effect of the pandemic has been serious in central Africa and other resource-limited settings, largely caused by the limited health infrastructure and capacity in the region. Building on the strong partnership with the Cameroon MOH, capacity established through global health programs of CDC was leveraged to support the COVID-19 response in Cameroon while implementing innovative strategies such as differentiated service delivery and granular site management to mitigate the effect of the pandemic on health programs. In addition to the need for strengthened disease preparedness and response capacity, key lessons learned from the response in Cameroon to the pandemic include the need for a well-trained and fit-for-purpose health workforce, timely mobilization of resources, and the need for coordination of multiple stakeholders to effectively manage response efforts.Despite ongoing security and humanitarian crises in Cameroon, efforts of CDC have helped to strengthen the health system and improve health outcomes by ensuring continuity of HIV and tuberculosis services during the COVID-19 pandemic and maintaining programmatic gains. Through support of CDC, Cameroon has accelerated progress to reach the 95\u201395\u201395 targets and is positioned to be the first country in West and Central Africa to achieve HIV epidemic control. As part of the mission of the US Government to improve health globally, CDC continues to provide support to Cameroon to respond to the COVID-19 pandemic and prevent and control other public health threats. The lessons learned from Cameroon might be applicable to other resource-limited settings and conflict-affected areas to respond to COVID-19 and prepare for future pandemics.Members of the Centers for Disease Control and Prevention Cameroon Team: Leonard C. Keleko, Ebako Takem, Christopher Coox, Adebowale Okunrinboye, Fabrice D. Nembot, Edwin Sah, Mohamadou Awalou, Yvan D. Mouzong, Anula C. Acho, Alexandre Forbin, Jeannette E. Bessem, Sidouanne Signing, Marie G. Dima, Peter T. Atonkah, Yaya N. Sale, Eric Kamleu, Richard Olemba, Johnson Teboh, Chrysantus Egbe, and Keanu Renee-Glover."} +{"text": "Strengthening organization quality-specific immune is the key linkage to improve the quality performance of intelligent manufacturing enterprises. organization quality-specific immune is constructed by selecting four state variables of organization quality cognition, monitor, defense, and memory. Based on the perspective of self-organization, self-organization theory and methods are used to construct the evolution model of organization quality-specific immune. According to four state variables, the evolution of organization quality-specific immune of fourteen typical intelligent manufacturing enterprises is studied, and the conclusion is drawn according to the relaxation coefficient. The empirical results show that self-organization theory and self-organization methods can effectively analyze the evolution of organization quality-specific immune and provide new inspiration for organization quality improvement and quality management of intelligent manufacturing enterprises. The finding results will present the framework for practicing engineering managers of intelligent manufacturing enterprises to enhance organization quality performance and organization quality-specific immune performance and promote organization quality-specific immune evolution. Industry 4.0 advocates the fourth industrial revolution, transforms the manufacturing industry to intelligence, actively develops intelligent manufacturing enterprises, continuously improves the intelligence level of manufacturing enterprises, and promotes intelligent production, intelligent technology, human-computer interaction, intelligent management, intelligent network, and the intelligent resources of intelligent manufacturing enterprises. Quality is the core element of the intelligent manufacturing enterprise , 2. QualScholars home and abroad adopt interdisciplinary research ideas and methods to transplant, integrate, and map immunology to the quality management field; derive analogy and metaphor research results; and generate the connotation, function, classification system, and construction elements of organization immune; organization immune includes organization-specific immune and organization nonspecific immune; organization-specific immune is the core architecture of organization immune \u201355. Lv aQuality is the life of intelligent manufacturing enterprise, on the basis of relevant research results of organization immune \u201355, 62; By drawing lessons from the relevant theoretical concepts of biological immunology, the scholars put forward the definition of organization quality immune, that is, enterprises find out the harmful factors that threaten product quality and organizational health, take the initiative and take immunization measures to deal with and eliminate the factors that threaten the quality, and generate the memory function as for the immunization process at the same time, in order to maintain the whole process healthy, quality performance, and stable development of enterprise , 57\u201363. Through the analysis, it is found that scholars at home and abroad mainly analyze organization quality-specific immune through system structure, system function, and function mechanism according to organization immune. There is a lack of qualitative and quantitative methods to probe into the evolution of organization quality-specific immune. Therefore, this study constructs theoretical framework of organization quality-specific immune evolution model; organization quality-specific immune is composed of four construct elements of organization quality cognition, organization quality monitor, organization quality defense, and organization quality memory by drawing lessons from absorbing a large number of relevant literature and conducts empirical analysis of organization quality-specific immune evolution model according to self-organization methods.Organization quality-specific immune refers to the systematic concept, which is a system. Organization quality-specific immune is divided into four components of organization quality cognition, organization quality monitor, organization quality defense, organization quality memory, which can dominate and determine the evolution of organization quality-specific immune \u201352, 56.Organization quality cognition includes two parts of perception and discovery. The organization subject collects the object and quality-related information actively through organization quality cognition behavior, which is the expression form of organization initiative consciousness . ThroughOrganization quality monitor is an important link, and it is an important tool for senior managers to detect damage to product quality and health in time. The tool can help the enterprise to monitor the quality environment all the time so that the enterprise has been in a stable quality environment . ThroughOrganization quality defense mainly includes three parts of variation, selection, and coordination. The defense process is carried out on the basis of effective monitoring of the organism, which refers to the process that the organization actively eliminates harmful factors of affecting quality in the organism . DefenseOrganization quality memory is the whole process of summarizing and digesting the immune process through memory behavior after a series of immune behavior . The memSelf-organization mainly studies the self-motion process of how the related subsystems of the system integrate into the regular structure , 73. TheThe principle of self-organization refers to the evolution theory within the system, which itself is a form of evolution . Self-orThe organization quality-specific immune is a system, it is necessary to explore the organization quality-specific immune from the perspective of the system. In this study, the relevant theory and methods of self-organization are used to study the evolution process. The scope of the research system and degree of grey correlations between the calculations are determined to find out the order parameters of the system , 74, 75.(1)Determining the Order Parameters of the System. The order parameter is a parameter at the macrolevel, and the order parameter can better express the behavior of the system. Order parameters are mainly used to express the disordered and ordered state of the system. Its core is the change of two phases after the phase transition occurs, and the order parameter is to describe the different physical quantities between two phases. The order parameters determine the direction of system evolution. Ha introduced the concept of order parameters into synergetics knowledge, that is, the variables that discovered and determined the formation and evolution of the system 2 \u2212 4\u2211j=14aijxj(1)(t)]2. According to the extreme value condition of multivariate function, the conclusion is drawn.According to the principle of least square method, There are various multiple relationships among the internal factors of organization quality-specific immune. To study its evolution system, it is necessary to analyze the scope of organization quality-specific immune and get the correlations among the factors so as to find out the order parameters of the system accurately.State variables of organization quality-specific immune evolution refer to organization quality cognition, organization quality monitor, organization quality defense, and organization quality memory.According to the evolution model, we calculate the grey correlation degree and get the correlation degree of each variable according to the numerical value so as to get the state variable of the system. In this study, fourteen representative large-scale intelligent manufacturing enterprises in eastern China are taken as the evaluation objects, and four subsystems are constructed, including organization quality cognition, monitor, defense, and memory. This study makes out dynamic evaluation on the organization quality-specific immune evolution of intelligent manufacturing enterprises in eastern China.X1\u2013X14) in eastern China are selected as samples. The questionnaire is divided into two parts of the basic information of the object and the score of the questionnaire. Among them, the basic information part of the survey object requires the survey object to fill in the personal information, and the scoring part will affect the four state variables and further affect the evolution of the system. This study uses organization quality cognition C1, organization quality monitor C2, organization quality defense C3, and organization quality memory C4 to score. Among them, 1\u20132 indicates weak influence on the evolution of organization quality-specific immune, 3\u20135 indicates average influence, 5\u20136 indicates higher influence, and 7\u20138 indicates strong influence.By the form of on-site distribution questionnaire, fourteen representative benchmark intelligent manufacturing enterprises XXi(t) represent the data of the first index of the t enterprise, and the data sequence after dimensionless processing is Xi(0)(t) as shown in Let variable Xit) is treated with AGO and recorded as Xi(1)(t) represents the synergistic and competitive effect of state variables on i variables.The external synergy among the system elements is recorded as 1)(t) is , 95, 96(bijxj(1)(t); the competition is expressed as aij(Xj(1)(t))2; fi(t) represents the external interference factors. \u2212bii=bi, then the nonlinear equation can be deduced toAmong them, the synergy is expressed as Xi(1)(t)/dt=Xi(1)(t) \u2212 Xi(1)(t \u2212 1)=Xi(0)(t).Assuming that dAccording to the principle of least square method, it can be concluded as follows:According to the extreme value condition of multivariate function, it can be concluded as follows:t=2,3,\u2026, 14, separate into the above formula, yN=BiPi.Substitute Bi to obtain B1, B2, B3, and B4 and replace the cumulative added data into yi to obtain y1, y2, y3, and y4; the results are as follows [Replace the dimensionless data into follows \u201396, 98: is the relaxation coefficient of each index system in the organization quality-specific immune system. According to the coevolution model, the relaxation coefficient of each index system is obtained: C1\u2009=\u20091.7480, C2\u2009=\u20090.5125, C3\u2009=\u20091.1552, and C4\u2009=\u20090.8899. The relationships among the relaxation coefficients of each index system are as follows: C2\u2009<\u2009C4\u2009<\u2009C3\u2009<\u2009C1.The relaxation coefficient represents the influence degree of the state variable on the evolution of organization quality-specific immune, that is, the smaller the relaxation coefficient is, the greater the effect and influence on the evolution of organization quality-specific immune is, and the greater the relaxation coefficient is when the state variable has a slight effect on the evolution of organization quality-specific immune. According to the empirical analysis results, organization quality monitor has the greatest influence on the evolution of organization quality-specific immune, organization quality memory has the greater influence on the evolution of organization quality-specific immune, organization quality defense has a general influence on the evolution of organization quality-specific immune, and organization quality cognition has the least influence on the evolution of organization quality-specific immune.The related theory and methods of self-organization are introduced into the evolution model of organization quality-specific immune of intelligent manufacturing enterprises. With the help of self-organization theory and methods , 74, thiAccording to the relaxation coefficient, it is concluded that different state variables have different influences on the evolution of organization quality-specific immune, that is, organization quality monitor has the greatest effect on the evolution of organization quality-specific immune, organization quality memory has the greater influence on the evolution of organization quality-specific immune, organization quality defense has a general effect on the evolution of organization quality-specific immune, and organization quality cognition has the least effect on the evolution of organization quality-specific immune. It is urgent to enhance organization quality-specific immunity in accordance with local conditions on the weak points of the evolution of organization quality-specific immune . The purTheoretical research framework of this study can be used by practicing engineering managers; engineering managers of intelligent manufacturing enterprises can understand the key role and significance of quality in the process of engineering management and organization management; comprehensively examine quality management problems from the perspective of immune; strengthen the soft and hard elements of quality management practice; activate the function and vitality of hard and soft elements of organization quality defense; develop institutional and social measures; focus on the core practice and basic practice of quality management; realize quality improvement cycle; form the virtuous cycle and context system of mutual promotion, coordination, correction, and feedback among organization quality cognition, organization quality monitor, organization quality defense, and organization quality memory; enhance organization quality trial and error ability; promote organization quality-specific immune evolution ; and improve organization quality competitiveness, quality innovation ability, quality management ability, customer satisfaction, organization operation efficiency, and organization finance performanceIn terms of the theoretical research framework of this study, engineering managers of intelligent manufacturing enterprises can also judge and examine quality management issues from the perspective of system and evolution; put emphasis on the functions of organization quality cognition, organization quality monitor, organization quality defense, and organization quality memory; activate and dredge the function of organization quality-specific immune; prevent hypersensitivity and hyperimmunity; enhance organization quality-specific immune response rate; continuously increase quality performance and core competitiveness; improve organization quality improvement efficiency, market share, productivity, and final product quality qualification rate; and reduce product quality assurance cost, total quality cost, and quality defects compared with competitorsThe empirical analysis results of this study can be applied by practicing engineering managers; engineering managers of intelligent manufacturing enterprises can recognize that organization quality-specific immune is a system; actively promote the orderly evolution of organization quality-specific immune; drive organization quality-specific immune to maintain the good evolution trend and development tendency; prompt the spiral upgrading, function optimization, and function renewal of organization quality-specific immune; introduce negative entropy flow; make organization quality-specific immune get into the virtuous cycle process and track; stimulate the niche change of organization quality system; enhance the maturity, survivability, robustness, disaster tolerance, and buffer capacity of organization quality-specific immune system; and reduce the vulnerability and redundancy of organization quality systemIn terms of the empirical analysis results of this study, engineering managers of intelligent manufacturing enterprises can also identify the key factors, dominant slow variables, and order parameters of organization quality-specific immune evolution; emphasize on the obstacle factors and weak links of organization quality-specific immune development; excavate the bottleneck factors that hinder the evolution of organization quality-specific immune; refine the operation paths of organization quality-specific immune evolution according to the relevant parameters of organization quality cognition, organization quality monitor, organization quality defense, and organization quality memory; actively guide the evolution direction of organization quality system; and complete organization quality strategy and missionThe practical implications for engineering managers of intelligent manufacturing enterprises lie in the following:"} +{"text": "Dysbiosis of gut microbiota plays a fundamental role in the pathogenesis and development of chronic kidney disease (CKD) and its complications. Natural products from plants and microorganisms can achieve recognizable improvement in renal function and serve as an alternative treatment for chronic kidney disease patients with a long history, yet less is known on its beneficial effects on kidney injury by targeting the intestinal microbiota. In this review, we summarize studies on the effects of natural products from plants and microorganisms, including herbal medicines and their bioactive extracts, polysaccharides from plants and microorganisms, and phytochemicals, on the prevention and treatment of chronic kidney disease through targeting gut microflora. We describe the strategies of these anti-CKD effects in animal experiments including remodulation of gut microbiota structure, reduction of uremic toxins, enhancement of short-chain fatty acid (SCFA) production, regulation of intestinal inflammatory signaling, and improvement in intestinal integrity. Meanwhile, the clinical trials of different natural products in chronic kidney disease clinical practice were also analyzed and discussed. These provide information to enable a better understanding of the renoprotective effects of these effective natural products from plants and microorganisms in the treatment of chronic kidney disease. Finally, we propose the steps to prove the causal role of the intestinal microflora in the treatment of chronic kidney disease by natural products from plants and microorganisms. We also assess the future perspective that natural active products from plants and microorganisms can beneficially delay the onset and progression of kidney disease by targeting the gut flora and highlight the remaining challenges in this area. With the continuous deepening of studies in recent years, it has been proved that gut microbiota is a potential target of natural active products derived from plants and microorganisms for chronic kidney disease treatment. Fully understanding the functions and mechanisms of gut microbiota in these natural active products from plants and microorganisms is conducive to their application as an alternative therapeutic in the treatment of chronic kidney disease. Chronic kidney disease (CKD) has become an increasing public health problem with a wide range of complications and high risk of mortality. The worldwide prevalence of CKD (8%\u201316%) brings a heavy economic burden for middle- and low-income countries in particular . Due to Proteobacteria and Actinobacteria and a decreasing level of beneficial microbes such as Lactobacillaceae has an important influence on obesity and Sophora japonica L. (SL) lowered the F/B ratio in spontaneously hypertensive rats in the normal group. The expansion of Proteobacteria abundance is considered a hallmark for dysbiosis mice. A. membranaceus and S. miltiorrhiza , Astragaccharide , Coptidiccharide , and a rccharide enhanced Nx rats . The abumia mice . Shenqi mia mice .Lactobacillus and Bacteroides enriched in the diabetic mice, which were significantly reduced by QiDiTangShen granules that increased in the 5/6 Nx group was found to be associated with kidney injury , claudin-1, and occludin, play an indispensable role in maintaining the permeability of the intestinal epithelial barrier. Once the expression of tight junction proteins in intestinal mucosa decreases, the paracellular permeability would increase and the tight junctions would be destroyed, resulting in intestinal barrier damage . Decreasmy model . Higher my model . Fermentmy model . Astragaccharide , rhubarbccharide , the comacterium and alisacterium treatmen mycelia , Bupleurupleurum , and Mouupleurum improvedupleurum and curcupleurum and the upleurum protectetoxicity . Thus, iIntake of choline, tyrosine, and tryptophan increases the amounts of trimethylamine (TMA), IS, hydrogen sulfide, and indole produced by intestinal bacteria. After absorption, these compounds are further metabolized in the liver to generate the typical uremic toxin trimethylamine N-oxide (TMAO), PCS, and p-indoxyl sulfate. These toxins, which cannot be removed efficiently even by hemodialysis and would accumulate in advanced CKD patients , are higBacillus, thereby reducing the accumulation of IS and PCS in CKD mice (via colonic irrigation (ECI) remodeled gut microflora and decreased the levels of urea and IS in CKD rats (Abelmoschus moschatus) inhibited the tryptophan transport in the main indole-synthesizing bacteria Enterobacteriaceae, resulting in the decease of uremic toxin IS production in CKD rats could disturb microbiota-mediated indole production by inhibiting the transport of exogenous tryptophan into indole-synthesizing bacteria and further reducing indole biosynthesis (Supplementation with amylose resistant starch HAM-RS2 could re longum) complete longum) . The com longum) . Oligofr longum) . FurtherCKD rats . HuangkuCKD rats . As a naynthesis . To sum Enterobacteriaceae, Vibrionaceae, and Pseudomonadaceae, was found to increase significantly in the CKD patients are generated from the fermentation of various types of cellulose by SCFA-producing gut microbiota such as nditions of systemic inflammation in hemodialysis (HD) patients could increase fiber intake, reduce IL-6 and IS plasma levels was effective in reducing IS in patients affected by advanced CKD in a randomized, double-blind, placebo-controlled, crossover trial , and resistant starch, are utilized as prebiotics that are selectively digested by host microorganisms, which could stimulate the growth of one or a limited number of beneficial bacteria and reduce the uremic toxin released in the colon. However, common side effects including mild diarrhea and gassiness were often accompanied with administration of these fibers , proteomics, metabolomics, and cultureomics. These strategies have pushed the development of novel disease-related probiotics, prebiotics, and functional proteins for the treatment of CKD by targeting the dysbiosis of the gut microbiota in recent years animals, and antibiotic treatments. Additionally, to understand how natural products from plants and microorganisms affect the gut microbiota in CKD patients and to develop new alternative therapies for CKD treatment, the strain- and molecular-level connections between the gut microbiome, natural products from plants and microorganisms, and host CKD phenotype should be established in future research based on the hypotheses developed from these correlative studies . The sysnt years . The synvia targeting gut microbiota. These natural products from plants and microorganisms have an impact on the biogenesis and progression of CKD and its relative metabolic complications through alteration of the diversity and composition of the gut microbiota. More research should be carried out to prove the causal role of intestinal microflora in the treatment of CKD by natural products from plants and microorganisms based on these associative studies.In summary, the literature analyzed in this review suggests a great advantage in the adoption of natural products from plants and microorganisms to treat CKD"} +{"text": "Ferroptosis, a new type of cell death, is mainly characterized by intracellular iron accumulation and lipid peroxidation. The complex regulatory network of iron metabolism, lipid metabolism, amino acid metabolism, p53-related signaling, and Nrf2-related signaling factors is involved in the entire process of ferroptosis. It has been reported that ferroptosis is involved in the pathogenesis of neurological diseases, cancer, and ischemia\u2013reperfusion injury. Recent studies found that ferroptosis is closely related to the pathogenesis of COPD, which, to some extent, indicates that ferroptosis is a potential therapeutic target for COPD. This article mainly discusses the related mechanisms of ferroptosis, including metabolic regulation and signaling pathway regulation, with special attention to its role in the pathogenesis of COPD, aiming to provide safe and effective therapeutic targets for chronic airway inflammatory diseases. In 2012, Dixon . The morThe mechanism of ferroptosis is shown in Iron is an element necessary for lipid peroxide accumulation and ferroptosis. Excessive iron load promotes the production of ROS through the Fenton reaction and iron-binding proteins, thereby promoting the occurrence of ferroptosis , 9, 10. Lipid metabolism is critical for regulating cellular susceptibility to ferroptosis. Because plasma membrane damage caused by iron-dependent excess accumulation is an important feature during ferroptosis , reducinFerroptosis caused by abnormal amino acid metabolism is mainly related to the abnormal metabolism of GSH. GSH is a key substance in amino acid metabolism in ferroptosis and is mainly synthesized from cysteine, glutamate, and glycine . ExtraceCystine/glutamate anti-transport system Xc- (System Xc-) on the cell membrane transports extracellular cystine and intracellular glutamate in a 1:1 ratio. Cells mainly acquire cystine from the extracellular space through System Xc-, where cystine is reduced to cysteine to participate in the synthesis of GSH, and erastin acts on System Xc- to inhibit the uptake of cystine by the cell membrane, thereby reducing the synthesis of GSH and further contributing to the accumulation of ROS . BecauseThe process of ferroptosis is affected by different signaling pathways. As a tumor suppressor gene for cell cycle inhibition, apoptosis, and senescence, p53 is also one of the main signaling pathways of ferroptosis in cells , 27. RelNuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant activity, and its targets play important roles in iron and lipid metabolism , 36. StuThe pathogenesis of COPD is based on the response of the body to inhalation of harmful particles and gases, and it is complex and has not been fully elucidated. Smoking is the main cause of COPD, and the pathogenesis of COPD is mostly related to inflammatory mediators, inherent immunity, oxidative stress, and protease/antiprotease imbalance , 44. AmoCigarette smoke (CS) and harmful particles induce the body to produce highly reactive molecules such as ROS and reactive nitrogen species (RNS), thus inducing oxidative stress. The accumulation of neutrophils and macrophages in airways and pulmonary blood vessels causes the release of a large number of inflammatory mediators, which induces an inflammatory response and leads to lung tissue damage and protease/antiprotease imbalance, ultimately accelerating the progression of COPD . OxidatiOxidative stress is an important pathogenic factor in COPD, and the presence of a large amount of ROS in the inflammatory response inactivates antiproteases and leads to lung tissue damage. Excessive secretion and accumulation of neutrophils lead to the production of a large amount of reactive oxygen species (ROS). The accumulation of ROS reduces the activity of histone deacetylases (HDACs) and increases the activity of histone acetyltransferases, leading to further accumulation of neutrophils, which exacerbates oxidative stress .Iron homeostasis may be disrupted in inflammatory diseases, resulting in the production of excess reactive oxygen species with deleterious effects on cells and tissues. Epithelial cells and macrophages in lung tissues produce iron metabolism-related proteins, which regulate iron homeostasis and prevent the occurrence of oxidative stress . DisruptLipid peroxidation is the loss of hydrogen atoms of intracellular lipids under the action of peroxidase or free radicals, resulting in oxidation, fragmentation, and shortening of carbon chains as well as lipid-free radicals, malondialdehyde (MDA), and 4-hydroxy-2-nonenal (4-HNE) peroxidation products, which eventually oxidatively degrade lipids and damage the lipid bilayer structure of cell membranes. CurrentlSmoking increases the content of lipid peroxidation in the body, and lipid peroxidation is closely related to the pathological progression of COPD . A surveThe role of ferroptosis in COPD is shown in In vivo studies showed that CS causes lung injury in COPD rats, increases inflammatory cell infiltration, increases inflammatory cytokine secretion, and induces ferroptosis in lung tissue cells of COPD rats. In vitro and in vivo studies showed that CSE/CS increases the MDA content, increases the iron content, downregulates GPX4, decreases ferritin heavy chain levels, and upregulates transferrin receptor levels and also reported that curcumin reverses CS-induced lung inflammatory damage and epithelial cell ferroptosis . These findings suggest new options for the treatment of patients with COPD.Morphological aspects of ferroptosis mainly manifest as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and increased mitochondrial membrane density. Liu et al. found that dihydroquercetin (DHQ) inhibits CS-induced ferroptosis in the pathogenesis of COPD by activating the Nrf2-mediated pathway and attenuating CSE-induced mitochondrial morphological changes . In vitrNrf2 is a key factor in maintaining the oxidative/antioxidative balance, which can prevent the occurrence of COPD by resisting oxidative stress and lung inflammation. Recent studies reported that CpG hypermethylation in the promoter causes downregulation of Nrf2 expression in the lung tissue of patients with COPD . Zhang ein vitro and in vivo studies, Liu et al. found increased levels of M2 macrophages, MMP9 expression, and MMP12 expression in patients with COPD, CS-exposed mice, and THP-M cells cocultured with CSE-treated human bronchial epithelial (HBE) cells, suggesting that NCOA4 and ferroptosis are involved in the pathogenesis of COPD , deferiprone, and deferasirox. DFO is one of the drugs that have been approved by the FDA for the treatment of iron overdose . In addiresponse . Howeverresponse . Anotherresponse . Throughresponse . TherefoOxidative stress is an important cause of airway inflammation, lung parenchyma destruction, and lung function decline in COPD, mainly induced by inhalation of air pollutants such as CS/CSE and dust. The acute exacerbation of COPD is closely related to oxidative stress and oxidant/antioxidant imbalance in the blood . Studiesin vitro and in vivo studies showed that ferroptosis is closely related to a variety of disease processes, and appropriate intervention in ferroptosis can treat the disease and delay the progression of related diseases. Although some progress has been made in the role of ferroptosis in lung cancer, ALI, and pulmonary fibrosis, the role of ferroptosis in COPD is not fully understood, and further clinical and experimental studies are needed. Although the existing ferroptosis inducers are effective, the therapeutic modalities for ferroptosis are still insufficient and only include iron inhibitors, iron chelators, and antioxidants. Identifying effective diagnostic markers of COPD may aid in the treatment of ferroptosis in COPD. For example, the known important regulator of iron metabolism, hepcidin, and its receptor, Fpn1, have been demonstrated to be effective diagnostic markers for COPD, and they may be promising targets for future drug development. In conclusion, with increasing studies on ferroptosis, new related regulators and their functions are constantly being explored. Considering ferroptosis as an entry point to develop COPD treatment regimens and targeted drugs has important clinical value.Ferroptosis, a new type of cell death, is involved in the pathogenesis of various diseases. Ferroptosis is a process involving abnormal metabolism of iron, amino acids, and lipids, which are involved in cell proliferation and differentiation. The metabolic process of ferroptosis is complex, and its mechanism has been preliminarily studied. Both The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.DM and CZ wrote the manuscript. RJ and ZL provided language assistance. WW proofread the manuscript. SS was involved in the design and review of this study. All authors contributed to the article and approved the submitted version."} +{"text": "Multidrug-resistant organisms (MDRO) are bacteria that exhibit acquired resistance to multiple antibiotics, reducing the efficacy of antimicrobial therapies. The spread of MDRO is currently one of the most important threats for public health, and it is associated with a remarkable burden in terms of increased morbidity, mortality, healthcare costs, and antibiotic use ,2,3.The extensive and, in most cases, inappropriate uses of antimicrobials, at both human and veterinary levels, contribute to the selective pressure at the basis of MDRO diffusion. Different factors contribute to the spread of resistant bacteria to humans and animals, including poorly prepared food, proximity, and inadequate hygiene. Resistant bacteria can be spread in the environment and food through contaminated wastewater or through wildlife. The best strategy to contrast the spread of MDRO is the implementation of a One Health approach, which involves the collaboration of multiple sectors to improve public health outcomes as defined by the World Health Organization .This Special Issue includes a collection of ten research articles, communications, and reviews focused on the epidemiology and pathogenicity of MDRO. Enterococcus spp isolates were investigated. Their results established the presence of nosocomial-associated clonal complex 17 and a variety of mobile genetic elements among the enterococci from backyard chickens, suggesting the possibility of their dissemination in backyard farms and related environments [Alzahrani and coworkers investigated the role of backyard healthy chickens as a potential reservoir for MDR and virulent enterococci. In this study, antimicrobial resistance and virulence determinants, biofilm formation, plasmid content, and the clonality of ronments .Escherichia coli (ExPEC) lineages. Meanwhile, rabbits were a source of resistant and virulent E. coli pathogens with acquired colistin resistance determinant mcr-1 [Animals, community, hospital, and industrial settings (including food-production) have been investigated as possible sources of Antimicrobial Resistance (AMR) by Massella and coworkers. Their article reaffirmed the role of food-producing animals as a reservoir of potential zoonotic pathogens, with variable antimicrobial and virulence traits among the sources investigated. In particular, rabbits and poultry represented the most concerning sources, carrying the highest number of antimicrobial resistance genes (ARGs) and virulence-associated genes. Poultry was associated with potential extraintestinal pathogenic nt mcr-1 .Enterobacterales (ESBL-E), carbapenemase-producing Enterobacteriaceae (CPE), and methicillin-resistant staphylococci (MRS) in a companion animal clinic in Switzerland. The study documented the plasmidic dissemination of blaOXA-48 in a companion animal clinic with low infection prevention and control (IPC) standards. This poses a worrisome threat to public health and highlights the need to foster standards in veterinary clinics to prevent the spread of MDRO into the community [The role of animals in the spread of MDRO has also been described by Schmitt and coauthors, who reported extensive environmental contamination with extended spectrum \u03b2-lactamase-producing ommunity .To reduce the circulation of MDRO, the programs of surveillance should be combined with the implementation of efficient disinfection protocols that employ various biocides. Geraldes and coworkers in the paper titled \u201cEvaluation of a Biocide Used in the Biological Isolation and Containment Unit of a Veterinary Teaching Hospital\u201d tested a recently developed biocide (Virkon\u2122S), presenting a complex formulation with mainly oxidative activity. Their results suggested that this novel biocide presented efficient antimicrobial activities against representatives of different bacterial species isolated from the Biological Isolation and Containment Unit (BICU). However, organic matter could interfere with its antimicrobial activity, and a slight change of antimicrobial susceptibility was observed in four enterococci, which is probably related to a general stress-induced response promoted by the sub-lethal levels of Virkon\u2122 S .Klebsiella pneumoniae clinical isolates in order to help the control and management of associated infections and to limit their spread in the hospital environment. In addition, the characterization of the emerging high-risk clones can support the implementation of protective actions and infection control procedures [The ability to produce biofilm and its correlation with antibiotic resistance was also reported by Fasciana and coauthors in their communication. The authors underlined the need to characterize the genetic diversity and biofilm formation properties of ocedures .K. pneumoniae and Acinetobacter baumannii in the intensive care unit (ICU) and of E. coli in non-intensive care units (non-ICUs). The authors stressed the importance of the implementation of large community-level programs to prevent bacteremia caused by MDRO. The authors observed that local surveillance and the implementation of educational programs remain essential measures for slowing down the spread of resistance and, consequently, for increasing antibiotic lifespan [A retrospective investigation from Southern Italy on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted by Di Carlo and coworkers. The authors reported a higher prevalence of lifespan .Gentile and coworkers reported the importance of surveillance programs for nosocomial drug resistance. They suggested that whole-genome sequencing (WGS) proved to be a useful tool for elucidating the spreading dynamics of MDRO and can help in limiting their diffusion. According to the authors, the analysis of resistome and virulome by WGS, if available in real-time, could help to survey the alert nosocomial pathogens by directing the infection control team to focus its attention and resources in departments where surveillance is more necessary .To reduce the diffusion of MDRO, the use of an appropriate antibiotic therapy is of paramount importance. Fiore and coworkers in a systematic review and meta-analysis titled \u201cCeftolozane-Tazobactam Combination Therapy Compared to Ceftolozane-Tazobactam Monotherapy for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis\u201d reported that combination therapy with ceftolozane-tazobactam (C/T), compared to C/T monotherapy, may reduce all-cause mortality in infections due to Gram-negative bacteria but did not increase the rate of clinical improvement .Helicobacter pylori. It is very important to have a good understanding of regional antibiotic resistance patterns of H. pylori for the implementation of effective empirical eradication therapies and adequate rescue therapies. The study conducted by Park and coworkers investigated the antibiotic resistance patterns of H. pylori and their impact on eradication in Seoul in recent years [H. pylori eradication in Korea.The rate of multidrug resistance is also increasing in nt years . Their rH. pylori and the consequent limited therapeutic options available against this pathogen represent an important topic in gastroenterology. The aim of the review presented by Krzy\u017cek and coworkers was to list compounds showing the ability to enhance the antimicrobial activity of classically used antibiotics against H. pylori. The antimicrobial properties, such as minimal inhibitory concentrations and minimal bactericidal concentrations, dose- and time-dependent mode of action, and, if characterized, anti-biofilm and/or in vivo activity of these compounds are also reviewed [The increasing spread of antibiotic-resistant reviewed . In conclusion, this Special Issue collected articles and reviews that underlined the need for robust surveillance systems that are essential for combating antibiotic resistance at both hospital and environmental levels, emphasizing the necessity of an \u201cOne Health\u201d approach. The importance of both phenotypic and genotypic approaches for the characterization of MDRO, and the necessity of novel effective antimicrobials and biocides active against MDRO was also emphasized."} +{"text": "Primary care stresses the importance of the relationship between physicians and patients . AccordiMoh et al.). Many infectious diseases such as malaria, tuberculosis, and human immunodeficiency virus (HIV) are major issues for the health system in C\u00f4te d'Ivoire, mainly because health resources remain inaccessible and inefficient, especially in rural areas . To solve this problem, Moh et al. conducted a study in three locations to improve the integration of HIV, malaria, and tuberculosis prevention. This project was planned for a duration of 3 years, including 2 years of field activities with six main activities . Through this project, Moh et al. proposed some strategies to improve the integration of HIV, malaria, and tuberculosis prevention, including selecting and strengthening the capacity of community health workers to provide care for these three diseases, providing monthly animation of village health committees by target groups, and using application and tablets for data collection.The studies collected on this topic cover a wide range of research on family medicine and primary care, including systematic review and meta-analysis of the prevalence and risk factors of disease, research exploring factors associated with disease, strategies aimed at improving the healthcare system, effects of different guidelines on mortality risk of disease, development of measurement technology, evaluation the price, availability, and affordability of essential medicines, as well as distribution of health problems. We expect that the research on this topic or the evidence they provide will act an informative role in family medicine and primary care. Community Health Workers (CHWs) are a key component in promoting population health and improving health systems, especially in many low- and middle-income countries with 17,708 subjects aged 45 years and older in 2011\u20132012, to examine the change in the prevalence and mortality, if the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline were adopted for Chinese adults. The study found that if the 2017 ACC/AHA guideline was adapted for Chinese adults aged 45 years or older, the hypertension prevalence would increase, which was mostly attributable to the change in the definition of systolic diastolic hypertension . However, the difference was minuscule in the proportion of people recommended for antihypertensive treatment among people with isolated diastolic hypertension or isolated systolic hypertension. Also, the study has found that the adoption of the 2017 ACC/AHA might be applicable to improve the unacceptable hypertension control rate for Chinese adults aged 45 years or older .This topic also collected a study regarding the policy for patients with hypertension in China, which highlighted how different guidelines would have an impact on the effects of primary care and patients' health outcomes. Specifically, the China Hypertension League (CHL) guideline is different from the guidelines in the United States , 7. TherLiu Z. et al. conducted a systematic review to explore the status quo of BP measurement technology and development trends of BP measurement. In general, the technology of auscultatory, applanation tonometry, and volume clam methods are mature, and new control methods of volume clamp are developing . However, the study found limitations and challenges in existing finger-end BPM technologies as well , indicating that further research on new technologies is still needed to facilitate the development of daily multi-scenario and multi-frequency BPM technologies and provide a basis for realizing long-term personal BP management strategies.Another study covered in this Research Topic also focused on primary care for blood pressure in the Chinese population. Previous research suggests that routine blood pressure (BP) monitoring may help predict mortality , 9. TherWang et al. based on the adjusted World Health Organization and Health Action International methodology. This study found that the Medication Possession Ratio (MPR) for lowest-priced generics (LPGs) was generally decreasing between 2016 and 2020 . In addition, the median availability of generic medicines increased in 2018 . These results indicated that the National Essential Medicines Policy (NEMP) has proceeded relatively well in the primary healthcare institutions (PHIs) in Jiangsu . In addition, this Research Topic also contains other related studies, including a systematic review on dyspnea measurement in acute heart failure , research exploring factors associated with childhood asthma and wheezing in Chinese preschool-aged children , a systematic review and meta-analysis of the prevalence and risk factors of depression in type 2 diabetes patients in China , and a cross-sectional study exploring the distribution of health problems at the general outpatients' clinic of the University of Hong Kong-Shenzhen Hospital . It has long been documented that characteristics such as gender, race, and socioeconomic status are associated with the use of healthcare services in routine care, which might further bring health disparities in health outcomes (As more and more new medicines become available, healthcare systems face considerable challenges in regulating drug prices, affordability, and affordability for primary care . To evaloutcomes \u201313. As toutcomes , 15. Furoutcomes . At lastXX, GL, XJ, HM, and KL conceived the idea for the editorial and wrote the initial draft. All authors approved the final version of the editorial."} +{"text": "Thyroid dysfunction such as hypothyroidism, is connected with numerous neurological and psychiatric disorders. However, the importance of assessing the interaction between brain, psyche and thyroid in clinical practice is often underestimated, and this has a direct impact on the planning of therapeutic interventions and treatment efficacy in patients with primary hypothyroidism.We examined 132 patients with primary hypothyroidism.Assessment of the presence and severity of psychopathology was performed using the technique SCL-90-R (questionnaire severity of psychopathology).The results showed the highest scores on the scales of somatization , depression , interpersonal anxiety , phobias . High rates of somatization scale showing a violation of bodily dysfunction of various body systems-cardiovascular, gastrointestinal, respiratory and headache, muscular discomfort and other unpleasant sensations in different parts of the body and manifest themselves in a complaint of patients. Scale depression revealed the presence of dysphoria, anhedonia, low affect, loss of vitality and interest in life. Relatively high on a scale of phobias indicate the presence in these patients persistent fear responses to certain situations and objects that are irrational and inadequate and lead to avoiding behavior. General index of severity of symptoms (GSI) and the index of an existing symptomatic distress (PSDI) were significantly higher in the following patients than in hypothyroid patients without mental disorders.Thus, these results should be taken into account when determining treatment strategy both in psychopharmacotherapy and different methods of psychological correction.No significant relationships."} +{"text": "Due to the many factors involved, the treatment of cancer by Chinese medicine is very complicated: it is not only a variety of components of Chinese herbal medicines but also a complicated cancer network among tumor cells, tumor microenvironment, human interior milieu, and the environment. In addition, the interaction between the gut microbiota and the host also has a potential impact on cancer progression. The complexity of Chinese herbal medicines and the pathogenesis of cancer makes it difficult to understand the pharmacological effects of anticancer Chinese herbal medicines, especially when the treatment is in the form of a mixture of multiple compounds, such as Chinese herbal formulas.To address such a high level of complexity, advanced approaches are needed. Thanks to the advent of systems biology and advanced OMICs techniques, including genomics, transcriptomics, proteomics, metabolomics, and bioinformatics, novel systems-based approaches have been developed and widely used in the research of Chinese medicine, leading to the rapid progress of this research field and more comprehensive understanding of the pharmacological mechanisms of Chinese herbal medicines in cancer treatment.Albuca Bracteata (Thunb.) J.C.Manning & Goldblatt in a colon cancer model. They found that the change of intestinal microbiota and therefore production of beneficial short-chain fatty acids might contribute to the anti-tumor effect of Albuca Bracteate Polysaccharides when used alone and in combination with the chemotherapeutic agent 5-fluorouracil Yuan et al. Another study by Shi and others performed 16S rRNA gene sequencing and metabolomics to study the mechanism of action of Siwu-Yin, a formula used in traditional Chinese medicine for the treatment of esophageal precancerous lesions and esophageal cancer. They found this formula traditionally used to replenish blood and nourish Yin improved the composition of intestinal flora by regulating the synthesis and secretion of bile acids. This action of Siwu-Yin contributed to the modification of the tumor microenvironment and inhibited the occurrence of esophageal precancerous lesions . These studies have provided us insights into the application of combined OMICs technologies in the pharmacological studies of botanical drugs.In this special collection, we aimed to highlight the application of OMICs and other advanced approaches in understanding the mechanisms of action of medicinal botanical drugs as a mixture of multiple components in the treatment of human diseases, especially gastrointestinal cancer. We have received 16 submissions by authors from mainland China, Macau S. A. R., and Hong Kong S. A. R, including both original articles and reviews, and seven of them are accepted for publication. Among these published studies, Yuan and others innovatively combined multiple OMICs platforms to analyze the modulation of gut flora metabolites by the polysaccharides extracted from a Chinese botanical drug Dai et al.). Li and others focused on the application of OMICs technologies as useful tools for deciphering the role of botanical drugs as an adjuvant therapy, both to improve therapeutic outcomes and to reduce the side effects of conventional therapies, in the treatment of gastrointestinal cancers. They highlighted that OMICs approaches can efficiently reveal potential key molecular targets and intracellular interaction networks of herbal medicines in gastrointestinal cancer, therefore guiding future research Li et al. Guo and others particularly reviewed the application of metabolomics in investigating herbal therapies against gastrointestinal cancers by targeting metabolism. They systematically summarized the actions of herbal compounds, extracts, and formulas on the metabolism of carbohydrates, lipids, amino acids, and nucleotides, as well as on other metabolic pathways, and highlighted the usefulness of metabolomics in guiding the further development of botanical drugs as novel and efficient adjuvant therapeutics against gastrointestinal cancer . In addition, Coptidis Rhizoma and Chinese Medicine-based carbon dots were introduced by He et al., and Li et al., respectively, as examples for a better understanding of the application of OMICs in pharmacological studies of herbal products. He et al. reviewed the broad pharmacological effects of Coptidis Rhizoma (C. Rhizoma) against cancers, highlighted recent studies on the botanical drugs, including the application of OMICS, novel drug delivery systems, combination therapy and clinical research, and provided new scientific and clinical evidence for future clinical use of the botanical drugs in treating gastrointestinal cancers . Li et al., reviewed the progress in Chinese herbal medicines-derived carbon dots for the treatment of hemorrhagic diseases and also discussed the application of nanomaterials, OMICS and other advanced technologies in the research and development of charcoal drugs against other refractory diseases, e.g., cancers Li et al.This special issue has also collected expert opinions and reviews on the application of OMICs technologies in the pharmacological studies of botanical drugs. Dai and others reviewed the state of art and provided their future perspectives on OMICs applications in studies on herbal treatment of gastrointestinal cancers. They highlighted how single and multiple OMICs approaches may facilitate unravelling signalling interaction networks and key molecular targets of botanical drugs with anti-gastrointestinal cancer potential. Their review suggested that, towards precision medicine, extensive application of high-throughput sequencing technologies to unravel tumor heterogeneity is urgently needed for stratified diagnosis of gastrointestinal cancers and better-targted herbal treatment (In conclusion, the applications of single and combined OMICs technologies, systems biology, and other advanced methodologies have been very useful in studying botanical drugs. We wish readers will enjoy reading articles in this special collection, which represent the state of the art of OMICs-based pharmacological studies of botanical drugs. As shown in"} +{"text": "The African region faced a large-scale public health crisis, with the outbreak of coronavirus disease 2019 (COVID-19). As of February 16, 2022, the region recorded 7,944,049 confirmed cases with case fatality of 2.1 percent [The WHO African region adopted and implemented the new WHO ACT-Accelerator strategy in its response to the pandemic . New ACTThe countries mounted and implemented several actions in response to the outbreak. Some actions entailed the use of innovative strategies in addressing transmissibility and spread of the virus, reaching the populations with vaccines, diagnostics, and therapeutics. Others were on surveillance and testing, infection prevention and control, public health and social measures as well as contact tracing, among others. The Incident Management Support Team (IMST) of the WHO AFRO further enabled the countries with evidence-driven innovations and guidelines in responding to the COVID-19 pandemic.Several experiences were gathered that could be useful for future public health interventions. This special issue of the Pan African Medical Journal documents the of the key lessons and experiences gathered from response to the COVID-19 pandemic in countries as well as the WHO AFRO IMST. The papers, written by those who were actively engaged in response to epidemics in countries, cover critical topics from preparedness and response to disease outbreaks, strengthening surveillance systems and integration as well as strengthening health workforce against pandemics. The comprehensive analysis of the success stories made in pandemic response will no doubt enhance response to future public health events within and outside the region. These articles therefore constitute a case of turning tragedy to gains!"} +{"text": "The inspiring digital event brought together international speakers and presented a multidisciplinary approach to one of the less-addressed topics in neurology. The event it was coordinated by Antonio Federico , Professor of Neurology at the Department of Medicine, Surgery and Neurosciences from the Medical School at the University of Siena , and Dafin Muresanu (Romania), EFNR President, and was divided into 4 sessions over the course of the day.The Antonio Federico and Dafin Muresanu (Romania), with the two highlighting the increased interest of stakeholders in this subject from neurology.The Teaching Course on Rare Neurological Diseases began with a welcome address by Kailash Bhatia (UK) and Antonio Federico . A presentation entitled \"Rare Neurologic Diseases, a Pandora Box for Neurology and Neurosciences\" was introduced by the latter, Antonio Federico , Professor of Neurology at the Department of Medicine, Surgery, and Neurosciences from the Medical School at the University of Siena . About 300 million people are affected by a rare disease \u2013 3.5\u20135.9% of the population \u2013 with a majority having genetic pathogenesis and more than half of the cases involving the central or peripheral nervous system and muscles. Prof. Federico firstly discussed what makes a disease rare, namely the standards for classification. Moreover, he went over why rare diseases and orphan therapies lead to many unacceptable inequities in the health systems, from trouble finding experts on the disease, limited availability of therapies, and the issue of pharmacological companies having little interest in developing drugs. Prof. Federico stated the crucial role of neurologists in diagnosing and treating rare diseases in general, as many affections present with neurological manifestations. Furthermore, he discussed the universal challenges faced by those living with a rare disease, mentioning the broad diversity of disorders and relatively common symptoms that can hide the correct diagnosis. He talked about the commonality of misdiagnosis and the variability of symptoms from one patient to another in the context of the same rare disorder. Prof. Federico also tackled in his presentation the importance of research and international collaboration of researchers and clinicians, as well as the involvement of multiple stakeholders, mentioning recent developments in Europe concerning networks aiming to improve the diagnosis and treatment of rare diseases. He further approached the European Reference Networks, especially those for rare diseases, underlining the European Brain Council Research Project \u2013 The \"Value of Treatment (VOT) for brain disorders\". Moreover, Prof. Federico highlighted the World Health Organization's (WHO) highly active endeavour on revising the ICD-10 Diseases of the Nervous System Chapter from a rare disease perspective. Lastly, he mentioned the problem of expensive orphan drugs leading to equity issues in rare diseases. He ended his presentation by stating the necessity for comprehensive global action to improve the quality of diagnosis and care.The first session was presided over by Kailash Bhatia (UK), Professor of Clinical Neurology at the Sobell Department of Movement Neuroscience \u2013 Institute of Neurology, UCL, in Queen Square, London (UK), discussed the \"Rare presentation of Parkinson's diseases and dystonia\". Prof. Bhatia covered several case studies on various disorders with variable presentations, from language and calculation difficulties to gait imbalance and cerebellar features of parkinsonism. He showcased imaging clues for different types of parkinsonism, the difficulties in diagnosis, and pointed to different affections, signs, and triggers to be avoided. Rare diseases causing movement disorders are a significant subset of conditions as they represent a substantial proportion of movement disorders. The importance of recognition and awareness of the treatable forms and the treatment implications were also discussed. Finally, Prof. Bhatia highlighted that many rare neurological disorders provide vital insight into the pathophysiology of more common movement disorders.Max Hilz (Germany), from the Department of Neurology, Icahn School of Medicine at Mount Sinai in New York (USA), discussed, during his presentation \"Evaluating autonomic dysfunction in Rare Neurologic Diseases \u2013 a diagnostic tool and predictor of increased risk\", about hereditary sensory & autonomic neuropathies (HSAN Types I-VIII), the steps in the assessment and consideration for the diseases' epidemiology and their timelines, along with prominent clinical features. Moreover, he presented HSANs types 1, 2, 3, 4, and 5, with insight into the sural nerve pathology, in addition to diagnostic steps to determine the type of HSAN, including history, clinical examination, motor & sensory nerve conduction studies, quantitative sensory testing, assessment of the sudomotor function, of sympathetic or parasympathetic deficits, and many more.Michelangelo Mancuso , began by introducing Michelangelo Mancuso , the Head of the Centre of Neurogenetics and Expertise for Mitochondrial Diseases and Rare Diseases \u2013 Department of Clinical and Experimental Medicine at the Neurological Institute, University of Pisa , with his presentation \"Stroke and Rare Neurologic Diseases. An EAN Consensus\". Prof. Mancuso discussed the importance of awareness and minimizing diagnostic delays. Moreover, he offered insight into cerebral small vessel diseases , along with some related issues. Prof. Mancuso followed the Delphi methodology to provide recommendations and proposed \"red flag\" features suggestive of the diagnosis of monogenic disease and discussed specific recommendations for the particular forms of monogenic cSVD. He further approached some rare diseases, including Fabry disease, CADASIL, and MELAS, and highlighted the EAN management and recommendations, pointing out that the EAN consensus provides a valuable framework to guide diagnosis and management.The second session, presided by Marianne de Visser (the Netherlands) and Marianne de Visser (the Netherlands), Senior Neurologist at the Amsterdam University Medical Center in Amsterdam (the Netherlands), presented \"HyperCKemia: from common to rare\". Dr. de Visser discussed asymptomatic and paucisymptomatic hyperCKemia, the most common causes, the steps leading to a differential diagnosis, and the most appropriate diagnostic tools. In addition, she offered a glimpse into variations of the disease in different populations and presented insightful case studies from her practice. One crucial point was the role of complex diagnostic assessment, including detailed family history and ancillary investigations , offering a lively and engaging presentation with interactive exercises for the public.Antonio Federico , Professor of Neurology at the Department of Medicine, Surgery and Neurosciences \u2013 Medical School from the University of Siena in Siena , then discussed \"Rare Neurologic Diseases mimicking a multiple sclerosis like phenotype\" through the presentation of a comprehensive set of disorders , mentioning the McDonald Diagnostic Criteria. For multiple sclerosis (MS), several genetic conditions need to be considered in the differential diagnosis. Prof. Federico offered a complex and all-encompassing view of this large set of disorders and offered the public a glance, through case studies presentation, into the fascinating world of rare neurological disorders.Davide Pareyson , the Head of Rare Neurodegenerative and Neurometabolic Diseases Unit at the Dept. of Clinical Neurosciences, IRCCS Foundation, Neurological Institute Carlo Besta in Milan , presented \"Clinical and diagnostic approach for diagnosis of rare forms of peripheral neuropathies\", discussing the time to consider them as a diagnosis and ways to diagnose these diseases, pinpointing that the most important forms are hereditary and immune-mediated neuropathies. He talked about the role of early diagnosis in detecting diseases and initiating early treatment, and also approached clinical phenotypes for acute neuropathies, chronic sensory-motor demyelinating/axonal, relapsing, pure motor neuropathy, and sensory ataxic or painful neuropathies. Next, Prof. Pareyson presented the steps for diagnosis and the use of next-generation sequencing in certain diseases and hereditary TTR-related amyloid neuropathies in non-endemic countries. Lastly, he discussed Charcot-Marie-Tooth and other chronic immune-mediated or neoplastic neuropathies and underlined the fact that various neuropathies are represented by different phenotypes.Session 3 was overseen by Wolfgang Grisold (Austria) and Jean-Marc Burgunder (Switzerland). Firstly, Wolfgang Grisold (Austria), President of the World Federation of Neurology (WFN), presented on the Paraneoplastic Neurological Syndromes, with mentions about the history of the syndromes, different types of most-likely cancers, their mechanisms, therapy, and prognosis. He also discussed the classification of paraneoplastic antibodies based on cancer risk and offered insight into Lambert Eaton Syndrome. One crucial point of his presentation was that the diagnosis of paraneoplastic syndrome is a diagnosis of exclusion.Dafin Muresanu (Romania), President of the European Federation of NeuroRehabilitation Societies (EFNR) and Chairman at the Department of Neurosciences from Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca (Romania), offered an inspiring glimpse into the neurorehabilitation for rare neurologic disorders in the context of rare causes of stroke, discussing the concepts of post-lesional brain regulation following two sequences (1) neuroprotection and (2) neurorepair. Prof. Muresanu mentioned that \"when neuroprotection is active, neurorecovery is silent\" and vice versa, showcasing that neurorehabilitation is represented by a mixture of neurorestorative and compensation capacities. He further discussed the intricacies of endogenous defense activity. Neurorehabilitation is a multidisciplinary concept aiming to improve biological function by creating therapeutic learning situations. Prof. Muresanu pinpointed the role of a specialized multidisciplinary neurorehabilitation team . Moreover, the 3 essential components of neurorehabilitation, (1) motor, (2) cognitive, and (3) mood, were discussed, and noteworthy examples of neurorehabilitation effects on different pathologies were presented.Maria Judit Molnar (Hungary), the Director at the Institute of Genomic Medicine and Rare Disorders Semmelweis University in Budapest (Hungary), on \"New therapies for Rare Neurologic Diseases\". Prof. Molnar discussed different therapeutic options, their mechanisms on various levels and how pharmacological or surgical approaches can influence the phenotype. She focused on gene therapy, ARN-based methods, and protein modification therapies, mentioning the importance of allogeneic hemopoietic stem transplantation in monogenic neurogenetic disorders. Her presentation showcased general applications of therapeutic gene transfer, gene delivery methods, approved gene therapies, future gene therapeutic approaches in neuromuscular disorders, and valuable lessons from clinical trials. Genetic therapies are increasing extremely fast, opening new options for patients with neurological disorders. Still, there are some limitations, such as the high prices and the ways in which clinicians can support the development of drugs and therapies.The last session of the day, Session 4, presided by Holm Graessner (Germany) and Maria Judit Molnar (Hungary), began with a presentation of Jean-Marc Burgunder (Switzerland), Professor of Experimental Neurology at the Faculty of Medicine, the University of Bern in Bern (Switzerland), discussed updates in neurogenetics and therapy. First, he offered examples of different diseases , discussed variations related to the age of onset, and presented an inspiring case study on hereditary spastic paraplegia in twins. The second part of his presentation was structured around the concept of gene therapy, the use of vectors for the restoration of dopamine production and the use of antisense oligonucleotides to modify gene expression. As neurology has a vast number of rare disorders (>7000), with many different genes, pathways, and pathophysiology, there is a dire need to better understand the presented concepts.Holm Graessner (Germany), Coordinator of the European Reference Network for Rare Neurological Diseases based at the University Hospital in Tubingen (Germany), showcased in his presentation \"Undiagnosed Rare Neurologic Diseases and the ERN Role\" the European reference networks for complex diseases. One insightful point was that the rareness of disease could refer to the rareness of:Patients;Experts;Care structures of knowledge;Therapies.He discussed the large number of expert centers in 25 EU countries which aim to improve care for patients with neurological diseases . They create added value based on the youth partnership plan built to integrate patient representatives and organizations in a structured manner. Moreover, these expert centers monitor the care to sustain improvements, offer e-health for cross-border care, work on expert opinion-based recommendations and provide guidelines.This awe-inspiring event stands as proof of the significant need for international collaboration and dissemination of knowledge in neurosciences overall, but even more direly for the fascinating yet less addressed topic of rare diseases. As rare neurological diseases can lead to significant inequities in the healthcare system and heavily impact the affected patients, it is paramount to find sustainable solutions, through joint efforts, to address these biases and provide an improved standard of diagnosis and care. It is important to remember that rare diseases not only reflect a reduced incidence but rather the fundamental problems identified by several speakers, namely the lack of specialists, resources directed for the research and development of pharmacological treatments, and the increased chance of misdiagnosis. All of these are completed by a lack of comprehensive understanding of the disease and the best treatment avenues to ensure a high quality of life for the patients."} +{"text": "This Special Issue aims to highlight the usefulness of microRNA (miRNA) as diagnostic and prognostic markers of gastroenterological cancer (GC). GC is one of the leading causes of cancer death worldwide. Despite advances in GC therapy, the prognosis of those patients remains poor due to the high incidence of recurrence. A better understanding of the pathogenesis during GC development brings effective outcomes for the diagnosis and treatment at the early stages.Over the past two decades, researchers have unveiled the association between miRNA and the biology of GCs. In fact, the critical role of miRNAs in the developmental process of GCs is increasingly evident. Aberrant miRNA expression in tumor tissue and blood of GC has been implicated in disease diagnosis, prognosis, and therapeutic efficacy in different tumor types ,2. It isThis Special Issue contains three review articles and three original papers, amounting to six in total, on the biological roles of miRNAs in different tumor types of GC and their potential clinical applications. For example, inhibition of miRNA-122, a representative liver-specific miRNA, promotes drug resistance by increasing the expression of oncogenes in hepatocellular carcinoma and faciIn addition, miRNAs are released into circulation. Circulating miRNAs include the following four types: (1) miRNAs encapsulated in exosome, which have recently been recognized as promising, noninvasive, and stable biomarkers (2) miRNAs bound to protein and lipid, (3) miRNAs in apoptotic body, (4) miRNAs leaked from the cell . RecentlThe main aim of this Special Issue is to contribute to the current development and future prospects of tissue and circulating miRNAs as biomarkers of carcinogenesis, progression, metastasis, or drug resistance to chemotherapy in GCs. In addition, through the contributions to this special issue, we clarify how these GC-related miRNAs are involved in the mechanism of GC proliferation and development, and how these miRNAs can be applied to various biomarkers and GC therapies. Further data accumulation and clinical trials are needed to implement clinical applications."} +{"text": "Clear documentation of the understanding of the problem, development process, and content of interventions is essential to understand why interventions succeed or fail. Transparent reporting will enable future researchers to build on previous evidence and replicate or adapt interventions for new contexts. This paper describes the theory- and evidence-based systematic development of the Bloom Trial - a home-based intervention to promote healthy weight development among infants and children in Denmark.Development of the intervention is guided by the six-step planning tool the Intervention Mapping protocol. Step 1: Needs assessment including identification of risk factors in infancy and existing interventions, interviews with parents, and an organizational capacity assessment. Step 2: Development of program theory and matrices. Step 3: Selection of theoretical methods and practical applications for modifying personal and environmental determinants. Step 4: Development of intervention tools. Step 5: Planning of program adoption, implementation, and sustainability. Step 6: Generation of an evaluation plan.The Bloom intervention is universal but with a strong focus on families with low socio-economic position and non-Danish ethnic background. It is aimed at first-time parents and addresses early risk factors for child overweight such as parental skills and healthy habits related to food and meals, movement, screen time and sleep, and introduce a new theme: sense of security in the family. It will be integrated in existing services delivered by community health nurses supplemented with extra elements such as telephone consultations, family groups and a video library.The transparency of the developmental process and theoretical, empirical, and contextual foundation of the Bloom Trial may enable future studies to build on our findings and accumulate knowledge to promote healthy weight development among infants and children.The development process resulted in a complex intervention addressing known risk factors for child overweight e.g., meals, movement, screentime and sleep, and introduce a new theme: sense of security.Transparency of the developmental process may enable future intervention studies to build on our findings and accumulate knowledge to promote healthy weight development among infants and children."} +{"text": "Burnout occurs in every stage of a medical graduation and career. In the first years of graduation, is affects 35-45% of medical and dentistry students. This has severe consequences, such as: higher levels of suicidal ideation, substance abuse, medical errors and medical neglect; lower levels of empathy and self-compassion - essential to the quality of healthcare. Students with certain personality traits are more vulnerable to emotional dysregulation when facing stressors of daily life. Our recent studies proved that mindfulness and self-compassion can attenuate the effect of perfectionism on psychological distress.To present the rational, materials, methodology and preliminary results of our project COMBURNOUT, aimed to develop, implement and assess the efficacy of a mindfulness and self-compassion-based intervention to prevent burnout in medical and dentistry students.Students with high levels of burnout, psychological distress and perfectionism will be randomly assigned to intervention (8 weekly sessions) or control groups. The sessions will be composed by psychoeducation about burnout, mindfulness and self-compassion practices, within and between sessions. The follow up will include three assessment moments until a year after the intervention.We expect that the experimental group will present significantly lower levels of burnout, psychological distress and perfectionism, and higher levels of emotional regulation skills.The facilitators training and the manualization are guaranties of standardization and sustainability. If the positive impact of COMBURNOUT is verified, we intend to provide the program to medical/dentistry students from all over the country."} +{"text": "Despite being disproportionately impacted by health disparities, Black, Hispanic, Indigenous, and other underrepresented populations account for a significant minority of graduates in biomedical data science-related disciplines. Given their commitment to educating underrepresented students and trainees, minority serving institutions (MSIs) can play a significant role in enhancing diversity in the biomedical data science workforce. Little has been published about the reach, curricular breadth, and best practices for delivering these data science training programs. The purpose of this paper is to summarize six Research Centers in Minority Institutions (RCMIs) awarded funding from the National Institute of Minority Health Disparities (NIMHD) to develop new data science training programs. A cross-sectional survey was conducted to better understand the demographics of learners served, curricular topics covered, methods of instruction and assessment, challenges, and recommendations by program directors. Programs demonstrated overall success in reach and curricular diversity, serving a broad range of students and faculty, while also covering a broad range of topics. The main challenges highlighted were a lack of resources and infrastructure and teaching learners with varying levels of experience and knowledge. Further investments in MSIs are needed to sustain training efforts and develop pathways for diversifying the biomedical data science workforce. The National Institutes of Health (NIH) has had long-term strategic interests in bolstering the diversity of the biomedical and behavioral research communities . While eData science has grown tremendously in the past several years due to its great potential to transform industries, economies, and scientific discoveries. Many data science initiatives from the NIH, e.g., All of Us Precision Medicine, Bridge to Artificial Intelligence (BRIDGE2AI), are largely focused on the generation of flagship data sets to accelerate health research and improve the health of racial and ethnic minority populations ,7. AlthoThis paper aims to summarize all the NIMHD-funded RCMI institutions and their efforts with the development, deployment, and delivery of their respective data science training programs. We evaluate and highlight the reach, breadth, and feedback of these training programs with a particular emphasis on the targeted population and topics covered in the curriculum, as well as challenges & successes faced while designing and implementing these programs. Specifically, we utilized a cross-sectional survey to measure the demographics of learners served, curricular topics covered, methods of instruction and assessment, challenges, and recommendations by program directors. In what follows, we provide an overview of the RCMI program and the funding announcement from the NIMHD. We then provide an overview of survey questions and report on the results using descriptive methods. We conclude with a discussion on challenges and recommendations highlighted by project directors and link these results with the broader literature on developing and sustaining training programs with the stated goal of enhancing diversity.The study design consisted of a cross-sectional survey administered at six minority-serving institutions awarded supplements from the NIMHD to develop new data science training programs. This included RCMI programs at the University of Puerto Rico\u2014Medical Sciences Campus, Meharry Medical College, Jackson State University, the University of Hawaii at Manoa, Howard University, and the RCMI coordinating center at the Morehouse School of Medicine.The Research Centers in Minority Institutions (RCMI) Program is a congressionally sponsored program initiated by the NIH in 1985 and administered by the National Center for Research Resources (NCRR) [Since its establishment, the RCMI program has proven itself as a research powerhouse, with extraordinary strength across the spectrum of translational medicine, health disparity research, and minority research participant enrollment. As noted by Ofili et al., between 2000 and 2015 RCMI investigators from 18 sponsored institutions leveraged $805 million in RCMI program funds into $3.7 billion in additional awards, including 1643 R01 awards, with >14,000 publications and >500 patent disclosures [To address a lack of diversity in biomedical data science and to be better positioned for the challenges posed by the complex, highly dimensional, and inherently transdisciplinary nature of health disparities, the National Institute of Minority Health Disparities (NIMHD) issued a notice of special interest (NOSI) to invite applications for administrative supplements from eligible RCMIs. This funding opportunity is aimed at enhancing data science capacity at recipient institutions and fostering further collaborations between RCMI-funded researchers and data scientists .The emphasis of the supplement was placed on the development of data science skill-building activities. In the notice, the activities of interest included the development of new modules focused on data analysis with health disparities datasets. Additionally, the NOSI cited interest in the integration of datasets representing \u201cmultiple levels and domains of influence in the NIMHD Research Framework\u201d .The survey consisted of 25 questions and focused on understanding the breadth of the curriculum marshaled at each program. They survey was modified to assess additional criterion, such as program-specific data, including demographics of trainees, knowledge areas covered in training programs, mechanisms for instruction, and assessed competencies. The questions in this survey were based on an ACM Data Science Task Force questionnaire administered to academic and industry participants to understand the landscape of curricular offerings in data science . The surDescriptive analysis was performed on all quantitative survey data, including frequencies and percentages. Additionally, themes were identified in open ended questions around challenges and recommendations inductively.Six NIMHD-funded RCMIs were awarded to increase data science capacity for resource-constrained, minority-serving institutions. These institutions included the Medical Sciences Campus at the University of Puerto Rico, Meharry Medical College, Jackson State University, the University of Hawaii at Manoa, Howard University, and the RCMI-Coordinating Center located at the Morehouse School of Medicine.The specific aims of each of these training programs are detailed below:University of Puerto Rico\u2014Medical Sciences Campus: To enhance and build capacity for investigators and students from biomedical informatics and other disciplines in DS/AI/ML topics such as Jupiter Hub, coding with R, RStudio, and Python, using ML libraries and other cutting-edge techniques to mitigate Hispanics\u2019 health disparities. To accomplish this aim, we developed of a new course \u201d), focused on data analysis using Hispanics datasets, that represents multiple levels and domains of influence in the NIMHD Research Framework.Meharry Medical College: Develop authentic and sustainable collaborations between Meharry\u2019s RCMI researchers and data scientists within Meharry\u2019s new School of Applied Computational Sciences. Enhance Meharry\u2019s RCMI capacity by providing data science training to the community. Assess the learning and data analytics skills of the RCMI investigators, post-docs, staff, and/or graduate students and research capacity enhancement of the RCMI program.Jackson State University (JSU): With the overarching goal to train the next generation of scientists to address the monumental challenge associated with the curation, integration, analysis, and interpretation of biomedical big data, the specific aims of the Biomedical Data Science Training Program (BDS-TP) at JSU are to foster collaborations between data scientists and biomedical, socio-behavioral, and/or clinical researchers at the RCMI Center for Health Disparities Research at JSU; and build the capacity of JSU and other Historically Black Colleges and Universities (HBCUs) in Mississippi in biomedical data science by developing the biomedical data science skills of science, technology, engineering, and mathematics (STEM) faculty, students, and post-doctoral research fellows.University of Hawaii at Manoa: Provide education and training of data science-related skills to RCMI Researchers and their collaborators. Enhance collaborations between RCMI-funded researchers and data scientists. In addition to training RCMI investigators and their collaborators in a group in Aim 1, we will also offer individual data science training for investigators to foster collaborations between investigators and our data science experts.Howard University: To develop a new and targeted intensive data science modular training workshop focused on data analysis with minority health and health disparities datasets. To develop hands-on experience in the utilization of data science in minority health and health disparity research, which includes: (a) develop mentored summer research projects for undergraduate, graduate, and post-doctoral trainees and, (b) host product driven Codeathon events to address an issue or issues related to minority health or health disparity research. To promote and support the institutionalization of data science efforts at Howard University by: (a) developing train-the-trainer programs that provide targeted training opportunities for HU educators and encourage them to incorporate data science principles and exposures in their class offerings; and (b) developing a train-the-researcher program that provides training opportunities for HU RCMI researchers with emphasis on junior faculty to effectively incorporate cutting-edge data science techniques and capabilities into their research efforts.RCMI-CC at the Morehouse School of Medicine: To enhance the data science capacity of RCMI investigators across the RCMI consortium by collaboratively developing a project-based curriculum and organizing workshops introducing data science fundamentals and tools, as well as NIH-funded resources and datasets relevant to minority health disparities. To stimulate data science collaborations across U54 centers, as well as between U54 and non-RCMI institutions by organizing Data Science and Health Disparities Demo Days and launching enrichment awards to support the development of collaborative research projects.Each program recruited a diverse cohort of trainees at differing stages in their careers, ranging from undergraduate students to postdoctoral fellows and early-stage investigators and senior faculty see . The parInstitutions utilized existing resources, created new resources, and invited instruction from outside faculty see . Funded Survey respondents were asked to enumerate the top three challenges faced when designing and implementing their training programs , generally. The responses were varied but focused on similar themes, summarized in Examples of these recommendations were \u2018training-the-trainer\u2019 models of didactics, embedded multi-level coursework inside training programs , and investments in diverse faculty and mentorship to broaden the interdisciplinary reach at partnering institutions.The purpose of this study was to shed light on the reach, curricular breadth, and best practices in data science training at resource-constrained, minority-serving institutions by summarizing the efforts of six NIMHD-funded RCMI programs that received funding to develop data science training programs. The programs surveyed shared curricular goals around the application of cutting-edge data science techniques to different data types and training development around data science resources and tools. The average program used four tools and discussed over ten (>10.6) computing knowledge areas over the course of their curriculum. Together, the programs targeted building capacity at every point in the higher-education process (from undergraduates to continuing education for professors). The shared goals of the RCMI programs were to increase training capacity, professional development, and institutional collaboration. These goals have been highlighted across several RCMI initiatives and in the evaluation of RCMI programming ,14,15.The survey results also emphasize several pertinent themes around challenges in, and recommendations for, designing, implementing, and sustaining training programs to enhance diversity in data science training. Notably, the challenges and recommendations were reflective of issues of long-term planning and investment. For instance, the need for broad infrastructure was a recurring theme in survey responses; the possibilities for infrastructure development to bridge the chasm in data generation, analysis, access, and distribution has been echoed for several years ,16,17. AWhile the recommendations were diverse, the most agreed upon recommendations can be summarized by the prioritization and development of long-lasting resources. Program directors independently recognized the ways that diverse data set development, training for learners at various levels of erudition, and a multiplicity of training options would provide a better outlook for future generations of diverse investigators with robust data science skills. A plethora of educational modalities for healthcare researchers at various stages of education have demonstrated comparable performance and increased the reach of educational objectives ,21,22 anThere are three limitations of our study that are worth considering: first, the six RCMI programs considered are not a random sample of RCMI institutions. The programs covered were awarded grants through a competitive process, which limits the generalizability of our findings. Second, the funding opportunity from the National Institute for Minority Health disparities did not require a formal evaluation plan. As such, the programs evaluated did not utilize the same approaches to evaluating their respective programming. While our analysis attempted to develop a better understanding of who took part and what would be required to sustain the program over time, future studies should incorporate a formal evaluation of the data science programs using an existing framework like RE-AIM . FinallyThis article adds to the literature on investments in minority-serving institutions with the twin aims of enhancing capacity in these resource-constrained environments and contributing to the diversification of the scientific workforce. Our descriptive study provides insight on federally funded data science training programs leveraging the breadth and depth of the NIMHD-funded RCMI network. Our results support the need for increased diversity in data sets, increased curricular materials and work sets reflective of the diverse audiences served, and further diversity of personal and professional exposure for underrepresented professionals in biomedical data science. Investment and funding efforts to build and sustain increased capacity at RCMI and minority-serving institutions are necessary and may prove increasingly so as the diversity of the nation continues to outpace the diversity reflected in NIH-funded datasets and research. Taken together, there is strong evidence for building capacity in biomedical data science at RCMI institutions and the downstream impact for enhancing diversity in the biomedical research and data science workforce."} +{"text": "Frontiers in Microbiology to describe the state of the art, recent developments, major accomplishments, as well as the challenges and potential directions to move the fields of Microbiological Chemistry and Geomicrobiology forward.As the pivotal players in all the ecosystems, microbes drive the biogeochemical processes that are of both fundamental and practical significance. Microorganisms exert multiple ecosystem services which are crucial for the pressing issues such as biodiversity conservation, remediation of environmental pollution, global climate change, food production, and public health , the group of enzymes catalyzing hydroxylation of medium\u2014to long-chain length alkanes, focusing on the arrangement of the electron transfer proteins that activate AlkB. In the most extensively studied model organism, Pseudomonas putida GPo1, the alkB gene occurs on the OCT plasmid within an operon containing all the genes necessary for the transformation of alkanes to fatty acids and AlkB activation occurs via electron transfer from a flavin reductase and an iron-sulfur protein. Although this mechanism is well-established, the authors note that the OCT operon is not common in sequenced microbial genomes that contain alkB and describe other alkane-oxidizing strains that employ alternative electron-transfer arrangements. The authors review the biochemistry of the electron-transfer proteins and speculate about their biological significance. They also propose future avenues to enhance the mechanistic understanding of AlkBs in terms of their in vivo and in vitro characterization, structural information and alternative substrates.Alkanes originating from a variety of sources represent an important component of the global carbon cycle on Earth. While selective activation of the non-polar carbon-hydrogen bonds is energetically challenging, a variety of aerobic microorganisms are capable of oxidizing alkanes. Takamiya et al. report ultra-small cells inhabiting the grain boundaries of metal sulfide mineral assemblages in samples collected from extinct chimneys located in the southern Mariana Trough. Combined nanoscale secondary ion mass spectrometry (NanoSIMS), transmission electron microscopy coupled with electron diffraction (TEM-SEAD), Raman spectroscopy, fluorescence microscopy, and in-situ biosignature analysis allowed visualization and identification of ultra-small cells coated with copper nanoparticles in the chimney interior. Taken together these analyses support the occurrence of a distinct microbial community in the oligotrophic and anoxic extinct chimney. This study of ultra-small cells inhabiting the interior of a chimney suggests that photosynthesis-independent microbial ecosystems in submarine metal sulfide deposits could have existed billions of years ago on the early Earth.Genetic evidence provided by high-profile sequencing, parallel geochemical coupled with microscopic and spectroscopic analyses provide convincing evidence for the microbe-environment nexus, especially for organisms that are challenging to be cultivated. Liu et al. investigated the interplay of light, minerals, and microbes that could occur in the marine euphotic zone. Based on a suite of mineralogical and photoelectrochemical analyses, photoreduction and electron conversion were demonstrated for goethite (\u03b1-FeOOH), a representative and widespread semiconducting natural mineral. The experiments simulating light-illuminated marine euphotic zones showed photoreduction of goethite and release of reduced Fe(II) which affected the structure and diversity of the mineral-associated microbial community. The results suggest that light-induced interactions between semiconducting minerals and microorganisms may regulate microbial carbon cycles in the marine euphotic zone.Increasing evidence has demonstrated the importance of previously unrecognized reaction pathways in biogeochemical processes comprised of synergistic abiotic and biotic reactions. One example is the photoelectric conversion system, in which natural semiconducting minerals act as catalytic shuttles to sustain electron and energy flow from light to non-phototrophic bacteria. Chen et al. investigate the microbial composition and the ecological processes controlling community assembly shaped by different cropping strategies. Amplicon sequencing, functionality prediction, statistical analyses and modeling demonstrated that various cropping treatments influenced microbial communities, interspecies interactions, and the ecological processes that shaped the community composition in different soil-plant compartment niches. Crop rotation intensified the interspecies competition and decreased heterogeneity of the rhizosphere via strengthened selection force. Furthermore, the indicator species significantly influenced by intercropping and crop rotations potentially facilitated nitrogen/phosphorous cycling and degradation processes, respectively. The results suggest appropriate agricultural management may improve farmland soil fertility, crop yields, biomass growth, and economic benefit.Insightful understanding of microbe-environment interactions can also facilitate practical applications such as agriculture management and treatment of hazardous algal blooms. Coyne et al. provide a comprehensive review on algicidal interactions to control harmful algal blooms. Bacteria are capable of driving algicidal or algistatic effects through physical contact (direct mode) or generation of algicidal compounds (indirect mode), which result in a wide range of reversible and irrevocable outcomes for the target algae. The range of algicidal interactions, including specificity of bacterial control, mechanisms for activity, and chemical and biochemical characterization of the algicidal mode, were discussed. Considering the constraints on the spectrum and concentrations of bacteria and target algal species in laboratory-scale experiments, the research and strategies to enhance the efficacy of algicides and stability of the algicidal microbial cohorts under environment-relevant conditions were emphasized. The avenues for future research of alternative applications of algicidal bacteria in biotechnology, their ecological effects on non-target species, characterization and optimization of novel algicides to control hazardous algal blooms were also proposed and discussed.Finally, Taken together, the reviews and articles published in this issue cover different aspects of microbiological chemistry and geomicrobiology, from insights on genetic and biochemical mechanisms of biogeochemical processes in unique ecosystems to advancing fundamental knowledge for practical applications . Active research in these areas and many more exciting discoveries ahead of us will pave the way toward a more comprehensive understanding of biogeochemical processes in diverse ecosystems and integral to support sustainable development goals and the wellbeing of human populations.Both authors contributed to the article and approved the submitted version.via China University of Geosciences (Wuhan). BT acknowledges research funding received from the U.S. National Science Foundation on grants EAR 2122086 and CHE 2120408.YD appreciates the funding support from National Natural Science Foundation of China under the contracts 92051111, 41877321, and 91851211 and the Fundamental Research Funds for the Chinese Central Government The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The burden of cirrhosis is increasing in North America where a significant proportion of the population (~20%) is comprised of recent immigrants and refugees. However, the incidence of cirrhosis among this population has not been described.The aim of this study was to describe the incidence of cirrhosis among recent immigrants and refugees to Ontario, Canada stratified by cirrhosis etiology and region of origin and compare incidence rates to those of Canadian-born and long-term residents.This is a population-based cohort study from Ontario, Canada from 2000-2017 using healthcare data housed at ICES. Individuals with incident cirrhosis using a 5-year lookback were identified along with cirrhosis etiology using validated algorithms. Recent immigrants and refugees to Ontario (since 1985) and their World Bank region of origin were defined based on linkage to the Immigration, Refugees, and Citizenship Canada\u2019s Permanent Resident database. Adjusted incidence rates of cirrhosis by immigration status, etiology, and region of origin were calculated and differences in rates were compared between recent immigrants and refugees to long-term residents (born in Canada or arriving before 1985) using age and sex adjusted Poisson regression to calculate rate ratios (RR).In total, n=25,054 recent immigrants/refugees with incident cirrhosis were identified. 59% were male, median age was 49 years (IQR 39-61), 99% resided in urban areas and 31% resided in neighbourhoods of the lowest income quintile. The most common regions of origin were East Asia and Pacific , South Asia , Europe and Central Asia and Latin America/Caribbean . The majority had NAFLD cirrhosis , followed by HBV , ALD , and HCV . Cirrhosis incidence stratified by etiology varied by region of origin, with HBV highest among the East Asia and Pacific and Sub-Saharan Africa cohort , HCV among Sub-Saharan Africa and South Asia , ALD among European/Central Asia and South Asia , and NAFLD among the Latin America/Caribbean, Middle East/North Africa, and South Asian populations . When comparing age and sex adjusted incidence of cirrhosis by etiology and immigration status, rates were lower among recent immigrants/refugees for all causes compared to long-term residents with the exception of HBV where it was over 4-fold higher .Rates of HBV cirrhosis are substantially higher among migrants to Ontario while rates of all other causes of cirrhosis are lower, likely explained by the healthy immigrant effect. NAFLD has emerged as the most common etiology of cirrhosis among migrants with rates approaching those of Canadian-born and long-term residents. These data add to our understanding of the evolving epidemiology of cirrhosis and the contribution of other etiologies outside of viral hepatitis among immigrants.NoneNone Declared"} +{"text": "Tourism eco-efficiency is a performance basis for evaluating green total factor productivity and sustainable development.The objective of this study was to measure tourism eco-efficiency in Inner Mongolia and explore its influencing factors. The aim was to provide an accurate reference for improving the quality and efficiency of tourism in Inner Mongolia and promoting the sustainable development of the regional economy and society.Tourism eco-efficiency in Inner Mongolia from 2009 to 2019 was calculated using a super-slacks-based measure (SBM) model with an undesirable output. The spatial variation function was used to explore the spatial evolution pattern of tourism eco-efficiency in Inner Mongolia, and the influencing factors of the spatial evolution were analyzed by geographically weighted regression.Tourism eco-efficiency in Inner Mongolia is relatively low. Eco-efficiency values among cities in Inner Mongolia vary, and their distribution is not balanced. The structural eco-efficiency of tourism in Inner Mongolia has been consistent from 2009 to 2019. The degree of homogenization in the overall direction is relatively good. Furthermore, its spatial distribution form and internal structure evolution show a certain regularity and continuity. The pattern evolution of tourism eco-efficiency in Inner Mongolia is jointly driven by the economic level, environmental regulation, industrial structure, traffic conditions, resource endowment, and tourism reception facilities. These influencing factors show obvious spatial heterogeneity.From the perspective of Inner Mongolia, the difference in the tourism eco-efficiency value from 2009 to 2019 was relatively large, but the number of effective areas in the efficiency frontier generally showed a fluctuating growth trend. The range parameters of tourism eco-efficiency showed a decreasing trend, and the spatial correlation effect of tourism eco-efficiency in Inner Mongolia showed a decreasing trend under the influence of structural and spatial differentiation. Tourism is one of China's strategic pillar industries. In addition to helping regional economic growth and poverty alleviation, tourism contributes significantly to aesthetics and ecological civilization in China . In receSchaltegger first proposed the concept of eco-efficiency in 1990 , and thevia exploratory spatial data analysis method.2, with abundant grasslands, forests, mountains, rivers, and deserts among other natural resources and Manchu and Mongolian culture, ethnic customs, border ports, and other human tourism resources. In recent years, Inner Mongolia has made a significant effort to create the brand image of \u201cbright Inner Mongolia is in the north of the motherland.\u201d In 2020, Inner Mongolia planned to promote epidemic prevention and control and cultural tourism, the year-round reception of domestic tourists and domestic tourism revenue reached 125 million people and 240.406 billion yuan (RMB), indicating that the development of tourism has developed well and Y(xi+k) are the observed values Y(x) of the geographic variables at the points xi and xi+k,N(k) are the sample sizes of the k segmentation distance.Geographically weighted regression focuses on the local effects of spatial objects. Based on the principle of regression, it attempts to explore the relationship between spatial variables under the premise of considering the spatial correlation of the samples. Based on this, the spatial variation and driving factors of the research object are extended forward, and the characteristics and laws of spatial variation are analyzed \u201346. The yi refers to the global dependent variable; xik is the independent variable; (uivi) is the coordinate of the capital city of the i region; \u03b2k is the spatial unit value of the continuous function in the i region; \u03b5i is the random error term,\u03b20 and \u03b2kare the parameters; and kis the number of regions.Where Based on the super-SBM model of the variable return scale (VRS) with an undesirable output, tourism eco-efficiency in Inner Mongolia from 2009 to 2019 was statically evaluated and obtained . OverallTourism eco-efficiency is a static measure that is independently measured yearly. Therefore, to determine the mobile changes in the tourism eco-efficiency levels in Inner Mongolia from 2009 to 2019, it is necessary to measure its growth rate. In this study, the VRS model was used for the measurement analysis considering the machine learning (ML) index, which refers to the growth rate of tourism eco-efficiency when the desired output is increased and the undesired output is reduced in equal proportion. The ML index includes two indicators: tourism eco-technical efficiency growth rate (EC) and tourism eco-technical progress growth rate (TC) . The ML First, the projection coordinate system of Inner Mongolia was measured, then the spatial variation function of 2009, 2013, and 2019 Inner Mongolia tourism eco-efficiency was measured, and finally, the optimal model for measuring the fractal dimension of each direction was selected. Ultimately, the Kriging interpolation simulation was performed to comprehensively analyze the evolution process of the spatial pattern of tourism eco-efficiency in Inner Mongolia. According to the results of the spatial variation value of tourism eco-efficiency in Inner Mongolia , the GauFrom the fractal dimension of the spatial variation function , the oveThe Kriging interpolation simulation of the variation function of tourism eco-efficiency in Mongolia shows thui, vi) as a i coordinate, the GWR model of tourism eco-efficiency is expressed as follows:Based on the objectivity of the spatial heterogeneity of the influencing factors of tourism eco-efficiency, the GWR method was used to measure the regression coefficients of the influencing factors in each region. Data from 2009, 2013, and 2019 were selected to construe the spatial evolution law of the influencing factors on the eco-efficiency level. Considering , industrial structure (tertiary industry share), traffic condition (ratio of the length of graded highways to the urban area), resource endowment (the weighted score of high-level scenic spots), and environmental regulation , respectively, in the period J of the region i.Where ArcGIS10.4 was used to calculate GWR, and the regression coefficients of each influencing factor were divided into five levels ranging from the high-value area to the low-value area based on five levels of natural fracture points . In termThis study uses a super-SBM model with an undesirable output to assess and analyze tourism eco-efficiency during 2009\u20132019 in Inner Mongolia. Then, using the spatial variation function analysis of the spatial and temporal evolution characteristics of tourism eco-efficiency in Inner Mongolia and based on the GWR analysis of the influence of factors of tourism in Inner Mongolia on eco-efficiency, the following conclusions were drawn.The average tourism eco-efficiency in Inner Mongolia is 0.74, which is relatively low. Furthermore, the tourism eco-efficiency values of the provinces vary significantly, and their distribution is unbalanced. In addition, technological progress contributes significantly to the growth rate of tourism eco-efficiency in Inner Mongolia, indicating that technological innovation has a relatively high impact on tourism eco-efficiency. The differences in tourism eco-efficiency from 2009 to 2019 in Inner Mongolia were relatively large, but the number of effective areas in the efficiency frontier generally showed a fluctuating growth trend. The results of this study echo previous studies. Jun shows that the extensive economic growth mode restricts the improvement of tourism eco-efficiency in Inner Mongolia . The impThe range parameters of tourism eco-efficiency showed a decreasing trend, and the spatial correlation effect of tourism eco-efficiency in Inner Mongolia showed a decreasing trend under the influence of structural and spatial differentiation. Tourism eco-efficiency in Inner Mongolia showed consistent structural characteristics in different periods. The general homogenization degree of tourism eco-efficiency is relatively good, and the spatial difference in the local direction is relatively obvious. The spatial distribution pattern and internal structure evolution of tourism eco-efficiency have a certain regularity and continuity, showing a high-value concentrated distribution, and low-value scattered contiguous distribution. Yuanyuan and Yuxiang pointed out that the spatial variation function can deeply describe the randomness and structure of regional variables and measure the degree of variation of the spatial pattern of economic units . The strThe pattern evolution of tourism eco-efficiency in Inner Mongolia is jointly driven by the economic level, environmental regulation, industrial structure, traffic conditions, resource endowment, and tourism reception facilities, and there is obvious spatial heterogeneity among the influencing factors. The spatial and temporal patterns of the impact of environmental regulation on tourism eco-efficiency are generally consistent with those of economic factors. The spatial and temporal patterns of the influence of traffic conditions and resource endowment on tourism eco-efficiency are generally consistent with those of the influencing factors of industrial structure. Zhilong and Diyun emphasized that the economic level, industrial structure, resource endowment, infrastructure, and environmental regulation are the key factors affecting tourism eco-efficiency , 41. TheThis study first constructs a tourism eco-efficiency evaluation index system based on Inner Mongolia and then explores the evolutionary path and spatial pattern of tourism eco-efficiency in Inner Mongolia from the perspective of the geographic spatiotemporal dimension. To provide an accurate reference for improving tourism quality and eco-efficiency in Inner Mongolia and the sustainable development of the regional economy and society.First, the study presents research on tourism eco-efficiency from the perspective of ecological and environmental protection, which conforms to the connotation of developing an ecological civilization and meets the requirements of high-quality economic development. This is of great significance for enriching the theory of ecological civilization construction and expanding the applicable category of ecological civilization construction. Second, tourism eco-efficiency is the application of the theory of tourism eco-efficiency. Tourism eco-efficiency can combine the development of the tourism economy with its environmental impact, which can also provide some academic reference for the study of eco-efficiency in other industries. Finally, this study tries to determine the temporal evolution path and spatial pattern of tourism eco-efficiency, which is the basic paradigm of geographic spatiotemporal analysis. With respect to research, this study incorporated the undesired output in the tourism eco-efficiency measurement and constructed a relatively scientific, systematic, and perfect tourism eco-efficiency evaluation index system. In addition, the rules of spatiotemporal evolution and the characteristics of tourism eco-efficiency based on Inner Mongolia were analyzed. This provides additional insight into the correlation between geographical spatial patterns and the ecological environment, and promotes the cross-integration of tourism economics and tourism geography and other marginal disciplines. With respect to research methods, this study adopts the super-SBM model with the undesirable output to calculate tourism eco-efficiency in Inner Mongolia from 2009 to 2019, and comprehensively uses the Malmquist\u2013Luenberger index to break down tourism eco-efficiency. The spatial variation function and GWR analysis describe its spatiotemporal evolution characteristics and allow the integration of econometrics, spatial geography, and other disciplines.Tourism eco-efficiency is an essential index for the formulation of a tourism development plan, the evaluation of tourism management, and the promotion of the sustainable development of the tourism destination. The evaluation of tourism eco-efficiency, the description of the time evolution path, the outline of the spatial distribution pattern, and the discussion of its dynamic correlation with the development of the tourism economy have significant practical value. In the face of increasing tourism energy consumption and the worsening of the ecological environment, Inner Mongolia tourism eco-efficiency evaluation can effectively reflect the relationship between economic activities and the ecological environment. This is validated by the development of the worsening situation of the tourism ecological environment, can boost sustainable blossom of the province tourism such as national macro policy takes root provides the beneficial reference. The exploration of the time evolution model and the outline of the spatial pattern of tourism eco-efficiency in Inner Mongolia elucidate the sustainable development of the entire region's tourism in Inner Mongolia from a macro perspective and provide scientific guidance for the \u201ctop-down\u201d decision and \u201cbottom-up\u201d policy of tourism ecological protection in Inner Mongolia. Moreover, this study explores the spatial and temporal patterns of tourism eco-efficiency and its influencing factors in Inner Mongolia, which provides a reference for the optimization of tourism eco-efficiency and the sustainable development of tourism in other regions.Under the national macro context of constructing an ecological civilization, Inner Mongolia should change its tourism development model, enhance tourism eco-efficiency, and promote the sustainable development of tourism. Therefore, this study proposes the following. In view of the performance of tourism eco-efficiency in Inner Mongolia, the environmental ecology of tourism in Inner Mongolia needs to be improved, and environmental protection needs to be considered while developing the tourism industry, to enhance the sustainable development of tourism , 18. FirThis study explores in depth the spatial pattern and influencing factors of tourism eco-efficiency in Inner Mongolia. The study provides a reference for future research on tourism eco-efficiency and sustainability in Inner Mongolia and other regions. However, this study has certain shortcomings that should be addressed. First, regarding the design of the index system, carbon emissions as an undesirable output of tourism eco-efficiency reflect the negative impact of tourism on the environment. However, related theoretical and empirical research is insufficient; the travel coefficient of carbon emissions for Inner Mongolia has not been evaluated. Therefore, the measurement results of tourism eco-efficiency may be slightly conservative , 22. SecThis study first constructs the tourism eco-efficiency evaluation index system and then explores the evolution path and spatial pattern of tourism eco-efficiency in Inner Mongolia from the perspective of the geographic spatiotemporal dimension. Inner Mongolia has a relatively low tourism eco-efficiency value, with an average value of 0.74. Furthermore, the tourism efficiency values of the provinces vary and their distribution is unbalanced. The range parameters of tourism eco-efficiency and the spatial correlation effect of tourism eco-efficiency in Inner Mongolia under the influence of structural and spatial differentiation showed a decreasing trend.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.XW contributed to all aspects of this work. YW wrote the main manuscript text and analyzed the data. Both authors reviewed this manuscript, read, and agreed to the published version of the manuscript."} +{"text": "Microbial biofilms are spatially organized communities of microorganisms attached to different surfaces and embedded within a self-produced matrix composed of extracellular polymeric substances (EPS). The formation of biofilms frequently occurs in the food industry, due to available nutrients, large areas for microbial growth, and the complexity of processing facilities. Microbial biofilms have represented an outstanding survival strategy against stressful conditions for both spoilage and pathogenic bacteria during food processing the mechanisms underlying the formation of mixed-species biofilms; (2) the persistence and resistance under food processing environments; (3) the development of appropriate methods to study mixed-species biofilms; and (4) the potential novel strategies to control the formation of mixed-species biofilms. This Research Topic comprises 4 original research articles from Austria, China, Canada, and South Korea, contributed by 24 authors. Two contributions focused on the evaluation of mixed-species biofilm formation, and the others designed potential effective methods to control the formation of multi-species biofilms.Voglauer et al. described the complexity of mixed-species biofilms formed in water hoses of a meat processing environment by high-throughput 16S rRNA gene sequencing, with Comamonadaceae and Pseudoxanthomonas being most abundant in biofilms. Opportunistic pathogens, including the genera of Neochlamydia, Legionella, and Pseudomonas, have also been detected with different abundances. However, knowledge of the effects of environmental factors on the formation of biofilms in water hoses is limited. The authors also stated that control strategies have to be taken to prevent the colonization and biofilm formation in water hoses in order to assure water safety for the health of workers and consumers. In another study, Nan et al. evaluated the formation and transfer of mixed-species biofilms by Escherichia coli O103:H2 and lactic acid bacteria or spoilage bacteria at different temperatures, storage time, and humidity conditions. They stated that the formation of mixed-species biofilms may increase or diminish the risk of beef contamination by E. coli O103:H2, depending on the bacteria community and environmental conditions in beef processing environment.Yan et al. confirmed the high antibiofilm efficiency of lightly acidic electrolyzed water by preventing surface adhesions and impairing biofilm cell membrane integrities, and the antimicrobial activity highly depends on its storage time. This study also investigated the inhibitory effect of slightly acidic electrolyzed water on mixed-species of Listeria monocytogenes Scott A and Staphylococcus aureus for the first time.It is generally believed that mixed-species biofilms exhibit higher resistance to biofilm control strategies in food processing facilities when compared to single-species biofilms the mechanisms underlying the formation of multi-species biofilms by omics, and (2) the development of appropriate methods to study multi-species biofilms and still needed for a better understanding of multi-species biofilms.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.This research was financially supported by the Natural Science Foundation of Jiangsu Province (BK20210814) and China Postdoctoral Science Foundation (2021TQ0274).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Dear Editor,Acquired generalized idiopathic anhidrosis (AGIA) is a rare disease without a defined etiology, non-related to dysautonomia or neurological abnormalities.A 20-year-old military male, of non Asian descent, without comorbidities, had developed diffuse anhidrosis for eight months, not affecting the palmoplantar and axillary regions, associated with multiple small normochromic papules, with an erythematous base, affecting the face, trunk, back region and upper limbs . The rasAGIA clinically presents as the absence of sweating after stimulation. The symptoms of heat intolerance and cholinergic urticaria are associated, corroborating the predominance in individuals whose work activity involves exposure to heat. Preserved palmoplantar and axillary sweating is justified by the adrenergic innervation and the predominance of apocrine sweat glands, respectively.The diagnosis is clinical, and pathological examination may reveal the presence of perieccrine lymphocytic inflammatory infiltrates.The differential diagnosis of anhidrosis includes congenital and acquired causes . Three sDespite reports of therapeutic success with corticosteroid use, there are no clinical studies to prove its efficacy. There is no consensus on the method of administration, dose, and duration of treatment.4None declared.Maisa Aparecida Matico Utsumi Okada: Design and planning of the study; data collection, or analysis and interpretation of data; drafting of the manuscript.Let\u00edcia Santos Dexheimer: Critical review of important intellectual content; approval of the final version of the manuscript.Renan Rangel Bonamigo: Critical review of important intellectual content; approval of the final version of the manuscript.Renata Heck: Critical review of important intellectual content; approval of the final version of the manuscript.None declared."} +{"text": "The application of human factors engineering for rehabilitation robots is based on a \u201chuman-centered\u201d design philosophy that strives to provide safe and efficient human-robot interaction training for patients rather than depending on rehabilitation therapists. Human factors engineering for rehabilitation robots is undergoing preliminary investigation. However, the depth and breadth of current research do not provide a complete human factor engineering solution for developing rehabilitation robots. This study aims to provide a systematic review of research at the intersection of rehabilitation robotics and ergonomics to understand the progress and state-of-the-art research on critical human factors, issues, and corresponding solutions for rehabilitation robots. A total of 496 relevant studies were obtained from six scientific database searches, reference searches, and citation-tracking strategies. After applying the selection criteria and reading the full text of each study, 21 studies were selected for review and classified into four categories based on their human factor objectives: implementation of high safety, implementation of lightweight and high comfort, implementation of high human-robot interaction, and performance evaluation index and system studies. Based on the results of the studies, recommendations for future research are presented and discussed. Stroke is a cerebrovascular disease that causes significant morbidity, disability, and mortality, often leading to motor dysfunction or permanent disability , 2. WithRehabilitation robotics is a specific branch that focuses on helping patients restore or reestablish motor function. Rehabilitation robotics can be used in many aspects of physical therapy. It attempts to combine multiple technologies to maximize the physical rehabilitation training needs of patients, making extensive advances in robotic prostheses and other fields . Thus, iThe direct target of rehabilitation robots is the patient, and human factors goals such as safety, comfort, reliability, and adaptability are key considerations. Some rehabilitation products, such as HAL-5, Lokomat, and Hero Arm, have entered the market . But in The above-given context raises the question of how far the research application of human factor engineering in rehabilitation robotics has progressed. In the field of rehabilitation robotics, review articles \u201318 can pTo this end, this study focuses on the specific connotation of human factors goals, analyzes and composes the four human factors goals currently focused on research from the perspective of the system level and characteristics, explores the shortcomings of existing human factors goals and research contents and technical solutions in terms of research depth and breadth, and provides supplements and suggestions for further research contents. This study is crucial for further securing and improving the effect of stroke or postoperative rehabilitation treatment and enhancing the human-robot interaction experience. In the long run, this work can also improve the quality and overall level of rehabilitation medical equipment and help the development of rehabilitation equipment iterations.In this regard, this study has the following contributions in various aspects: (1) the research progress of robotic rehabilitation systems is analyzed from a brand new perspective, such as human factor engineering, and this is used as an innovation and entry point to analyze and sort out the four human factors objectives that are currently the focus of research. (2) The importance of human factor engineering in rehabilitation robotics research is clarified by highlighting the motivation and challenges of improving the adaptability and user experience of rehabilitation robots through human factor engineering research. (3) Suggestions are offered from the perspectives of the connotation categories of human factors goals and key technology solutions to provide a theoretical foundation and a direction for future study. (4) The results of various datasets and available sources are explained to support the classification of human factors goals, and tables are provided comprising all relevant datasets.This study is organized as follows. In order to address our research topic, we conducted a systematic review of the literature related to this topic, drawing on the methodology and process of Bal et al. In the study of , a literA systematic search was conducted to collect and summarize all research on human factor engineering in rehabilitation robotics as the research topic. We searched for the literature in three steps. First, databases, such as Web of Science, ScienceDirect, IEEE, EI, SCOPUS, and SpringerLink, were selected and searched, with the database time limit set from January 2011 to May 2022. These databases were systematically searched using Boolean algebra. Three columns of search terms were freely combined: the first and second columns were synonymous with rehabilitation robotics and human factor engineering, respectively. The third column of search terms is a paraphrase of the \u201chuman factor engineering\u201d connotation due to the broad scope of \u201chuman factor engineering.\u201d A total of 510 Boolean-configured search terms were composed and examined in each database. A complete view of the search terms can be found in The studies need to be empirical and examine the human factor engineering research component of rehabilitation-oriented robots. For this purpose, quantitative, qualitative, and mixed methods studies were considered.The research needs to involve research that enhances the human factors suitability of rehabilitation robots, such as safety, comfort, light weight, human-robot relationships, task allocation, the naturalness of human-robot interaction, and system performance evaluation. The research also needs to include technical solutions and measures.The research needs to be an academic paper. However, as the emerging field of human factor engineering research in rehabilitation robots is thus far in its infancy, we decided to expand the journal research to include book chapters and conference papers.Studies that met the following selection criteria were included in the review, and studies that failed to meet any of the following criteria were excluded:Following the initial screening, the subject staff critically assessed qualitative , quantitData extraction was carried out in two main ways. First, the essential characteristics of the final included studies were sorted to include the date of publication, the study's country, and the literature type. Correspondingly, the research design and data collection methods used in the selected studies were summarized, and information on the study participants was added to count the number of participants in the study. Second, under the human factor engineering connotations category, we report the human factor engineering research components involved in the studies reviewed, using specific human factors targets as the basis for classification.We found that in human factor engineering research on rehabilitation robots, the achievement of the same research goal maps to multiple dimensions of rehabilitation robot system design; similarly, the design of the same dimension of a rehabilitation robot system affects the achievement of multiple human factors embedded goals under the category of human factor engineering. To provide a clear and intuitive overview of the results of human factor engineering research on rehabilitation robots, the results of the data analysis have been reviewed using the former classification approach. This approach summarizes and integrates the current state of research on each human factors goal within the human factor engineering research scope of the selected studies in a multifactor and multimethod classification of one human factors goal.This study used the style of systematic reviews and meta-analyses guidelines illustrated in In addition, 10 studies were quantitative, 2 were qualitative, and 9 were based on mixed methods. All of these studies were experimental. 18 studies used actual experiments, basically choosing healthy people or rehabilitation patients with motor dysfunction as experimental subjects; 7 studies used virtual simulation in the form of experiments, of which 4 studies used a combination of both simulation and actual experiments and controls, while none of the more subjective research methods, such as questionnaires, were involved.We found that in human factor engineering research on rehabilitation robots, the achievement of the same research goal maps to multiple dimensions of rehabilitation robot system design; similarly, the design of the same dimension of the rehabilitation robot system affects the achievement of multiple human factors embedded goals under the category of human factor engineering. To provide a clear and intuitive overview of the results of human factor engineering research on rehabilitation robots, the results of the data analysis are reviewed using the former classification approach. This approach summarizes and integrates the current state of research on each human factors goal within the scope of human factor engineering research on rehabilitation robots in the selected studies in a multifactor and multimethod classification of one human factors goal.As a typical human-robot interaction device, safety design is a primary consideration. There are two central safety control schemes in everyday use today: an external control system scheme based on external monitoring and an internal control system scheme based on the robot's body design. Pan et al. designedThere is still room for weight reduction in the quality of existing rehabilitation robots, and portability and wearability need to be improved. In recent years, research has increased into reducing the structural weight of rehabilitation robots and enhancing wearer comfort.Using lightweight composite materials plays an active role in reducing the structural weight of rehabilitation robots and improving the wearing comfort. For example, using materials such as polyethene and polypropylene can significantly achieve lightweight designs for rehabilitation robots. One study reduced Weight reduction can also be achieved by simplifying complex structures and softening rigid structures. In addition, it has been found that using the principle of gravitational balance to balance some of the weight in terms of structural simplification makes the exoskeleton simple, lightweight, and well-followed, minimizing the physical footprint while maximizing mechanism isotropy and device functionality , 45. AnnThe rational weight distribution configuration, i.e., improving the drive layout and optimizing the drive method, can also achieve lightweight and comfort goals. Some studies have reduced the total weight by using a cord and pneumatic drives \u201349 whileFlexible exoskeleton robots can be said to combine all three of these aspects: eliminating the rigid frame of traditional exoskeletons, optimizing the actuation methods based on the use of lightweight materials \u201358, and A rehabilitation robot is a human-robot collaborative intelligence system with a human core. Good human-robot interaction performance includes flexibility, coordination, adaptivity, on-demand assistance, and pathological adaptability of rehabilitation movements, all of which are prerequisites for efficient human-robot collaboration. Many factors affect human-robot interaction performance, including human-robot interaction control, anthropomorphic structure, human-scale adaptability, motion planning, and many other aspects, mainly involving control systems, mechanical systems, software systems, and others.The suppleness of human-robot interaction is influenced by the interaction control, but it also focuses on three main aspects mapped on the drive mechanism, structure, and interface connection components of the rehabilitation robot . RegardiDrive mechanisms are essential for realizing flexibility, with the series elastomeric actuator (SEA) becoming the most popular drive option . The SEALi et al. proposedThe variation in the rehabilitation solutions required by different patients or the same patient at different stages of rehabilitation places a demand on adaptive on-demand assistance for robotic rehabilitation systems. Adaptive control strategies can provide many benefits for exoskeletons, as the controller can automatically adjust for the variability between each patient and the changing needs of individual patients. Adaptive control of rehabilitation exoskeletons is currently immature . Two stuThe coordination of rehabilitation movements is based on precisely recognizing the patient's movement intentions. EMG signal control is noninvasive, flexible, precise in the patient's movement intentions, and highly operable and safe. At present, the application of surface electromyography signals in rehabilitation robotics has been increasingly studied \u201387, suchEMG-based control methods can usually be divided into two types: neuro-fuzzy control methods based on EMG and muscle model-based EMG control methods, in which a matrix is associating the user's joint torque with a specific muscle is used to obtain the boost torque . For theEffective performance evaluation methods and indicators are the basis for optimizing the performance of human-machine equipment. A total of eight papers deal with performance evaluation studies, mainly focusing on ergonomic comfort, stability of muscle activity and movement, compatibility, fit, and other aspects of human-robot effectiveness performance evaluation.Safety is a critical evaluation index for human-robot interaction devices and is an essential prerequisite for transforming experimental results into clinical applications. The safety evaluation of rehabilitation robots aims to achieve safe interaction between patients and rehabilitation robots and currently focuses on the safety performance of the rehabilitation robot system itself during human-robot interaction. Wang et al. defined As a wearable device that acts directly on the surface of the human body, comfort is the critical performance of human-robot interaction. The comfort of rehabilitation robots is mainly evaluated in terms of their appearance, materials, operational comfort, and wear fatigue. The main methods for evaluating the comfort of rehabilitation robots are subjective evaluation and objective experimental methods, with subjective evaluation usually taking the form of questionnaires and objective evaluation mainly taking the form of pressure distribution and physiological electrical signal experiments.Two studies dealt with comfort evaluation. De Rossi et al. applied There is no unified index system for evaluating human-robot efficacy performance. Four studies evaluated the motion performance of rehabilitation robots, such as matching, compatibility, and stability, and one involved the evaluation of human-robot ergonomics. Zhang et al. and Di NIn this study, we conducted a systematic review of human factor engineering research on rehabilitation robots and classified the human factors research content from the perspective of human factors objectives. The research mainly focuses on human factors objectives and content, such as safety, weight and comfort, human-robot interaction, and performance evaluation of rehabilitation robots.Research on human factor engineering in rehabilitation robots has already achieved some milestones, which not only solves many drawbacks, such as low efficiency of rehabilitation by traditional rehabilitation methods but also achieves high efficiency, high precision, and personalized rehabilitation treatment to a certain extent. Therefore, applying human factor engineering in rehabilitation robots is a necessary technical means to achieve effective rehabilitation treatment in the future. However, some critical human factors issues regarding safety, lightness and comfort, human-robot interaction, and performance evaluation have not yet been carried out or require in-depth research. On the basis of an analysis of the aforementioned human factor engineering research for rehabilitation robots, it is proposed that safety protection mechanisms, individual difference compatibility mechanisms, human-robot interaction incentive mechanisms, and human-robot system evaluation indicators and systems can be further developed in future research.The safety design of the rehabilitation robot should include two levels: (1) the rehabilitation robot and the human being are in the same movement space to jointly complete the corresponding task, and it is necessary to prevent the robot from colliding with the human body to ensure the user's safety. (2) The safety of the rehabilitation training mode, intensity, and range of motion for the patient's current disease condition. In terms of safety protection mechanisms, most of the current safety research focuses on the internal control system designed by the rehabilitation robot itself, with little research involving the external control system between human and robot and a lack of safety assessment of the functional parameters of rehabilitation training for the patient's pathology.To achieve multiple protections for patient safety, future research should focus on two critical aspects of the rehabilitation robot: mechanism design (hardware) safety and control system (software) safety. Regarding robot hardware safety, limit blocks can be used for mechanical protection. At the same time, the mechanical structure design can fully avoid the invasive design of the robot to the human body by establishing the robot's kinematic model and analyzing the robot's reachable space. Regarding robot software safety, the stability of the existing closed-loop system for the interactive control of rehabilitation robots should be addressed with emphasis due to the dynamical uncertainty of the robot system and the fact that some action conflicts often occur during the physical human-robot interaction. At the same time, the damping response performance of the system should be improved.Although some studies have been conducted on adaptive aids and postural and motor adaptations, there is a lack of systematic and targeted research. The number of rehabilitation patients is growing annually, and the parameters of the rehabilitation programs vary greatly depending on the individual's posture, degree of motor impairment, pathology, and stage of rehabilitation. In response to individual differences in body shape and pathology, rehabilitation robots should be individualized in configuration, control systems, movement trajectories, training modes, and functional parameters. In this regard, further research should be conducted on the adaptive mechanism of individual and pathological differences, the adaptability and stability of the control system, the application of sensor technology, and the design of control algorithms so that the rehabilitation robot can sense the state information of the patient's force and position and adopt the corresponding training mode, control strategy, and matching training parameters. In addition, the flexibility of the structure should be considered, and modular designs can be utilised to make the structure and size of the rehabilitation robot adaptable to individual differences.Patients can interact with robots in a secure, pleasant, and natural environment if interaction control is effective. Impedance control and hybrid force/position control are the most common control mechanisms employed in the former case. In the latter, the most widely used strategies are myoelectric signal control and EEG signal control. The principles, advantages, and disadvantages of various interactive control methods are shown in . Among tIn addition to the HCI performance factors mentioned above, HCI strategies can also affect the HCI experience and rehabilitation outcomes. In the case of rehabilitated patients, the weak motor skills of the affected limbs and the lack of motivation to participate in a rigid, boring, and repetitive training paradigm will directly lead to poor rehabilitation efficiency and effectiveness. A robust incentive mechanism is a way forward for human-robot interaction in rehabilitation. Future research should combine rehabilitation robots with virtual reality (VR) technology to integrate task-oriented training paradigms. While exciting and diverse virtual scenarios can effectively increase patients' motivation for rehabilitation training, the immersive VR environment can also effectively stimulate mirror neurons in the motor cortex of the human brain and promote neural recovery.As a typical human-robot interaction system, the human factors evaluation of the rehabilitation robot only stays in the study of human comfort or the performance of the equipment from a single aspect in the human-robot system. It has not yet involved a comprehensive, systematic, and in-depth study of human-robot adaptability issues, such as safety and comfort, human-robot fit, pathological adaptability of movement patterns, and trajectories from the mapping matching relationship of human-robot characteristics and lacks perfect evaluation indexes and evaluation systems. Therefore, future research should effectively integrate psychological, subjective evaluation, and physiological human response parameters to achieve a comprehensive human-robot suitability evaluation of rehabilitation robots using geometrical and functional characteristics as direct inputs, which is essential for optimizing the overall performance of rehabilitation robots, developing more targeted training methods and maximizing human-robot matching.On the one hand, human factor engineering research for rehabilitation robots is cross-disciplinary research. In human factor engineering research for rehabilitation robots, there is a one-to-many cross-mapping relationship between human factors goals and rehabilitation robot system design. For example, the realization of the same human factors goal is mapped to multiple levels of rehabilitation robot system design, and the design of the same system level is also mapped to various human factors goals. Therefore, the categories of \u201chigh safety implementation,\u201d \u201clightweight and high comfort implementation,\u201d and \u201chigh human-robot interaction implementation\u201d in this study are based on the human factors goals and system levels. The contents of the three classifications will inevitably overlap. On the other hand, these classifications are derived from a series of processes, such as literature search, review, evaluation, and statistics, to arrive at high-frequency terms safety and control system (software) safety are small dimensional suggestions based on the general direction of \u201csound safety protection mechanism.\u201dThis review provides an exhaustive review of research advances in human factor engineering in rehabilitation robotics through a series of methodological processes, including literature search and screening, quality assessment, and data extraction. This study classifies existing human factors research in the context of the rehabilitation robotics field, using specific human factors goals as the classification criteria. Based on the four categories of human factors goals, the research progress in rehabilitation robotics is systematically sorted, and the benefits of the corresponding technical solutions for the practical use of rehabilitation robots are analyzed in detail. This systematic review focuses on the lack or inadequacy of current research in terms of the connotation categories of human factors goals, and suggestions are made for subsequent human factors research.The application of human factor engineering in rehabilitation robots can guarantee that rehabilitation robots can better replace rehabilitation therapists in providing patients with safe, comfortable, and efficient human-robot interaction training. Under the scope of human factor engineering connotation, this study innovatively provides information on human factors goals and technical solutions related to rehabilitation robots, emphasizing the benefits, challenges, goals, and recommendations for the application of human factors in rehabilitation robots, further improving the scope of human factors research on rehabilitation robots and helping to promote rehabilitation robots to maximize the \u201crobots fits human.\u201dFuture research should give full attention to the characteristics of human factor engineering in the development of rehabilitation robots and explore the solutions of sound safety protection mechanisms, human-robot interaction incentive mechanisms, individual difference adaptation mechanisms, and human-robot suitability evaluation systems from multiple perspectives, for example, from the dual dimensions of institutional design (hardware) safety and control system (software) safety. For example, the safety protection mechanism can be improved from both institutional design (hardware) safety and control system (software) safety. At the same time, through multidisciplinary collaboration and the combination of various research techniques, the hypotheses and solutions can be verified to enhance the safety, usability, ease of use, and inclusiveness of the rehabilitation robot as a new rehabilitation tool and instrument. This is important for developing a harmonious human-robot relationship, enhancing rehabilitated patients' motor function and quality of life, and assisting rehabilitation robots in gradually becoming practical, mature, and finally achieving large-scale application."} +{"text": "Having a child with autism spectrum disorder can have significant psychological effects on parents. This systematic review summarizes the current state of literature underscoring the impact of autism spectrum disorder (ASD) on parents in Arab countriesA systematic search of seven databases was performed, which identified 24 studies that included 3,299 parents or caregivers of children with ASD. These studies were conducted in 10 Arab countries .The majority of the included studies found that ASD has a significant negative impact on the mental health and wellbeing of Arab parents. It was found that parents of children with ASD have a poor quality of life (QoL) and an increased risk of psychological disorders. These findings were in contrast to findings of parents of typically developing children and children with other developmental disorders. Challenges faced by parents of children with ASD were associated with several child- and parent-related factors. The most common coping strategy used by parents was religious coping.The impact of ASD on parents has only recently gained traction among researchers in Arab countries. Despite several knowledge gaps, published studies have provided useful information outlining the impact of ASD on parents in some of these countries. Further research comprising larger random samples and using varied research and data-collection methods is required to understand the multifaceted challenges experienced by parents raising children with ASD in Arab countries. Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that intersects racial, ethnic, and socioeconomic boundaries, and is characterized by persistent impairments in social interactions, verbal and non-verbal communication, as well as restricted and repetitive patterns of behavior, interest, or activities and the United Kingdom (UK) of the included articles. Disagreements among the authors were resolved through discussion. Finally, the information was analyzed to identify themes and gaps in the literature and to suggest implications for future research and practice.The authors developed a coding form to assist with the data extraction. The coding form comprised sections designed to obtain information regarding the author(s), publication year, country, purpose, methods, and key findings. Thereafter, the first author used this chart to extract data from the included articles. The second author independently extracted data for 29% (Twenty publications (84%) were quantitative studies, which were mostly cross-sectional, while four publications (16%) were qualitative studies. The samples used in eight of the studies included only mothers , the Depression, Anxiety and Stress Scale (DASS-21), the Perceived Stress Scale (PSS), the 36-Item Short Form Survey (SE-36), the Brief Version of the Coping Orientation to Problems Experienced Inventory (Brief -COPE), the Hospital Anxiety and Depression Scale (HADS), Oberst Caregiver Burden Scale time and difficulty subscales (OCBS-T and OCBS-D), Bakas Caregiving Outcome Scale (OCBS), Zarit Burden Interview (ZBI-12), Patient Health Questionnaire (PHQ)-9, Parenting Stress Index\u2014Short Form (PSI\u2014SF), Ways of Coping Checklist-Revised (WCC-R), Beck's Depression Inventory (BDI), the Standard Recall Short Form 36 (SF-36 v2), Family Stress and Coping Interview-Adapted Scale (FSCI-A), the Satisfaction with Life Scale (SWLS), Interpersonal Support Evaluation List (ISEL), General Health Questionnaire (GHQ-12), and the Positive Reappraisal Coping (PRC) Subscale of the Cognitive Emotion Regulation Questionnaire (CERQ).n = 16, 67%) were conducted between 2017 and 2021.The included studies were all published in the past 10 years and most of these studies (In total, 3,299 parents or caregivers, namely, 2,415 parents or caregivers of children with ASD and 884 controls, were included as participants in these studies. The total number of mothers and fathers of children with ASD was 813 and 327, respectively. Eleven studies comprising 1,275 parents or caregivers of children with ASD did not specify the gender of the parent and referred only to the term \u201cparents\u201d (Kheir et al., Data from studies included in this review revealed that parents raising children with ASD in Arab countries experience considerable stress and strain. Nine studies reported high levels of parental stress (Dababnah and Parish, In six studies, parents raising children with ASD were compared with parents raising children with other disabilities and children without any disabilities (Fido and Al Saad, Factors associated with psychological disorders and the burden experienced by parents of children with ASD were explored in some of the studies. These studies found that several factors were associated with the impact of ASD on parents, including the severity of ASD, social support, economic status, maternal education, financial hardship, marital status, parental age, and the gender of the child (Al-Kandari et al., Limited studies have investigated coping strategies used by parents raising children with ASD in Arab countries. Religious coping was the most common coping strategy found in some of these studies (Dababnah and Parish, Only two studies examined the psychological resilience of parents. Dababnah and Parish reportedThis systematic review was conducted to identify studies that addressed the impact of ASD on parents in Arab countries. The included studies were reviewed in terms of participants, general characteristics, methodology used, and the main findings. This review found that the impact of ASD on parents and caregivers has only recently gained traction among researchers in some Arab countries. Approximately 80% of the studies included in this review were conducted in Saudi Arabia, Jordan, Egypt, Kuwait, and Bahrain. Most of these studies used cross-sectional study designs and included non-random samples. Furthermore, the study participants of the included studies comprised more mothers than fathers. Moreover, most of the included studies did not distinguish between the different subtypes of ASD.The majority of studies found that ASD has a significant negative impact on the mental health and wellbeing of Arab parents. This finding is consistent with previous studies conducted in several countries, suggesting that parents of children with ASD experience significant levels of stress, depression, and anxiety (Loukisas and Papoudi, Studies exploring the factors associated with stress in parents and caregivers of children with ASD are limited in Arab countries. These factors include the severity of ASD, social support, economic status, maternal education, financial hardship, marital status, parental age, and the gender of the child. Overall, these results are consistent with literature indicating a relationship between the impact of ASD on parents and various characteristics among the child and extended family (Karst and Van Hecke, Furthermore, studies addressing the coping strategies used by parents raising children with ASD are even more limited in Arab countries. Although limited, these studies found that the most common coping strategy used by parents was religious coping followed by acceptance, positive reframing, withdrawal from the community, denial of the ASD diagnosis, increasing social interactions, and accessing information. Moreover, two studies found high levels of resilience in parents and caregivers. However, since the studies are limited, these results should be interpreted with caution. Moreover, most of the studies used self-report questionnaires and lacked a qualitative measurement. As a result, socially desirable responses may have been provided by the parents and caregivers, underscoring the limitations of the data collection methods used.The findings of this systematic review have several important implications for future research in Arab countries. Parents that have a child with ASD are severely impacted (Picardi et al., Furthermore, further research is required to underscore the difference in the experience of the burden associated with raising a child with ASD between mothers and fathers. While several studies have indicated that mothers of children with ASD suffer from increased levels of mental health challenges and burdens compared to fathers, some studies have yielded mixed results (Picardi et al., Moreover, the majority of the studies included in this review used small non-random samples based on a limited number of countries. Consequently, this limited the generalizability of the findings to all parents in the Arab region. Thus, future research including larger random samples is required.Several limitations should be considered when interpreting the findings of the current review. First, only studies published in English in peer-reviewed journals were included in this review. The researchers excluded literature published in the Arabic language due to the severe lack of Arabic electronic databases. Furthermore, conducting a comprehensive manual search would have been a formidable task (Alkhateeb and Alhadidi, This systematic review summarized the results of studies underscoring the impact of ASD on parents in Arab countries. Twenty-four studies met inclusion criteria and most of the included studies were quantitative studies that were conducted within the last 5 years in Saudi Arabia, Jordan, Egypt, Kuwait, and Bahrain. Furthermore, most of the identified studies found that ASD has a significant negative impact on the mental health and wellbeing of Arab parents. Moreover, significant gaps were found in the evidence base, including research on coping strategies and interventions aimed at reducing stress and burden among parents and caregivers. However, this review contributes valuable insights for future studies on parents of children with ASD in Arab countries.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.JA conceptualized the manuscript and research questions, performed the initial article search, and reviewed all articles identified during the search. MH and WM participated in the acquisition of data, analysis, and manuscript drafting. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "A relationship was found between the use of breast milk and infant formula milk and a decrease in the incidence and number of clinical complications caused by hypoxic-ischemic encephalopathy hypoxic-ischemic encephalopathy.To assess the efficacy and safety of breast milk and infant formula milk in terms of reducing of hypoxic-ischemic encephalopathy, the level of morbidity, the severity of damage to brain structures, the time before switching to full-fledged enteral nutrition and the frequency of detecting feeding intolerance in premature infants.Prospective observation of the development of 254 premature babies were treated up to six months of corrected age at the Department of Neurology of Early Growth in 2016-2018. The effect of breast milk and formula milk on neurological status was compared.In comparison, breast milk and formula milk didn\u2019t show any effect on the frequency of severe hypoxic-ischemic encephalopathy , the severity of brain damage. Breast milk showed a statistically significant effect in terms of reducing the average number before switching to full enteral nutrition .Breast milk and formula milk does not affect the frequency of development of hypoxic-ischemic encephalopathy, the severity of brain damage. Breast milk significantly reduces the frequency of feeding intolerance, accelerates the transition to enteral nutrition, reduces the duration of hospitalization in premature infants.No significant relationships."} +{"text": "Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. This condition is enhanced by stress. In turn, stress symptoms are a risk factor for the onset and progression of MS. However, knowledge about predictors of stress in patients with MS is scarce.This preliminary study aimed to verify whether the number of relapses, fatigue, physical disability (MS characteristics), experiential avoidance and self-judgment (emotion regulation processes) predict stress symptoms in patients diagnosed with MS.A convenience sample of 101 patients diagnosed with MS and without other neurological diseases participated in this study. Participants completed the Depression Scale of the Depression, Anxiety and Stress Scales-21, Analog Fatigue Scale, World Health Organization Disability Assessment Schedule-12, Acceptance and Action Questionnaire-II, and Self-Judgment Subscale of the Self-Compassion Scale.All predictors initially hypothesized and years of education have significant correlations with stress symptoms. Simple linear regression analyses showed that the variables significantly predicted stress symptoms and were, therefore, included in the multiple linear regression model. This model explained 51.8% of the variance of the stress symptoms and showed that years of education, the number of relapses, fatigue, and experiential avoidance significantly predicted those symptoms.The promotion of mental health mental in patients with MS must develop functional skills to deal with stress induced by years of education (possibly responsible for the degree of awareness about MS and its consequences), recurrence of relapses and fatigue, and should minimize emotion regulation strategies focused on experiential avoidance."} +{"text": "Schizophrenia spectrum disorders are related with prolonged stay in hospital and high cost for treating them. As a consequence, the determination of the factors that affect the duration of hospitalization is essential.The purpose of the study is the determination of the psychosocial characteristics of inpatients in a public psychiatric hospital and their association with the duration of hospitalization.A total of 103 patients with a diagnosis of Schizophrenia (according to ICD-10) participated in the study. The socio demographic characteristics were recorded and the following psychometric tools were used: NEO- Five Factor Inventory, Connor-Davidson Resilience Scale (CD-RISC25), Multidimensional Scale of Perceived Social Support, Multidimensional Scale of Perceived Social Support (MSPSS), Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning scale (GAF).All instruments were adapted to greek population. All statistical analysis was performed using SPSS v.25.The median length of hospital stay was 40,7 days. The number of previous admissions , the type of admission (compulsory or voluntary) , the physical restrain , the duration of restrain as well as the existence of social support networks and in particular social support from friends , seem to affect the duration of hospitalization.The present study underlines the signification of the psychosocial factors that could contribute to the prediction of longer hospitals stays, the planning of appropriate interventions and as a result the reduction of hospital costs."} +{"text": "The fifth health sector directors\u00b4 policy and planning meeting for the World Health Organization (WHO) regional office for Africa convened to focus on building health system resilience during the COVID-19 pandemic to ensure continuity of essential health services, primary health care (PHC) revitalization, and health system strengthening towards achieving universal health coverage (UHC). In this paper, we present short summaries and experiences shared by 18 countries, for which their practices and outcomes have been documented in this manuscript. These actions are aligned with six key themes: (i) defining and making more essential health services available, (ii) increasing service coverage targeting hard to reach populations, (iii) financial risk protection, (iv) improving user satisfaction with services, (v) improving health security, and (vi) improving coverage with health-related sector services. It is through these shared country experiences that lessons are learned that can influence the region\u00b4s work and advancement to achieve UHC through a PHC approach. Universal health coverage (UHC) is central to the 2030 sustainable development agenda, and the employment of a comprehensive PHC approach is critical for its attainment. Looking to the heightened prominence of UHC, entailing \u201call people have access to the health services they need, when and where they need them, without financial hardship\u201d , COVID-1The influence of piecemeal initiatives remains limited to catapulting action towards attainment of UHC and other health related SDG targets . Such plCase study: country lessons sharedDefining, and making more essential health services availableBurundiPractice: Burundi held a national conference on primary health care revitalization on 16-18 September 2019 to take stock of the implementation of the country\u00b4s commitments related to PHC and the health-related SDGs.Outcomes: the government, in collaboration with its partners, made relevant recommendations with the establishment of a unit to monitor the implementation of these recommendations at the presidential level. These include: focusing on leadership and governance to improve intra, inter, and multi-sectoral coordination, international aid, develop a health in all policies strategy, and others; ensuring sustainable, quality, integrated and person-centred PHC that takes into account the needs of individuals, families, and communities in all policies is relevant; improving health human resources through strengthening training, ensuring equitable distribution of providers across the country, and ensuring the strengthening of mechanisms for the remuneration, motivation, and retention of specialized personnel; and ensuring individual and community empowerment through their participation at all stages of public health interventions, joining the UHC global compact 2030, establishing multi-stakeholder platforms to ensure heightened participation in regular policy dialogue, strengthen the performance of community health worker groups and other community-based associations, and others.CameroonPractice: established the UHC national technical group in 2015 and performance-based financing (PBF) was implemented to improve the coverage and quality of maternal and child health services by purchasing quantity and quality bonuses from health facilities. This has been ongoing since 2012 with 14 pilot demonstration sites in three regions and implemented in the 10 regions of the country. The focus has largely been on maternal and child health and adolescent health indicators , among other key country indicators. Interventions implemented included: signature of performance contracts; purchase of cover; quality control by higher level stakeholders; and common verification.Outcomes: performance-based financing found that it improved: maternal and child health vaccination rates (which are now over 17%), direct payment of radiology and laboratory fees , direct payment of illegal service fees , quality of services with respect to the technical platform, and the overall satisfaction of women (improving 8.6% points). However, no improvements were recorded for the quality of care in terms of technical and interpersonal quality.ComorosPractice: Comoros established a vision (2015-2024): \u201can efficient national health system that enables the entire population, particularly the most vulnerable and disadvantaged, to have access to quality health care, with the effective involvement of all public and private actors and stakeholders, in a spirit of solidarity, equality, equity and social justice\u201d. In alignment with this vision, various initiatives and steps have been carried out, including: assessing financial flows; joining the International Health Partnership; receiving the commitment of the head of state; adopting a law establishing health insurance; hosting a capacity-building workshop; undertaking a feasibility study; revising the national pharmaceutical policy; undertaking construction for a 600-bed university hospital centre; providing free services to those with HIV, TB, leprosy and malaria; providing services targeting maternal and neonatal health, children under five years of age, those with neglected tropical diseases, and those with non-communicable diseases; and many others.Current steps for improvement and/or ongoing challenges faced: despite the several actions taken, challenges remain, such as around: strengthening effective coordination and sectoral dialogue mechanisms; weak technical and institutional capacity of the national health information system; implementation of the legal and regulatory provisions of the new health code; development of the public-private partnership; weak mobilization of financing for the implementation of generalized health insurance; and implementation of a national community health strategy in alignment with the Astana declaration.Increasing service coverage targeting hard to reach populationsAlgeriaPractice: undertook a twinning study (instituted and regulated by the government) which sought to: provide care to patients in the southern regions and the highlands whose specialties and/or skills are in short supply; provide training to medical, paramedical, administrative and management staff on a cyclical basis; establish links and networks between institutions to organize the transfer of complex cases for their certified education program (CEP) at the pilot institution level; and avoid the displacement (travel) of patients to university cities, by having the teams move to these populations in these health structures which generally have the necessary equipment.Outcomes: the work resulted in numerous twinning agreements and developments, including: 109 public hospitals, 101 agreements signed, and 45 agreements in the process of being signed. As well, embraced a strong stakeholder communication strategy and drew commitment from the state with 100% matched funding. However, challenges remain around telemedicine and exchange programs which are increasingly developed in healthcare institutions to support remote local teams in helping patients with diagnosis or CEP and distance education for health professionalsSouth SudanPractice: South Sudan has implemented a community health strengthening strategy, the \u201cboma health strategy\u201d, which trained community health workers in over 55 counties deliver a package of health promotion, disease prevention, and selected curative maternal and child health services.Outcomes: numerous successes have been realized, such as increasing access and demand for health services in the community. Due to the availability of health services within the community, families no longer have to walk long distances to access health services at distant health facilities, nor are they financially impacted, as these services are provided free of charge. Additionally, available health services (including drugs) have improved demand for services, more community members have utilized health services, and drug consumption has increased. Service delivery has been regular with minimal disruption due to continued partner support. However, challenges remain around: the sustainability of free services ; limited ownership of the program by the community and local authority; quality of care ; need to adopt the patient safety strategy and associated development of guidelines and protocols; and select locations not yet fully implementing the service package.Republic of CongoPractice: establishment of the national health policy designed to improve equitable access of the population to packages of essential and quality services. For which the priority is to strengthen PHC, through the revitalization of the health districts to move towards UHC and achieve Sustainable Development Goal (SDG) 3 .Current steps for improvement and/or ongoing challenges faced: an evaluation of WHO support to the ministry of health in the 12 districts in 2020 is underway and will show the evolution of the 18 indicators selected in the monitoring and evaluation plan. However, to-date, 50% of cases of yaws have been detected and notified by the community relays. The indigenous population is concerned about prevention and protection against all forms of violence. To address this, since 2017, 200 indigenous community relays have been trained in order to improve the social demand for the use of health services. Further, health workers in health facilities are aware of the principle and importance of non-discrimination against indigenous people in public and private health care structures. While equitable access to quality essential care and services for vulnerable populations remains a challenge in the Republic of Congo, the country has embarked on a process of decentralization for the implementation of PHC to address this challenge.Financial risk protectionGhanaPractice: Ghana has worked towards achieving FRP through scaling up various interventions, including: electronic mobile phone renewal of national health information system membership, increased recruitment of community health nurses, improved claims reimbursement time, investment into health facilities at the primary level and nurses and midwives, supply chain management systems, and reforms .Outcomes: numerous successes have been realized in Ghana, such as: increased active membership in the insurance scheme (over 40.5% of the population), over 60% of beneficiaries in the scheme exempt from fees, improved health service utilization, over 90% of out-patient department services provided at the primary level , reduction in malaria fatality rate (from 0.51% in 2015 to 0.1% in 2019), and others. Additional successes have been realized in four key areas: physical access to essential health services, financial access to essential health services, demand for essential health services, and resilience of health systems.RwandaPractice: Rwanda\u00b4s efforts have focused on financial risk protection (FRP) and have accordingly introduced a Community-Based Health Insurance (CBHI) scheme to improve access to healthcare services and reduce significantly out-of-pocket expenditures, in particular, for the poor and most vulnerable. 90% of the population was covered by health insurance . Interventions that have been scaled up to facilitate improved FRP: insurance coverage for the informal sector through CBHI; moving from flat to stratified premiums according to socio-economic categories; fully subsidizing the poor and most vulnerable population in Ubudehe Category I; access to broadened benefit package over time ; reduced fragmentation of CBHI pooling risks from 31 pools to one single pool; and increased CBHI revenues for financial sustainability.Outcomes: efforts on FRP have resulted in successes in four key domains: physical access to essential health services through improved health worker density, effective referral system, task-shifting of select services at the community-level, establishing non-communicable disease clinics in hospitals and health centres, and ensuring one health post in every administrative cell to reduce travel time; financial access to essential health services though increasing the sources of revenue for CBHI to ensure sustainability, full subsidization of select populations, moving from flat to stratified premiums by socioeconomic status, and others; demand for essential health services has increased, as the utilization rate for CBHI beneficiaries has increased from 0.3 to 2.05 visits per capita (from 1997-99 to 2018/19); and quality of care through pursuing accreditation programs, digitalization of health services through scaling up electronic medical records, improving claim management, and enhancing the pharmaceutical supply chain.MauritaniaPractice: despite efforts to reduce the burden of current health expenditure on households in Mauritania, it remains at 52% of health expenditures as of 2017. Mauritania carried out specific interventions to address this. In 2020, a national program aimed at strengthening social security coverage and direct income for the most vulnerable families, financing: free resuscitation for all; a 55% reduction in the amount of the Obstetrical Package with the extension of the package to all the needs of pregnancy and postpartum and everywhere in public structures; free medical transportation during referrals and treatment of road accidents; and ongoing medical insurance for the poorest households on the social register.Current steps for improvement and/or ongoing challenges faced: a program to improve social supply and support demand was launched by the public authorities in 2020, and is investing more than $45 million over 30 months through nine health projects to help reduce financial and geographic barriers to access to health services for the poorest, accelerate progress towards UHC, regulate the sector, strengthen geographic coverage, and improve health system resilience. This financing should be sustainable after 30 months by being integrated into the public financing of the sector in order to make progress towards UHC. An additional budget line of 7.7 million dollars has been included in the 2020 finance law to reimburse health facilities for expenses incurred for this free service. The anticipated outcomes include: reducing the share of direct payments in current health spending; contributing to the reduction of the poverty rate; and faster progress toward UHC.Sierra LeonePractice: while about 60% of Sierra Leoneans live below the poverty line, over 60% (2018) of total health expenditure come from households (while the government contributes around 4% and donors account for about 36%). As such, Sierra Leone selected to address the high out-of-pocket payments at points of service delivery. Accordingly, the Social Health Insurance Law was passed in 2017 and was to be implemented as a prepayment health insurance scheme with the government providing the major source of funding.Current steps for improvement and/or ongoing challenges faced: various initiatives have been undertaken and are ongoing in Sierra Leone, including: completing the UHC Roadmap to be implemented through the National Health Strategic Plan, to make quality health care accessible to all, everywhere, and at all times; abolishing user fees for pregnant women, lactating mothers, children under five years of age, and Ebola victims under the Free Health Care Initiative; revisiting school health; engaging over 30,000 community health workers, especially in rural and challenged communities; increasing health human resources by 4,000 people (40%) and receiving approval for the recruitment of another 3,000; implementing mandatory social health insurance; engaging the community for partnership and ownership through the revised primary health care handbook; and continued commitment to the global quality of care network.Improving user satisfaction with servicesBurkina FasoPractice: Burkina Faso undertook an evaluation to assess response to needs with attention to select characteristics: dignity; autonomy; confidentiality; prompt decisions; access to social support services; quality of basic amenities; and the choice of health care providers. Based on the analysis carried out, Burkina Faso adopted a reform of its healthcare system based on quality management, the integrated person-centered care approach (ASICP), and patient safety. Specific interventions carried out included: National Strategy Combining Quality, Country Policy and Institutional Assessment (CPIAA), and patient safety; ASICP tools; Regulatory Quality Charter; quality reference; certification/accreditation; community watch; management of adverse care events; traditional medicine interface; and community health.Outcomes: the implementation of these approaches has improved access and demand through free health care, universal health insurance, taking into account the needs of users, the involvement of other profiles in health care , and the involvement of the population in self-management . Health care channels and networks have been created and strengthened. It also made it possible to strengthen the resilience of the health system for continuity of care in insecure areas and in the context of COVID-19. However, Burkina Faso experiences difficulties with the inclusion of people-centered care indicators in the reporting of the national information system.EswatiniPractice: following various client satisfaction surveys, a client satisfaction and feedback mechanism (CSFM) was developed and deployed in 2019 in all health facilities across the country to strengthen capacity of health managers to manage client feedback. It consists of questions in multiple choice form and responses are used by healthcare workers to improve the quality of the healthcare service provision. Between 4th February and 31st August 2020, a total number of 12,677 respondents/customers have given feedback. Outcomes: the CSFM has resulted in numerous outputs, including: customers satisfied with service provision (ranging from 85 to 90% between February to August), availability of drugs (ranging from 64 to 76% in this same period), average waiting time , cleanliness in the health facility (majority of respondents indicating very good and good), and attitude of health care workers (majority of respondents indicating very good). However, some challenges remain, such as some clients who are reluctant to share mobile numbers, no offline version in case of power/network interruptions, need to fund the CSFM through government, insufficient feedback mechanism to the client that submitted the issue of concern, and inadequate practice of \u201cclient first\u201d culture in entire continuum of health care.GabonPractice: Gabon undertook an assessment of user satisfaction levels to identify areas of dissatisfaction, in order to improve health system performance. The evaluation of the service's response to needs involves the following characteristics: dignity, autonomy, confidentiality, prompt decisions, access to social support services, quality of basic amenities, and the choice of health care providers. Gabon elected to focus on the reception of patients in health facilities, as users raised concerns about the quality of basic amenities, confidentiality, and wait times.Outcomes: the Ministry of Health has therefore initiated several reflections to improve the quality and supply of care. As such, numerous interventions were introduced, including: adopting a law that considers the rights of patients, dissemination of this charter to all health facilities, creating centralized services to receive patients, establishing mobile screening units in all health regions, mass awareness campaigns, and others. This required investments made to improving essential health services through access, demand, resilience, and quality of care. Improvements measured included: mass awareness campaigns for several years during the month of October for female cancers has enabled the population to adopt more responsible habits for monitoring their health ; the realization of CAP and socio-anthropological studies on cancer and other pathologies has led to a better understanding of the determinants of the population's demand for care; mobile screening units considerably improved the geographical accessibility of patient care ; and others.ZimbabwePractice: Zimbabwe implemented the first generation of RBF which was aligned with and supportive of the National Health Strategy of 2010-13 by design. This included: user fee removal to improve access and utilization of health services; rebuilding basic standards of health services delivery-capital investment in facilities; strengthening the referral system from primary to secondary; and a strong thrust towards PHC. The RBF was piloted in two front runner districts (Zvishavane and Marondera). After evaluation, it was scaled-up initially to 18 districts in 2012 and all additional 42 districts.Current steps for improvement and/or ongoing challenges faced: the RBF has resulted in: enhanced capacity to accurately report and utilize data, decentralized planning and investments of subsidy earnings for performance improvement at facility and district levels, significant improvements in coverage of maternal and child health indicators , significant improvement in the quality of select antenatal care services, and notable improvements in uptake of vouchers in past quarters. However, not all indicators show relative improvement under RBF. In the future, additional attention should be afforded to: careful selection of indicators to maximize efficiency in spending, revisiting how quality of care is measured and incentivized under RBF, combine RBF with complementary investments in quality improvement, and involve community health workers through a package of indicators and enhance demand through various initiatives.Improving health securityLesothoPractice: the main health security issue/policy problem Lesotho faced amidst COVID-19 was rising co-morbidities and excess mortalities from communicable and non-communicable diseases. This included the: inadequate integration of health system strengthening and health security efforts; inadequate coordination of efforts between ministry of health and partners; low level of community awareness and engagement; and weak information systems.Outcomes: to combat this, Lesotho scaled up interventions to facilitate the protection of populations from health risks and vaccines). This work was due to successes with multi-stakeholder collaboration , which led to enhancing health security and better targeting susceptible populations.GuineaPractice: Guinea drew on experiences from the Ebola epidemic to make necessary investments to strengthen their health system. Some of these investments include: developing strategic frameworks, plans, and policies; setting up a coordination framework; strengthening community health; significantly increasing the number of health structures; increasing health human resources at the health and community structure level; increasing the health care budget; modernizing the National Health Information System; and strengthening the supply chain and system for health products.Current steps for improvement and/or ongoing challenges faced: strengthening the health system has increased access, demand creation, resilience, and quality of care. However, challenges remain around maintaining the quality of health care and services and early recovery through state ownership.Democratic Republic of the Congo (DRC)Practice: established a strategic framework and undertook a review of essential health services, including: vaccination, maternal and child health, HIV/AIDS, bed net usage, and tuberculosis.Outcomes: determined various successes, including: vaccination coverage is greater than 80% (as of early May 2020), more pregnant women received prenatal care from a trained health professional (88% in 2013 compared to 80% in 2007), childbirth assisted by a health personnel (80% in 2013 compared to 64% in 2007), households had and used impregnated mosquito nets (9% of households in 2007 compared to 70% in 2013), and decreased deaths due to malaria . Challenges remain around: health financial resources are limited and efficient use needs to be improved; frequent and health emergencies related to Ebola virus and the COVID-19 pandemic tend to inhibit progress and the ongoing work and interventions being undertaken to reach UHC; the persistent insecurity in various regions; and health in all policies, as health interventions and progress are dependent on other sectors.SenegalPractice: Senegal incorporated the Primary Health Care Performance Initiative approach , adjusted their targets based on these various ODD as well as their strategic plan, and established a multi-sectorial compliance plan in the response to the COVID-19 pandemic to ensure continuity of health services .Outcomes: the ministry of health and advocacy began improving the quality of healthcare services through various experiences at hospitals and health centers (centres de sant\u00e9 and the laboratories). This initiative is designed to assist and help develop an environment in which health system\u00b4s actors will know what to do in order to provide quality health care, have the competence to do so and that they stay engage with available resources. These numerous initiatives, policies and actions resulted in better health indicator outcomes, including a decrease in maternal mortality and infant mortality . The ministry of health and advocacy will continue to improve PHC performance through developing more community approaches, multidisciplinary strategies, and using health information.Cross-country experience sharing opportunities provide an opportunity for peer learning, experience sharing and assessment of the direction of systems development amongst countries of the region. It aims to build a common understanding, and knowledge on taking forward the UHC agenda in the region. Across the three six themes highlighted, it has emerged clearly that countries in the region are making progress towards attainment of these goals of improved health security; defining, and making more essential health services available; increasing service coverage targeting hard to reach populations; improving financial risk protection; and improving user satisfaction with services. Against the background of a rapidly changing context of health, driven by the COVID-19 pandemic, countries have all faced significant and un-anticipated challenge to their health system capacities. Together with this, the Astana Declaration on Primary Health Care and the adoption of the SDG 3 Global Action Plan all call for a re-think of the design, focus and monitoring of health systems development in the WHO Region for Africa. The experiences shared have demonstrated that countries are actively rethinking policies and actions to re-align with the current needs of their health sectors to make them fit for purpose in the current and future health environment and in regard of the overall 2030 agenda. Beyond these experiences sharing sessions, WHO AFRO continues to provide technical support to countries in health systems strengthening, through the UHC flagship program, and implementation of the regional framework for primary health care operationalization. One key aspect of this support, particularly in the context of the COIVID-19 pandemic, is the support for strengthening health systems to ensure continuity of essential health services. Tools including health facility assessments for readiness and service capacity have been implemented across the region, as well as support for embedding measures for assessing health service resilience in routine health information systems.The country experiences shared here provide evidence of the importance of lessons sharing to galvanize action and improve knowledge of ongoing work towards the 2030 agenda. Through such platforms, south-south collaboration across countries can be strengthened. While these interventions are not completely exhaustive, this paper has been designed to pull together high-level actions and lessons for policy consideration. Having these ideas presented through the experiences of countries in the African Region, action is within grasp to achieve UHC through PHC."} +{"text": "Oil is the mainstay revenue for a number of African countries. However, extraction can result in multiple impacts on the health and wellbeing of communities living in oil-rich areas. This review explored evidence of oil industry-related social exclusion on community health and wellbeing on the African continent.We used a systematic approach guided by PRISMA to search six databases for empirical and descriptive sources focused on oil industry impacts, in any African country, between 1960 to 2021. Findings were grouped according to four dimensions of the Social Exclusion Knowledge Network (SEKN) framework: political, social, economic, and cultural.Fifteen articles were identified, of which 13 articles focused on Nigeria; while one focused on Sudan, and one on C\u00f4te d'Ivoire and South Africa. Evidence relating to political aspects of social exclusion encompassed marginalization of indigenous communities through land grabs and unequal representation in political decision making. Limited compensation for environmental damage and livelihood displacement caused by oil-extraction, and high rates of unemployment and poverty were key themes of the economic dimension. Evidence of social impacts included lack of government, or oil-industry investment in social infrastructure; poor health and wellbeing linked to land, air, and water pollution; homelessness and lack of social cohesion. The cultural dimension of social exclusion was comparatively underexplored and only six sources included data collection with indigenous residents, and comparatively more sources were written by non-citizens or non-residents of oil-industry affected areas. Major themes included impacts on collective identity, ways of life and values, particularly where loss of ownership or access to land was experienced.Oil industry activities in African countries are clearly associated with multiple exclusionary impacts. However, the narrow body of empirical research limits understanding of the lived experiences and management of social exclusion by residents of oil-rich areas themselves and is an area deserving of further attention. Oil is among the most impactful of the various extractive industries globally and in Africa. In 2020, 10 African countries were identified as being the top oil producers despite of Nigeria over the past 30 years shows that four million barrels of oil spilled between 1991 and 2011 and a further 12,381 spilled between 2011 and 2019 . AlongsiResource extraction activities degrade the environment, reducing residents' ability to farm, fish and live in an unharmed environment , 17. Lossocial exclusion methodology and was guided by the six steps of the Arksey and O'Malley Framework for conducting a scoping review. This systematic process included identifying research questions, identifying, and selecting all relevant studies, charting the relevant data, collating, summarizing, and reporting the results . This apSix electronic databases were searched for both peer-reviewed papers and gray literature: Scopus, Psyinfo, Pubmed, Medline, Proquest platform and Web of Science. In consultation with a university librarian, search terms were refined, and a search strategy devised that included four rows of search terms focusing on \u201coil industry\u201d and like terms; African countries; \u201csocial exclusion\u201d and like terms, and \u201ccommunity wellbeing\u201d and like terms . Following title and abstract review and application of inclusion and exclusion criteria, 51 full text articles were assessed, and 8 studies met the inclusion criteria. Following manual scanning of reference list seven additional records were identified. A total of 15 records are included in the final review.The identification and screening process is summarized in n = 6) were read in full by the first author; theses and dissertations were evaluated, and specific chapters selected and read based on their relevance to the review topic. Categorization of data in each dimension was initially based on examples of previous applications of the SEKN framework and iteratively adapted in consultation with co-authors as data extraction progressed. Natural overlap in some areas of impact were discussed and assigned based on consensus. The details of each of the 15 selected studies are summarized in All works, except for theses and dissertations in Nigeria or elsewhere in Africa between 1960 and 2004.Of the articles identified, 13 of the total of 15 focused on Nigeria , 38, 40 n = 10 of 15) discussed political aspects; more than half the sources also mentioned discussed economic dimensions (n = 11) and social dimensions (n = 9) while comparatively fewer sources identified cultural dimensions of social exclusion (n = 6).Nine studies used qualitative methods , 36\u201339 tn = 8) and published peer reviewed papers (n = 3). Nine of the empirical works used qualitative methods and two used mixed methods. Most empirical works (n = 10) were focused on Nigeria . Empirical works included theses and dissertations were focused on Nigeria and published peer reviewed papers (n = 3). Three of the empirical works used mixed methods and six used qualitative methods. Most of the empirical works (n = 8) focused on Nigeria include lack of basic social infrastructure reduces communities' ability to engage in traditional social activities such as team fishing and family farming , 32, 33.n = 3) and published peer reviewed papers (n = 3). Four of the empirical works used qualitative methods and two used mixed methods. Most of the empirical works focused on Nigeria framework to explore oil industry social exclusion in Africa.Although the empirical literature identified was not as extensive as expected, sources identified clearly pointed to significant social, economic, political and cultural social exclusion impacts of the oil industry in African countries, but Nigeria in particular. Most of the empirical literature in this review (13 of 15 sources) focused on Nigeria and the Niger Delta Region with one additional source focused on multiple countries including Nigeria. This reflects, in part, the longer history of oil-related industry activities in that country as well as the attention that local conflict over oil industry presence has garnered in recent years. Indeed, at the screening stage of this review we found many articles focused on describing oil-related civil conflict and violence in the Niger Delta region . ConcernOverall, the review highlighted multiple aspects of political, economic, social and cultural exclusion that interact and influence each other to the detriment of local communities. For example, in the political dimension, articles reported how political marginalization and unequal representation of community interests in the Niger Delta region, interacted with unequal wealth sharing and loss of livelihoods in the economic dimension to exacerbate the exclusion of local communities , 34, 39.cultural aspects of social exclusion, which were comparatively under-explored in the sources identified in this study . The review also highlights a need to conduct research that promotes a better understanding the links between cultural aspects of social exclusion and political, social and economic marginalization and of the different types of responses of residents to these experiences of social exclusion.Notwithstanding the evidence of political, social and economic forms of social exclusion, this review revealed that there is still limited empirical work on the topic of social exclusion given the long history of oil extraction on the continent, and in particular, limited research that centers the lived experiences of residents or communities in oil-rich regions. A range of non-empirical sources not included in the formal review , 43\u201345 mThis review was conducted using thorough and systematic search approach with assistance from a research librarian. Deliberately inclusive date ranges were adopted to try to ensure all potentially relevant literature dating back to the inception of oil-industry activity in Africa was capture. Nonetheless, our primary reliance on academic data bases and restriction to English language sources means it is possible that some studies may not have been identified which could have added further depth of understanding to the topic being explored. Another limitation was the exclusion of literature specifically focused on oil conflict which prevented deeper reflection on the role of oil conflicts themselves on social exclusion and its implications. Furthermore, because of the extensive nature of gray literature, our gray literature search was necessarily targeted, and important sources kept in local repositories that the authors were unaware of may have been missed.Oil industry activities in African countries are clearly associated with multiple exclusionary impacts. This review provides evidence of how oil industry activities affect the political, social, economic, and cultural lives of oil communities' residents in Africa and impact on health and wellbeing. Exploring the perception of the residents toward oil industry-related social exclusion on political, social, economic, and cultural aspect of their lives would enhance the understanding of the impacts of social exclusion on the health and wellbeing of oil communities and thus, help to inform effective policies toward improving inclusion in oil communities in Africa. However, the narrow body of empirical research limits understanding of the lived experiences and management of social exclusion by residents of oil-rich areas themselves and is an area deserving of further attention.The original contributions presented in the study are included in the article/AN, ST, and WL: conceptualized the study. AN: wrote first draft, data search, and extraction. AN, ST, and SD: data analysis. AN, SD, ST, and DO: critical edits. All authors approved final version.This study was conducted with support of a James Cook University Postgraduate Research Scholarship to (AN) and the College of Public Health, Medical and Veterinary Sciences (CPHMVS) Higher Degree by Research Enhancement Scheme (HDRES) Publication Grant.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Falls are the leading preventable cause of death and disability in older adulthood. Subjective experiences of aging could facilitate fall prevention and adaptation to post-falls life. We use data from the 2008-2018 waves of the Health and Retirement Study to follow self-perceptions of aging (SPA), health-domain control (HDC), and physical activity (PA) in 12,000+ adults to examine trajectories of subjective experiences and health behaviors preceding and following a fall. In total, 57% experienced falling. Both SPA and HDC were lower among fallers. Spline growth models showed that HDC, SPA, and PA significantly decreased over time. Additionally, the rate of decline in HDC and PA increased following the fall. After falling, the protective effect of HDC amplified, while positive SPA dampened change in PA. Our study illustrates the importance of subjective experiences of aging on adaptation and recovery in the context of falling."} +{"text": "The achievements made by scientists in the fast-growing field of COVID-19 have been exceptional over the last 2 years, leading to major advancements in understanding and managing the new disease, but also transforming the fields of infectious diseases and public health in general. Following the SARS-CoV-2 outbreak and subsequent pandemic, the multi-disciplinary work of researchers worldwide has provided an in depth understanding of COVID-19 pathogenesis, of clinical treatments and outcomes, of models and dynamics governing disease spread, period of infectivity and containment interventions. Immunological research focused on the understanding of acquired immunity, and development of innovative vaccines and effective vaccination schemes, which have greatly improved disease outcomes across the globe. The required rapid processing and dissemination of scientific information would not have been possible if not for the special focus and attention given by scientific journals such as Frontiers in Public Health and Frontiers in Medicine.Following on from the success of the first Frontiers COVID-19 Research Topic, featuring 400 original research articles , a dedicTo provide a backdrop, at the time of the launch of this Research Topic in June 2021, the first wave of the rollout of population-wide SARS-CoV-2 vaccinations with two doses was nearing completion in most European countries, while a severe lack of vaccine availability was still recorded for resource-restricted settings. Following the vaccination successes in Europe and North America a gradual relaxation of public health restrictions was afforded while many countries worldwide were preparing for resurgences. In total, 176 manuscripts were submitted, 83 (47%) of which were accepted. As of August 2022, the special topic achieved approximately 255,000 views and 31,000 article downloads, with readership distributed across the globe. Frontiers made a significant contribution to the timely generation and distribution of peer-reviewed COVID-19 publications as the publisher of this special topic, as well as many other related topics. At the time of writing, the top five most viewed Research Topics on COVID-19 published in Frontiers in Medicine and Frontiers in Public Health , followed by Clinical Management (19), Epidemiology (14). Pathophysiology (12) and Screening Methods (12). The accepted submissions comprised of Original Research (50), Brief Research Report (11), Reviews (8), Opinion (5), Case Report (4), Methods (2), Community Case Study (1), Hypothesis and Theory (1) and Perspective (1).Lu et al.), the Czech Republic , Germany , Portugal , Romania , Saudi Arabia and the USA . Awareness about the virus transmission within public education settings and protective practices were also examined in the studies by Lordan et al., Middleton et al., Sombetzki et al., and Qin et al., as well as within areas of precarious housing conditions by Zimmermann et al..The understanding and comparison of public health responses has been vital in the design and quick adaptation of effective mitigation strategies. A number of manuscripts shared details of investigations of SARS-CoV-2 transmission patterns and non-pharmaceutical control interventions implemented in defined geographies, such as China . Some of these early data was summarized by the systematic review of Norhayati et al. The perspectives and responses of different communities toward COVID-19 were considered, such as pharmacists being both vaccinated and vaccinators ; of patient groups being vaccinated ; as well of wider communities within specific geographical areas . Related to the safety of vaccination programs and providing a holistic view of the subject within this special topic, were also the studies describing vaccine reactions in the USA, EU (Montano) and China . Finally, the protective properties of breast milk for infants from COVID-19 were outlined in the Hypothesis and Theory study by Quitadamo et al..As population-wide vaccination programs were implemented across the world, a number of studies emerged considering the overall COVID-19 vaccination acceptance, providing survey-based quantitative estimates and pancreatitis . Various approaches to assessing prognostic factors and indicators were reported. Enocsson et al. looked at soluble urokinase Plasminogen Activator Receptor (suPAR) as a specific prognostic biomediator. On the other hand, Ranard et al., looked at a wider set of indicators reporting different patient endotypes that might be prognostic for COVID-19. One study by Kurban et al., provided examples of simple triage tools that can be used to predict severe disease.The topic of COVID-19 was approached from a clinical management perspective as well, with Masi\u00e1 et al.); the effect of tocilizumab monotherapy on biomediators ; the infusion of umbilical cord mesenchymal stromal cells ; the use of A2 adrenergic receptor agonist ; as well as the case report of blood purification for 5 severely ill patients . Regarding the prevention of symptoms or at least the reduction of symptom severity, studies looked into the supplementation with vitamin D and zinc (Hardigan and Gordon). The breadth of topics covered demonstrate the multitude of approaches still being considered in the effort to improve the current standard of care for COVID-19, as well as indicating the many clinical specialties involved in those investigations. This aspect of plurality in COVID-19 treatments was captured well in the meta-analysis of randomized control trials by Zhang et al., while W\u00fcstner et al., looked into the clinical evidence informing treatment guidelines, specifically on repurposed drugs for hospitalized patients during the early waves of the COVID-19 pandemic, including for corticosteroids, anticoagulants and other.Among the articles with a primary focus of clinical management, another main area of interest was the evaluation of various new or concomitant therapies with respect to benefits for COVID-19 progression and outcome. Treatments evaluated included the addition of baricitinib to standard care and specifically, as they relate to chronic fatigue syndrome . Frontiers journals have initiated distinct special topics on COVID-19 sequelae, especially on emotional/mental health and post COVID syndrome assessment , the Ecuadorean army , the Colombian army , South Korea , China , as well as the incidence in cannabis users . In order to complement the picture on symptomatic case identification, Syangtan et al. focused their systematic review on investigating asymptomatic cases. Finally, the study by Yadav et al. described an outbreak of Nipah virus concurrent to COVID-19 in India, reminding that COVID-19 is cumulative to existing pathogen pressures in many countries.Of the articles primarily focused on Epidemiology, disease surveillance remained an area of focus in order to elucidate the geographical, demographic and behavioral distribution of confirmed cases at specific time points (or over time). As such, there were studies regarding COVID-19 epidemiologic patterns in Burkina Faso , Morfeld et al. provided an estimate of the excess mortality attributable to acute COVID-19 and highlighted limitations of routine demographic surveillance systems. The goal of these investigations was to achieve a better understanding of the individuals/groups with increased risk, and thus, prioritizing any public health interventions to decrease the transmission risk to susceptible populations.Accurate disease surveillance remains a cornerstone for healthcare systems for the timely implementation of public health measures as warranted, and for resource and treatment planning relative to available service capacity. Thus, a clear area of interest remained the modeling and testing of prediction models that might be implemented in subsequent waves of the pandemic. These included work by Chua et al.), at schools , at healthcare facilities . As with any diagnostics, a greater than acceptable threshold of false-positive or false-negative outcome, can cause considerable damage both at individual and public health levels. Therefore, a number of studies focused on the evaluation of the individual performance of such test and/or methodologies . The investigation of saliva as a suitable detection fluid was discussed by Pierri et al.; while the implementation of ELISA-based seroprevalence for the understanding of asymptomatic transmission levels was considered by the studies of Sherman et al., and Breedon et al..Asymptomatic and pre-symptomatic transmission of SARS-CoV-2 has introduced a greater degree of difficulty and uncertainty for monitoring the spread of the infection into new clusters. Thus, population-wide or high-risk group screening policies have been implemented at various scales in many countries. The studies included in this special topic describe the implementation of such screening policies at national borders (Hayes et al. provided a scoping review of over 100 persistent symptoms of long COVID-19; while the study by Cheng et al. described a text clustering method to identify symptom clustering. The systematic review by Sodeifian et al. looked into the drug-induced liver injury in COVID-19 patients; and Zhang et al. investigated liver fibrosis scores and clinical outcomes in COVID-19 patients. There were two Opinion papers in this special topic, one by Kozlakidis, considering the relative lack of evidence of genomic recombination for SARS-CoV-2; and another by Dubina, considering a potential non-immune prophylaxis against COVID-19 by targeting tolerance for Angiotensin II.Understanding the pathophysiology of COVID-19 and its many clinical manifestations is crucial in dealing with the severe forms of the disease, identifying individuals with increased risk, and taking timely action toward development and/or implementation of appropriate treatments. Teshome et al. investigated the impact of vitamin D on COVID-19 infection; while Chen et al. investigated the relationship between plasma vitamin C and COVID-19 susceptibility and severity. The investigation of such relationships allows the deeper understanding of molecular mechanisms and their link to clinical outcomes. The relationship between platelet count and COVID-19 mortality was investigated by Yang et al.; while another relationship, between cellular and humoral immune responses after two doses of vaccination were studied by Mangia et al. The brief research report by Jimah et al. focused on the monitoring of COVID-19 positive pregnant women. Finally, Holm-Jacobsen et al. investigated the clinical implications of rectal SARS-CoV-2 shedding in Danish patients.The link between vitamin intake and COVID-19 clinical outcomes remains a focal point of research. To this end the systematic review by As the COVID-19 pandemic continues and as the SARS-CoV-2 virus continues to evolve and produce a greater number of variants, it is likely that the case numbers and hospital admissions will persist their fluctuations globally. Thus, it is not surprising that epidemiological studies continue to feature strongly in the published scientific literature as understanding of the changing dynamics of COVID-19 remains a public health priority. To this end, the greater emphasis on public perceptions, attitudes and behaviors is a welcome development, further strengthening public health responses and gradually involving an active participation of \u201ccitizen scientists\u201d as advocated previously .Building on understanding the pathophysiology and epidemiology of the disease, the development of efficacious vaccines and treatments have made a clear difference in addressing severe forms of the disease and mitigating its public health impact. More contagious and/or virulent variants of the virus that are able to evade acquired immunity may continuously emerge, and their widespread dissemination is of concern in the near future. Novel and/or improved virus screening methods, therapeutics and vaccines are likely to remain key tools toward pandemic mitigation. The cumulative burden of \u201clong COVID\u201d sequelae as well as psychological/psychiatric impact of the disease and its control measures are crucial topics to study for guiding long term medical and public health management. Therefore, concerted research efforts on current topics remain a crucial part of the continued fight against COVID-19.ZK compiled/wrote the first draft. MS contributed to the outline. Both authors reviewed and edited for final revisions. All authors approved the final version for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The process of recovery of mental reactions in children after acute traumatic brain injury is determined by complex methods with an interdisciplinary approach. Studies of emotional, communicative and behavioral reactions are based on an assessment by a psychiatrist and a teacher-defectologist.To study mental reactions and identify predictors of positive recovery of consciousness after acute brain injury in children in early rehabilitation.48 children (14\u201336 months) with acute severe traumatic brain injury who were admitted for treatment and rehabilitation (in CRIEPST). Methods: psychiatric and pedagogical examinations; also - neuroimaging data and others.Three groups of children were identified, depending on the different severity of emotional, communicative and behavioral indicators: Group 1 (11%): The level of consciousness is minimal positive. Reactions: stable gaze fixation; emotional reaction to sound (smile) and the face of an adult; short-term tracking of the gaze of the object; the ability to touch an object and hold it; sits himself. Group 2 (33%): The level of consciousness is minimal positive / negative, with an advantage of positive. Reactions: unstable gaze fixation; emotional reaction and involuntary movements to sound; reflex seizure of an object; sits with support. Group 3 (56%): The level of consciousness is minimal negative. Reactions: no emotional reactions, low motor and sensorimotor activity.Predictors of emotional-communicative and behavioral indicators of recovery of the level of consciousness were identified: sensory and motor, cognitive and socially-oriented. These predictors are the basis for choosing a rehabilitation program with interdisciplinary support and a treatment strategy."} +{"text": "Dear Editor,Since the beginning of the new coronavirus SARS-CoV-2) pandemic, several cases of extrapulmonary involvement have been reported, including cardiovascular, gastrointestinal, neurological, and cutaneous manifestations. A wide variety of dermatological conditions related to COVID-19 infection have been reported; pandemic4A 56-year-old male patient complained of pruritic lesions that appeared on his lower limbs six months before. He mentioned that the lesions appeared approximately one week after the onset of COVID-19 infection symptoms, which was confirmed by RT-PCR. The patient had a mild respiratory clinical picture, without the need for hospitalization, and used ivermectin and hydroxychloroquine, prescribed at the service where he was originally treated. After the rash appeared, he used oral fluconazole and topical ketoconazole, with no improvement. The patient had a history of HIV infection, with an undetectable viral load for several years, without other comorbidities and with negative serology for syphilis, hepatitis B, and hepatitis C. He was undergoing regular treatment with lamivudine (3TC), tenofovir disoproxil fumarate (TDF) and dolutegravir (DTG), without recent changes in medications.On dermatological examination, the lesions were clinically and dermoscopically compatible with LP . He had Lichen planus is an immune-mediated dermatosis of unknown cause, which affects less than 1% of the population, mainly middle-aged adults, and may affect the skin, hair, nails, and mucous membranes.4A possible association between HIV infection and LP has already been reported. In the present case, we consider that the LP was triggered by the COVID-19 infection, since the patient had been diagnosed with HIV 24 years before, without changes in the medications of chronic use, with the appearance of lichenoid lesions timely associated with COVID-19. SARS-CoV-2 infection can stimulate cytotoxicity by TCD8+ lymphocytes and Th17 cells, changes that also participate in the pathogenesis of LP, and this can persist even after the resolution of the triggering viral infection.We report a case of annular LP that appeared one week after infection with COVID-19, suggesting an association between the diseases. There is a scarcity of reports of lichenoid lesions associated with COVID-19, with only one other report of the rare LP annularis variant triggered by SARS-CoV-2 infection having been identified.4None declared.Laura Murari Mondadori: Design and planning of the study; data collection, or data analysis and interpretation; statistical analysis; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Helena Barbosa Lug\u00e3o: Design and planning of the study; data collection, or data analysis and interpretation; statistical analysis; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.Fernanda Andr\u00e9 Martins Cruz Perecin: Design and planning of the study; data collection, or data analysis and interpretation; statistical analysis; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.Marco Andrey Cipriani Frade: Design and planning of the study; data collection, or data analysis and interpretation; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.None declared."} +{"text": "Editorial on the Research TopicPeriod povertyEach month, half of the world's female population, estimated at 1.9 billion individuals, experience menstruation . MenstruThe American Medical Women's Association defines period poverty as the lack of accessibility or affordability of menstrual hygiene tools and educational material, such as sanitary products, washing facilities, and waste management . The terPeriod poverty does not only affect menstruating people in lower income countries; it also affects them in higher income countries . It is eSwe et al.). These findings were similar to those highlighted in the systematic review by Patel et al. on period poverty in lower and middle income countries, which included three emerging themes:1.Availability and affordability of menstrual products, and accessibility to water, sanitation and health (WASH) services,2.Availability of support system and coping with \u201cperiod poverty,\u201d and3.Gender dimensions of menstrual hygiene management.Age appropriate education, using innovative approaches such as interpersonal practical guidance (IPG) as face-to-face communication and mediated practical guidance (MPG) as social and behavior change communication (SBCC), was successful in improving menstrual health and hygiene management (MHHM) knowledge, attitudes, and practices in India, while addressing the existing menstrual health challenges in similar settings . Another country that suffered drastically from the consequences of period poverty amidst an economic recession and political turmoil was Lebanon .The gap in the literature and the lack of data on period poverty is a continuous challenge to measure its deteriorating impact on women's health. The following special issue aimed to address this gap by including a diverse set of qualitative, cross-sectional, and review studies exploring the menstrual experiences of girls and women from different regions across the world. For instance, the menstrual health challenges reported by adolescent girls in Myanmar ranged from access to information and social support, to behavioral restrictions, stigma surrounding menstruation, and difficulties managing menstrual bleeding and pain . Similarly, adults working with U.S-based communities of color revealed tension between school responsibility and family authority in providing menstruation and puberty education in schools, school- and teacher-related delivery challenges, and inadequate and disengaging menstruation and puberty content .When it comes to the United States, low-income menstruating adults were seen to be disproportionately affected by period poverty during the COVID-19 pandemic because the pandemic acted as a barrier to period supplies and an underlying factor for missing work due to the lack of such products (Social, physical, and mental issues imposed by period poverty and encountered by females globally are inhumane and require immediate attention of policymakers and healthcare professionals to attain positive and sustainable menstruation outcomes. Findings from this issue will provide the readers with an overview about the current situation of period poverty in high-income and low-income countries. It will also guide research experts in the design and implementation of interventions seeking to address structural, social, and individual factors among populations impacted by such a phenomenon."} +{"text": "Zoonotic diseases account for at least 60% of all infectious diseases and no less than two-thirds of new emerging ones, which underlines the importance of monitoring them as early as possible. Understanding the nature of the animal-to-human transmission of zoonotic diseases is a fundamental requirement for their effective anticipation and control. The SARS-CoV-2 pandemic, and more recently, the monkeypox epidemic, have revealed our limited preparedness against a diversity of emerging and re-emerging pathogens. There are different modes of transmission of zoonotic diseases: direct or indirect contacts, vector-borne, or environmental , making their monitoring more complex. Effective control of zoonotic diseases requires early detection of the source of the disease and the factors that contribute to its spread. Combining wildlife, farm animal, and domestic animal health monitoring with human health monitoring can greatly reduce the risk of major epidemics or pandemics of zoonotic origin.The changes in our environment caused mainly by human activity and the evolution of human\u2013animal interactions are and will undoubtedly be responsible for several new health crises. These crises will be manifested in particular by an increase in the frequency and intensity of epidemics and epizootics. Numerous factors favor the increase in interactions between humans, animals, and their environment, such as the increase in animal and human population movements, or the demographic increase in the human population and its expansion into new geographical areas (ultimately increasing human/wildlife interactions). Over half of known human pathogenic diseases can be aggravated by climate change, including warming, precipitation, and floods . These pThe links and analogies between animal health and human health have been known since Antiquity, particularly with the transposition of anatomical knowledge from animals (particularly from dissections) to humans. This notion was expressed more concretely in the mid-1800s by a Prussian pathologist, Rudolf Virchow, who emphasized the lack of distinction between animal and human medicine. The \u201cOne Health\u201d concept has since developed by basing the study of these issues on multidisciplinary and multisectoral approaches . Its genEscherichia coli), and parasites [In this Special Issue, we invite colleagues to submit original research articles and scientific reviews to assemble a collection of papers highlighting the progress in our understanding of all aspects related to surveillance and control of zoonotic diseases, including (1) the development of new diagnostic tools, (2) outbreak investigation and surveillance programs of emerging pathogens , and 3) understanding the mechanisms of pathogen emergence. The first 10 papers published in this Special Issue address topics related to viruses , bacteria ( understasmodium) ,7,8,9,10"} +{"text": "Beach waste is an important pollutant in the Bohai Sea and coastal cities around the Bohai Sea and has raised many social and environmental concerns in China. The semi-closed characteristics of the Bohai Sea, the well-developed tourism, the special industrial structure and residents\u2019 living habits endow the beach waste around Bohai sea with a unique character that should be explored. This study investigated changes in the sources and composition of beach waste in coastal cities around the Bohai Sea of China during the tourist peak and off-peak seasons. Beach waste from twenty beaches in thirteen coastal cities around the Bohai Sea was sampled and analyzed in March and August 2021, respectively. The results showed that beach waste around the Bohai Sea was characterized by large quantities and small weights and was greatly affected by human coastal activities. The sources and composition of beach waste from different coasts and different seasons varied, whereas the overall trend was consistent. In terms of composition, beach waste in both the tourist peak season and off-peak season was mainly composed of plastics, fabrics and paper, which accounted for more than 70% of the total in weight. Meanwhile, the proportion of plastics in the total quantity of beach waste was greatest (maximum of up to 71%) and exhibited seasonal fluctuations, trending higher in the tourist peak season than in the off-peak season. In contrast, trends in the proportion of paper and fabrics in the total quantity and total weight of beach waste were relatively stable in different seasons. In terms of sources, beach waste mainly derived from human coastal activities, the proportion of which in the total quantity of beach waste in the tourist peak season reached 70.55% and was 11% higher than that in the tourist off-peak season. Shipping/fishing activities were the second largest source of beach waste, and their proportion in the total quantity of beach waste in the tourist peak season was 5% lower than that in the tourist off-peak season, as the tourist peak season around the Bohai Sea coincides exactly with the fishing moratorium. The quantity of smoking-related waste only accounted for 9.35% and 7.73% of beach waste in the tourist peak and off-peak seasons, respectively. The special semi-enclosed structure of the Bohai gulf, surrounded by land on three sides, aggravated the accumulation of beach waste on the coast. Source reduction and classified recovery, collaborative management of marine waste and beach waste, and joint prevention and control mechanisms of three provinces and one municipality (Tianjin) were suggested for comprehensive management of beach waste in coastal cities around the Bohai Sea of China. This study provided valuable information for beach waste management in coastal cities around the Bohai Sea of China. The world\u2019s oceans have been overexploited. Human activities are greatly affecting the marine and coastal environment and coastal ecosystems . Large qBeach waste is very complex and mainly composed of plastics, woods, metals, glass, rubber, clothing, foam and other materials ,12. Beac2, a mainland coastline of 2796 km, and an average water depth of 18 m. There are about forty rivers along its coast, including the Yellow River, Liaohe River and Haihe River. The Circum-Bohai-Sea region is an important strategic region for the coordinated development of Beijing, Tianjin and Hebei province in China, a significant ecological region for marine biodiversity protection as well as a vital functional region for the lives of local residents. Liaoning, Hebei, Shandong and Tianjin surround the Bohai sea, and their total gross marine output reached CNY 2621.9 billion, accounting for 31.4% of the national gross marine output of China. For decades, the Bohai Sea has paid a great price in its resources and environment to support the economic development around the Bohai region and has become the most degraded coastal area in China [Bohai Sea is the sole semi-closed marginal sea in China, with a sea area of about 78,000 kmin China . In partin China .At present, most research studies concerning the environment around the Bohai Sea region have focused on its seawater quality , marine 2, accounting for 1.63% of the total territorial sea area of China. The Bohai Sea includes Liaodong Bay, Bohai Bay, Laizhou Bay, Central Sea Basin and Bohai Bay. It is surrounded by thirteen coastal cities belonging to Liaoning, Hebei, Tianjin, and Shandong provinces. The Bohai Sea has a unique natural ecology, obvious geographical advantages and a prominent strategic position. Meanwhile, it is confronted with many challenges, including unstable environmental quality, a degraded ecosystem and high environmental risks. The Bohai Sea is a major ocean dumping area, accounting for 20.3% of the total amount of marine waste dumped in China, as shown in The Bohai Sea is a semi-closed, shallow sea located deep inside the Chinese mainland , as shown in The sampling points are shown in After collection, samples of beach waste from each sampling point during the tourist peak and off-peak seasons were sorted, counted and weighed, respectively. The composition of these beach waste samples was divided into nine categories: plastic, wood products, paper, metal, polystyrene plastic foam, rubber, fabric, glass, and others. According to the Northwest Pacific Organization, the sources of beach waste were divided into five categories : human cThe composition of beach waste obtained from twenty beaches in thirteen coastal cities around the Bohai Sea of China during the tourist off-peak and peak seasons is shown in Following plastics, paper waste and fabrics were also major components of beach waste around the Bohai Sea. In terms of average quantity, the proportion of waste paper in beach waste from twenty beaches in the tourist off-peak and peak season reached 18.32% and 17.97%, respectively. These waste paper components in beach waste mainly included food packaging, towels and cigarette boxes discarded by tourists. Meanwhile, in terms of average weight, the proportion of fabrics in the tourist off-peak and peak season remained relatively stable, reaching 28.65% and 27.28%, respectively. Polystyrene foam is a key material in fishing net buoys and life vests and is often found in beach waste. The percentages of polystyrene foam in beach waste from twenty beaches in thirteen coastal cities were highly variable and random. Among them, the percentages of polystyrene foam by weight and quantity were highest in Dongjiang Construction and Development Memorial Park of Tianjin, reaching 21.40% and 24.44% in the tourist off-peak season and 10.81% and 34.15% in the tourist peak season, respectively. The perniciousness of polystyrene foams to the marine environment and marine organisms is not less than that of plastic waste. The polystyrene foams are broken up and disintegrated into many pieces of micro-plastic by mechanical (wind and wave), biological (microorganisms) and chemical (ultraviolet radiation) degradation . Waste wThe sources of beach waste in samples obtained from twenty beaches in thirteen coastal cities around the Bohai Sea of China during the tourist off-peak and peak seasons are presented in The second greatest source of beach waste was shipping/fishing activity. This mainly included buoys, ropes and fishing nets. By quantity and weight, the average proportions of beach waste from shipping/fishing activity on these twenty beaches during the tourist off-peak season reached 19.12% and 27.75%, respectively, which were higher than their levels during the tourist peak season . One reason was that the tourist peak season between July to September for coastal cities around Bohai Sea coincided exactly with the seasonal fishing moratorium on the Bohai Sea. At that time, shipping/fishing activities were greatly decreased, which reduced their contribution as a source of beach waste. Meanwhile, the frequency of beach pollution cleanup operations was much higher during the tourist peak season than during the tourist off-peak season. These buoys, ropes and fishing nets washed ashore by the seawater would not stay on the beach for very long before they were cleaned up during the tourist peak season. Moreover, during the lengthy tourist off-peak season, a great deal of marine waste (including many buoys and fishing nets) would be washed ashore by strong winds, waves and ocean currents.Counting as the third greatest source of beach waste were other discarded materials, including construction waste and other debris from unidentifiable sources. In terms of average quantity and weight, the proportions of other discarded materials in beach waste during the tourist off-peak season on these twenty sampled beaches were also higher than their levels during the tourist peak season. Many waste materials were degraded into unidentified debris by waves. In particular, by weight, the proportions of other discarded materials in total beach waste at Panjin Jinbotan Beach, TDC&DM Park, Binzhou Shell Island and Yantai No. 1 Bathing Beach even reached above 40% during the tourist off-peak season. From 2, and the average density was 1849 kg/km2. It was reported that plastic waste (75.9%) was the overwhelming type of beach waste. China has been highly attentive the issue of marine waste pollution and has already issued a series of relevant laws, regulations and documents concerning marine environmental protection and marine waste management, as shown in Currently, marine and beach waste are important pollutants for the Bohai Sea and its surrounding coastal cities and have spurred many social and environmental concerns in China. Due to the semi-closed nature of the Bohai Sea and its low water exchange ability with the outer sea, marine waste and beach waste are exchanged only within a certain range of time and space. Thus, marine and beach waste should be taken into account together. According to the 2021 China Marine Ecological Environment Status Bulletin , the ave2/cycle; that was the lowest in four major sea areas of China [The quantitative proportions of different components and sources of beach waste on twenty beaches during the tourist off-peak and peak seasons were averaged to approximate the beach waste situation for the whole year in these thirteen coastal cities around the Bohai Sea of China, as shown in of China . In receAs shown in The waste scattered on beaches has a major negative impact on the natural landscape and the ecological environment of the coastal region. The high mobility of beach and marine waste materials due to frequent winds, waves, ocean currents and tsunami has further magnified their perniciousness.In particular, the Bohai Sea is the sole semi-closed marginal sea in China. There are about forty rivers along its coast, including the Yellow River, Liaohe River and Haihe River. The Bohai Sea is surrounded by Liaoning, Hebei, Shandong and Tianjin and is a vital functional region for the lives of local residents as well as a significant ecological region for marine biodiversity protection. The semi-closed nature of the Bohai Sea, the well-developed tourism, the special industrial structure and residents\u2019 living habits endow the beach waste around Bohai Sea with a unique character. In order to control the beach and marine waste pollution of coastal cities around the Bohai Sea, a series of suggestions are proposed as follows:(1) Source reduction and classified recovery. The production, sale and use of disposable plastic products should be further restricted. Reusable tools and products should be encouraged in shipping and fishing activities. The behaviors of individuals (tourists and marine industry practitioners) and relevant enterprises must be well-regulated. The random waste dumping into the sea and on beaches must be strictly prohibited. The identification of the sources, components and distribution of beach waste around the Bohai Sea should be well-investigated. The classified recovery of beach waste is indispensable. Valuable components and materials in beach waste should be recycled.(2) Collaborative management of marine waste and beach waste. Marine waste and beach waste will exchange positions within a certain range of time and space. Beach waste management should also be incorporated into the comprehensive governance of the Bohai Sea. Laws and regulations concerning collaborative management of marine waste and beach waste should be established. Deeper insights into the whole life cycle of beach waste combined with marine waste should be developed.(3) Joint prevention and control mechanisms in three provinces and one municipality (Tianjin). The Bohai Sea is surrounded by Liaoning, Hebei, Shandong and Tianjin. These four regions must keep pace in the comprehensive governance of marine waste and beach waste in the Bohai Sea. The joint prevention and control mechanisms of the three provinces and one municipality for marine waste and beach waste pollution are indispensable. With the efforts of the government, enterprises, institutions, environmental protection organizations and the public, the three provinces and one municipality will form a leading force for beach waste prevention and control.Beach waste around the Bohai Sea was characterized by large quantities of small, lightweight materials and was greatly affected by human coastal activities. The sources and components of beach waste from different coasts and in different seasons were varied, whereas the overall trend was consistent. In terms of composition, beach waste in both the tourist peak season and off-peak season mainly of plastics, fabrics and paper, which together accounted for more than 70% of the total in weight. Meanwhile, the proportion of plastics in the total quantity of beach waste was the greatest (up to a maximum of 71%) and exhibited seasonal fluctuations that were higher in the tourist peak season than in the tourist off-peak season. In contrast, the percentages of paper and fabrics in the total quantity and total weight of beach waste maintained relatively stable trends across different seasons. In terms of sources, beach waste was mainly derived from human coastal activities, which accounted for 70.55% of the total quantity of beach waste during the tourist peak season, 11% higher than that in the tourist off-peak season. Shipping/fishing activities were the second largest source of beach waste, and their share of the total quantity of beach waste during the tourist peak season was 5% lower than that during the tourist off-peak season, as the tourist peak season around the Bohai Sea coincides closely with the seasonal fishing moratorium. Smoking-related waste only accounted for 9.35% and 7.73% of the quantity of beach waste during the tourist peak and off-peak seasons, respectively. The special semi-enclosed structure of the Bohai gulf surrounded by land on three sides aggravated the accumulation of beach waste on the coast. Source reduction and classified recovery, collaborative management of marine waste and beach waste, and joint prevention and control mechanisms of the three provinces and one municipality (Tianjin) were suggested for comprehensive governance of beach waste in coastal cities around the Bohai Sea. Although this study provided valuable information concerning sources and components of beach waste in coastal cities around the Bohai Sea, the physical, chemical and biochemical properties of beach waste are still not clear. In the future, the characteristics of beach waste should be further investigated, and the treatment technologies should be taken into consideration."} +{"text": "Art-therapy is a promising and acceptable management strategy of eating disorders (ED). It has the potential to improve well-being and therapeutic alliance, targeting psychological dimensions of ED, and dealing with difficulties of expression and rationalization of patients. Nevertheless, the efficacy of this approach is difficult to evaluate because of the lack of studies in this area.We sought to provide an overview on the efficacy of art therapy in the management of ED, by a systematic review of all controlled trials using art therapy on patients with ED.This systematic review included all controlled trials using art-therapy on a population of adolescent and adult patients with ED. The effect of art therapy on clinical indicators such as anthropometric variables, symptoms and dimensions of ED was evaluated.Of the 1286 screened records, only four respected inclusion criteria. These four trials evaluated plastic art therapy, music therapy, writing therapy, and dance-movement therapy. A large number of bias and strong heterogeneity of inclusion criteria, techniques and variables prevented any attempt of quantitative synthesis. Music therapy appeared to have a significant effect on post-prandial anxiety, while dance-movement therapy showed an effect on body dissatisfaction.The generalizability of the results found is weakened by the high heterogeneity of trials. Replication studies and a rigorous methodologies are necessary for more reliable conclusions. Art therapy could help improving some specific dimensions of ED.No significant relationships."} +{"text": "Explosive growth in computing power has increased by orders of magnitude the complexity of data structures and the number of analyses that may be performed per unit time. Contemporary gerontology utilizes diverse data ranging from continuous longitudinal assessments (e.g. motion capture) to complex single-timepoint assessments (e.g. bioimages) to systems-level administrative descriptions of the healthcare delivery environment. Paradoxically, this abundance of resources presents a considerable challenge, as the availability of information threatens to overwhelm mechanistic models of aging supportive of intervention development. To inform precision medicine, gerontological biostatistics therefore embraces the opportunity of collaborating with allied quantitative disciplines to bolster the coherence, reproducibility, and generalizability of findings. This presentation will demonstrate the salient advantages of such interdisciplinary collaborations using the example of design and analysis of an intensely longitudinal study of wearable and environmental sensors, conducted with teams in exercise science and architectural design."} +{"text": "Dear Editor,Cutaneous Pseudolymphoma (CPL) refers to reactive lymphoid proliferation simulating cutaneous lymphomas. CPL may occur in response to many kinds of foreign antigens or factors, such as injected substances, tattoos, arthropod bites, and so on.A 31-year-old man presented with a 3-month history of two asymptomatic subcutaneous nodules on his back. He was otherwise healthy and there was no history of preceding illness, injected substances, vaccination, or insect bite. Physical examination revealed two coin-sized subcutaneous nodules palpable on his back . The skiCutaneous Pseudolymphoma (CPL) is not an uncommon condition, which considers a group of benign cutaneous lymphoproliferative disorders and very rarely progresses to lymphoma. The clinical presentation of CPL has a wide spectrum. The most common clinical manifestations are red to violaceous nodules, papules, or plaques on the exposed areas, especially on the face and neck. Subcutaneous nodules, as in our case, are the uncommon presentation of CPL, which have been described in several cases occurring secondary to feline scratches or injection of vaccines.None declared.Ying Wang: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript.Sitong Li: Approval of final version of the manuscript; participation in the design of the study.Yanping Bai: Approval of final version of the manuscript; conception and planning of the study.Zhancai Zheng: Approval of final version of the manuscript; conception and planning of the study; drafting and editing of the manuscript; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "The COVID-19 pandemic caused dilemmas for the most vulnerable populations around the world. This article describes the gendered effects of the pandemic on Ugandan women\u2019s rights and wellbeing and provides suggestions for local and international practice. Mandatory lockdowns and movement restrictions created negative implications for women\u2019s attainment of economic, social, cultural, political and civil rights and intensified pre-existing gender inequalities between women and men. The findings of intensified gender inequities, gender-based violence, sexual abuse, scanty access to reproductive health services and social justice, and barriers to participation in education, employment and politics indicate that response measures were not aligned with the government\u2019s legal and policy framework for addressing gender inequities. This research indicates that governments, civil society organisations and the international community must undertake proper gender analysis in designing response measures and guidelines not only for COVID-19 but also in other emergencies. All response measures during emergencies must be coordinated, monitored and evaluated to ensure efficient and effective protection of the vulnerable and conformity to human rights standards. The Sustainable Development Goals (SDGs)\u2014a plan to achieve 17 goals with 169 targets in 15\u00a0years evolved in 2015. These cover all aspects to transform lives. The goals provide hope that the world can transcend biting poverty, food insecurity, unhealthy lives and discriminatory gender practices and achieve equality and women empowerment and sustainable and inclusive development. The corona virus disease (COVID-19) pandemic emerged while international partners were struggling to redress imbalances as set out in the SDG plan to secure good futures for their populations. This global enemy was declared a public health emergency by the World Health Organisation (WHO) on 30 January 2020.In March 2020, Uganda reported its first confirmed COVID-19 case and cases gradually increased to 163,301 as of March 2022 Women, Based on a comprehensive literature review, this article describes the impact of the pandemic on women\u2019s rights and wellbeing. It explains the recurrence of gendered inequalities from the COVID-19 crisis. This research contributes to global attempts for strengthening women\u2019s capacities and rights. It is expected that national response teams across sectors will consider the gendered implications of COVID-19 and put in place a broad and gender-responsive COVID-19 prevention and response plan to reduce conditions of vulnerability and strengthen resilience across various disadvantaged groups.The article begins with a brief description of methods and provides the legal and policy context of the rights and management of COVID-19 in Uganda. The second part analyses the gendered effects of COVID-19 on women\u2019s rights and wellbeing under six themes: the implications of COVID on women\u2019s economic rights, COVID-19 and its effects on women\u2019s unpaid work, COVID-19 and women\u2019s health needs, COVID-19 and gender-based violence (GBV), COVID-19 implications on the young women\u2019s right to education and COVID-19, discrimination and the legal protection of women\u2019s rights. The final section provides local and international implications for practice.Uganda has made some advancements in the achievement of women and girls\u2019 rights in the political, economic and social spheres. For instance, the Universal Primary Education (UPE) programme increased the overall enrolment of women from 2.7 million in 1995 when it was rolled out to the recent 4. 4 million in 2017 (Uganda Bureau of Statistics (UBOS), Women have progressively become visible in leadership and public decision-making. The Ugandan Constitution provides for the reservation of one seat for a woman member of parliament for every district and at least one-third of local council seats are reserved for women. Women's reproductive health packages have also been promoted by the government and women\u2019s organisations and this facilitates their participation in the productive economy and ability to meet their survival needs. For example, the total fertility rate declined from seven to five children per woman between 1995 and 2016 UBOS, .Despite these achievements, research indicates high school dropout rates for girls in primary and secondary education, increased gender disparities in enrolment and completion rates and more women than men in low-paid occupations NPA, . BesidesUganda has a rich legal framework that addresses gender-responsive planning and programme design at the national, regional and international levels. Uganda\u2019s Constitution guarantees equality of all people under the law in all spheres of political, social and cultural life and the enjoyment of equal protection by the law in all aspects. Chapter four of the constitution lays down fundamental rights and freedoms of women and fair representation of marginalised groups, freedom from discrimination, and proposes affirmative action in favour of marginalised groups based on gender or any other reason created by tradition or customs is mandated to spearhead and coordinate sectors to ensure that the concerns and experiences of women and men are fully integrated into the design, implementation and monitoring and evaluation policies and programmes.With this initiative, the GOU has mainstreamed gender issues in several policies and programmes including, the Gender Equity Budgeting Policy, the National Priority Gender Equality Indicators 2016), the National Policy on the Elimination of Gender-based Violence in Uganda, the Uganda Vision 2040, the Third National Development Plan (NDPIII) 2020/21 \u2013 2024/25, the Uganda Gender Policy 2007 (UGP), the Gender in Education Policy, the Education Sector Strategic Plan (ESSP) 2007\u20132015 and the Business, Technical, Vocational Education and Training (BTVET) Strategic Plan (2012/3- 2021/2) to improve the status of women and girls. For instance, Gender Education Policy promotes the implementation of universal and compulsory education, engendered education curricula, gender equality in teacher recruitment, and deployment, sex education, re-entry into formal education for young mothers and advocacy for stay-in-school campaigns for girls (Ministry of Education and Sports (MoES), , the NatIn addition, Uganda is a signatory to regional instruments that promote gender equality and empowerment including the East African Community (EAC) Treaty (2000), the Common Market for Eastern and Southern Africa (COMESA) Gender Policy , the Protocol on the Rights of Women in Africa , the Inter-Government Authority on Development (IGAD), Gender Policy and Strategy , the New Partnerships for African Development (NEPAD) and the AU Heads of State Solemn Declaration on Gender Equality . Internationally, the country ratified the Convention on Elimination of All Forms of Discrimination Against Women , the Beijing Declaration and Platform for Action (1995), the International Conference on Population and Development (1994) and the United Nations Declaration on Violence Against Women .This allegiance obliges the government to enact programmes to enhance women\u2019s human rights and wellbeing. In 1997, the government enacted a National Gender Policy (NGP) which was revised in 2007. The NGP presents strategies focused on developing and implementing livelihood interventions that respond to diverse gender needs, address women\u2019s rights and access to justice, strengthen women\u2019s participation in administrative and political processes and address gender inequalities in macro-economic policy formulation, and implementation and evaluation 2020/21 \u2013 2024/25. The NGP stresses that all national programmes must advance equal gender relations by eliminating gender discriminatory practices, norms and values, preventing and responding to gender-based violence, executing sexual and reproductive health rights programmes, implementing legal literacy programmes for women, supporting social protection for vulnerable women, promoting time-saving technologies, developing incentive frameworks for poor women and eradicating exploitation of women and girls.This article is based on policy documents and published literature on COVID-19 and its impact on women and girls. It draws on official GOU documents about the management of COVID-19, international human rights instruments, national health and development policy documents, WHO publications and reports and journal articles covering COVID-19 and its impacts on women and girls. The majority of these documents were accessed from the government of Uganda websites. The first search for journal papers resulted in thirty-eight (38) papers but only nineteen (19) that were judged to be of high quality were included in the review covering Africa and other parts of the world. Literature published between 2005 and 2022 was considered for inclusion with a high number focused on the period 2020 and 2022 when the COVID-19 pandemic was confirmed.The policy documents were analysed using content analysis Bryman, . The proUganda confirmed the first COVID-19 case in March 2020, and the number of cases has since then increased to 163,301 as of March 2022 , In addition, all government ministries, agencies and departments were directed to work out plans to ensure that only essential staff would physically report for duty in the offices. Additional public health measures to contain the pandemic were instituted such as the closure of the country\u2019s borders, quarantining of individuals of healthy persons who may have been exposed to the virus and immediate suspension of public transport to minimise movement and contact among people. , The GOU recognises gender inequality as a constraint to growth in the country NPA, . Gender To ensure growth and prosperity, states are required to pursue progress in a fair way that grants women equal rights with men in the political, social, economic and cultural life of their countries. Gross inequalities in work and wages, unpaid women\u2019s work, discrimination in public decision-making, violence and exploitation of women and girls, harmful practices and unequal access to universal reproductive rights and health need to be exposed and eliminated. Elimination of these would foster equal rights and empowerment of women and lead to sustainable and inclusive development.The National Development Plan III (2020/2021\u20132024/2025) guides the establishment of strategies to increase household incomes and improve the quality of life of all people. Women have equal rights as men, to participate in the economic life of their countries at all times and in all contexts. Under this initiative, States must create an enabling environment where women and men are empowered to join gainful employment. This obligation requires a gender sensitivity lens to recognise different situations and needs of women and men throughout the decision-making processes. For instance, some women may require affirmative action to balance their roles both in the monetised and non-monetised sectors of the economy.However, Uganda\u2019s COVID-19 response measures did not take into account the economic and livelihood needs of women and girls. Previously, there has been marked gendered segregation of Ugandan women in the formal sector with many being concentrated in client-facing roles, leisure, travel and hospitality business \u00a0 revealedAlthough an economic shutdown of predominant female sectors has affected women in both developed and low-income states Peck, , women iUganda\u2019s National Equal Opportunities Policy 2006 envisioned a just, free and fair development process and establishment of affirmative action where imbalances exist compared to men (11%) left their jobs/careers to attend to household needs Peck, . Though The pandemic has worsened maternal health outcomes globally. Uganda has registered an increase in maternal deaths due to involuntary confinement and resultant financial uncertainty exacerbates maternal mortality and morbidity and increases the risks of early and unwanted pregnancies, HIV and other sexually transmitted diseases.A situation analysis of the impact of COVID-19 on school-going girls and young women in Uganda by the United Nations Children's Fund (UNICEF) reported a 22.5% increase in pregnancy among girls aged 10\u201324 seeking first antenatal care from 80,653 to 98,810.The National Policy on Elimination of Gender-Based Violence in Uganda aimed to eliminate gender-based violations and impunity ; UN WomeIn the public sphere, market women were forced to sleep on the job due to curfew with some being humiliated, injured and arrested by security personnel suffered , The decision to close schools possibly saved learners worldwide NPA, ; howeverArticle 2 of the CEDAW imposes an obligation on states to establish effective legal protection of the rights of women on an equal basis with men. Women need protection from exploitation and discrimination especially because emergencies intensify violence and disrupt existing protective structures and sexual harassment MOFPED, . For exaThe pandemic risked women\u2019s rights because services in different ministries and institutions including the health sector, justice sector, internal security, local government (districts) and non-government organisations services were disrupted due to limited financial and human resources. This restricted monitoring, evaluation and coordination efforts for apprehending perpetrators and support to victims. For instance, at a certain point, MoGLSD lacked funds to support GBV prevention and response while the closure of the court system delayed justice and GBV-related legislation revised and stringent roadmap. For example, the EC banned political rallies and processions and made the entire process unaffordable for the poor. Expensive restrictions and curfew rules curtailed general participation in these elections Babirye, . Women, The foregoing discussion shows the gendered effects of the COVID-19 pandemic on women\u2019s economic and education rights, unpaid work and health needs and indicates a resurgence of gender-based violence (GBV) and discriminatory practices against women and girls. This is concerning because they are happening with minimal or no protection because available resources are highly prioritised in the management of the pandemic. This raises an important question: how to stitch these gaps to protect rights and improve the wellbeing of women, girls and other marginalised populations during crises like the COVID-19 pandemic?At the outset, the GOU, civil society organisations and the international community need to re-examine COVID-19 measures and guidelines and ensure that they are gender-responsive and conform to human rights standards. To ensure that COVID-19 responses are gender-responsive, various social protection measures must be in place to shelter the most disadvantaged (such as the provision of food relief and cash transfers) and most importantly, women must be represented in professional and technical COVID-19 task forces. Given that most of the COVID-19 containment efforts are largely funded by development partners, they should avail sustainable and prompt funding to facilitate the formation of country-specific functional gender-sensitive management committees to promote gender equality initiatives and women\u2019s rights.It is also important to anticipate the gendered impacts of the lockdowns and stay-at-home orders on women and girls and other vulnerable groups. This is necessary to establish policies, systems, structures and practices that meet their specific needs and priorities, for example, measures to minimise delays in accessing specialised health care and affordable legal protection. Sustainable recovery strategies may involve recognition of women\u2019s unpaid work, provision of equal opportunities and social protection schemes UN, .Furthermore, affirmative action as enshrined in legal and human rights instruments must be pursued to bridge gender gaps and address historical and present forms of discrimination against women and girls in the economic, social, political and cultural spheres. For instance, social security protection measures to cover informal workers or capital and economic stimulus packages and emergency measures as implemented in other countries UN, can be aThe role of professionals in different ministries and institutions including the health, education, justice, internal security sectors and local governments must not be overlooked. This research has revealed several issues including violation of women\u2019s rights, gender-based violence and discrimination and their consequences on individual women and national development. Health workers, social workers, counsellors, lawyers and other professionals must provide seamless practice in terms of needs assessments, information sharing, management and referral. For example, probation officers are versed in human rights. They could form useful partners for assessing risks associated with response measures (such as lockdown and restrictions on movement) and monitoring the COVID-19 situation in communities and providing required individual and group counselling.Professionals over the world need to innovate ways of advocacy to ensure that the voices of disadvantaged groups reach COVID-19 management task forces in all contexts, for example, social workers can aid the transformation of the education system to integrate teaching methods that can address the special needs of traumatised or teenage mothers. This will ensure prioritisation of their rights and needs for safety, health and wellbeing and foster inclusive development in the long run.Gender equality is not only a right but also a necessity for the achievement of further development goals. The COVID-19 containment measures adopted by GOU have impaired women\u2019s rights and escalated unequal power relations causing high levels of violence against women and girls, death, disability, teenage/early pregnancies and school dropouts. Mandatory lockdowns and movement restrictions created negative implications for women\u2019s attainment of economic, social, cultural, political and civil rights and intensified pre-existing gender inequalities between women and men.The oversights (in the design and implementation of COVID-19 control measures) discussed in this article are great lessons for upgrading the management of ongoing and future pandemics. Uganda\u2019s government planners and development partners need to design and implement comprehensive and integrated response services to safeguard the wellbeing and survival of vulnerable populations. Such interventions must also consider and address their routine challenges.This research has indicated a need for policymakers, community leaders and service providers to apply gender analysis in the delineation of public health measures and standard operating procedures on women\u2019s wellbeing and rights.https://www.health.go.ug/https://www.unicef.org/uganda/press-releases/prioritize-re-opening-schools-secure-childrens-well-being"} +{"text": "Immunogenic cell death (ICD) is a type of cell death that leads to the regulation and activation of the immune response, which is marked by the exposure and delivery of damage\u2010associated molecular patterns (DAMPs) in the tumor microenvironment. Accumulating evidence has revealed the significance of ICD-related genes in tumor progression and therapeutic response. In this study, we obtained two ICD-related clusters for glioblastoma (GBM) by applying consensus clustering, and further constructed a risk signature on account of the prognostic ICD genes. Based on the risk signature, we found that higher risk scores were associated with worse patient prognosis. Besides, the results illustrated that ferroptosis regulators/markers were highly enriched the high-risk group, and ferroptosis were correlated with cytokine signaling pathway and other immune-related pathways. We also discovered that high-risk scores were correlated to specific immune infiltration patterns and good response to immune checkpoint blockade (ICB) treatment. In conclusion, our study highlights the significance of ICD-related genes as prognostic biomarkers and immune response indicators in GBM. And the risk signature integrating prognostic genes possessed significant potential value to predict the prognosis of patients and the efficacy of ICB treatment. Immunogenic cell death (ICD) is a form of cell death that leads to the regulation and activation of the immune response, which is characterized by the exposure and release of damage\u2010associated molecular patterns (DAMPs) in the tumor microenvironment such as calreticulin (CRT), secreted HMGB1and ATP . These mGlioblastoma (GBM) the most fatal brain cancer with a median survival time of 12 to 18 months and 5-year survival rate of less than 10% . At preshttp://www.tcga.org/ ). For the validation dataset, the RNA-Seq data were obtained from TCGA. The information about the response of tumor patients to anti-PD-1 checkpoint inhibition therapy was acquired from the Gene Expression Omnibus (GEO) datasets GSE67501 and GSE78220.For the training set, the RNA-Array data and corresponding clinicopathological information of GBM patients were retrieved from TCGA , progression free survival (PFI), and disease-specific survival (DSS) of patients in different clusters or risk groups. ROC curve was utilized to estimate the predictive performance of different classification methods in various aspects, including 1 -, 3 -, and 5-year survival, GBM subtypes, and IDH status.The DEGs between different risk groups were identified by utilizing the R package \u201cLimma\u201d. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the aberrantly expressed genes were determined by the gene set variation analysis (GSVA), which compared the variation levels of gene sets between groups . We alsoESTIMATE is an implement to estimate tumor purity and the presence of infiltrating stromal cells/immune cells in tumor tissues utilizing gene expression according to the enrichment analysis of single sample gene set .The immune infiltration heterogeneity between groups was estimated by the R package integrating six state-of-the-art algorithms, which include TIMER , MCP-couhttp://tide.dfci.harvard.edu/) assessed two different indexes of tumor immune escape, including dysfunction of cytotoxic T lymphocytes (CTLs) and rejection of CTLs by immunosuppressive molecules (Tumor immune dysfunction and exclusion (TIDE) analysis was performed to evaluate the potential response to ICB treatment. TIDE collects numerous cell drug sensitivity information and drug disturbance-based cell expression signature, which provides specific information for integrating a large number of drug sensitivity and genomic data to promote the discovery of novel therapeutic biomarkers for cancer treatment (The Genomics of Drug Sensitivity in Cancer (GDSC) database was utilized to locate the drugs with the specific target potential as anti-cancer candidates based on the correlation between the risk score and drug response AUC. GDSC database were compared in both the TCGA array , the key molecules mediating antigen presentation in cancer immunotherapy, were upregulated in the high-risk group (at/home) . NotablyThen, we applied the GDSC1 and GDSC2 databases to assess potential effective anti-cancer drugs based on risk scores and the AUC values of drugs. We identified 341 and 175 kinds of potential drugs in GDSC1 and GDSC2 databases respectively, and 15 kinds of them were overlapped whose AUC values were negatively correlated with risk scores (http://gepia2.cancer-pku.cn/#index) to obtai#index) can be found in the article/SF, XX, and QC made substantial contributions to the design of this study. XL, JL, ZL, and ZW carried out the analysis and interpreted the data. SF, XL, and XX made contributions to the drafting of the manuscript. HZ, ZD, PL, and JZ made contributions to the review of previous literature. SF, XX, XL, and QC contributed substantially to the revision of the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China ; Hunan Provincial Natural Science Foundation of China ; Hunan Provincial Health Committee Foundation of China (NO.202204044869); Natural Science Foundation General Program of Changsha City (kq2014290); and Xiangya Hospital Central South University postdoctoral foundation.All authors thank TCGA and GEO database for providing the wothy patient cohort data for research, and we also thank Central South University for providing the High Performance Computing Center.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Maintaining low ecological consumption and high well-being while making economic progress and thus achieving sustainable development is a significant issue facing the world today. Ecological well-being performance (EWP) is one indicator that tracks this progress. Although EWP has been typically assessed at the national, provincial and urban levels, investigations into EWP units in the Great Lakes region are lacking. This study applied the two-stage super-efficiency slack-based measure (Super-NSBM) model and DEA window analysis to evaluate the EWP and sub-stage efficiency in the Poyang Lake (largest freshwater lake in China) area and analyzed its spatial differences at the local level. Redundancy analysis was conducted to explore the EWP improvement paths of different counties in the Poyang Lake region and Dagum\u2019s Gini coefficient was applied to clarify the policy priorities of coordinated regional development. Results showed that the EWP of the Poyang Lake area presents an improving trend from 2007 to 2019, although the overall level is still low. The Poyang Lake area mainly faces the incongruity of ecological and economic development, which is the main reason for the low overall level of EWP. Excessive resource input and severe environmental pollution are common in most counties, but the focus of measures to improve EWP differs from county to county. The expansion of spatial differences in eco-economic efficiency leads to the spatial differences of EWP in the Poyang Lake area being still apparent at the local level. Reducing inter-basin disparities while alerting the widening of intra-basin differences is the policy focus for the future coordinated development of the Poyang Lake area. Achieving economic prosperity and social progress within ecological limits is the essential requirement of sustainable development for improving human well-being . Daly [4 [7] firIn recent years, scholars have successfully conducted numerous sustainable development studies through EWP. They have mainly used two methods to evaluate EWP, namely, ratio and the efficiency model . HDI 1313 and liSome scholars have argued that the ratio method presents two limitations . On the In addition, regional differences are a popular part of EWP research and have been studied extensively by scholars. For example, Wang et al. (2021) applied Although EWP has been successfully applied, it can still improve in the following aspects. First, most studies on spatial differences in EWP have been conducted under the large-scale levels of regions, provinces and cities and there is a lack of spatial difference analysis at the local level of the Great Lakes region. Second, studies typically consider ecological inputs but ignore nonecological inputs, such as scientific and technological expenditures and human capital inputs, in the process of indicator selection. These elements are indispensable intermediate means of converting ecological consumption to human well-being. Finally, existing studies only consider EWP as a simple direct conversion process from ecological consumption to well-being output and lack the analysis of sub-stage efficiency.Compared with previous studies, the main objectives of this study are presented as follows. First, nonecological inputs, such as science and technology expenditure and human capital input, are included in the evaluation index system to assess the level of EWP in the Poyang Lake area comprehensively and accurately. Second, the spatial differences of EWP and its sub-stage efficiency in the Poyang Lake area at the local level are analyzed and the Dagum Gini coefficient is used to explore the characteristics and sources of spatial differences. Third, the redundancy analysis is used to reveal what measures each county should take to enhance EWP. We hope that the analysis of this study can provide scientific policy reference for the local level of the Poyang Lake area to enhance EWP in a coordinated manner.The specific study area identified in this thesis includes 25 counties (districts or cities) within the Poyang Lake area, given the availability of data. Notably, Yujiang County was renamed Yujiang District in 2018, Jiujiang County was renamed Chaisang District in 2017, Dongxiang County was renamed Dongxiang District in 2016, Xingzi County was renamed Lushan City in 2016 and Xinjian County was renamed Xinjian District in 2015. However, this adjustment only changes the name and district boundaries remain the same. Names of administrative divisions after the adjustment are used in this study to ensure uniformity in presentation. The two main regional classification methods for the Poyang Lake area in the literature are \u201ccenter\u2013periphery\u201d and \u201cby The Poyang Lake area is divided into two parts: the lakeside area and the peripheral area around the lake. Poyang Lake basin belongs to the lakeside area and Ganjiang River basin, Xinjiang River basin, Raohe River basin, Xiuhe River basin, Yangtze River basin and Fuhe River basin belong to the peripheral area around the lake.On the basis of Long (2019) and WangThe evaluation index system of EWP in the Poyang Lake area is presented in Output indicators of the first stage also include both desired and undesired outputs. If the process of converting ecological inputs into economic outputs results in environmental pollution, then it can harm public health . TherefoHDI has been commonly used to measure the well-being output in existing studies. However, sub-indicators of the HDI cover only economic and social dimensions but ignore the importance of environmental well-being. Xiao and Xiao (2021) incorporNotably, the indicators of environmental pollution and total well-being output in this study are selected in large numbers, while the number of decision making units (DMUs) is small. This study adopts the entropy value method to accurately measure the EWP of each county (district or city) within the Poyang Lake area and reduce the dimensionality of environmental pollution and total well-being output. Finally, the indices of environmental pollution, economic well-being and social well-being are obtained.Data for the selected indicators are extracted from the 2008\u20132020 China County and the Jiangxi Provincial Statistical Yearbooks. Data for average years of education are obtained from the sixth and seventh national census bulletins published by the government of each county (district or city). Data on nighttime lighting were obtained from the Harvard Dataverse platform . Data foWe calculated the EWP of 25 counties (districts or cities) in the Poyang Lake area using MAXDEA 6.0 software. We then applied MATLAB R2015b to estimate spatial differences of EWP in the Poyang Lake area.km and kv represent the input and output of the stage k, respectively; k\u03c6 represents the number of intermediate indicators; represents the connection from stage k to stage h; x, y, z and represent the input, output and intermediate output, respectively; k\u03bb represents the model weight of stage k; and k\u03c9 represents the weight of stage k; k\u2212s represents the slack variables of input indicators; and gks and bks represent the slack variables of desired and undesired outputs, respectively.This study adopted a two-stage Super-NSBM model to measuThe DEA window analysis was adopted in this study to measure EWP in the Poyang Lake area and analyze differences in EWP and trend of efficiency changes in each county (district or city) comprehensively. This method first treats the same DMU in varying periods as different DMUs for efficiency calculation. The efficiency of each year in other windows is then weighted and averaged to obtain the final efficiency value of the evaluated DMU. Notably, this method can increase the number of DMU and compare the efficiency in both horizontal and vertical dimensions . On the G) of EWP in the Poyang Lake area is decomposed into intra-regional (intra-basin) differences (jjG), inter-regional (inter-basin) differences (Gjh) and super-variable density (tG) and satisfy: G = jjG + jhG + tG.The Dagum Gini coefficient method improved the shortcomings of the traditional methods of measuring spatial differences and solved the problem of cross-over between samples . It can \u03bc represents the mean value of EWP in each region, n represents the number of counties (districts or cities) in Poyang Lake area, k represents the number of regions, jn(hn) represents the number of counties (districts or cities) in the j(h) region (basin) and jiy(hry) represents the EWP of the i(r) counties (districts or cities) in the j(h) region (basin).jjG denotes the Dagum Gini coefficient of the j-th region (basin), jhG denotes the inter-regional (inter-basin) Dagum Gini coefficient of the j-th and h-th regions, jhD denotes the relative impact of EWP between the j-th and h-th regions (basins), jF(hF) is the cumulative density distribution function of the j-th (h-th) region (basin) and jhd denotes the differences of EWP between regions (basins). The Dagum Gini coefficient varies between 0 and 1. Spatial differences of EWP among counties (districts or cities) in the Poyang Lake area are small as the value of the Dagum Gini coefficient approaches 0 and vice versa.The formula for measuring the Dagum Gini coefficient can be expressed as follows:EWP is still at a low level from the overall perspective despite its rapid improvement in the Poyang Lake area . The aveSpecifically, among 25 counties (districts or cities) in the Poyang Lake area, only Duchang County, Poyang County and Gao\u2019an City demonstrate a decreasing trend of EWP, thereby indicating that the overall EWP in the Poyang Lake area is improving. Among them, Nanchang County, De\u2019an County, Xinjian District and Yongxiu County rank in the top four in terms of annual growth rate at 16.453%, 14.089%, 13.183% and 13.067%, respectively, and all achieved the relatively effective DEA. However, the overall level of EWP in the Poyang Lake basin is pulled down due to the low EWP in Lushan City, Xinjian District and Hukou County and the decreasing trend of EWP in Duchang and Poyang Counties. Similar to that of Duchang and Poyang Counties, the EWP of Gao\u2019an City also exhibits a decreasing trend with an average annual decrease of 1.529%. The average annual growth rate of EWP in Anyi and Wuning Counties was only 1.210% and 0.141%, respectively; hence, the Xiuhe River basin showed the lowest average annual growth rate of EWP among the seven basins.The significantly high results of the Super-SBM model, which takes into account the undesired output from a single-stage perspective, indicated that the two-stage Super-NSBM model selected in this study is accurate and reasonable. Moreover, this study can provide a methodological reference for similar studies that measure multistage efficiency.The EWP of counties (districts or cities) in the Poyang Lake area was generally at a low level in 2007. Only the EWP of Duchang and Poyang Counties were located on the production front surface. At this time, differences in EWP between the lakeside and peripheral area of the lake are small. The range of high EWP counties (districts or cities) in the Poyang Lake area showed an expanding trend in 2011. EWP of Jinxian County, Fuliang County, Leping City, Wuning County and Yujiang District improved. However, the EWP of Duchang and Poyang Counties dropped below 1. The scope of high EWP counties in the Poyang Lake area continued to expand in 2015. The EWP of counties (districts or cities), such as Nanchang County, Guixi City, Yujiang District and Fuliang County, improved significantly. EWP in the Poyang Lake area improved significantly in 2019 and counties (districts or cities) with low-level EWP are mainly located in the peripheral area of the lake. The EWP of De\u2019an County, Yongxiu County and Xinjian District improved to the efficiency frontier surface and the overall level of EWP of the lakeside area was significantly higher than that of the peripheral area of the lake. Thus, the EWP of the Poyang Lake area shows this spatial distribution pattern\u2014\u201chigh EWP counties spread from the lakeside area to the peripheral area of the lake and the EWP of the lakeside area is higher than that of the peripheral area of the lake\u201d\u2014from 2007 to 2019.This study further analyzed the sub-stage efficiency of EWP and the redundancy of input-output indicators in the Poyang Lake area to open the \u201cblack box\u201d of EWP in converting ecological consumption into well-being output.As can be seen from Specifically, the improvement of EWP in the Lakeside area is mainly constrained by the efficiency of economic well-being. Compared with the peripheral area of the lake, the economic level of the lakeside area results in a significantly higher value for eco-economic efficiency because the area is more developed, more technologically advanced and presents stricter environmental protection policies. By contrast, the low EWP in the peripheral area of the lake is mainly due to constraints of eco-economic efficiency. Only the Xinjiang River basin in the region shows higher eco-economic efficiency than economic well-being efficiency. Among the 25 counties (districts or cities), only Poyang County achieved DEA relative effectiveness in both eco-economic and economic well-being efficiencies in 2019. Notably, Dongxiang District\u2019s economic well-being efficiency improves yearly and achieved DEA comparative effectiveness in 2019 despite an eco-economic efficiency of only 0.280. Dongxiang District must improve its eco-economic efficiency to enable coordinated economic, ecological and social development. Jinxian County achieved an effective DEA for economic well-being efficiency but faced the same problem of incompatible economic and environmental development. The eco-economic efficiency of Yogan County, Nanchang County, De\u2019an County, Xinjian District, Yongxiu County and Yujiang District increased beyond the production frontier surface and the efficiency of economic well-being needs further improvement.Although some counties achieved an effective DEA for EWP in 2019, the majority still present a low EWP. Therefore, this study selected 2019 as the time point for redundancy analysis. This section focuses on the redundancy of input-output indicators in counties (districts or cities) with low EWP. Lushan City and Hukou County not only spend too much on education but also produce a large amount of carbon and wastewater emissions in the development process and thus have a low EWP. Low land resource use efficiency, high PM2.5 concentration and per capita sewage discharge and a severe shortage of sanitation technicians in Xinkan County are the main reasons for its low EWP. Zhangshu City, Gao\u2019an City and Dongxiang District not only have higher land consumption, water consumption and pollution discharge but also have redundancy in education expenditure. Guixi\u2019s low EWP is caused by low land resource use efficiency and per capita public finance expenditure, while education expenditure and per capita sewage discharge are too high. There is redundancy in education expenditures in Anyi County and the efficiency of water resources utilization, sewage treatment rate and per capita social security and employment expenditures are below average. Wuning County has excessive consumption of land and water resources and the economic output efficiency of education and science and technology expenditure needs to be improved. Chaisang District and Ruichang City are overly redundant in terms of energy consumption, land consumption, water consumption and spending on science and technology. Their PM2.5 concentration and per capita sewage discharge are also much higher than average. In addition, Chaisang District needs to improve its forest cover and sewage treatment rate to contribute to the improvement of environmental well-being.The analysis results demonstrated that the efficiency of EWP and its sub-stages in the Poyang Lake region differ significantly at the local level. Therefore, this study applied the Dagum Gini coefficient to analyze EWP\u2019s characteristics and sources of spatial differences in the Poyang Lake area.As shown in We decomposed the spatial differences of EWP in the Poyang Lake area in a basin division according to Equations (3)\u2013(11) to illustrate the characteristics and sources of spatial differences further. The annual average values of inter-basin differences in EWP in the Poyang Lake area from 2007 to 2019 are listed in Finally, we analyzed the intra-basin differences of EWP in the Poyang Lake area. The Dagum Gini coefficient of the Fuhe River basin is 0 from 2007 to 2019 given that it only contains Dongxiang District; therefore, the intra-basin differences of EWP in the Fuhe River basin are not shown in The sustainable development status of the Poyang Lake area has attracted considerable research attention since the State Council of China approved the Poyang Lake Eco-economic Zone Plan in 2009. However, there is no study in existing research to analyze the sustainable development of the Poyang Lake area through EWP. In this study, a two-stage Super-NSBM model was applied to divide the process from resource input to well-being output into two stages and then analyzed the EWP of the Poyang Lake area. Compared with the study of Long (2019) , who alsAlthough the EWP of the Poyang Lake area demonstrates an improving trend from 2007 to 2019, the overall level is still low. Most counties have problems of over-input of natural resources and environmental pollution. At the same time, counties should beware of over-investment of funds, which fails to improve EWP significantly and may lead to increased debt. Specifically, each county and region should apply differentiated measures. Lushan City and Hukou County must reduce excessive spending on education, introduce advanced technology and promote the green transformation of industries. Xinkan County should improve land use efficiency, increase the number of health technicians and strictly limit PM2.5 and wastewater emissions from enterprises. Zhangshu City, Gaoan City and Dongxiang District must reduce land and water consumption, minimize education expenditure redundancy and limit pollution discharge. Guixi City should improve land use efficiency and public finance expenditure, reduce education expenditure redundancy and limit wastewater discharge. Chaisang District and Ruichang City must reduce the consumption of various resources and pollution discharge and increase the forest coverage and sewage treatment rate. Anyi County should pay attention to the utilization of water resources and wastewater treatment, improve the efficiency of education expenditures and increase social security and employment expenditures. Wuning County must reduce the consumption of land and water resources and excess spending on education, science and technology.The differences of EWP and its sub-stage efficiency and indicator redundancy among counties and districts confirmed that EWP in the Poyang Lake area indeed has spatial differences at the local level. The widening spatial differences in eco-economic efficiency are a significant reason why the spatial differences of EWP in the Poyang Lake area are still apparent. Meanwhile, we found that inter-basin differences are the primary source of spatial differences in EWP in the Poyang Lake area. Therefore, the policy focus of the future coordinated development of the EWP region in the Poyang Lake area should be to introduce a cross-regional collaboration mechanism. Regions with advantages in production efficiency, technology level and resource endowment are targeted to help lagging areas to smooth their development mode and realize green economic transformation. The government should also actively help lagging regions increase their income, improve infrastructure construction and social security systems and enhance people\u2019s well-being. Finally, strengthening the construction of ecological civilization within each basin, establishing regional environmental regulatory agencies and establishing long-term cooperation for sustainable development are crucial to avoid intra-basin spatial disparities from widening while narrowing inter-basin differences.However, this study also has some limitations. Regarding the selection of well-being indicators, due to the lack of survey data on subjective well-being in the Poyang Lake area, we can only select objective well-being indicators. Our future research direction is to investigate residents\u2019 subjective well-being in the Poyang Lake area and then analyze EWP by combining subjective and objective well-being indicators. Besides, applying the system dynamics method to the analysis of EWP in the Poyang Lake area is also worth exploring.The main conclusions of this research are as follows.First, the EWP of the Poyang Lake area shows an improving trend from 2007 to 2019, but the overall level is still low. The EWP of all seven basins failed to achieve DEA effectiveness. The spatial distribution of EWP in the Poyang Lake area shows this apparent pattern\u2014\u201cthe high EWP counties spread from the lakeside area to the peripheral area of the lake and the EWP in the lakeside area is higher than that in the peripheral area of the lake.\u201dSecond, there is a complex problem of uncoordinated development between the economy, ecology and society in the Poyang Lake area as a whole. The low eco-economic efficiency mainly constrained the improvement of EWP in the Poyang Lake area and the redundancy of resource input and environmental pollution were more severe in all counties and districts in general. The eco-economic efficiency of the lakeside area is higher and the primary goal is to coordinate the relationship between economy and well-being to promote the efficiency of economic well-being. The redundancy analysis revealed that measures to improve EWP varied across counties.Third, the spatial differences of EWP in the Poyang Lake area are gradually decreasing and show the overall trend of coordinated development. However, the spatial differences of eco-economic efficiency are progressively expanding, resulting in the spatial differences of EWP in the Poyang Lake area at the local level being still evident. Inter-basin differences are the primary source of spatial differences in the Poyang Lake area\u2019s EWP. Reducing the inter-basin differences of EWP in the Poyang Lake area while avoiding the elevated intra-basin disparities is crucial."} +{"text": "S\u20136. Se.g.iologies , 8.Alkabie and Budrham reviewed the methodologies used for the testing of the two most common antibody-associated demyelinating myelitis, namely myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD) and aquaporin-4 (AQP4) positive neuromyelitis optica spectrum disorders (NMOSD). They compare the performance of fixed and live cell-based assays, the yield of antibody detection in different specimens , and address the important topic of antibody titer cut-offs, which is particularly relevant for diagnostic accuracy of MOGAD. This latter point is also at the core of the original research of Manzano et al., who investigated the positive predictive value of serum anti-MOG antibody testing in a real-world institutional cohort, using well-established live cell-based assays. While on one hand the authors identify an assay cut-off 1:40 as the one yielding the highest positive predictive value, they also noted a sizeable number of cases with phenotype aligned with typical MOGAD that would have been missed with the use of such threshold, underscoring the need for further work in the optimization of diagnostic assays.For this Research Topic, the characteristics of different immune-mediated myelopathies and common associated diagnostic tests have been extensively reviewed. Cacciaguerra et al. provide an overview of the key imaging features, pitfalls and mimics of the most common demyelinating syndromes and of some rare, recently characterized immune-mediated myelopathies. Recent years have seen an exponential rise in the number of biological agents that can be applied for the treatment of systemic inflammatory disorders and malignancies, and neurologists are increasingly challenged by possible secondary neurological manifestations of these treatments. This expanding field of iatrogenic myelopathies is the focus of the review of Gritsch et al., which provides useful recommendations for workup and management, while Passeri et al., provide an in-depth discussion of paraneoplastic myelopathies. Recognizing these rare but important causes of myelopathies has important treatment implications, and is now particularly relevant as the testing for many of the associated antibodies has become commercially available in the United States. Lastly, Fadda et al. compare the typical evolution, clinical and radiological short and long-term outcomes of spinal cord involvement in multiple sclerosis, MOGAD and AQP4 antibody positive NMOSD, emphasizing the importance of accurate diagnosis and prompt treatment initiation to alter the disease course of these disorders.These articles altogether highlight how, even in the presence of useful biomarkers, the diagnosis of immune mediated myelopathies rests on clinical acumen, and the recognition of characteristic disease features remains the fundamental step to achieve diagnostic accuracy. To aid clinicians in the differential diagnosis of inflammatory myelopathies, Our knowledge on many of the immune-mediated myelopathies discussed in these articles is still at its early stages, and many spinal cord syndromes observed in clinical practice continue to be labeled as idiopathic. While this field will likely continue to evolve in the upcoming years, physicians should familiarize with the current landscape of immune mediated myelopathies, as prompt recognition of these syndromes and early and targeted therapies are often key to provide the most optimal patient outcomes.GF, EF, and ES: study concept, design, and drafting the manuscript and figures. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The first part of the SSNN Summer School of Neurology 2022, which covered the first day's events, is highlighted in a previous publication.Natan Bornstein (Israel) and Dafin Muresanu (Romania). The beginning session of the day, Session 5, started with Natan Bornstein (Israel), the Director of the Brain Division and Chairman of the Israeli Stroke Society (ISS), and his two presentations: \"Secondary Stroke Prevention \u2013 The DAPT Story \u2013 A Journey of 25 Years\" and \"Post-stroke cognitive decline \u2013 current concepts and treatment approaches\". Prof. Bornstein firstly stated the importance of tertiary prevention of stroke with the syntagm \"don't let stroke strike twice\", as stroke represents a major cause of long-term disability, and went further into discussing current guidelines and the long-term story of Dual Antiplatelet Therapy (DAPT) research, beginning back in 1996. His second presentation discussed treatment options following ischemic stroke, highlighting the lessons from double-blind randomized trials in patients with acute mild ischemic stroke or high-risk Transient Ischemic Attack (TIA). Moreover, as post-stroke depression (PSD) represents the most frequent non-cognitive neuropsychiatric complication and is associated with higher mortality, poorer recovery and decreased quality of life, the investigation of its mechanisms remains a subject of utmost importance. Due to this, approaches should be multidimensional, involving a multidisciplinary team for the best results.The second day of the congress was introduced by Dafin Muresanu (Romania), President of the The European Federation of NeuroRehabilitation Societies (EFNR), presented microcirculation and stroke and discussed the 3 crucial pillars in neurorehabilitation and brain protection and recovery:Developing a solid theory and strong hypothesis, validating the ideas with basic research;Testing the effectiveness of the intervention;Using evidence-based parameters.He then pinpointed two critical aspects of rehabilitation: the limit of the disability and the individual biological reserve. In addition, the importance of creating promising paradigms and protocols for treatments and aligning the mechanisms of action with the design was showcased, and the two anticorrelated sequences of post-lesional brain regulation (NEUROPROTECTION and NEURORECOVERY) were also highlighted. Moreover, Prof. Muresanu discussed endogenous defence activity, damage mechanisms, and the levels of central nervous system (CNS) endogenous modulation. One crucial point touched upon was the importance of the proportion and interactions as more relevant factors than the separate effects of each function. Furthermore, he offered an in-depth view of the anticorrelated processes of 3 different levels, discussing the vertical correlation between functional and gene networks. The principal therapeutic approach in acute ischemic stroke was also outlined, which refers to:Arterial revascularization;The substantial predictive effect on clinical outcomes of the final recanalization;The factors on which brain tissue perfusion depends.European Federation of NeuroRehabilitation Societies (EFNR).In his comprehensive presentation, he discussed the combination of approved methods, avenues for enhancing thrombolysis, and the role of Cerebrolysin in inhibiting endogenous inflammatory pathways. Prof. Muresanu closed the session with a lesson on performing neurorestorative treatments with extended therapeutic windows and recommended that specialists work together in integrative approaches, highlighting the role of the th session, hosted by Dafin Muresanu and Adina Stan, began with the presentation of Jesse Dawson (UK), Professor of Stroke Medicine at the Institute of Cardiovascular and Medical Sciences in Glasgow (UK) on \"Stimulation (neuromodulation) for post-stroke recovery\". Prof. Dawson highlighted that there are many mechanisms for upper limb impairment, therefore, many avenues for recovery. As a result, the interventions should be related to the cause of impairment. The approach in stroke rehabilitation refers to causing task-specific plasticity, as neuro-connectivity and activity are altered post-stroke. Also, with plasticity being task-specific, neuromodulation \u2013 the alteration of neuro-activity to target the delivery of a stimulus to specific neurological sites \u2013 encompasses both advantages and disadvantages, showcased in his presentation. Prof. Dawson discussed different types of stimulation and their respective roles and effects, as well as approached VNS (vagus nerve stimulation) after ischemic stroke for upper limb motor function, highlighted in his research.The 6Andreas Winkler (Austria), Medical Director and Head of Department in Neurological Rehabilitation at Klinik Bad Pirawarth in Vienna (Austria), presented \"How can we be more efficient in motor recovery after stroke?\". Prof. Winkler discussed the possibility of improving endogenous plasticity and introducing a new window of opportunity to obtain a better neurological outcome for the patient. He approached the enhancement of post-stroke plasticity and the limitations of current undertakings, including selective serotonin reuptake inhibitors (SSRIs), and discussed three clinical trials to highlight his previous point. Moreover, he showcased the usefulness of Cerebrolysin in stroke patients as outlined by different medical societies and the shift from past approaches to this innovative agent, underlining the positive effects of Cerebrolysin on neuroplasticity. The role of Brain-derived neurotrophic factor (BDNF) as a biomarker in stroke and the enhancement of post-stroke plasticity through electrical stimulation were also tackled. One important point of his presentation was combining different approaches to boost plasticity.Adina Stan (Romania), Primary Neurologist and Lecturer of Neurology at the University of Medicine and Pharmacy Iuliu Hatieganu in Cluj-Napoca (Romania), presented a case study on stroke, showcasing the disease progression and process of examination, discussing the affections of the patient, and engaging the public to suggest the most probable diagnosis based on the available information. She also tackled the differential diagnosis, discussed the TOAST classification of stroke subtypes and underlined the role of stroke prevention. Following her presentation, Hanna Dragos (Romania), from Cluj-Napoca Emergency County Hospital (Romania), offered an inspiring approach to a rare disease, discussing the symptoms, disease progression, medical history examinations, and, similarly, asked for public input on the most likely diagnosis. Finally, after covering multiple aspects, she touched upon the molecular genetic diagnostic pathway for stroke-like episodes and the management of the disease.th session, presided by Cristina Tiu (Romania) and Rodica Balasa (Romania), Cristina Tiu (Romania), Head of the II Neurology Department and Head of the Neurology Discipline at the Neurology Clinic from the Bucharest University Emergency Hospital in Bucharest (Romania), introduced the public to her presentation \"About immunosenescence and inflammaging in multiple sclerosis (MS). Therapeutic options in older patients\". With elderly patients being a challenging population and real-life patients differing from those presented in clinical studies, complex and multimodal approaches to diagnostics and treatment are needed. Prof. Tiu discussed the prevalence of MS and various epidemiological characteristics, the immunosenescence of innate immune systems, the meningeal inflammation, and the influence of age on the pathophysiology of MS and imaging features for identifying comorbidities. Two scenarios were tackled: (1) diagnosis at older age vs. (2) patients with known MS who are aging naturally, with particularities detailed for each. Finally, she argued whether the discontinuation of immunomodulatory therapy is recommended in patients over 60 years of age from a therapeutic perspective, pinpointing the aspects of biological age, epigenetic factors, and lifestyle strategies.During the 7Mihaela Simu (Romania), Professor and Chairman of the Neurology Department II \u2013 the University of Medicine and Pharmacy Victor Babes in Timi\u0219oara (Romania), presented \"Cognitive impairment in MS \u2013 from theory to practice\". Historical notes, statistical facts, and the science of cognition and neuropsychology were discussed first. The presentation then focused on statistical data on cognitive deficits in MS and various neuropsychiatric aspects of the disease, with an outline of the neuropsychological patterns in MS cognitive impairment according to phenotypes and the similarities of cognitive profiles of different MS phenotypes. Further on, Prof. Simu offered a view into the types of cognitive deficits, assessment of MS, and the prevalence of cognitive deficits in MS depending on the subtype, mentioning the pediatric population. The classification of MS and the various tests and screening methods were also discussed, and the presentation ended with recommendations for cognitive impairment (CI) evaluation in MS, as CI is a common feature of MS, which direly impacts patients' quality of life, with 40\u201370% of patients affected at any time during the course of the disease.Rodica Balasa (Romania), the Head of the Neurology 1 Clinic at the Emergency Clinical County Hospital of Mures (Romania), ended the session with \"Plasmatic exosomal microARN from brain cells in the evaluation of immunological treatment in multiple sclerosis patients\". During her presentation, Multiple Sclerosis (MS) was discussed, its impact \u2013 as the leading cause of chronic neurological handicap in young adults \u2013 was showcased, and the difficulty in treatment due to its heterogeneity and the unknown aetiology as a probable result of the interplay of several different factors were touched upon. Prof. Balasa tackled the role of inflammation in demyelination and axonal loss, the processes of neurodegeneration and remyelination, and highlighted disease-modifying therapies, underlining that the best choice for the patient is based on the specific biological mechanism of CNS inflammation. As a result, the best-suggested response is precision medicine.Hari Shanker Sharma (Sweden), the Director of Research at the International Experimental Central Nervous System Injury & Repair (IECNSIR) from the University Hospital, Uppsala University (Sweden), presented \"Methamphetamine exacerbates Alzheimer's disease pathology\". Neuroprotective effects of nanowired Cerebrolysin with Neprilysin, discussing the particularities of the blood-brain barrier in the Alzheimer's disease and the effect of methamphetamine. As Alzheimer's disease (AD) represents a devastating neurological affection leading to lifetime disability, investigating the risk factors, which can accelerate the pathogenesis of AD, including substance abuse, is of utmost importance. Prof. Sharma also focused on the effects of methamphetamine intoxication on the spinal cord and the rapid morphological changes after acute intoxication, highlighting his research on the matter.The last session of the day, Session 8, was introduced by Hari Shanker Sharma (Sweden) and Xianshuang Liu (USA). First, Xianshuang Liu (USA), Associate scientist at the Department of Neurology from the Henry Ford Hospital, Detroit (USA), offered his presentation together with Michel Chopp (USA), Vice Chairman for Research of the Department of Neurology and Scientific Director at the Henry Ford Neuroscience Institute, Detroit (USA), on \"Exosomes enhance the coupling of neurogenesis and angiogenesis by transfer of microRNA\", where the functions and uses of exosomes were explained, the process of neurogenesis and angiogenesis described, and the impact of stroke on their association was tackled.Ioana Mandruta (Romania), the Head of the Epilepsy Monitoring Unit at the University Emergency Hospital of Bucharest (Romania), presented \"Semiology of epileptic seizures \u2013 the new glossary of terms\". Prof. Mandruta discussed epilepsy, its subtypes, the classification of seizures, the need to address the terminology, and presented a case with epilepsy. She explained the definition of myoclonic jerks, offering examples, discussed seizures with focal onset and the appearance of seizure symptoms based on the affected part of the brain, and provided a glossary definition of elementary motor signs. Further on, Prof. Mandruta presented complex motor behaviors, subjective ictal symptoms, also called \"aura\", autonomic events, and the localization of seizure generators. Moreover, she exemplified another case of seizures with impaired consciousness and the exploration of the patient. Finally, she discussed temporal lobe epilepsy and posterior cortex epilepsy, ending with additional case studies on patients with epilepsy.Peter Jenner (UK), Emeritus Professor at the Institute Of Pharmaceutical Sciences from the Faculty of Life Sciences and Medicine at King's College in London (UK), presented \"Can we develop non-dopaminergic approaches to the treatment of Parkinson's disease?\" and began his lecture with a discussion on \"breaking out of the dopaminergic box\", highlighting the need for more complex approaches to PD and suggesting a multimodal pharmacological perspective as the best way in the future. Dopaminergic approaches dominate the field as they are highly effective for this disorder but can lead to complacency, considering there are still some needs in PD that cannot be treated with a dopaminergic approach. He suggested that although the dopaminergic treatment helps non-motor symptoms it is not the complete solution, and discussed safinamides as a treatment option. An essential point of his presentation was that there are non-dopaminergic components to both motor and non-motor symptoms of Parkinson's disease. Cristian Falup-Pecurariu (Romania), the Head of the Department of Neurology at the County Clinic Hospital from Brasov (Romania), presented \"Autonomic dysfunction in Parkinson's disease\", discussing the spectrum of dysautonomia symptoms in PD and the prevalence of different symptoms (dependent on study methodology). Parkinson's Disease (PD) has a wide variety of non-motor symptoms and one of the frequently encountered ones \u2013 autonomic nervous system dysfunction \u2013 direly impacts the quality of patients' lives. In advanced stages, dysautonomia significantly impacts the activities of daily living. He then discussed the relationship between disease progression and survival rates of autonomic dysfunction and dysautonomia in patients with a high risk of PD, pinpointing on the autonomic dysfunction and disease severity. Methods of dysautonomia assessment and specific symptoms were additionally presented. Comprehensive approaches to treatment management were showcased.Alla Guekht (Russia), Director at the Moscow Research and Clinical Center for Neuropsychiatry in Moscow (Russia), presented \"Post-stroke cognitive impairment and dementia \u2013 Treatment challenges\", addressing epidemiology, the populations at risk, potential targets, prevention, treatment, and current strategies and perspectives. As the population is growing older, people 65 and over represent the fastest growing group, posing several issues, with post-stroke cognitive dysfunction representing an important factor of morbidity. With shifting demographics, increased post-stroke survival and life expectancy can also mean an increased number of patients with post-stroke cognitive impairment. Prof. Guekht discussed the importance of implementing results for clinical trials in different groups and addressing the challenges and unresolved issues in post-stroke cognitive decline. For this, the trajectory is of utmost importance. The complexity of the affection requires combined approaches and assessment at different time points, as well as consideration of the emotional and cognitive problems. She presented some risk factors that increase the magnitude and speed of post-stroke cognitive decline, highlighting early seizures after stroke and the post-stroke development of epilepsy. The relationship between stroke location and cognitive outcomes, the association of cognitive impairment with early seizures, and the multidomain lifestyle interventions to prevent cognitive decline after stroke were also subjects touched upon. Moreover, Prof. Guekht encouraged integrative approaches in diagnosing and treating neurological disorders and discussed the need for increased research and more clinical trials to address the best strategies for post-stroke cognitive impairment.Jozsef Szasz (Romania), Associate Professor at the Department of Neurology at George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures (Romania). He described the Romanian context for testing and initiating therapy by means of a multicenter study from 9 university teaching hospital centres on 113 patients. The presented research demonstrated the effects of therapy on patients with advanced Parkinson's disease. Prof. Szas detailed his research on the matter, highlighting, through video presentations of the patients over the years, the effects of the treatment.Next, Session 10, presided by Jozsef Szasz (Romania) and Cristian Falup Pecurariu (Romania) was introduced with a presentation on \"Management of advanced Parkinson's disease with Levodopa intestinal gel\" by Dafin Mure\u0219anu (Romania), the president of the European Federation of NeuroRehabilitation Societies (EFNR) and Chairman at the Department of Neurosciences from Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca (Romania), then presented \"Is neurorehabilitation useful in Parkinson's Disease?\". Prof. Muresanu began with an introduction to brain functions and the shifting paradigm in neuroscience, offering a brief parallel between the physics and biology approaches in neuroscience. He further discussed the three circuitries of the nervous system, namely the limbic, the associative, and the sensorimotor, underlining the importance of said mechanisms working in harmony. Next, Prof. Muresanu masterfully described the \"small-world\" network organization of the brain, the endogenous modulation based on balancing anticorrelated processes, and the interrelation between the brain's levels of organization. Further on, he discussed basal ganglia and behavior regulation, the relationship between dopamine and executive dysfunction, and the relationship of rehabilitation with the biological reserve, highlighting the differences between the classic medical model and the rehabilitation model. Moreover, prof. Muresanu pinpointed the role of restoration versus compensation in neurorehabilitation, the specialists needed for developing a comprehensive rehabilitation team, and the functional rationale for neurorehabilitation in Parkinson's Disease. Prof. Muresanu also discussed guidelines for occupational therapy in PD, mentioned the importance of cueing in the rehabilitation process, and ended on a brief note on neurorehabilitation in different PD stages.Stanislav Groppa (Moldova), Head of Neurology Department at the State University of Medicine and Pharmacy Nicolae Testemitanu in Chisinau (Republic of Moldova) presented \"Nonconvulsive Status Epilepticus \u2013 A Complex and Often an Under-Recognized Entity\". Prof. Groppa discussed status epilepticus as a neurological emergency and a challenge of modern neurology, as the condition is difficult to delimit, and current clinical options remain unsatisfactory. This affection is often unrecognized, leading to delays in diagnosis and treatment, mostly due to failure to request an electroencephalogram (EEG). He showcased issues in diagnosis, the role of EEG on epidemiology, and pinpointed \"borderline syndromes\" where electrographic convulsive activity appears without obvious clinical seizures. The discussion then centered around the primary forms (nonconvulsive and convulsive), their causes, the trigger factors, clinical manifestations \u2013 including chameleon presentation and mimic disorders. Furthermore, he approached the management, complications, and treatment recommendations for this disorder, the need for tailored interventions, the importance of research with prospective studies on the effects of extended continuous EEG monitoring on outcomes and cost-effectiveness strategies for early identification and treatment.Adina Roceanu (Romania), Primary Neurologist and Research Scientist at the Neurology Department from the University Emergency Hospital Bucharest (Romania), on migraine treatment. Beginning with the definition and symptoms of migraines, she offered insight into one of the most common affections for the larger population. Prof. Roceanu discussed the classifications of migraines with and without aura, highlighting specific criteria for each of the two presentations. She underlined related affections, including chronic migraines and medication-overuse headaches, while also showcasing the clinical phases of migraines and the role of specific agents in their treatment. Dr. Roceanu ended her presentation with a mention of some non-pharmacological approaches which are appropriate in situations where pharmacological treatment proves ineffective.The following session, Session 11, introduced by Adina Roceanu (Romania) and Corina Roman (Romania), began with a presentation by Corina Roman (Romania), the Head of the Neurology Department at the County Hospital Sibiu (Romania), approached case presentations on secondary headaches. Prof. Roman discussed the international classification of headache disorders, the general principles, and the pharmacological agents that can cause headaches. She described red flags suggestive of secondary aetiology of headache in patient history and introduced clinical case presentations on headaches attributed to arteriovenous malformation, headaches caused by cerebral tumors, and patients with MS with associated secondary trigeminal neuralgia. Prof. Roman suggested that headache is prevalent and headache disorders are among the most common signs of nervous system disorders, making it vital to consider the patient history, neurological examinations, and the SNOOP mnemonic as the best predictors of pathology.Vitalie Vacaras (Romania), Lecturer of the Neurology and Pediatric Neurology Discipline at the Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca (Romania) presented \"When headache hides neurocysticercosis \u2013 Case presentations\", an interesting clinical case with some unexpected characteristics. He began by discussing cysticercosis \u2013 what it is, what some of the risk factors and its most common manifestations are \u2013 and followed with the specific case, detailing the diagnostics and examination of the patient, the prognosis of the disease, initial treatment, evolution, and outcomes, discussing the implications and rationality for choosing the previously mentioned case.Catalin Jianu (Romania), Professor of Neurology, Head of the First Department of Neurology, and Head of Advanced Research Centre for Cognitive Research in Neuropsychiatric Pathology at the Victor Babes University of Medicine and Pharmacy in Timisoara (Romania), \"An integrated approach on the diagnosis of cerebral veins and dural sinuses thrombosis\", in which Prof. Jianu began by offering the public information on the epidemiology of the disease. Then, he discussed cerebral veins anatomy, the anatomy of intracranial dural sinuses, the aetiology and risk factors, genetic and acquired thrombophilia, the most common risk factors, and the impact of COVID-19. Next, he covered the pathophysiological mechanisms leading to the clinical presentation of cerebral venous thrombosis (CVT), and also discussed clinical diagnosis, the importance of laboratory data and tests, and imaging methods. Further on, Prof. Jianu presented the experience of the hospitals, an analysis of 70 patients admitted between 1998 and 2021 and the results, as well as a review of an integrated approach to the diagnosis of cerebral veins and dural sinuses thrombosis. He then showcased another case review on cavernous sinus thrombosis in a woman with inherent thrombophilia and one on acute isolated lateral sinus thrombosis. One important takeaway from his presentation was that a comprehensive clinical spectrum with an often-misleading presentation might cause diagnosis delays.The last session of the event, Session 12, presided by Catalin Jianu (Romania) and Vitalie Lisnic (Republic of Moldova), was introduced with the presentation of Mihail Gavriliuc (Republic of Moldova), Professor of Neurology and Chairman of the Neurology Department from the State University of Medicine and Pharmacy Nicolae Testemitanu in Chisinau (Republic of Moldova), presented on Neuroborreliosis, an antropozoonosis also known as Lyme disease. Prof. Gavriliuc discussed the aetiology of different species of Borrelia, the biological basis and different presentations, Lyme disease vectors, and the deer tick's life cycle. He approached epidemiology, pathogenesis and pathophysiology, and clinical manifestations for early and late neuroborreliosis. He highlighted the Bannwarth triad symptoms and outlined differential diagnosis of Lyme neuroborreliosis, diagnostic workup, the management of the disease in the early and late stages and the importance of individualized therapies.Vitalie Lisnic (Republic of Moldova), Professor of Neurology at the Nicolae Testemitanu State University of Medicine and Pharmacy in Chisinau (Republic of Moldova), ended the congress with his presentation \"Wilson disease \u2013 a constellation of phenotypes\". First, he discussed the history of the disease, its aetiology, prevalence, and other epidemiological aspects and highlighted the clinical picture and the existence of a delay in diagnosis. Further on, Prof. Lisnic described hepatic, psychiatric, ophthalmic, and neurological manifestations, followed by methods of diagnosis. Lastly, he presented clinical cases and treatment with different cure options for various presentations and discussed new treatment avenues. One fascinating insight of his proceedings is an algorithm for treating Wilson's disease. He ended by stating the importance of investigating Wilson Disease (WD) in any patient with neuropsychiatric manifestations of unknown cases. The disease can be fatal without therapy, yet treatment has an excellent prognosis.The conclusions of the event were drawn by Dafin Mure\u0219anu (Romania), Natan Bornstein (Israel), Volker Homberg (Germany), and Wolfgang Grisold (Austria), with Prof. Muresanu sharing his hopes for an in-person next edition of the Summer School of Neurology. Prof. Muresanu touched upon the possibility of future hands-on programs and extended his gratitude to everyone who contributed to the development of the program."} +{"text": "Dear Editor,Plasma Cell Cheilitis (PCC) is a rare inflammatory disorder of unknown origin within the spectrum of plasma cell mucositis. Clinically, it manifests as a circumscribed, flat to slightly raised, eroded erythematous plaque or patch involving the lower lip of elderly male patients.An otherwise healthy 52-year-old man, an agricultural worker, was referred to our hospital with a ten-year history of painful erythematous erosion on the lower lip. Physical examination revealed an erythematous plaque with diffuse desquamation along with erosions and crusts A. DermosOne of the main differential diagnoses in the context of our patient was Actinic Cheilitis (AC) or even progression to Squamous Cell Carcinoma (SCC). Dermoscopy could be a useful tool to help differentiate these entities. We found some similarities between our case and the previously reported regarding border regularity and vascular enlargement and proliferation.Although PCC is considered a benign disorder is usually refractory to various topical treatments, including topical and intralesional corticosteroids, topical calcineurin inhibitors, antibiotics, and antifungal agents.None declared.Daniella Truffello: Approval of the final version of the manuscript; critical literature review; data collection, analysis, and interpretation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; study conception and planning.Carolina Cevallos: Approval of the final version of the manuscript; critical literature review; effective participation in research orientation; manuscript critical review; preparation and writing of the manuscript; study conception and planning.Claudio Escanilla: Approval of the final version of the manuscript; critical literature review; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; study conception and planning.Pauline Morgan: Approval of the final version of the manuscript; data collection, analysis and interpretation; intellectual participation in propaedeutic and/or therapeutic management of studied cases.None declared."} +{"text": "Based on the panel data of thirty-one provinces in China from 2003 to 2020, we constructed an evaluation index system of urban-rural integration development level from the perspective of factor flow. The combined weighting model of GI and CRITIC were used to evaluate the regional urban-rural integration development. The coefficient of variation and panel fixed effect model was used to explore convergence, absolute convergence, and conditional convergence. The impact of capital, labor, and technology factor flow on the convergence of urban-rural integration development level was further investigated. In addition, the difference analysis in time scale and impulse response function analysis was performed to explore the regular pattern of factor flow on the convergence of urban-rural integration development. The main conclusions were as follows: first, the growth of urban-rural integration development had an absolute convergence trend and tended to conditional convergence faster. Second, the capital flow positively affected the convergence of urban-rural integration development, while labor and technology flow had a slowing effect on the convergence of urban-rural integration development at this stage. Third, the impact of factor flow on the convergence of urban-rural integration development was dissimilar during different phases. The convergence rate of urban-rural integration development after 2012 was drastically slower than before. The urban-rural disparity is a critical headspring of social structure differences. For a long time, \u201cUrban bias\u201d has existed and been popular due to people's wrong concepts and restrictions of development. In recent years, problems have become more and more apparent, like the gap between rural and urban economic development is increasingly widening, and the rural economy has been aggravating in some areas. The proportion of urban population and output rises due to the \u201cSiphoning effects.\u201d Agriculture has languished and lost development vigor, and rural areas face the issue of growing depopulation . The ecoOne of the important performances is the unbalanced development between urban and rural areas and inadequate development in rural areas. Promoting the integrated urban-rural development is the key to alleviating the unbalanced and inadequate development between urban and rural areas and the objective requirement of ensuring common prosperity between urban and rural residents. Urban and rural integration breaks the contrary state of the urban-rural dual structure and gradually realizes the rational flow and optimal combination of factors in urban and rural areas. Urban-rural coordinating development had been proposed as a strategy as far back as 2002. \u201cPromote the integration of urban and rural development\u201d was proposed in 2012. Furthermore, on this basis, integrated urban and rural development was proposed in 2017, emphasizing the interaction of urban and rural factors. The evolution of the policies might fully embody the development of cognition on urban-rural relations [Factor mobility between urban and rural areas might change the fundamental structure of urban and rural elements, influence the evolution of urban-rural relations, and then affect urban-rural integration development. At the micro-level, factor flow might put idle resources to work, promote balanced marginal returns growth in urban and rural elements, and realize complementary functional advantages and maximization of integral benefit . At the Along with the development of urban-rural relations, the concept of urban-rural integration is continually developed . FurtherIn recent years, the study on the flow of urban and rural factors has been roughly divided into three aspects . Some stIt is normal to have a certain degree of development gap in social and economic development , 22. HowIn short, other studies on the overall development of urban and rural areas and their index systems cover three dimensions: society, economy and ecology, mainly adopting the ratio of urban and rural indicators, and then making a descriptive analysis of the results. The research on the combination of urban-rural integration and factor flow focuses on the internal logic and relationship, lacking specific empirical research. The possible marginal contributions of this paper are as follows: Firstly, given that urban and rural areas are two different social forms, the state indicators and dynamic indicators showing the integrated of urban-rural development are added on the basis of the mainstream of urban-rural comparative indicators in the past; the spatial integration dimension is added to the indicator system for the closer spatial connection between urban and rural areas. Secondly, from the perspective of factor flow, this paper analyzes the regional gap and convergence of the integrated urban-rural development. It also further explores the differences of labor, technology, and capital factor flow on the integrated urban-rural development convergence, which not only provides reference for further promoting integrated urban-rural project but also provides theoretical support for guiding the free and orderly flow of factors. Thirdly, by means of using provincial data, this paper examines the distribution and convergence of the overall integrated urban-rural development at a macro level, and explores the influence of the flow of factors between urban and rural areas in different provinces on the overall integrated urban-rural development and regional economy.From the perspective of spatial evolution, the difference of factor resource endowment between urban and rural areas is the initial reason for the low level of urban-rural integration development. With the advancement of industrialization, the centripetal force formed by the city's market effect and price index effect makes the factors gather in the urban area, which gradually improved the production conditions and quality of life in urban area. The flow of factors promotes rapid urban economic growth. At the same time, this process also accelerates the process of element agglomeration. Once the accumulation of factors in urban reached a specific size, the cost of living and production in cities is gradually rising, which might create centrifugal forces and crowding effect, and progressively transfer factors to rural areas, promote rural economic development, narrow the development gap between urban and rural areas, and improve the development level of urban-rural integration. By promoting the two-way flow of urban and rural factors in various regions, urban-rural integration development gradually balances. Finally, the convergence of urban-rural integration is realized. Our growth function of urban-rural integration development level is as follows:yt+1i \u2212 ln\u2009\u2009yti) is affected by the urban-rural integration development level (yti) of the region and the gap between areas ) and other factors (xti). The gap between areas is affected by the stock and flow of labor, capital, and technology. Based on this, Hypothesis 1 is proposed in this study.\u2009 H1: factor flow might play a critical role in converging urban-rural integration development.As shown in the above formula, the growth of urban-rural integration development level Hti indicates the natural growth (WHti \u2212 WHtj/WHts) and suggests the transfer ratio caused by the reward gap of H factors between regions. The scale of labor mobility increases with the increase of the pay gap. However, there is an upper limit on labor transfer. The congestion function is defined as m = Ht + (Lt/Nt)Nt+1 = (1 + \u03c6)Nt, indicating that the regional population capacity limits the proportion of labor mobility. Similarly, the meaning of the labor mobility equation is similar to that of H. When the pay gap between regions of H factor is higher than that in L, its proportion of labor transfer is also higher. With the increase H, the scale of subsequent labor flow is limited in places of influx and finally the number of H and L reaches a balance in the process.The above formula /Rts). The former fixed capital transfer is multiplied by the realization coefficient t based on this proportion. Therefore, the simplified form of capital transfer equation is as follows:The capital transfer is affected by the differences in regional interest rates. It is worth noting that fixed and new capital transfer speed is different. It is assumed that the transfer proportion of new capital i is lower than in region j, the item (Rti \u2212 Rtj) becomes negative. Currently, the elements in the j area show a trend of backflow. Affected by the difference of interest rates between regions, the capital flow might promote the capital flow, which affects both the regional economic development and the urban and rural integration and development. Based on this, hypothesis 2b is proposed:\u2009 H2b: capital flow has a critical impact on the convergence of urban-rural integration development.As shown in the above formula, when the interest rate in region Technology transfer is affected by the proportion of science and technology funds in financial expenditure (the rate of technology investment). Like the above capital transfer equation, the simplified form of the technology transfer equation is as follows:i is lower than the regional technology input rate of region j, (Tti \u2212 Ttj), it becomes negative. The elements of the j area show a return trend. Affected by the difference in technology input rate, technology flows between regions, affecting regional economic development and urban-rural integration development. Based on this, hypothesis 2c is proposed:\u2009 H2c: technology flow has a crucial impact on the convergence of urban-rural integration development.The setting of the above formula does not limit the inflow and outflow places. When the interest rate of region Based on the abovementioned, promoting the integrated urban-rural development is actually promoting the two-way flow of elements between urban and rural areas. For a long time, a large number of productive factors in rural areas have continuously flowed into cities unidirectionally, resulting in serious \u201cblood loss\u201d in rural areas. In the new relationship between urban and rural areas, rural elements flow to cities, and urban elements also flow to rural areas, which will form a virtuous circle of two-way flow of urban and rural elements. It is essential to guide the factors to flow freely and orderly between urban and rural areas, and activate the endogenous power of rural development through \u201coptimizing the combination effect of factors,\u201d \u201cspillover effect of knowledge dissemination technology,\u201d and \u201cexpanding market scale effect by division of labor,\u201d so as to promote the integrated development of urban and rural areas.The growth level of urban-rural integration development. Based on Chang et al. , the difDevelopment level of urban-rural integration, labor flow, capital flow, and technology flow. The development level of urban-rural integration is measured by establishing an index system and calculating the urban-rural integration development index. We construct an evaluation index system for urban-rural integration development, following the scientific and creative principles. Labor flow equals the ratio of the number of employees in this province and the average number of employees in other regions in the current year. Capital flow equals the balance of the number of capital formation rates to the average value of capital formation rate in the current year in other provinces. Technology flow equals the ratio of this province's science and technology expenditure (R&D expenditure) to the average science and technology expenditure of other regions.Per capita GDP (logarithm), fiscal decentralization, and rural financial services in this region. The higher the regional GDP, the better the regional economic development, which could drive regional urban-rural growth and impact urban-rural integration development. The higher the level of fiscal decentralization, the more autonomy the local government has, which could reasonably arrange urban and rural resources, promote resource allocation, and promote regional urban-rural integration and development. Rural financial services mean financial support for rural areas. The more thoughtful rural financial services are, the more funds might be provided for rural development, which could accelerate the speed of urban-rural integration and development. The above control variables are measured by the proportion of local government income in total income and per capita agriculture-related loans (logarithm).The econometric model selected in this study refers to the research on the setting of the convergence model by Bakbak and Kansu and Cholyi,t is the development level of urban-rural integration in the region i during the periodt, yi,t\u2212T is the development level of urban-rural integration in the region i at the beginning of the intervalT. Due to the short observation period, this study investigates the growth rate of urban-rural integration development in one (1/T)ln year. The average annual growth rate of the development level of urban-rural integration in the region \u03b2 is the convergence rate of the development level of urban-rural integration in the region. Variable Z includes fiscal decentralization, rural financial services, industrial structure, and other factors that might affect the growing convergence of urban-rural integration development. At the same time, to avoid simultaneous errors of variables, we deal with the first-order lag of critical investigation variables and control variables.Among them, yi,t \u2212 ln\u2009\u2009yi,t\u22121 refers to the growth of regional urban-rural integration development level in the year; yi,t\u22121 is the development level of urban-rural integration that lags behind the first stage; Ki,t\u22121 is the factor flow that lags behind the first period in the region, including labor flow lm, capital flows cf, technology flow tf; Xi,t\u22121 is a series of control variables that affect the growth of regional urban-rural integration development; ui refers to the individual effect; vt indicates the time effect; \u03bei,t is a perturbation term.According to formula , the fol\u03c3 convergence model belongs to the concept of convergence in neoclassical economic growth theory. If there is \u03c3 convergence in the level of urban-rural integration, then the urban-rural integration converges in absolute value and finally realizes the balanced development of urban-rural integration. The coefficient of variation was used to measure the convergence of urban-rural integration, as shown in the following formula:The Values were expressed as mean\u2009\u00b1\u2009SD.https://olap.epsnet.com.cn, accessed on December 16, 2021)). Some missing data are supplemented by interpolation. Due to the lack of data from Hong Kong, Macao, and Taiwan, 31 provinces and cities are selected as the research objects. The following table is the basic descriptive statistics for the samples. To avoid the objective deviation caused by experts' subjective judgment and incomplete data statistics and make up for the lack of single weighting, we adopt the combination of the G1 method and critical subjective and objective weighting method. Taljaard and Mare [The data used in this study are from the relevant years of \u00abChina Financial Statistics Yearbook\u00bb, \u00abChina urban and rural construction statistics yearbook\u00bb, provincial statistical yearbooks, EPS database , rural financial services (L. lnrfs), and per capita GDP (L. lnpgdp). Before the empirical analysis, the unit root inspection was carried out on the panel data, and the results demonstrated that the variables were stable. There are three models for panel data model estimation: mixed regression model, fixed-effect model, and random effect model , 31. TheThe fixed effect was estimated for the panel data to validate whether there was absolute convergence of the development level of urban-rural integration. The benchmark regression results are exhibited in \u03b2 Convergence trend in the growth of urban-rural integration development in China with provinces and cities as samples by using the fixed effect estimation of panel model \u03b2. After controlling the time effect in model (2), the coefficient of L. lny was still negative, indicating that this result was relatively robust. After adding variables such as fiscal decentralization (FD), rural financial services (Lnrfs), and per capita GDP (lnpgdp), the regression coefficient of L. lny was still negative regardless of whether the time effect was controlled. The convergence rate in model (3) was 0.087 percentage points higher than that in model (1), and that in model (4) was 0.053 percentage points higher than that of model (2). These data indicated a trend of absolute convergence in the growth of regional urban-rural integration development. Moreover, this growth might tend to conditional convergence at a faster speed.As shown in We next investigate the convergence of factor flow on the growth of urban-rural integration development, the interaction terms of capital flow and urban-rural integration development, labor flow and urban-rural integration development, technology flow, and urban-rural integration development were introduced into the model, respectively. The benchmark regression results are shown in As shown in As shown in As shown in \u03c3 convergence verification, we first understood the improvement process of regional urban-rural integration development. Here, we depicted the density diagram of urban-rural integration development before and after the year of the promulgation of the policies of \u201ccoordinating urban-rural economic and social development,\u201d \u201cpromoting urban-rural integration,\u201d and \u201curban-rural integration.\u201dBefore the \u03c3 convergence) of regional urban-rural integration development and factor flow was measured by the variation coefficient of urban-rural integration development and factor flow. As shown in \u03c3 convergence). The coefficient of variation of factor flow was greater than that of urban-rural integration. From big to small, the coefficient of variation of factor flow among provinces and cities was technology flow, labor flow, and capital flow [As shown in tal flow .Affected by the implementation of the policy, the impact of factor flow on the growing convergence of the development of urban-rural integration in provinces and cities might be diverse during different phases. After the proposal of \u201ccoordinating urban-rural economic and social development\u201d in 2002, the relationship between urban and rural areas had changed from Urban-Rural separation to urban-rural integration. \u201cPromote urban-rural integration\u201d was proposed in 2012. It is reasonable to believe that there might be pronounced period heterogeneity in the impact of factor flow on the growth of urban-rural integration development in different provinces and cities. It is necessary to further explore the time difference of factor flow on the convergence of urban-rural integration development in China. Here, the two-way fixed effect model of panel data were employed to investigate the situation in different regions in 2003\u20132011 and 2012\u20132020, respectively. The results are shown in As shown in Impulse response function could directly reflect the dynamic interactive relationship and effect between variables and urban-rural integration development. To avoid orthogonalization dependence caused by the order of variables, VAR models of general impact response between variables and the development speed of urban-rural integration were established, respectively. The impact results of impulse response are shown in To test the robustness of the above empirical results, the independent weight coefficient method is used to recalculate the regional urban-rural integration development index, which is substituted into the two-way fixed effect model of the panel data model for re-estimation. The results are shown in As shown in Provinces and cities with the extreme growth trend of urban-rural integration development might have substantial heterogeneity and significantly impact the empirical results. Therefore, to overcome the possible impact of this situation, the top and bottom five provinces and cities in the urban-rural integration development were excluded, and the robustness of the above empirical conclusions was assessed. As shown in \u03b2 convergence model. We further explored the time difference of factor flow on the growing convergence of regional urban-rural integration development and assessed the robustness. The main conclusions were as follows:Based on the perspective of factor flow, we constructed the evaluation index system of urban-rural integration development using the panel data of 31 provinces in China from 2003 to 2020. The combined weighting model of GI and CRITIC were used to evaluate the regional urban-rural integration development. The impact of capital, labor, and technology factor flow on the convergence of urban-rural integration development was evaluated using the coefficient of variation and The growth of urban-rural integration development had an absolute convergence trend and tended to conditional convergence faster. The variation coefficient of urban-rural integration development and the regression coefficient of L. lny in model (1) was negative, indicating a definite convergence trend in urban-rural integration development. Furthermore, the estimated coefficient was still negative after controlling the time effect, indicating that the conclusion was stable. After introducing the variables such as fiscal decentralization (FD), rural financial services (Lnrfs), and per capita GDP (lnpgdp), the regression coefficients of L. lny were negative regardless of whether the time effect is controlled. The convergence rate of model (3) was 0.087 percentage points higher than that of model (1). Moreover, the rate of model (4) is 0.053 percentage points higher than that of model (2), implying that the growth of regional urban-rural integration development had the trend of absolute convergence, and it might tend to conditional convergence at a faster speed.Nowadays, the capital flow has a positive effect on the convergence of urban-rural integration development, while labor flow and technology flow have a slowing effect on the convergence of urban-rural integration development. After adding the interaction term between capital flow and urban-rural integration development, the coefficient of urban-rural integration development in the base period was negative, whereas the coefficient of interaction term was positive, and the convergence rate increased. Capital flow positively affected the growth and convergence of urban-rural integration development. After adding the interactive term of labor mobility and urban-rural integration development, the coefficient of urban-rural integration development in the base period and the coefficient of the interactive term was negative, and the convergence rate decreased. After adding the interaction term between technology flow and urban-rural integration development, the coefficient of urban-rural integration development level in the base period and the coefficient of interaction term were negative, and the convergence speed also decreased. Labor and technology mobility slowed the growth and convergence of urban-rural integration development at this stage.There were time differences in the impact of factor flow on the convergence of urban-rural integration development. The convergence rate of urban-rural integration development after 2012 was markedly slower than before. Before and after the proposal of \u201cpromoting urban-rural integration\u201d in 2012, the growth of urban-rural integration development of provinces and cities in China showed a convergence trend, and the convergence rate was about 0.030 percentage points lower than before 2012. We also found significant differences in the impact of factor flow on the convergence of regional urban-rural integration and development around 2012. The convergence rate of urban-rural integration development before 2012 is higher than after 2012. Furthermore, the interaction coefficient of capital flow, technology flow, and urban-rural integration development also showed the opposite direction before and after 2012. However, the interaction coefficient of labor flow and urban-rural integration development had not changed before and after 2012.We should further promote the rural revitalization strategy and the two-way flow of urban and rural factors. The core of the rural revitalization strategy is talent revitalization. Establishing an institutional mechanism for the rational flow of urban and rural populations could attract rural and urban labor to stay in rural areas and start businesses to build rural areas. Establish and improve the introduction and training mechanism of professional farmers, cultivate new agricultural business entities, and improve the labor skills and quality of the rural population by establishing a talent training and exchange platform, strengthening the contact and cooperation between urban and rural talent markets, and establishing an information-sharing mechanism to provide institutional basis and policy guarantee for the rational flow and optimal allocation of urban and rural resources. Build the benefit-sharing mechanism for factor subjects, build a mechanism combining the complementary functions of the government and the market, and build the endogenous development mechanism of rural areas to promote the two-way flow of urban and rural factors, which guide the flow of production factors to rural areas.Develop the financial allocation capacity of local governments and guide financial funds flow to rural areas. Financial support is the first element to develop a new countryside. Coordinating urban and rural development is a systematic project, which might not be realized only by market mechanism regulation. We should develop the positive guiding role of government funds, increase capital investment, leverage financial funds and social resources, and speed up the construction of a new countryside. We should increase fiscal expenditure on rural education, agricultural science, and technology; insist education as the foundation and technology as a means; improve the actual productivity of rural areas; and attract more talents to participate in rural construction. Establish and improve the government investment guarantee system to increase the public budget for agriculture and rural areas to fill the lack of agricultural and rural development. We should plan new financing ideas, strive for external progress, tap internal potential, and raise funds through multiple channels. Through the cross-regional transaction of land-saving indicators, more funds will be attracted to rural areas, and more rural people will share the urban development.Focus on areas with slow urban-rural integration development and seek novel points. Promote the development of regional urban-rural integration, which tends to high-level convergence. We should promote the equalization of basic public services between urban and rural areas, improve the benefit-sharing mechanism for residents, and enable urban and rural residents to share the development of new urbanization. We might build basic public service facilities in urban and rural areas following unified allocation standards; further improve the security system for the elderly, the weak, the sick, and the disabled; and promote the integration of health care, old-age care, education, and employment. Promote the integration of urban and rural undertakings, increase investment in rural preschool education, and consolidate and enlarge teachers' teams. Insist overall consideration, individual breakthroughs, suit local conditions, fully consider the different stages of urban-rural integration development in different regions and the vast differences between diverse rural areas, and form a unique and practical development model of urban-rural integration."} +{"text": "Knowledge of the main markers of bipolarity, clinical features and the course of depression within BPAD in men and women will contribute to the correct diagnosis, prog- nostic assessment of the disease course and administration of an adequate therapy.The aim of the investigation was to study the clinical features of depression in men and women with BPAD in order to identify markers of bipolarity, facilitate a diagnostic search and determine therapeutic tactics.The study was conducted from 2018 to 2020 in outpatient and inpatient conditions of the S. S. Korsakov Psychiatric Clinic of Sechenov University. 100 patients (50 women and 50 men) with a diagnosis of F31.3-F31.5 according to ICD-10 were examined by the clinical method.In the structure of the depressive phase in men, the following were more common: pronounced seasonality (with deterioration in autumn-winter) and daily fluctuations in the state (with improvement in the evening), anesthesia of the senses, depersonalization-derealization syndrome, decreased libido, difficulty falling asleep and increased appetite and / or body weight, comorbid depression, panic attacks and alcohol and surfactant abuse. Depression within the BPAD in women was characterized by a more frequent presence of apathy, tearfulness, self-harm, dysmorphophobic inclusions, decreased appetite.The revealed features of psychopathological symptoms and correlations between some characteristics and factors, taking into account gender differences, can be used as markers of bipolarity, which will allow for an earlier and more accurate diagnosis of BPAD and adequate therapy.No significant relationships."} +{"text": "This study aimed to investigate the effect of self-management behavior on the rehabilitation of stroke patients to lay a theoretical basis for using patient-reported outcome (PRO) for rehabilitation evaluation of stroke patients.t-test and analysis of variance. Bonferroni method was used for multiple comparison correction. The correlation between rehabilitation results and patients\u2019 basic conditions and self-management was investigated through Pearson correlation analysis. The main factors for self-management behaviors were studied through multiple stepwise regression analyses.396 patients hospitalized in the Department of Neurology of 4 tertiary general hospitals in Datong from August 1st 2018 to March 31st 2020 were included in accordance with the inclusion and exclusion criteria. The included patients were randomly assigned into a self-management intervention group and a control group. Only the control group received the clinical pathway intervention of stroke rehabilitation. The stroke patients in the intervention group received the self-management intervention in addition to the clinical pathway intervention of stroke rehabilitation. The self-management status and rehabilitation results of the patients were evaluated in 24 h and 3 months after the patients were enrolled, respectively. Statistical description and analysis were conducted using SPSS20.0 statistical software. The general data of the patients were expressed by percentage. The data regarding patients\u2019 self-management and rehabilitation results were statistically described by percentage, mean and standard deviation. The comparison between groups was drawn through P < 0.01). In this study, there was no statistical difference in different genders and medical insurance status (P > 0.05). The total scores of self-management behaviors and the scores of the respective dimension were positively correlated with the health education, exercise intervention, functional training, psychological intervention, food intake, living habits, and functional training of stroke patients at the recovery stage. Educational level and marital status were positively correlated with the rehabilitation results of patients. The PRO questionnaire for the stroke scored higher in married patients and highly educated patients, and there were statistically significant differences (P < 0.01). Family history was negatively correlated with the rehabilitation results of patients. Exercise intervention and functional training were positively correlated with the rehabilitation results of patients.The total scores of self-management behaviors of the investigated subjects achieved statistical significance in different ages, occupations, educational levels, income levels, exercise intervention, past medical history, BMI, as well as marital status (Education level, health education, food intake, exercise and rehabilitation training, sleep, and psychological intervention were the main factors for self-management behavior in stroke patients at the recovery stage. Self-management interventions can effectively increase the health education level of stroke patients, strengthen their self-confidence in disease self-management, facilitate the establishment of effective self-management behavior of patients, and improve their quality of life and subjective well-being. Stroke PRO scale can be used to evaluate the clinical intervention effect of self-management on stroke patients in multiple dimensions, especially evaluating the improvement of subjective mental and psychological state of patients, thus revealing the intervention effect of self-management on stroke patients comprehensively. The rehabilitation of stroke patients at the recovery stage (2 weeks to 6 months after onset) is a vital factor in the prognosis and quality of life of stroke patients . ExistinThis study gained approval from the Medical Ethics Committee of Shanxi Datong University. A total of 396 patients with a stroke at the recovery stage from August 1, 2018 to March 31, 2020 in the Fifth, Third, and Second People\u2019s Hospitals of Datong City, Affiliated with Shanxi Datong University and Tongmei General Hospital of Datong City were included as the subjects for investigation.The inclusion criteria of subjects are elucidated below: \u2780 Patients meeting the diagnostic criteria established at the Fourth National Academic Conference on Cerebrovascular Diseases in 1996 and confThe exclusion criteria of subjects included patients with severe illness, the degree of ADL deficiency was BI \u2264 20 and BI = 100,unclear consciousness , or cognThe general demographic characteristics, lifestyle, health status, treatment and intervention of the subjects were investigated and evaluated by the self-made questionnaire. The PRO scale for the stroke developed by Wei Xiaoyuan of Shanxi Medical University was used to evaluate the rehabilitation results of patients. The PRO scale was investigated using the self-rating scale method, and its reliability, validity, and feasibility were examined, which confirmed its high reliability, validity, fairness, and feasibility .The serious and responsible medical staff in the neurology department should be recruited as the investigators for unified training. Subjects with a consistent baseline were included in accordance with the inclusion and exclusion criteria. \u2780 Patients were randomly assigned to a control group and a self-management intervention group by computer random number method, with 198 patients in the respective group. The patients\u2019 condition was evaluated within 24 h and 3 months after the patients were enrolled by the self-made general questionnaire and the PRO Scale for the stroke. \u2781 The patients in the control group received the clinical pathway intervention of stroke rehabilitation in a standard hospitalization period of 22\u201328 days. According to the specific type, course and main complications of stroke, appropriate clinical treatment measures were selected according to the Clinical Diagnosis and Treatment Guidelines \u2013 Neurology; during the standard hospitalization period of 22\u201328 days, the patients in the intervention group received self-management education while receiving the clinical pathway intervention of stroke rehabilitation. On the day of admission, the third week of hospitalization and the day of discharge, the nurse in charge of the patient carried out self-management education in the ward to improve the patient\u2019s self-efficacy, daily functional activities, and eliminate negative emotions. Methods: The form of mobile phone WeChat official account combined with bedside nursing was used for propaganda and education . \u2782 The st-test and analysis of variance. Bonferroni method was used for multiple comparison correction. The correlation between rehabilitation results and patients\u2019 basic conditions and self-management was investigated through Pearson correlation analysis. The main factors for self-management behaviors were studied through multiple stepwise regression analyses. When P < 0.05, the difference is statistically significant.After the questionnaire was collected, the data of study materials were entered into an Excel spreadsheet by two people and two computers, and a database for logical examination and correction was built. The statistical description and analysis were conducted using SPSS20.0 statistical software. The general data of patients were statistically denoted as percentages. The data regarding patients\u2019 self-management and rehabilitation results were statistically described by percentage, mean and standard deviation. The comparison between groups was drawn through t-test or one-way analysis of variance. The results indicated that the total scores of self-management behaviors of patients at the recovery stage of stroke achieved statistical significance in different ages, occupations, educational levels, income levels, exercise intervention, comorbidities, BMI and marital status (P < 0.01), whereas they did not achieve any statistical difference in different genders, family histories, stroke type and medical insurance (P > 0.05), as listed in No data loss in the study, for the 396 subjects included, 176 were male (44.5%), and 220 were female (55.5%), aged from 31 to 97 years, with an average age of 65.8 12.5. The demographic data of patients included and exercise intervention), which may affect the self-management behavior of stroke patients at the recovery stage, were investigated through independent sample The PRO scale for the stroke used in this study included four domains and 10 dimensions, including the physiological domain , psychological domain , social domain and therapeutic area (satisfaction), which involved a total of 46 items. Stroke PRO scale items were all scored using the Likert five-stage scoring method. All negative scores of the respective dimension were converted and then added with the positive scores to develop the total score. The higher the score, the higher the quality of life will be . Table 2P > 0.05). Statistical difference was found in the PRO scores of the self-management intervention group and the control group after the self-management intervention (P < 0.05). After Bonlemmi correction, the PRO scores of the self-management intervention group and the control group after the implementation of self-management intervention were statistically different (P < 0.017), and the differences between the other groups were not statistically significant . There was no statistical difference in the PRO scores of the self-management intervention group and the control group before the self-management intervention were compared in the included patients at the rehabilitation stage of stroke .P > 0.05). After the 3-month self-management intervention in the behavioral period, there were statistically significant differences in the scores of self-management behaviors of the two groups (P < 0.05). After Bonlemmi correction, there was a statistical difference between the self-management intervention group and the control group in the scores of self-behavior dimensions after the implementation of self-management intervention (P < 0.013), and there was no statistical difference between the other groups . Before the self-management intervention, there was no significant difference in the scores of self-behavior dimensions among different groups (The correlation analysis was conducted between the total score of self-management behavior and scores of the respective dimension and a total of 10 dimensions in four fields of the PRO questionnaire. The results indicated that health education, exercise intervention, psychological intervention, food intake, living habits, and functional training of stroke patients at the recovery stage were positively correlated with the total score of self-management behavior and scores of the respective dimension.Taking the total PRO score of stroke patients as the dependent variable, and introducing the above factors into the equation, a multiple linear regression model was established. The results indicated that there was a relationship between educational level, marital status, family history, exercise intervention, and functional training and the rehabilitation results of stroke patients. Educational level and marital status were positively correlated with the rehabilitation results of patients. Married patients and highly educated patients had high scores in the stroke PRO questionnaire and the differences achieved statistical significance. Family history was negatively correlated with rehabilitation results. The total rehabilitation scores of patients with a family history of stroke were lower than those of patients without a family history, and the differences were statistically significant. Participation in exercise intervention and functional training was positively correlated with the rehabilitation results of patients. Active exercise intervention and functional training can lead to higher scores of rehabilitation results of patients and significant differences. Stroke recovery patients with a better self-management ability and having mastered several systematic, scientific and effective methods and relevant knowledge and basic rehabilitation skills required for self-management can improve their confidence in self-management of their diseases and play their subjective initiative. They are capable of increasing the rehabilitation results by actively establishing correct self-management behavior patterns .In this study, there were differences in scores of different dimensions of self-management behavior, and the self-management of food intake was the best, probably because of the traditional concept of \u201cdisease entering from the mouth\u201d and the significant treatment effect of diet control for patients. Moreover, the medical staff emphasized the role of the healthy nutrition concept and the significance of long-term adherence during the patients\u2019 hospitalization and discharge education, so the patients\u2019 management of food intake can be effectively performed. The self-management of living habits, exercise intervention, health education, and functional training was better, probably arising from the strengthening of hospital education for patients and popular science education on stroke-related knowledge via the media, newspapers, television and community. Patients developed an awareness that excessive intake of tobacco and alcohol, unreasonable dietary structure, lack of exercise, and emotional abnormalities were significantly correlated with the occurrence and development of stroke. The management time and economic cost in diet, daily life and other aspects were reported to be low and acceptable, thus enabling patients to actively change their dietary structure, conduct the moderate exercise and functional training and maintain a relatively stable and optimistic mood . SpecialSeventy-three percent of the patients surveyed in this study had educational culture below junior middle school level, and their understanding of disease-related knowledge and mastery of rehabilitation training skills were poor, thus resulting in their poor knowledge level of stroke and preventing them from effectively implementing self-management and monitoring of the disease. Accordingly, nursing staff should increase health education for the stroke patients and pay more attention to health education regarding common chronic non-communicable diseases of the elderly and training in rehabilitation skills, so as to help patients understand the significance of self-management after stroke. Furthermore, they should carry out targeted guidance on systematic knowledge and skills in accordance with the patients\u2019 age, educational level, and economic situation, enhance the patients\u2019 behavioral abilities of self-management and scientific rehabilitation training after illness .The results of multiple regression analysis indicated that marital status of being married, active physical exercise and rehabilitation training were the protective factors for self-management scores of stroke patients; family history, past medical history and complications were the risk factors for self-management of stroke patients. The self-management score of married patients was higher than that of unmarried/divorced/widowed patients. The family relationship and family income of married patients were reported to be relatively stable, and they were significantly supported and encouraged. The patients\u2019 emotions were stable, and they faced stress with a positive attitude, thus improving their self-management ability. The rehabilitation scores of patients actively doing physical exercise were higher than those of patients not doing physical exercise. Regular and appropriate physical exercise improved the physical quality of patients and the rehabilitation of the diseases of stroke patients . The resThis study aimed to investigate the effect of self-management on stroke patients at the recovery stage. Due to the constraints of test time and test conditions, patients from the community and rehabilitation pension institutions were not included, and the sample representation was not comprehensive. When choosing the self-management evaluation scale, no more comprehensive reliability and validity evaluation was conducted due to the test conditions.The information was acquired directly from the patients based on the clinical outcomes reported by them, in which the explanation by the medical staff and any other staff was excluded. The information of this study can provide a more valuable reference for doctors in diagnosis and treatment of stroke, and it is of great significance in the clinical treatment practice. For patients at the post-stroke rehabilitation stage, medical intervention in accordance with the feelings and wishes directly from the patients can be the starting point for smooth work.Education level, health education, food intake, exercise and rehabilitation training, sleep, and psychological intervention were the main factors for self-management behavior in stroke patients at the recovery stage, which revealed that medical staff should improve the health education level of stroke patients and give more support to patients with lower educational levels. Self-management interventions can effectively increase the health education level of stroke patients, help them gain self-confidence in disease self-management, and facilitate the establishment of effective self-management behavior of patients, which is conducive to improving the quality of life and subjective well-being of patients. Stroke PRO scale is a novel sensitive and effective efficacy evaluation tool, which is capable of evaluating the clinical intervention effect of self-management on stroke patients from multiple dimensions, especially evaluating the improvement of the subjective psychological state of patients and thus revealing the intervention effect of self-management on stroke patients comprehensively.First, this study is only a multicenter study of a regional Grade III hospital, and did not include inpatients in the department of neurology of hospitals below Grade III in the region during the same period; Second, in order to facilitate research, we only used the PRO scale, no other scale is used, such as SF36 scale; Third, the cognitive function of the subjects was only evaluated with MoCA and MMSE neuropsychological evaluation scales, without further hierarchical evaluation. This requires us to further expand the sample in future research. On the basis of operational research, we should try our best to select various evaluation tools to comprehensively evaluate the research object, compare them with other similar research tools, and select the evaluation tool with the best reliability and validity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Medical Ethics Committee of Shanxi Datong University. The patients/participants provided their written informed consent to participate in this study.YSS, NPZ, and XZ proposed the idea of the article, formulated the inclusion and exclusion criteria, and wrote the first draft of the manuscript. DBY and JM conducted literature retrieval and screening. YSS and JM conducted data analysis and result writing. CGM and XZ reviewed the first draft of the manuscript. CJL revised the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "In order to improve the overall structural stability and thermal insulation capacity of existing buildings in severe cold areas, green energy-saving ecological transformation methods of existing buildings in severe cold areas are proposed. The concrete stress analysis method of the joints in the frame is used to calculate the bearing capacity and prestress of the beam-column joints. Based on the method of parameter analysis, the calculation model of shear capacity is established. The embedded anchoring method is adopted to realize the equal strength connection of beam-column joints. Increase the unbalanced moment between reinforcement and steel plate, and improve the stability and reliability of beam-column joint fixation. The overall structural optimization method of joint shear performance is adopted to reduce the distance between lap reinforcement and steel plate, so as to realize the green energy-saving ecological transformation design of existing urban buildings in severe cold areas. The test results show that the service stress and tensile resistance of the reconstructed existing building area are higher than 60, the tensile capacity is good, and the slip of the lap reinforcement is effectively controlled. At the same time, this method improves the stability of beam-column elements and the overall thermal insulation performance of existing buildings in cities in severe cold areas. The next research will focus on the transformation of other structures. In recent years, with China's great emphasis on the ecological environment, the concepts of low-carbon cities and green energy-saving buildings have been gradually popularized. With the constant improvement of China's green energy-saving construction, the growth of building energy consumption has been effectively restrained. However, there are still some problems, such as people's ignorance of building energy-saving ideas, imperfect building energy-saving renovation methods and technologies, lack of energy-saving ideas in building construction , 2, and At present, for residential units, there are often some problems, such as unreasonable layout of residential buildings, inefficient use of space, ventilation and lighting of residential buildings failing to meet the requirements of residents, wasting a lot of energy and so on. Therefore, the application of low-carbon concept and low-carbon technical measures in planning and architectural design to build energy-saving green communities and energy-saving buildings is not only of great significance to China's energy conservation and utilization \u20136, but aChina's research on the application of low-carbon energy-saving theory and space syntax in building energy-saving renovation is still insufficient, and the current research results in this area are also lacking, and have not formed a complete system. This study systematically sorts out the application theory of low-carbon energy conservation and the practice method of spatial syntax by analyzing the Reference, reports and excellent cases of the implementation and application of low-carbon energy conservation concepts at home and abroad, perfecting and enriching the energy conservation theory of existing residential areas and residential buildings, and supporting the construction of low-carbon energy-saving communities in China. In this study, the spatial syntax theory is applied to the quantitative and visual analysis of existing residential areas, which can more intuitively analyze the energy-saving transformation of residential areas and buildings. The comprehensive application of space syntax and low-carbon energy-saving theory will provide a new direction and path for the renovation of low-carbon energy-saving residential areas in the future. The design of green energy-saving ecological transformation of existing buildings in cold regions is based on the optimization design of mechanical parameters of beam-column joints of existing buildings in cold regions, and the optimization of green energy-saving ecological transformation of existing buildings in cold regions is realized by combining numerical simulation and mechanical analysis. At present, for the green and energy-saving ecological transformation methods of existing buildings in cities in severe cold areas, the anchor joint fixing method, the foundation pit fixing method, and the tensile steel bar strain stability fixing method are mainly adopted, and the double steel plate concrete composite wall design method is adopted to realize the stability control of beam-column joints of existing buildings in cities in severe cold areas.Reference proposedThe vast majority of existing buildings belong to non-energy-saving high-energy buildings. In the energy-saving transformation of existing buildings, local practices basically focus on large-scale public buildings and government office buildings with high-energy consumption, as a breakthrough in energy-saving transformation. Therefore, this paper proposes a green and energy-saving ecological transformation method of existing buildings in cities in severe cold regions based on the overall structural optimization of node shear performance. Firstly, in assembling the integral shear wall structure, the concrete stress analysis method of the joints in the frame is adopted, the embedded anchorage method is adopted, and the prestressed reinforcement degree analysis and yield response analysis are combined to realize the equal strength connection of the beam-column joints of the existing urban buildings in severe cold areas. Then, the static monotonic tensile test method is adopted to increase the moment of force between steel bars and steel plates, improve the stability and reliability of the beam-column joints, and the overall structural optimization method of the shear performance of the joints is adopted to reduce the distance between the overlapping steel bars and steel plates. Finally, the experimental test shows the superior performance of this method in improving the green energy-saving ecological transformation ability of existing urban buildings in severe cold areas.Parameter analysis method is widely used in various reservoir parameters. Through cluster analysis and discriminant analysis, the types of flow units in the study area are reasonably divided, and the discriminant functions of various flow units are established to identify the unit types. These parameters mainly include porosity, permeability, median grain size, shale content, formation coefficient, net-gross ratio, saturation, conductivity coefficient, storage coefficient, pore throat radius, pore throat ratio, and cross-well flow capacity index.Cans identifies the flow unit by using the cross-well flow capacity index Interwell Flow Capacity Index (IFCI). IFCI is defined as the ratio of flow between two adjacent wells. The denominator is the flow rate of high permeability layer. The results show that if the two wells are located in the same flow unit, the ratio of formation coefficient of the two wells has a good correlation with its flow rate ratio. Otherwise, the correlation is poor. Therefore, the distribution range and connectivity of flow units can be judged.Identification of flow unit by repeated formation test and tracer test. The main principle is to identify the flow unit according to the measured pressure change and tracer concentration change.Prediction of flow unit by production pressure difference. According to the flow of fluid in oil\u2013water two-phase obeying Darcy's law, the calculation formula of production pressure difference of flow unit is established. This method can avoid the contradiction between resource waste caused by shut-in pressure measurement and less pressure measurement data by layers, and its accuracy depends on the accuracy of parameter selection and the reliability of flow unit division.Fluid Inclusion Stratigraphy (FIS) is used to identify oil\u2013water interface and seepage barrier, and production logging and pressure data are used to identify flow units. It is worth noting that when the physical and chemical properties of fluid inclusions between adjacent wells are different, it can indicate the existence of barrier layer. However, when there is no difference in physical and chemical properties of fluid inclusions between adjacent wells, it cannot be concluded that the barrier layer does not exist.Based on the research and analysis of domestic and foreign cases, it is concluded that domestic green low-carbon energy-saving residential communities usually pay attention to the application of low-carbon energy-saving concept from the early planning and design stage. In the construction stage, domestic residential areas also adopt construction methods such as assembly to reduce energy consumption and waste of resources in the construction stage. Many technologies and methods are also used in the residential operation stage, which play a substantial role in the energy conservation and utilization of the whole residential area, but the public participation is not high and the enthusiasm is not strong. Compared with foreign low-carbon energy-saving communities, they have invested a lot of financial resources and manpower in the active energy-saving and passive energy-saving design of residential areas, and paid great attention to public participation and the cultivation of residents' low-carbon energy-saving concept in the whole process, which is very worthy of our reference \u201314. CombVerify through the node count in the software. If the value of node count is positive, it indicates that the drawing is correct, and the color of the line segment is green. If the value is negative, the model is wrong and the color of the line segment is red.Using reinforced concrete raft as foundation, combining embedded anchoring and embedded anchoring methods, the anchoring connection module of beam-column joints of existing buildings in cities in severe cold areas is established. According to three anchoring forms, double steel plate concrete composite wall configuration method is adopted, and bolts on both sides of beam-column joints of existing buildings in cities in severe cold areas are used to achieve anchoring. Considering raft foundation, embedded steel plates of beam-column joints of existing buildings in cities in severe cold areas are perforated. The cracks of reinforced lap specimens are fixed by anchor bolts, and the ribbed steel bars are lapped in concrete by embedded anchorage. Through strain detection and mechanical parameter analysis of tensile steel bars and steel plates, the wall-reinforced concrete foundation parameters of beam-column joints of existing buildings in cities in severe cold areas are determined. Based on the code for design of building thermal insulation (GB 50011-2010), the thermal insulation design of beam-column units of existing buildings in cities in severe cold regions is carried out. In AISC N690-12, the tensile reinforcement is configured in combination with the technical standard requirements of cylindrical head welding nails for arc stud welding (GB/T 10433-2002).Through field investigation, case comparison and spatial syntax model analysis, this paper analyzes the constitutive relationship of beam-column joints of existing buildings in severe cold regions.In order to comprehensively consider the green energy-saving design level of buildings in residential areas and the maintenance degree of green environment in residential areas, the building materials of residential buildings and the property management of residential areas are also analyzed. In the assembled integral shear wall structure of existing buildings in cities in severe cold areas, the concrete stress analysis method of the joints in the frame is adopted, and the spatial structure, planning layout and traffic flow lines of two existing residential areas are analyzed at the macro level. For the overall layout and traffic, through the axis model of two existing residential areas, it is analyzed according to two indicators: selectivity and integration. According to the axis model established by the urban road network, the roads represented by each axis have corresponding index values. The values are arranged according to the size, and the color is attached for visual analysis. In the model, the red, yellow and blue axes represent high, medium, and low index values in turn. Among them, the main syntactic index of axis: Choice\u3009 indicates the potential of axis to attract crossing traffic. Integration represents the traffic accessibility of the axis. In assembling the integral shear wall structure, the concrete stress analysis method of the joints in the frame is adopted to calculate the bearing capacity and prestress of the beam-column joints of the existing buildings in cities in severe cold areas, and the constitutive model of the materials of the beam-column joints of the existing buildings in cities in severe cold areas is constructed \u201317. The Vt1 represents the internal force of tensile reinforcement configuration of existing buildings in cold regions relative to the node performance, Vu1 represents the standard anchorage length of reinforcement, and \u0394Vt represents the distance between lap reinforcement and steel plate of existing buildings in cold regions. The static loading test method is adopted to analyze the correction factor of lap reinforcement diameter as follows [dei is the hysteretic coefficient of the cross-section and steel plate of the existing building specimen in the cold area city, and dpti represents the buckling relation of large local deformation. The template parameters on both sides of the existing building concrete pouring in the cold area city, and the stress parameters of the anchoring reinforcement are:\u03bb is the index of compression and tensile damage of existing buildings in cities in severe cold areas, and t is the volume stirrup ratio of energy-saving ecological renovation of existing buildings in cities in severe cold areas. Considering the size and loading capacity of the loading device, it is found that the index coefficient of tensile damage of beam-column joints of existing buildings in cities in severe cold areas satisfies u : I \u00d7 IRd\u27f6IR, and the elastic modulus of concrete of existing buildings in cities in severe cold areas is:s \u2265 0, 1/p=1/p1+1/p2=1/p3+1/p4. The index coefficients of compressive and tensile damage of existing building concrete in cities in severe cold areas are analyzed. When \u2203x0 \u2208 R2, the tensile damage index of concrete in steel tube:P(Y|\u03bbj) is the biaxial compressive yield strength of existing urban buildings in severe cold areas, P(Y|\u03bbj) is the uniaxial tensile stress of existing urban buildings in severe cold areas, and P(Y|\u03bbT) is the initial elastic modulus. If a > 1, the constitutive relation model of beam-column joints of existing urban buildings in severe cold areas is established, and the constitutive relation analysis of beam-column joints of existing urban buildings in severe cold areas is realized under uniaxial stress.In the above formula, follows :(2)di=deP is the applied prestress, \u03c6x is the anchor parameter of the existing buildings in the cold region, v is the prestress, b is the structural fitting parameter, a is the yield response of ecological design, and t is the constitutive model parameter.On the basis of the above-mentioned constitutive relation model of beam-column joints of existing buildings in cities in severe cold areas, the overlapping force transmission analysis of beam-column joints of existing buildings in cities in severe cold areas is carried out by adopting the arrangement of overlapping steel bars, and the stress parameter analysis model of beam-column joints of existing buildings in cities in severe cold areas is established by analyzing the bearing capacity, stiffness, and other parameter information of beam-column joints of existing buildings in cities in severe cold areas. Steel plates are welded at the bottom of steel plates, Calculate the stress parameters of the anchorage zone between column and foundation, build the calculation model of shear bearing capacity, adopt the embedded anchorage method, and combine the analysis of prestressing tendons and yield response to obtain the longitudinal strength of the beam-column joints of existing urban buildings in severe cold areas, and establish the finite element model of the beam joints . The comThe calculation model of shear capacity includes the main influencing factors, such as beam geometric size, shear span ratio, stirrup ratio, axial prestress, concrete strength, load form, and so on. During the construction, 987 beams without web reinforcement were selected, including 531 beams with web reinforcement, 136 beams without web reinforcement, and 42 beams with web reinforcement under uniform load. Other prestress, bearing capacity, concrete strength, load, and other parameters are set in the test.Therefore, combined with the finite element analysis of composite frame joints, the relationship between compressive stress and compressive strain is shown in aii is the stress\u2013strain joint distribution characteristic of green energy-saving ecological transformation of existing buildings in cold regions, bi is the deviation value of green energy-saving flow potential of existing buildings in cold regions, xjk)( is the strain corresponding to uniaxial compression of green energy-saving ecological transformation of existing buildings in cold regions. According to the analysis of the overall structural parameters of shear performance of beam-column joints of existing buildings in cold regions, the standard anchorage length of steel bars is calculated by the method, and the influence of anchorage length on the performance of beam-column joints of existing buildings in cold regions is analyzed.According to the relationship between compressive stress and compressive strain of green energy-saving ecological renovation of existing buildings in cities in severe cold areas shown in Is is the vertical and horizontal spacing, \u03bcj is the distribution of compressive stress\u2013strain relationship, Aj is stress\u2013strain under uniaxial compression, W\u2032 is the parameter value of uniaxial tension descending section, F is the biaxial compressive yield strength.By adopting the static monotonic tensile test method, the moment of force between steel bars and steel plates is increased, and the lap joint model of beam-column joints of existing buildings in cities in severe cold areas is constructed . The indF is 0.1, the biaxial compressive yield strength obtained satisfies:\u03bbn is the uniaxial tensile strength of beam-column joints of existing buildings in cities in severe cold areas [fvk is the standard value of the parameter value of uniaxial tension descending section, \u03c9 is the deviation value of flow potential; Ac, Aw are the cross-section parameters and distribution area of concrete restrained by stirrups, and \u2211Af is the stiffness recovery coefficient. N is the initial elastic modulus of steel [When ld areas , 22, fvkof steel , 24.According to the supporting sequence of the bolt body, the concrete supporting column project is adopted to realize the analysis of the stress structure parameters of the beam-column joints of existing buildings in cities in severe cold areas. In the steel-inserted anchorage joints, the bearing capacity of the specimens is analyzed, and the specific operation process is shown in To sum up, to realize the equal strength connection of beam-column joints of existing buildings in cities in severe cold areas, the static monotonic tensile test method , 26 is aIn the experimental test of green energy-saving ecological transformation of existing buildings in cities in severe cold areas, the strength grade of steel bars is set to HRB400, and the ultimate strength detection model of beam-column joints of existing buildings in cities in severe cold areas is established by using I-beam, steel tube, and internal reinforcement design method. The yield prestress degree is 234.1\u2009MPa and 232.0\u2009MPa. See According to the parameter evaluation index system in In According to the stress analysis in The steel bars are planted on the brick wall at the post-cast strip. The depth of the holes for planting steel bars is 200\u2009mm, and the spacing is 300\u2009mm. An 8-screw with an implanted depth of 150\u2009mm is arranged in the hole, which is anchored by pouring steel bar glue, and 180\u2009mm is thrown out of the hole. Eight long-length steel bars are placed in the post-cast strip, and the long-length steel bars are tied together with the bolts implanted in the wall. At the same time, the hooks of the embedded steel bars at the bottom of the precast reinforced concrete slab hook the long-length steel bars. This test is loaded in the vertical and horizontal directions, and a jack is used to apply a constant vertical force of 30\u2009t to the steel beam. The load is transmitted to the concrete loading beam at the top of the test body through the loading steel beam, and then to the specimen to ensure that the axial force is evenly transmitted to the specimen. Load horizontally with electrohydraulic servo actuator and adopt displacement control, and get the comparison of force characteristics of existing buildings in cities in severe cold areas after green energy-saving ecological transformation, as shown in According to the analysis of The yield response of beam-column joints of green buildings is tested. The comparison of cloud pictures of green energy-saving ecological transformation of existing buildings in cities in severe cold areas is shown in In It can be seen from This paper puts forward the green energy-saving and ecological transformation methods of existing buildings in cities in severe cold areas. The connection model between concrete foundation and double steel plate composite wall of beam-column joints of existing buildings in cities in severe cold areas is established, which improves the bearing capacity of buildings. Combined with embedded anchoring and embedded anchoring methods, the mechanical reliability of beam-column joint fixation is optimized. The embedded anchoring method improves the stability and thermal insulation performance of the building.Since the weather environment in most cities in China is hot in summer and cold in winter, this study is only aimed at the reconstruction of existing buildings in cities in cold regions. Therefore, the next research will start from the energy-saving transformation of the building envelope, energy-saving transformation of existing buildings in hot summer and cold winter areas."} +{"text": "There is a paucity of research on the impact of caregiving on the quality of life of unpaid caregivers for older adults aged 60 years or older with visual impairments (VI). The purpose of this study is to test multimodal interventions to improve quality of life and well-being in unpaid caregivers of older adults with VI. The objectives were: (1) to implement multimodal interventions targeted towards improving the quality of life of family caregivers of older adults with a VI; (2) to evaluate the efficacy/effectiveness of the interventions in improving the quality of life of older adults with a VI. The outcomes of interest include: quality of life, health, stress, burden, problem-solving, and barriers. For this study, a 10-week virtual intervention was implemented with 12 caregivers and eight older adults with visual impairments, for a total of 20 participants. The intervention was held for one hour for 10 consecutive weeks and included activities such as tai chi, yoga, meditation, music, nutrition, and other de-stressing techniques. Participants completed a series of questionnaires before and after the intervention period. These questionnaires include: Satisfaction with Life Scale, Living Arrangement and Indicators of Social Interaction survey, Caregiver quality of life (EQ-5D), the Perceived Change Index, and the Geriatric Depression Scale. Findings from the data analysis show excellent caregiver engagement throughout, including participation in the pre and post surveys. Results show the benefits of multimodal interventions for caregivers as well as older adults with VI. Future studies should focus on interventions that are most promising."} +{"text": "Give Peace a ChanceJohn Lennon 1969ICONS-5, organized during from August 31 to December 02, 2022, was the fifth edition of the on-line magnetic resonance conference series called Konstantin Ivanov InterCONtinental Magnetic Resonance Seminar, named after our untimely deceased colleague and friend. The ICONS conferences are an off-shoot of the weekly Intercontinental NMR Seminar Series that started on April 8, 2020. This seminar series has enabled the communication and dissemination of research ideas among the magnetic research community in the times of the COVID-19 pandemic and will continue to do so beyond. In the framework of the ICONS series, until now, more than 130 scientists from five different continents have presented their recent results. While the weekly seminar series gives both early-stage and experienced researchers an opportunity to give seminar talks and interact with colleagues from all over the world, the ICONS conference is a platform for experienced researchers. The ICONS-5 conference attracted registrations from nearly 200 people from 30 countries and spanned 17 time zones from Japan over Europe to the US West Coast. The meeting talks were broadcast across the Zoom and YouTube platforms. The average combined attendance was around 120.The ICONS seminar series is open to all areas of magnetic resonance and covers the full range of Magnetic Resonance, i.e., EPR, NMR, MRI, and their various hybrids. While the summer ICONS conferences and its pros and cons compared to other hyperpolarization techniques. Then he reported on recent developments on the application of DNP towards studies of RNA ribozymes and discussed the application potential of DNP for the simplification of crowded spectra of biomolecules. At the end, he gave an overview of 1\u03c1. At the end, he reported a combination of REDOR and VT-NMR studies of side-chain dynamics of proteins.Paul Schanda, Austria, gave a fascinating overview of recent developments in the investigation of protein dynamics in the solid state employing a combination of solid-state NMR and molecular dynamics simulations. At the start of his presentation, he explained why relaxation is intrinsically multi-exponential. Then he discussed the effects of deuteration on the relaxation times and gave a Redfield analysis of RThomas Theis, USA, first gave an introduction into Parahydrogen-based hyperpolarization techniques in Chemistry, Biochemistry, and medical imaging. He then discussed the advantages of reversible PHIP (SABRE), in particular in bio-related questions, owing to the large number of available metabolites of interest that are or are likely to become SABRE active, and showed a number of recent results from his group. Next, he gave a fascinating overview about the construction and physical principles of a RASER NMR setup in his group and demonstrated the astounding coherence length and spectral resolution of this system and the resulting line resolution.Jamie Walls, USA, discussed the application potential of diffusion NMR for the investigation of NMR diffusion experiments for the analysis of the pharmaco-kinetics of emulsion-based formulations of drugs and its application to isoflurane, a widely employed common anesthetic. He discussed the kinetics employing Bloch-McConnell model.Patrice Bertet, France, gave a fascinating introduction into recent results in the detection of small numbers of electron spins employing micro-waves in a miniaturized resonator. He explained how the relaxation properties of the spins are optimized and discussed the SMPD device for the detection of the signals. Then he showed the tremendous improvements obtained in the last twelve month where the detection limit was increased from 1000 to one spin. Finally, he showed a number of basic experiments, such as Rabi oscillations on these systems.N). By CEST an excited state of the protein was detected, whose structure was studied via 1H-15N RDCs .Ashok Sekhar, India, discussed the application of NMR for the investigation of order/disorder phase transitions in intrinsically disordered proteins, employing the cytidine repressor, which binds its cognate operator DNA through the N-terminal DNA-binding domain for the processing of diffusion NMR spectra.Jean-Pierre Korb, France, reported on recent studies of water dynamics in protein hulls, employing a multi-scale approach. From the combination of the experimental dispersion of the NMR relaxation data and theoretical modeling he investigated the surface water diffusion in hen egg-white lysozyme (LZM) and bovine serum albumin (BSA) solutions and the influence of the addition of different salts on these dynamics. He found an excellent agreement between experiments and modeling over 4 decades in Larmor frequency (10\u00a0kHz to 110\u00a0MHz).Eva Meirovitch, Israel, gave an intense theoretical introduction into the combination of the slowly relaxing local structure (SRLS) approach for the analysis of NMR relaxation from proteins and molecular dynamics (MD) simulations and the application of these techniques towards the study of NH-bonds.Thomas Barbara, USA, gave a fascinating historical overview about the development of NMR relaxation theories. In this overview, he showed that already Felix Bloch had developed a full density matrix approach for the description of relaxation, which later fell into oblivion in favor of Redfield's simpler semiclassical approach and how this old approach by Bloch is related to the recent rediscovery of the Lindblad master equation.Organization and future developments: The conference was organized by Daniel Abergel , Gerd Buntkowsky , and P. K. Madhu . Suman Saurav, TIFR Hyderabad, provided technical assistance. The conference and seminar series were sponsored by Alexander von Humboldt Foundation, Wiley, Springer, HyperSpin, and Adani. Following the scheme of a general MR conference in summer alternating with a specialized conference on cutting-edge topics in winter, there are already plans for a specialized ICONS-6 in spring of 2023. For updates and the schedule of upcoming talks, see the home page of the meeting ICONS-Seminar."} +{"text": "In addition to the global negative impact on mental health of general population, as well as psychiatric patients, Covid-19 pandemic affected significantly research. Initially, lockdowns and restrictions of human contacts temporarily disrupted clinical research activities, but the unprecedented health crisis also provided unique opportunity to study epidemiology of mental disorders, direct and indirect effects of the pandemic on psychiatric disorders, underlying pathophysiological mechanisms, or long-term neuropsychiatric consequences. Research has refocused now on better understanding of the causes, presentations, outcome trajectories, and therapy of mental illnesses. New research topics are followed by the surge in publications covering Covid-19 and mental health and/or psychiatric disorders and treatments. The impact of the pandemic on research and publications is also evidenced by the results of a survey among psychiatric researchers.No significant relationships."} +{"text": "Database of Journal Citations in Science Education to collect studies on teacher education published from 2015 to 2019 and analyzed the issues described therein. Fifteen categories of issues described therein. Regarding our suggestions for future research on teacher education, this study recommends strengthening the body of literature on the following themes: (1) the professional development of preservice teachers, (2) teacher education for special education, (3) quality assurance for teacher education, (4) the career development of preservice teachers, (5) teacher education for experimental education and rural schools, (6) the sociology of teacher education, and (7) the operation of teacher education centers. Our findings may serve as a reference in efforts to improve the quality of teacher education, and promoting the sustainable development of Taiwan's education system.In this study, the researchers analyzed the issues in teacher education research after the implementation of the 12-Year Basic Education policy and developed suggestions to improve the quality of teacher education in Taiwan. The researchers used Taiwan's http://w1.dorise.info/JCSE/. The implementation of education affects a country's development and success, and a key component of an effective education system is the cultivation of high-quality teachers. The quality of education often depends on the quality of teachers, and teachers' professional development is closely linked to teaching effectiveness and student learning outcomes. In discussions on teacher education reform, high-quality teachers are often considered the foundation of student achievement, and the cultivation of high-quality teachers depends on research-based teacher education. Practice and theory must be integrated to ensure high-quality teacher education. Theory can improve practice, and practice can be used to revise theory; that is, teacher education theory can guide the implementation and thus improve the quality of teacher education. The development of the theoretical basis of high-quality teacher education requires extensive research on teacher education. Studies on teacher education can contribute to the development of the theoretical basis of teacher education , promote best teaching practices in the workplace, and enhance the quality of teacher education in November 2014. The New Curriculum reflects the idea that the 12-year basic education curriculum guidelines should be based on the principle of holistic education, incorporating the ideas of \u201ctaking initiative\u201d, \u201cengaging in interaction\u201d, and \u201cseeking the common good\u201d. The practice of the New Curriculum is based on \u201ccore competency\u201d as its main axis and consists of three dimensions: \u201cautonomous action\u201d, \u201ccommunication and interaction\u201d, and \u201csocial participation\u201d preservice teacher education courses; (2) international comparison; (3) teacher education policy; (4) student teachers; (5) teaching materials, methods, and practicums; (6) educational issues; (7) practices in teacher education; (8) test construction; (9) professional development of preservice teachers; (10) teacher education for special education; (11) quality assurance of teacher education; (12) career development of preservice teachers; (13) experimental education and teacher education; (14) sociology of teacher education; and (15) operation of teacher education centers. The number of articles related to each issue is presented in Regarding the studies on teacher education courses, one study discussed the development strategy of the teacher education system through the lens of the religious concept of servant leadership Chang, . AnotherOne study examined the possibility of offering capstone courses, which are widely offered by universities, as part of the teacher education system , which comprises the \u201cWork Values Scale for Teachers\u201d, \u201cSituational Judgment Tests for Teachers\u201d, and \u201cPersonality Scale for Teachers\u201d. The TAA involves conducting tests close to the actual teaching site; exploring students' teaching quality, emotions, and behavioral performance in the context of work; and supplementing the content that cannot be measured using cognitive test performance and academic achievement. The TAA can be used for preservice teacher selection and to evaluate whether preservice teacher education courses are useful. Finally, the TAA can also be used to evaluate the performance of student teachers in teacher education research after the implementation of 12-Year National Basic Education in Taiwan. The researchers offer the following suggestions for future research on teacher education.No consensus has been reached on teachers' professional ethics in Taiwan. Professional ethics courses are rarely offered in preservice teacher education programs. According to the standards of professional competence for preservice teachers announced by the Ministry of Education in 2019, teachers' recognition and practice of professional ethics are necessary. However, further research on the alignment of teachers' professional ethics with 12-Year Basic Education is warranted.Schools have trended toward an integrated education approach for the education of special education students at the senior high school level and below. Teachers play a key role in protecting these students' right to learn. Therefore, teachers' knowledge of special education and of how to cooperate with special education teachers and students' parents are crucial. Although preservice teacher education programs at most teacher education centers offer 3-credit \u201cIntroduction to Special Education\u201d courses, few studies have been conducted on improving the quality of teachers' knowledge in special education.Taiwan's teacher education system is superior to those of many countries in its recruitment and selection process and elements of quality assurance remain crucial concerns in Taiwan. In addition, various major social issues, including a decreasing birth rate, an aging population, diversified interactions between ethnic groups, rapid development of the Internet and information technology, emergence of new job types, increasing democratic participation, growing awareness of social justice, attention to ecologically sustainable development, and transformations brought about by globalization and internationalization, pose numerous challenges to education and contribute to the need for reform to ensure that Taiwan's education system can keep pace with changing social needs and global trends. In addition, Taiwan, a small island in the western Pacific Ocean, has been influenced by international tendencies in terms of its politics, economics, academic research, etc., and the development of teacher education is no exception Huang, .Since the implementation of the 12-Year Basic Education in 2014, many major educational reforms and corresponding reforms in teacher education have been enacted. After the implementation of the New Curriculum in 2019, preservice teacher education courses have also moved toward competency-based curriculum reform. Broadly speaking, the teacher education reforms enacted in response to 12-Year Basic Education span four key areas: (1) implementation of the development and design of competency-based preservice education courses; (2) guidance of teacher education universities in the development of school-based teacher education characteristics; (3) encouragement of teacher education universities to ensure the quality of preservice teachers and teaching experience; and (4) development of preservice teachers' inquiry and practical abilities, cross-disciplinary teaching, and international mobility. Therefore, teacher education in Taiwan is closely related to the 12-Year Basic Education curriculum, and the findings of this study may serve as a reference in the effort to promote the quality of teacher education in Taiwan and the sustainable development of Taiwan's education system within the context of the curriculum's implementation.This study collected the relevant research on teacher education in Taiwan from 2015 to 2019, evaluated the developments in research on teacher education, and analyzed the themes that have been emphasized in this body of research so far. The main research issues were as follows: (1) preservice teacher education courses; (2) international comparison; (3) teacher education policy; (4) student teachers; (5) teaching materials, methods, and practicums; (6) educational issues; (7) practices in teacher education; (8) test construction; (9) professional development of preservice teachers; (10) teacher education for special education; (11) quality assurance of teacher education; (12) career development of preservice teachers; (13) experimental education and teacher education; (14) sociology of teacher education; and (15) operation of teacher education centers.Overall, the research on teacher education reflects the focus on curricula and the Taiwanese system of teacher education. However, it still fails to consider all aspects of system reform, such as teacher education for special education and experimental education and quality assurance of teacher education. In addition, studies on the career development and professional development of preservice teachers have remained scarce. Finally, research on teacher education for rural schools, the sociology of teacher education, and the operation of teacher education centers should be prioritized. Regarding our suggestions for future research on teacher education, the body of literature on the following research issues must be further developed: (1) the professional development of preservice teachers, (2) teacher education for special education, (3) quality assurance for teacher education, (4) career development of preservice teachers, (5) teacher education for experimental education and rural schools, (6) sociology of teacher education, and (7) operation of teacher education centers. Our findings may serve as a reference in improving teacher education, and promoting the sustainable development of Taiwan's education system as well as for future research on the theoretical basis and quality of teacher education worldwide.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.Conceptualization, methodology, investigation, resources, data curation, writing-original draft preparation, and writing-review and editing: R-JW and Y-HS. Formal analysis: Y-HS. All authors have read and agreed to the published version of the manuscript.This study was funded by the Taiwan Ministry of Science and Technology (Grant No. 110-2420-H-002-003-MY3-Y11014).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "In China, studies on the regional risk assessment of hazardous chemicals have been carried out for only a few years, and there are few studies on hazardous chemicals leaking into seas. Previous regional-risk-assessment methods considered a single risk factor for most assessment targets, and comprehensive considerations of risk sources and sensitive resources for a study area are not sufficiently included. Based on previous work, this study established a regional-risk-assessment method for hazardous chemicals leaking into seas. This method considered the hazards of hazardous chemicals and the tolerance of the regional environment by means of a case study in Tianjin. The results showed that the risk level of the enterprise was Grade I, classified as a high-risk source of hazardous chemicals; the main reasons were the strong toxicity and large quantity of hazardous chemicals. This method provides technical support for scientifically assessing marine-environmental-risk levels for hazardous-chemical-leakage areas and for carrying out risk-prevention and restoration assessments of hazardous chemicals leaking into seas. The chemical industry has gradually become the leading industry in China. While the use of many chemicals improves production quality and quality of life, their inherently dangerous properties also pose a great threat to human health and the natural environment . At the In the 1960s and 1970s, developed countries enacted laws on the management of chemical substances, which prompted United Nations agencies to gradually establish and implement relevant international conventions . InitialResearch outside China on the risk assessment and prediction of hazardous chemical accidents began earlier, and it is more systematic in both theory and method. In terms of policy, many developed countries have incorporated environmental risk assessment into the scope of environmental management, with policies such as the guidelines on \u201cControlling Accidents Affecting People inside and Outside Factories and Major Environmental Hazards\u201d issued by the Department of Environment and Science of the World Bank in 1985; the European Union (EU) legislation from 1987, which stipulates that environmental risk assessments must be carried out for factories that may be at risk of chemical accidents; and the Appel Plan (APELL), developed in 1988 by the United Nations Environment Programme (UNEP), which is used to deal with environmental pollution accidents that are difficult to prevent and may cause serious harm to human health and the ecological environment [In 1996, the EU published the first edition of the Technical Guidelines for Risk Assessment (TGRA), applicable to various chemicals , which dBP International, a well-known British multinational company, absorbed the methodology of major-accident-risk management used by multinational oil companies and formed a set of major accident risk-management processes . Marhavi(1)Theoretical research on risk assessment of hazardous chemicals. At present, risk-assessment research on major sources of hazardous chemicals mainly focuses on four aspects: multiobjective fuzzy theory , grey th(2)Qualitative-risk-assessment technology for hazardous chemicals. In March 2013, the Ministry of Environmental Protection issued the Guidelines for the Preparation of Environmental Risk Assessment Reports for Hazardous Chemicals under Key Environmental Management , and in (3)Quantitative risk-assessment technology for hazardous chemicals. Li Qiujin et al. conducte(4)The innovative application of computer technology in the risk assessment of major sources of hazardous chemicals. In terms of the risk assessment of major hazards in petrochemical enterprises, Liang Chenghao and L\u00fc Dong used theThe research status of risk-assessment technology used for hazardous chemicals in China can be divided into the following aspects:In summary, regional-risk-assessment research on hazardous chemicals in China started late, and there has been less research on the methods for assessing the leakage of hazardous chemicals into the sea. In the existing regional-risk-assessment methodology, most of the assessment objects are single risk factors, and there is a deficiency in that the comprehensive impact of other risk sources and sensitive resources in the study area is not fully considered.In this study, to carry out the risk assessment and zoning of hazardous chemicals leaking into seas, we developed a regional-risk-assessment index system for hazardous chemicals spilling into the sea, focusing on the whole coastal area of China.Due to the insufficient accumulation of risk data in the environmental field in China, it is difficult to scientifically define the risk level of each evaluation index. Therefore, by comprehensively drawing on the grading methods from previous research at home and abroad, based on the responsibilities of the Ministry of Natural Resources, this study initially established a risk-grading index system that incR is the regional-risk-assessment score, iC is the weight value of the specific indicator, and iS is the score of the indicator.Considering that environmental risks may arise from defects in any link in the risk system, the comprehensive evaluation of risk zoning adopts a combined algorithm of weighted summation and weighted multiplication. In the calculation of the criterion layer from specific indicators, different specific indicators represent different aspects of the same risk factor, and the weighted summation method is used to calculate the criterion layer following Equation (1). In addition, the analytic hierarchy process (AHP) and Delphi method (Delphi) are used to determine the weights, the weight coefficients between the criterion layer and each specific indicator are then determined, and the sum of the coefficients is maintained as 1 when determining the weights between specific indicators.The hazard assessment of hazardous chemicals should comprehensively consider the types of risk sources involved in hazardous chemicals, the types of hazardous chemicals, and the quantity of hazardous chemicals. The details are as follows:H1. Risk-source type: The probability of environmental accidents in various industry types is different, and we devided into three types: high-risk-industry types (H1. 1), medium-risk-industry types (H1. 2) and low-risk industry types (H1. 3). High-risk-industry types include chemical raw materials and chemical manufacturing, crude-oil processing and petroleum-product manufacturing; medium-risk-industry types include medicine, printing and dyeing, coatings, metal surface treatment and hot processing; low-risk industry types include steelmaking and steel rolling.H2. Hazardous chemical types: Different types of hazardous chemicals have different degrees of impact on the environment, and internationally, the European Standard Behaviour Classification System is generally used to classify the physical behavior of chemicals after entering the sea . AccordiH3. Toxicity of hazardous chemicals: The Joint Group of Experts on the Scientific Aspects of Marine Pollution (GESAMP) comprehensively considers the bioaccumulability, stability, and aquatic biological toxicity of hazardous chemicals and divides the ecotoxicity of hazardous chemicals into grades 1 to 6 ,36,37,38H4. Quantity of hazardous chemicals: Refers to the number of hazardous chemicals used, stored, and produced in the region. Based on the division of the \u201cList of Hazardous Substances and Critical Quantities of Environmental Emergencies\u201d of the Ministry in Environmental Protection\u2019s \u201cGuidelines for Risk Assessment of Environmental Emergencies in Enterprises ,\u201d considering the critical amount of hazardous chemicals in the region, it is divided into three levels: high, medium, and low.Regional risk tolerance is divided into two factors: disaster bearer and disaster-mitigation capacity. Disaster bearer comprehensively considers the background values of characteristic pollutants in the marine environment, the impact of topography and geomorphology, the connection to the ocean, the category of sensitive resources, and the distance from sensitive resources. Disaster-reduction capacities should take into account regional-risk-control capacities. The specific instructions are as follows:E1. Diffusion condition: Refers to the drift diffusion of hazardous chemicals after they enter the sea; the wider the scope of the diffusion, the greater the degree of its impact on the marine environment. The spread situation is divided into open sea, semi-enclosed bay, and harbor pool, and its impact on the marine environment is open sea > semi-enclosed bay > port pool.E2. Sensitive-resources category: With reference to the marine-water-quality standard , sensitiE3. Distance from sensitive resources: The distance from sensitive resources reflects the degree of damage caused by environmental accidents. After a spatial analysis of environmental risk sources and surrounding sensitive points through GIS, the distance from the most direct leakage point to the nearest environmentally sensitive point according to the risk source is divided into 3 levels: <3 km, 3 to 10 km, and \u226510 km.E4. Enterprise safety-production-standardization level: According to the provisions of the Administrative Measures for the Evaluation of Enterprise Safety Production Standardization , the safTo make the weights determined more representative and maximize the sample size, the relevant experts of the First Institute of Oceanography of the State Oceanic Administration, Xiamen University, Beijing Normal University, Beijing University of Chemical Technology, Dalian Maritime University, CNOOC Safety Technical Service Company, Beihai Environmental Monitoring Center of the State Oceanic Administration, and other units were invited to comprehensively construct a judgement matrix of expert scores to determine the relative importance of weights of each layer of indicators .According to the hazard scores of hazardous chemicals, the hazards of hazardous chemicals were divided into four levels .According to the regional-risk-tolerance scores, the regional risk tolerance was divided into four levels .According to China\u2019s current administrative management system, with the county (district) as the unit, a regional risk assessment was carried out, and the assessment scope was 10 km on the seaward side of the coastline and, on the landward side, up to the maximum-high-tide line, focusing on the risk sources for sources of dangerous chemical leakage into the sea, such as hazardous-chemical enterprises located within 1 km of the coastline on the landward side or adjacent to rivers entering the sea. The risk-assessment-level relationship of dangerous chemicals leaking into the sea area is shown in To test the applicability of the risk-source-assessment-index system, a typical enterprise in Tianjin Binhai New Area was selected as a research case for risk-source-level assessment. First, basic information, such as the geographical location coordinates, the types and quantities of hazardous chemicals involved, and the level of the enterprise\u2019s safety-production standards, was collected and sorted. Second, according to the \u201cTianjin Marine Functional Zoning\u201d (2011\u20132020), the conditions for the potential diffusion of chemicals into the sea from the company, the types of sensitive resources nearby, and their distance from sensitive resources were determined. Finally, the scores for each risk factor were calculated according to the established risk-assessment method for the leakage of hazardous chemicals into the sea . The comBy applying the recent research conducted at home and abroad to comprehensively consider the hazard and regional risk tolerance of hazardous chemicals, this study established a regional-risk-assessment-index system for hazardous chemicals spilling into the sea, including the type of risk source, the types of hazardous chemicals, the quantity of hazardous chemicals, the toxicity of hazardous chemicals, the diffusion conditions, the types of sensitive resources, the distance from sensitive resources, and the level of enterprise-safety-production standards. At the same time, a combination of the AHP and the Delphi method was used to determine the weights of the indicators, and comprehensive expert scores were assigned to the indicators. The index system not only takes into account the scientific rationality of index-setting and weight assignment, but also considers the applicability of the operationalization of risk assessment in the area in which hazardous chemicals are leaked into the sea. Unquestionably, there are still deficiencies in the risk assessment of hazardous chemicals leaking into the sea. The indicator system needs to be further adjusted and screened, the weight assignment needs to be further optimized and improved, and it is still difficult to obtain some indicators, such as the quantity of hazardous chemicals and the level of enterprise-safety-production standards.In the next step, we will select the Bohai Sea area, carry out the application of the risk-assessment methods for hazardous chemicals leaking into the sea, further improve the assessment method and indicator system, and provide good technical support for the comprehensive management of the Bohai Sea."} +{"text": "Neisseria gonorrhoeae and gonorrhoea treatment failures were increasing, a response plan to control and manage multidrug-resistant N. gonorrhoeae (MDR-NG) in Europe was published in 2012. The three main areas of the plan were to: (i) strengthen surveillance of antimicrobial resistance (AMR), (ii) implement monitoring of treatment failures and (iii) establish a communication strategy to increase awareness and disseminate AMR results. Since 2012, several additional extensively drug-resistant N. gonorrhoeae (XDR-NG) strains have emerged, and strains with high-level ceftriaxone resistance spread internationally. This prompted an evaluation and review of the 2012 European Centre for Disease Prevention and Control (ECDC) response plan, revealing an overall improvement in many aspects of monitoring AMR in N. gonorrhoeae; however, treatment failure monitoring was a weakness. Accordingly, the plan was updated in 2019 to further support European Union/European Economic Area (EU/EEA) countries in controlling and managing the threat of MDR/XDR-NG in Europe through further strengthening of AMR surveillance and clinical management including treatment failure monitoring. The plan will be assessed biennially to ensure its effectiveness and its value. Along with prevention, diagnostic, treatment and epidemiological surveillance strategies, AMR surveillance is essential for effective control of gonorrhoea.Because cefixime and ceftriaxone resistance in Neisseria gonorrhoeae (NG) has developed antimicrobial resistance (AMR) to all classes of therapeutic antimicrobials, most recently to third-generation cephalosporins [N. gonorrhoeae across Europe, but the degree of representativeness is affected by suboptimal isolate numbers and low completeness of reporting [Gonorrhoea is the second most commonly reported bacterial sexually transmitted infection (STI) in the European Union/European Economic Area (EU/EEA), with 117,881 cases reported in 2019, representing an increase of 17% since 2018 [osporins . Surveilosporins . Euro-GAosporins . Additioosporins . A revieeporting .Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe in 2012 [As a response to the emergence of in vitro resistance to cefixime and to treatment failures with cefixime and subsequently ceftriaxone in the EU/EEA and internationally , ECDC an in 2012 . Similar in 2012 and by n in 2012 and by t in 2012 . In addi in 2012 .Regular monitoring of the gonococcal AMR situation and AMR response plan indicators, and evaluating, reviewing and subsequent updating of national and international response plans are essential. Since the 2012 ECDC response plan was publDecreasing azithromycin susceptibility and sporadic resistance to ceftriaxone threaten the effectiveness of dual-therapy and ceftriaxone monotherapy regimens . CeftriaOur aim was to describe the evaluation of the 2012 ECDC response plan, by analysing the progress of indicators from 2012 to 2017, as well as the subsequent review and update of the response plan to further support EU/EEA countries in implementing national strategies and interventions to control the threat of multidrug-resistant (MDR)- and XDR-NG in a multidisciplinary approach.The main goal of the 2012 ECDC response plan was to mitigate the impact of MDR-NG on the prevention and control of gonorrhoea by serving as a guide for EU/EEA countries . Three mTo evaluate the effectiveness of the 2012 ECDC response plan , membersWe also assessed indicators related to Euro-GASP . The numDecreasing susceptibility to azithromycin, along with increasing reports of ceftriaxone-resistant strains and gonorrhoea treatment failures and of MDR/XDR-NG, made an evaluation, detailed review and update of the 2012 ECDC response plan imperative . The 201N. gonorrhoeae isolate data to the epidemiological and clinical data of the gonorrhoea cases.There are three main components in the 2019 ECDC response plan . FirstlyN. gonorrhoeae isolates should be collected and ideally reported promptly to ECDC. Where possible, N. gonorrhoeae XDR or ceftriaxone-resistant isolates and those from suspected treatment failures should be shared with the Euro-GASP hub for further verification, including whole genome sequencing, in order to inform the European guideline on the diagnosis and treatment of gonorrhoea [N. gonorrhoeae strain before and after treatment and to identify the presence of AMR determinants in treatment failure cases, but additionally has a role in improving AMR surveillance by providing a genomic background to monitor the molecular epidemiology of circulating strains , to detect new and emerging AMR determinants, to ultimately predict AMR and to investigate the genetic relatedness of isolates from national and international outbreaks [Secondly, a national agreement on adopting the treatment failure case definitions proposed in the 2019 ECDC response plan and an onorrhoea and to mutbreaks .Thirdly, the effectiveness of the 2019 ECDC response plan should be monitored at the national and European level . More deN. gonorrhoeae is imperative. The 2019 ECDC response plan should assist in controlling and managing the threat of MDR/XDR-NG in Europe through strengthening AMR surveillance and clinical management including treatment failure monitoring. The effectiveness of the 2019 ECDC response plan should be monitored regularly to identify and address areas for improvement promptly. Control of AMR in N. gonorrhoeae is ineffective without a comprehensive approach, therefore the 2019 ECDC response plan needs strong support from comprehensive management and control strategies nationally and internationally, including appropriate STI prevention (e.g. promotion of condom use), diagnostic and testing algorithms (e.g. triple-site testing in men who have sex with men), treatment, test of cure, notification and treatment of partners and robust epidemiological surveillance to identify key groups at risk of gonorrhoea and gonococcal AMR.Preventing further emergence and spread of AMR in"} +{"text": "Plants have developed a complex biochemical system for interacting and coping with dynamic environmental challenges throughout their whole life. Plant secondary metabolites are specifically produced and accumulated in low quantities in response to numerous factors such as bacteria, viruses, fungi, nematodes, insects and herbivores, as well as to climatic factors and seasonal fluctuations, soil and water parameters, etc.To optimize secondary metabolites production, plants have fine-tuned early signal systems for differentiating general mechanical damage from an attack by an insect/herbivore, for example. In addition, plants distinguish the degree of damage caused by herbivore feeding guilds, insect oral secretions, oviposition fluids, etc. The consecutive steps of the production of the respective defense secondary metabolites is mediated by cellular messengers and events such as metabolic changes, gene activation, jasmonic acid (JA) accumulation, kinase cascades, hydrogen peroxide production, cytosolic calcium ion fluxes, as well as membrane potential changes and refeThe key role of secondary metabolites for plant survival also underline the pharmacological roles that these substances play in mammalian organisms and hence their applicability in veterinarian and humanitarian medicinal practices. Plant cell tissue and organ cultures are based on the \u201ctotipotency\u201d of the plant cell and its capability to regenerate up to a whole integral organism. The technique allows for the cultivation of separate cells, tissues, differentiated organs, or integral plants in a growth medium in sterile conditions and out of the indigenous natural environment of the plants. The contemporary development of the method has nowadays led to its routine use as a supplementary to conventional plant breeding for an array of applications such as the rapid and disease-free micropropagation of plantlets, independent of seasonal, climatic, and geographic factors; the rapid testing and practical introduction of new cultivars using conventional or genetic engineering selection approaches. An important and rapidly developing field of the application of plant biotechnology is its use for the yield of plant secondary metabolites, allowing for the standardization of the levels of the secondary metabolites produced due to the capability of tissue culture techniques to optimize culture conditions and obtain the desired environment for the production of the target compounds.Plants dedicated to \u201cPlant Tissue Culture and Secondary Metabolites Production\u201d. The present collection aims to provide readers with up-to-date research dedicated to the scientific accomplishments in the production of plant secondary metabolites of different chemical types through the development of plant cells, tissues, and organs in diverse in vitro culture systems.Considering the importance of plant secondary metabolites and the high relevance of the establishment of scientifically based approaches for their biotechnological production, we are pleased to present this Special Issue of We have received seven scientific research papers on tissue culture development and secondary metabolite production of medicinal and aromatic plants of different regions of the world.Bidens pilosa L. (Asteraceae), dominated by chlorogenic acids consisting of caffeoyl and feruloyl derivatives of quinic acid. Xanthones production in differentiated shoot cultures of the endangered Gentianella lutescens (Gentianeceae) was evaluated for the first time by Krsti\u0107-Milo\u0161evi\u0107 et al. [Daucus carota, Apiaceae) callus culture experimental design of a combination of the components of the Gamborg [3:NH4 ratio affected carotenoid accumulation. In this work, changes to the medium other than N, such as microelements, vitamins, growth regulators, and sucrose, had no effect on callus growth and carotenoid accumulation. Mamdouh et al. [Lycium schweinfurthii (Solanaceae). Investigations on genetic stability, phenolic, flavonoid, ferulic acid contents, and antioxidant activity were performed, leading to the selection of an effective protocol for the in vitro propagation of plant material with desired quality. Erst et al. [3, as well as NH4:K+ ratio and the cytokinins BAP and naphthylacetic acid (NAA) on the growth and production of total phenolics callus culture of Rhodiola rosea (Crassulaceae). The study of Pieracci et al. [Artemisia caerulescens L. (Asteraceae) demonstrated the potential of the tissue culture technique for both the ex situ conservation and production of essential oils and phenolic compounds of this species.Ramabulana et al. establis\u0107 et al. in an ex\u0107 et al. proposed Gamborg and Mura Gamborg culture Gamborg establish et al. developet et al. studied i et al. on shoot"} +{"text": "Allium sativum L., Persea americana Mill., Moringa oleifera Lam., Mangifera indica L., and Allium cepa L. are the five most utilised plant species. The preferred plant parts include the leaves (36%), roots (21%), barks (14%), fruits (7%), and seeds (5%), which are mostly prepared by decoction. Benin, Mauritius, Nigeria, South Africa, and Togo had the highest reported use while most of the investigations were on diabetes and hypertension. Despite the nutraceutical advantages of some of these MPs, their general toxicity potential calls for caution in their human long-term use. Overall, the study established the need for governments of SSA countries to validate the efficacy/safety of these MPs as well as provide affordable, accessible, and improved modern healthcare services.Cardiovascular diseases (CVDs) are the leading cause of global mortality, including deaths arising from non-communicable diseases in sub-Saharan Africa (SSA). Consequently, this study aimed to provide details of medicinal plants (MPs) employed in SSA for the treatment of CVDs and their related risk factors to open new avenues for the discovery of novel drugs. The extensive ethnopharmacological literature survey of these MPs in 41 SSA countries was based on studies from 1982 to 2021. It revealed 1,085 MPs belonging to 218 botanical families, with Fabaceae (9.61%), Asteraceae (6.77%), Apocynaceae (3.93%), Lamiaceae (3.75%), and Rubiaceae (3.66%) being the most represented. Meanwhile, Cardiovascular diseases (CVDs), a group of disorders involving/affecting the heart and blood vessels, are the chief cause of death in the world ,2,3,4,5.2 were used.An extensive literature retrieval, principally from published scientific journals, was used to obtain the required ethnopharmacological information. This was based on studies from 1982 to 2021 with the application of single or combinations of keywords such as medicinal plants, cardiovascular diseases and treatment, diabetes, hypertension, obesity, stroke, and the different names of SSA countries. Major scientific electronic databases , as well as other internet sources, were consulted. To verify the scientific names and families of the identified MPs, other databases such as The Plant List and The World Flora Online [Based on the goal/theme of the review, information gathered from the literature survey, which include the name of the MPs , family, plant part used, modes of usage/preparation, therapeutic use, and the SSA countries involved, were analysed, as well as grouped accordingly.Descriptive statistical analysis of the ethnopharmacological data obtained was achieved using Microsoft Excel software while a readily available bioinformatics web tool was usedA. sativum is the most employed MP, which indicates its obtainability in many parts of the region and suggests the presence of potent bioactive compounds in the plant against the development of these diseases.To aid the research on CVDs and production of novel drugs, this comprehensive ethnopharmacological review provides the necessary details of MPs used for the treatment of CVDs and their associated risk factors in SSA. The study revealed that SSA has a rich history in the use of MPs for the treatment of the diseases of focus and a wealth of knowledge in TM, which some individuals in the region rely on for their health needs. The results showed that there are five dominant botanical families of MPs that have been used in SSA for CVD treatment, with some of the MPs having nutraceutical applications because of their edible parts. The ease of collection of MPs\u2019 leaves contributing to their high percentage use shows that the availability of effective and affordable drugs for the treatment of these diseases in the region would assist in encouraging the use of modern medicine. This will also safeguard consumers against the unexpected risk of certain toxic compounds in these MPs and the possible negative effects of overdoses arising from unregulated use. The reliance on decoction as a mode of preparation of these MPs (despite its inherent short shelf-life disadvantage), as well as the major focus on diabetes and hypertension, call for enlightenment, scientific engagements, and urgent government intervention to reduce the number of people suffering from CVDs in the region.Most importantly, the investigation points out the need for governments of SSA countries such as Nigeria and South Africa, with the high percentage use of MPs reported for these diseases, to provide affordable/accessible high-quality modern healthcare services for the populace. Validation of the claimed medicinal/pharmacological potentials and safety assessment of MPs used in the region for CVDs treatment are also encouraged."} +{"text": "The problem of coexistence of heteroaggression and autoaggression most clearly manifests itself in the field of forensic psychiatry. For example, in Russia, about 25% of criminals who committed aggressive actions had a history of suicide attempts.Identification of specific personality traits in individuals with multidirectional aggression.In a continuous one-step study, relatively sane adults of both sexes were examined: 38 persons undergoing forensic examination with multidirectional aggression and 34 violent criminals. A wide range of forensic psychological techniques is used to identify aggression, suicidogenic and inhibitors of aggression. Nonparametric statistical methods were used: Spearman rank correlation coefficient (r) and Mann-Whitney (U).The leading role in the genesis of multidirectional aggression, in contrast to other types of aggression, playing the combination (p<0.01) to the presence of motivational aggressiveness and the willingness to show negative feelings at the slightest arousal , along with suicidal personal qualities, which is combined with the deficiency of auto- and heteroaggression inhibitors . However, the psychological mechanisms of multidirectional aggression are relatively non-nosospecific and are similar in mentally healthy individuals and individuals with personality and organic mental disorders.Multidirectional aggression in view of the increased risk of recidivism and personal and public danger should be taken into account by forensic experts when recommending psychocorrective measures in places of deprivation of liberty.No significant relationships."} +{"text": "As a urinary dysfunction disorder, stress urinary incontinence (SUI) is more common in women than in men. Acupuncture, a traditional minimally invasive technique, has potential efficacy in the treatment of SUI. The purpose of this overview is to critically assess the available evidence on acupuncture for the treatment of SUI in women. Two researchers searched seven databases for systematic reviews (SRs)/meta-analyses (MAs) of randomized controlled trials (RCTs) on acupuncture for SUI. Two researchers assessed the included SRs/MAs using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Eight published SRs/MAs were included in our overview. According to the results of the AMSTAR-2 assessment, all SRs/MAs were of very low quality. According to the ROBIS evaluation results, no SR/MA was assessed as low risk of bias. According to the results of the PRISMA checklist assessment, no SR/MA was fully reported on the checklist. According to GRADE, a total of 27 outcomes extracted from the included SRs/MAs were evaluated, and only 1 was rated as high quality. Acupuncture may be an effective and safe complementary treatment for SUI in women. However, further standard and comprehensive SRs/MAs and RCTs are needed to provide an evidence-based medical rationale for this. As a form of dysfunction disorder, stress urinary incontinence (SUI) is the most common type of urinary incontinence. It is defined as the involuntary flow of urine due to physical exertion or effort, coughing, or sneezing . SUI hasThe main treatment modalities for SUI include lifestyle interventions, electrical stimulation, pelvic floor muscle training (PFMT), medication, and surgery . The AmeAs a minimally invasive treatment method, acupuncture has a history of more than 2,500 years in China and is gaining more and more international attention in the field of healthcare . With itThe methodology of this study follows the Cochrane manual, as well as the study methods of some high-quality SRs/MAs overviews \u201312.The criteria for inclusion of SRs/MAs in this overview are as follows: (1) Study design: This overview includes SRs/MAs of randomized controlled trials (RCTs) of the acupuncture on SUI; (2) Type of participants: Female subjects diagnosed with SUI based on any authoritative national or international diagnostic criteria regardless of race, age, gender, time of onset, and source of cases; (3) Intervention: The control group received the following treatments: Conventional medication (CM), rehabilitation training (RT), sham acupuncture (SA), and placebo. The intervention group received acupuncture treatment, including plum blossom acupuncture, fire acupuncture, electro-acupuncture, body acupuncture, manual acupuncture, warm acupuncture, or acupuncture therapy in combination with the treatments received by the control group; (4) Outcome indicators: Outcomes assessed in this overview include: Effective rate, 1-hour pad test, international consultation on incontinence questionnaire short form (ICIQ-SF) score, visual analog scale (VAS) score, and adverse reactions.The criteria for exclusion of SRs/MAs in this overview are as follows: (1) Animal studies; (2) Network MAs, research protocols, narrative reviews, overviews, dissertation, and conference abstracts.Literatures were retrieved from PubMed, Cochrane Library, EMBASE, Chongqing VIP, Wanfang Database, CNKI, and SinoMed on 1 January 2022. We adopted a search strategy combining keywords with free words, and the keywords include acupuncture, urinary incontinence, systematic review, and meta-analysis. The literature search strategy shown in of the PThe literature screening (HS-S and LZ-Z) and information extraction (WB-L and ZC-W) were performed independently by two researchers. We firstly input the retrieved documents into Endnote X9 document management software, and then removed the duplicates. The literatures that potentially met the inclusion and exclusion criteria were then obtained by reading the titles and abstracts. Eventually, we finalized the included SRs/MAs by reading the full text. A standardized data extraction form was adopted to extract relevant information for the inclusion of SRs/MAs. The following information was extracted from each SR/MA: First author, year of publication, author nationality, number of RCTs included, sample size, intervention group measures, control group measures, tools used to assess the risk of bias, and main findings.Two researchers (PL-L and D-W) independently assessed the methodological quality and certainty of quality of the included SRs/MAs.The methodological quality of the included SRs/MAs was assessed by the Assessment System for Evaluating Methodological Quality 2 (AMSTAR-2) . Seven (The Risk of Bias in Systematic Review (ROBIS) scale waThe quality of each SR/MA report of the included SRs/MAs was evaluated by the list of PRISMA which coThe certainty of quality for each SR/MA outcome was evaluated by The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) , and fivA total of 166 publications were retrieved from seven electronic databases. Nine publications were retrieved for full-text evaluation after the duplicates removal and title/abstract screening. One paper was exclThe characteristics of the 8 SRs/MAs included in our final evaluation were summarized, as shown in Regarding the methodological quality of the included SRs/MAs, all were considered to be of very low quality because more than one key item was missing from the SRs/MAs included in the quality assessment. Methodological quality limitations come from the following items: Items 2 was the most common downgrading factor, followed by risk of bias (n\u2009=\u200913), inconsistency (n\u2009=\u200913), imprecision (n\u2009=\u20099), and indirectness (n\u2009=\u20090). GRADE specific assessment details are shown in The 8 SRs/MAs included 27 outcomes related to the effectiveness of acupuncture for SUI. For all the outcome indicators, 1 was rated as high quality, 10 moderate, 6 low and 10 very low by means of the GRADE evaluation. Publication bias SRs/MAs were published in the last five years, indicating that acupuncture had received increasing attention as an important intervention modality for SUI in women.Based on the results of the AMSTAR-2, ROBIS, and PRISMA evaluation in this overview, the methodological and reporting quality of the SRs/MAs were unsatisfactory. Only two SRs/MAs contained initial research protocol registrations, the lack of which could lead to non-standardization of the research process, increase the risk of bias and impact the rigor and credibility of the final SRs/MAs results. All of the included SRs/MAs lacked a search of the gray literature, which made it difficult to ensure the comprehensiveness of the literature search and tended to generate publication bias. None of the SR/MA provided a complete list of exclusions for each study, which may affect the reliability of the results and assessment of publication bias. The provision of a list of exclusion researches can be a stronger demonstration of the rigor of the literature screening process. No SR/MA reporting was included in the RCT's funding resources, which may increase the bias in clinical trials as the results of corporate-funded studies may be biased in favor of the funder. None of the SR/MA provides comprehensive search strategies, which reduced the reproducibility and credibility of the study. In addition, the lack of reporting of conflicts of interest also potentially affected the credibility of the article.Based on the GRADE assessment, publication bias was deemed as the most significant downgrading factor. Further analysis revealed a risk of publication bias for the outcome indicators included in the SRs/MAs, which may be related to incomplete searches and the insufficient number of RCTs included in the relevant outcomes. In addition, other reasons for the downgrading risk of bias included: Most of these RCTs mentioned randomization without giving the randomization method; most didn't conceal allocation; and most didn't use blinding method or just used single blinding. Declining certainty of quality due to inconsistency may stem from substantial clinical and methodological differences in the included RCTs, which could be avoided by standardizing the inclusion and exclusion criteria as well as the literature screening process.Descriptive analysis suggested that acupuncture was an effective treatment for SUI in women with a high safety profile. However, due to the low methodological quality and certainty of quality of the included studies, these findings may deviate from the actual results. Therefore, caution should be exercised when recommending acupuncture as a complementary intervention for SUI in women.Featuring unique advantages, acupuncture therapy plays an integral role in the treatment of urinary incontinence. Acupuncture works by repeatedly stimulating the points within the body by needling the control points of the bladder and sphincter muscles, thus effectively repairing and improving the body's various control functions .This paper gave a comprehensive assessment of all aspects of the included SRs/MAs using AMSTAR-2, PRISMA, ROBIS, and GRADE, and the methodological quality and certainty of quality were found unsatisfactory. As implied, there is still considerable scope for addressing the quality issues in the process of conducting SRs/MAs. When selecting topics for SRs/MAs, investigators should register or publish study protocols in advance to minimize the risk of bias and ensure the standardization of SRs/MAs. The search for gray literature, complete search strategy and the list of excluded literature need to be supplemented in SRs/MAs, which can reduce publication bias and improve the certainty of quality. A list of funding for RCTs and declarations of conflicts of interest need to be provided to increase the credibility of SRs/MAs. In addition to this, the specific nature of acupuncture treatment makes it difficult to perform a blinded acupuncture-related RCT. However, patients, care providers, and outcome evaluators should be blinded whenever possible to minimize the risk of bias. A well-designed and rigorously executed RCT is believed to be the gold standard for evaluating interventions to minimize or avoid bias . AcupuncOur overview is the first to use AMSTAR2, ROBIS, PRISMA, and GRADE to evaluate SRs/MAs regarding acupuncture for the treatment of female SUI. The evaluation process revealed clear limitations of the current relevant SRs/MAs and RCTs, which may help boost the quality of future clinical studies. However, the overview may have some limitations due to the subjectivity of the evaluation. Although our evaluation had been assessed and reviewed by two independent reviewers, different reviewers may have their own judgments about each factor, so the results may vary. In addition, for different SRs/MAs included in this overview, the definition of effective rate is not mentioned.In conclusion, acupuncture is a beneficial and safe way to treat SUI in women. However, due to the generally low methodological quality and certainty of quality in the included SRs/MAs, clinicians should approach these findings with caution in their practice."} +{"text": "Having valid information on mortality within a country is of great importance for public health planning. This includes knowing the causes of death (CoD) within a population. However, these data are not always suitable for Burden of Disease calculations from the start and hence, need some realignment in advance. The CoD statistics in Germany include a relatively high share (26% in 2017) of ill-defined deaths (IDD) - using the definition of the Global Burden of Disease Study. Additionally, only the underlying CoD is included in the national statistics and no multicausal data are available yet. As part of the German Burden of Disease project BURDEN 2020 we redistributed IDD to valid CoD using a process of proportional redistribution. To do so, we made use of the distribution of the valid ICD-codes in the data. In the proposed presentation, we use examples of stroke, diabetes, and heart failure to illustrate how IDD were reallocated. After redistribution, the largest increases for both women and men were seen for lower respiratory infections, diabetes mellitus, and stroke. The numbers of deaths for these causes more than doubled after redistribution. Within this project, we carried out the first comprehensive redistribution of IDD for German CoD statistics."} +{"text": "Sedation and analgesia (SA) management is essential practice in the pediatric intensive care unit (PICU). Over the past decade, there has been significant interest in optimal SA management strategy, due to reports of the adverse effects of SA medications and their relationship to ICU delirium. We reviewed 13 studies examining SA practices in the PICU over the past decade for the purposes of reporting the study design, outcomes of interest, SA protocols used, strategies for implementation, and the patient-centered outcomes. We highlighted the paucity of evidence-base for these practices and also described the existing gaps in the intersection of implementation science (IS) and SA protocols in the PICU. Future studies would benefit from a focus on effective implementation strategies to introduce and sustain evidence-based SA protocols, as well as novel quasi-experimental study designs that will help determine their impact on relevant clinical outcomes, such as the occurrence of ICU delirium. Adoption of the available evidence-based practices into routine care in the PICU remains challenging. Using SA practice as an example, we illustrated the need for a structured approach to the implementation science in pediatric critical care. Key components of the successful adoption of evidence-based best practice include the assessment of the local context, both resources and barriers, followed by a context-specific strategy for implementation and a focus on sustainability and integration of the practice into the permanent workflow. Optimal sedation and analgesia (SA) management are critical components of care in the pediatric intensive care unit (PICU) and an essential piece of the ICU Liberation ABCDEF Bundle , 2. SedaSeveral studies have examined the impact of SA regimens on clinical outcomes in critically ill infants and children over the past decade 5\u201316). \u201316. 5\u201316A variety of outcomes were considered in these studies. Exposure to SA medications was the most common outcome assessed after the implementation of an SA regimen. Of the 13 studies included in this review, 12 92%) studies had interventions examining initiation and titration of SA medications and 8 (62%) included a sedation/analgesia weaning protocol. In total, 11 studies 85%) demonstrated a significant reduction in either duration or total dose of opiates, benzodiazepines, or another sedative of interest. Patient-centered benefits were explored in some of the studies with variable results % demonst, 9\u201314. M2% studieImplementation strategies were described in 11 (85%) studies and predominantly included educational modules, visual aids, and bedside local champions. The majority of implementation strategies center around educational efforts, despite the fact that educational efforts are known to be relatively weak interventions . Some stRandomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), a multicenter unblinded cluster-randomized trial that included 31 PICUs in the United States , was theThe 2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility (PANDEM guidelines) reviewed many of these studies , inability to engage non-verbal patients with non-pharmacologic interventions, concerns about medication effects on long-term neurocognitive outcomes, and the need to balance the depth of sedation with patient safety (such as unplanned extubations or line/tube dislodgment events) . ProtocoThe evidence for best SA practices remains scarce with respect to patient-centered outcomes, which may limit provider buy-in, even in the context of increased interest or motivation to change practice. The lack of newer effective drugs with acceptable pediatric safety profiles limits our choice of sedative agents. For example, the use of propofol as a long-term sedative agent is declined in children over the past decade due to concerns for propofol infusion syndrome and increased mortality . MidazolAdditionally, most of the interventions in this cohort relied on weak implementation methods, such as educational modules. Several studies recognized the importance of providing bedside clinical decision support (CDS), particularly in the early phase post-implementation, to ensure compliance and sustainability beyond the immediate implementation period , 10, 12.Further barriers in implementation include cultural context barriers, i.e., readiness of the local environment for change, as well as other practical limitations, such as resource requirements, staffing models, lack of PICU or institutional leadership investment, and lack of effective teamwork and collaboration skills , 28. TheThe studies of SA regimen efficacy in the PICU highlight an important gap in IS in pediatric critical care. IS addresses the effective translation of evidence-based guidelines into bedside practice and is an emerging field of study in critical care . SpecifiIn pediatric critical care, barriers to effective implementation of new guidelines are multifactorial and span different levels of the healthcare delivery system. A recent study using the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) framework across 58 professionals in 8 United States PICUs utilized structured interviews to examine barriers, facilitators, and processes for change . Common In addition to continuing clinical research studies targeted at understanding best SA practices in pediatrics, there should be a parallel effort to specifically examine the adoption and sustenance of the intervention using IS-specific methodology. In addition to the development of an evidence-based intervention, strategically ensuring the successful implementation and sustainment of the intervention is critical to short-term and long-term success. Successful implementation may require effective education, ongoing just-in-time CDS, continuous feedback and evaluation, and strategic planning based on local contextual factors. IS seeks an understanding of why or how an intervention is successful. For example, although the comprehensive ICU Liberation Bundle highlights guidelines related to early mobility, SA practices, and daily extubation readiness assessment for improving patient outcomes, successful implementation has not been consistently demonstrated, and current investigations focus on barriers, such as culture change , 28, 30.Implementation science methodology includes tools, such as implementation mapping, traditional quality improvement (QI) tools, education, and concept mapping , 31. ImpA recent review provides an overview of the associated theories, models, and frameworks of IS . The autAnother potentially useful tool for IS is the Dissemination and Implementation (D&I) Models in Health Research and Practice available through the National Institutes of Health . The D&ISince many protocols and materials rely on team-based approaches, educational material should emphasize the role clarity of team members, as well as identify and employ specific skills and knowledge unique to each team member. This requires an interdisciplinary approach at all stages of implementation, from intervention design to execution to auditing, maintenance, and accountability . Common There is heightened interest in employing best practices related to SA regimens in pediatric critical care. There are several studies that have examined the role of evidence-based novel SA regimens in the PICU population, and this area of research has the promise to achieve improvements in patient outcomes. The existing literature on the subject could be significantly enhanced by emphasis on the systematic implementation of the interventions. Research in SA protocol implementation is met with numerous challenges . The intYY and NM conceived the design of the manuscript. YY performed the review of the studies and prepared the manuscript draft. AG, KM, and NM reviewed and edited the manuscript. All authors approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The proceeding focused on case studies of patients with diverse affections, mainly depression, cognitive impairment, and discussed the role of neurotrophic factors.Within the \"17th year of intense collaboration, benefitting from a strong endorsement from the World Federation of Neurology (WFN), World Federation of Neurorehabilitation (WFNR), European Federation of NeuroRehabilitation Societies (EFNR), European Academy of Neurology (EAN), and many other organizations. Prof. Muresanu made a stance on working together on a significant topic at the European level, namely the concept of \"brain health\", which presumes a close collaboration between neurology and psychiatry, outlining his belief that the future would bring together the two disciplines due to the fantastic advances, with a strong accent being placed on the interdisciplinary approach.Prof. Dafin Muresanu, the EFNR President, delivered his thoughts on the 17Adela Ciobanu (Romania), Habilitated Professor of Psychiatry at Carol Davila University of Medicine and Pharmacy in Bucharest (Romania), and Head of 1st Clinical Department at Professor Dr. Alexandru Obregia Hospital (Romania), presenting the management of treatment-resistant depression in the elderly. Prof. Ciobanu followed the case of a 75-year-old woman with a depressed mood, anxiety, and insomnia, describing behavioral traits, treatment history, and symptoms. A very in-depth presentation of the mental state examination was provided, the diagnosis \u2013 including differential diagnosis \u2013 and the treatment approach. One crucial point of her lecture was that treatment-resistant depressive disorders often occur in current medical practice, raising issues on differential diagnosis. Moreover, Prof. Ciobanu stated that these clinical cases must be addressed individually and highlighted the role of Cerebrolysin as adjuvant therapy for addressing treatment resistance.The first session of the day introduced Brindusa Focsaneanu (Romania), Senior Lecturer at the Department of Psychiatry from the Faculty of Medicine at Titu Maiorescu University of Bucharest and the Head of the Psychiatry Department VIII within the Hospital Prof. Dr. Al. Obregia (Romania), presented the topics of depression and cognitive impairment, discussing therapeutic approaches for a case report on a 60-year-old woman experiencing a depressive episode with anxiety, behavioral and mood imbalance, somatic symptoms and others. She discussed the public health and epidemiological aspects of mental and neurological disorders in older adults, signalling the role of neurotrophic factors in the modulation of synaptic transmission and their part as a therapeutic strategy in certain neurological disorders. The fascinating presentation showcased a descriptive insight into the patient's pathway in the medical system. Dr. Focsaneanu compared the expected and actual outcomes and pinpointed the importance of cognitive testing, obtaining a detailed patient history, and implementing longitudinal follow-up. Moreover, Dr. Focsaneanu discussed the risks of dementia for older people with depression and the role of neurotrophic factors in aiding neurorecovery and the preservation of cognitive function.Andreea Szalontay (Romania), Associate Professor of Psychiatry at Grigore T. Popa University of Medicine and Pharmacy and Head of Clinical Psychiatry VI from the Socola Institute of Psychiatry in Iasi (Romania), presented a case of mild cognitive impairment after infection with SARS-CoV-2. Offering an epidemiological context on SARS-CoV-2 and cognitive decline, Prof. Szalontay mentioned the effects of COVID on bodily systems and highlighted the cognitive decline and the persistence of symptoms in patients with the infection. One point of her presentation was that the pandemic might contribute to the future increase in the world dementia burden. Her insightful and comprehensive case studies showcased the importance of multidimensional approaches and the effect of neurotrophic factors, such as Cerebrolysin, in the treatment of cognitive deterioration.Romeo Dobrin (Romania), Associate Professor of Psychiatry at Grigore T. Popa University of Medicine and Pharmacy and Head of Section IX at the Socola Institute of Psychiatry in Iasi (Romania), approached the efficacy of neurotrophic factors in neurocognitive disorders. Prof. Dobrin discussed the concept of senescence and dementia, presenting the stages of the disease and highlighting the symptoms and manifestations. Furthermore, based on a case report on mixed dementia, he highlighted the importance of comprehensive approaches, including mental state examination, Alzheimer's assessment, anamnesis, differential diagnosis and clinical data, showcasing the disease progression and presenting therapeutic objectives and further assessment. Finally, he outlined essential points on the management and perspectives of dementia, pinpointing the importance of a larger-picture approach, including research, medicine, and public health perspectives.Mihai Mutica (Romania), Psychiatrist at Elisabeta Doamna Psychiatry Hospital in Galati (Romania), ended the session with \"Mild Cognitive Impairment in a Patient with Polymorphic Symptoms\". Dr. Mutica showcased a case study with complex presentation and favorable outcomes, discussing the results of psychiatric examination, the effect of the treatment, and the management of the patient, pinpointing the importance of individualized approaches for anxiety affective symptoms presenting with cognitive impairment, advising the audience to take precautions when making assumptions about psychiatric disorders and their relation to future dementia.Virgil Enatescu (Romania), Habilitated Professor of Psychiatry at the Victor Babe\u0219 University of Medicine and Pharmacy in Timisoara (Romania), who presented \"The Efficacy of Neurotrophic Factors in A Case Of Minor Cognitive Disorder Comorbid With Bipolar I Disorder And Sequelae Of Cerebral Infarctions\". Prof. Enatescu discussed, based on a case study on bipolar disorder presenting with mild cognitive symptoms, the prognosis of bipolar disorders, genetic vulnerabilities, and comorbidities. Furthermore, he described the patient's pathway and the outcomes, pinpointing the impact of cognitive dysfunction on the psychosocial outcomes in patients with bipolar disorder. Cerebrolysin, as the potential aid in the treatment of a variety of debilitating neurological conditions, was also an important topic touched upon.The second session introduced Catalina Giurgi-Oncu (Romania), Senior Lecturer in Psychiatry at the Department of Neuroscience from Victor Babes University of Medicine and Pharmacy of Timisoara (Romania), presented \"A significant improvement of affective symptoms and Theory of Mind abilities in a patient treated with neurotrophic factors for a Mild Cognitive Disorder\". Dr. Giurgi-Oncu discussed mild cognitive impairment and the risk of developing further dementia, approached the impact of emotional health on social functioning, and glimpsed through the effect of depressive disorders on social interactions, highlighting the \"Theory of Mind\" concept encompassing affective and cognitive components. An exciting case study was presented, highlighting diagnostic criteria for mild cognitive impairment, epidemiology and risk factors, procedures of screening, evaluation, and early detection, and recommendations for follow-up and prognosis.Adriana Mihai (Romania), Associate Professor at the Psychiatric Department from the University of Medicine, Pharmacy, Science and Technology George Emil Palade in Targu Mures (Romania) and Director of the Centre of Psychotherapy and Personal Development (IPPD), showcased her presentation \"Vascular neurocognitive disorder \u2013 presentation of a clinical case with language disturbances\", highlighting cognitive disorders, especially vascular dementia, as a common cause of neurocognitive disorders post-Alzheimer's disease. Furthermore, Prof. Mihai presented epidemiological aspects and the characteristics of vascular dementia and introduced a fascinating clinical case presentation of acute psychotic disorder. Lastly, prof. Mihai discussed the importance of collecting comprehensive information on patients, especially on cases with less common manifestations, as the paradigm for treatment in psychiatry is a symptomatic one.Claudia Anghel (Romania), Psychiatrist at the Psychiatric Hospital Dr. Gh. Preda in Sibiu (Romania) and President of the NGO Psychiatric Hospital Association Dr. Gh. Preda, focused on \"Electroconvulsive therapy \u2013 between necessity and stigma\", discussing the mechanisms of electroconvulsive therapy and the impact of technological advancements while mentioning the possible complications and contraindications when using this therapy. For a better understanding, Dr. Anghel pinpointed the history of ElectroConvulsive Therapy (ECT) therapy in their hospital and the issues related to stigma and the portrayal of ECT in media, urging for improved education on this therapy. Lastly, in a case study on undifferentiated schizophrenia, the impact of ECT was highlighted. In the end, she invited the public to reflect on some aspects of ECT, including the avenues for changing societal perception of this medical technique.Doina Cozman (Romania) underlined the importance of showing great attention to mild cognitive impairment in people over 50 years of age, as this syndromologic diagnostic is chameleon-like, taking many possible forms and, in some cases, leading to dementia or depression, or even causing several psychiatric or somatic issues. Other critical points showcased were the relevance of the Montreal Cognitive Assessment (MoCA) test in cognitive assessment, the vital role of multidisciplinarity, and the interrelations of psychiatry and neurology. The parallel psychiatry session from the 17th International Summer School of Neurology stands as an example of the importance of transdisciplinary perspectives in neurosciences.In the form of discussions and final remarks,"} +{"text": "RSC Advances article due to concerns with the reliability of the data in the published article. The authors confirmed that the western blot images in Fig. S3A had been inappropriately manipulated. Given the significance of the concerns about the validity of the data, the findings presented in this paper are no longer reliable.The Royal Society of Chemistry, with the agreement of the named authors, hereby wholly retracts this Fang Liu, Jing Wang and Xiu-Wei Yang were contacted but did not respond.Signed: Qi Zhao, Rui Yang, Dan-Dan Hu and Fei LiDate: 23rd January 2023RSC AdvancesRetraction endorsed by Laura Fisher, Executive Editor,"} +{"text": "Mental disorders in Europe represent the leading cause of disability and the third leading cause of overall disease burden, following cardiovascular disease and cancers. As future healthcare professionals, with an imminent role in tackling this global health issue, we acknowledge that Mental Health is not adequately included in the medical curriculum. To address this gap, this workshop was created to equip medical students with the knowledge and skills that will empower them to lead a pioneering role in advocating for mental health for their patients, peers, and communities.By the end of the workshop, all participants should have: - Increased their knowledge in the field of Mental Health disorders - Increased their skills in the field of Mental Health - Explored the relations between stigma, vulnerability, and Mental Health - Strengthened the international perspective and global understanding concerning mental health issuesThis workshop utilized principles of non-formal education and was planned according to the 4MAT system to meet all four learning styles through theory blocks, space for reflection, practical application of knowledge, and future opportunities for application of content. This was achieved through various methodologies including presentations, self-discovery activities and exercises, roundtable debates, simulations, and role-playing.obtainedThis workshop highlighted the importance of building the capacity of medical students to tackle the burden of Mental Health globally and within the region, and how similar student-led initiatives can further empower them to be change agents and impactful advocates for better Mental Health in their own communities."} +{"text": "To examine links between Adverse Childhood Experiences (ACE) categories and diagnosis of antisocial personality disorder (ASPD) in this population; it is predicted that there will be a positive association between number of ACEs and ASPD. The effectiveness of high secure hospital admission and treatment in reducing number of risk incidents was also examined. ACEs are known to impact significantly on the development of the personality and future psychiatric risk. Currently, research into links between distinct ACE categories and the diagnosis of ASPD in the high-secure inpatient population is limited.Data were collected from a sample (n = 221) including all patients in the Mental Health, Personality Disorder and Women's Services at a high-secure hospital. Records were examined for evidence of abuse/neglect during childhood, and a number of markers of household dysfunction. The statistical relationship between each ACE category and subsequent diagnosis of ASPD was examined through paired t-tests. Frequency of incident reports (IR1s) involving violence was compared in the first, third and fifth years post-admission.Significant associations with adult diagnosis of ASPD were seen in categories of childhood physical abuse, sexual abuse, divorced/separated parents, Looked After Child (LAC) status and parental substance misuse, and total number of ACE categories present overall. Significant reductions in frequency of IR1s were seen in all services between first- and fifth- year post admission.A significant association between ACEs in specific domains and ASPD in adulthood was found. The importance of detailed exploration of childhood circumstances in this group is highlighted, as well as the need for further investigation of the psychological and social mechanisms underlying."} +{"text": "Parkinson\u2019s disease (PD) is taking a staggering toll on healthcare systems worldwide, with the bulk of the expenditures invested in the late stages of the disease. Considering the rising life expectancy and the increasing prevalence of PD across the globe, a clear understanding of the early signs and treatment options available for advanced PD (APD), will facilitate tailoring management programs and support services. This task is complicated by the lack of both global consensus in defining APD and standardized care guidelines. This perspective prepared by a panel of movement disorder specialists, proposes to extend and optimize currently accepted PD coding to better reflect the diverse disease manifestations, with emphasis on non-motor features. The panel seeks to promote timely diagnosis by adjustment of evaluation tools for use by community neurologists and suggests modification of eligibility criteria for advanced therapy. Moreover, it advocates multidisciplinary assessments of APD patients to drive personalized, patient-centered and holistic management. Overall, earlier and more targeted intervention is expected to markedly improve patient quality of life. Parkinson\u2019s disease (PD) currently affects 41 in 100,000 individuals between the ages of 40 and 49 and 1,607 in 100,000 individuals over the age of 80 . In IsraHistorically, motor syndrome was the main recognized clinical manifestation of PD and the prevalence of severe disability and mortality within 5 and 10 years of onset was 25 and 65%, respectively . Yet, sivia pumps, are needed to improve response fluctuations.This stage is characterized by moderate to severe motor deficits (Hoehn & Yahr stage III-V during off periods), generally accompanied by troublesome motor and non-motor symptoms: fluctuations, dyskinesias, frequent off-periods, postural instability leading to frequent falls with increased risk of fractures, sleep disturbances, hallucinations, and cognitive decline, among others. However, with close support, patients are not entirely dependent at this stage and are still capable of independent activity, and may be effectively managed by timely adjustment of the treatment. As PD patients progress to the advanced stage, they typically require intensive and individualized multidisciplinary pharmacological and non-pharmacological care to manage disease and treatment-related complications . FurtherDespite the wealth of knowledge of PD pathology and its natural course, there is a lack of global consensus regarding the precise definition of APD. This is largely due to its heterogenic origins, the vast variety of subphenotypes, variable trajectories and prognostics, as well as the absence of robust biomarkers for disease progression. In turn, it has challenged development of standardized care guidelines, and has brought to a lag in appropriate alignment of diagnostic instruments and grading scales for classification of disease severity and evaluation of treatment and management strategies. Furthermore, it has stymied early APD identification, and tailoring of interventional programs and appropriate allocation of funds. The most popular assessment tools use PD duration as an anchor and primarily focus on cardinal overt motor features. They have been proven to lack universality due to different phenotypes and rates of disease progression and generally fail to recognize the true weight of non-motor features on patient performance and quality of life . Recent In line with the global efforts to moderate PD impact on quality of life, the authors, representing a panel of Israeli movement disorders specialists, propose to define APD in the International Classification of Disease 11th revision (ICD-11) as a unique health entity that demands adjusted healthcare provider attitudes and relevant social services. Modification of the ICD-11 PD coding should include severity- and fluctuation-based subcodes that accurately capture APD and distinguish it from early-stage PD. While very few diseases have been assigned severity-based subcodes in ICD-10 , the growing evidence of the distinct clinical manifestations and medical needs of this patient subpopulation, justifies reconsideration of its coding status.In addition, we call for optimization of the Delphi criteria by extending them to include a more extensive list of non-motor features, such as autonomic disturbances , pain, daytime somnolence, and apathy. Furthermore, in the opinion of the Israeli panel, the Delphi criteria for APD from motor fluctuations, regardless of their duration and severity, should be the main eligibility criteria for advanced therapy. Evaluation of PD patients should be based on a structured questionnaire applied as a preliminary tool geared to be implemented by community neurologists or case managers . Patients with suspected APD should undergo multidisciplinary evaluation, ideally in specialized APD centers, to define the extent of disability, outline an individualized treatment program, and weigh the need for rehabilitation and social support services. Routine evaluations should be adequately sensitive to allow for timely diagnosis of palliative-stage PD, which should be addressed by end-of-life palliative/hospice referral .Management protocols should implement personalized patient-centered and holistic approaches to target the heterogenic manifestations and course of PD. These should include tools for timely diagnosis and treatment of osteoporosis. Furthermore, patients should be informed of opportunities to participate in relevant clinical trials. In addition to the clinical benefits of integrated and coordinated care , such prThe panel also suggests standardization of DAT eligibility and prioritization of its use to early-stage APD patients, while minimizing its use in palliative-stage patients. Furthermore, integration of telemedicine and nurse practitioners can tighten surveillance and improve treatment optimization efforts.These can be further supported by establishment of a network of community physicians, led by movement disorder specialists, to promote case-sharing, research dissemination and exchange of professional know-how.Expanded APD-geared health baskets clearly outline eligibility for reimbursement for a part/full time paid attendant, mobility allowance, and rehabilitation services. In parallel, attention should be paid to informal and non-specialized caregivers by providing them PD-specific education and support . PatientIn summary, the globally rising life expectancy has increased the prevalence of PD in general, and of APD, in particular. Appreciation of the heterogeneity of PD etiology and manifestations has underscored the need for updated PD coding. Precise and standardized definition and evaluation of APD will promote earlier APD identification and timely referral to adequate therapies and specialists. Moreover, it will enhance holistic management, which is expected to markedly improve APD patient quality of life. Future works should focus on validating the proposed extension of the Delphi APD criteria, and on tailoring treatment to APD phenotypes.TG: draft preparation and literature search. All authors conceptualized, critically revised, and approved the submitted version."} +{"text": "Advances in Theranostics: Novel Nanotools for the Treatment and Diagnosis of Tumors\u201d presents a small series of articles reporting the most exciting research, novel application studies and scientific progress in the field of nanostructures and functional materials used in the field of oncological theranostics. The limitation in the effectiveness of traditional approaches in treating cancer are largely demonstrated in this Topic Research Topic, providing examples of stimuli-sensitive and technologically advanced novel nanoplatforms that, in a multidisciplinary and collaborative approach, involve the contribution of different disciplines ranging from material sciences, biology, immunology, medicine as well as diagnosis. Nanotechnology platforms that can combine both therapy and diagnosis are especially interesting, as this approach allows combining targeted therapy and monitoring of efficacy with minimal invasiveness and systemic toxicity. Multifunctional nanomedicines combining responsiveness to tumor microenvironment, targeting, therapy, sensitivity, and early-stage detection are highly advantageous and are most likely the future clinical direction of cancer management. The high number of views obtained by the articles published in this Research Topic Collection shows a clear interest of the scientific community for nanomedicine and theranostics and motivated the edition of this Topic Research Topic. Our goals are to facilitate access to thematically related papers and draw attention to the current activity and trends in addressing remaining challenges, ultimately serving as a valuable resource to the biomedical and pharmaceutical science community and beyond. The Research Topic is comprised of four selected peer-reviewed manuscripts derived from the fields of (bio) materials science and engineering, pharmaceutics, and biology.The Research Topic entitled \u201cCong et al. opens this Topic Research Topic by overviewing the abnormal pathophysiological characteristics of the tumor microenvironment, including acidosis, overexpression of special enzymes, hypoxia, and high levels of ROS, GSH, and ATP. These characteristics are exploited in drug delivery systems (DDSs) design to trigger the spatial and temporal control of drugs and/or diagnostic agents in tumor tissues. The latest advances in the field of DDSs responsive to stimuli found in tumor microenvironment are highlighted in this review paper, emphasizing their ability to effectively realize tumor-site specific drug, decrease the injected dose and systemic toxicity. Finally, a critical analysis of the existing bottlenecks to the clinical translation of these technologies are also critically discussed and include, among others, DDS complexity, sub-optimal biocompatibility, patient biological heterogeneity, leading to varying response, size control and immune system reaction.The review paper by Xu et al., who proposed a nanoparticle-based platform for the effective presentation of sonosensitizers to hypoxic tumor tissues. In this work, a core-shell structured nanoparticle (IR780/PLGA@MnO2NPs) loaded with IR780 and manganese dioxide (MnO2) was developed as a nanocarrier to transport the sonosensitizer IR780 and the generated oxygen into the tumor tissue. The MnO2 shell layer of IR780/PLGA@MnO2NPs was designed to respond to tumor microenvironment, by releasing IR780 and generating reactive oxygen species in response to tumor acidity and excess of H2O2. As a result, the generated oxygen relieves tumor tissue hypoxia and kills tumor cells, while the generated Mn enhances magnetic resonance imaging (MRI) signal intensity by acting as a contrast agent for MRI. The developed multi-layer core-shell nanostructure was validated in vitro and in vivo on a breast cancer mice model, providing a promising strategy for cancer diagnosis and sonodynamic treatment, with potential future application in cancer theranostics.An example of stimuli-sensitive nanoDDS for tumor diagnosis and treatment if offered by Ranjbari et al. described nanostructure two-dimensional Mxene as potential materials in the diagnosis and treatment of breast cancer. Different synthetic methods for producing biocompatible Mxenes and their application to the detection and therapy of breast cancer are overviewed. The authors point out the high biocompatibility profile of. MXenes\u2019 and their surface modification flexibility, leading to multifunctional properties, such as preferential agglomeration at tumor sites for photothermal treatment by the non-covalent reactions on the MXene surface with PEG, CS, SP, and PVP materials. The synthetic MXenes could be potentially applied in the fields of, antimicrobial materials, attributes, drug delivery, engineering of tissue, and extensive near-infrared sorption.Wang et al., dealing with the assessment of the diagnostic value of 18F-NaF PET/CT in diagnosing bone metastases in patients with nasopharyngeal carcinoma (NPC) using, for the first time, visual and quantitative analyses. The study was carried out retrospectively, analyzing 164 patients with NPC who underwent 18F-NaF PET/CT between 2017 and 2021. They showed that visual analysis of 18F-NaF PET/CT findings is accompanied by high sensitivity and specificity for the diagnosis of bone metastases in NPC. Furthermore, the quantitative analysis of PET/CT (SUVmax), displaying the advantage of higher objectivity and reproducibility than visual qualitative analysis, was demonstrated a valuable tool for the differential diagnosis between bone metastases in NPC and benign bone lesions.Breast cancer is also tackled in the original research article by In conclusion, this Research Topic Collection represents a small cross-section of the research work performed around the topic of novel nanotools for the treatment and diagnosis of tumors, having the scope to promote ideas, show new technologies, present the state of the art in the field, and critically discuss current challenges still existing in this area and possibilities for overcoming these challenges. We are convinced that this article Research Topic will be significantly relevant to the scientific community and beyond to spotlight cutting edge studies and start initiatives and collaborations among scientists in this field.This Research Topic aims at collecting recent advances in theranostic nanoplatforms, with a special emphasis on originally designed systems. Nanoplatforms combining drug delivery, targeting, and tumor monitoring approaches could be of particular interest when designed to address the challenge to specifically reach tumors in specific body districts, or treat tumors of different stages."} +{"text": "Background: Six diverse Demographic Development and Environmental Surveillance System (DDESS) sites were established in urban slum, urban resettlement, peri-urban, rural, and tribal areas located in Northern, North-East, Eastern, and Southern regions of India from June 2020 to March 2022. Understanding the community dynamics and engaging people in the community is critically important in the process of establishing DDESS. We ascertained the barriers, challenges, and facilitators during the establishment of multiple DDESS sites across India. Methods: This was a cross-sectional descriptive mixed-methods study. Results: Multiple barriers and challenges encountered were reported in the process of community engagement (CE), such as geographical inaccessibility, language barriers, adverse weather, non-responsiveness due to perceived lack of individual benefit or financial gain, fear of contracting COVID-19, COVID-19 vaccine hesitancy, etc. Facilitators in the CE process were pre-existing links with the community, constitution of community advisory boards, community need assessment, concomitant delivery of outreach health services, and skill-building facilities. Conclusion: Most community barriers in the development of DDESS sites in resource-limited settings can be overcome through a multipronged approach, including effective community engagement by focusing on demonstrating trust at the local level, enlisting community mobilization and support, utilizing pre-existing community linkages, initiating community diagnosis, and meeting perceived community health needs. Demographic Development and Environmental Surveillance Systems (DDESS) enable the development of novel, innovative, and real-world solutions for achieving healthier, prosperous, and sustainable communities in resource-limited settings ,2,3. In Globally, there are over thirty demographic surveillance sites across Asia, Africa, and America . For obtAccording to the Centre for Disease Control (CDC), community engagement (CE) is the process of working collaboratively with and through groups of people affiliated by geographic proximity, special interest, or similar situations to address issues affecting the well-being of those people . Local cThere is a paucity of evidence towards understanding the real-world strategies and solutions that enable effective CE in public health and developmental research . MoreoveStudy Design: This was a cross-sectional descriptive mixed-methods study. Baseline data were collected from the ongoing multi-site DDESS project in India.Study Setting: Six diverse DDESS sites across India established during the period from June 2020 to March 2022 were included .All these sites were pre-existing field practice areas of the concerned medical colleges and research organizations. At each site, data were collected on the type of settlement , demographic, and health characteristics from both DDESS surveys and non-DDESS secondary data sources, such as previous local surveys, census data, community and facility-based research studies conducted in the area, and medical and health records from the local government primary care facilities. Description of the study sites (DDESS): The six DDESS sites were slated to be developed by six respective institutions: MAMC, Gokulpuri, New Delhi; CHRD-SAS, Dakshinpuri, New Delhi; INCLEN, Mawphlang and Sohiong, Meghalaya; ICMR-RMRC, Bhubaneswar, Tigiria, Cuttack, Odisha; AMC, Vishakapatnam, Andra Pradesh; and PIMS, Marakanam-Villupuram district, Chitamur-Chengalpet district, Tamilnadu, and Muthialpet in U.T. Puducherry). The basic sociodemographic characteristics of the study population are reported in The Gokulpuri DDESS is an urban low-income neighbourhood in the North-East district of Delhi comprising an urban resettlement colony, urban slum, and a village. Of the total population, 91.6% are literate, 94.94% belong to the Hindu religion, and 52.28% belong to the scheduled caste. The settlement has very few health care facilities, while the nearest referral health facility is around 6\u20137 km away.The Dakshinpuri DDESS is an urban low-income neighbourhood located in the Southern district of Delhi. A total of 99.55% of the population is urban and 78.91% follow the Hindu religion, followed by the Muslim and Sikh religions. The settlement has 3 healthcare facilities for local residents.The Mawphlang DDESS spreads across the 364.48 Sq Km area in the Mawphlang and Sohiong administrative blocks of the East Khasi Hills district of Meghalaya state. The site is predominantly occupied by the Khasi tribal community (99.5%). In total, 80.7% of the population are Christians and the site has very high literacy rates (82.8%). There are 2 community health centres, 1 primary health centre and 9 sub-centres.The Tigiria DDESS is a predominantly rural area (89.2%). A total of 95.17% of people belong to the Hindu religion, followed by other minority communities. The majority belong to the upper caste (83.4%), followed by the schedule caste (13.2%) and the schedule tribe (3.4%). Cultivation is the main occupation. While the site has 2 community health centres, 4 primary health centres and 13 sub-centres, the referral health centre is around 15\u201320 km away.The Simhachalam DDESS is located in the western part of Visakhapatnam and is predominantly peri-urban. A total of 95.9% of the population belong to the Hindu religion. The scheduled caste (7.6%) and scheduled tribe (14.3%) constitute one fourth of the population. Occupations are mostly service or running small businesses. The site has the fair availability of 92 hospitals in the urban setting and 13 hospitals in the rural setting, respectively. The Marakanam, Chitamur, and Muthialpet DDESS is predominantly rural, with the average literacy rate being 65.2%. The major occupations are agriculture and fishing. The site has an availability of 48 hospitals in the rural setting, compared to only 2 hospitals in the urban facilities for the residents.Sample size and sampling strategy: A universal sample (census) of all the households located in the DDESS sites were included in this study through a standardized house-to-house survey process. Data collection (quantitative) was conducted following a systematic process followed for the establishment of comprehensive community-based surveillance sites . BroadlyData entry: All 6 DDESS sites used Android-based electronic questionnaires called \u2018SOMAARTH 1 & SOMAARTH 3\u2019. The enumerator asked the respondent questions in a face-to-face interview and the responses were recorded by the enumerator directly into their data collection tablet. Data were securely saved in the Amazon Web Service (AWS\u00a9) server. Data analysis: Data were downloaded from the server and cleaned using STATA Version 15 and IBM SPSS Statistics for Windows, Version 25.0. . Data related to key sociodemographic characteristics of the study populations were reported as frequency and percentages.Written transcripts were prepared for the interviews as part of this study. Thematic analysis was used for identification of recurrent themes, all of which had been identified a priori from a comprehensive review of the literature. Key findings from each of the sites were centrally analysed using qualitative synthesis techniques, such as textual narrative and framework synthesis for the identification of the key barriers, facilitators, and coping strategies in community engagement during the establishment of DDESS sites. Analytical conceptual framework: The CE activities undertaken by the study teams were classified within a conceptual framework comprising the previously validated five stages of the CE continuum ,18, whicThe locations of six DDESS sites included in this study are presented in (A)Limited or lack of understanding of locally spoken languages: India is the world\u2019s most linguistically diverse country. Absence of familiarity with the locally spoken language and dialect posed challenges for investigators and project staff, especially in remote and tribal regions with predominantly indigenous populations. For instance, Khasi, an Austroasiastic language, is predominantly spoken in the tribal areas of Mawphlang and Sohiong blocks of the North-Eastern state of Meghalaya, having just over 1 million speakers. This caused difficulty for site investigators unfamiliar with the local language to communicate with members of the local community that precluded effective CE and the data collection processes.Poor road connectivity and difficult terrain: Some DDESS sites were located in areas that were not connected with all-weather motorable roads and caused difficult access. The survey team had to travel considerable distances by foot to reach these remote villages. The interior areas located in forest and hilly terrain were difficult to reach, and more so during the rainy season.Inclement weather and extreme climatic conditions: While DDESS sites in Meghalaya were the wettest, the site of Odisha is near the riverine regions. Such sites are prone to flood and difficult to carry out field activities in during the rainy seasons. The temperature extremities (summer in southern DDESS sites and winter in the northern part) and heavy rainfall were also detrimental to conducting routine project activities.Expectation for financial benefits: Some community members had expectations of financial gain or compensation for participating in or facilitating the project and research activities in their sites. In the absence of provision for any direct financial benefit, such members were disinclined to participate or consent.Fear of wage loss: Some family members, especially the adults who were mainly involved in earning livelihoods for their family, could not afford to spend time with the team during their working hours.Migration: Some people migrate in search of jobs, even with their family. This causes a loss in follow-up of the registered population and a challenge to DDESS sustainability.Dispute over land ownership: Households with prevailing legal disputes about their land ownership were initially found to be resentful and reluctant to share any of their personal information as part of the study. In hilly areas, even the village councils are involved in disputes over the village boundaries, and some of them do not agree with the inter-village boundaries given in the government records.Pandemic and fear of COVID-19 infection: The COVID-19 pandemic created a lot of panic among the community, and the imposed restrictions created hindrance for initiating interactions with outsiders in the sites. The unavailability of hospital beds for COVID patients during the COVID peak resulted in non-cooperation of the community with the research team.Distrust for COVID-19 vaccination: Communities, particularly rural and tribal communities, were reluctant to accept COVID-19 vaccination. They were panic-stricken and agitated at the prospect of engaging with people working in the health sector or associated with hospitals. There was also resistance among communities against the implementation of non-pharmaceutical measures, such as social distancing and following COVID norms. Dissatisfaction with suboptimal functioning of primary care facilities during the pandemic, reduced staffing, and services as a result of the pandemic were a major issue faced by the surveillance team.Unpleasant past experiences: Some of the community members had unpleasant experience of supporting governmental or non-governmental activities in the past, resulting in non-cooperation. For instance, no personal benefits were received by the community members for previous participation in other surveillance activities. Some community members had unpleasant experiences of not receiving any financial or other benefits promised to them for their participation in prior community-based research activities conducted in their areas, which further compounded their unwillingness to participate in the present research project.Engagement of locally hired people in the enumeration team may bring undue demands and interference from the local community, such as mounting pressure to hire undeserving candidates, negotiations for the payment amount or rolling back the termination order, etc.Barriers encountered during community engagement (CE). The significance of CE exists both during the establishment of the DDESS and ensuing quality data collection from the sites. The research teams encountered many barriers and challenges in the process of ensuring adequate CE. While some common challenges were observed in multiple sites, some were site-specific:(B)Pre-existing community links with the research teams by virtue of being the field practice areas of the respective institutions; b. broadcasts of the activities conducted by the SOMAARTH DDESS among the public by the village council through the public announcement system; c. involvement and engagement of community-level frontline health workers ; and d. involvement of village volunteers were helpful in ensuring community engagement activities.Enablers to achieve CE: Many enabling factors were noticed that facilitated CE, which are described below.(C)Formation of a community advisory board (CAB) at each DDESS site: Each study site formed a CAB by identifying and recruiting significant stakeholders following a common CAB charter for better functioning of the DDESS site. Meetings among the members of the advisory committee were held to identify and address existing community-level issues to achieve trust and better community involvement and participation. The CAB helps in supporting advocacy, sensitization campaigns related to the project, and mitigation of any conflict, while ensuring that beliefs and cultural disparities among community members are respected. The CAB gives advice and recommendations to the research team but has no administrative or legal responsibilities. The research team informs the CAB before carrying out any new activities. The board provides guidance and assistance in planning and implementing the activities of the project by ensuring that the activities are conducted in an informed and transparent manner that is acceptable to the community.Identifying and involving community volunteers: Some of the DDESS sites identified and involved local community volunteers, such as Panchayati Raj Institution (PRI) members, schoolteachers, ASHA, Anganwadi workers, etc. These community volunteers were engaged during the community mobilization process. They provided enormous support during community consultation, village boundary mapping, and for health awareness initiatives towards strengthening surveillance activity. In order to avoid the interference of the community in the recruitment and research processes, a detailed SOP for the village volunteers\u2019 recruitment was developed and followed by the sites. The formal recruitment process for the engagement of village volunteers included vacancy announcements in all the site villages/localities, organization of written examinations and tablet tests at clusters for ensuring the participation of volunteers from the villages which are far from the office location, followed by face-to-face interviews with the successful candidates. A merit list was prepared and publicly displayed for the transparency of the process and recruitment of the village volunteers was carried out on the basis of the merit list.Community consultations involving key stakeholders: Prior to data collection, the population was consulted and appraised of the project objectives. During the meetings, key stakeholders, such as local health care providers, schoolteachers, and community leaders were also involved. Many stakeholders played a role as a link between the community and researchers. This improved the trust among the people to participate and support the project\u2019s activities.Undertaking other health-related activities: Apart from the project-related activities, the DDESS sites also organized some other health initiatives, such as health camps, COVID-19 Serosurveys, screening for non-communicable diseases (NCDs), and oral health problems. Community awareness and sensitization programs based on prevailing key health issues, such as the COVID-19 pandemic situation, prenatal/postnatal care, multidrug-resistant tuberculosis (MDR-TB), and vector-borne diseases, such as dengue, chikungunya, etc., were supported by the community stakeholders.The participatory mapping and data collection approach helped in gathering updated relevant information in the manner in which the community perceived them. In villages where boundaries were not available in the government census maps, research teams were able to gather information through the community consultation process.Strategies adopted for better community engagement: In view of the existing barriers, challenges and enablers, various site-specific strategies were undertaken in order to achieve better community engagement .FormatiThe barriers and enablers encountered for CE, and the strategies adopted to achieve better CE, are depicted as a conceptual framework .A comparison od the barriers and enablers encountered, and strategies adopted for better community engagement, across the six DDESS sites, is presented in The establishment of DDESS is important to study a population cohort through collecting data longitudinally and monitoring their health and wellbeing. This helps to understanding the community dynamics, the existing challenges, and barriers better to developing appropriate disease-control and prevention strategies. These sites enable epidemiological surveillance through prospective data collection on population dynamics and health measures in a specific geographical area, generating data on a country\u2019s vital statistics related to disease burden and demographic information that instructs and advances public health policy formation .There is growing global recognition of the role of CE in facilitating and accentuating research activities planned and conducted within communities. However, there is a lack of global consensus guidelines on assessing the quality of CE processes . FurtherIn this study, all the participating organizations had been functioning in their respective sites for >10 years and were engaged in various public health services, and this activity helped the research team to acquire knowledge and understand the beliefs and socio-cultural practices of the local population. Operational challenges for the sustained functioning of the DDESS sites are evident from the requirement of frequent updating of population data prospectively often resulting in research fatigue amongst respondents . InaccesSome DDESS sites are being developed amongst vulnerable communities, such as tribals, rural, and urban poor, necessitating the need for community consultation to identify community concerns which may influence community participation. In this regard, Community Advisory Boards (CABs) were frequently used to support CE by helping research teams honour the community values, and frequently also guide decision-making when deliberating on the choice of community-based research and supportive activities ,28,29. AFurthermore, the suboptimal functioning of existing health surveillance systems in the more geographically inaccessible remote, rural, and tribal locations renders the monitoring and detecting of the vital events and associated data management difficult ,32. All Effective community mobilization and collaboration with motivated community partners are also crucial towards identifying the prevalent social determinants of health that impact population health ,6. In thThe establishment of DDESS sites intends to bridge the health- and demography-related data gaps necessary for informing and strengthening public health policies in developing countries. The specific challenges encountered in establishing DDESS sites in different areas, and the approaches and strategies implemented to overcome these, may be instructive in developing comparable platforms under similar conditions. Most community barriers exist in the development of DDESS sites in resource-limited settings, but most can be overcome through effective community engagement by focusing on enlisting local community trust, mobilization and support, utilizing pre-existing community linkages, community diagnosis, and meeting health needs. The study underscores the need for rigorous community mobilisation and regular stakeholder participation, for a better understanding of community dynamics, and aiding community engagement."} +{"text": "Screening and brief intervention (SBI) is a low-intensity, time-limited psychosocial treatment for substance misuse. The therapeutic principle is grounded on the social cognitive theory encompassing different combinations of personalized feedback, styles of motivational interviewing (MI), decisional balance, advice, identifying and managing high-risk situations, and providing a personalized menu of options to reduce or stop substance use . SBI couAlthough there are several screening instruments to detect and monitor substance misuse, the validity of those screening tools across countries, age groups, and study settings are not yet consistent . For insThe effectiveness of alcohol BI among adults in primary and general healthcare is consistent and robust , 12. HowThe implementation gap of BI is possibly much wider than the evidence gap, especially for alcohol misuse. The practice of alcohol BI in clinical settings, despite the support from policymakers, is sub-optimal. Scandinavian countries, the UK, and Italy, which have integrated alcohol BI into their healthcare system, show only a minority population are screened (10\u201337%) for alcohol use by their primary care physicians, and a further minority receive advice to cut down . The posLevy et al. examined the uptake and preliminary outcomes of a teleconsultation model for pediatric primary care. The teleconsultation program from Massachusetts, US, provides an implementation model for SBI in children and adolescents in a limited resource context. Another electronic health record system-based study from the USA tested the changes in unhealthy alcohol use pre- and post-pandemic. The authors identified vulnerable subgroups and suggested using telehealth to reach out to these groups. Al Mahmud et al. explored the format and themes of another digital self-help option for alcohol cessation, the YouTube videos. In another study, the authors explored the need for brief counseling and intervention based on a theory-driven approach in the context of sexualized drug use, also known as Chemsex. Future studies on BI in special populations and contexts might use a theory-driven, tailor-made approach . Finally, a South African study proposes screening for suicidal behavior in persons with heroin misuse- increasing the ambit of screening in SBI.This Research Topic revisits the evidence of alcohol BI in the criminal justice system and the integration of alcohol intervention into general healthcare settings. The latter study focuses exclusively on sub-Saharan Africa. These two studies aim to review and update the evidence of alcohol BI in non-primary care and low-resource settings. This Research Topic highlights the evidence and the implementation gap of SBI in substance misuse. This unpacking of the research gaps may motivate further research on SBI. It may provide directions to funders and policymakers.AG, SM, and DN-B jointly conceived the idea of the Research Topic and the editorial. AG wrote the first draft. SM and DN-B reviewed and edited the draft. All authors reviewed the final draft and approved it.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "A 46-year-old female patient came to the Dermatology outpatient clinic complaining of asymptomatic breast lesions for ten years. She reported a weight gain of approximately 50\u202fkg during this period and reported being an active smoker with a tobacco load of 42 pack/year. Dermatological examination showed erythematous to violaceous reticulated lesions on both breasts. Some areas showed shallow ulcerations .Figure 1Histopathology revealed a rectified epidermis and proliferation of small vessels, more intense in the upper dermis, but extending to the middle dermis without cell atypia . The imma)Kaposi's Sarcomab)Low-grade angiosarcomac)Diffuse dermal angiomatosis of the breastd)CalciphylaxisBased on the clinical-pathological correlation, a diagnosis of diffuse dermal angiomatosis of the breast was made. Laboratory tests including ANF, lupus anticoagulant, anticardiolipin, anti-beta-2 glycoprotein, C and S proteins were normal. The CT angiography excluded venous or arterial thrombosis. The patient lost 20\u202fkg in one year and there was complete regression without any medical or surgical treatment . DespiteDiffuse dermal angiomatosis of the breast (DDAB) is a poorly described entity that affects exclusively middle-aged, obese women with macromastia and who are smokers.The pathogenesis likely involves tissue ischemia leading to an increase in endothelial growth factors and neoangiogenesis.The management of DDAB requires treatment of the underlying cause of tissue ischemia. The investigation to exclude the causes of ischemia is mandatory. Advice on weight loss, smoking cessation, and control of cardiovascular risk factors such as hypertension or hyperlipidemia are essential. Drug therapy includes the use of isotretinoin, anticoagulants, acetylsalicylic acid, pentoxifylline, and oral corticosteroids, but responses are variable.None declared.Bruno de Castro e Souza: Drafting and editing of the manuscript; critical review of the literature.Esio Pessoa Caracas de Souza: Collection, analysis, and interpretation of data; drafting and editing of the manuscript; critical review of the literature.Neusa Yuriko Sakai Valente: Design and planning of the study; drafting and editing of the manuscript; critical review of the literature; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case.Jos\u00e9 Antonio Sanches: Design and planning of the study; drafting and editing of manuscript; critical review of the literature; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied case.None declared."} +{"text": "The coronavirus pandemic (COVID-19) has affected the functioning and capacity of healthcare systems worldwide. COVID-19 has also disproportionately affected older adults, including those living with dementia. In the context of COVID-19, decision-making surrounding place of care and place of death in this population involves significant new challenges.To explore key factors that influence place of care and place of death decisions in older adults. A secondary aim was to investigate key factors that influence the process and outcome of these decisions in older adults. To apply findings from current evidence to the context of COVID-19.Rapid review of reviews, undertaken using WHO guidance for rapid reviews. Ten papers were included for full data extraction. These papers were published between 2005-2020. Data extracted was synthesised using narrative synthesis, with thematic analysis and tabulation.Papers included discussed actual place of death, as well as preferred. Results were divided into papers that explored the process of decision-making, and those that explored decision-making outcomes. Factors such as caregiver capacity, the availability of multidisciplinary teams, cultural appropriateness of care packages and advanced care planning were found to be key.The process and outcomes of decision-making for older people are affected by many factors \u2013 all of which have the potential to influence both patients and caregivers experience of illness and dying. Within the context of COVID-19, such decisions may have to be made rapidly and be reflexive to changing needs of systems and of families and patients."} +{"text": "Cancer, the second leading cause of death worldwide, continues to represent an impressive challenge for researchers and clinicians. Indeed, radiotherapy and chemotherapy are still the main therapeutic options, associated, however, with undesirable toxicity. Furthermore, chemotherapy is frequently accompanied by the appearance of the drug resistance, which, in turn, further limits the overall success of the therapy. In the last decades, much work has been devoted to the development and/or implementation of strategies of cellular and molecular targeted therapies. For instance, Tamoxifen, which specifically targets the estrogen receptor in breast cancer, is the first drug approved by the Food and Drug administration (FDA) in 1977 as cellular targeted therapy for the treatment of metastatic breast-cancer-affected patients . On the In the \u201cTargeted Therapies for Cancer\u201d Special Issue, six original articles, one perspective article and three reviews intend to provide an overview on the state-of-the-art of targeted therapies for cancer, covering some of the aspects of this broad field. This Editorial briefly summarizes findings and highlights derived from the published manuscripts.Jebali and colleagues focused The involvement of Lamin A/C (LMNA gene) in the tumorigenesis and progression of glioblastoma multiforme (GBM) was instead investigated by Gatti and colleagues . It was In addition, the study conducted by Yu and colleagues is focusThe implication of Nuclear factor erythroid-2 related factor-2 (Nrf2) in breast cancer (BC) responses to chemotherapy was instead investigated by Bovilla and colleagues . The expEliseev and colleagues focused Rango and colleagues investigFresnais and colleagues presenteA new and interesting approach of cancer therapy consisting in the targeted osmotic lysis (TOL) was presented by the review article of Gould and Paul . This apAdvances and limitations in the development of Antibody-Drug Conjugates (ADCs) are discussed in the review article from Mckertish and Kayser . ADCs arThe review article by Wolf focuses,"} +{"text": "Traumatic Brain Injury (TBI) represents a major medical, healthcare, and socioeconomic problem worldwide and one of the most important causes of disability and mortality. Over 700 participants from various countries attended the much-expected educational event, which aimed to set the stage for lively debates on a plethora of aspects under the broad domain of neurosciences. Thrilling lectures and presentations took place over two days and the event included 6 sessions and 4 interactive panels held by 26 speakers.The 20The event brought together a lively audience with diverse backgrounds, such as neurology, psychology, neurosurgery, neurorehabilitation, psychiatry, psychotherapy, and public health. The Congress was opened by the steering committee, which included Klaus von Wild (Germany), Dafin F. Muresanu (Romania), Johannes Vester (Germany), Nicole von Steinb\u00fcchel (Germany), and Volker H\u00f6mberg (Germany).Session one introduced the audience to the topic of TBI research and was structured into two presentations. The former, by Johannes Vester (Germany), the AMN president and Associate Professor at the Department of Neuroscience from Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca (Romania), was centered around the multidimensional approaches in TBI research and presented insights from the Cerebrolysin Asian Pacific Trial in Acute Brain Injury and Neurorecovery (CAPTAIN) I and II trials. Moreover, Prof. Vester discussed the limitations of the dichotomization of results, of binary thinking in TBI research, and the importance of full-scale analysis.e.g. Intelligent Mechanical Training Devices, Gaming Technology for motor and cognitive training, Brain-Computer Interfaces, Neuromodulation) in contrast to low-tech options , comparing their limitations and benefits. Furthermore, Prof. H\u00f6mberg offered insight into the role of digital communication strategies in allowing the dissemination of knowledge and skills to larger populations.The second presentation, by Volker H\u00f6mberg (Germany), Chairman of AMN Scientific Program Committee and President-Elect of the World Federation for Neurorehabilitation (WFNR), approached the vast and complex subject of neurorehabilitation, discussing future approaches. Neurorehabilitation of TBI represents a vast topic, ranging from early rehabilitation of patients to support and reintegration into the social and professional environment. Therefore, discussing solutions for neurorehabilitation is of utmost importance, especially considering the gap experienced in low- and middle-income countries (LMIC) with regard to meeting the needs of the patients, as well as the disruption caused by the COVID-19 pandemic. Prof. H\u00f6mberg discussed the role of high-tech options , ended the session with a presentation entitled \u201cNew developments in TBI clinical research from a C-RETURN study\u201d highlighting the importance of continuous research in the domain of neurotrauma. Prof. Muresanu suggested that the functional effects of lesions on brain networks require a change in our approach to neurorehabilitation, shifting the emphasis of treatment and restorative trials towards modulating the activity levels in preexisting networks and showcased the role of multimodal drugs in both neuroprotection and neurorecovery. Moreover, Prof. Muresanu discussed the importance of the CAPTAIN trials in TBI research as the first series of trials with multidimensional approaches based on full outcome scales, and the vital role of the C-RETURN study.Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). The inspiring CENTER-TBI is a longitudinal prospective study describing Intensive Care Unit (ICU) admission policies, management, and outcome for TBI patients. Prof. Maas showcased the importance of care in the initial phase at the emergency scene and the post-acute care phase. The necessity for the CENTER-TBI study was two-fold, first, the need for improved characterization and classification, and secondly, the issue of the heterogeneity of TBI as a disease, which motivated the search for best practices. Moreover, the importance of guidelines was discussed, as well as the shift towards multimodal approaches in treatment, the disparities in care, and the risk of incomplete recovery following a mild TBI. Lastly, the presentation ended with a statement on the importance of the CENTER-TBI study.The second session, having Prof. Johannes Vester (Germany) and Prof. Andrew Maas (Belgium) as chairpersons, further discussed the role of research in TBI. The session began with a presentation by Andrew Maas (Belgium), Emeritus Professor of Neurosurgery at the Antwerp University Hospital and University of Antwerp (Belgium), on the continuity of care in the trauma chain, presenting the experience of Furthermore, the session was followed by an insight into the CAPTAIN trial from Christian Matula (Austria), Professor and Vice-Chairman at the Department of Neurosurgery from Medical University of Vienna (Austria). In the past years, a few studies significantly impacted the management and outcomes of TBI. The CAPTAIN trial reveals impactful insight into the effect of the pharmacological agent Cerebrolysin. After discussing the neuroprotective and neurorecovery mechanisms of the brain following an acute lesion, he highlighted the importance of neurotrophic factors in the process of protection and recovery. Moreover, Prof. Matula discussed the objectives of the CAPTAIN trial while showcasing the problems of reductionist approaches, and the importance of multidimensional analysis in providing a new direction for clinical and statistical thinking. The results of the trials could be a door opener for future guidelines. Lastly, the grim realities of post-TBI depression encountered in nearly half of all TBI patients were discussed, highlighting the need for proper approaches. As proof of the necessity of multimodal approaches, he ended the presentation with a glimpse into the exciting Neurotrauma Treatment Simulation Center from Vienna, a training program focusing on the patient pathway to recovery.The final presentation offered an immersive incursion into the tools and instruments necessary for developing and providing the best practices in neurotrauma care by Mark Bayley (Canada), Program Medical Director and Psychiatrist-in-Chief at UHN-Toronto Rehabilitation Institute (Canada), underlining the constant need to improve existing therapies and find new treatments. Prof. Bayley aided the participants in discovering evidence-based resources to support TBI care and rehabilitation, including reviews and clinical practice guidelines, navigating web-based resources developed in Canada, providing demonstrative cases, and, lastly, using the TRICORDRR (Toronto Rehabilitation Institute Concussion Outcome Risk Determination & Rehab Recommendations) tool for the identification of patients most likely to require long-term special care for conclussions.rd session, having Prof. Nicole von Steinb\u00fcchel (Germany) and dr. Juan Carlos Arango-Lasprilla (Spain) as chairpersons. The session centered around neuropsychological aspects of TBI as well as TBI rehabilitation.The first day of the online AMN Congress of 2022 was completed by the 3Firstly, Nicole von Steinb\u00fcchel (Germany), Director of the Institute of Medical Psychology and Medical Sociology of the University Medical Center at Georg-August-University of Goettingen (Germany), outlined the domains and new trends in neuropsychological rehabilitation. The presentation started with an incursion into the past, presenting a reality that remains in place to this day, respectively that only a minority of patients suffering a stroke or traumatic brain injury receive adequate rehabilitation aid. This reality supports the need to enhance and personalize the post-TBI treatment and rehabilitation, especially regarding cognitive function, but also in treating psychiatric, psychological, and daily life problems arising after neurotrauma. With physical treatment receiving more attention in TBI, it is essential to consider the need for proper neurorehabilitation. The sequelae of TBI can be complex and could hamper the reintegration of patients into society, as well as their quality of life. With depression, anxiety, and Post-Traumatic Stress Disorder (PTSD) presented in a significant number of patients early on after a TBI and persisting up to one year, the need for systematic longitudinal evaluation and therapy is apparent. Prof. von Steinb\u00fcchel described how neurological rehabilitation aims to improve functions through restitution, substitution, activation, or integration, with each of the above-mentioned requiring specific evaluation and therapeutic strategies in the context of a multidimensional perspective. Recent years have brought the development of new therapeutic technologies, the improvement of neuroimaging techniques, as well as the development and implementation of international multicenter studies to address the gaps in information on neuroimaging and analytic algorithms, the influence of biomarkers on outcomes, the multidimensional outcome assessment, thus paving an encouraging road towards comprehensive neurotrauma care and rehabilitation.Secondly, Marina Zeldovich (Germany), Dr. rer. nat. at the Institute of Medical Psychology and Medical Sociology in G\u00f6ttingen (Germany), discussed the results of the CENTER-TBI study on patient-reported and neuropsychological outcomes after TBI. Patients after a TBI often report anxiety, depression, PTSD, post-concussion symptoms, and a decreased quality of life. In addition to clinical diagnosis tools, the patient-reported outcomes offer a more comprehensive image of the subject. To assess modifications in cognitive functions, information on performance-based outcomes provides relevant insight into patient status after a TBI. Dr. Zeldovich presented the findings of the CENTER-TBI studies, highlighting the need for multimodal outcome assessment, the inclusion of health-related quality of life evaluations, and evaluation of cognitive performance.The presentation was followed by a glimpse into the complexity of rehabilitation after mild traumatic brain injury, by Nada Andelic (Norway), Head of Research and Development at the Department of Physical Medicine and Rehabilitation from University Hospital in Olso (Norway), describing evidence-based recommendations for the treatment of physical, cognitive, and emotional symptoms following a mild TBI. Prof. Andelic familiarized the audience with strategies for treating physical, cognitive, and emotional consequences post mild TBI as well as facilitating the return to pre-morbid functioning. Mild TBI is characterized by the level of consciousness at the time of the injury or half-hour post-injury, along with the presence of other neurological symptoms. Rehabilitation aims to optimize function and reduce disability in patients, as stated by the World Health Organization (WHO). Prof. Andelic pinpointed the effectiveness of rehabilitation efforts in the acute phase, highlighted the importance of comprehensive assessment, and supported the use of biopsychosocial conceptualization in the rehabilitation of persistent symptoms encountered after mild TBI. The importance of contextual factors stems from their interaction and the possibility to negatively or positively impact the outcome and brings forward the need for patient-centered rehabilitation models and evidence-based treatments. Further aspects on neuropsychological rehabilitation, focusing on memory and attention after traumatic brain injury and new technologies were also discussed by Juan Carlos Arango-Lasprilla (Spain), Research Professor at BioCruces Vizcaya Health Research Institute in Bilbao (Spain).The last presentation of the session approached the topic of neurorehabilitation of psychiatric sequelae after TBI and was conducted by Katrin Rauen (Switzerland), Consultant in Neurology, Psychiatry & Psychotherapy at the Department of Geriatric Psychiatry from University Hospital of Psychiatry Zurich (Switzerland). Nowadays, traumatic brain injury scientifically becomes more important, however, the society is still unaware of its significant medical and healthcare implications and neuropsychiatric repercussions for the patients. Therefore, neuropsychiatric complications are one of the most important factors to consider, as they represent a constant challenge for all medical specialties and can significantly impact the lives of patients and their families. Most TBI patients are seen by GPs rather than TBI specialists, underlining the neglected relevance of the disease in the field of Neuropsychiary. Some of the most important aspects to consider are depression, anxiety, fatigue, and insomnia, as well as PTSD and the increased risk of suicide. It is of utmost importance to detect patients with neuropsychiatric sequelae early on and consider the importance of quality-of-life assessment after neurotrauma. The Quality of Life after Brain Injury (QOLIBRI) instrument comes as a solution to this problem. Finally, Dr. Rauen pinpointed strategies for cognitive rehabilitation and the importance of psychiatric diagnosis and rehabilitation in TBI guidelines.\u2013 how to minimize the risks of failure?\u201d, where a respected set of panelists, including Michael Chopp (USA), Karin Diserens (Switzerland), Andrew Maas (Belgium), and Johannes Vester (Germany) had a lively discussion on fitting approaches for the challenges of TBI research. TBI research can be difficult as there is tremendous variability when considering the best approaches. A comprehensive approach should consider the best models, the outcomes and mechanisms, and have a thorough understanding of the selected population. A multidimensional approach from research teams members of varying specialties could offer a more complex vision of the problems and lead to innovative solutions.The AMN Congress introduced the first Panel, \u201cResearch in TBI is full of challenges \u2013 what should be done to offer effective treatment solutions?\u201d, having Nada Andelic (Norway), Juan Carlos Arango-Lasprilla (Spain), Peter Lackner (Austria), Katrin Rauen (Switzerland), Nicole von Steinb\u00fcchel (Germany) and Marina Zeldovich (Germany) as panelists, highlighted approaches to treatment for the cognitive problems resulting from neurotrauma. Cognitive problems are often developed following a TBI and can affect attention, learning, memory, concentration, speech, problem-solving, and planning. As attention is the basis for higher cognitive skills , impairment in attention can lead to a wide array of manifestations, from understanding information, following directions, reacting, managing tasks, learning and remembering, making informed decisions, or understanding social boundaries.The impact of the cognitive impairments can reflect significantly on the personal and professional lives of those who have experienced TBI due to difficulty in carrying out executive tasks, distractibility, and difficulty in conversations. The issue of post-TBI cognition is complex and multidimensional, having a substantial impact on the patient and their social circle . For this, early identification of the individual at risk and the development of effective treatment solutions, as well as having a follow-up of the patient is of utmost importance.The impact of the cognitive impairments can reflect significantly on the personal and professional lives of those who have experienced TBI due to difficulty in carrying out executive tasks, distractibility, and difficulty in conversations.The second Panel, \u201cThe incidence of post-TBI cognitive problems is known etc.). For this, early identification of the individual at risk and the development of effective treatment solutions, as well as having a follow-up of the patient is of utmost importance.The issue of post-TBI cognition is complex and multidimensional, having a substantial impact on the patient and their social circle (family, employers, healthcare providers,"} +{"text": "International Journal of Molecular Sciences, entitled \u201cNon-Covalent Interactions in Coordination and Organometallic Chemistry\u201d, is to cover the most recent progress in the rapidly growing field of non-covalent interactions in coordination and organometallic chemistry. Both experimental and theoretical studies, fundamental and applied research and any types of manuscripts are welcome for consideration.Non-covalent interactions are one of the key topics in coordination and organometallic chemistry. Examples of such weak interactions are hydrogen, halogen, and chalcogen bonds, stacking interactions, metallophilic contacts, etc. Non-covalent interactions play an important role in materials science, catalysis, and medicinal chemistry. The aim of this Special Issue of Non-covalent interactions are one of the key topics in coordination and organometallic chemistry. Examples of such weak interactions are hydrogen, halogen, and chalcogen bonds, stacking interactions, metallophilic contacts, etc. Non-covalent interactions control the structure of solids , as well as the properties of supramolecular systems in liquid and gas phases, in addition, the elementary stages of chemical reactions are due to such weak inter- and intramolecular contacts. In the context of bio(organic/inorganic)chemistry, non-covalent interactions are necessary for the formation and folding of the three-dimensional structure of proteins and nucleic acids as well as their metal complexes and ligand-protein binding. These inter- and intramolecular interactions have a significant effect on the properties of polymers, gels and membranes, on the dissolving abilities of liquids and their boiling points. Non-covalent interactions play an important role in materials science, catalysis, and medicinal chemistry. Information about inter- and intramolecular interactions can be obtained experimentally, for example, based on X-ray diffraction analysis data, from phonon spectra and elastic characteristics of crystals, using thermogravimetric analysis and measurements of sublimation energies, from spectral characteristics . At the same time, these experimental methods provide only indirect information, largely mediated by the experimental conditions, and often do not allow one to establish the nature and the energy of non-covalent interactions, what can be the goal and task for computer modeling and computational chemistry. In particular, the most promising theoretical methods in this context are the topological analysis of the electron density distribution within the formalism of Bader\u2019s theory (QTAIM) using additional auxiliary methods: visualization of van der Waals potential, Interaction Region Indicator (IRI) analysis, Independent Gradient Model (IGM) analysis, Density Overlap Regions Indicator (DORI) analysis, localized orbital locator (LOL) analysis, electron localization function (ELF) analysis, reduced density gradient (RDG) analysis, etc.); visualization and mapping of non-covalent interactions analysis) and the study of the degree of influence of crystal packing on the structure of isolated molecular associates stabilized by non-covalent contacts using Hirshfeld surface analysis; analysis of orbitals and charges, in particular, within the formalism of Weinhold\u2019s theory (NBO); study of energy and charge decomposition within the formalism of EDA and CDA theories, respectively. Thus, the most adequate, comprehensive, and promising approach to the study of non-covalent interactions in chemical compounds and their supramolecular associates seems to be a combination of experimental observations and computer simulation results using the latest advances in quantum and computational chemistry. Finally, processing of large amounts of data , machine learning and artificial intelligence is very promising goal for data scientists.International Journal of Molecular Sciences, entitled \u201cNon-Covalent Interactions in Coordination and Organometallic Chemistry\u201d, is to cover the most recent progress in the rapidly growing field of non-covalent interactions in coordination and organometallic chemistry. Both experimental and theoretical studies, fundamental and applied research and any types of manuscripts are welcome for consideration.The aim of this Special Issue of -experimental studies of non-covalent interactions;-theoretical modeling of supramolecular systems;-1D, 2D, 3D coordination polymers;-weak contacts in bio(organic/inorganic)chemistry;-non-covalent interactions in material science;-application of machine learning and artificial intelligence in studies of non-covalent interactions.This Special Issue will address the following topics:We welcome researchers to contribute their works to our Special Issue. We hope that the materials of this Special Issue will prove valuable and useful to a wide range of readers and researchers and will serve as a starting point for new fruitful work in the field of non-covalent interactions in coordination and organometallic chemistry. All types of manuscripts are welcome for consideration."} +{"text": "The study reviewed the progress and outcomes of rolling out IDSR in South Sudan.this descriptive cross-sectional study used epidemiological data for 2019, 2020, and other program data to assess indicators for the five surveillance components including surveillance priorities, core and support functions, and surveillance system structure and quality.South Sudan expanded the priority disease scope from 26 to 59 to align with national and regional epidemiological trends and the International Health Regulations (IHR) 2005. Completing the countrywide rollout of electronic Early Warning Alert and Response (EWARS) reporting has improved both the timeliness and completeness of weekly reporting to 78% and 90%, respectively, by week 39 of 2020 in comparison to a baseline of 54% on both timeliness and completeness of reporting in 2019. The National Public Health Laboratory confirmatory testing capacities have been expanded to include cholera, measles, HIV, tuberculosis (TB), influenza, Ebola, yellow fever, and Severe Acute Respiratory Syndrome 2 (SARS-COV-2). Rapid response teams have been established to respond to epidemics and pandemics.since 2006, South Sudan has registered progress towards using indicator and event-based surveillance and continues to strengthen IHR (2005) capacities. Following the adoption of third edition IDSR guidelines, the current emphasis entails maintaining earlier gains and strengthening community and event-based surveillance, formalizing cross-sectoral one-health engagement, optimal EWARS and District Health Information Systems (DHIS2) use, and strengthening cross-border surveillance. It is also critical that optimal government, and donors\u2019 resources are dedicated to supporting health system strengthening and disease surveillance. Public health security is essential to minimizing the impact of acute public health events and is critical for countries\u2019 social and economic stability and transformation . Health Numerous years of civil strife in South Sudan and inadequate public health and healthcare investments have contributed to the increased risk of outbreaks and insufficient capacities to detect and respond to public health threats. Within this context, in 1998, South Sudan experienced a relapsing fever outbreak that is estimated to have resulted in more than 400,000 cases, including 2,000 deaths CFR 5 0.5%) [ 0.5% [5]Since the adoption of IDSR by the WHO Africa (WHO-AFRO) Region in 1998, the strategy has been implemented successfully in stable countries. The strategy has been used to improve capacities to respond to cholera, meningitis, Ebola Virus Disease (EVD) and other outbreaks or public health events. In this present paper, we share the experiences and impact of using IDSR to strengthen national surveillance and response systems in a country experiencing a protracted grade 3 humanitarian crisis that has persisted since 2014 with a scale that warrants major support from WHO and other United Nations Agencies . These eAnnex 1). The surveillance system components assessed include the availability of a list of priority diseases, conditions, and events for surveillance; the structure of the surveillance system; the core and support functions; and the quality of the surveillance system (Annex 1) [Annex 1) [This was an observational, descriptive cross-sectional study that used the quantitative program and aggregate epidemiological data for all the epidemiological weeks in 2019 and 2020 to document the progress of implementing IDSR and building national surveillance and response capacities in South Sudan. Additionally, other IDSR program data from 2006, were compared with program benchmarks to document the implementation progress. The study used Ministry of Health (MoH) IDSR and Early Warning Alert and Response Network (EWARN) data collected routinely at the health facility, county, and state levels or from periodic program monitoring reports during the study period. Program reports, including monitoring, training, support supervision, and periodic assessment reports, were reviewed to obtain the information on the program performance indicators (Annex 1) . We idenAnnex 1) . We usedThe periodic indicator measures were compared to the program targets during the study period to document quantitative and qualitative changes that demonstrate program performance concerning set indicator-specific targets. Quantitative changes in program performance indicators entailed absolute measurements, proportions, or rates. These descriptive analyses were undertaken in Microsoft Excel. We used aggregate data from routine Ministry of Health epidemiological bulletins and program reports with no personal identifiers, and therefore, an ethical review was not warranted for this present study.Ethics approval and consent to participate: administrative clearance for publication of this paper was provided by the Ministry of Health of South Sudan and WHO (WHO e-Pub no: ePub-IP-00331294-EC).We present the performance on indicators aligned to the five surveillance system components starting with the surveillance priorities, then the core and support functions, and surveillance system structure and quality.Surveillance priorities: South Sudan adopted the IDSR strategy in 2006, but systematic implementation aimed at establishing national surveillance structures aligned to the strategy started in 2009. These initiatives were further buttressed when South Sudan became a WHO Member State on 27 September 2012 and after the country committed to the IHR (2005) on April 16, 2013.Objectives for disease surveillance: the national surveillance goals are aligned to the IHR (2005) and the IDSR strategy for the African region 2020-2030. Thus, the South Sudan Ministry of Health adapted the third edition IDSR guidelines and training materials during a 5-day WHO-facilitated workshop from October 21, 2019. The Government eventually adopted these guidelines on November 13, 2019 thus paving the way for their dissemination and use by counties, health facilities and communities. Based on these guidelines, the main objective of the national surveillance system is to improve the country\u00b4s capacities to detect, report, confirm, and effectively respond to priority diseases, conditions, and events. The updated guidelines are explicit on one-health surveillance for zoonotic diseases, the use of eHealth to enhance surveillance, cross-border surveillance strengthening, and surveillance in humanitarian contexts.Prioritization of diseases for surveillance: as part of the revised 2019 national IDSR guidelines, the priority list was updated from the 26 diseases, conditions, and events prioritized in the 2012 guidelines to 59 diseases, conditions, and 19 events for indicator and event based surveillance (Annex 2 and Annex 3). The broad categories include diseases, conditions, or epidemic-prone events, diseases targeted for eradication or elimination; other major diseases of public health importance; and diseases or events of international concern (Annex 2 and Annex 3). The top cause of morbidity in South Sudan in 2019 was malaria that accounted for 75.9% of outpatient consultations and hence is top on the priority list and the National Health Sector Development Plan (2017-2022) to facilitate the implementation of IDSR in South Sudan. However, the public health bill and the animal health bill have not been enacted as Acts of Parliament as of writing this report.Legislation to facilitate outbreaks and emergency response: the overall mandate for regulation and provision of healthcare and health emergency response is constitutionally vested in the national and state governments. Consequently, the Minister of Health has sanctioned the formation of national and state-level outbreak task force committees to control outbreaks of cholera, measles, hepatitis E, and other public health events in recent years. In the same way, presidential orders were issued to establish the National COVID-19 task force to provide the overall policy, strategic, and oversight guidance and coordination of the national COVID-19 response.Designation of National International Health Regulations Focal Point: in line with the IHR (2005) requirement, the office of the Director General International Health and Coordination in the National Ministry of Health is the designated IHR (2005) National Focal Point (NFP) for coordinating IHR (2005) core functions implementation in collaboration with other sectoral focal points.Functioning International Health Regulations communication facilities: while the National IHR Focal Point has been designated, staffing and communication logistics remain inadequate for the office to meet functional and communication objectives. Official communication email and telephone facilities have not been designated for efficient communication with the other sectors and the WHO IHR focal point.International notification of outbreaks to World Health Organization: in compliance with the IHR (2005), an outbreak of yellow fever in Sakure, Nzara County and measles outbreaks in 20 counties were notified to WHO as potential Public Health Emergencies of International Concern (PHEIC) in 2019.National Integrated Disease Surveillance and Response and Early Warning Alert and Response Network Coordination: the Emergency Preparedness and Response (EP&R) department under the Directorate of Preventive Health Services in the national MoH is the designated IDSR coordination unit at the national level. It is supported by state-level surveillance focal points in the respective state MoH and the health promotion department. The committee also provides strategic and operational guidance on strengthening IDSR core and support functions at all levels. The EP&R committee convenes weekly to review and support preparedness for anticipated outbreaks and public health emergencies; coordinates initial investigations and responses to new and ongoing suspect or confirmed outbreaks and other public health emergencies. In 2019, there were 14 (27%) documented weekly EP&R meetings with minutes on the record.Evidence of sharing resources: to optimize IDSR functional capacities at all levels, integrated use of resources occurs through detection and reporting of acute flaccid paralysis (AFP), Guinea worm, other vaccine-preventable diseases (VPDs) to the respective vertical programs for case-based investigations. The integrated use of IDSR rapid response teams (RRTs) and surveillance focal points to investigate and respond to AFP, Guinea worm disease (GWD), and other VPDs. The use of IDSR/EWARS reporting resources to support reporting needs under the DHIS2 has also been initiated. Further, influenza sentinel surveillance resources under IDSR have been used to support Ebola virus disease, yellow fever, and COVID-19 investigations and laboratory testing.Intersectoral collaboration, networking, and partnership: effective control of outbreaks like cholera, Rift Valley Fever, Ebola virus disease, and COVID-19 requires the competencies of a designated intersectoral committee for systematic risk assessment, contingency planning, and effective response. However, South Sudan lacks a formalized multisectoral platform to take on this role. Moreover, recent intersectoral engagements are timebound and restricted to the active phase of outbreaks and emergencies. During the cholera outbreaks of 2014-2017, the Ministry of health and partners worked alongside the Ministry of water and irrigation and Juba City Council to implement water quality surveillance and improve access to safe water sources. In the same way, the Ministry of Livestock and Fisheries (MLF) has worked with the Ministry of Health and partners under the task force constituted to respond to the Rift Valley Fever (RVF) outbreak of 2017.Existence of functional laboratory networks: South Sudan has one National Public Health Laboratory (NPHL) that was founded in 1974 but was not inaugurated until 2014 and has capacities to test for cholera, measles, human immunodeficiency virus (HIV), tuberculosis (TB), influenza, Ebola, Marburg, yellow fever, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), and routine water quality testing . The committee members share disease surveillance information regularly, and a social media platform was created to complement the other official communication channels. The tripartite cross-border surveillance committee meets annually and has conducted one joint cross-border outbreak response simulation exercise on the Ebola virus in 2019. The committee has also conducted two cross-border outbreak investigations on Rift Valley Fever and yellow fever in 2019 and 2020, respectively. The later investigation resulted in the confirmation of a yellow fever outbreak in Kajo-keji county in March 2020. Synchronized yellow fever vaccination campaigns were implemented on either side of the international border by October 2020. Alongside Uganda, the Democratic Republic of Congo (DRC), and Uganda, South Sudan has participated in the Goma cross-border surveillance initiative. The initiative strengthened cross-border surveillance to mitigate the risk of cross-border spread during the 2018/ 2019 Ebola virus disease (EVD) outbreak in North Kivu and Ituri, DRC. South Sudan is also participating in intercountry meetings to strengthen regional health security. In May 2019, WHO-AFRO convened an intercountry meeting in Kigali, Rwanda, to strengthen regional health security for operational readiness and surveillance in response to the EVD outbreak in DRC. The meeting involved the four high-risk countries bordering DR Congo.Case detection and registration: South Sudan is implementing both indicator and event-based surveillance to detect and register new cases of priority diseases or other public health events. As part of strengthening indicator-based surveillance, case definition charts and booklets have been printed and disseminated for use at health facilities. In 2019, 3,540 case definition booklets and charts were printed and distributed to the 1,260 functional health facilities. This number of case definition job-aids translates into at least three case definition job-aids distributed per functional health facility. As part of community-based surveillance, the Boma health workers (BHW) and community health workers (CHW) use simplified and translated community case definitions for case detection and registration at the community level. These simplified community case definitions are included in the case definition booklets. Indicator-based surveillance is complemented by event-based surveillance, which entails informal alerts of potentially serious public health events from the community, health facility, county, state, or national level. The log of rumors and suspect outbreaks is used for recording new alerts or suspected outbreaks. In 2019, at least one log of rumors and suspect outbreaks was distributed per functional health facility. A national toll-free center hotline exists in the call center and is used to report community alerts. Additionally, the electronic Early Warning Alert and Response (EWARS) reporting platform includes an event based platform that facilitates alert recording, verification, and risk assessment by health facility, county, and state surveillance officers and watch officers in the Public Health Emergency Operations Center (PHEOC).In 2019, 3,184 alerts were detected and reported through the national event-based disease surveillance system using EWARS. The alerts reported in 2019 are four times higher when compared to the alerts (771) reported in 2018 . The sigCase confirmation and response to outbreaks and other public health emergencies: during 2019, at least 104 suspect outbreaks were reported and investigated, with 35 (33.65%) confirmed. Of the 35 confirmed outbreaks; 4 (11.4%) were due to Hepatitis E virus; 20 (57.1%) were due to measles; 9 (25.7%) were due to rubella;1 (2.9%) due to yellow fever; and 1 (2.9%) due to mass casualty (burns) ( (burns) . Since tReporting, data analysis and feedback: all priority diseases and events should be reported to the next high level either immediately, weekly, or monthly to facilitate appropriate public health action. Since the adoption of IDSR in South Sudan in 2006, routine IDSR reporting relied on a combination of paper-based, Microsoft Excel or Access datasets transmitted by email or radio calls to the next level. These approaches were fragmented, incomplete, and were associated with reporting errors and delays. Hence, in 2017, WHO, through the Global EWARS project, initiated support to the Ministry of Health and partners to streamline reporting. The support entailed modular training and technical support to facilitate the Early Warning Alert and Response System (EWARS) deployment. The EWARS is a web-based desktop and mobile application that can be rapidly configured and deployed to support early warning, alert management, and outbreak response. The EWARS mobile reporting has been deployed to support reporting in at least 1,260 functional health facilities in 10 States and three administrative areas. As part of the EWARS rollout from January 2019 to March 2020, WHO, in collaboration with the local governments and partners, has trained over 1,500 frontline health workers and distributed 21 \u201cEWARS in a box\u201d kits to facilitate real-time submission routine IDSR and disease outbreak reports. Each EWARS in a box kit contains 60 mobile phones with SIM cards, 25 solar power banks, and 60 EWARS quick start guides.The completion of electronic EWARS reporting rollout has positively impacted the timeliness and completeness of weekly IDSR reporting from the health facilities. The average timeliness for submitting weekly IDSR reports from the health facilities by the end of week 39, 2020 was 78% compared to 54% by week 39, 2019, representing an increase of 24%. In the same way, the average completeness rate of reporting from the functioning health facilities across the country by week 39, 2020 was 90% as compared to 54% in week 39, 2019 representing an increase of 36%. Overall, the completeness of weekly reporting from the health facilities by county improved in 2020 when compared to 2019 and 2020 . Early wEpidemic preparedness: epidemic preparedness and contingency plans are developed and updated within national and state-level efforts to improve public health security. The updated preparedness and contingency plans include cholera, epidemic meningitis, yellow fever, Rift Valley Fever, and floods. Emergency funds are incorporated into the overall MoH budget to facilitate the implementation of the plans for providing primary health care as defined in the basic package for nutrition and health (BPNH). Epidemic preparedness and response is also incorporated into humanitarian response in prioritized populations and supported using the Country-Based Pooled Funds (CBPF) and through the ongoing support to IDSR implementation by ECHO and USAID.Response and control: with support from the WHO, the MoH has established a national multi-hazards rapid response team and state rapid response teams in each of the 10 states with regular multi-hazard training and simulation exercises. The operations of the rapid response teams are guided by standard operating procedures that define the team composition, roles of each team member, and the procedure for activation, mobilization, and deployment in response to suspect and confirmed outbreaks. Once an outbreak is confirmed, the Minister of Health designates a task force committee to coordinate the overall response in liaison with other sectors and stakeholders.Performance on support functions: in November 2019, the South Sudan MoH adapted and adopted the third edition of IDSR technical guidelines. The guidelines are expanded to include guidance on event-based surveillance, cross-border surveillance, the use of information technology to enhance surveillance functions, guidance on surveillance in the humanitarian context, and the one-health approach. The initial training of trainers on the third edition IDSR technical guidelines have been completed. The cascade county county-level training plan has been finalized though the implementation was delayed and modified in the context of COVID-19. A dedicated national IDSR plan of action is updated annually and incorporates all the activities required to implement the support functions and strengthen the core functions at all levels. However, the plan of action is primarily donor-supported, thus raising sustainability issues in the medium to long term.The present study assessed performance for five core surveillance components to document the impact and experiences of deploying IDSR in a humanitarian context. Through the implementation of the IDSR strategy, South Sudan has registered significant progress towards strengthening the national disease surveillance system as demonstrated from the performance on key surveillance indicators for each of the surveillance components assessed in the present study.Objectives of disease surveillance: in line with the IHR (2005) and the regional strategy for IDSR 2020-2030, the South Sudan Government adopted the IDSR to expand and strengthen the national surveillance and response system. Over the years, the Government adapted the requisite guidelines, expanded the priority disease list, and provided technical oversight to establish surveillance focal points, train and equip them, and monitor the implementation of IDSR functions at all levels [l levels . Howeverl levels . Achievil levels ,11. SincIDSR structure: the South Sudan Ministry of Health has established coordination structures and technical focal points to optimize IDSR functions at the community, health facility, county, state, and national level. The cross-sectoral engagement has been exploited in response to recent cholera outbreaks (2014-2017), Rift Valley Fever (2017), and COVID-19. However, these efforts are timebound and confined to the active outbreak phase. Furthermore, these efforts need to be formalized and should be extended to span the entire epidemic and emergency management cycle. Hence, as part of the NAPHS, there are plans to formalize cross-sectoral linkages with relevant line Ministries [nistries . Furthernistries .Existence of laboratory networks: laboratory capacities are critical to the IDSR function of detecting and confirming public health hazards [ hazards . South S hazards . Over th hazards . This wiCross border collaboration: the regional outbreaks of EVD in West Africa in 2014 spread to at least five countries in West Africa. Moreover, exported cases were reported in Europe and the United States in 2014 and 2015. Cross border EVD spread was again reported during the 2018 DRC Ebola outbreak in Ituri and North Kivu that spread to Uganda. These incidents highlight the need to enhance cross-border surveillance and response [Performance on core and support functions: in line with the third edition IDSR technical guidance, South Sudan is expanding community and health facility-based surveillance using the indicator and event-based surveillance [eillance ,9. Boma eillance . Gaps ineillance . Reportieillance -19. A noeillance ,20.The limitations of this study entail incomplete program and epidemiological data and the cross-sectional nature of the study that is not ideal for demonstrating the program\u2019s impact. Therefore, we used multiple sources of data to triangulate information and reduce data gaps. Also, we used standardized program performance indicators to document progress on core and support IDSR functions.Since the adoption of IDSR in 2006, South Sudan has registered progress towards strengthening the national disease surveillance system. In compliance with the IHR (2005) and IDSR, the priority disease scope has been expanded, with indicator and event-based surveillance used to detect and report alerts and suspect cases. In addition, the countrywide rollout of electronic EWARS reporting has improved the reporting performance. Further, laboratory capacities continue to be strengthened following the inauguration of the National Public Health Laboratory, which now possesses capabilities for confirming priority bacterial and viral pathogens supported by a countrywide network for specimen referral. To facilitate investigation and response to suspect and confirmed outbreaks, national and state rapid response teams have over the years been trained, drilled, and deployed to support investigation and response to outbreaks of cholera, Rift Valley Fever, yellow fever, viral hemorrhagic fevers, and COVID-19. Epidemic preparedness is effectively supported through the national EP&R team. In contrast, the response to confirmed outbreaks is supported by task force committees of experts from varied disciplines and sectors using the incident management system (IMS) principles. The rollout of the third edition IDSR guidelines will further bolster this progress. The rollout will facilitate formal cross-sectoral one-health engagement, enable optimal use of EWARS and DHIS2, and allow effective cross border engagement. In collaboration with the health cluster partners, the MoH will continue using the IDSR to address fragile, vulnerable, and conflict-affected populations\u2019 surveillance and response needs. To ensure that these investments in IDSR are optimized and sustained, budget support towards strengthening the health system and surveillance system must be optimized. To address the challenge of high healthcare workers turnover, the working conditions of health workers in public health facilities must be enhanced. The NAPHS, which embodies IHR (2005) and IDSR priorities, should be implemented to enhance national and international health security. Finally, as the country works towards emerging from decades of conflict and economic downturn, donor support to the IDSR program must be sustained to reduce morbidity and mortality from priority health diseases, conditions, or events and enhance national and international health public health security.The integrated disease surveillance and response (IDSR) strategy provides a framework that countries in the WHO African region are using to attain core capacity requirements for the international health regulations (IHR (2005)). The member states in the African region have demonstrated that IDSR is a cost-effective strategy for effective preparedness, detection, investigation, response and control of epidemics and pandemics in the African region.Whereas the IDSR strategy has largely been used in stable settings, in this paper, we have demonstrated how the IDSR functions can be used to support Early Warning Alert and Response (EWARN) in humanitarian settings where the performance of surveillance systems is sub optimal. The sustained investment of resources towards IDSR implementation has improved the program reporting performance, thus allowing detection of major outbreaks, and averting morbidity and mortality;Program funding from domestic resources is critical for sustainability in the long-term."} +{"text": "Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio\u2019s phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology. M. leprae to dapsone, rifampicin and ofloxacin. The patient was submitted to a new regimen of multibacillary multidrug treatment (MB-MDT), prednisone 80\u202fmg/day and systemic antibiotic therapy, with significant clinical improvement after three weeks.A 32-year-old man with a history of multibacillary leprosy under treatment for ten years with negative bacilloscopy at discharge reported the appearance of erythematous papules on the upper limbs. He used prednisone 40\u202fmg/day on his own for five months and, when it was discontinued, pustules, vesicles, painful crusts and bullae with purulent content appeared on the plantar region , togetheMycobacterium leprae.Leprosy is a chronic granulomatous infectious disease with polymorphic manifestations caused by None declared.Larissa Daniele Machado G\u00f3es: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Patr\u00edcia Motta de Morais: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Paula Frassinetti Bessa Rebello: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Ant\u00f4nio Pedro Mendes Schettini: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Constipation is a common disorder of gastrointestinal motility, which usually causes infrequent stools, and difficulty in the passage of stools. Many aspects, including genetic predisposition, daily diet and behavior, socioeconomic status, and other biological and clinical factors are considered to be associated with the pathogenesis of constipation . ConstipBacillus coagulans BC01, Bifidobacterium lactis TY-S01, and Lactobacillus plantarum KFY02 increased the fecal moisture and gastrointestinal transit rate in mice . Furthermore, the authors found that these strains can promote the homeostasis of gut microbiota in the constipated mice . Bifidobacterium lactis TY-S01 and Lactobacillus plantarum KFY02 increase the community richness and bacterial diversity. More importantly, the structure and composition of intestinal flora in the constipated mice are markedly changed by these three strains, and the change in the abundance of special species depends on the strain specificity of probiotics. The mechanisms underlying these effects on constipation are summarized as follows.This Research Topic mainly focuses on the attenuation effect and potential mechanism of new probiotics on constipation. To date, five papers, including four research articles and one review article have been collected in this Research Topic. Bifidobacterium lactis TY-S01 increases the content of SCFAs, such as isobutyrate acid, butyrate acid, acetic acid, valeric acid, and propionic acid, in the feces of the constipated mice . These SCFAs may inhibit the growth of pathogenic bacteria by reducing the pH in the small intestine, and improve gut motility by increasing colonic smooth muscle contraction, therefore contributing to the amelioration of constipation symptoms (Ara\u00fajo and Botelho).Yi et al.). The destruction of gut barrier may result in the further invasion of pathogenic bacteria and their toxins, which aggravates intestinal inflammation. The maintenance of gut barrier integrity can inhibit the adherence of pathogens bacteria and their metabolites and facilitate stool passage (Ara\u00fajo and Botelho). Zhou et al. reported that the nuclear factor (NF)-\u03baB signaling-mediated inflammation in the small intestine of mice with constipation is inhibited by Bacillus coagulans BC01. Bifidobacterium lactis TY-S01 decreases the mRNA expression of colonic inflammatory cytokines in the constipated mice . Furthermore, the expression levels of gut barrier-associated key genes, including transient receptor potential vanilloid-1, mucin 2, stem cell factor, claudin-1, occludin c-kit, and glial cell line-derived neurotrophic factor are significantly regulated by Bifidobacterium lactis TY-S01 and Lactobacillus plantarum KFY02 , indicating that these probiotics have the potential ability to restore the gut barrier.The imbalance of intestinal bacteria can cause the release of inflammatory cytokines, thereby damaging the integrity of gut barrier . These intestinal hormones can regulate intestinal peristalsis and improve constipation symptoms . Besides, Zhou et al. reported that Bacillus coagulans BC01 reduce the production of vasoactive intestinal peptide and somatostatin in the constipated mice, contributing to the slowing down of intestinal transit time and the relief of constipation.The content of motilin, 5-hydroxytryptamine, and substance P in the constipated mice is increased by Zhang et al. examined the regulatory effect of synbiotic consisting of Bifidobacterium lactis BL-99 and fructooligosaccharide (FOS) on the intestinal flora from constipated individuals in vitro. They found that this synbiotic enhances the level of acetic acid, but also changes the structure of intestinal flora, and increases the abundance of beneficial bacteria. However, human and animal studies evaluating the improved effect of synbiotics on constipation are scarce (Ara\u00fajo and Botelho).Apart from the regulation of gut microbiota in the constipated mice by probiotics, in vivo studies and mechanism of synbiotics on constipation.In summary, although the above-mentioned probiotics show a good efficiency in improving the constipation of mice, randomized clinical trials are needed to further confirm their anti-constipation effect. The molecular mechanisms underlying probiotics effect on constipation, including the identification of key metabolites and their mode of action need to be further investigated. In addition, it is necessary to further strengthen the JS wrote the whole manuscript. XZ, K-yP, and HS provided some valuable comments. All authors contributed to the article and approved the submitted version."} +{"text": "Psychological health problems, especially emotional disorders, have become an important topic of considerations for many scientists, because the epidemiology of these disorders is strongly influenced by stressful events, such as the SARS-CoV-2 coronavirus pandemic.The aim of this study was to evaluate selected parameters of psychosocial functioning as well as socio-demographic correlates of depression, anxiety, sleep disorders and perceived stress among the residents of the West Pomeranian Voivodeship.An online questionnaire was completed by 323 participants, in whom the parameters of psychosocial functioning were assessed: symptoms of depression (PHQ-9), anxiety (GAD-7), severity of sleep disorders (AIS) and perceived stress .The majority of the respondents (75.2%) scored high on the Perceived Stress Scale, almost half of the respondents (47.1%) had sleep disorders and 26% of the participants had no depressive symptoms. Age statistically significantly correlated with the severity of depressive symptoms and sleep disorders. Parental status statistically significantly correlated with the severity of depressive symptoms. There was a strong correlation between the severity of depression and anxiety and a strong correlation between depression and sleep disorders.Age and parental status contributed to the severity of depressive symptoms and the occurrence of sleep disorders among the residents of the West Pomeranian Voivodeship during the SARS-CoV-2 pandemic. Some of the residents of the West Pomeranian Voivodeship showed high levels of stress or insomnia. The severity of depressive symptoms significantly influenced the levels of anxiety and perceived stress, as well as the occurrence of sleep disorders.No significant relationships."} +{"text": "The challenges of supporting the health and social needs of older adults and caregivers in rural and frontier areas are well-documented. It is common for rural older adults to experience barriers in accessing geriatric specialists, care coordination services, and caregiver support and education programs. The Wyoming Geriatric Workforce Enhancement Program (WyGWEP) is an innovative partnership comprising an academic geriatrics program, primary care delivery sites, single-unit on aging representing community-based organizations, and a tribal health program. This partnership, funded by the Health Resources and Services Administration, provides the infrastructure to assess needs, provide education and training, create programs to address gaps in care, implement practice innovation, and advocate for needs of rural older adults. This symposium includes five presentations detailing the unique projects of the WyGWEP partnership and the impact of this collaborative work on a variety of stakeholders. The results of a mixed-methods evaluation of the WyGWEP partnership will describe the benefits to the partners and areas for growth. A collaborative effort to assess the needs of older adults informs recommendations to support rural aging in place. Schenck et al. will describe the adaptation of the widespread ECHO model for use with dementia caregivers in rural and remote locations. Representatives from Wyoming\u2019s only Program for All-Inclusive Care of the Elderly (PACE) will explain the cost of a recent decision to de-fund and close this important program. Finally, the impact of a novel Chronic Care Management implementation program will be discussed, including sustainable billing revenue produced by rural primary care clinics."} +{"text": "The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD. Although several therapeutic approaches are explored for the management of AMD, no approved therapy can substantially slow down the progression of dry AMD into the later stages. The focus of researchers in recent times has been engaged in developing targeted therapeutic products to halt the progression and maintain or improve vision in individuals diagnosed with AMD. The delivery of anti-VEGF agents using intravitreal therapy has found some success in managing AMD, and novel formulation approaches have been introduced in various studies to potentiate the efficacy. Some of the novel approaches, such as hydrogel, microspheres, polymeric nanoparticles, liposomes, implants, etc. have been discussed. Apart from this, subretinal, suprachoroidal, and port delivery systems have also been investigated for biologics and gene therapies. The unmet potential of approved therapeutic products has contributed to several patent applications in recent years. This review outlines the current treatment options, outcomes of recent research studies, and patent details around the novel drug delivery approach for the treatment of AMD. Age-related macular degeneration (AMD) is one of the common causes of irreversible loss of vision in individuals above 65 years ,2. AccorBased on pathophysiologic features, AMD is majorly classified into dry and wet-type. The initial presentation of the disease is the dry or non-exudative type, which may further advance in the later stage into wet or neovascular AMD ,15. AlthThe pathologic mechanisms involved in the development and progression of AMD are mainly related to the impairment and degeneration of RPE . The risApart from the difficulty in developing novel therapeutic agents due to the complicated pathophysiologic processes involved in the disease progression, the currently available therapies are limited due to safety, efficacy, and delivery issues . AMD affSeveral attempts have been made to develop reliable therapeutic and diagnostic tools for the effective management of AMD. The investigated therapeutic approaches as depicted in The inhibition of the complement system is one of the approaches which involves the suppression of complement proteins to downregulate the complementary pathways and the formation of the membrane attack complex . The comIn AMD patients, the visual cycle involving enzymatic reactions in the RPE and photoreceptor cells of the retina along with phototransduction cascade events may produce significant inflammatory and metabolic waste. The progressive build-up of these wastes culminates in GA and retinal impairment . Visual The transplantation or implantation of the cell can be an alternative therapy in AMD. Although a substantial number of cells of RPE may be damaged in AMD patients, other cells such as photoreceptors, ganglion cells, bipolar cells, etc. may sustain efficient retinal connections . TherefoInflammation has been reported to play a major role in the progression and pathogenesis of AMD . TherefoNeuroprotection involves the use of therapeutic agents to enhance neuronal endurance by protecting the anatomical and physiological features of the neurons. The neuroprotective agents in AMD are very important along with other therapeutic strategies for slowing down the progression and preventing the loss of vision ,63. ElamThe pathogenesis of AMD involves complicated pathways pertaining to fluctuations in angiogenesis and pro-angiogenesis factors, such as; (i) VEGF overexpression, (ii) pigment epithelium-derived factor (PEDF) deficit, (iii) the reduced expression of the extracellular domain of VEGF receptor 1, and (iv) the inhibition of pro-angiogenic factors ,67. TreaDespite the high efficacy of intravitreal therapy, it is associated with the burdens of frequent injections, high treatment costs, and is associated with the risk of an increase in intraocular pressure . RGX-314The delivery devices of anti-VEGF based on the port delivery system allows for their sustained release into the eyes. Ranibizumab (anti-VEGF antibody fragment) has been formulated and encased in sustained-release devices. The devices were able to achieve similar treatment outcomes with a considerably reduced frequency of administration ,77.The delivery systems used for therapeutic agents against AMD primarily revolve around using either implantable devices or intravitreal injectable liquids. Recently, scientists have made considerable attempts at improving the potential of therapeutic agents used for AMD by designing novel carriers that can reduce invasiveness at a low cost ,79. DespIntravitreal space is the most employed route for the delivery of therapeutic agents for AMD. The main reason behind the popularity of this route is its high safety, minimum invasiveness, convenient application, and adequate efficacy . Table 1The mesoporous silica nanoparticles (MSNs) functionalized with 3-aminopropyltriethoxysilane (3-aminopropyl) triethoxysilane (APTES) and mPEG-succinimidyl carboxymethyl ester (mPEG-NHS) were also reported to show improvement in the anti-VEGF potential of bevacizumab. In vitro studies showed that MSNs were effective in inhibiting proliferation, migration, and tube formation of endothelial cells induced by VEGF. Furthermore, the MSNs exhibited in vivo inhibition of corneal and retinal neovascularization . BevacizVollrath et al. developed sustained-release solid lipid implants of ranibizumab using the twin-screw extrusion method. The implant could load a high amount of protein (3 mg/implant) with consistently sustained release profiles for 120 days. The implant showed a predominantly high release of the monomeric form >95%) of the ranibizumab initially, followed by the formation of the hydrophobic type upon the completion of 18 weeks. The stability of the ranibizumab in the implant was exceptional with no signs of aggregation or alterations in secondary structures . PLGA mi% of the The researchers used a similar delivery system for the encapsulation of aflibercept. The rate and extent of release of aflibercept was also in a controlled manner depending upon the concentration of the cross-linking agent and the loaded microspheres. The drug released from the microspheres showed no signs of cytotoxicity from its degraded byproducts, and bioactivity was maintained throughout the complete release period . The preThe region between the RPE layer and the photoreceptors is considered as a subretinal space which allows the direct delivery of drugs to the RPE and photoreceptor cells. The subretinal injections utilize trans-scleral and trans-corneal routes in animal studies for attaining the required desired concentration of a drug in subretinal space ,114. It \u00ae) based on an equine infection-causing anemia virus was developed for delivering two anti-angiogenic genes (endostatin and angiostatin) to the retina to suppress angiogenesis and enhance the vision of patients [\u00ae was studied for subretinal delivery for the management of wet-AMD. The amount of endostatin and angiostatin increased after subretinal administration in rabbit eyes throughout the study. Ocular inflammation was reduced with 1 month of continuous dosing, with no considerable changes in electroretinograms and intraocular pressure [Gene therapy is one of the effective approaches for dealing with AMD by incorporating healthy genes in the cells of patients to avoid or treat defective genetic pathways. The benefit of using gene therapy is that it provides long-lasting treatment and enables targeted ocular regions to generate their protective agents . Streptopatients . RetinoSpressure . The recpressure . A phasepressure . Lambertpressure .The novel drug delivery techniques have facilitated better access to the suprachoroidal space for the treatment of ocular diseases. The drugs administered through the suprachoroidal space allow the attainment of higher concentrations in the retinal region, thereby reducing the undesirable delivery to the anterior ocular areas . A novelThe suprachoroidal graft of autologous cells was also proposed as a treatment for dry AMD, owing to its impact on the enhancement of visual acuity and microperimetric responses. The technique involved the implantation of adipose stem cells in the suprachoroidal space to stimulate the secretion of growth factors. The outcome was a significant improvement in visual acuity after six months, along with the maintenance of growth factor secretion and choroidal flow . The resImplantation containing adipose tissue-derived mesenchymal stem cells was evaluated for its safety and efficiency in patients with dry AMD. There were no occurrences of systemic or ocular complications in any of the patients with improvement in the visual field, visual acuity, and mf-ERG recordings . Zhang eA port delivery system (PDS) encompasses a robust reservoir fabricated for the prolonged delivery of the drug into the vitreous cavity after being implanted. The ability of PDS to release the anti-VEGF medication for a longer duration helps in reducing the overdependency on intravitreal injections for the treatment of AMD. PDS is applied through the surgical insertion of the device into the scleral space through conjunctival peritomy. After implantation, the drug diffuses from the release control element in a sustained manner into the vitreous, which can be filled again once emptied . A phaseSeveral studies have explored the utilization of some of the less preferred routes of administration to combat the limitations associated with existing therapies. Some of the routes reported in recent times chosen for drug delivery for AMD are the subconjunctival, topical, oral, etc. The subconjunctival region is located under the conjunctival membrane covering the sclera. The subconjunctival space is mostly chosen for delivering drugs to anterior ocular regions . A depotNumerous efforts were also made to deliver drugs and biologicals through the topical route owing to convenient and non-invasive administration . A topicAlthough the oral delivery of drugs provides a means of convenient and non-invasive administration, it is rarely chosen for the treatment of AMD due to the presence of ocular barriers, preventing effective delivery to the posterior regions. The phase II trial of an oral tablet formulation (X-82) containing anti-VEGF/PDGF agents was conducted to examine the efficacy of wet AMD. Although the product showed comparable improvement in visual acuity at higher doses, the limitations in safety and tolerability of the formulation resulted from the halt in further development. A case-control study reported the correlation between the oral administration of metformin and a reduction in the chances of developing AMD. The assessments indicate that metformin may possess therapeutic potential for AMD. However, there is a need for a comprehensive clinical study to assert the benefits of oral metformin therapy in preventing AMD development . StewartAMD management involves continuous observation, regular follow-up, and documentation for timely recognition of visual function, or else the condition leads to mortality. Several studies reported on the management of AMD, as presented in the previous section, both with the safety and efficacy of formulations alone and in combination with treatments such as photodynamic therapy. Practical therapeutics strategies for a complex disease such as AMD require the combination of multiple factors, including diet, lifestyle, and improved pharmacological interventions, and the direct development of not only effective but also safe treatment strategies. The systemic quality, safety, and efficacy of many investigated products after successful clinical trials leads to the granting of such patents, indicating the extreme necessity of these products . BesidesThis section is included to provide an outline of the patents granted or applied in recent years related to the use of novel delivery approaches for the treatment of AMD. A recent US patent application of mesozeaxanthin for the management of macular diseases, specifically AMD, proposed that the supplementation of mesozeaxanthin (dosage 0.5 and 50 mg/day) either alone or in combination with other carotenoids and vitamins may increase macular pigments . AnotherExpert opinion on the patent registered by Borodic for the administration of botulinum-toxin as an extra ocular infusion avoiding the risk of direct intraocular injections and complications associated with the patent indicated that co-administration with proteins such as hemagglutinin and monoclonal antibody makes a novel system for the development of the combined approach in the management of AMD . MoreoveOcular barriers pose challenges in the treatment of AMD, leading to therapies with suboptimal efficacy. To overcome this, there is a requirement for the development of novel therapies and drug delivery strategies to fulfill the unmet need. This review was focused on discussing drug delivery in AMD concerning currently available therapeutic approaches, emerging therapies, and the situation of patents. The intravitreal space is the most targeted route for AMD treatment for the delivery of anti-VEGF agents such as bevacizumab, ranibizumab, aflibercept, etc. The studies have also reported the use of novel delivery systems such as polymeric nanoparticles, liposomes, implants, microspheres, etc., which could help in enhancing therapeutic efficiency. The efforts were mostly towards controlling/sustaining release, prolonging residence time, reducing the incidence of adverse events, improving stability, etc. Subretinal and suprachoroidal routes were also investigated for cell-based and gene therapies for dry and neovascular AMD. The PDS of Ranibizumab is another interesting prospect for sustained delivery of the therapeutic agents, allowing for the reduction in dosing frequency. Lastly, the current patent situation included in the review showed that the suppression of the VEGF system is the major target for the treatment of AMD."} +{"text": "Domains of social privilege are predictive of a number of key aging outcomes, such as physical and cognitive functioning. However, less is known about the dynamic interplay of - related but distinct- domains of privilege and how they are associated with cognitive and physical functioning. In the following project, we aim to close this gap by examining the role of multidomain identity and social background factors for initial levels and subsequent changes in psychological, cognitive and physical functioning. Specifically, we identified predefined social privileges within the Berlin Aging Study II (BASE-II) sample and related these categories, interactively, to markers of physical health (multimorbidity), perceptual speed (digit symbol), and psychosocial functioning (loneliness). Results highlight the dynamic interplay of multidomain identity and social background factors with aging related outcomes across a number of key domains."} +{"text": "RecentlKosten et al.). Huang et al. reviewed fMRI papers of small animals under the state of stimulation categorized into electrical, visual, olfactory, auditory and other ways, and analyzed the similarities and differences, advantages and disadvantages of the stimulation sites, electrodes, and stimulation methods. The study provided invaluable comparative information on brain fMRI of small animals combined with stimulation .It is difficult to expound brain function at cellular, systematic and functional levels. Multimodal neuroimaging approaches are able to combine techniques such as calcium imaging, optogenetics, electrophysiology, chemogenetics with functional magnetic resonance imaging (fMRI) and help scientists uncover the relationship between neuronal activity and vascular network dynamics, which would promote our knowledge of the brain from the level of single cells or circuits to the whole brain implantable monopolar carbon electrodes were used to treat alcohol use disorder. This method of implantation generates smaller MRI artifact and serves clinical and basic research . In terms of data processing, Bao et al. constructed an automatic method for individual parcellation of rat brain MEMRI images, which further benefited case-control statistical analysis and improved the accuracy of ROI-based imaging analysis.Maharjan et al.). At the same time, resting state fMRI of AD mice after electroacupuncture(EA) at Baihui and Shenting indicated that the ReHo value of local neuronal integration in hippocampus, entorhinal cortex and other brain regions increased, as well as the number of functional connectivity and neural fiber connections between entorhinal cortex and hippocampus increased, suggesting that EA intervention may be an effective strategy to treat memory defects in AD recognition .Alzheimer's disease (AD) is the most common cause of dementia. Many clinical and basic studies have aimed at improving effective identification strategies for AD .Hippocampus is closely associated with cognition and emotion. Sepsis associated encephalopathy (SAE) has been identified as a common complication of sepsis. SAE-induced pathological changes in the hippocampus may lay the foundation for the development of cognitive dysfunction and affective disorders. Pan et al. used 18F-FDG PET/CT to identify the subregions of the posterior splenic cortex, the role of RSCDS and RSCGS in the coding process of rat contextual fear conditioning model, and the underlying brain network mechanism. The results showed that the role of rat RSCS in the formation of scene fear memory mainly depends on the RSCDS rather than the RSCGS.Chen et al.).In segmental sampling of rat's sciatic nerve imaging in DTI, RS-5 EPI sequence-derived FA and RD may be highly sensitive quantitative biomarkers for detecting histopathological changes of sciatic nerve in rats. These findings provide some reference value for the optimization of DTI sequence in the future peripheral nerve MRI research (We hope that the aforementioned studies which were included in this special topic can inspire new studies and novel future applications of small animal MRI in the fields of data acquisition, analysis methods, pre-clinical applications, biomarker detection and can contribute in more accurate prediction of disease progression and bring us a step close to clinical applications.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication."} +{"text": "The impact of COVID-19 on older adults goes beyond a higher risk for serious infection to long-term consequences such as decreased well-being and disability. In 2020, we formed an international and interdisciplinary research group and adopted a biopsychosocial model as a conceptual framework to guide our collaboration. Our ultimate goal is to mitigate the long-term health consequences of the pandemic and utilize affordable technology-based interventions to enhance the quality of life for older adults in Hong Kong, Singapore, Thailand, and the US. Five empirical studies will be presented with topics ranging from quality of life, fear of falling, attitudes toward technology, and the utilization of technology-based interventions. A path analysis from the first study indicated that physical frailty was the strongest direct power on quality of life followed by depressive symptoms, and life-space mobility. The second study found that fear of falling was predicted by falls risk, resistance, COVID fear, and health conditions. The third study revealed a strong connection between the COVID severity and positive attitudes toward technology, and social support facilitates the adoption of technology. The fourth study reported the benefits of using a technology-based body-mind intervention to alter a mismatch between fear of falling and actual fall risk and to increase the accessibility of the fall intervention. The final study indicated that utilizing an alternative online exercise program during the pandemic increased exercise regularity and enhanced motivation. Together, all five studies contribute to strategic implications on global mitigating long-term health consequences and essential issues for further research."} +{"text": "COVID-19 has caused unprecedented disruptions to health, social and economic systems in countries worldwide including Ireland. Weaknesses in Public Health capacities have undermined health system resilience compounding the effects of the pandemic. The Essential Public Health Functions (EPHFs) provide a comprehensive, cost-effective approach to operationalising public health and a means to build health systems resilience. As Ireland looks to recovery, the Department of Health engaged the World Health Organization (WHO) to undertake a mapping of the current state of delivery of EPHFs to identify opportunities for improvement and support wider health system strengthening towards resilience.A strategic review of the delivery of EPHFs in Ireland was conducted with respect to policy, infrastructure, service provision and coordination and integration. Findings were reported in the context of international lessons identified through experience with COVID-19 and major health system challenges within the Irish context.There are significant capacities present within the Irish context to support the delivery of the EPHFs though they are limited in strategic cohesion, coordination and implementation. These include a high level of Public Health expertise, an agile and resourceful workforce, a strongly engaged community and significant evidence generation and synthesis capacities. Gaps recognised included ICT infrastructure and capacity, workforce resourcing and support, pandemic planning and public health governance, visibility, legislation, strategy and resourcing. COVID-19 has led to the development and strengthening of mechanisms to leverage a whole-of-government and -society approach to health that should be sustained to tackle ongoing and future stressors.The use of the EPHFs within the Irish setting provides a comprehensive approach to strengthening capacities for public health and enhanced population health and wellbeing."} +{"text": "Mitochondria are organelles that serve as a central hub for physiological processes in eukaryotes, including production of ATP, regulation of calcium dependent signaling, generation of ROS, and regulation of apoptosis. Cancer cells undergo metabolic reprogramming in an effort to support their increasing requirements for cell survival, growth, and proliferation, and mitochondria have primary roles in these processes. Because of their central function in survival of cancer cells and drug resistance, mitochondria are an important target in cancer therapy and many drugs targeting mitochondria that target the TCA cycle, apoptosis, metabolic pathway, and generation of ROS have been developed. Continued use of mitochondrial-targeting drugs can lead to resistance due to development of new somatic mutations. Use of drugs is limited due to these mutations, which have been detected in mitochondrial proteins. In this review, we will focus on genetic mutations in mitochondrial target proteins and their function in induction of drug-resistance. Mitochondria consist of double membranes, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM), with intermembrane space in between. Invagination of IMM into the mitochondrial matrix results in formation of cristae, a structure that is essential for the function of mitochondria. Mitochondria serve as a central hub for physiological processes in eukaryotes, including production of adenosine triphosphate (ATP), regulation of calcium dependent signaling, generation of reactive oxygen species (ROS), and regulation of apoptosis and defects of mitochondrial enzyme leading to tumorigenesis and tumor progression due to abnormalities of the metabolic pathway or resistance to apoptosis domains, through control of mitochondrial outer membrane permeabilization (MOMP). Among the members of the BCL-2 family, anti-apoptotic proteins such as BCL-2, BCL-XL, and MCL-1 induce inhibition of apoptosis leading to tumor promotion with G101V, F104C, F104L, and D103Y mutations in the MCL-1 with L267V mutation detected in myeloma patients, the mutation does not interfere with binding of MCL-1 inhibitors such as S63845 and AZD-5991 to MCL-1, rather it prevents displacement of pro-apoptotic proteins by the drug, resulting in disruption of the process of apoptosis occurs upon induction of apoptosis, leading to an increase of MOMP, resulting in loss of membrane potential and release of cytochrome c is the first step of glycolysis. ATP-dependent phosphorylation of glucose is catalyzed by HK for generation of glucose-6-phosphate (G6P) which is also utilized in OXPHOS and the pentose-phosphate pathway most likely has an anti-apoptotic function. which might be responsible for its overexpression in most cancers. HK2 is bound to the outer membrane protein VDAC in mitochondria and probably gives HK2 an advantage regarding access to ATP generated during OXPHOS , a selective inhibitor of mIDH2, displays a potent inhibition of 2-HG production in the context of the ROS, a byproduct of normal metabolism of oxygen in cells, are highly reactive oxygen-containing molecules that react readily with other molecules in cells. Production of ROS occurs through recurring biochemical reactions during OXPHOS in the ETC with passage of electrons through a series of proteins in order to finally reach oxygen in mitochondria. Increased levels of ROS detected in cancer cells has long been regarded as tumorigenic through promotion of genomic instability. A moderately increased level of ROS in cancer cells can promote tumorigenesis and progression through activation of signaling pathways responsible for regulation of cellular proliferation, metabolic alterations, and angiogenesis as well as induction of DNA mutation and induction of apoptosis by release of cytochrome c by BAX/BAK harboring the T14634C mutation of ND6 that showed no change in expression of ND6 of complex II. Upon gaining electrons, ubiquinone is reduced to ubiquonol in order to supply electrons to complexes III and IV Cecchini . InteracMitochondrial dysfunction is a major cause of tumorigenesis and tumor progression in many cells. Many anticancer drugs that target dysfunctional mitochondrial metabolism and apoptosis pathways have been developed Fig. . HoweverPositive combination therapy can have a synergistic effect on efficacy (Duarte and Vale Therefore, selection of an optimal mitochondria-target in order to minimize drug toxicity, identification of patients who show resistance to the drug to be administered, and design of an alternative strategy for treatment in patients who show resistance are important. Combination drug therapy or another single drug capable of evading resistance might be an alternative strategy. Finally, as various anti-cancer drug therapies have been developed, cases of resistance to the drug have also been reported; thus, conduct of many clinical studies is still required in various cases in order to achieve a successful treatment outcome for cancer patients."} +{"text": "Osteoporosis (OP) is a systemic bone disease characterized by the decreased bone mass and destruction of bone microstructure, which tends to result in the enhanced bone fragility and related fractures, as well as high disability rate and mortality. Exercise is one of the most common, reliable and cost-effective interventions for the prevention and treatment of OP currently, and numerous studies have revealed the close association between gut microbiota (GM) and bone metabolism recently. Moreover, exercise can alter the structure, composition and abundance of GM, and further influence the body health via GM and its metabolites, and the changes of GM also depend on the choice of exercise modes. Herein, combined with relevant studies and based on the inseparable relationship between exercise intervention-GM-OP, this review is aimed to discuss the moderating effects and potential mechanisms of exercise intervention on GM and bone metabolism, as well as the interaction between them.The online version contains supplementary material available at 10.1186/s12967-022-03700-4. Osteoporosis (OP) is a kind of systemic metabolic bone disease characterized by descending bone mass and destruction of bone microarchitecture, predisposing to the enhanced bone fragility and associated fractures, as well as the high disability rate and mortality \u20133. AccorCurrently, a variety of drugs with different mechanisms of action have been applied in preventing and treating OP. Nevertheless, in the process of integrated management of OP, the pivotal contribution of exercise intervention still cannot be ignored , 7. In tIn addition, as the largest and most complicated micro-ecosystem in human body, the gut microbiota (GM) and its metabolites play a critical role in the regulation of host metabolism, nutrition, immunity, and so on . MeanwhiImportantly, exercise is of great significance for the maintenance of whole-body health. On one hand, exercise can directly act on various tissues and organs of the body to regulate different functions. On the other hand, exercise could significantly alter the structure, composition and abundance of GM, and further affect the body health through GM and its metabolites . Meanwhi14 orders of magnitude bacteria are colonized in the intestine, and the number of genes in the genome of GM is about 150 times that of the total number of genes in human genome [As the largest micro-ecosystem in human body, more than 10n genome . The GM n genome . Currentn genome . Especian genome . MeanwhiFirmicutes and Bacteroidetes. Fuhrman et al. [Clostridium and Bacillus were positively related to urinary estrogen metabolites, and the diversity of GM also increased with the enhancement of proportion of hydroxylated estrogen metabolites in urine. Meanwhile, the use of probiotics and prebiotics could change the composition, structure and abundance of GM, indicating the benefits of probiotics and prebiotics for bone metabolism. Regarding this, a previous randomized controlled trial conducted by Nilsson et al. [10 CFU of Lactobacillus reuteri ATCCPTA 6475 had a significantly lower reduction in BMD than individuals in control group after 12 months of treatment. Lei et al. [Lactobacillus casei Shirota for a period of 6 months. Moreover, van den Heuvel et al. [Transgalactooligosaccharides was able to enhance the intestinal calcium absorption in postmenopausal women, thus enhancing the bone mass and preventing OP.Specifically, in terms of the clinical studies, Wang et al. conducten et al. examinedn et al. suggestei et al. observedl et al. showed iAs for the animals\u2019 studies, by constructing the mice model of postmenopausal OP induced by ovariectomy (OVX), Tu et al. revealedTaken together, there is a close link between GM and OP, and a healthy intestinal microenvironment state has a significant protective effect on the bone. Importantly, GM mainly affects the balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, which plays a vital role in the regulation of bone metabolism and provides a novel target of intervention for the prevention and treatment of OP. Nevertheless, the relevant studies on the association between GM and OP are still in the initial stage, and more researches are needed to further clarify its deep-level mechanisms and explore more effective conditioning measures.As a kind of homeostatic stimulus, exercise intervention may diversify the GM and increase the number of beneficial microbial communities in gut. Exercise intervention contributes to enhancing the gastrointestinal peristalsis of body and promotes the timely excretion of feces, so as to reduce the contact time of intestinal mucosa with pathogens and harmful substances, further affect the characteristics of the intestinal contents and alter the composition of GM , 41. MeaThe dynamic balance between GM and host physiological function determines the possibility of host morbidity caused by GM imbalance. However, several previous studies have revealed that long-term chronic moderate-to-low intensity exercise has beneficial effects on body , 51. MorAkhmann mucophilus and Clostridium praevia, and these bacteria have been verified to be anti-inflammatory bacterial species [Verrucomicrobia, Verrucomicrobiaceae, Akkermansia and Dorea in the feces of the sedentary and overweight women increased after 6 weeks of moderate-to-low intensity power cycling training. Therein, Akkermansia and Dorea were verified to be able to ferment with dietary fiber as the substrate to generate the butyric acid. Besides, Hamasaki et al. [Enteric acidophilus, Bifidobacteria and Lactobacillus in their intestines increases, resulting in a decrease of the content of malondialdehyde and an increase of the activity of antioxidant enzyme, so as to improve a variety of metabolic processes in the body and then promote health [In addition, compared with the sedentary women, the premenopausal women who exercise continuously at the low intensity are equipped with the increased abundance of species . Moreove species also indi et al. also coni et al. , 64. Fore health , 66. HenNevertheless, different from the moderate-to-low intensity exercise, in the case of acute/vigorous exercise, the ischemic effects of intestinal mucosa and the enhancement of intestinal permeability resulting in the intake of bacteria and toxins could induce the inflammatory response of body . Accordi2max might reduce the visceral blood flow by 60\u201370%, and when the blood flow was reduced by 50%, the exercise-induced ischemia may result in the increased intestinal permeability. On the basis of this, the blood flows from the gastrointestinal tract via surrounding organs may also result in the loosening of tight junction proteins (mainly expressed by zonula occludens-1 (ZO-1) and Occludin), so as to further damage the intestinal mucosal barrier [With regard to this, Zouhal et al. suggeste barrier . Moreove barrier observedFirmicutes and Bacteroidetes. Li et al. [Autonomous exercise is a significant part of the structure of exercise modes. With regard to this, Matsumoto et al. first obi et al. also sugAgrobacterium reduced significantly in autonomous exercise group, suggesting that exercise intensity and exercise amount might be the variables influencing the function of GM. In addition, the changes in GM caused by exercise also seem to depend on the physiological state of individuals. A previous study conducted by Gordon et al. [In animal models, the most common type of forced exercise is the forced treadmill exercise. Compared with the autonomous exercise, the forced exercise has significantly different influence on the GM of experimental animals. With regard to this, in the mice model of colitis, Cook et al. observedn et al. indicateThe musculoskeletal system plays an indelible role and significance in the human health. In addition to acting as a scaffold for body, it also continuously communicates with other organs through the biochemical signals, and has basic neural, immune and endocrine regulatory functions , 86. TheFirmicutes and Bacteroides. Moreover, in terms of the clinical practice, Ilesanmi-Oyelere et al. [Recently, there have been research reports that the promoting effects of exercise on the bone is closely associated with GM. In a previous study, McCabe et al. focused e et al. conductee et al. concludee et al. \u2013101.Blautia, Roseburia, Anaerostipes, Butyricicoccus) in the intestine of athletes under high intensity exercise conditions. Butyric acid can directly supply the energy to the intestinal epithelial cells and repair injury, thereby reducing the injury to intestine of body caused by high intensity exercise training [Veillonella isolated from the feces of marathon athletes into experimental mice, and the exercise endurance of mice was significantly improved. Besides, several studies have also reported that the production of butyric acid is related to the production of heat shock protein 70 (HSP70) [As one of the significant metabolites of GM, SCFAs are mainly composed of the carboxylic acids and small hydrocarbon chains , 103. SCtraining , 111. Metraining suggestetraining transpla (HSP70) , 115. HSBacteroides enterica and Escherichia coli were involved in the production of secondary BAs in the colon, and exercise may increase the level of secondary BAs by increasing the contents of beneficial bacteria. Meanwhile, Meissner et al. [In addition to SCFAs, the metabolic disturbance of bile acids (BAs) is also involved in the occurrence and progression of OP. As a kind of signal molecule, BAs not only play a significant role in the absorption, transport and distribution of fat and fat-soluble vitamins, but also participate in the regulation of energy metabolism, thereby inhibiting the excessive proliferation of GM . Fukiya r et al. also revr et al. showed tr et al. , 121. ItDifferent exercise amount and exercise intensity may have different effects on the intestinal mucosal barrier and mucosal immune function, and regular moderate exercise may reduce the incidence of infection in body . MeanwhiIn addition, the long-term aerobic exercise can enhance the adaptability of body to exercise, and the intestinal mucosal barrier function can also be significantly improved under the long-term exercise intervention . Kang etOn one hand, GM is involved in immune maturation and anti-infection protection of the body, and in this process, the microorganisms are involved in immune system to recognize and distinguish between the beneficial and harmful bacteria . On the Lactobacillus and Bifidobacterium [Lactobacillus yeast, while the levels of IgA, IL-4 and IL-12 in saliva were not significantly changed. Furthermore, as a kind of indigestible polysaccharide, the prebiotics can stimulate the activation and growth of one or more beneficial bacteria in intestine. Similarly, Drakoularakou et al. [Galactooligosaccharides (GOS). Regular supplementation of Fructooligosaccharides (FOS) is also related to increased serum intestinal peptide concentrations and decreased circulating C-reactive protein (CRP) levels [In addition, the supplementation of probiotics/prebiotics also has a crucial impact and repercussion on exercise-mediated immune regulation. Athletes might also benefit from the regular probiotic supplementations, while with certain strain specificity , 143. Practerium , 145. Practerium \u2013148. Beracterium revealedu et al. revealed) levels . As a re) levels , more anFirmicutes and Bacteroidetes, induce the proliferation of beneficial bacteria and metabolites, and improve the function of intestinal mucosal barrier, so as to further modulate the bone metabolism. Hence, the appropriate exercise has indelible effects on prevention and treatment of OP. However, there are still various issues need to be negotiated in the researches on relationship between exercise, bone metabolism and GM and its metabolites, specifically including: (1) The mechanisms of exercise-related GM and its metabolites directly regulating bone metabolism needs to be further improved; (2) Whether the exercise-related GM and its metabolites have the linkage effects with other important organs in body to indirectly modulate bone metabolism; (3) Paying attention to and screening out the specific GM suitable for different races around the world and the specific flora for improving the motor function may provide the novel insights for the healthy development of motor system and the improvement of motor function level. Nevertheless, with the increasing maturity of microbiome technologies and the wide application of sterile or GF animals, it is believed that further in-depth exploration might provide new perspectives for the researches on link between exercise, GM and its metabolites, and bone metabolism, and also promote the interdisciplinary and integrated researches of exercise physiology, microbiology and metabolomics.In general, there is increasing evidence that exercise is an independent factor of external environmental stressors that affects the composition and diversity of GM, and improves the body metabolism and immune system. The imbalance of GM has a direct impact on the normal physiological function and the health status of host. Exercise can enrich the abundance and diversity of GM, improve the proportion of Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2"} +{"text": "The Inner Mongolia Autonomous Region ranks first among the five major pastoral areas in terms of lamb breeding of China. The Inner Mongolia Autonomous Region has a vast territory, with many famous grasslands and thousands of forage plants and multiple local high-quality lamb breeds. After hundreds of years of artificial breeding and improvement, Mongolian sheep have developed many varieties. Different diets, feeding and treatment methods have effects on the production performance, lipid deposition and flavor composition of mutton sheep. Therefore, understanding the relationship among Inner Mongolian lamb, meat quality, and flavor will improve the production of high-quality mutton. The regulation of meat quality and flavor will have a profound impact on the deep processing and income-generating capabilities of mutton. Non-genetic factors affect the quality and flavor of mutton, which are more intuitive than genetic factors. In this review, we cover the contributions made by scientists to explore and improve the quality and flavor of Inner Mongolia lambs through non-genetic means, compare the differences between grazing and drylot-feeding in detail, and summarize some feed additives. We hope that based on our review, we can provide some inspiration to improve the meat quality of Mongolian sheep. China is the world's largest producer of mutton. Among the five major pastoral areas in China, the Inner Mongolia Autonomous Region ranks first in the mutton industry in the country, accounting for 33% of the country's total mutton production . There aAccording to geographical distribution and genetic relationship classification, there are Tibetan sheep, Mongolian sheep and Kazakh sheep in China. Mongolian sheep is a short fat-tailed sheep, which is the most abundant and widely distributed sheep breed in China, and is suitable for extensive management of nomadic grazing throughout the year . MongoliMutton is an indispensable source of high-quality protein in the human diet . The conlongissimus thoracis, biceps femoris, and triceps brachii) are mainly glycolytic type II B fibers. With the increase of months, the muscle fiber has a trend of I \u2192 IIA \u2192 IIB. The diameter and cross-sectional area of muscle fiber gradually increase with the number of months, but the increase is slower after the age of 6 months , and whole-drylot-feeding . As the longissimus thoracis muscle of the grazing group were significantly higher than those of the drylot-feeding group; the fat content, slaughter, net meat rate, and redness value of the drylot-feeding group were higher than those of the grazing group . Th. Thlongiopposite 57, 58), 58longiopposite . The expas lower . The n-3as lower . Of couras lower . The maias lower . Owing tas lower . The umaas lower . Althougsemitendinosus and longissimus thoracis muscle of the grazing group and the heat denaturation temperature were higher than those of the drylot-feeding group . After sheep have eaten odorous forages, and are then fed without odorous forages for 7\u201314 days, the odor can be eliminated produce significantly higher volatile indole content in the rumen than those grazing on other types of pastures, so their flavor is poor , indicating that A. mongolicum polysaccharide has an immunomodulatory effect on sheep peripheral blood lymphocytes in the diet reduced the crude fat, SFA, and SA content of mutton and increased crude protein, crude ash and dry matter, MSFA, and PUFA, among them, the content of ALA increased by 13.89%, and no heavy metal residues were detected (Jujube) in the diet can effectively promote the immunity, growth and development of Bamai sheep, and increase the crude fat content and IMP content in Bamei mutton.Chinese herbal medicine is based on natural animals, plants, and minerals; contains many flavor substances and antibacterial ingredients; and has dual functions of nutrition and medicine , 131. Itdetected , 136. Gadetected pointed Lycopene is a carotenoid, mainly found in tomato pulp. This natural plant pigment has strong antioxidant properties, can regulate cell growth and metabolism, and enhances the body's immunity. The polyunsaturated double bond structure of lycopene has the effect of scavenging free radical groups, so that lycopene has strong antioxidant properties. Ma et al. found thAlfalfa and silage are considered important feeds for herbivores, providing abundant feed protein and physically effective neutral detergent fibers. Alfalfa saponin is one of the most valuable plant secondary metabolites. Saponins are composed of a fat-soluble core with a steroid or triterpene structure and are amphiphilic. This structure gives saponins membrane-dissolving activity and explains their antibacterial, antitumor, and anti-inflammatory properties in animals. In addition, saponin can act on cholesterol and control lipid metabolism through its ability to bind cholesterol in the intestine and other tissues put forward different requirements for the tenderness, intermuscular fat content, flavor, and other attributes of lamb. Therefore, the identification of mutton in different regions should be made through two aspects. On the one hand, the local government should regulate the mutton industry chain in accordance with policies as soon as possible; On the other hand, the identification of sheep grazing in different grasslands depends on the whole-process traceability technology and the correlation between different geographical environment characteristics and local meat quality.Factors such as livestock age, gender, castration, tail docking, feed additives, nutritional level of the diet, grazing and drylot-feeding all affect the quality and flavor of mutton, which are more intuitive than genetic factors. Feed is a key factor in improving the quality and flavor of mutton; the rumen fermentation process and biohydrogenation have a great influence on the composition of intramuscular fatty acids; antioxidant levels of lamb during storage and cooking are also worth investigating. Through the combination of appropriate breeding methods, nutritional control factors and scientific management, the quality and flavor of mutton can be improved, the mutton taste problem of mutton can be fundamentally controlled, and the needs of consumers can be met.YL: writing\u2014original draft and writing\u2014review and editing. RL and YY: writing\u2014review and editing. YZ and YH: resources. HW: supervision and funding acquisition. KL: supervision. All authors contributed to the article and approved the submitted version.This research was funded by the Science and technology projects in Inner Mongolia Autonomous Region (No. 2021GG0029) and Central Public-interest Scientific Institution Basal Research Fund (Nos. 1610332022013 and 1610332022009).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "PRESENT . Moreover, the two Panels of the second day brought together respected specialists who discussed the focus of the AMN as a society and on TBI in low- and-middle-income countries.The second day of the 2022 Academy of Multidisciplinary Neurotraumatology (AMN) Virtual Congress began with Session 4, with Prof. Karin Diserens (Switzerland) and Dr. Pieter Vos (the Netherlands) as chairpersons. The day encompassed a plethora of presentations on TBI, with the speakers approaching subjects such as disorders of consciousness, the role of Brain-Derived Neurotrophic Factor (BDNF), diffuse axonal injury, the impact of TBI on the Alzheimer's Disease, personalized approaches to TBI management, traumatic brain hemorrhage, the role of oxiracetam nanodelivery for the enhancement of memory, the complications of decompressive craniotomies following TBI, neurovascular therapies and the innovative The first presentation regarded the modern concepts of disorders of consciousness, where Karin Diserens (Switzerland), Head of the Acute Neuro-rehabilitation Unit at the Department of Clinical Neurosciences from Lausanne University Hospital (Switzerland), shared her expertise on neurotrauma. The pathologic alteration in consciousness represents one of the most challenging aspects of TBI since the simple definition of consciousness during history proved to be problematic from a scientific point of view and from a philosophical one. The evolution of medicine has led to better outcomes secondary to brain injuries, prolonging survivability. Several aspects of the disorders of consciousness have led to a better and deeper understanding of the Disorders of Consciousness (DOC) from an anatomical, biological, and functional perspective.In modern medicine, the concepts of DOC have changed with the help of electroencephalogram (EEG) or functional Magnetic Resonance Imaging (MRI) studies and translational neurology. These concepts are a mirror to the continuous development of medicine.Secondly, Anton \u00c1lvarez (Spain), Director at Medinova Institute of Neurosciences and Clinical Research and Director at QPS-JSW Life Sciences (Spain), presented an intriguing insight into the role of Brain-Derived Neurotrophic Factor (BDNF) in clinical and basic research. BDNF represents the most abundant neurotrophin in the brain with an essential role in synaptic plasticity, cell differentiation and survival, playing a vital role in neuropathology and treatment and exerting a positive influence on TBI neurorecovery by promoting endogenous processes of regeneration, thus enhancing survival, and improving TBI outcomes. It is, therefore, essential to enhance BDNF in the brains of TBI patients to improve cognition and prevent dementia after TBI. Lastly, it is crucial to consider the shift from acute neuroprotection to sub-acute and chronic neurorestoration.Moreover, Pieter Vos (the Netherlands), Neurologist at the Department of Neurology at Slingeland Hospital in Doetinchem (the Netherlands), conducted a fascinating presentation regarding diffuse axonal injury. Diffuse axonal injury is one of the significant complications of TBI that can lead to impairment and death. With an unknown incidence, this insult to the brain leads to malfunction of the neuronal networks, affecting various functional structures of the brain. Diffuse axonal injury is found mainly in severe TBI cases, predominantly affecting the white matter of the frontal and temporal lobes and the structures of the brainstem and corpus callosum. The definitive diagnosis is made post-mortem, although imagery like Computed Tomography (CT) or MRI can identify various lesions secondary to diffuse axonal injury. Therefore, Dr. Vos highlighted that for TBI patients with diffuse axonal injuries, preventing secondary injuries and providing physical, neuropsychological, and pharmacological rehabilitation is of utmost importance in decreasing morbidity and mortality.The session ended with a presentation by Alexandru V. Ciurea (Romania), Vice President of the Romanian Ministry of Health Neurosurgical Committee, Chief of Neurosurgery and Scientific Director at Sanador Medical Center Hospital in Bucharest and Professor of Neurosurgery at Carol Davila University in Bucharest (Romania), on the role of TBI as a trigger or aggravating factor in Alzheimer's disease. Several pathophysiological aspects of TBI remain an enigma. Thus, the gap between translational and clinical research represents a need, an opportunity, and the future of TBI. A close collaboration between clinicians and translational researchers will lead to the further development of this field, mainly by finding comparable data between human and animal models. Prof. Ciurea presented a current study on Alzheimer's Disease and TBI on 19 patients, from 2013 to 2022, showcasing that TBI is an aggravating factor for Alzheimer's disease, as it affects synaptic transmission. Prof. Ciurea discussed further prevention strategies for Alzheimer's Disease.th session, Prof. Christian Matula (Austria) and Prof. Martin Rakusa (Slovenia) represented the chairpersons, and exciting topics related to neurosurgical aspects of TBI and inspiring approaches towards TBI were showcased.During the 5At the beginning of the session, Felix Brehar (Romania), Head of the Stereotactic and Functional Neurosurgery Department at Bagdasar Arseni Clinical Emergency Hospital in Bucharest and Associated Professor at Carol Davila University of Medicine and Pharmacy in Bucharest (Romania), presented current and future trends toward a personalized approach to TBI management. A successful individualized approach should pinpoint the presence, the severity, the possibility that the patients would recover on their own, the best treatment option, and what the long-term disability would be. A personalized approach integrates clinical diagnosis, multi-omics approach, and tailored treatment. The multi-omics integrates data on genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Prof. Brehar showcased the role of biomarkers in TBI in the diagnosis, stratification, delivery of targeted therapy, and prognosis. A take-home conclusion from the presentation regards the variability in TBI, the need for further research and the importance of multimodality and interdisciplinary efforts in the approach of TBI.th session of the Congress ended with the skillful presentation of Prof. Stefan Florian (Romania), Head of the Department of Neurosurgery at Cluj County Emergency Hospital and Vice President of the Romanian Society of Neurosurgery. Prof. Florian delivered a detailed perspective regarding the complications of decompressive craniectomy in TBI.Bringing forth another inspiring approach, Martin Rakusa (Slovenia), Consultant Neurologist in the Division of Neurology and Head of the Medical Research Department at University Medical Centre Maribor (Slovenia) discussed the topic of traumatic brain hemorrhage. Prof. Rakusa pinpointed the rarity of traumatic hemorrhage in TBI, with a more common occurrence in more severely affected patients, as well as the lack of association of anticoagulants with hemorrhage. An equally insightful presentation was that of Hari Shanker Sharma (Sweden), director of Research at the International Experimental Central Nervous System Injury & Repair (IECNSIR) at Uppsala University. Prof. Sharma discussed on the role of oxiracetam nanodelivery for the enhancement of memory, functional recovery, and induction of neuroprotection following a concussive head injury. The 5The last session of the AMN Congress, Session 6, having Prof. Michael Chopp (USA) and Prof. Hari Shanker Sharma (Sweden) as chairpersons, discussed neurovascular therapies and the innovative TBI registry, PRESENT. The first speaker of the session, Michael Chopp (USA), Vice Chairman for Research of the Department of Neurology and Scientific Director of the Henry Ford Neuroscience Institute in the USA, discussed the topic of exosomes and neurotrophic factors in Neurovascular Therapy. On a microscopic level, exosomes represent a valuable structure with various functions. For example, they can assure intercellular connection by transporting different nucleic acids, proteins, or lipids. Prof. Chopp further discussed on the progression of diseases, and potential biological markers of different lesions.It was dr. Iulia Vadan (Romania), Neurologist at RoNeuro Institute for Neurological Research and Diagnostic in Cluj-Napoca (Romania), who then discussed the status of PRESENT. PRESENT, short for Patient Registry, Short Essential Neurotrauma, has been developed as an international, multidisciplinary longitudinal, prospective registry. The registry represents an electronic platform for TBI patients, covering the patient's pathway during the hospital stay and discharge, with possibility of implementation at national and international levels. PRESENT will be able to mirror the multimodal treatment in TBI. One of the main characteristics of TBI is the heterogeneity of mechanisms, causes, and types of brain injuries, as well as the patient's particularities that lead in a first phase to the primary injury and then to secondary injuries. Furthermore, the patient's rehabilitation after TBI is of utter importance by influencing the degree of posttraumatic disability and the patients' quality of life, as well as their families. Based on an electronic platform, it is a valuable tool in obtaining a TBI patients database that will cover several elements from epidemiology to the pathway of care, outcomes, treatments, and rehabilitation measures.Finally, Prof. Andriy Huk (Ukraine), Chief of the Department of Endoscopic and Craniofacial Neurosurgery at Romodanov Neurosurgery Institute, painted an inspiring portrait of the role of PRESENT in the multimodal treatment following a TBI.rd Panel \u201cThe AMN is an ambitious medical society-what should be its focus?\u201d, Volker H\u00f6mberg (Germany), Jongmin Lee (South Korea), Johannes Vester (Germany), Lynne Lucena (The Philippines), Christian Matula (Austria), Nicole von Steinb\u00fcchel (Germany), Pieter Vos (The Netherlands) and Dafin Muresanu (Romania) discussed the focus of AMN as a modern medical society. The AMN aims to advance research, practical application, and education in neurotraumatology and is determined to become a leading example of multidisciplinary cooperation. However, considering the complexity of TBI, especially with the fast-growing advancement of research and innovation, finding the right path for scientific societies can be a challenging pursuit.During the 3The AMN Congress was finalized with the last of the panels, respectively Panel 4 \u201cTBI in low- and middle-income countries \u2013 what are the specifics, what are the pragmatic solutions for improvements\u201d, where panellists like Felix Brehar (Romania), Volodymyr Golyk (Ukraine), Ignacio Previgliano (Argentina) and Tarek Lotfy (Egypt) alongside members of the AMN board and specialists from Romania, including Andriy Huk (Ukraine), Johannes Vester (Germany), Nicole von Steinb\u00fcchel (Germany), Stefan Strilciuc (Romania), Razvan Chereches (Romania), Irina Vlad (Romania), Iulia Vadan (Romania), Constantin Radu (Romania) showcased the specific problems of neurotrauma in low- and middle-income countries (LMIC), as well as discussed possible approaches.LMIC are more affected by TBI than more resourceful ones and experience specific challenges in practice and research, the availability and reliability of data. Pragmatic solutions, such as PRESENT are needed to obtain more profound knowledge about TBI.Moreover, it is crucial to consider the needs and particularities of the specific countries when discussing TBI research and consider the patient's pathway through the medical system. Therefore, having an \u201cecological\u201d approach and considering the larger picture when approaching TBI remains of utmost importance.AMN website.The exciting event showcased insight into a wide-range of TBI-related themes, offering a glimpse into the complex and intricate world of neurotraumatology. The multidisciplinary principle of the AMN is reflected in the variance of perspectives presented, standing as the cornerstone of future research and medical practice. In a fast-changing and unpredicted environment, collaboration and dissemination of knowledge, skills, and innovation support the pursuit of science and bring optimistic perspectives for the future. More information on the congress can be found on the"} +{"text": "In the United States most adults have a preference to die at home and is an indicator of good end-of-life care. In the context of dementia, family members and caregivers are decision makers and part of good and equitable care involves understanding cultural variation in attitudes and social norms related to dementia, death and dying, and the meaning of a good death. This symposium explores racial and ethnic variation in lifetime dementia diagnosis and end-of-life care quality indicators. The first presentation examines racial, ethnic, and geographic variation in the rarely discussed lifetime prevalence of dementia and survival time from dementia diagnosis to death using national Medicare data. The second presentation describes the relationship between end-of-life care planning and satisfaction with end-of-life care using data from the Health and Retirement Study. The third presentation describes variation in place of death, a key indicator of end-of-life care quality, by dementia diagnosis and race/ethnicity using national Medicare data. The fourth presentation examines variation in hospice use, another indicator of end-of-life-care quality, and place of death by dementia diagnosis, race, and ethnicity using national Medicare data. The symposium concludes with a presentation examining the relationship between place of death and satisfaction with care received using data from the Health and Retirement Study. The Institute for Healthcare Improvement\u2019s Triple Aim serves as a lens for discussing policy and practice implications of the major findings from each presentation."} +{"text": "Participatory action research (PAR) is a promising approach to engage older adults in self-determined research that influences policies and practices; however, the voices of older adults are very often missing from most PAR projects. The purpose of this paper is to reflect upon the challenges and opportunities of engaging lesbian, gay, bisexual, transgender, and queer (LGBTQ+) elders of color in PAR during the Covid-19 pandemic. Data were generated through interviews with LGBTQ+ elders of color and their caregivers and analyzed thematically. Findings illustrate several barriers and facilitators of conducting PAR during the pandemic. Barriers included feelings of distrust toward research(ers), pandemic related issues and illnesses, and competing priorities and interests. Facilitators included leveraging community connections and participating in community-based activities. Study findings have the potential to advance a critical turn in gerontology that is committed to the liberation of marginalized older adults in aging research, policies, and practices."} +{"text": "The COVID-19 pandemic was declared a Public Health Emergency of International Concern on January 30, 2020. The government of Zimbabwe through the Ministry of Health and Child Care set up the COVID-19 national preparedness and response plan in which the laboratory was a key pillar. The implementation of PCR testing, genomic sequencing, and the establishment of quality management systems during the COVID-19 response strengthened the capacity of the public health laboratory system in responding to the pandemic. Here we present the different strategies taken by the government that strengthened laboratory capacity, the lessons learned during the COVID-19 response, and recommendations on how the capacity can be sustained and leveraged for outbreak response in the future. On the 30The development of the National COVID-19 Laboratory testing strategy and the review of the National Health Laboratory Strategy and policy documents in the context of COVID-19 played an important role in strengthening the laboratory in Zimbabwe. Tools for guidance and standard operating procedures for use during implementation were developed, reviewed, and approved as a matter of urgency, adopting WHO guidelines for SAR-CoV-2 infection detection.th of March 2020 [Typical of health systems in sub-Saharan Africa, the capacity to respond to the COVID-19 pandemic in Zimbabwe was low due to inadequate funding and a lack of trained personnel to conduct COVID-19 testing and genomic sequencing . Zimbabwrch 2020 . The govThe Ebola virus disease (EVD) outbreak in West Africa provides useful lessons on how emergency responses can impact health systems, . Novel tThe Ebola virus disease (EVD) outbreak in West Africa provides useful lessons on how emergency responses can impact health systems, . Novel tThe emergency use listing of two Ag-RDT, Abbott and SD Biosensor by WHO in September 2020 led to tThe COVID-19 response demanded strict adherence to quality when performing COVID-19 testing to ensure accuracy, reliability, and timely release of results. Before the COVID-19 pandemic in Zimbabwe, a few government and private laboratories were participating in external quality assessment programs (EQA) such as proficiency testing (PT). During the COVID-19 pandemic, the MoHCC and partners through the DLS facilitated the setting up of quality management systems (QMS) and participation of laboratories in PT programmes offered by organisations such as the WHO, Thistle (South Africa), and One World Accuracy (Canada). To standardise laboratory testing of COVID-19, Africa CDC in collaboration with ASLM and PanaBIOS as technical leads, introduced the COVID-19 Laboratory testing certification Program (CoLTeP) to ensure accuracy, and reliability of test results and that testing procedures be conducted under appropriate biosafety and biosecurity conditions . A totalThe COVID-19 response brought about collaborations and partnerships in the form of inter-governmental, government to private, government to institutions and institution to institution collaborations. These partnerships strengthened the public health laboratory system in Zimbabwe in areas of the supply chain and logistics, training of laboratory personnel, sequencing, QMS, and outbreak response. Different partners came aboard to support the pandemic response by providing technical support for SARS-CoV-2 testing, outbreak response, building sequencing capacity, buying of reagents, and capacitating laboratory personnel e.g. the WHO, the Jack Ma Foundation , BiomediEarly response to the COVID-19 pandemic in Zimbabwe was slowed due to a lack of skilled personnel to perform SARS-CoV-2 molecular testing among other reasons. Many laboratory cadres also lacked training and skills in disease outbreak response. Collaborative efforts with organisations such as the Kwazulu-Natal Research Innovation and Sequencing Platform (KRISP), QIB in the United Kingdom, and the Africa CDC facilitated the training of Zimbabwean scientists in genomic sequencing and bioinformatics analysis. It will be important to retain the trained staff through improving remuneration and working conditions and supporting continuous improvement towards building a resilient public health laboratory system capable of responding to future outbreaks.The COVID-19 response in Zimbabwe generated capacity and strengthened the public health laboratory system. However, the implementation of various strategies was not devoid of challenges. We propose recommendations to address some of the challenges and to maintain and improve existing capacity. Beyond the COVID-19 pandemic, a robust public health laboratory system will be important to address existing public health problems as well as respond to the next pandemic. 1)There is a need to maintain existing partnerships between the government and different local and international partners beyond the COVID-19 pandemic to enhance disease surveillance and cooperation in areas of public health interest. The government must maintain the existing partnerships with local private laboratories and research institutions to improve the overall surveillance and response efforts to disease outbreaks. The government through the DLS can play a role in supporting private laboratories to set up sustainable quality management systems with the goal of certification and accreditation. 2)The COVID-19 pandemic exposed the low capacity for genomic surveillance in Zimbabwe. There is an urgent need to invest in next-generation sequencing (NGS) platforms with high throughput and training of many laboratory cadres in performing sequencing and bioinformatics analysis of sequencing data [st century.Before the COVID-19 pandemic, several deficiencies characterized the public health laboratory system in Zimbabwe. For instance, there were a few PCR and sequencing platforms as well as trained and skilled personnel in the areas of sequencing and bioinformatics analysis. However, during the pandemic, a significant shift in the paradigm of strengthening the public health laboratory system occurred characterised by improved laboratory infrastructure, training of laboratory cadres, and setting up of QMS and participation in EQA programmes, decentralised Ag-RDT testing, and important partnerships between the government and various organisations. In the post-pandemic period, further gains in strengthening the public health laboratory system can be achieved by constant capacity building in molecular techniques training, bioinformatics analysis, and setup maintaining of quality management systems. The current experiences have strengthened the public health laboratory system in Zimbabwe and this has laid the foundation for a significant post-COVID-19 transformation so that the public health laboratory system can be better prepared to address existing public health problems and the next global threat(s) of the 21"} +{"text": "Over the last two decades, imaging techniques have become irreplaceable tools in nanotechnology: electron microscopy techniques are routinely used to observe the structural features of newly manufactured nanoconstructs, while light and electron microscopy, magnetic resonance imaging, optical imaging, positron emission tomography, and ultrasound imaging allow dynamic monitoring of the biodistribution, targeting and clearance of nanoparticulates in living systems, either for the whole organism or at the level of single cells, tissues and organs .The first Special Issue, \u201cMolecular Imaging in Nanomedical Research\u201d, contained five research articles and two reviews on diverse imaging techniques applied to the development of novel nanoconstruct-based strategies for diagnosis and therapy . In thisChang and co-workers used polSu and co-workers aimed toMagnetic iron oxide nanoparticles are potential contrast agents for magnetic resonance imaging and magnetic particle imaging. Baki and co-workers modifiedWo\u017aniak and co-workers reviewedDopamine-related tracers are a powerful tool used to assess the status of presynaptic nigrostriatal terminals in the brain; Palermo and co-workers illustraAptamers are short, single-stranded, non-coding DNA or RNA nucleotides that specifically bind molecular targets and may be functionalized via radioisotope labeling for use as diagnostic and therapeutic agents. Due to their high specificity and adjustable binding affinities, aptamers targeting HER2 are promising agents in nuclear medicine for the early detection, diagnosis and potential treatment of HER2-positive breast cancer. In their review, Vi and co-workers describeAfter describing the concepts and characteristics of general optical coherence tomography systems, Wang and co-workers describeAmong the existing contrast agents for magnetic resonance imaging, smart nanoprobes that respond to selective stimuli may provide information on tissue and cell functional features. This subject was reviewed by Wang and co-workers , who focElucidating the interactions between the nanoconstructs and the biological environment is crucial in nanomedicine, and transmission electron microscopy provides direct evidence of the uptake and biodistribution of nanoparticles, as well as of their relationships with the cell and tissue components. My paper presentsOverall, this Special Issue confirms the key contribution of molecular imaging techniques, which support and foster the creativity and inventiveness of scientists engaged in nanomedical research."} +{"text": "The magnitude and exceptional opportunity to research the psychological distress of shelter in place resulted in a publication frenzy on a smorgasbord of research studies of variable scientific robustness. Confinement, fear of contagion, social isolation, financial hardship, etc. equated to stratospheric stress levels. The decline in protective factors as a function of quarantine anecdotally reflected historic rates of anxiety and depression.In this study, we combined 12 variegate datasets and developed an algorithm to build a model to identify key predictors of pandemic-related stress with high accuracy and generalizability.This study reports on existing published data. We first describe the International and then the Italian dataset . The time-frame (first wave of lockdown), method (survey), measurement tool , and outcome measures were extremely similar to enable consolidation of datasets . The Flesia et al., (2020) data set was integrated into the Adamson et al., (2020) dataset as the first step towards data validation construction of the ML predictive model.We aim to demonstrate the strength of combining cross-cultural datasets, and the applicability of ML algorithms to facilitate the process and generate a predictive model that identifies and validates key predictors of pandemic-related stress and accommodates for interaction with demographic, cultural, and other mitigating factors while concurrently having high generalizability.We believe our model provides clinicians, researchers, and decision-makers with evidence to investigate the moderators and mediators of stress, and introduce novel interventions to mitigate the long-term effects of the COVID-19 pandemic.No significant relationships."} +{"text": "Community-based treatment of possible serious bacterial infection (PSBI) in young infants, when referral to a hospital is not possible, can result in high treatment coverage and low case fatality. However, in Ethiopia, the coverage of PSBI treatment remains low, worsened by COVID-19. To understand the challenges of delivery of PSBI treatment and design and test adaptative strategies to mitigate the impact of COVID-19 on neonatal mortality, we did implementation research (IR) employing Implementation Research Logic Model (IRLM). In this paper, we describe IRLM application experiences in designing, implementing, and evaluating strategies to improve community-based treatment of PSBI during the COVID-19 pandemic in Ethiopia.This IR was conducted between November 2020-April 2022 at Dembecha and Lume woredas of Amhara and Oromia regions, respectively. We employed narrative reviews, formative assessment and facilitated stakeholder engagement to develop the PSBI treatment IRLM to identify barriers, understand the conceptual linkages among determinants, choose implementation strategies, elicit mechanisms, and link to implementation outcomes. In addition, we used the IRLM to structure the capture of emerging implementation challenges and resulting strategy adaptations throughout implementation.This IR identified COVID-19 and multiple pre-existing contextual factors. We designed and implemented implementation strategies to address these challenges. These adaptive strategies were implemented with sufficient strength to maintain the delivery of PSBI services and improve mothers\u2019 care-seeking behavior for their sick young infants.The IRLM offers us a clear process and path to prioritize implementation challenges, choose strategies informed by mechanisms of action, and where the adaptive implementation of community-based management of PSBI would lead to high-implementation fidelity and change in mother behavior to seek care for their sick young infants. The IRLM was also an effective tool for stakeholder engagement, easily explained and used to structure discussion and decision-making during co-design meetings.The use of the IRLM helps us to specify the conceptual links between the implementation challenges, strategies, mechanisms of action, and outcomes to explore the complex community-based management of PSBI during complex contexts to improve high-fidelity implementation and integration of PSBI treatment in the primary healthcare delivery systems through active engagement of stakeholders.The online version contains supplementary material available at 10.1186/s12913-022-08945-9. Possible serious bacterial infection (PSBI) was identified as a leading cause of mortality in young infants (0\u201359\u00a0days of age) in Sub-Saharan Africa, contributing to 37% of the 2.1 million neonatal deaths \u20136). The Ethiopia introduced community-based newborn care (CBNC) in its flagship Health Extension Program (HEP) to improve access to and use of appropriate treatment for neonatal sepsis when a referral was not possible in 2012 . HoweverThere is limited evidence of the level of impact of the COVID-19 pandemic on care-seeking for neonatal sepsis programs in Ethiopia. Implementation research (IR) was conducted between November 2020-April 2022 in Dembecha and Lume districts of Amhara and Oromia regions, respectively. The research was carried out by JSI Research & Training Institute Inc./The Last Ten Kilometers (L10K) Project, funded by the Bill & Melinda Gates Foundation. The aim was to understand the demand- and supply-side challenges of delivery of PSBI treatment during the COVID-19 pandemic and to develop and test adaptative strategies to mitigate the impact of COVID-19 and other barriers on community-based management of PSBI implementation and uptake. Implementation research is the scientific study of methods to promote the systematic uptake of research findings and other evidence-based practices into routine practice, to improve the adoption, high-fidelity implementation, and maintenance of quality, effective, evidence-based practices in health care services . The ImpIn this paper, we describe the use of the IRLM for stakeholder engagement and incorporate formative research to inform the design, implementation, and evaluation of strategies to improve community-based management of neonatal bacterial infection during the COVID-19 pandemic. The utilization of the IRLM in Ethiopia represents important insights into using this tool and IR to inform adaptive implementation, engaging key stakeholders, and generating generalizable knowledge to inform the broader, context-adapted implementation of PSBI treatment.This implementation research was conducted between November 2020-April 2022 in Dembecha and Lume woredas of Amhara and Oromia regions Fig.\u00a0 DembechaWe employed narrative review, formative assessment, and facilitated stakeholder engagement to develop the management of PSBI IRLM. The work was designed to articulate determinants, choose implementation strategies, and link these through mechanisms to targeted implementation outcomes. In addition, during the implementation phase, we captured ongoing implementation challenges and adaptations of strategies using a tracker. We applied the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) . We alsoIn April 2021, we conducted a narrative review of existing literature to quickly identify the overview of previously described barriers and facilitators of community-based management of PSBI implementation in Ethiopia. One author (GT) searched Google Scholar and PubMed for publications in English between 2012 to 2021, starting after the initiation of CBNC services in Ethiopia. Search terms used included: possible serious bacterial infection, community-based management of newborn illnesses, neonatal sepsis, uptake, utilization, barriers, facilitators, determinants, and Ethiopia. The title or abstract of the article was downloaded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram frameworWe conducted a cross-sectional population-based household survey of 4,242 mothers who gave live birth 2\u201314\u00a0months before data collection and resided in the two woredas. Survey captured information including household and sociodemographic characteristics, experiences related to using maternal and newborn health services across the continuum of care, care-seeking for sick infants and children, and Knowledge and risk perception of COVID-19. A structured questionnaire translated into local languages (Amharic and Oromiffa) was used to capture the data using a web-based mHealth platform (SurveyCTO) using smartphones , development partners (4), direct service providers (16), and community volunteers (8). The interview guide was designed using CFIR to understand what factors facilitate or hinder community-based management of PSBI implementation, including characteristics of the health system, intervention, individual, inner, and outer settings.We engaged stakeholders throughout the research process as a keystone of our implementation research in the selection, prioritization, and operationalization of tailored and appropriate implementation strategies to improve the adoption, implementation, and sustainment of community-based management of PSBI. For this purpose, we followed a rigorous and thoughtful development process to systematically plan for the implementation strategies by facilitating a national stakeholder consultation which expanded on adapted expert recommendations for implementing change (ERIC) protocol employinFollowing the formative assessment and exploration of potential strategies from the literature, we developed an initial IRLM. Then, we conducted a national co-designing workshop on May 11\u201312, 2021. The workshop involved the Ministry of Health (MOH), National Child Health Technical Working Group, including program managers and development partners; it also included the National RMNCH-N Research Advisory Council Child Health and Immunization group, including their program managers, academics, researchers, and development partners. The workshop also included development partners active in neonatal care in Ethiopia. The workshop\u2019s primary aim was to share the assessment findings and design tailored solutions to address implementation challenges.On the first day, the research team presented an overview of implementation research and formative assessment findings, followed by a discussion on the barriers to community-based management of PSBI implementation. On the second day, the research team presented the draft IRLM, including the identified determinants and preliminary implementation strategies from the literature. Next, the team facilitated a group process of identification and prioritization of implementation strategies. The research team then populated the determinants and strategies of the IRLM raised through an iterative discussion with stakeholders and used the matrix to understand the conceptual links between determinants, implementation strategies, mechanisms, and outcomes.In the last week of May 2021 and the first week of June 2021, we conducted a woreda-level co-creation workshop with regional health bureaus, zonal health departments, woreda health offices, facility-level managers, service providers, kebele managers, and HEWs. Through the co-creation workshop, L10K and participants contextualized and validated the nationally co-designed implementation strategies, identified additional local contextual community-based management of PSBI implementation challenges that had not been captured during the national co-design phase, designed relevant strategies, and developed micro-plans to improve PSBI treatment implementation. All HPs and health centers in the two implementation woredas developed micro-plans. of childhood illnesses and newborn care, particularly for sick young infants (SYI). A higher proportion of mothers who resided in Dembecha (11%) compared to Lume woredas (5%) reported symptoms of severe neonatal infection in their infants. Communities in Dembecha demonstrated lower care-seeking behavior compared to Lume woreda, with only 52% of mothers receiving antibiotics for neonatal sepsis there compared to 70% of mothers in Lume. Most women sought care for their SYI at health centers and bypassed the HPs. Additionally, the following pre-existing factors were identified as external barriers to the delivery of PSBI treatment: phase-out of partner support, low community care-seeking behavior, negative community attitudes toward services for neonatal illness and PSBI, lack of community trust in HEWs\u2019 capacity to manage PSBI, and low functionality of organized female community volunteers called Women Development Armies (WDAs).The following characteristics were identified as barriers to HEW management of PSBI implementation: lack of competency and confidence in their PSBI knowledge and skills; lack of training, mentoring, and coaching; low motivation, attendance, and engagement regarding PSBI care implementation; competing workload and engagement in non-health activities; and fear of contracting COVID-19. In Dembecha, HEW knowledge of all PSBI signs was lower than in Lume, with 33% and 41%, respectively. Likewise, a higher number of HEWs untrained in the basics of PSBI were identified in Dembecha compared to Lume.Process: The formative assessment, as well as the stakeholder consultation, identified the following implementation process barriers to PSBI care: poor integration of management of PSBI services in the woreda health system, weak coordination, ownership, and stakeholder engagement, and a weak culture of learning.Previous implementation research on the management of PSBI when referral was not feasible conducted in Ethiopia, Malawi, Nigeria, Bangladesh, Pakistan, and India identified several strategies critical to supporting effective implementation at the individual, community, facility, and systems levels. At the individual and community level, these included: training health care workers, in-field technical support, performance reviews , and comDuring the stakeholder engagement, based on the formative assessment and narrative review findings, we grouped major management of PSBI implementation challenges that existed before COVID-19 and were exacerbated by the pandemic into the following categories: 1) low competency, confidence, and motivation of HEWs; 2) weak primary health care system; 3) suboptimal community engagement; 4) other systemic factors ; and 5) weak coordination and integration. We also presented results from the literature review and formative assessment. In consultation with stakeholders, we adopted and adapted a number of the strategies from the literature and developed new ones, including reflecting on COVID-19 -related challenges to enhance the adoption, acceptability, and high-fidelity implementation of community-based management of PSBI interventions, with the aim of further integration and scale up.As presented in Table Using the IRLM, we described the mechanisms of action that the proposed strategies would operate to influence the desired outcomes. For example, building the organization's capacity for better integration, coordination, and stakeholder engagement would lead to strong district-level operational management and high-fidelity intervention delivery during/after study to maintain strategies. Adoption of the strategies, training and supportive supervision increased skills and interest in delivering PSBI treatment effectively and with higher fidelity. It also strengthened referral systems, addressed community knowledge and fears while increasing fidelity, effectiveness, and adoption Fig.\u00a0.Fig. 3ThReach: number of newborns identified and visited by community health workers, percentage of treatment coverage, and percentage of referral refusal; Effectiveness: recovery, and case fatality rate; Fidelity: percentage of patient adherence to antibiotic treatment, percentage of patients who received follow-up care, percentage of classification errors, and percentage of patients who received correct antibiotic; Acceptability: number of parents/family who refused referral but accepted community-based PSBI treatment, barriers and facilitators of acceptability and care-seeking, percentage of PSBI cases who accepted the referral, and rate of adherence to outpatient treatment. We developed a matrix of indicators and data sources for adaptive implementation of PSBI treatment during COVID-19 in Ethiopia from 42 HPs reported participation in at least one PHCU level PRCMM in the last six months HPs treated at least one sick young infant in the previous six months, significantly improving from 36% in the last six months.During implementation, we tracked ongoing implementation challenges and adaptive strategies. We used the IRLM framework to capture these emerging or persistent challenges and adapted strategies to articulate the mechanisms of action and link them to outcomes Fig.\u00a0.During the implementation, adaptive implementation strategies were also incorporated, including facilitating the redistribution of gentamicin 20\u00a0mg/ml, intensifying the support and monitoring visits, and increasing offsite PSBI treatment training of HEWs and their supervisors at HPs in Dembecha. Due to the civil war in the northern part of the country, a regional emergency decree was issued on October 31, 2021, halting the regular services of public institutions. This subsequent shift in attention and resources away from the management of the PSBI program emerged as a challenge in Dembecha. We provided one round of supervision when the national and regional situations improved. The district health office conducted monitoring visits, performance reviews, and corrective measures to reestablish prior support for community-based management of PSBI services and strengthen their implementation.In the Lume district, NGO support for maternal and child health was identified as a facilitator for the management of PSBI service during implementation. In addition, the MOH introduced a digital version of the PSBI/iCCM module into the electronic Community Health Information System (eCHIS) in Lume in August 2021. The eCHIS was developed to replace the paper-based information system, a family folder containing household information, registration for incoming and leaving household members (member registration), data regarding service provision, and referral services rendered. The eCHIS incorporated job aids to support service provision, improve quality of care, and improve data use for decision-making. As such, digitization of the PSBI/iCCM treatment module aided HEWs as a decision support tool. It also facilitated digital referral, identification, and registration of newborns and SYI in the app during household visits, leading to improved delivery of community-based management of PSBI services Table .Table 5AWe successfully employed implementation research frameworks in designing, implementing, and evaluating the adaptive implementation of PSBI treatment during COVID-19 in Ethiopia. The RE-AIM and CFIR frameworks were used to design the COVID-19 pandemic that needed to be addressed to improve the reach, adoption, fidelity, and uptake of community-based management of PSBI services. In addition, we populated an initial IRLM. We used the framework to meaningfully engage stakeholders to systematically develop, identify, categorize, and prioritize implementation strategies to address identified and newly emerged barriers. We found that using an increasingly used framework, which combines CFIR and RE-AIM using concept mapping, effectively identifies strategies by integrating existing evidence and stakeholder engagement and expertise.The learnings demonstrated the unprecedented challenges of the COVID-19 pandemic, and the pre-existing health system-level barriers exacerbated the fragile community-based management of PSBI in Ethiopia. Previous studies revealed significant service disruptions in outpatient care and child vaccinations ; a decliUsing implementation research methods to inform the evidence synthesis using narrative review and formative assessment helped us better identify the challenges and provide an initial understanding of the conceptual links between determinants, implementation strategies, mechanisms, and outcomes. The use of concept mapping is essential in informing the choice of implementation strategies and is associated with more effective implementation , 37. StaThroughout our implementation research, we employed IRLM and expanded the adapted ERIC protocol and concept mapping technique to engage stakeholders to gain insights and clarity for developing the PSBI IRLM. This allowed for the systematic planning and application of the community-based management of PSBI implementation strategies that consider determinants, mechanisms, and outcomes. Consequently, we bridged implementation gaps by selecting strategies that improved the implementation process, increased adoption, and sustained effective intervention uptake . CurrentThe IRLM enabled the development of adaptive implementation strategies based on an in-depth understanding of the barriers and facilitators. The application of the framework also allowed us to identify implementation challenges, strategies, and mechanisms of action for adaptive implementation of PSBI treatment to increase implementation fidelity, reach, and adoption. Furthermore, these adaptive implementation strategies elucidated changes in the care-seeking behavior of mothers for their sick young infants. IRLM helped guide the measurement of the activities, intermediate outputs, and outcomes and synthesizing lessons from implementation.During implementation, we tracked ongoing implementation challenges and adaptive strategies, using the IRLM framework to conceptualize the mechanisms of action and outcomes. We also employed this framework to document the implementation learnings and share them with the broader community. This allowed us to examine what happened during the implementation and accurately report the hypothesized relationships we observed. For instance, the digital version of the iCCM module, which is a mobile health solution for HEWs that incorporates job aids\u2014 to counsel mothers on essential newborn care and educate them on danger signs of PSBI, assess newborns for possible signs of infection, diagnosis, treat and counsel mothers to adhere to treatment protocols\u2014improved the delivery of PSBI treatment. Specifically, it facilitated identifying and registering newborns and sick young infants and aided clinical and referral decisions and adherence to PSBI treatment protocols. This is in contrast to the responses from the data in Dembecha, where the iCCM module was not incorporated into eCHIS and where few or none of the above advantages from eCHIS were reported. At the same time, close monitoring and timely corrective measures to address emerging contexts like the effect of civil war are critical.We continued using this framework to share examples of our work in the cross-country community of practice with the community-based management of PSBI Kenya and India teams to cross-map implementation strategies, adaptations, mechanisms of action, and implementation outcomes. We also explored efficient ways to capture contextual factors to build on our IRLM to inform the management of PSBI work at scale. This has informed our continued work across country projects to identify areas that could benefit from standardized processes, approaches, methods, and metrics.Despite our efforts of exploring all possible challenges, co-designing and implementing strategies with active engagement of stakeholders, capturing ongoing challenges, and adapting strategies throughout the implementation period, we might not include all possible barriers affecting the community-based management of the PSBI program in the model. In addition, some of the determinants of this study may have been affected by social desirability and recall biases which would, in turn, affect the logical links between each component of the IRLM. Though the IRLM provides formats for a standard IR study that include multiple contexts and comparative implementation, it doesn\u2019t explicitly show how to synthesize and report implementation outcomes across various contexts to compare variations in implementation processes and influences across contexts for understanding what works for whom, and how .In conclusion, we found that the IRLM used in this research helped us organize the formative work and facilitate stakeholder engagement to specify the conceptual links between the implementation challenges, strategies, mechanisms of action, and outcomes to design and strengthen the management of the PSBI program under complex contextual factors, including COVID-19, as well as an existing health system and community barriers. The capturing of ongoing implementation challenges and document modifications of strategies during implementation allowed us to update the IRLM to provide better generalizable knowledge on adapting and implementing management of PSBI in similar and different settings.The participatory design and implementation of adaptive COVID-19 strategies effectively maintained the quality delivery of PSBI treatment during the pandemic. These approaches effectively engage community volunteers, HEWs, and the primary health care system and better integrate PSBI treatment for sustained implementation and scale up. Continuous support and feedback systems, continuous supply of essential drugs, and strategies to alleviate HEWs\u2019 workload to deliver quality services should be prioritized.Additional file 1.Additional file 2.Additional file 3.Additional file 4.Additional file 5.Additional file 6."} +{"text": "Driven mostly by an aging population, the utilization of spine surgery has increased exponentially over the last decades . ChronicPatient-centered care and the use of multidisciplinary collaborations inside and outside of the operating room is a cornerstone of safe and effective management of spinal disorders. Multiple studies have shown the benefits of multidisciplinary case conferences, tumor boards, and shared-decision making in the management of these conditions ,10. NaidThe second strategy to improve safety and outcomes includes the use of advanced techniques and enabling technologies. Anand et al. reported a 13-year experience treating severe adult spinal deformity with minimally invasive circumferential strategies without posterior osteotomies ,15. EchtThe third aspect that will most likely improve the safety and outcome of complex spine surgery is the use of advanced predictive analytics, particularly artificial intelligence. Machine and deep-learning algorithms can offer high predictive capability and can aid in complication prediction, survival prediction, and the identification of high-risk patients ,17,18,19The field of spinal surgery is rapidly changing and we must adapt to it. As specialists dealing with such complex conditions, we must focus on providing humanized and personalized high-quality care to our patients. The use of the approaches described herein will most certainly help us achieve that."} +{"text": "Urban production energy consumption produces a large amount of carbon emissions, which is an important source of global warming. This study measures the quantity and intensity of carbon emissions in 30 provinces of China based on urban production energy consumption from 2005\u20132019, and uses the Dagum Gini coefficient, kernel density estimation, carbon emission classification and spatial econometric model to analyze the spatial and temporal distribution and driving factors of quantity and intensity of carbon emissions from China and regional production energy consumption. It was found that the growth rate of carbon emission quantity and carbon emission intensity of production energy consumption decreased year by year in each province during the study period. The imbalance of carbon emission was strong, with different degrees of increase and decrease, and there were big differences between eastern and western regions. The classification of carbon emissions differed among provinces and there was heterogeneity among regions. The quantity and intensity of carbon emissions of production energy consumption qwre affected by multiple factors, such as industrial structure. This study provides an in-depth comparison of the spatial and temporal distribution and driving factors of quantity and intensity of carbon emissions of production energy consumption across the country and regions, and provides targeted policies for carbon emission reduction across the country and regions, so as to help achieve China\u2019s \u201cdouble carbon\u201d target quickly and effectively. The massive emission of greenhouse gases has led to an increase in global temperature and an accelerated frequency of extreme hot weather, which has seriously damaged ecological health , and hasAs a region where human activities are concentrated, China has seen a significant increase in carbon emissions due to the production of various industries in the process of urbanization and industrialization, and the contradiction between economic development and resource consumption and environmental pollution problems has become more and more prominent ,13,14,15There are many factors affecting carbon emissions, mainly in economic development, energy use, population structure, urban development, etc. Relevant studies show that China\u2019s carbon emissions have a strong correlation with the level of economic development, and China\u2019s industrial carbon emissions show an inverted U-shaped non-linear relationship with the level of economic development . MeasuriThe influence of different indicators on carbon emissions shows the diversity of carbon emission pathways, and in the process of economic and social development, large consumption of energy is one of the important sources of carbon emissions. Existing study shows that energy consumption and carbon emissions show a certain spatial correlation , and theIn addition, scholars have conducted a lot of research on the regional nature of carbon emissions. Chen et al. (2022) used the Theil index and the Moran index to conduct spatial analysis of China\u2019s carbon emission intensity and found that the spatial differences of carbon emission intensity from 2000 to 2019 were obvious, mainly intra-regional, with significant spatial correlation and local agglomeration characteristics . Yang etIn general, the existing studies on carbon emissions are rich, but there are still certain shortcomings. Firstly, existing studies have deeply analyzed the relevant influencing factors of carbon emissions, which can clearly sort out the theoretical relationship between carbon emissions and related influencing factors. However, carbon emissions have a spatial nature, and current studies lack discussion on the spatial relationship between carbon emissions and their influencing factors. Secondly, carbon emissions in China come from a wide range of sources, and carbon emissions from energy consumption are a key source in the process of industrialization and urbanization in China, so research on carbon emissions from energy consumption is necessary, and most existing studies have been conducted on carbon emissions from energy consumption. Energy consumption can be divided into rural energy consumption and urban energy consumption, and the corresponding urban energy consumption is divided into production energy consumption and domestic energy consumption. A more detailed division of energy consumption sources and the study of its carbon emission nature and influencing factors can propose more targeted energy saving and emission reduction policies. Thirdly, carbon emissions are spatially imbalanced, but the degree of imbalance and how it evolves still need to be measured and analyzed further in order to clarify the regional differences and spatial distribution characteristics of carbon emissions. Based on the above three analyses, this paper decided to measure the carbon emission quantity and carbon emission intensity of urban production energy consumption, and analyze the spatial and temporal distribution of carbon emissions and the driving factors. The carbon emissions of urban production energy consumption refer to the carbon emissions generated by the energy consumption of production activities in industries, raw materials and materials, construction, transportation, storage, postal services, wholesale and retail trade, and accommodation and catering, in addition to agriculture. After measuring carbon emission quantity and carbon emission intensity, the national and regional imbalance and spatial distribution characteristics of carbon emissions from urban production energy consumption were further measured and analyzed using the Dagum Gini coefficient and its decomposition and kernel density estimation, and, finally, the driving factors of carbon emissions and the regional heterogeneity of the driving factors were investigated using spatial econometric models. The results of this paper aim to provide quantitative support for the formulation of national and regional carbon emission reduction policies, so as to achieve China\u2019s \u201cdouble carbon\u201d target quickly and effectively.In this paper, the carbon emission quantity and carbon emission intensity of urban production energy consumption were used to measure the regional carbon emission level, and the carbon emission quantity of urban production energy consumption was calculated using energy in industry, raw materials and materials, construction, transportation, storage, postal industry, wholesale, retail trade, accommodation, catering production and other end consumption.At present, there are many accounting methods for carbon emissions from energy consumption, including the IPCC measurement method, field measurement method and model estimation method . In thisiE is the energy consumption, iNCV is the average low level calorific value of the fuel, iEF is the carbon content per unit calorific value of the fuel, iO is the oxygen content, and 44/12 is the conversion factor for converting C to 2CO.In Formula (1), The carbon emission intensity of urban production energy consumption is the carbon emission of urban production energy consumption per unit of GDP. The calculation formula of carbon emission intensity is as follows:In Formula (2), secondary industry refers to the mining industry (excluding mining auxiliary activities), manufacturing , electric power, heat, gas and water production and supply industry, and construction industry. The third industry, or tertiary industry, refers to the service industry, including wholesale and retail, transportation, warehousing and postal services, accommodation and catering industries, etc.The Gini coefficient and its decomposition are important methods to study regional differences, and the sample is divided into three parts: between-group differences, within-group differences and hyper-variance density to explore regional differences and their sources in depth ,52. In tk is the number of research subjects grouped. In this paper, it was divided into three regions: eastern, central and western China, containing a total of n research subjects. The values ijy and mry are the carbon emission levels of the j(r)th province in the i(m)th research region, and \u03bc is the average value of carbon emissions of all provinces.The value The intra-regional Gini coefficient measures the difference in carbon emission levels within each region, and the inter-regional Gini coefficient measures the difference in carbon emission levels between regions. The specific formulae are as follows:iiG is the intra-regional Gini coefficient, imG is the inter-regional Gini coefficient, in (m) and i\u03bc (m) are the number of research objects in region i (m) and the mean carbon emission level of provinces in region i (m).The overall Gini coefficient is decomposed to further measure the contribution of intra-regional differences, inter-regional differences and supervariable density to the overall differences. The formulae are as follows:wG, nbG and lG are the intra-regional, inter-regional and hypervariable density difference contributions, respectively. imD is the relative impact of carbon emission levels between regions i and m, imd is the difference in carbon emission levels between regions i and m, i.e., the mathematical expectation of the sum of all sample values of ij \u2212 ymry > 0 in regions i and m, and imp is the hypervariable first-order matrix, i.e., the mathematical expectation of the sum of all sample values of ij \u2212 ymry > 0 in regions i and m.Kernel density estimation is an important nonparametric estimation method, which can further explore the absolute differences and dynamic evolution of regional carbon emissions ,54. In tiy is the carbon emission level of province i, p is the sample size, h is the bandwidth, and K is the Gaussian kernel function.To explore the changes of carbon emission levels of urban production energy consumption and their carbon emission types from 2005 to 2019, the carbon emissions of urban production energy consumption were divided into four categories, namely high-high (high carbon emission quantity-high carbon emission intensity), high-low (high carbon emission quantity-low carbon emission intensity), low-high (low carbon emission quantity-high carbon emission intensity) and low-low (low carbon emission quantity-low carbon emission intensity), using the average value of carbon emission quantity and carbon emission intensity as the measure. Those above the average value were high carbon emissions, and those below the average value of carbon emissions were low carbon emissions.It is considered that the carbon emission level of urban energy production consumption in provincial in China may have the characteristics of spatial correlation. This paper proposed to test the drivers of carbon emission levels of production energy consumption in towns using the spatial error model (SEM), spatial lag model (SLM) and spatial Durbin model (SDM). The spatial correlation of carbon emission levels of urban production energy consumption in China was tested using the global Moran index . If the (1)Spatial error model (SEM)(2)Spatial lag model (SLM)(3)Spatial Durbin Model (SDM)i, j represents a province, t represents the year, itCE is the carbon emission level of the ith province in year t, \u03b2 is the coefficient of the explanatory variable, i\u03bc is the individual fixed effect, t\u03b7 is the time fixed effect, w is the spatial weight matrix, \u03bb is the spatial error term coefficient, \u03c1 is the spatial autocorrelation coefficient, x is the explanatory variable, and \u03b3 is the coefficient of the explanatory variable of the neighboring province affecting the home province.In the formulae, In this paper, the spatial weight matrix used the adjacency space weight matrix, and the neighborhood under the spatial structure was represented by 0 and 1. If the spatial units had a non-zero common boundary, they were considered to be spatially adjacent and represented by 1; otherwise, they were considered to be non-spatially adjacent and represented by 0.The driving factors of carbon emissions from urban production energy consumption are complex. In this paper, 11 explanatory variables were selected for analysis from five dimensions as the driving factors of carbon emissions from urban production energy consumption: urban economic level, living standard of urban residents, urban energy consumption level, urban population size and urban development level.(1)Urban economic level. The transformation of industrial structure can be realized through the upgrading of industrial structure and the rationalization of industrial structure to reduce carbon emissions, so industrial structure is an important influencing factor of carbon emissions ,58. Fore(2)Living standard of urban residents. Wen and Zhang found that per capita disposable income has a significant impact on carbon emissions . Therefo(3)2 emissions, and the proportion of coal consumption to total energy consumption was used to measure the energy consumption structure.Urban energy consumption level. Studies have shown that the high proportion of coal consumption in China directly determines the energy consumption structure, which, in turn, is the driving factor of carbon emissions . Therefo(4)Urban population size. As the main body of economic development, the population structure has a profound impact on carbon emissions. Labor force and dependency ratio are important demographic indicators, and have significant space differences in the impact of carbon emissions . In addi(5)Urban development level. Studies have shown that the green coverage of built-up areas has a significant impact on provincial carbon emissions in China . The spaThe urbanization rate was measured by the proportion of urban population in the total population, and the education level was measured by the average years of education: number of primary school students *6+ number of junior middle school students *3+ number of senior high school students *3+ number of junior college students and above *16/number of people aged 6 and above. Technological innovation was measured by the turnover of the technology market. The original data of all the explanatory variables were obtained from China Statistical Yearbook and China Energy Statistical Yearbook from 2005\u20132019, and individual missing data were completed using the trend prediction method and interpolation method. The abbreviations, definitions, and data sources for variables are shown in The carbon emission level of production energy consumption varies widely among different regions, and this paper divided China into three study regions: the eastern region, including Beijing, Tianjin, Hebei, Liaoning, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong, Guangdong, and Hainan; the central region, including Shanxi, Jilin, Heilongjiang, Anhui, Jiangxi, Henan, Hubei, and Hunan; the western region, including Inner Mongolia, Guangxi, Chongqing, Sichuan, Guizhou, Yunnan, Shaanxi, Gansu, Qinghai, Ningxia, Xinjiang. The study area is shown in The results of calculating carbon emissions of urban production energy consumption in inter-provincial in China from 2005 to 2019 showed that carbon emission levels have obvious spatial distribution characteristics . Carbon (1)Overall differencesIn order to explore in-depth the overall regional differences and sources of carbon emissions from urban production energy consumption, this paper used the Dagum Gini coefficient and its decomposition to calculate the overall Gini coefficient of carbon emissions and further decomposed this to measure the Gini coefficients of eastern region, central region and western region.The overall difference of carbon emission quantities is shown in (2)Intra-regional differencesThe intra-regional differences in carbon emission quantity and their evolution trends are shown in Since 2012, the intra-regional difference in carbon emission quantity in the central region decreased, while the intra-regional difference in carbon emission quantity in the western region increased, so that the intra-regional difference in the western region was much higher than in the central region by 2019. As shown in (3)Inter-regional differencesThe inter-regional differences in carbon emissions and their evolution trends are shown in Based on the Dagum Gini coefficient and its decomposition, the overall differences and evolution trends of carbon emission levels were analyzed, and the relative differences of regions were identified. In order to further study the dynamic distribution characteristics of carbon emission levels and absolute regional differences, this paper used Kernel density estimation to study the overall pattern and dynamic evolution of carbon emission distribution in China and each region. Matlab software was used to draw a three-dimensional perspective view of carbon emission levels in China and each of its regions from 2005 to 2019.(1)The evolution of carbon emission quantity dynamicsAs shown in The above analysis showed that the imbalance of carbon emission quantities in China deepened, and there was a trend of polarization, with large differences between regions and an increasing trend of differences between provinces within each region. The largest differences between provinces were within the eastern region, followed by the central region, and with polarization within the western region, but the polarization was gradually decreasing.(2)The evolution of carbon emission intensity dynamicsAs shown in The above analysis showed that the imbalance of carbon emission intensity of urban production energy consumption in the country weakened, but the deepening of the polarization phenomenon indicated an obvious gradient effect. Compared with the eastern region and western region, the central region had the weakest imbalance, followed by the eastern region, and the western region had the strongest imbalance. The emergence of side peaks in the eastern region and central region also showed a certain polarization phenomenon. There was an obvious gradient effect, namely most provinces\u2019 carbon intensity decreased obviously and became gradually numerically close, but there were still some provinces where the decrease in carbon emission intensity was small and there was a large gap with the carbon emission intensity in most provinces, so the phenomenon of multi -polarization was generated.The carbon emission classification of urban production energy consumption inter-provincially is shown in In the previous section, the analysis of carbon emission levels of urban production energy consumption inter-provincially found that there were significant spatial distribution characteristics. In order to further explore the strategies to reduce the carbon emission levels of production energy consumption, it was necessary to conduct an in-depth study of the driving mechanism. By calculating the global Moran\u2019s I index of carbon emissions for spatial correlation analysis , it was As shown in Carbon emission intensity was also affected by multiple factors, as shown in The results of the analysis of carbon emission driving factors of urban production energy consumption in the three major regions of China are shown in As can be seen from In order to test the feasibility and robustness of the research results, this article adopted a replacement indicator method for a robustness test. The per capita disposable income of important indicators was replaced by per capita consumption expenditure. The robustness test results are shown in the This study measured the carbon emission levels (carbon emission quantity and carbon emission intensity) of urban production energy consumption in inter-provincial areas in China based on data from 2005\u20132019. The study measured and decomposed the overall regional differences in carbon emission levels using the Dagum Gini coefficient, analyzed the dynamic characteristics of the distribution of carbon emission levels and absolute regional differences using the Kernel density estimation method, and used a spatial econometric model to analyze the driving factors of carbon emission levels in the whole region and three regions . The main research findings are as follows.First, the carbon emission quantity increased year by year during the study period, but the growth rate decreased, and the carbon emission intensity had an obvious decreasing trend. Besides this, the carbon emission quantity and carbon emission intensity showed obvious spatial differences, i.e., the carbon emission quantity showed the characteristic of eastern region > central region > western region, while the carbon emission intensity, on the contrary, showed the characteristic of western region > central region > eastern region, and the spatial characteristics were more obvious as time went on.Second, the overall difference of carbon emission quantity showed a decreasing trend. The intra-regional difference of carbon emission quantity evolved from eastern region > central region > western region to eastern region > western region > central region, and the overall difference of carbon emission intensity showed an increasing trend, and the intra-regional difference of carbon emission intensity was always western region > eastern region > central region. The imbalance of carbon emission quantity increased in the country, and the imbalance of carbon emission quantity increased in different degrees in the eastern region, central region and western region. There was a significant gradient effect in the carbon emission intensity, and there was also a trend of multi -level differentiation in the provinces in various regions. From the perspective of carbon emission classification, the inter-provincial carbon emission classification had some changes from 2005 to 2019, but most of the carbon emission provinces were in the low-low category.Third, carbon emission level was influenced by multiple factors, among which carbon emission quantity was mainly influenced by industrial structure, per capita disposable income, energy consumption structure, urbanization rate, cultural level, scientific and technological innovation. Carbon emission intensity was mainly influenced by industrial structure, foreign direct investment, energy consumption structure, the dependency ratio of elderly population and scientific and technological innovation. Different regions had heterogeneity, and the level of driving factors was different. Industrial structure, per capita disposable income, energy consumption structure, urbanization rate were the important driving factors of regional carbon emissions.Based on the above findings, this paper proposes the following recommendations to reduce carbon emissions from urban production energy consumption in China, to promote the achievement of carbon peaking and carbon neutral goals, and to realize green and sustainable economic and social development.2 emissions [First, on a national scale, the energy consumption structure has more room for transformation. On the one hand, China\u2019s natural resource profile of \u201ccoal-rich and oil-poor\u201d has influenced the energy consumption structure, so China\u2019s current production energy consumption is still coal-based fossil energy, which leads to a large amount of COmissions . On the missions . AdjustiSecondly, the regional differences should be balanced to achieve dual balance between carbon emission quantity and carbon emission intensity. The regional differences in carbon emission quantity and carbon emission intensity of urban production energy consumption reflect imbalance in intra- and inter-regional economic development and energy utilization. The eastern region as a whole has a relatively developed economy and higher technology level, but its internal imbalance is also stronger. Therefore, important provinces in the eastern region, such as Shanghai and Zhejiang, should actively play the role of central cities to strengthen the economic and technological radiation to the surrounding areas, improving the economic levels of the surrounding provinces while reducing the differences in the level of carbon emissions of production energy within the region. The eastern region should give full play to its advantages in high and new technology, and transport technical talents to the central region and western region, so as to provide important support for the industrial development and upgrading of the central region and western region. The difference of carbon emission level and economic development within the central region is smaller, therefore, as an important hub between the eastern region and western region, the central provinces should play a good role as a mediator, while maintaining a stable and positive development. The western region should pay more attention to economic construction and low-carbon development of secondary and tertiary industries, while industrial structure transformation is crucial to strengthen the upgrading of low-end manufacturing industries to high-end manufacturing industries, accelerate the transfer from labor and capital-intensive industries to high-tech-intensive ones, and narrow the economic differences with the eastern region and central region, so as to reduce the carbon emission intensity of production.Finally, the construction of new urbanization should be strengthened. The increase of urbanization rate has significant heterogeneity for regions, and the urbanization rate is higher in the eastern region and central region at the present stage. Further increasing the level of urbanization rate will raise the level of production of carbon emissions, so the transformation of new urbanization should be accelerated, and new urbanization should play an important role in revitalizing the economy, while being a key step in the coordinated development of economic and ecological environments . Therefo"} +{"text": "Pregnant women frequently use prenatal screening and diagnostic tests to detect fetal structural and chromosomal anomalies; however, the regulation and financing of these examinations differ substantially across countries. In this paper we focus on the provision, financing and setting of the following tests in selected European countries: First Trimester Screening (FTS)/Combined Test (CT), Non-invasive Prenatal Test (NIPT), second-trimester ultrasound screening for fetal anomalies, amniocentesis/chorionic villus sampling.We chose 6 European countries that differ in various criteria to illustrate the range of possible regulations and forms of funding: Germany, Switzerland, Netherlands, United Kingdom, Norway, Italy. We conducted a comprehensive hand search and consulted experts from the 6 countries using a questionnaire.The results are based on 11 completed expert questionnaires and 22 published sources. The heterogeneity of the provision, regulation and financing of the tests concerns in particular the choice of the first-line screening test for fetal trisomies , the implementation of the NIPT, the reimbursement of the tests, the uptake of the examinations, but also the professional groups responsible for antenatal care . There are some similarities between countries, e.g., concerning the provision and financing of invasive tests and of the ultrasound screening for fetal anomalies in the second trimester.The results highlight the significant heterogeneity between European countries regarding prenatal screening and diagnostic testing for fetal anomalies. Due to the many ethical aspects of the topic, a broad societal discourse with the relevant interest groups and stakeholders seems to be necessary. Decision-makers should pay particular attention to high-quality and non-directive counselling.European countries take different approaches to offer and fund prenatal screening and diagnostic tests for fetal anomalies.The implementation of screening strategies should focus in particular on the importance of high-quality counselling to enable informed decision-making."} +{"text": "Working conditions at universities are often considered precarious. Employees complain of fixed-term contracts and extensive unpaid overtime . Studies from various fields of work show that occupational groups with a high workload suffer particularly from a conflictual compatibility of work and family.The aim of this study was to assess the WFC in the context of working conditions.N=844 university employees were asked about the burden of work/life balance using Work-family-conflict (WFC) - Family-work-conflict (FWC) -Scales (Netemeyer 1996). The dichotomously formulated question on overtime worked was supplemented by a five-step scaled item on the burden of overtime. The correlation analyses were calculated according to Spearman.Overtime performed by 83% of the total sample and 64% feel burdened by it. 95% of the scientists and physicians, 68% of the administrative staff, 63% of the service providers work overtime and 90% of the physicians and 72% of the scientists feel burdened by it. Significantly high correlations were found between the burden of overtime and the conflict of compatibility. The higher the burden of overtime, the higher the WFC and FWC. The highest correlation was found among physicians (r=.649), followed by scientists (r=.533), administration (r=.451), services .The additional work and strain caused by this, as well as the connections with the problem of compatibility, show need for action for employers regarding the working conditions of physicians and scientists. Especially with regard to reducing overtime and improving the compatibility of work and family."} +{"text": "This symposium engages diverse methods and analyses to discover and reimagine possibilities for individuals aging with and into disability. The presentations advance an understanding of the diversity of service/care needs as well as of social capital, with exploration into assistive technologies, educational attainment, and assessment of successful aging. In the first presentation, the authors delineate key informant interview data identifying capacity-building needs in professional skills, organizational operations, service/care models, and public policies to effectively serve older adults aging with and into disability. The second presentation offers a content analysis of how researchers conceptualize, measure, and apply social capital to developmental disability throughout the life course, reviewing peer-reviewed articles from 5 disciplines, across more than 20 years. In the third presentation, using National Health and Aging Trends Study data, the authors investigate the longitudinal associations between disabilities, assistive technologies, and subjective well-being among older adults. In the fourth presentation, the author uses multivariate regression analysis to analyze National Health Interview Survey (NHIS) data, building on prior research analyzing the association between educational attainment and the perceived need for future help with activities of daily living (ADLs), often measuring disability in the literature. In the fifth and final presentation, the authors use the National Health & Aging Trends Study data to understand successful aging from the perspectives of those who experience disability, integrating subjective components of self-rated health and well-being, and providing insights on subjective perceptions on successful aging among older adults with disabilities."} +{"text": "The food supply chain operates in a complex and dynamic external environment, and the external uncertainties from natural and socio-economic environment pose great challenges to the development of the food industry. In particular, the COVID-19 pandemic and Russia\u2013Ukraine conflict have further exacerbated the vulnerability of the global food supply chain. Analyzing the dynamic impacts of external uncertainties on the stability of food supply chain is central to guaranteeing the sustainable security of food supply. Based on the division of food supply chain and the classification of external uncertainties, the TVP-FAVAR-SV model was constructed to explore the dynamic impacts of external uncertainties on food supply chain. It was found that the impacts of external uncertainty elements were significantly different, the combination of different external uncertainty elements aggravated or reduced the risks of food supply chain. And some uncertainty elements had both positive and negative impacts in the whole sample period, as the magnitude and direction of the impacts of various uncertainties in different periods had time-varying characteristics. Food security is the guarantee for human survival, economic development, and social harmony. The outbreak of the global food crisis in the early 1970s and in 2008 caused food insecurity in many countries and induced great tension in the world ,4, whichStudies on the food supply chain from different perspectives has played an important role in promoting the development of food supply chain. Based on the general supply chain theory, Ouden et al. found a The food supply chain usually faces complex challenges from external economic, social and natural environment when maintaining stability ,32. ThusChina is the largest grain producer and importer. Limited by the natural environment, China has to ensure food and nutrition security of 18% of the world\u2019s population with only 9% of the world\u2019s cultivated land and 6% of the world\u2019s water resources . China aResearch on the impacts of external uncertainties (or risks) on food supply chain is of great significance to eliminate global hunger and achieve sustainable security of food supply . The resTo improve these deficiencies, this paper first divides the main sectors of the food supply chain and selects a large number of indicators from the two aspects of natural and socio-economic environment to measure the external uncertainties, which serves as entry points for the study. Then, the TVP-FAVAR-SV model is constructed, and the common factors reflecting the external economic environment uncertainties are extracted through latent factor extraction method. With the help of the three-dimensional impulse response of the representative variables in the sectors of the food supply chain to all external uncertainty elements, this paper studies the dynamic impacts of a single external uncertainty element on the food supply chain, and the different impacts of the combination of multiple external uncertainty elements on the food supply chain. Compared with existing research, the three-dimensional impulse responses based on the TVP-FAVAR-SV model can depict the dynamic and complex impacts of external uncertainties more clearly. The impulse response results show the time-varying characteristics of the uncertainties\u2019 impacts, and reveal that the combination and transmission of various uncertainties\u2019 impacts are the main reason for aggravating or reducing the food supply chain risks.In this section, first, we divide the major sectors of food supply chain and classify the external uncertainties, which serve as entry points for the study. Second, the impact mechanisms of external uncertainties on all sectors of the food supply chain are identified. Finally, the construction of empirical model and data sources are introduced.The food supply chain comprises multiple sectors and sub-elements, and each sub-element is independent but closely linked . The synThe external uncertainties include economic uncertainties, social and natural public emergencies ,19,22. TThe impacts caused by the external uncertainties on the primary agri-products supply sector are mainly reflected in labor force reduction, disaster area increase, agricultural production input increase, variety selection, premature harvesting, policy changes, and subsidy shortage ,57,64,65The impacts caused by the external uncertainties on the food production sector are mainly reflected in the impacts on the cost, inventory, production strategy, support services and financial risks of food production enterprises (including agri-products processing enterprises and food manufacturing enterprises) ,67,68, wThe impacts caused by the external uncertainties on circulation and trade sector are mainly reflected in the impacts on food supply, operation costs, market selection, market access, market sanctions, and trade agreements in the food market, which lead to price volatility, consumption fluctuation and trade fluctuation ,22,69,70In the consumption sector, the decision-making behavior of consumers on food purchase is the main content. The impacts of external uncertainties on consumption are mainly realized by changing consumers\u2019 purchasing power, consumption habits, and expectations . In the The external uncertainties to be investigated in this paper cover many indicators, especially 67 economic indicators are used to measure the economic uncertainty, and which cannot be fully included for analysis. In order to show as many of the impacts of external uncertainties as possible, it is necessary to be more prepared to grasp the time-varying characteristics of various impacts, and to improve the ability to explain the relationship among the variables in the system, so it is crucial to analyze with the help of an appropriate model. Considering that the characteristics of some indicators can be described by the common part, the dimensionality reduction of indicators can be achieved by extracting the common part . Kazi etIn order to study the time-varying quality of the parameters, the model needs to be extended to a time-varying parameter form. The basic expression of the time-varying parameters factor-augmented VAR (TVP-FAVAR) model takes the form:According to the methods of Primiceri and NakaStacking the row vector of Following the assumptions as Koop et al. , for eacThus, Equation (1) can be rewritten as:Inserting Equation (10) into (9) can obtain the final TVP-FAVAR-SV form:Monthly data are selected in this paper to describe the external uncertainties as carefully as possible and maintain the consistency of data frequency. Considering data availability, the sample interval selected in this paper is from March 2005 to June 2020. In primary agri-products supply sector, primary agri-products trade includes vegetable products and animal products, and the specific product types and corresponding HS codes are shown in This paper draws on the latent factor extraction method proposed by Bernanke et al. to extraIn p-value of ADF-statistic, all variables have passed the unit root test.Since this paper studies the relationship between time series, before empirical analysis, this paper uses unit root test to examine the stationarity of all variables in the TVP-FAVAR-SV model, in order to eliminate the influence of random law differences in non-stationary series ,81. The Based on the common factor extraction and unit root test, this paper further explores the three-dimensional impulse responses of representative variables in each sector of food supply chain to positive shocks of public health emergencies (PHE), disaster emergencies (DE), interest rate uncertainty factor (IRU), financial uncertainty factor (FU), social development uncertainty factor (SDU), and consumption uncertainty factor (CU).The impulse responses of primary agri-products purchase price (PAPP)The positive shocks of external uncertainties mainly have positive impacts on PAPP. FU and DE have relatively large impacts, while that of CU is the smallest. The impacts of DE have obvious intermittence.From October 2009 to September 2010, IRU had great impacts on PAPP, and the Chinese government implemented moderately loose monetary policies to cause an increase in the positive impacts of IRU on PAPP ,82. WhenFrom April 2007 to February 2008 and from May 2009 to March 2010, FU had great positive impacts on PAPP, because the agri-products price rose rapidly with the high liquidity of domestic currency and assets in these two periods .From February 2009 to October 2010, the impacts of SDU on PAPP increased remarkably, mainly due to the significant growth of PAPP driven by the \u210cfour trillion\u210d economic stimulus plan implemented by the Chinese government ,82. FromFrom November 2008 to April 2011, the positive impacts of CU on PAPP were significantly greater than that in other periods. Reasons include the high level of consumer confidence and expectation, and the depreciation of CNY exchange rate. Therefore, strong demand in both domestic and international markets significantly increased PAPP .The continuous heavy rainfall in the Yangtze River Basin from July to August 2010 seriously impacted agricultural production, which led to the increase of PAPP from October 2010 to February 2011, due to the lagging effect of agricultural production on prices. From March 2015 to September 2016, due to severe droughts and floods in North China, Northeast China, and Northwest China, as well as the Yellow River and Yangtze River Basins, PAPP increased significantly during this period.From March 2010 to August 2010, the positive impacts of PHE on PAPP decreased significantly, because the outbreak of influenza A (H1N1) at the end of 2009 reduced consumption of livestock products and pork . Moreove2.The impulse responses of production value of primary agri-products (PVPA)The positive shocks of external uncertainties have both positive and negative impacts on PVPA, with the greatest impacts being of SDU, followed by DE, and CU has the least impacts .Before 2006, IRU mainly had negative impacts on PVPA due to the downturn of the primary agricultural product market, and the rise of interest rate further increased the loan pressures of agricultural enterprises, agents, and purchasers . After 2FU increases PVPA by improving the financing environment of agricultural enterprises and raising primary agri-products price , and hasSince 2006, the Chinese government has implemented a series of agricultural support policies, which have made great contributions to ensuring agricultural production, narrowing the income gap of farmers and maintaining the number of rural laborers ,54,89. TCU has negative impacts on PVPA first, and then positive impacts, but the overall level of impacts is small. With the improvement of residents\u2019 income level, people will increase the consumption of durable goods, high-end goods, or luxury goods, resulting in the negative impacts on PVPA; meanwhile, people\u2019s consumption upgrading can also stimulate agricultural production value ; thus, CDE has negative impacts on PVPA first, and then positive impacts. The occurrence of DE, especially natural disasters, has relatively great negative impacts on PVPA in the short term. Meanwhile, due to the support and protection of agricultural policies, primary agri-products will quickly resume production after disasters, so PVPA will experience compensatory increase in the long term ,90. Due PHE has negative impacts on PVPA first, and then positive impacts, but both positive and negative impacts are small. It reflects that policies implemented by the Chinese government to support and protect agriculture, as well as the emergency prevention and control measures have effectively reduced the impacts of PHE on PVPA.3.The impulse responses of primary agri-products export (PAE)The positive shocks of IRU mainly have negative impacts on PAE, while FU, SDU, and CU, DE, and PHE have both positive and negative impacts. Among them, DE has the greatest impacts on PAE, followed by FU and FU, while CU has few impacts .The increase of IRU means the increase of loan interest rate or price index. On the one hand, it affects PAE by influencing the borrowing costs of exporters ; on the FU first has short-term negative impacts, followed by long-term positive impacts. The reason for the short-term negative impacts is that the FU raised the price of agri-products, thus reducing the price competitiveness of its exports. The long-term positive impacts are realized by improving the financing environment of export enterprises .SDU increases PAE by improving quantity and quality of agricultural production, and strengthening interregional agricultural trade consultation . HoweverCU increases PAE by raising the exchange rate of foreign currency to CNY, and reduces PAE by stimulating consumption when the exchange rates are relatively stable, such as the time from October 2009 to October 2012 .DE and PHE first have great negative impacts on PAE, followed by positive impacts. It indicates that the occurrence of DE and PHE reduce PAE in the short term , but when the disaster passes and agriculture production recovers, PAE will experience compensatory growth .4.The impulse responses of primary agri-products import (PAI)The positive shocks of financial uncertainties, CU and PHE, mainly have positive impacts on PAI. IRU, SDU, and DE have both positive and negative impacts. DE has the greatest impacts on PAI, followed by SDU, and FU has the least impacts . IRU incSDU reduces the dependence on agri-products imports by increasing domestic supply and applying relevant trade policies . It is also found that during the implementation of the \u201cfour trillion\u201d economic stimulus plan (from February 2009 to October 2010), SDU had significant positive impacts, which reflects the strong orientation of the plan . The impDE and PHE have significant positive impacts on PAI, and impacts of DE are relatively great. It indicates that DE is still the main factors affecting the PAI compared with the impacts of economic uncertainties.The impulse responses of sales price of food enterprise (SPFE)The positive shocks of external uncertainties mainly have positive impacts on SPFE, with the greater impacts of FU and SDU, and the smallest of DE . IRU hasThe positive impacts of SDU on SPFE increased significantly from April 2007 to February 2008 and from May 2009 to March 2010. CU has greater pulling effects on SPFE in time of high liquidity, and the impacts of CU on SPFE decreased with time. The continuous heavy rainfall in the Yangtze River Basin from July to August 2010 led to the unstable supply of primary agri-products, so the impacts of DE on SPFE also increased significantly during this period.PHE mainly has positive impacts on SPFE, but it had significant negative impacts from January 2010 to October 2010. The outbreak of influenza A (H1N1) from October 2009 to April 2010 led to a significant decrease in the consumption of poultry and pork products , which f2.The impulse responses of production value of food industry (PVFI)The positive shocks of external uncertainties have both positive and negative impacts on PVFI, with the greatest impacts of DE, followed by PHE, and IRU having the least impacts . The priThe positive shocks of FU increase PVFI by improving the food enterprises\u2019 financing environment and raising food price. The impacts of FU on PVFI will increase in time of high liquidity . SDU hasDE and PHE first have great negative impacts on PVFI, followed by positive impacts. It shows that when DE and PHE occur, PVFI will decrease in the short term; after the disaster pass and enterprises resume production, PVFI will experience a compensatory increase .3.The impulse responses of profit margin of food industry (PMFI)The positive shocks of IRU mainly have negative impacts on PMFI. The positive shocks of SDU mainly have positive impacts. FU, CU, DE, and PHE have both positive and negative effects. DE has the greatest impacts on PMFI and IRU have the smallest impacts .IRU increases food enterprises\u2019 production and operation costs, so IRU mainly has negative impacts on PMFI. FU increases the production costs of food enterprises in the short term, which have negative impacts on PMFI. In the long term, it has positive impacts on PMFI by improving the financing environment and reducing financial risks. In time of high intensity of agricultural policies, the impacts of FU are greater . SDU hasWith the continuous improvement of consumption level, people\u2019s eating habits are constantly upgraded , and fooDE and PHE first have great negative impacts on PMFI, and then have positive impacts. When DE and PHE occur, PMFI will greatly reduce through direct and indirect impacts in the short term. After food enterprises resume normal production, the profit margin will recover .The impulse responses of food retail (FR)The positive shocks of FU and SDU mainly have positive impacts on FR, while positive shocks of IRU, CU, DE, and PHE have both positive and negative impacts. The impacts of DE and PHE are relatively large, while the impacts of IRU are the smallest .In the period of high liquidity (from April 2007 to December 2007 and from October 2009 to September 2010), due to the income effect of savings, people increased food consumption considerably, resulting in positive impacts on IRU during this period. If the money liquidity is at a moderate level, people increase savings due to the substitution effect of savings. Therefore, IRU mainly had negative impacts after 2012 ,96.FU increases FR by raising food prices. Meanwhile, it also stimulates food consumption by increasing residents\u2019 income. SDU increases FR by improving residents\u2019 income and enhancing food market construction . The impDE and PHE rapidly increase FR in the short term by changing consumer expectations ; however2.The impulse responses of food products export (FPE)The positive shocks of IRU mainly have negative impacts on FPE. SDU mainly has positive impacts, while FU, CU, DE, and PHE have both positive and negative impacts. DE and SDU have greater impacts on FPE, while CU has the least impacts .IRU has negative impacts on FPE by affecting the borrowing costs of export enterprises and raising domestic food prices. After 2016, with the rise of loan interest rate and the continuous growth of agri-production material price index, the negative impacts of IRU on FPE increased. In the short term, FU can raise food prices, which causes negative impacts on FPE; in the long term, FU has positive impacts on FPE by improving the financing environment of food exporters ,88.SDU increases FPE by improving food quality, diversifying food supply, and improving the trade environment of food enterprises and the development prospects of food exporters . SimilarDE and PHE first have great negative impacts on FPE and then have positive impacts. When DE and PHE occur, FPE decreases greatly in the short term; after the disasters or pandemics, FPE will experience a restorative growth .3.The impulse responses of food products import (FPI)FU mainly has positive impacts on FPI, and other external uncertainties have both positive and negative impacts. DE has the greatest impacts on FPI, followed by SDU, and IRU having the least impacts . In the FU mainly increases FPI by improving the credit level and financing scale of import enterprises . With thDE and PHE first have positive impacts on FPI, and then negative impacts. The increase of FPI caused by the influenza A (H1N1) outbreak in October 2009 and H7N9 in December 2016 was significantly greater than that caused by COVID-19; considering the safety of imported food, global outbreaks of infectious diseases will strengthen quarantine on imported goods and reduce the food products import.Since the sales amount in the food market equals the purchase amount of consumers , and the impacts of external uncertainties on food retail have been discussed in the circulation and trade section, this section is devoted to analyzing the impacts of external uncertainties on the food consumption price.The impulse responses of food consumption price (FCP)The positive shocks of FU and CU mainly have positive impacts on FCP, while IRU, SDU, DE, and PHE have both positive and negative impacts . IRU hasThe positive impacts of DE on FCP have great volatility. PHE has positive impacts on FCP first and then negative impacts, but both positive and negative impacts are small, reflecting the Chinese government\u2019s effectiveness of food prices regulation.The impacts of IRU on the sales price of food enterprises and food consumption price are significantly greater than that on the purchase price of primary agri-products. On the one hand, this difference is because the food products are at the end of the supply chain, and prices are directly affected by IRU shocks, as well as the transmission of impacts that caused by IRU on other sectors. On the other hand, the price support and protection policies implemented by the Chinese government have effectively restrained the fluctuation of primary agri-products price.IRU affects the production value of primary agri-products, production value, and sales profit of food enterprises by changing production, sales, and operating costs. In the time of high liquidity, positive shocks of IRU lead to a significant decline in the sales profit margin of food enterprises, despite the increase in its production value.aThis phenomenon causes by the sensitive responses of production costs and loan costs to changes in the interest rate.IRU affects food retail through income effect and substitution effect of savings. The substitution effect is dominant during periods of moderate liquidity, while the income effect plays a major role during periods of high liquidity.IRU has an impact on trade of primary agri-products and food products by affecting the agri-production material price and enterprise credit costs, and the impacts on exports are greater than that on imports. It indicates that preferential loan interest rate policy for export processing enterprises can effectively improve their resistance against risks in primary agri-products and food products exports, which is consistent with the conclusions of Qu and Kang and NordFU increases the purchase price of primary agri-products, sales price of food enterprises, and food consumption price through financialization. The impacts on the sales price and food consumption price are greater than that on the purchase price of primary agri-products. Because the purchase of agri-products is at the front of the supply chain and is less affected by risk transmission from other sectors. And price support and protection policies implemented by the Chinese government reduce the price volatility of primary agri-products, and the results verify the findings of Assefa et al. .FU affects the production value of primary agri-products by changing the financing environment of primary agricultural producers and raising the price level of primary agri-products, and affects the production value and sales profit margin of food enterprises by changing the sales price, financing environment, financial risks, non-operating income, etc. FU has greater impacts on the sales profit of food enterprises. It shows that internal operation management of the enterprises reduces the risk transmitted from sales profit to production value, consistent with Kuiper and Lansink and GoliFU has great impacts on primary agri-products exports and small impacts on primary agri-products imports and food products trade, indicating that the relevant policies by the government and financial institutions to support the financing of agricultural export enterprises are important measures to increase agri-products exports. And this is consistent with Nordhagen et al. and ZhanSDU has greater impacts on the sales price of food enterprises and food consumption than on the purchase price of primary agri-products. This is caused by the differences in risk transmission from other sectors and the implementation of agricultural protection policies. The Chinese government has implemented policies such as grain supporting procurement and agricultural production subsidies, which are of great significance to stabilize the price of agri-products. Especially from 2008 to 2013, the steady implementation of the minimum purchase price policy for wheat and rice, temporary purchase and storage policy for corn, soybean and cotton, and the substantial increase of agricultural production subsidies led to corresponding increase in the response value of agri-products purchase price during this period.SDU has positive impacts on production value of primary agri-products, production value, and sales profit margin of food enterprises through the agricultural policies to protect primary production and improve farmers\u2019 income , as well as a series of positive policies to support food enterprises , and have a greater impact on the sales profit margin. It indicates that the preferential policies implemented by the Chinese government to support the development of food enterprises have effectively reduced the internal operation costs and risks of food enterprises, and can significantly improve the profit margin. The results verify the findings of Golini et al. and NordSDU increases sales by increasing consumers\u2019 income and improving construction of food market. The purpose of improving construction of food market is to promote the diversification of consumers\u2019 dietary structure and to meet their needs for balanced nutrition.SDU increases the export of agri-products and food products by improving product quality, increasing varieties, and improving the trade environment, and has negative impacts on agri-products import . However, economic development also brings about upgrading of the consumer market, which increases the import of high-quality and diversified food products.CU has positive impacts on the purchase price of primary agri-products, sales price of food enterprises and food consumption price by increasing consumer confidence and expectation. The positive impacts are more significant in time of high liquidity.Due to the necessity of agricultural production and the rigidity of food demand, the impacts of CU on production value of primary agri-products and food industry are volatile, but the overall impacts are small; these findings are consistent with Davis et al. .CU first has negative impacts on the profit margin of the food industry and then positive impacts. The reason for this change is the mismatch between food supply and consumer demand caused by upgrading dietary habits. The shift from negative to positive impacts is also the process in which new products are produced and then accepted by the market, and finally growth of sales profit is achieved. This result verifies the finding of Dania et al. .The impacts of CU on food retail have significant volatility. Especially when zoonotic infectious diseases occur , the positive impacts on food retail sales are significantly reduced. This phenomenon is affected by consumers\u2019 attitudes toward the risk perception, which is consistent with the conclusions of Lobb et al. and SeegCU increases the export of primary agri-products and food products by increasing the exchange rate of foreign currency to CNY, and increases the import of primary agri-products and food products by stimulating consumption.The impacts of DE on the purchase price of primary agri-products are greater than that on the sales price and consumption price. Agricultural production has features of periodic planting and the concentrated harvest, so the occurrence of natural disasters has relatively great impacts on the price of primary agri-products. Food enterprises can reduce the transmission of domestic agri-product price fluctuations to food prices through imports, so DE has smaller impacts on the sales price of food enterprises.With the end of the disaster and the implementation of agricultural protection policies and risk response measures, the production value of primary agri-products, the production value, and profit margin of food enterprises will gradually recover, which is consistent with Zhan and Chen . AlthougDE changes consumers\u2019 consumption expectations and increases food reserve in the short term to ensure future living needs, which lead to increased food retail. Consumption of reserved food after the disaster leads to a decline in food retail.DE significantly reduces exports and increases imports of agri-products and food products in the short term. After the disaster, exports of agri-products and food products experience restorative growth, and their imports declined significantly. With the continuous improvement of agriculture-related policies, agri-products trade is gradually affected by policies, while the impacts of DE are gradually reduced.The impacts of PHE on the purchase price of primary agri-products are smaller than that on sales price and food consumption price, which is consistent with Nordhagen et al. . This diPHE has relatively small impacts on the production value of primary agri-products, mainly due to the series of agricultural support and protection policies, as well as the emergency prevention and control measures. PHE first has great negative impacts on the production value and profits of the food enterprises, and then have positive impacts. Especially after the occurrence of zoonotic infectious diseases, the negative impacts on the production value and profit margin increase, and the positive impacts decrease. After the pandemic, the production value recovers rapidly, but sales profit margin recovers slightly, which may lead to the long-term loss of enterprises, and it is consistent with Nordhagen et al. . TherefoThe impacts of PHE on food retail sales are much greater than that on the production value, price and profit margin of the food industry, reflecting that China\u2019s food supply chain has a certain resilience, and this result verifies the findings of Fan et al. . MeanwhiPHE significantly reduces export and increases imports of agri-products and food products in the short term, but export of agri-products and food products experiences restorative growth after the pandemic. Import of food products can be reduced during the global infectious diseases (such as COVID-19 in 2020), and the terms of trade will be more stringent (such as strengthening quarantine and screening import markets), because of concerns over the safety of imported goods.This study divided the main sectors of the food supply chain and fully considered the time-varying quality, complexity, and high-frequency occurrence of external uncertainties as the entry points, then selected a large number of monthly indicators to measure the external uncertainties, and used three-dimensional impulse responses based on the TVP-FAVAR-SV model to depict the dynamic impacts of external uncertainties on food supply chain. The impacts of combination of various uncertainty elements and the transmission of these impacts among various sectors of the food supply chain are the focus of this study. It was found that the impacts of all external uncertainty elements were significantly different: social and natural public emergencies had great impacts on aspects of retail sales, profit margin, and international trade, while economic uncertainties had great impacts on aspects of price, production, and international trade. It was also found that the combination of different external uncertainty elements aggravated or reduced the risks of food supply chain. With the continuous improvement of the agricultural policy system, the negative impacts of economic uncertainties on the food supply chain were gradually diminished, and the appropriate liquidity improved the positive impacts of relevant policies. The integrated emergency measures and complete market systems reduced the negative impacts of disaster emergencies and public health emergencies on the production sector, and shortened the time for food enterprises to resume operation and end the profit losses. Unlike risks, some uncertainty elements had both positive and negative impacts in the whole sample period. The magnitude and direction of the impacts of various uncertainties in different periods had time-varying characteristics, and the time-varying characteristics were caused by the impacts of combination of various uncertainty elements and the transmission of these impacts.This paper recognizes and acknowledges that some limitations are still in variable selection and content analysis when analyzing the dynamic impacts of external uncertainties on the food supply chain, which provides approaches for future research. When identifying the external uncertainties of the food system, the paper tried to summarize the socio-economic environment and natural environment, and finally selected many indicators from public health emergencies, disaster emergencies, and economic uncertainties to measure the complexity of external uncertainties. However, the uncertainty risks of the food system are multifaceted, and especially in recent years, the pressure of resources, environment, and energy consumption has seriously challenged the sustainable stability of the food system. This paper is short of risk analysis from the aspects of resources, environment, and energy. Moreover, the Chinese government has implemented a series of policies and measures to achieve the carbon peak and neutrality goals. These policies and measures also have long-term and important impacts on the sustainable development of the agri-food system. However, this paper is short of the uncertainty analysis of relevant policies and measures. ITo comprehensively analyze the impacts of external uncertainties to ensure the sustainable stability of the food system, future research could focus on: (1) selecting impact factors from energy and environment as important indicators and summarizing them into the external uncertainty system, such as energy prices, production, trade, as well as carbon emissions, land use, agricultural material consumption, and other elements; (2) using a variety of quantitative methods to study the impacts of relevant policies and measures implemented by the Chinese government on the food system, such as data crawling technology, event and text analysis method, etc., to achieve multi-scale research on the sustainable security of the food supply chain."} +{"text": "High-quality talent cultivating Internet of Things (IoT) Engineering is the basis for the rapid development of IoT technology. To train high-quality application-oriented IoT technical talents, guided by educational psychology, this article conducts in-depth research; analyzes the characteristics of IoT Engineering; makes professional talent cultivating programs and cyclical adjustment plans; builds a high-quality teaching system based on the professional knowledge system of the IoT; explores the \u201cspiritual level\u201d and \u201cpsychological level\u201d characteristics of teachers and students in teaching; highly integrates \u201cIndustry-University-Research-Competition\u201d from the perspective of students, teachers, and colleges; infiltrates positive psychological cues appropriately; formulates the construction method of the \u201cstudent teaching assistant\u201d auxiliary system to enhance the efforts to promote learning by learning; and finally innovates the talent cultivating system for the IoT Engineering. The implementation results show that the students trained by this system have a solid foundation of knowledge related to IoT Engineering and strong engineering practice application, adaptability, and innovation ability. Based on sensing technology, information recognition technology, communication technology, and control technology, the Internet of Things (IoT) realizes the connection among things and is one of the global strategic emerging industries. At the fifth session of the 11th National People\u2019s Congress on 5 March 2010, the IoT was written into the Government Work Report for the first time. Since then, the industrialization process of IoT technology has been fully promoted, combining the development strategies of energy conservation, consumption reduction, green and low carbon with the sustainable development industry, food safety, disaster monitoring, modern logistics, intelligent transportation, and other industries as the entry point. The research and development of IoT technology promotes the development of devices, chips, materials, services, and other industries; forms an industrial cluster effect; promotes the integration of the undertaking of traditional industries and the independent innovation of emerging industries; and leads to the enduring demand for IoT technical personnel in the talent market. The talent cultivation of IoT has become the key to the sustainable and rapid development of the IoT.To train technical talents for the IoT, universities in China have started to offer the major of IoT Engineering successively since 2010, and our university (Luoyang Institute of Science and Technology) also added the undergraduate major of IoT Engineering in 2014. Compared with the traditional established major, this major is an interdisciplinary subject, involving the integration of computer, automation, communication engineering, and other multidisciplinary knowledge. The development time is short, and the talent cultivation scheme is not mature. Therefore, the talent training system of IoT Engineering must be constantly improved and perfected based on the development needs of society and school .Educational psychology mainly slanding.zhaopin.com and 51job.com), we can learn the types and levels of current demand for IoT talents, get the multidisciplinary demand for IoT technology, and determine the industry fields for talent cultivation. According to the college development plan, the key points of talent cultivation are determined: talent cultivation of IoT technology with big data in building materials industry. Questionnaires are used to obtain feedback on graduates\u2019 employment, such as industry and salary. Shortcomings of existing talent cultivation programs are found while exploring the space for improving the quality of talent cultivation.In view of the characteristics of interdisciplinary integration, the development of talent cultivation programs for IoT Engineering majors needs to fit social needs, school positioning, and teacher-student status analysis based on educational psychology. By investigating official websites of government departments, public institutions, large enterprises , and recruitment websites Meet the needs of the development of innovative talents, with all-round development of both political integrity and ability, showing good humanistic quality, professional ethics, and social responsibility.(2)Have a solid mathematical foundation and a good basis of natural science.(3)Master the professional knowledge and skills of the IoT; be able to analyze, research, and design solutions; solve the application problems of the IoT in the research and development of building materials with big data; have strong engineering practical ability and unique thinking mode of the IoT Engineering; and become the technology backbone.(4)Have engineering organization ability, teamwork ability, and international vision.(5)Have lifelong learning ability and be able to update and expand their knowledge and ability through appropriate ways.Curriculum system is the core of higher education, reflecting social needs, scientific knowledge, and ability development . The conConstructivism holds that \u201clearners do not transfer knowledge from the outside world to memory, but construct new understandings based on existing experience through interaction with the outside world.\u201d To cultivate high-quality application-oriented talents, the curriculum system must be able to cultivate students with correct world outlook, outlook on life, and values.To cultivate students majoring in IoT Engineering to have a good sense of appreciation, be rich in knowledge and experience and get excellent ability, at present, the curriculum system of this major should include four categories, namely, general courses, basic engineering courses, professional basic courses, and professional courses, as shown in General courses mainly include Ideological and Political Theory Courses, Physical and Mental Development Courses, Language and Tool Courses, and Quality-Oriented Education Elective Courses. At present, the Ideological and Political Theory Courses in our college include Morality and Law, Basic Principles of Marxism, Introduction to Mao Zedong Thought and the Socialist Theory with Chinese Characteristics, and Outline of Contemporary and Modern Chinese History. Physical and Mental Development Courses include Physical Education, Military Theories, Mental Health Education for Undergraduate, Career-Ready Skills with Innovation, and Entrepreneurship Practice. Language and Tool Courses include College English and College Applied Writing. Quality-Oriented Education Elective Courses include courses about humanities and art, social science, natural science and technology, economic management, and general development of foreign languages .Basic engineering courses for IoT major mainly include mathematics and physics. Mathematics courses include Advanced Mathematics I, Linear Algebra I, Probability and Statistics I, and Discrete Mathematics. Physics courses include College Physics II and College Physics Experiment.Professional basic courses mainly focus on the basic theory and program design of IoT technology, aiming to train the student to gain IoT technology learning foundation and prepare for the study of knowledge required by the design and development of IoT systems. This type of course covers Electrical and Electronic technology, Program Design of C Language, Computer Organization and Architecture, Data Structures, Database Systems and Applications, Computer Networks, Operating Systems, and Digital Logic.Professional courses are divided into professional required courses and professional elective courses, which mainly train students to have the ability of IoT system design, development, management, and maintenance; to serve the IoT application in building materials industry; and to provide direction for employment and further study. Professional required courses for IoT mainly include Specialty Introduction for IoT Engineering, Java Programming, Information Security, IoT Communication Technology, Embedded System, IoT Identification Technology (college-enterprise), IoT Application Software Development for Building Materials Industry, and IoT Engineering Design and Implementation. The professional elective courses are divided into two directions: Direction One (Cloud Computing-IoT): Cloud Computing Technology (college-enterprise), Big Data Technology, Smart City System, and IoT VR Design; Direction Two : Artificial Intelligence, Linux-C Programming, IoT Middleware Development, and Smart Agriculture System.At present, the curriculum system of IoT Engineering major in our college highlights the knowledge that students of this major should master in quality-oriented education and engineering education. Professional basic courses constitute the most core basic knowledge of this major, and the setting of professional courses reflects the common requirements of IoT technology application ability and the training focus of IoT Engineering major in our college.Our college is positioned as application-oriented, and its teaching activities focus on \u201capplication,\u201d aiming at cultivating high-quality application-oriented talents with strong social adaptability and competitiveness. IoT Engineering itself is closely related to practical application, so practice teaching is the key to make students digest kinds of theoretical knowledge and applThe application ability of students majoring in IoT Engineering includes engineering practice ability and innovation and entrepreneurship ability . Around The IoT Comprehensive Experiment Center of our college is one of the Experimental Teaching Demonstration Centers in Henan Province. It has an IoT experience experiment platform, a communication experiment system, a smart experiment platform of agricultural machinery, Cisco network routers and switches, high-performance servers and computers, optical fiber fusion splicers, IoT Comprehensive testers, FLUKE network testers, and embedded experiment boxes and provides experiment environment for professional experiments such as a single-chip microcomputer, embedded system, RFID, wireless sensor networks, communication and switch, upper computer, cloud, and AI. We utilize educational psychology to set up three-level experiment courses. These courses incorporate the application of the IoT in the building materials industry, smart agriculture, and advanced manufacturing industry. Step by step, they can mobilize the initiative of students in the experiment/experimental training and can cultivate engineering practice ability in cement production simulation, smart livestock farm, industrial Internet, and other industries, highlighting the characteristics of the IoT Engineering major of our college and the good teaching quality.Experiment is the foundation for cultivating ability to apply knowledge flexibly, and practical training is the basis for students to improve their personal abilities and possess engineering practice and innovation/entrepreneurship capabilities. By rationally setting up on-campus practical training courses, using educational psychology scientifically to analyze students\u2019 practical training status and arrange corresponding practical training details, students can consolidate their learned knowledge and cultivate their practical ability in the actual trial production environment. Based on educational psychology, our college guides students to contact, understand, and serve the society through reasonable planning of corporate training, IoT project engineering design, and graduation project; and cultivate students\u2019 IoT comprehensive practical ability, especially the service and innovation capabilities of IoT in building materials industry with big data. Our college has set up a practical training center for IoT and further built practical training and scientific research platforms such as \u201cCisco Network Technology Institute,\u201d \u201cHuawei Institute of Information and Network Technology,\u201d \u201cRenesas Electronic Joint Laboratory,\u201d and \u201cShuguang Ruiyi Big Data Innovation Center.\u201d At the same time, our college has signed eight off-campus practice bases with Shenzhen Xunfang Communication Technology Co., LTD., Wuxi NIIT (China) Institute of Service Outsourcing, and other related enterprises, to ensure the quality of on-/off-campus practical training courses in terms of software, hardware, and teachers.\u201cIndustry-College-Research-Competition\u201d (ICRC) refers to the cooperation between colleges and enterprises , which iTo achieve the deep integration of ICRC Student perspective: In four years of college, complete a scientific and technological research in the field of IoT independently, complete several experimental projects related to the needs of enterprises and competition, participate in scientific research activity for teachers at least 1 time, participate in enterprise IoT projects at least 2 times, complete a comprehensive innovative experimental project cooperatively, and participate in IoT-related competition at least 1 time.(2)Teacher perspective: Link their own scientific research with enterprises College perspective: Establish good and stable college-enterprise cooperation with IoT-related enterprises, take the market demand as the guidance, serve Luoyang economy and building materials industry, explore the cultivation mode based on the ICRC integration for the training of high-quality applied talents, improve multi-evaluation subsystem reflecting the characteristics of ICRC with respect to the curriculum system, teaching team, college-enterprise joint practice bases and competition training mode, and construct the talent cultivation subsystem of ICRC integration, carrying out efficient and high-quality teaching work.The relevant theories of educational psychology point out that the teacher\u2013student relationship is the most basic and important interpersonal relationship when implementing teaching activities, and the teacher\u2019s attitude toward students affects the quality of teaching directly. Therefore, the cultivation of high-quality application-oriented talents is dependent on the harmonious teacher\u2013student relationship and the smooth development of student-centered teaching activities . At presBy studying the cooperative learning theory in educational psychology, our college has set up a mechanism \u201cStudent Teaching Assistant (STA)\u201d . This meCourse assistants are responsible for maintaining classroom discipline; supervising pre-class preview, after-class review, and homework; and organizing flipped classrooms. CAs\u2019 solid efforts in learning are conducive to creating a good atmosphere for class learning. They assist teachers to detect students\u2019 psychological changes timely; promote healthy competition in learning in the class; encourage all students to develop good habits for listening to classes, previewing and reviewing; improve the utility of flipped classroom teaching activities such as teaching video watching and cooperative discussion; organize curriculum knowledge of IoT Engineering in series by mind mapping and other methods; and organize course knowledge competition. CAs give full play to the role of mentoring and guiding poor students and make progress together. They are selected within the same grade. Each course has 3\u20134 CAs, and each CA is responsible for a study group of less than 10 students. With the help of CAs, the phenomenon of \u201cphubber\u201d in class, homework copying, etc., can be reduced. Good college study habits can be established, and students are more active and solid in learning the theoretical knowledge related to IoT, which is many, complex, and difficult.In addition to experimental classes, our college has an open system to facilitate students to use the laboratory to complete practical tasks after class. One role of PA is the laboratory-assisted management. PAs assist teachers to urge students to maintain a good experimental environment and follow laboratory discipline consciously, and this mechanism cultivates students\u2019 sense of ownership about the laboratory. Another role of PA is to assist teachers to guide various IoT-related experiments, internships, and practical training courses. PAs take the initiative to solve common problems in practice for other students, promote mutual assistance among students, discover and summarize problems, and give feedback to teachers to solve them in a timely manner. PAs are produced from the students in senior grades and the same grade, among which the PAs from senior grades assist in the practice and training and the PAs from the same grades assist in course experiments. With the help of PAs, the interaction between teachers and students is enhanced, so that detailed practical guidance can cover each student, which is conducive to the cultivation of students\u2019 practical ability.Competition and research assistants are mainly responsible for the collection and promotion of competition information, the auxiliary organization of competition training, the leading participation of enterprise projects, and teachers\u2019 scientific research projects (such as IoT software coding and project data collation). They assist teachers to optimize the allocation of personnel and resources for competition and scientific research and shorten the distance between competitions/projects and students. Besides, they take themselves as examples to drive all the students majoring in IoT to learn the frontier knowledge. The selection of such assistants is based on the awards of the competition, and their responsibilities are determined according to the award level. Students with low levels of awards provide introductory training to lower grade students . High-level award-winning students assist teachers in training and guiding IoT technology competitions . In addition, all CRAs participate in the project as team leaders responsible for the implementation of sub-tasks and the management of student members. With the help of CRAs, students are encouraged to form a healthy and upward competitive psychology and stimulate their innovative consciousness. In this way, competitions and participation in scientific research activities can become the norm for the IoT Engineering major, and students can develop their ability to discover, analyze, and solve engineering application problems.In 2014, our college started to recruit students for the IoT Engineering and followed the above methods to build a talent cultivation system. At present, certain results have been achieved in cultivating high-quality applied talents.To check students\u2019 subjective initiative, questionnaires for students\u2019 self-evaluation in learning are released at the 1/4 semester, 1/2 semester, 3/4 semester, and the end of the semester. The scores of the questionnaires from 2014 to 2021 were sorted out, and the results are shown in The execution quality of experiment and practice directly affects the quality of IoT Engineering talent cultivation. Collecting the assessment results of experiments and practice sessions, the average proportions of excellent, good, medium, and poor grades are calculated separately according to Eq. 1 every year from 2015 to 2021, and m and n are the number of courses and practice sessions, respectively; Exp Li and Pra Lj are the number of students who gain grade L in experiments attached to course i and practice session j separately; and Ci and Pj are the number of students attending the course i and practice session j, respectively.where Participating in competitions and teachers\u2019 scientific research is an effective way to enhance the core competitiveness of students. We counted the number of students who take competition and scientific research in IoT Engineering, with results shown in Students are the objects of talent cultivation and the core of teaching activities, and their psychology directly affects the training quality. To this end, we can use educational psychology with student learning psychology as the core to improve the cultivation quality of application-oriented talents in IoT Engineering.The construction of a high-quality application-oriented talent cultivation system for IoT Engineering involves many aspects. We analyze the existing knowledge architecture of IoT technology according to educational psychology. Based on the characteristics of the IoT major, we provide the formulation and adjustment strategies of talent cultivation programs and then put forward the idea of building a high-quality talent cultivation teaching system based on constructivism. Considering the psychological characteristics of teachers and students, we explore the deep integration mode of industry, college, research, and competition. Finally, we construct an STA auxiliary mechanism using a positive energy psychological hint. To sum up, all of these conduct the cultivation of high-quality application-oriented talents for IoT Engineering.The rapid and sustainable development of IoT technology determines that it is a long way to cultivate high-quality application-oriented talents for IoT Engineering. In the future, efforts should be made to integrate educational psychology and teaching practice to obtain more efficient and high-quality methods of training application-oriented talents.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.YN: investigation, writing original draft, data analysis, and method design. HW: applied research in educational psychology, investigation, and method design. BL: editing, writing, checking, and data collection. SY: implementation plan of educational psychology. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The nanopatterning of bionic materials, performed by means of laser processes that utilize pulsed laser sources with short and ultrashort pulse durations, is a rapidly growing field. The method\u2019s applications are varied, being used mainly to tailor special industrial, medical, and scientific applications. This process is significantly driven by the exciting properties of micro- and nanopatterned materials found in natural biological species. These include being self-cleaning, capable of adapting color and reflectivity, the possession of pronounced adhesive and anti-adhesive properties, the aptitude for wetting and directional fluid transport, reduction of wear and friction, control of cell growth, and antimicrobiotic properties .This Special Issue, entitled \u201cNanopatterning of Bionic Materials\u201d, represents an extension of the former review and includes a collection of recent top-quality articles in this research area. Particular attention has been devoted to the functionalization of medical implants and other surfaces, relevant for biomedical applications owing to the widespread need for improved approaches in medicine in our aging society. A comparable scenario applies for miniaturized sensors concerning the sensitivity of small traces of biologically hazardous or metabolic gases.(i)Functionalization of Ti-based medical implants by means of laser-induced micro- and nanostructures for cell repellence as well as for osteoblastic proliferation and differentiation ,3,4;(ii)Polymer surfaces with antimicrobiotic and antiadhesive properties induced by laser-induced periodic surface structures (LIPSS) in connection with nanofibers or nanowires ,6,7;(iii)The generation of novel hybrid carbon nanotube materials for biosensing applications by means of laser-induced forward transfer (LIFT) .Herein, only original research articles have been considered for publication. The present Special Issue includes contributions on the following research topics:Overall, I am grateful to all the authors for their fine contributions to the present Special Issue, and hope that the published studies will pave the way for the novel real-world applications of nanomaterials in medicine and biotechnology."} +{"text": "A 34-year-old female was referred to our department, complaining of multiple asymptomatic lesions that appeared two weeks previously. The patient had active nephritis with nephrotic syndrome and was treated with immunosuppressive therapies. Physical examination revealed multiple well-circumscribed rounds of flat brownish plaques with slightly elevated borders, some of which were covered by scales. The number of lesions was nine in total. Skin biopsy specimens showed dyskeratotic cells in the thinned epidermis with cornoid lamella, and the absence of a granular cell layer. The development of porokeratosis was considered to be related to immunosuppressive therapy or the activity of nephritis. Dear Editor,A 34-year-old female was referred to our department, complaining of multiple asymptomatic lesions that appeared two weeks previously. Physical examination revealed multiple well-circumscribed rounds of flat brownish plaques with slightly elevated borders, some of which were covered by scales . The numEruptive porokeratosis is characterized by rapid onset of porokeratosis, which occasionally presents with more than 100 lesions involving multiple regions, in association with paraneoplastic, immunosuppressive, inflammatory, and other conditions.None declared.Masato Ishikawa: Designed the study; performed the research and contributed to analysis and interpretation of data; wrote the initial draft of the manuscript; read and approved the final version of the manuscript.Toshiyuki Yamamoto: Designed the study; assisted in the preparation of the manuscript; read and approved the final version of the manuscript.None declared."} +{"text": "Vector-borne diseases (VBDs) are a major threat to human health. Climate change has a significant impact on VBDs. To clarify the complex effects of climate change on VBDs, we concluded the effects of climate on the transmission and spread of VBDs from an ecological perspective and summarized VBD changes in response to climate change, specifically including: the nonlinear effects of local climate on VBD transmission, especially temperature showing n-shape effects; regional climate (the El Ni\u00f1o\u2013Southern Oscillation and North Atlantic Oscillation) has time-lag effects on VBD transmission through indirect impact on local climate; and the u-shaped effect of extreme climates can lead to the geographical spread of VBDs. In terms of non-climatic factors, land use and human mobility through the interactions with climatic factors, will affect transmission and spread of VBD. We further explored the uncertainty of the impact of climate change on VBDs under the COVID-19 pandemic. A systematic understanding of the impact of climate change on the transmission and spread of VBD can provide insights and suggestions for future research on VBD prevention and control.Climate change affects ecosystems and human health in multiple dimensions. With the acceleration of climate change, climate-sensitive vector-borne diseases (VBDs) pose an increasing threat to public health. This paper summaries 10 publications on the impacts of climate change on ecosystems and human health; then it synthesizes the other existing literature to more broadly explain how climate change drives the transmission and spread of VBDs through an ecological perspective. We highlight the multi-dimensional nature of climate change, its interaction with other factors, and the impact of the COVID-19 pandemic on transmission and spread of VBDs, specifically including: (1) the generally nonlinear relationship of local climate and VBD transmission, with temperature especially exhibiting an n-shape relation; (2) the time-lagged effect of regional climate phenomena (the El Ni\u00f1o\u2013Southern Oscillation and North Atlantic Oscillation) on VBD transmission; (3) the u-shaped effect of extreme climate on VBD spread; (4) how interactions between non-climatic (land use and human mobility) and climatic factors increase VBD transmission and spread; and (5) that the impact of the COVID-19 pandemic on climate change is debatable, and its impact on VBDs remains uncertain. By exploring the influence of climate change and non-climatic factors on VBD transmission and spread, this paper provides scientific understanding and guidance for their effective prevention and control. Climate change, which has affected the world since the last century, has caused a general rise in temperatures over the period of 1906\u20132005 and poseThe ten publications in this Special Issue illuminate the impacts of climate change on ecosystems and human health from different perspectives in diverse disciplines, including phytology, biology, epidemiology, pathology, and molecular biology. In phytology and biology, the geographical ranges of plants and animals have been shown to be affected by climate change ,7,8. In As a climate-sensitive type of disease, VBDs are assessed on a global scale with the aim of shedding light on possible future trends, particularly given the increased likelihood of climate change . The impThe influence of climate factors on the transmission and spread of VBDs can be considered at the levels of local climate, regional climate, and extreme climate. Local climate, represented by temperature, rainfall, and wind, mainly affects the transmission of VBDs by affecting their vectors ; regionaThe effects of local climate factors on VBD transmission are generally nonlinear. These factors can affect the distribution range, population dynamics, and virus transmission ability of vectors , and henThe non-linear effect of temperature on VBD transmission generally follows an n-shape . Under sPrecipitation has also demonstrated a nonlinear effect on VBD transmission in many studies. A suitable level of precipitation may be beneficial for the formation of vector breeding habitats , especiaHigh wind speeds hamper mosquitos in their flight, can decrease the density of mosquitoes, and make them less likely to stand on and bite their hosts. An example to support this view is the finding that high wind impeded the rate of West Nile virus transmission; conversely, there is no obvious negative trend in the effect of low wind speed on mosquitoes. ,45. ThisClimate change has an important impact on the transmission of vector-borne diseases, which in general will expand the climate-adaptive transmission zone of vector-borne diseases. In Europe, climate change is likely to expand ticks into higher latitudes and altitudes, thereby increasing the incidence of tick-borne diseases . In SoutRegional climate mainly exerts its influence on VBDs through local climate factors, which in turn affect the ecological habitat, distribution, and population dynamics of the vectors , and henNumerous studies have concluded that local climate has a time-lag effect on VBD transmission in the short term. For rodent-borne diseases, many studies have also demonstrated a time-lag effect of regional climate, such as on renal hemorrhagic fever ,57, leptTime-lag effects of regional climate have wider ranges and longer timespans than local climate effects, and hence are more relevant to making predictions for disease prevention in advance. ENSO is the most significant example of quasi-periodic climate variability on an interannual scale that can affect weather all over the world . The patWith the frequency of climate extremes increasing as climate change accelerates, it is increasingly important to understand the impact of climate range edges and limitations on VBDs A. Most eDifferent types of extreme climate events have different effects on the distribution expansion of VBDs. The impact of heat waves on mosquitoes depends on the onset time and duration; such events usually promote mosquito population growth in early developmental stages, but often suppress the entire life cycle . Thus, uAedes aegypti can expand its distribution in mountainous areas by up to 4215 km2, which would put over 12,000 people at risk of disease [Ixodes ticks in Europe, especially Northern and Central Europe; however, extreme weather is expected to expand the distribution of Ixodes ticks in Europe by 3.8% during 2040\u20132060, and tick-borne encephalitis (TBE) is expected spread to high altitudes and latitudes [Thus, in the context of climate change, climate extremes are increasingly expected to create additional risks and possibilities for the spread of VBDs ,89. When disease . In Indi disease . Extremeatitudes . In New atitudes .Beyond climate factors alone, the interactions of non-climatic factors (land use and human mobility) and climate factors are important to consider for their impacts on VBD spread ,28,94. The interaction of land use and climate change will provide opportunities for pathogen exchange among geographically isolated wildlife, and thus in some cases will promote disease spillover . ProjectHuman mobility is also a major factor in the global spread of VBDs ,97. With2 emissions was found to weaken the aerosol cooling effect, which can lead to warming [The impact of the COVID-19 pandemic on climate change is debatable in the short term ,100,101; warming . These pBesides climate change, lack of vector testing and control activities ,105,106 However, lockdown policies have greatly reduced imported cases and blocked sources of VBD transmission ,111,112.In this paper, we summarized the different impacts of multiple climatic factors on the transmission and spread of VBDs in the context of climate change. Local climate exerts non-linear direct effects, resulting in rapid transmission in suitable conditions and decline in an unsuitable environment, with local temperature in particular showing a clear n-shape. Regional climate has an indirect impact on VBDs, affecting transmission through its effects on local climate, which by necessity produces a certain time-lag for the effect on disease transmission. Extreme climate events can increase the spread of disease, leading to the expansion of VBD distributions. Moreover, land use and human mobility have an important interaction effect on VBD spread, increasing the possibilities for spread and spillover. The impact of the COVID-19 pandemic on how climate change affects VBD transmission and spread is yet uncertain.Quarantine policies during the COVID-19 pandemic successfully blocked the import of VBD cases; this effective prevention and control policy is worth adopting and applying in the field of VBDs. Meanwhile, the impact of COVID-19 on climate change is controversial, and its potential effect on VBDs may gradually become clear in the future. Accordingly, it remains necessary to further explore the potential of COVID-associated climate change to drive effects on VBDs. Meanwhile, the improvement of surveillance systems in relation to the COVID-19 pandemic and the construction of a surveillance network are also worthy of application in VBD surveillance. With the continuous improvement of monitoring systems, it also becomes necessary to adopt methods from the fields of machine learning and artificial intelligence to handle large databases with complex algorithms in the future.There is still a lot of research worth undertaking with regard to climate change and VBDs. One important research direction is to integrate multidisciplinary factors to analyze the impact of climate change on VBDs, especially with reference to the fields of computer science, zoology, entomology, ecology, and epidemiology. Through the integration of multiple disciplines, we can not only better understand the impacts of climate change on VBDs, but also develop a deeper understanding of the occurrence and development mechanisms of these infectious diseases. Such findings could contribute to achieving a better understanding of how climate change drives effects on VBD risk and spread, thereby improving the prevention and control of VBDs and so improving human health."} +{"text": "Recognizing an urgent need to understand the dynamics of the pandemic\u2019s severity, this longitudinal study is conducted to explore the evolution of complex relationships between the COVID-19 pandemic, lockdown measures, and social distancing patterns in a diverse set of 86 countries. Collecting data from multiple sources, a structural equation modeling (SEM) technique is applied to understand the interdependencies between independent variables, mediators, and dependent variables. Results show that lockdown and confinement measures are very effective to reduce human mobility at retail and recreation facilities, transit stations, and workplaces and encourage people to stay home and thereby control COVID-19 transmission at critical times. The study also found that national contexts rooted in socioeconomic and institutional factors influence social distancing patterns and severity of the pandemic, particularly with regard to the vulnerability of people, treatment costs, level of globalization, employment distribution, and degree of independence in society. Additionally, this study portrayed a mutual relationship between the COVID-19 pandemic and human mobility. A higher number of COVID-19 confirmed cases and deaths reduces human mobility and the countries with reduced personal mobility have experienced a deepening of the severity of the pandemic. However, the effect of mobility on pandemic severity is stronger than the effect of pandemic situations on mobility. Overall, the study displays considerable temporal changes in the relationships between independent variables, mediators, and dependent variables considering pandemic situations and lockdown regimes, which provides a critical knowledge base for future handling of pandemics. It has also accommodated some policy guidelines for the authority to control the transmission of COVID-19. Coronavirus disease 2019 (COVID-19) is a public health crisis that has afflicted more than 225 countries all over the world ,9,10,11.Furthermore, the socioeconomic makeup and institutional structure of a country can influence pandemic severity, human mobility, and the rigor of various lockdown measures. Our previous research investigated the complex relationships between the COVID-19 pandemic, lockdown measures, and people\u2019s social distancing and mobility behaviors . HoweverIn the preceding study , we empiConsidering that the early effort was limited by the cross-sectional nature of the analysis, where each population sample was observed at a single point in time, the present study situates the clinical, behavioral, social, and institutional aspects of the pandemic in a broader temporal context and examines sampled countries repeatedly at different periods to detect seamlessly any changes in the variables and parameters in different phases of the pandemic. Moreover, the availability of time-series data would ensure the dynamic properties and stability of our model, which is critically important to assess the vigor of the pandemic and better empower the world for effective action under changing socio-politico-medical contexts. Despite meaningful insights from the previous study after a few months of the pandemic, a longitudinal study comprising of time series data is necessary to capture the temporal aspects of the pandemic, how they evolve and influence the mobility of the people, and how people adjust with the changing environment. This spatial-temporal data analysis is critical to mitigating the pandemic efficiently by taking data-driven decision-making .What are the impacts of various lockdown measures on reducing people\u2019s mobility patterns and the severity of the pandemic?What are the consequences of the pandemic severity on mobility patterns and, therefore, on the practice of social distancing of people?What are the impacts of human mobility on the severity of the pandemic?What are the effects of socioeconomic factors of domestic populations and institutional arrangements and dispositions on population mobility and on the pandemic severity?Thus, this longitudinal study aims to investigate the evolution of complex relationships between the incidences of the COVID-19 pandemic, lockdown measures on populations, and their social distancing and mobility behaviors throughout the time of the pandemic from March 2020 to February 2021 across 86 countries of the world. Thanks to the integrated analytical framework of SEM, the following four research questions are formulated to understand the evolution of these intertwined relationships in different waves of the pandemic:The rest of the paper is organized as follows. A number of studies have investigated the complex relationships between the COVID-19 pandemic, lockdown measures, social distancing, and human mobility patterns. The following sub-sections summarize and discuss the associations between the conditions related to this pandemic after critically reviewing and analyzing previous studies.The COVID-19 pandemic has drastically changed mobility systems due to enacted lockdown and confinement measures, social distancing practices, and personal hygiene requirements, most strikingly with an increase in private travel modes and a decrease in public transport ,21,22. SHaving compiled mobility data of mobile phone users by country/region/sub-region/city, Apple Inc., Cupertino, CA, USA, has estimated changes in human mobility around the world . CompareMany studies have investigated the impacts of COVID-19 on human mobility patterns in more detail. For example, Bucsky calculatSimilarly, observing travel patterns of 1439 people in Switzerland, researchers in estimateSome studies also investigated how transport accessibility and human mobility may have stimulated the spreading of the COVID-19 virus. For example, researchers in quantifiHadjidemetriou, Sasidharan investigFrom the above discussion, it is conceived that COVID-19 and human mobility influence one another . A higheWhile the fear of infection and of serious health complications has gripped the state of mind of many segments of human societies, lockdown and confinement measures adopted by governments during the COVID-19 pandemic may have tangibly influenced travel patterns of people. A number of empirical studies have investigated and compared the movement of people before, during, and after the lockdown regimes to understand the impacts of NPIs on travel patterns ,37,38,39Saha, Barman investigResearchers in investigIn Australia, Beck and Hensher noticed 2 of 0.998. The model indicated that, after 6 weeks of the lockdown measures, confirmed cases had dropped threefold below the initial level, which sanctions the effectiveness of control measures to mitigate the severity of the pandemic. As a whole, lockdown and confinement measures may play a critical role in curtailing the transmission of viruses by reducing human mobility, contacts, interactions, and social gathering. Several studies have investigated the effectiveness of lockdown and confinement measures for travel restrictions on COVID-19 transmission in cities and regions. For example, applying a data-driven epidemic model, researchers in investigIn the same geographical context of India, Gupta, Mohanta used an Oum and Wang determinLockdown and confinement measures tend to curtail human mobility immediately, however, they may do so differentially according to trip purposes. In addition, incubation would delay the damping of infection cases and deaths by one or two weeks , hence, The socioeconomic status of people, living environments, and community structures are very important factors in viral diffusion. Much research has been conducted on the socioeconomic factors of COVID-19 transmission. These studies also investigated the temporal and spatial dependence in the associations of these factors with COVID-19 transmission. For example, Andersen, Harden studied Maiti, Zhang exploredSome studies also investigated the impacts of urban form on COVID-19 transmission. For example, Carten\u00ec, Di Francesco found thSome studies have also evaluated COVID-19 incidence in different environmental and climatic conditions. For example, researchers in quantifiHowever, adjusting for city-level socioeconomic and disease control factors , researchers in found onJust as the COVID-19 pandemic is conditioned by socioeconomic and spatial factors, so may human mobility, including aspects of travel mode choice, travel distance, and travel time. Some studies also investigated the variations in the mobility of people from diverse sociodemographic backgrounds and geographical contexts. For example, Molloy, Schatzmann observedCollecting travel flow data from 1436 administrative areas of mainland France, researchers in noticed Based on the comprehensive review of the extant literature summarized above, a conceptual framework is developed to study the relationships between lockdown measures, mobility patterns, pandemic severity, and socioeconomic and institutional factors of countries across all world regions . The conTo test and validate the conceptual model internationally at the scale of countries and determine the relative strength of the complex relationships between the factors outlined in Data related to changes in human mobility due to lockdown measures were collected from Google Mobility Reports ,75. ThisThe total daily number of coronavirus infection cases and death cases for the study period were sourced from Our World in Data, a research project at the University of Oxford . They coSEM is used to investigate the causal relationships between socioeconomic and institutional factors, lockdown variables, coronavirus infection and death rates, and social distancing measures and validate the model depicted in Human mobility : TS, RR, WP, and RDPandemic severity: l_case and l_deathLockdown measures: NL, WPC, SH, and SISocioeconomics and institutional factors: MA, AGE65, KOFGI, AE, SE, HE, FS, EI, and IDV.Based on exploratory factor analysis (EFA) and extant theories reviewed in the previous section of this article, latent dimensions are created to reduce dimensions and easily understand the data and represent underlying concepts. The following four latent dimensions are constructed: Moreover, a path diagram is constructed to graphically represent the interdependencies of the independent variables, mediators, and dependent variables in the model specification. Finally, a set of fit indices are estimated to establish the goodness-of-fit of the model. Two models evenly spaced on the timeline are estimated from each month from March 2020 to February 2021, to capture the temporal aspects of the pandemic, how they evolved and influenced the mobility of people, and how people learned and adjusted to the changing environment . Hence, The models were calibrated using the SEM Builder on the STATA 15 platform . The maxThe robustness of the calibrated models was assessed with several goodness-of-fit statistics, as presented in The Chisq/df values of all models presented in The direct, indirect, and total effects of lockdown and confinement measures on human mobility from 17 March 2020 to 28 February 2021 are depicted in In addition to their direct effect on social distancing patterns, lockdown measures can also have an indirect impact on humanThe impacts of lockdown and confinement measures on each of the factors of human mobility patterns can be estimated by the same token d. OveralConsidering the direct and indirect effects discussed so far, The impacts of COVID-19-related lockdown and confinement measures on overall pandemic severity, COVID-19 confirmed cases, and deaths, are presented in The direct, indirect, and total effects of the pandemic on human mobility over the study period are captured in The indirect impact b of the Drilling down deeper into human engagement in various activities, Combining direct and indirect impacts, The indirect impact b of humaCombining direct and indirect impacts, the overall trend c shows tThe direct, indirect, and total effects of socioeconomic and institutional factors on social distancing are presented in The indirect effects b of sociThe total impact of socioeconomic and institutional factors on social distancing measures c shows aThe direct, indirect, and total effects of socioeconomic and institutional factors on pandemic severity are shown in Indirect effects b of sociThe overall impacts c of sociConsidering the direct and indirect effects and their temporal variation, this study reported a negative association between lockdown measures and human mobility at the onfall of the pandemic from March 2020 to mid-May 2020. People maintained strong social distancing when the government imposed strict lockdown measures and restrictions on mobility. On the other hand, citizens defied social distancing practices when authorities eased lockdown measures between mid-May and mid-October 2020, and they aspired to go back to normal life and break the dullness of their confined life. However, a further reduction in human mobility was observed from November 2020 to mid-January 2021 due to the reinstatement of lockdown measures induced by the sharp rise in coronavirus cases and deaths. Thus, strict lockdown measures significantly reduced human mobility across countries, which upholds the findings from our previous study , where wWe have also shown that lockdown and confinement measures indirectly influence the COVID-19 pandemic by moderating social distancing/human mobility patterns. The study findings indicate that the pandemic severity intensified in some countries from March to May due to the inadequate practice of social distancing and from mid-October to February due to the increase in human mobility induced by relaxed lockdown measures and people\u2019s eagerness to return to normal life. However, the study noticed that adequate and timely adopted lockdown measures reduced the severity of the pandemic from June to mid-October, which corroborates the findings from previous studies ,86,87,88Socioeconomic and institutional conditions encourage people to practice social distancing , considering the greater vulnerability of the elderly, higher treatment costs, higher level of globalization, increasing employment in the service sector, decreasing employment in agriculture, and the degree of independence in national societies. These factors also motivate people to maintain social distancing while the pandemic is more severe and lockdown measures are more strict, considering the greater risk of COVID-19 infection due to fragile public health conditions, higher risk of infection from globalization, and open interactions. Thus, socioeconomic and institutional factors have significant impacts on maintaining social distancing to reduce the severity of the pandemic ,90,91.This study also found a significant impact of socioeconomic and institutional factors on the severity of the pandemic. Considering direct and indirect impacts, we observed that socioeconomic and institutional factors increased the severity of the pandemic due to a higher number of elderly people who are physically susceptible to COVID-19, a higher level of globalization, increasing employment in the service sector, a reduction in agriculture, and a higher degree of independence in society. Thus, socioeconomic and institutional factors increase the severity of a pandemic by reducing social distancing practices and increasing human mobility for essential and non-essential purposes ,90,91,92The study found mixed effects of the COVID-19 pandemic on maintaining social distancing. The negative association at the early stage of the pandemic (March to June) indicates that the increasing severity of the pandemic reduced human mobility and increased time spent at their residence. Early on, people reduced their movement due to lockdown measures and self-awareness induced by fear of infection, which endorses the findings from previous studies ,26,93,94Investigating the impact of human mobility on pandemic severity, we observed a strong negative and sustained impact of mobility/social distancing on pandemic severity throughout the study period compared to the baseline scenario, with the greatest impacts in late December 2020 and early January 2021. The study showed that countries with a sharper reduction in personal mobility had experienced an increased severity of the pandemic due to the absence of other NPIs and the possibility of infection from other family members while home confinement. Thus, maintaining social distance lessens the severity of the pandemic by reducing human trips to retail and recreations, transit stations, and workplaces and encouraging people to stay at home, which confirms the results from previous studies ,95,96. HGiven the adverse effects of the COVID-19 pandemic, there is a pressing need to understand the root causes of the pandemic, associated risks, and conditions that exacerbate its impacts and promising mitigation measures. This study intended to perform a longitudinal study spanning a great diversity of countries, with data from March 2020 to February 2021. The main objective of this longitudinal study was to explore the evolution of complex relationships between the incidence of the COVID-19 pandemic, lockdown measures on populations, and their social distancing and mobility behaviors in 86 countries. A conceptual framework was developed to hypotThe study results indicate that implementation of lockdown and confinement measures are necessary to reduce human mobility and encourage people to stay home to control COVID-19 transmission through community infection. However, delayed implementation of lockdown measures, relaxation of lockdown measures, and people\u2019s failure to maintain social distancing and their travel for work and discretionary activities can worsen the pandemic. Thus, it is suggested to evaluate mobility changes after the implementation of lockdown measures, which can guide policymakers on when to implement stricter lockdown measures or ease them, to curtail the diffusion of coronavirus. The study also found that national context defined by socioeconomic and institutional factors influences social distancing patterns and the severity of the pandemic. Additionally, this study observed an intertwined two-way association between the COVID-19 pandemic and human mobility. Higher severity of the pandemic reduces human mobility and on the other hand, higher human mobility increases the severity of the pandemic. However, the impact of human mobility on pandemic severity is stronger and more significant compared to the reverse relationship. Overall, the study displays considerable temporal changes in the relationships between independent variables, mediators, and dependent variables considering pandemic situations and lockdown regimes.Several policy decisions have been outlined based on the analysis. The timely implementation of strict and comprehensive lockdown and confinement measures is critical to mitigating the severity of the pandemic by reducing the movement of people and person-to-person interactions. Moreover, estimating the changes in human mobility during lockdown periods is an effective policy option to evaluate the social distancing patterns of people. If necessary, a targeted campaign among the less responsive communities or individuals could be effective in enhancing social distancing practice, in addition to vaccine administration at a large scale ,100. SinAlthough this study has revealed the changing faces of the pandemic and provides significant policy implications, adopting an SEM using actual longitudinal data and showing temporal effects in path diagrams could reveal complex causal relationships between COVID-19 pandemic, lockdown measures, and human mobility . Since mThe goodness-of-fit statistics of the models showed a"} +{"text": "Decision Support Systems (DSS) are appropriate tools for guiding policymaking processes in Mental Health (MH) management, especially where a balanced and integrated care provision is required.To assess the performance of a MH ecosystem for identifying benchmark and target-for-improvement catchment areas according to the Balanced Care model.The MH provision, distinguishing inpatient, day and outpatient main types of care, has been assessed in the Mental Health Network of Gipuzkoa using a DSS, integrating Data Envelopment Analysis, Monte-Carlo Simulation and Artificial Intelligence. 13 catchment areas, defined by a reference MH centre, are the units (universe) for the analysis. The indicators for MH ecosystem performance were: relative technical efficiency, stability and entropy, for identifying both benchmarking and target-for-improvement areas. The analysis of the differences between the two groups can be used to design organizational interventions.The Mental Health Network of Gipuzkoa showed high global efficiency scores, but it can be considered statistically unstable . For a global performance improvement, it is recommended to reduce admissions and readmissions in inpatient care, increase workforce capacity and utilization of day care services and, finally, increase the availability of outpatient care services.This research offers a guide for evidence-informed policy-making to improve MH care provision in the main types of care and provide aftercare. The characteristics of the area to be improved are critical to design interventions and assess their potential impact on the MH ecosystem.No significant relationships."} +{"text": "The coronavirus disease (COVID-19) presented a unique opportunity for the World Health Organization (WHO) to utilise public health intelligence (PHI) for pandemic response. WHO systematically captured mainly unstructured information for public health intelligence purposes. WHO used the Epidemic Intelligence from Open Sources (EIOS) system as one of the information sources for PHI. The processes and scope for PHI were adapted as the pandemic evolved and tailored to regional response needs. During the early months of the pandemic, media monitoring complemented official case and death reporting through the International Health Regulations mechanism and triggered alerts. As the pandemic evolved, PHI activities prioritised identifying epidemiological trends to supplement the information available through indicator-based surveillance reported to WHO. The PHI scope evolved over time to include vaccine introduction, emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, unusual clinical manifestations and upsurges in cases, hospitalisation and death incidences at subnational levels. Triaging the unprecedented high volume of information challenged surveillance activities but was managed by collaborative information sharing. The evolution of PHI activities using multiple sources in WHO\u2019s response to the COVID-19 pandemic illustrates the future directions in which PHI methodologies could be developed and used. The World Health Organization (WHO) uses public health intelligence (PHI) as one element of its approach to improve population health. A PHI approach encompasses the detection, verification, risk assessment and investigation of events that pose a potential risk to human health, and communicating this information for effective decision making and action -3. PubliEvent-based surveillance involves the detection, triage and verification of new public health threats and changes in ongoing events. Signals, defined as raw data or information with potential acute human health risk , are detOne of the tools used by WHO for PHI to monitor all hazards, including COVID-19, is the Epidemic Intelligence from Open Sources (EIOS) system . Here, pWith the emergence of COVID-19, additional event-specific criteria were established and adapted over time to reflect the pandemic\u2019s evolution and the evolving response needs. These additional criteria were determined as a result of a discussion between a team of WHO epidemiologists who took into account surveillance objectives and scope, the epidemiological context in which the pandemic took place, and available human resources. The criteria were continuously reassessed every several months, or when the characteristics of the pandemic changed. COVID-19 PHI provided a more complete understanding of disease dynamics rather than relying on IBS alone.The EIOS system was one component key for WHO PHI activities during the COVID-19 pandemic. EIOS is an adaptable, user-oriented and constantly evolving web-based system designed to support, augment and accelerate PHI activities. It is used by communities and organisations from national to international levels . The EIOPrior to the detection of COVID-19, the WHO was conducting standardised EBS daily, employing an all-hazards approach and using official government reports, EIOS and other sources of information. Building on this established mechanism at the onset of the pandemic, the WHO intensified EBS to track initial cases and deaths from COVID-19 while an IBS system was being established to complement International Health Regulations (2005) reporting mechanisms. Due to the volume of information, the number of analysts dedicated to screening for COVID-19-related events was increased. In addition, a separate set of filter criteria was created within the EIOS system exclusively for monitoring information related to COVID-19, which reduced the volume of articles on the routine EBS boards. Systematic information sharing for COVID-19-related signals and events was put in place among WHO country offices, Regional offices and headquarters.Since the first detection of COVID-19 cases, the processes and scope for COVID-19 EBS activities have evolved to reflect changing response priorities. During the early months of the pandemic, EBS complemented official COVID-19 case and death reporting according to the International Health Regulations (2005) and trigThe scope of PHI evolved over time to include vaccine introduction, emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, unusual clinical manifestations, upsurges in cases, hospitalisations and deaths at subnational level. Granular information collected through PHI provided valuable contextual information, which is not always available through IBS sources alone, including the burden on the health system and at-risk and vulnerable groups such as healthcare workers, rapid response teams, indigenous populations, children, pregnant women, elderly people and refugees.The PHI approach combined signals detected via EBS and IBS along with contextual information which provided WHO response teams that supported the assessment and interpretation of COVID-19 epidemiological situations at national and subnational level. Analysts working on COVID-19 PHI activities validated and risk-assessed relevant signals, and communicated them through internal and external information products, including WHO Regional weekly briefing documents and the WHO\u2019s weekly epidemiological update on COVID-19 . In addiBetween 31 December 2019 and 31 December 2021, 4,794 COVID-19 signals were detected and followed up by the WHO at the global level using the EIOS system .In May 2021, the WHO developed a situational alert system to support the early detection of countries where immediate action may help to mitigate the impact of a COVID-19 surge on morbidity and/or mortality. From May 2021 to June 2022, a collaborative, multi-disciplinary, mixed-methods process took place weekly, integrating information and input from teams across the three levels of the organisation. The first stage of the situational alert system employed an automated statistical risk assessment algorithm, based on daily incidence of cases and deaths, to predict COVID-19 disease severity within the near future. This produced an initial alert level for each country. The second stage integrated a PHI-based qualitative context assessment, which provided important information including pressure on the healthcare system; the impact of other concerning epidemiological signals such as concurrent outbreaks and large changes in circulating variants of concern; and the impact of factors affecting response activities such as acute events resulting in insecurity, or mass gatherings and population movement. This was combined with information on vaccination coverage, public health and social measures, and an assessment of the trust in available data for each indicator to produce a standardised recommendation for whether a country should be maintained at the initial alert level, or whether it should be updated. Based on this, teams at WHO global and regional levels jointly agreed on a final classification where the process supported a shared understanding of risk and operational priorities across the COVID-19 incident management teams at different levels of the organisation and, for specific contexts, the rapid release of response funds, distribution of oxygen, distribution of testing supplies, and technical support.WHO was able to effectively adapt its PHI processes and systems including EIOS to align with surveillance strategies across different WHO offices as the pandemic evolved. An example of the unique adaptations implemented at the regional level was seen in the Western Pacific Region. Here, a media statement on cases of \u2018unknown viral pneumonia\u2019 in China (the first detection of COVID-19 cases) was detected through routine EBS processes on 31 December 2019 . EIOS piAdditionally, the WHO and partners conducted PHI for mass gathering events from December 2019 to December 2021, including the Union of European Football Associations championship that took place in 11 countries in Europe, the Tokyo Olympic and Paralympic Games in Japan, Hajj in Saudi Arabia, Al-Arbaeiin in Iraq and the World Handball Championship in Spain.There are many strengths to the COVID-19 PHI activities implemented by WHO during the pandemic. WHO was able to develop a PHI approach throughout the course of the pandemic, used the findings to guide response activities and later to contextualise and supplement information derived from EBS and IBS as processes were established. The WHO\u2019s PHI activities have remained flexible, scalable and resilient, adapting to the changing epidemiological context and availability of the WHO and partners\u2019 person-time. Furthermore, the location of COVID-19 PHI activities within WHO\u2019s Health Emergencies Programme and the Incident Management Support team structure was essential for coordinating and collaborating with key technical experts, ensuring relevancy and usefulness of information gathered, in order to better support Member States.While the WHO\u2019s experience with PHI during the COVID-19 pandemic illustrates its value for the timely detection of health threats using muIn response to these limitations and challenges, several initiatives have been developed to improve EBS activities for COVID-19 and other public health events. WHO offices established a COVID-19 PHI working group to strengthen collaboration, maximise resources and brainstorm solutions. From 31 March 2020 to 31 December 2021, the working group initiated a collaborative use of the EIOS system as one tool for detecting relevant information. The working group also provided regular feedback to further improve the process, including enhanced signal detection and verification, broadening of source types, geographical and language coverage and the use of tools to optimise shared workflows in rapid signal detection and monitoring. In addition to establishing the working group, WHO increased the number of personnel working on PHI, added and formalised trainings on PHI activities for COVID-19 and conducted a survey-based assessment of the system to further understand its strengths and weaknesses.Public health intelligence is a rapidly evolving approach that is necessary for WHO and Member States . The COV"} +{"text": "Rhizopus microsporus var. microsporus through culture for fungi and PCR examination.COVID-19 disease caused by the SARS-CoV-2 coronavirus causes a wide range of clinical manifestations, ranging from mild to severe, with the main ones affecting the respiratory tract, such as pneumonia. In patients with greater severity, the high frequency of bacterial and fungal coinfection stands out, a situation related both to the patient's pre-existing comorbidities and due to the hospitalization itself. Cases of mucormycosis associated with COVID-19 were highlighted in the lay and scientific media, with the increase in mycosis cases being directly and indirectly attributed to the viral infection. This report describes a case of rhino-orbito-cerebral mucormycosis in a diabetic patient hospitalized for COVID-19, whose diagnosis was confirmed by identifying the agent Rhizopus sp. reported eye pain and a decrease in visual acuity on the right eye for ten days, which started during a recent hospital stay in another hospital for COVID-19. His medical file reported treatment with corticosteroids, unspecified antibiotic therapy, and respiratory physical therapy. He was discharged from this hospital and immediately sought the service with edema and intense erythema on the right conjunctiva, mild erythema on the upper eyelid , and ocuopus sp. . The colRhizopus and Mucor genera.5Mucormycosis is a rare, opportunistic, globally distributed fungal disease whose physiopathology is centered on angioinvasion that leads to tissue necrosis. Among the most often described etiological agents are the coenocytic fungi of the In a study conducted before the COVID-19 pandemic, 71% of the world's cases of mucormycosis were reported in India.SARS-CoV-2 also promotes changes in the host, especially in the severe forms of infection, favoring the development of mucormycosis agents. Among them are the direct damage to pancreatic cells, causing acute DM and ketoacidosis, the use of corticosteroids, which alter glycemic homeostasis and indirectly favor the progression of mycosis, the alteration of iron metabolism leading to an internal environment with high rates of ferritin, a key factor for the development of the fungus, and finally, endothelitis caused directly by the virus, facilitating fungal angioinvasion.The case described herein maintains the classic line of mucormycosis presentation, the rhino-orbito-cerebral type, in a patient with a history of DM, who shares another severity factor, COVID-19 infection. Prompt and correct treatment with antifungals and surgical approaches resulted in a disfiguring outcome, but with the preservation of the patient's life in this serious and fatal disease.None declared.Sandy Daniele Munhoz: Design and planning of the study; data collection; analysis and interpretation of data; drafting and editing of the manuscript; obtaining, analyzing, and interpreting data; critical review of important intellectual content; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Rute Facchini Lellis: Analysis and interpretation of data.Ana Paula Carvalho Reis: Analysis and interpretation of data.Gilda Maria Barbaro Del Negro: Obtaining, analyzing and interpreting data.Maria Gl\u00f3ria Teixeira Sousa: Analysis and interpretation of data.John Verrinder Veasey: Design and planning of the study; data collection; analysis and interpretation of data; drafting and editing of the manuscript; critical review of important intellectual content; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.None declared."} +{"text": "Biomolecules demonstrates the almost unlimited possibilities of modern protein engineering in gene expression, protein production and modification, as well as the design and creation of new proteins. The research teams behind the articles included in this Special Issue deal with a variety of proteins of possible medical and/or biotechnological interest, but all of these proteins apply state-of-the-art protein engineering techniques in their research. These techniques include the engineering of chimeric bispecific antibodies, modification of protein stability, enzyme activity and specificity, multiple mutagenesis to analyze the role of amino acid residues in functionally important regions of proteins, etc. This Special Issue of Developing the theme of the membrane-active properties of cytochrome c, Chertkova R. and coworkers evaluateXenopus oocytes and three of them showed enzymatic activity. RhoPDE from Choanoeca flexa exhibited the highest value of light/dark activity ratio. Protein engineering of natural enzymes can be used to improve their properties for optogenetic applications. For example, point mutations in the SrRhoPDE catalytic domain demonstrated the reduced dark activity of this enzyme. Rhodopsin phosphodiesterases (RhoPDEs) possess light-regulated enzyme activities towards cGMP and cAMP and can be used as optogenetic tools. Tian et al. expresseRybchenko V. et al. describePseudomonas sp. E2-15 [Exiguobacterium sibiricum (EsOgl) [Extremophilic enzymes are of special interest for biotechnology due to their unusual properties and activity in specific conditions. The Special Issue includes two papers in which new examples of such enzymes are reported, including a novel esterase Est19 from the Antarctic bacterium p. E2-15 and a coIn the paper by Khan et al. , new bioT. thermophilis and similar chaperones, their domains and mutants obtained in their laboratory and described in the literature, and discussed their possible biotechnological applications for scientific and biotechnological purposes.In their review, Yurkova M. and Fedorov A. describeBiomolecules includes research and review papers that use the best methods of modern protein engineering to modify and investigate proteins of biomedical importance. The studied proteins include therapeutic antibodies, cytochrome c, GroEL, extremophilic enzymes and others. The data obtained may be of great interest for a better understanding of the structure and structural\u2013functional relationships in proteins and their possible use for the development of new therapeutic and biotechnological forms.To conclude, this Special Issue of"} +{"text": "The active development of psychosocial rehabilitation (PSR) has been taking place in Russia within latest two decades. In this regard, analysis of the accumulated experience and problems\u2019 identification in the PSR field is relevant.Conducting a sociological study in the Volga Federal District (VFD) to work out measures for further PSR system development.Sociological, statistical, original semi-structured questionnaire on PSR application, including 26 questions.63 institutions providing psychiatric care in 14 large regions of the VFD participated in the study. Achievements in the field of PSR include: introduction of new forms of rehabilitation care, modern psychosocial interventions; development of the volunteer sector and others. A number of systemic problems were also identified: more pronounced decrease in the availability of psychiatrists in VFD compared to the Russian Federation (RF) as a whole ; insufficient provision with psychotherapists, psychologists, social workers, which varies considerably in different territories (up to 10 times); insufficient use of non-profit organizations\u2019 (NPOs) potential; lack of a unified system for assessing PSR effectiveness.Measures for development of PSR were proposed: improving staffing levels and qualifications of employees, introducing psychosocial interventions with proven effectiveness; dissemination of successful experience of NPOs, development of methodological tools for assessing effectiveness of PSR, its standardization and others."} +{"text": "Program targets professionals from Ministries of Health, including Immunization and Screening Program Managers, and cervical cancer stakeholders.Under the framework of the Global Strategy to Accelerate the Elimination of CC as a Public Health Problem, The University of Texas MD Anderson Cancer Center (MD Anderson), the US National Cancer Institute (NCI), and the Pan American Health Organization (PAHO) partnered to develop the Project ECHO for the elimination of CC in Latin America (ECHO ELA). ECHO ELA is modeled on Project ECHO\u00ae a hub-and-spoke knowledge-sharing approach where expert teams lead virtual didactic lectures and case discussions, building capacity for participants to deliver best-practice programs to their regions.In the first year of the program (2020-2021), 294 participants from 22 countries were registered. Fourteen sessions were held averaging 77 participants per session on topics spanning comprehensive program planning, presenting country experiences on HPV vaccination strategies, new technologies for screening and treatment. Eighteen participants completed the post survey addressing priorities, capacity, and desired outcomes, and two focus groups collected facilitators/barriers to achieving goals.ECHO ELA is potentially an effective tool to enhance collaboration and support countries\u2019 progress towards the elimination of CC."} +{"text": "Editorial on the Research TopicDigital health adoption: Looking beyond the role of technology By Kyratsis Y, Scarbrough H, Begley A and Denis J-L. (2022) Front. Digit. Health. 4: 989003. doi: 10.3389/fdgth.2022.989003Accelerating the adoption of proven digital health technologies and advancing their embedding into routine care operations has the potential to revolutionize human health by boosting efficacy, driving costs down, and increasing access to and capacity for care delivery . It can Shaw and Donia propose a broader socio-technical approach to the ethics of digital health, which spans domains from software, devices and supply chains to inter-personal relationships, organizational and government policies. They emphasize issues of social justice, the need to address inequalities in digital access and advocate anticipatory forms of governance to minimize potential negative consequences. Greenhalgh et al. discuss a conceptual framework\u2014PERCS\u2014used to evaluate remote healthcare consultation services in the UK. The authors focus attention on digital maturity and digital inclusion, examining seven inter-related domains, spanning from the reason for consultation, to patients, care delivery, home and family and the wider system. They identify tensions and contradictions along these domains and elaborate on related practical ethical issues. Shaw et al. analyze the accelerated implementation of video consulting during the COVID-19 pandemic. Using comparative and interpretive policy analysis, the authors identify key variations across the four UK health systems in terms of enabling and limiting conditions at both policy and delivery levels. The authors also caution against inequalities in accessing video consulting services.Reflecting on adoption Nantume et al. explore the commercialization of a wearable vital signs monitor in low resource settings and argue for a holistic implementation perspective, from idea and product design to market. They highlight implementation being intertwined with development and evaluation, involving local stakeholders as co-creators. The authors also stress the role of social dynamics, such as trust in regulatory authorities, and public misperceptions about the technology. Rainey et al. in their survey study explore perceptions of AI by UK radiographers for successful application and integration into clinical practice. The authors highlight important aspects of the professional roles of clinicians, and the need for learning, capability-building and de-mystification of the opacity of AI-in use. Bouabida et al. evaluated two platforms for remote patient monitoring following hospital discharge in the context of COVID-19 in Canada. The authors highlight issues of social acceptability by diverse stakeholders during adoption, maintaining human contact and balancing concerns for confidentiality and data security. They underline the need for user participation in technology development and deployment, also bringing to the fore organizational, social and ethical aspects.Bennet et al. describe the experience of ID-Liver implementation and use in northern England for integrated, pro-active management of patients at risk of developing chronic liver disease. From setting up to piloting and using ID-Liver, the authors argue for the need to mobilize a network of collaborators including commercial partners, healthcare organizations and professionals. Yan et al. in their commentary on digital therapeutics raise the broader question of cost and reimbursement. The authors identify a set of dilemmas for policy-makers, which are related to the specificities of digital therapeutics including the ability of patients to afford and use technological devices and the possibility of reimbursing these therapeutics. Cripps and Scarbrough present a perspective on a sustainable approach to digital applications in the UK's NHS. The authors argue to shift the focus from the technology itself to considering the motivations of users and constraints within specific contexts. They advocate for a wider approach to change that incorporates clinical and behavioral insights, process engineering and knowledge management.Co-creating through digital inclusion and user engagement. (b) Bridging local and trans-local stakeholders including partners from the wider economy and the private sector. (c) Adapting to ethical issues and social forces, beyond technical and clinical aspects, such as public (mis-)perceptions, professional and organizational dynamics, regulatory elements, as well as issues of cost and reimbursement. (d) Demystifying the opacity of digital health applications and assessing digital maturity in practice.The papers' contribution can be grouped into four themes, which highlight key non-technology related aspects of digital health adoption : (a) Co-five key levers that can help drive more effective digital health technology adoption.1.Understanding and responding to the needs and preferences of diverse individuals and communities is critical . A number of authors highlight inequalities in digital health. While inequality is often considered at the point of care in terms of the ability of patients and clinicians to use technology, inequalities also arise when more marginalized groups are unable to voice their concerns and preferences upstream, and to influence the development and evaluation of digital innovations. Aptly, the question of co-creation underpins many papers in the collection.2.Early and active stakeholder engagement in both design and technology use . This highlights the need to partner with and incentivize innovators (including the private sector) to bring in their technical expertise , as well as effective collaboration with patients, healthcare providers and commissioners.3.Building the capability and confidence of all actors to acknowledge and raise quality, privacy, security and safety concerns relating to digital health care . Reskilling, learning and modifying professional roles play a vital role in adoption as the Rainey et al. paper illustrates.4.Adopting a holistic, rather than a piecemeal approach to build a supportive ecosystem. This suggests the need for a long-term strategy, appreciating politics, the regulatory groundwork, reimbursement mechanisms, cost .5.Considering seriously the wider ethical implications of digital health to establish and maintain trust, transparency and accountability.Reflecting on implications for policy and practice, the papers in this Research Topic highlight"} +{"text": "The Silk Road, a historical network of interlinking trade routes across the Afro-Eurasian landmass, was of great importance to the transport of peoples, goods, and ideas between the East and the West. Although its main use was for importing silk from China, traders moving in the opposite direction carried to Central China jewelry, glassware, and other exotic goods from the Mediterranean, jade from Khotan, and horses and furs from the nomads of the Steppe. In historical records, communication between China and Central Asia has been unbroken ever since the opening of the Silk Road in the Han Dynasty. However, relics unearthed from archaeological sites indicate that communication between people along the Silk Road began during the Bronze Age. The Silk Road brought together the achievements of the different peoples of Eurasia to advance the Old World as a whole.Ethnic groups with different religions, cultures and customs inhabited the Ancient Silk Road and experienced complex histories. Patterns in genetic variation between individuals can tell us about the population history of these groups. In recent years, using relatively direct means of studying ancient samples through osseous material, alongside indirect means of analyzing the genomes of modern populations, demographic history\u2014migrations, expansions and colonizing events - have been progressively revealed in numerous genetic studies of early human populations. However, until the present, the origins of the populations along the Ancient Silk Road and relationships have been examined in far less detail.Kairov et al.; Allen et al.; Guarino-Vignon et al.) or microarray technologies , or various kinds of markers, including mtDNA , Y chromosome , forensic STRs , SNPs , and InDels data For example, a novel 6-dye direct and multiplex PCR-CE-based typing system has now been validated and could be considered as a reliable tool for human identification and intercontinental population differentiation In this special editorial, we collected 15 genetic investigations involving the populations living along or related to the Silk Road from ancient times to the present day. These studies approach academic and public Research Topic of the targeted populations through genome-wide sequencing .The eastern end of the Silk Road lies on the middle reaches of the Yellow River. The Shimao site in Shaanxi Province is an important Neolithic archaeological culture in this area. To further reconstruct the genetic structure of Silk Road-related populations, it is necessary to understand the genetic compositions of such early local populations as these. The Shimao population showed a mostly local origin and showed a maternal affinity with Taosi site, a Longshan culture population in the middle Yellow River valley . The former site dates back to the Han Dynasty (118BCE-191CE) and the latter to the Wei - Jin Dynasties and Sui and Tang Dynasties (220CE- 907CE). For the two sites, from the paternal Y-chromosome perspective, all male individuals showed the Sino-Tibetan speaking origin of Yellow River-related populations, while Foyemiao samples demonstrated a higher proportion of an Altaic speaking and North Eurasian ancestral component, alongside a small proportion of southern East Asian ancestry. From the maternal perspective, female Heishuiguo individuals showed a northeast Asian origin and revealed a sex-biased migration from the middle and lower reaches of Yellow River to Hexi corridor. This was consistent with evidence in historical records, especially unearthed slips and was an integral component of the eastern section of Silk Road. Heishuiguo site and Foyemiao site lie in the central and western portion of the Hexi corridor, respectively Another site, Shichengzi, a Han Dynasty agricultural garrison, also located in ancient Xinjiang, has revealed to us genetic makeup of a Frontier population in early imperial China . Archaeogenomics at Shichengzi has revealed two subgroups with East Asian origin and Northeast Asian origin, respectively, occupying a single burial space. Interestingly, stable isotope analysis showed that dietary patterns among site inhabitants could be split among agro-pastoral and agricultural groups. Considering ancient DNA and stable isotope evidence together, it has been argued that Northeast Asian origins of Altaic pastoralists and East Asian origins of Han agriculturalists lived together in the Shichengzi military outpost.Population admixture also can be observed in the Western Regions (present Xinjiang), where individuals at the Xiabandi reveal genetic flow from Central Asian populations and thus the influence of Middle and Late Bronze Age steppe pastoral cultures , Kazakh , Hui , Dongxiang , Bonan , Yugur , Salar , Mongol , and Manchu groups have been investigated using genetic markers and/or genome sequencing at the population level. Generally speaking, population from the same language group exhibit a closer genetic affinity. Furthermore, the Turkic-speaking population from China and Kazakhstan both present a closer genetic relationship to Central Asian populations, while Hui and Tungusic-speaking populations had a significant admixture with Han Chinese. Mongolian\u2019 mitochondrial genomes show a dominant East Asian related ancestry, an outcome of Bronze Age events and Mongol Empire expansion along the Silk Road.The Altaic language family is divided into Mongolic, Tungusic and Turkic language groups. Altaic speaking nomads played an important role in shaping the northern steppe Silk Road. However, their history is often only recorded sporadically in ancient writings of surrounding civilizations. In this special edition, the genetic history of Uyghur .In addition to the northern steppe Silk Road, the Tea and Horse Ancient Road or South Silk Road were another part of the ancient Silk Road. Beginning at approximately 1200\u00a0years ago (Tang Dynasty), the Tea and Horse Ancient Road emerged as a famous caravan road system for tea, salt and horse trading in Southwest China. Guizhou Province, located near the Tea and Horse Ancient Road has been documented as a critical depository of substantial sociocultural, genetic, and linguistic diversity for studying southern Silk Road related populations. The southern Han constitute the majority ethnic group within Guizhou. Guarino-Vignon et al.). The use of recent aboriginal paleogenomes, combined with the genomes of related modern humans, will help us to understand further details of the genetic history of regional populations.At the western end of the Silk Road, Guarino-Vignon et al. found that a bronze age individual from Oxus Civilization at the Ulug-depe site in Turkmenistan, shared genetic affinity with a local BMAC population, and further revealed that modern Central Asian Indo-Iranian\u2013speaking populations primarily harbored ancient BMAC related ancestry (In summary, this special edition focuses on the population history along the Silk Road, covering the eastern limits of the Silk Road, the Western Regions, the northern steppe, and southern Tea and Horse Ancient Road, and western end. The genetic diversity and population structure of modern populations in these regions are dissected using ancient forensic markers. Moreover, combined with modern human DNA data, ancient DNA researches discuss the formation of targeted populations in greater detail. In future work, fine temporal-spatial scales using enlarged sample sizes should be considered when outlining changes in population dynamics along the ancient Silk Road."} +{"text": "Diagnostics of Apocalyptic variant of end-world Delusion with Religious Content (ADRC) in schizophrenia is related with insufficient exploration and recognizability, despite the severity of the state, social risks and resistance to psychopharmacotherapy.To define psychopathological and phenomenological features of ADRC in schizophrenia, to identify the clinical dynamics of delusional disorders due to specifics of the delusional behavior, and to develop diagnostic and prognostic criteria.28 patients with ADRC in schizophrenia were examined . Clinical-psychopathological and statistical methods were applied.Delusional ideas of end-world, Apocalyptic variant, occurred in the structure of affective-delusional state . Two types of ADRC were identified: with the predominance of acute sensory delusions of perception and with the predominance of visual-figurative delusions of the imagination. These types differed in the severity and depth of psychotic manifestations and in the specifics of a delusion formation, were characterized by the mono- or polythematic delusional disorders.Cases of ADRC differ both in the clinical-psychopathological specifics of delusional constructions, and in the socio-behavioral aspect. Among these cases, there is a high risk of delusional destructive behavior, with auto-aggressive, suicidal attempts and hetero-aggressive behavior. In cases with ADRC the strong persistence of delusional pseudo-religious beliefs occurs, with the refusal of any medical and psychological assistance, as well as implication of socially dangerous acts associated with the spread of delusional ideas and their induction of religiously inclined persons, which leads to the emergence of pathological pseudoreligiosity .No significant relationships."} +{"text": "I believe that business is nothing more than a group of people trying to make a difference.\u201d\u201c\u2014Sir Richard BransonAntimicrobial Stewardship and Healthcare Epidemiology (ASHE) journal is a momentous step for the scientific mission of the Society for Healthcare Epidemiology of America. All of us on the editorial team are both honored and deeply excited about the future of ASHE. Before looking forward, it is important for us to pause and reflect on the multiple events of the last year and the coronavirus disease 2019 (COVID-19) pandemic to gain a better perspective on and clear commitment to what lies ahead.The launch of the open-access The COVID-19 pandemic affected us in multiple ways. As healthcare epidemiologists and healthcare providers across varied components of the healthcare delivery spectrum, we faced tremendous challenges in infection prevention, patient quality and safety antimicrobial stewardship, disinfection, the use of personal protective equipment, diagnostic testing and the clinical management of SARS-CoV-2 infected patients. All of this was coupled with rapid scientific discovery and dissemination in the medical literature.The COVID-19 pandemic further exposed the many weaknesses in the fabric of society, including significant healthcare disparities by race and inequalities in access and outcomes for individuals with COVID-19. The tragic death of George Floyd reignited an intense awareness of racism, diversity, justice, equity, and intersectionality. The year 2020 also witnessed an explosion of misinformation across multiple spheres including medicine and politics. More than ever, the medical infodemic underscored the important role of epidemiologists as both content experts and scientists to drive an evidence-based public health response in critical times.These unique times shaped the vision of ASHE. The journal is committed to the rapid dissemination of high-quality, timely, evolving science in antimicrobial stewardship and healthcare epidemiology in an open-access model, to serve both developed and low- and middle-income countries. To do so, we are committed to diversity in professional backgrounds, nationalities, and gender across the editorial team, such that journal leadership reflects not only the membership of the Society for Healthcare Epidemiology of America but also the antimicrobial stewardship and healthcare epidemiology community at large. Next, we will seek innovative original science, reviews, and commentaries that represent a diversity of perspectives, issues, evolving challenges, and controversies in the varied field of healthcare epidemiology and antimicrobial stewardship, with the ultimate goal of maximal content accessibility to a worldwide readership. Additionally, SHEA members will benefit from a highly discounted rate and the journal will waive publishing costs for invited reviews.Authors submitting to ASHE will find that the journal provides constructive peer review, competitive turnaround times, immediate online publication, and social media promotion. As a fully gold open-access journal, ASHE readers will benefit from free and easy access to all journal content, bringing the widest possible impact, reach, and discoverability for our authors and readers. The journal is engaged in efforts to ensure that article processing charges (APCs) are not a barrier to publication. Our publisher, Cambridge University Press, has recently signed a number of read-and-publish agreements with hundreds of institutions worldwide, which will cover APCs for corresponding authors from those institutions. APCs for authors from low- or middle-income countries will be waived or discounted through initiatives like Research4LifeAs we move forward and view the COVID-19 pandemic in the rearview mirror, we must not forget the valuable lessons learned from scientific responsiveness and the publication of high-quality science, under a vigorous peer review, in an open-access manner. With a diversity of both content and contributors, ASHE will aim for a global audience for advancing patient safety, antimicrobial stewardship, and healthcare epidemiology, with the aspiration of making a difference."} +{"text": "The Yellow River basin spans nine provinces and autonomous regions and plays an important role in China's economic and social development and ecological security. However few studies have integrated the concept of carbon neutrality into research to evaluate the carbon-neutral development level. This paper calculates the comprehensive evaluation value of the provincial carbon-neutral capacities comprehensive evaluation index in the Yellow River basin through the driving-force-pressure-state-impact-response (DFPSIR) index system and the global entropy method based on provinces data between 2008 to 2019. The final results indicated that from 2008 to 2019, the carbon-neutral capacities of the provinces in the Yellow River basin were in a state of rapid development and had achieved a grade leap. However, seven provinces had carbon-neutral capacity levels at the Grade III standard in 2019, thereby leaving scope for substantial improvement. Through the above research, we identified the changes in the trend and driving mechanisms of the carbon-neutral capacity of the Yellow River basin and provide a theoretical reference value for a comprehensive realization of carbon neutrality in China in 2060. Unchecked emissions of greenhouse gases lead to global warming and aggravate problems such as ecological and environmental deterioration and energy crises. Therefore, an increasing number of countries have switched to developing low-carbon economies as an effective way for sustainable development since the advent of the twenty-first century. As a special low-carbon development mode, carbon neutrality promotes the balancing of carbon emissions and carbon absorption through the innovation and reform of technologies and systems, industrial transformation and upgrading, and the promotion and utilization of clean energy. Finally, the coordinated development of society, the economy, the environment, and energy is being emphasized. The terrain of the Yellow River basin is high in the west and low in the east. The western region of the basin is covered with snow throughout the year. Its central area is covered with loess; therefore, the soil and water losses are significant in this region. The eastern region of the basin is comprised mainly of the alluvial plain of the Yellow River. The Yellow River basin spans nine provinces and autonomous regions and plays an important role in China's economic and social development and ecological security. Therefore, the objective and comprehensive evaluation of the carbon-neutral development level of the Yellow River basin is of high significance for the sustainable development of the provinces and cities in the Yellow River basin.3, regional low-carbon economy5, low-carbon transportation6, evaluation of ecological level7 and analysis of influencing factors of carbon emissions are mature. The evaluation indicators are roughly divided into three categories: basic indicators, core indicators, and different orientation indicators according to the research purpose9. There are some differences in the selection of indicators by different scholars11. Jing et al.12 collected a set of 21 indicators covering the economic, social and environmental levels, constructed an indicator system, and proposed the comprehensive TOPSIS-ORM method to evaluate the sustainable development performance of shrinking cities in northeast China. Chaofeng et al.13 established a low-carbon city construction and evaluation index system in view of the carbon emission problem in urban construction and development. Yuzhao et al.14 studied the ecological security index system of the river basin, proposed the improved DPSIR model, and verified the applicability and importance of the improved DPSIR model in the ecological security assessment of the river basin scale. Guo et al.15 established the evaluation index system of ULCC from the perspective of driving force and resistance, respectively used the principal component analysis method and cluster analysis method to evaluate and classify the ULCC of Wuhan metropolitan area, and tested the results with fuzzy analytic hierarchy process to find out the problems existing in the city. Duan et al.16 constructed the evaluation system of Dalian's low-carbon economic development level based on AHP\u2009+\u2009entropy weight method. The comprehensive evaluation index of the development level of low-carbon economy in Dalian from 2005 to 2014 was calculated. Cheng et al.17 used correlation analysis, fuzzy rough set and entropy weight methods to select and analyze 21 indicators and construct a regional green competitiveness index. The above studies are all studies on evaluation indicators and evaluation methods between low-carbon and related industries or economies in different regions. However, in the evaluation of multi-provincial regions, river basins and heterogeneous regions, the characteristic indicators increase, and further research on the index system and evaluation methods is also needed.There are few researches on the development level of carbon neutrality, but the establishment and methods of sustainability evaluation system18 constructed an evaluation index system including 20 indicators at six levels. An improved TOPSIS method is proposed for analysis and calculation, and the results show that the use of renewable energy, the maintenance of ecological environment quality and low carbon technology are the important factors affecting the carbon neutrality ability of China. Liu et al.19 used China's provincial panel data from 2004 to 2016 and the Dubin spatial model based on the Stippart model to empirically analyze the impact of the three subsystems of ecological civilization on carbon emission intensity. Cao et al.20 proposed an evaluation model based on the improved matting element extension cloud model to evaluate China's ecological and environmental performance in 2019, taking Jiangsu Province as an example. Wei et al.21 adopted the PSR method to identify the influencing factors of China's carbon emissions. Jiang et al.22 respectively studied the impact of structural changes in internal and external inputs on global carbon emissions, and used structural decomposition analysis to decompose changes in global carbon emissions into six factors: carbon emission intensity, domestic input structure, international input structure, consumption pattern, consumption and population. Wei et. al.24 took Xiamen City as an example to establish a calculation method for the carbon footprint accounting of urban buildings. Ghaffar et. al.25 establishes baseline information on urban energy use and CO2 emissions. Built-up areas verify the increment of urban CO2 sources.In terms of carbon neutrality capacity evaluation and its influencing factors, Niu et al.In summary, the current research results show that the DPSIR model can effectively represent the concept and structure of the composite system, and can be well applied to the evaluation of low-carbon or carbon neutral development levels in river basins or multi-province regions. However, there are the following problems in the research: (1) most of the research objects of low-carbon development are urban areas or single industries, and there are few studies on the evaluation of low-carbon development level in river basins, multi-provincial or multi-heterogeneous regions. (2) At present, most of the research focuses on the field of low-carbon economy. (3) At present, most of the evaluation indicators of low-carbon development level are aimed at both carbon emission and carbon absorption, and no evaluation indicators have been established for the process of carbon transmission.In view of the shortcomings in the above studies, this paper builds the DPSIR analysis model of carbon neutrality capacity evaluation on the basis of the existing studies, and integrates the ecological evaluation index according to the actual situation of carbon emission, carbon absorption, economy, population, technology, resources and environment in the Yellow River Basin. Improve the driving mechanism analysis, pressure measurement, state assessment, impact analysis, response evaluation and other index systems of the carbon neutrality evaluation system in the Yellow River Basin. Combined with statistical data, the analytic hierarchy process and entropy weight method are used to evaluate the carbon neutrality capacity of the nine provinces in the Yellow River Basin. To verify the applicability and importance of DPSIR model in the evaluation of carbon neutral development level in the Yellow River Basin, and to provide theoretical reference for promoting the sustainable development of the Yellow River Basin.The driving-pressure-state-impact-response (DPSIR) model has evolved from the pressure-state-response (PSR) model proposed by the Organization for Economic Cooperation and Development and the driving-pressure-response (DPR) model proposed by the United Nations Commission on Sustainable Development. It is comprehensive, systematic, holistic, and flexible. The model can reveal the causal relationship between the environment and economy. The DPSIR model divides the system into five factors: driving, pressure, status, impact, and response. Figure\u00a0TO objectively and scientifically evaluate the carbon-neutral capacity of the Yellow River basin, this study follows the principles of the DPSIR model: science, system, compatibility, regional, hierarchy, operability, and regional economic and social development. The evaluation index system includes three levels: the target layer, subsystem layer, and index layer. The determined index layer comprises 37 specific indicators. It determines its attributes as positive (+) or negative indices (\u2212) for the index characteristics. The specific carbon-neutral-capacity evaluation index system is listed in Table The research objects of this paper are nine provinces in the Yellow River basin, mainly including Qinghai, Sichuan, Gansu, Ningxia, Inner Mongolia, Shaanxi, Henan, Shanxi,and Shandong. As shown in Fig.\u00a0The data on economic and social development were mainly sourced from China Statistical Yearbooks from 2008 to 2019 and included data for nine Yellow River basin provinces. The data on the use of resources were sourced mainly from the China Energy Statistical Yearbooks from 2008 to 2019. The data on environmental quality and environmental governance were sourced mainly from the 2008\u20132019 China Environmental Statistics Yearbooks, China Bulletin on the Status of the Marine Environment and the Department of Ecology and Environment of the nine Yellow River Basin provinces. The indicator data on per capita carbon emissions, annual average temperature change rate, GDP proportion of secondary industry, tertiary industry GDP proportion, and provincial health cities were calculated using their respective formulas from the index description and explanation given in Table Standardized processing of index data Because the original data of the N index may have different units and dimensions, these data must be standardized to obtain standardized data Normalization of index standardization data:Calculate the information entropy of each index Calculate the redundancy of each index Calculate the weights of each index After the evaluation index system was established, an appropriate evaluation method was selected to evaluate the development level of the system. Commonly used comprehensive evaluation methods include hierarchical analysis, fuzzy comprehensive evaluation, main component analysis, factor analysis, and entropy methods. The entropy method is an objective empowerment method that calculates the degree of numerical dispersion among the indicators. However, the traditional entropy method can handle only cross-sectional data. It cannot handle the panel data of a multi-index system spanning years. Therefore, this study used the global entropy method to determine the weight of the evaluation index system for the provincial carbon-neutral capacity of the Yellow River basin.d), pressure subsystem evaluation value (Sp), state subsystem evaluation value (Ss), impact subsystem evaluation value (Si), and response subsystem evaluation value (Sr).The DPSIR model subsystem layer evaluation formula is as follows:dpsir) of the DPSIR subsystem layer was determined using the expert evaluation method. The five subsystem weights were as follows: driving (wd), pressure (Wp), state (Ws), impact (Wi.) and response (Wr) weights.The weight was obtained asConsidering the score of the comprehensive evaluation index of the provincial carbon-neutral capacity of the Yellow River basin and referring to the relevant comprehensive index classification method at home and abroad and the actual situation of this study, the grading standards for establishing provincial carbon-neutral capacities in the Yellow River basin are listed in Table Driving subsystemThe evaluation values of the carbon-neutral capacity driving subsystems in nine provinces in the Yellow River basin generally exhibited an upward trend, as depicted in Fig.\u00a0Pressure subsystemAlthough the evaluation values of the carbon-neutral pressure subsystems in the nine provinces of the Yellow River basin decreased slightly in some years during 2008\u20132019, the overall trend exhibited a small increase, as depicted in Fig.\u00a0State subsystemFigure\u00a0Impact subsystemFigure\u00a0Response subsystemFigure\u00a0The DPSIR subsystem was thoroughly analyzed by comparing the evaluation values of the carbon-neutral capacity DPSIR subsystem of the nine provinces in the Yellow River basin from 2008 to 2019 and combining the characteristics of resources and environment and the specific characteristics of the basin.Overall, the provincial carbon-neutral capacities in the Yellow River basin were gradually enhanced.the State Council on Printing and Distributing the National Sustainable Development Plan for Resource-based Cities (2013\u20132020) was issued. The development plan for sustainable economic development in the next seven years was introduced. From 2013 to 2019, nine provinces responded positively to state calls. Governments at all levels need to rationally develop and use environmental resources and strengthen environmental governance and protection in accordance with relevant work arrangements. The strong development of the response subsystem and gradual comprehensive and stable implementation of the regulation measures improved the quality of economic development, the pressure and negative impact on the ecological environment of the Yellow River basin decreased continuously, and the CCCEI increased rapidly.During 2008\u20132019, the provincial carbon-neutral capacities in the Yellow River basin were continuously enhanced, and the CCCEI exhibited an upward trend. Since 2013, the concepts of a low-carbon economy and sustainable development have attracted wide attention from society and governments at all levels. In 2013, However, driven by the ever-increasing population and economic aggregate, the increases in the coal-dominated industrial energy consumption structure and cars per capita ensure that the evaluation values of the pressure and impact subsystems fluctuate, thereby impeding the development of the provincial CCCEI in the Yellow River basin.The development of carbon-neutral capacity in the Yellow River basin varies.Qinghai and Inner Mongolia have relatively good ecological environments, large vegetation coverage areas, and underdeveloped economies. Therefore, the provincial CCCEIs were above 0.8 in 2008.From 2008 to 2012, the provincial CCCEI values of Henan, Shanxi, Ningxia, and Shandong were less than 0.8. The overall levels of the carbon-neutral capacities of these provinces were level II, which were poor. Economic development leads to the destruction of resources and the environment. The evaluation values of the driving, pressure, and state subsystems were low.The provincial CCCEIs of Qinghai and Inner Mongolia were the first to attain level IV in 2017, which indicated that their carbon-neutral capacities were good. In 2019, the provincial CCCEIs of Sichuan, Shaanxi, and Gansu were above 1.1, i.e., slightly lower than the lower limit of the standard of IV. These provinces entered the initial stage of development with good carbon-neutral capacities. However, owing to the environmental damage and reduced green areas caused by economic development, the carbon-neutral capacities of Shanxi, Ningxia, Henan, and Shandong are relatively low. In 2019, their provincial CCCEIs were higher than 0.95 but lower than 1.1, thereby indicating their middle development stage of standard III.The provinces in the Yellow River basin have significant development potential.During 2008\u20132019, the carbon-neutral capacities of provinces in the Yellow River basin achieved a grade leap. However, there is a huge scope for development beyond the upper limit of standard IV. Furthermore, no province has reached standard I, thereby leaving scope for further development of provinces. Ningxia and Shanxi are important coal carbon bases in China, and the coal energy industry is an important industry. With the development of green energy technology, the carbon-neutral capacities of these provinces will be significantly improved. Shandong and Henan Provinces have large populations. A small cultivated land area per capita, a small proportion of renewable energy power, and a large proportion of secondary industry lead to increased pressure on carbon-neutral capacities in these provinces. Therefore, it is necessary to increase the utilization of new energy, vigorously develop tertiary industry, strengthen carbon-capture technology, and strive to achieve the sustainable development goal of carbon neutrality at first.The provincial CCCEI in the Yellow River basin from 2008 to 2019 is depicted in Fig.\u00a026. The index system is scientific, complete, and easy to obtain and provides a basic framework for a comprehensive analysis of the causal relationship between carbon neutrality and social and economic activities in the Yellow River basin.A carbon-neutral-capacity-evaluation index system for the Yellow River basin is established based on the DPSIR model. The index system has three levels and 37 indicators13, the practicability of DPSIR model and the scientificity of the result are further verified.The global entropy method was used to calculate the capability evaluation value of each subsystem of the DPSIR, the CCCEI model of the Yellow River basin was constructed, and a classification standard for the carbon-neutral capability was proposed. This method can be used to perform quantitative analysis on each subsystem of the carbon-neutral capacity of each province in the Yellow River basin. It can dynamically describe the evolution trend of the subsystems and objectively measure the level and future development scope of the carbon-neutral capacity of each province. Compared with referenceThe comprehensive evaluation of carbon neutrality capacity in the whole Yellow River basin shows a significant upward trend, showing the spatial difference of the comprehensive evaluation of carbon neutrality capacity in the middle and lower reaches of the river basin than that in the upper reaches of the river basin. The evolution trend of spatial differences among each subsystem is basically consistent with the evolution trend of comprehensive evaluation.Based on DPSIR model and global entropy method, the comprehensive evaluation Index (CCCEI) of provincial carbon neutrality capacity in the Yellow River Basin was established to evaluate the carbon neutrality capacity of the Yellow River Basin from 2008 to 2019. The logical relationship among subsystems in DPSIR model and the spatial and temporal differences of each province are revealed, and the dynamic evolution trend of carbon neutral capacity of each province is analyzed.From 2008 to 2019, the carbon neutrality capacity of the provinces in the Yellow River Basin was in a state of rapid development and achieved multi-level leapfrog, but there is still a great room for improvement. The carbon neutrality capacity of each subsystem shows two time differences: fluctuation and rise from 2008 to 2019. Driven by the continuous growth of population and economic aggregate, the continuous fluctuation of the evaluation index of pressure subsystem and influence subsystem hinders the consubstantial growth of the comprehensive evaluation index of carbon neutrality capacity of provinces in the Yellow River Basin to a certain extent.The index system based on the DPSIR model is capable of evaluating the impacts of economic and social developments in various provinces on their carbon-neutral capacities, as well as those of positive measures adopted to achieve carbon neutrality. The proposed index system is broad based and can be extended to the carbon-neutral assessments of other river basins.Provinces have actively developed emerging industries, strengthened ecological and environmental protection in the Yellow River basin, formulated and implemented low-carbon development plans, and effectively eliminated obstructive indicators. The carbon neutrality status of most provinces in the Yellow River Basin is relatively severe, and the resource and environment problems in the middle reaches are prominent. To improve the carbon neutrality capacity of the Yellow River basin, the resources and environment in the Yellow River basin need to be further rationally utilized, managed and protected. It is necessary to establish a reasonable resource and environmental utilization mechanism, strictly control the emission of industrial pollutants, advocate public transportation, promote the implementation of low-carbon economic development plans, and improve the comprehensive capacity of carbon neutrality in the provinces along the Yellow River Basin.The distribution of the middle and lower reaches of the Yellow River provincial carbon neutral pressure generally larger, strengthen the response and the implementation of the policy, increasing factors of flow across the land, digging in the middle and lower reaches of the Yellow River and Yangtze river along the Banks of the leading type carbon neutral city experience, give full play to their ability of carbon neutral spillover effect and is a progressive effect, formation of the carbon cycle in the Yellow River urban agglomeration, It will drive the improvement of provincial carbon neutrality capacity in the form of urban agglomeration. Based on the development advantages of each region, the differences in factors hindering carbon neutrality shown by each region should be solved.While dredging economic development, the government should constantly coordinate the contradiction between environmental protection and economic development, improve the overall coordinated development level at the material level such as industrial support and the accumulation of development factors, and formulate relevant policies according to local conditions.Combined with the research and analysis, it is not difficult to see that the carbon neutrality capacity level of the provinces in the Yellow River Basin has been significantly improved. The evaluation of carbon neutrality capacity shows obvious regional heterogeneity and distinct regional characteristics. Accordingly, according to the provincial characteristics and differences carried by different river basins, policy suggestions are put forward to promote the carbon neutrality capacity of the Yellow River Basin as follows:"} +{"text": "The most frequent and severe non-cognitive disorders in dementia are hallucinatory-paranoid disorders (HPD), which cause social dysfunction and financial burden of this pathology.To study the features of HPD in vascular dementia (VD), an approach using clinical-psychopathological, psychometric, psychodiagnostic and mathematical-statistical methods was used.The study was based on the examination of 75 patients with HPD in VD and 63 patients with VD without HPD.In patients with VD in the middle stage of development in the structure of clinical manifestations was dominated by frequent paranoid and paranoid disorders with a systemic delusional plot material damage, robbery, theft , relationships and jealousy , which ran in the form of paranoid delusional disorder (63.4%), acute paranoia (12.2%) and hallucinations (24.4%). In patients with VD in the late stage of development, the clinical and psychopathological structure of GPR was characterized by a predominance of frequent, hallucinatory disorders in the form of healthy , tactile and auditory hallucinations, which took the form of hallucinations , confusion and paranoid delusional disorder .The study of the clinical and psychopathological structure of HPD in patients with dementia of different stages of development revealed their dependence on the stage of development of the pathological process."} +{"text": "To evaluate the global research productivity in the field of discectomy for lumbar disc herniation (LDH) through bibliometric analysis and mapping knowledge domains.A systematic literature search was performed on the Web of Science (WoS), including the Science Citation Index Expanded (SCIE) database and PubMed. The number of publications, countries of publications, journals of publications, total citation frequency, impact factors of journals, and Institutional sources were analyzed by Microsoft Excel 2019, the Online Analysis Platform of Bibliometrics, and VOSviewer. Hotspots were also analyzed and visualized based on VOSviewer.Spine has published the largest number of papers (289) in this field with the most citation frequencies . Hotspots could be divided into three clusters: surgery, lumbar disc herniation, and diagnoses. The most recent topic that appeared was symptomatic re-herniation.A total of 2,066 papers were identified. The United States ranked first in the number of total citations . China ranked first in the number of publications , which has surpassed the United States in terms of the number of publications published annually since 2016. Wooridul Spine Hospital published the most papers (43). For journals, The United States is the most significant contributor to the development of discectomy for LDH. The current research focus of discectomy on LDH was the comparison between surgical approaches and evaluation of current minimally invasive discectomy. At present, minimally invasive techniques, such as endoscopic discectomy, cannot completely replace non-endoscopic discectomy (open discectomy and microdiscectomy) through bibliometric analysis and mapping knowledge domains. Sciatica in adults is mostly caused by lumbar disc herniation (LDH) , leadingBibliometrics is a method to assess the trends in global research productivity based on literature databases and literature metrology characteristics. Moreover, its application has become more and more mature in various medical disciplines in recent years, including spinal surgery \u201317. BaseA systematic literature search was performed on PubMed, Web of Science (WoS), and the Science Citation Index Expanded (SCIE) database. The search terms were as follows: theme\u2009=\u2009((discectomy) AND (lumbar disc herniation or lumbar disk herniation OR LDH)) AND publishing year\u2009=\u2009 based on MeSH on PubMed. Original articles and reviews were identified.Two researchers extracted the data from databases and imported it into Microsoft Excel 2019 independently. The data were imported as follows: number of publications, countries of publications, journals of publications, authors of publications, total citations, impact factors of journals, and institution sources. Disagreements between the two researchers were resolved by consensus after discussion.http://bibliometric.com/) was also used for analyzing and visualizing the data extracted from databases as a complement.The number of publications, contributive countries of publications, contributive journals of publications, total citation frequency, and impact factors of journals and institution sources were analyzed by Microsoft Excel 2019 , which were visualized by GraphPad Prism 8 . VOSviewer is used for visualizing the bibliometric mapping, including literature coupling, co-citation, collaboration, and co-word analysis . VOSviewA total of 2,066 papers were identified in this analysis. An overview of global publications in discectomy on LDH over the past 20\u00a0years is shown in Spine has published the largest number of papers (289) in discectomy on LDH with the most citation frequencies . World Neurosurgery ranked second in the number of publications (163). European Spine Journal ranked second in citation frequencies (2586).The top 10 contributing countries, institutions, and journals by the number of publications are shown in The top 20 keywords sorted by frequency of occurrence are shown in The citation status of papers in discectomy on LDH is shown in With the improvement of patients' requirements for prognosis, discectomy continued to improve as the treatment for symptomatic LDH under the general trend of minimally invasive surgery. By 2020, China ranked the first in the number of publications in the field of discectomy in worldwide , followed by the United States . However, the citation frequency of Chinese articles was less than that of the United States. In terms of time, China has surpassed the United States in terms of the number of publications published annually since 2016. China started to get involved in the research of discectomy on LDH relatively late, whereas the incidence rate and absolute value of LDH are relatively high in China based on great population, which could provide great number of clinical data. China has considerable experience in the application of various discectomy approaches to LDH. However, none of these surgical approaches to discectomy was invented by the Chinese. China was not as contributive as other countries such as the United States and South Korea, when it came to the creation or renewal of surgical techniques. Similar situations existed in the research institutions. Among the top 10 institutions that contributed the most publications, the number of citations from Chinese institutions was relatively small compared with institutions in other countries. These findings in this study suggest that the United States is the most significant contributor to the development of discectomy in LDH. China developed rapidly in discectomy on LDH but lack of research depth and citation.Spine (118 citations) (Spine (198 citations) (Spine (172 citations) (Advances in Neurosurgery (81 citations) (Techniques in Neurosurgery (80 citations) (Neurosurgery (65 citations) (Spine (87 citations) , Carragetations) , and Mixtations) , Ruettentations) , and Maytations) . Clustertations) , Mauricetations) , and Pertations) . Clustertations) , Cinottitations) , and Swatations) \u201330. WherIn the top 20 keywords sorted by frequency of occurrence, half were associated with surgical techniques and the research of minimally invasive surgery occupied a quite dominant position. In the bibliometric map generated by VOSviewer, clusters 1 and 4 mainly focus on surgical techniques and postoperative clinical outcomes in A consensus has been reached that the operation for re-herniation is associated with more cost and is less effective \u201337. HencThe objective of this study was to evaluate the global research productivity in the field of discectomy on LDH through bibliometric analysis and mapping knowledge domains. Previous published studies have investigated the quantity and quality of articles in the field of full-endoscopic spine surgery . The advThe United States is the most significant contributor to the development of discectomy for LDH. Some countries developed rapidly in the number of publications but lacked research depth and citations, such as China. The current research focus of discectomy on LDH was the comparison between surgical approaches and evaluation of current minimally invasive discectomy. At present, minimally invasive techniques such as endoscopic discectomy cannot completely replace non-endoscopic discectomy (open discectomy and microdiscectomy) through bibliometric analysis and mapping knowledge domains. One of the research hotspots in the future is the control of the recurrence rate and the solution of symptomatic re-herniation after lumbar discectomy."} +{"text": "Internationally, an increasing body of scholarship has focused on the experiences of transgender individuals when accessing gender-affirming healthcare. However, the experiences of transgender individuals who belong to the foreign background population in Finland have rarely been studied. This study aims to fill the gap in research and contribute to the understanding of the experiences of acquiring gender-affirming healthcare among those, who fall into the intersections of transness and also identify of foreign origin in Finland.Fourteen semi-structured qualitative interviews were conducted and analyzed with reflexive thematic analysis (RTA), through the framework of intersectionality. The interviews were part of a broader sample of qualitative data, collected about the experiences of sexual and gender minorities among the foreign origin populations in Finland.The analysis showed two main interconnected themes. Firstly, perceived barriers when accessing gender-affirming care. In this theme, the intersections of transgender identity, foreign background, class, and age affected the experiences of the individuals. Secondly, the necessity of \u201cperforming identities:\u201d the intersections of class, transgender identity, and race affected those.The findings of the current study suggest that the intersectional aspects of individual identities create structural inequalities in the Finnish gender-affirmation healthcare system. To tackle these inequalities, further research is needed on the healthcare experiences of gender minorities in Finland both within and outside the scope of transgender-specific healthcare.\u2022\u2002Intersectional aspects of individual identities create structural inequalities in accessing gender-affirming healthcare.\u2022\u2002Further research is needed on the healthcare experiences of gender minorities that examines health and wellbeing using an intersectional lens."} +{"text": "Neurodegenerative diseases (NDDs) are associated with the accumulation of a range of misfolded proteins across the central nervous system and related autoimmune responses, including the generation of antibodies and the activation of immune cells. Both innate and adaptive immunity become mobilized, leading to cellular and humoral effects. The role of humoral immunity in disease onset and progression remains to be elucidated with rising evidence suggestive of positive and negative outcomes. In this study, we review advances in research of neuron-targeting autoantibodies in the most prevalent NDDs. We discuss their biological origin, molecular diversity and changes in the course of diseases, consider their relevance to the initiation and progression of pathology as well as diagnostic and prognostic significance. It is suggested that the emerging autoimmune aspects of NDDs not only could facilitate the early detection but also might help to elucidate previously unknown facets of pathobiology with relevance to the development of precision medicine. Neurodegenerative diseases (NDDs) are chronic incurable disorders of the Central Nervous System (CNS) characterized by a progressive decline of synaptic functions and irreversible neuronal loss, with devastating personal impact and overwhelming socio-economical costs. With aging as the main risk factor, the most prevalent NDDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Neurodegeneration (FTLD), Amyotrophic Lateral Sclerosis (ALS), and Vascular Dementia (VD) are currently on the rise 2+ homeostasis Amongst shared features of NDDs, deposition of misfolded proteins and fragments across CNS, neuroinflammation, dysregulation of glutamatergic signaling, oxidative stress with cytotoxic effects are the most prominent, contributing to neurological and psychiatric symptoms with behavioral impairments. Disruption of neuronal activity, synaptic transmission, and plasticity mechanisms are thought to be caused primarily by the accumulation of aggregation-prone toxic amyloid proteins in the CNS and dysregulation of CaCurrently, there is a major unmet need for low-cost, non-invasive, and reliable methods for the early detection of CNS diseases. With advances in sensing technologies, it is expected that new approaches will be developed to facilitate the accurate diagnosis of NDDs and timely interventions Antibodies (Ab) are large Y-shaped proteins used by the immune system for recognizing and neutralizing foreign materials, through activating the complement system and phagocytosis. Abs are generated by two types of B lymphocytes: B1 and B2. B2 cells produce Abs in follicles of secondary lymphatic organs, which in their majority are regular proteins derived after specific antigenic stimulation As natural immunoglobulins (Ig), Aabs occur in three isotypes: IgM, IgG, and IgA. IgM recognizes and binds post-apoptotic antigens and markers of cell senescence CNS is considered immunologically privileged with very limited exposure to antigens and restricted infiltration of Abs taking place under physiological conditions. This is due to physical and molecular barriers at the blood-CNS interface and elaborate system of meningeal lymphatic vessels (mLVs) which control the concentration and isoforms of Abs entering the CNS and guide immune cells out to cervical lymph nodes Many disorders affecting CNS, including NDDs, are associated with the disintegration of BBB, which may lead to an out-of-control outflow of neuronal and glial proteins with activation of autoimmune response Gaskin et al. presented the first evidence for A\u03b2 Aabs in the peripheral circulation of AD patients Using an affinity purification approach, Mruthinti et al. found a higher titer of IgG binding A\u03b242 peptide in plasma of AD Microtubule-associated protein tau, which in AD becomes hyperphosphorylated (p-tau), is the main constituent of neurofibrillary tangles. An increase in the level of p-tau in the brain and CSF has been considered as one of the key biomarkers of AD Using circulating IgGs, it was shown that they can recognize modified tau variants, which differ in their characteristics Neurofilaments (NFs) belong to a family of intermediate filaments with their diameter (~10 nm) falling between two other cytoskeletal polymers, i.e., microtubules (~25 nm) and actin (~6 nm). Based on their gene sequence and structural characteristics, NFs are divided into six types (I-VI) NF deposits were found to co-localize with tau tangles in brains affected by AD Soussan et al. compared NF Aab profiles in serum of AD patients and healthy controls. Unlike controls showing equal binding for different isoforms of NF-H without changing their specificity during aging, in AD, the levels of Aabs against ventral root cholinergic NF-H was higher than those directed against dorsal root NF-H. The phosphoserine content analysis of NFs showed its higher levels in ventral as compared to that of dorsal root NF-H, with Aabs from AD patients binding more effectively phosphorylated epitopes, which show higher prevalence in ventral root NF-H Accumulation of insoluble and misfolded \u03b1-syn in neurons leads to synaptic failure with the build-up of fibrils constituting Lewy bodies (LB) and neurites of DLB and PD The results of the analysis of \u03b1-syn Aabs in the blood of PD patients and comparison with controls vary considerably Table . While sDespite two decades of in-depth research and major progress in developing biomarkers for CNS disorders, the definitive diagnosis of NDDs remains a major challenge. The current diagnostic gold standard - positron emission tomography (PET) - has low sensitivity and is of limited availability, due to high costs and requirements for specialized infrastructure and skilled staff, as well as potential health risks related to the use of radioactive tracers. Substantial drawbacks are also associated with the use of CNS tissue as well as CSF-based assays involving biopsies and lumbar puncture, which necessitates invasive procedures and related major health risks. The emerging Aabs based blood tests seem to offer a specific, rapid, and affordable approach for diagnosis of NDD without major risks and adverse effects. Nevertheless, significant challenges and questions remain, which impede their effective translation and widespread clinical use, calling for further research and optimization in clinical trials. One of the key difficulties is imposed by the discovery of significant amounts of neuronal Aabs in the peripheral circulation in healthy subjects, inferring their potential physiological role, and questing the specificity of selected Aabs for a particular NDD. Another major challenge is imposed by the results of comparative studies, which demonstrate considerable variations of Aabs levels in the peripheral circulation of NDDs that frequently deviate from changes in Aabs titers in CSF. These observations also substantiate the highly complex nature of the immune response to NDDs and underscore the potential shortcomings of utilized detection methods. Together with numerous conflicting reports and outstanding methodological issues, the above-listed considerations call for revision and improvements of sample preparation and standardization of sensing methods. They also highlight the need for more stringent stratification of target groups and profiling of Aabs, to ensure accurate and specific detection and quantification of Aabs. In this context, the use of genetic methods is especially warranted, given the causative and predisposing effects of specific genes in NDDs. Because of the association of NDD with genetic alterations"} +{"text": "There has been increasing interest in functionalised mineral materials in terms of both scientific research and the development of the world economy. This arises from the growing interest in clean manufacturing technologies that use mineral sorbents, and is related to current issues in environmental and civil engineering, which are receiving significant attention both in the European Union and in international legislation. The price paid for technical progress and economic development in the 20th century was environmental pollution. In the 21st century, modern approaches based on functionalised mineral material technologies are an opportunity for world economic development and for increased industrial competitiveness in global markets while improving environmental conditions. These issues address the challenges faced by industry in protecting the environment, and in the rational use of natural resources in the creation of modern economies and in the development of industry. From the point of view of the world economy, it is important for researchers to create innovative production technologies. To meet these goals, close cooperation between science and industry is needed; thus, studies on the properties and uses of functionalised mineral materials are important.The great focus placed on functionalised mineral materials by modern science and industry is due to their particular properties, knowledge of which interdisciplinary. The interaction of sorbents with organic and inorganic substances, and the use of mineral materials in ceramics, foundries and metals, are the subject of many publications, patents and industrial practices. These effects are fuelled by technological progress and growing demand for increasingly efficient and cost-effective technologies. Moreover, they enhance the capacity of researchers to determine the mineral and chemical composition of mineral materials, as well as their structure and texture. The second group of reasons for the developing interest in functionalised mineral materials is the progressive threat to and degradation of the environment, which demands new means of reducing the impact of industry.Functional minerals are materials inspired by geological systems originating from Earth\u2019s several billion-year-long history. Each of them has a unique chemical composition and structure that determine its properties and possible functions. Natural, synthetic and anthropogenic minerals, both in their original and modified forms, serve as agents in environmental and industrial applications. The functions of mineral materials include: cation and anion exchange, sorption, immobilisation, energy storage, use as catalysts and photo-activity. Layered clay minerals, zeolites and zeolite-like structures, layered double hydroxides (LDHs), are particularly suited to such functions. Modifications of minerals to obtain functional mineral materials include: surface modification, functional loading, intercalation, grafting, doping and structure reformation. This Special Issue, in which we will discuss topics from interdisciplinary studies, aims to highlight the current top trends in the innovative functionalisation techniques of mineral materials. Additionally, reports on unique properties of functionalised materials and their expected applications are presented.The mineralogical and chemical characteristics of Ukrainian volcanic tuffs from the Khmelnytskyi region were determined in . Their p2MnSnS4 (CMTS) acknowledged as an alternative to traditional semiconductors, two different sources of sulphur have been successfully used to synthesise CMTS particles via solvothermal methods [The main objective of was to s methods . The expIron-Based Water Treatment Residuals (WTRs) are an extremely interesting material, formed as a result of de-ironing and de-manganising drinking water . The higS. saccharatum (L.) biomass, and its application significantly reduced the heavy metal content of S. saccharatum (L.) biomass. Based on data reported in the literature, Ref. [The aim of the was to ere, Ref. presents"} +{"text": "Dear Editor,Melanocytic matricoma is a rare benign cutaneous adnexal tumor that recapitulates the early anagen hair follicle.A 60-year-old man with HIV under antiretroviral therapy presented with a 2-month history of a rapidly growing papule affecting his left preauricular area. Physical examination showed a well-defined 6\u202fmm papule with an uneven coloration ranging from pink to grey . CompletMelanocytic matricoma typically presents as a sharply demarcated, small unevenly pigmented papule or nodule, arising on sun-damaged skin of elderly individuals, with a male predominance.Clinical differential diagnosis of this entity includes malignant melanoma, pigmented Basal Cell Carcinoma (BCC), and hemangioma.Despite being considered a benign tumor, the clinical behavior of melanocytic matricoma remains unknown because of the few reported cases and the lack of long-term follow-up.5None declared.I\u00f1igo Aranguren-L\u00f3pez: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Sara Ibarbia-Oruezabal: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Nerea Segu\u00e9s-Merino: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Alpine grassland on the Tibetan Plateau (TP) accounts for about 62% of the total area of the TP . These gClimate changes have been evident across the TP since the beginning of the 1970s . For insIn the past 20 years, numerous efforts have been done to explore the patterns, functions, and processes of alpine grassland ecosystems, including transect surveys, field observations, model simulation, comprehensive meta-analyses, and literature reviews. These studies have following characteristics: (i) with the improvement of testing methods, a diversity of technologies have been applied at the technical level such as remote sensing, model simulation, large-scale transect sampling survey, aerial filming, and long-term observation. Scales of these studies range from regional, landscape, ecosystem, and community to micro-molecular and genomic levels; (ii) the observation indexes have evolved from basic to comprehensive, which includes moisture, soil, biology, watershed, and climate; (iii) various factors such as the environmental, natural, human activities, and the impact of the whole habitat on alpine ecosystems were taken into account, and (iv) studies have evolved from trophic levels, food webs, and independent processes of ground and underground to the integration of above and below ground processes of the whole ecosystem. Despite remarkable knowledge gains, there are still some areas that require in-depth research, such as the driving mechanism of the impact of global change alpine ecosystems with new technologies and theories.To advance our understandings of the patterns, functions, processes, and mechanisms of alpine grassland ecosystems responding to changing environments ., we organized a Special Issue (SI) entitled \u201cPatterns, Functions, and Processes of Alpine Grassland Ecosystems under Global Change\u201d. This SI comprises 49 articles, sharing new ideas, techniques, and findings about this subject from field experiments, large-scale transect surveys, alongside remote sensing . These sThe spatial-temporal patterns and drivers of alpine grassland ecosystem under the changing environment are the top priority for the grassland conservation. Due to the scale of the TP, remote sensing is critical for studies on the spatial and temporal heterogeneity of the grassland. Four papers in this SI discuss the spatial-temporal patterns and drivers of alpine grassland ecosystem under the changing environment based on patch, landscape or pixel based remote sensing observations. Seven papers in this SI assess the variations of alpine ecosystem functions, and the response and feedback of ecological processes using long-term simulated experiments and large-scale transect surveys. Some of the studies used the entire TP as the study area and evaluated the complex biodiversity-ecosystem function relationships , the effClimate change and human activities dominate the recent changes in grassland patterns and processes on the TP, thus affecting the ecosystem functions and services. Many of the articles in this SI reveal the driving mechanism of the impact of climate change and human activities on alpinSeven papers in this SI explored the mechanisms of alpine ecosystem dynamics using new analytical methods, e.g., artificial intelligence learning, network analysis , Bayes aIt is well known that human activities and their feedbacks affect regional sustainable development, but relevant policy measures have rarely be evaluated at the household level. Although some findings on the ecological system of TP may still be somewhat preliminary, all studies included in this SI have undoubtedly promoted our understanding of the patterns, functions, and processes of alpine grassland ecosystems in the context of global change. Some important questions remain unanswered, though. Further explorations need to focus on the following two aspects: (i) more long-term localized observations and manipulative experiments should be employed to reveal long-term change of coupling of plant-soil-livestock-human system and its driving mechanisms. Two TP-wide programs, namely, the Alpine Fence Observation Net (AFON) and the Alpine Climate Change Observation Net (ACON) were established in 2020 and 2022, respectively Figure\u00a01JS, YW, SL, and JL drafted the story line of the editorial. SL, HZ, GW and NH refined the story line and contributed references and insights to the impact of the papers included in this editorial. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (No. 41871040), the National Natural Science Foundation of China Joint Fund Project (U21A20186), the Joint Research Project of Three-River-Resource National Park Funded by the Chinese Academy of Sciences and Qinghai Provincial People\u2019s Government (LHZX-2020-08), Qinghai Natural Science Fund Innovation Team Project (2021-ZJ-902).We thank all the authors who submitted their work to this Research Topics, the professional editorial staff at Frontiers in Plant Science for their support in creating this Research Topic, and the invaluable help of reviewers in manuscript evaluation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Saudi Arabia\u2019s ambitious Vision 2030 project was launched in 2016 as a strategy for economic development and national growth, with 11 Vision Realization Programs put in charge of its implementation. The backbone of its Transformation Program for the Health Sector has been the definition of a new Model of Care aiming to deliver 42 coordinated interventions across 6 Systems of Care, with the development of clinical guidelines identified as a key cross-cutting intervention to foster the use of national, evidence-based practices across KSA, reduce care variation, and promote accountable care. This article provides an overview of the history, progress to date, and future outlook of the recently initiated National Guidelines Center in Saudi Arabia, established in collaboration between the Health Holding Company and the Saudi Health Council represented by its National Center for Evidence-based Medicine. The lessons learnt from previous guideline initiatives are grouped under the Center\u2019s design principles of high quality, relevance, practical implementation, and sustainability. Aspects setting the project apart from previous endeavors have been its focus on extensive engagement with key stakeholders in the Saudi guideline ecosystem, the co-development of evidence-based recommendations with aligned key performance measures, and the implementation of guideline recommendations in the clinical workflow via integrated electronic order sets. Nine activity streams aim to enable the Center to take its place among the leading regional and global guideline developing organizations and to optimally support clinicians and patients, Saudi Arabia\u2019s health sector transformation, and the work of guideline communities worldwide. Saudi Arabia (KSA) has one of the highest healthcare expenditures in Gulf Cooperation Council countries (GCC), as well as one of the highest densities of medical professionals per thousand residents . This alHowever, non-communicable diseases, particularly diabetes and obesity, continue to burden the kingdom, and are a major target of preventive care screening policies. It has been estimated that the obese population will reach 73% by 2025 . ConversIn response to this situation in 2016, Saudi Arabia launched the ambitious Vision 2030 project as a strategy for economic development and national growth. Eleven Vision Realization Programs (VRPs) have been put in charge of its implementation, including a dedicated VRP and Transformation Program for the Health Sector .The backbone to healthcare transformation is the definition of a new Model of Care that, among other objectives, aims to deliver 42 coordinated interventions across 6 Systems of Care responsible for the delivery of all health services Fig.\u00a0 5]. The. The5]. Key to achieving the healthcare transformation within the kingdom\u2019s Vision 2030 program was to promote the use of national, evidence-based practices across KSA to reduce care variation and promote accountable care, through regular adaptation/development, alignment, training, and dissemination of localized clinical practice guidelines.In close collaboration with the Saudi Health Council (SHC) represented by its National Center for Evidence-based Medicine, the Health Holding Company (HHC)\u2014established by the Saudi Ministry of Health to drive its Model of Care Health Sector Transformation strategy\u2014has initiated a National Guidelines Center to guide clinical practice and be the advocate for evidence-based medicine, thereby improving the wellbeing of its nation in a sustainable, standardized, and accountable manner.The SHC was established by a Royal Decree issued in June 2002, with its council under the chairmanship of the Minister of Health and whose current members include all health care providing sectors in the kingdom like Ministry of Health, Military hospitals, Saudi Red Crescent Authority and the special regulatory entities i.e Saudi Food and Drug Authority (SFDA), Council of Collaborative Health Insurance (CCHI ) and Saudi Commission for Health Specialties (SCHS) and other ministries like the Ministry of Economy and Planning, the Ministry of Labor and Social Development and the Ministry of Finance. Key among its many tasks of the SHC was to prepare the healthcare strategy in KSA, issue appropriate regulations to ensure that hospitals run by the Ministry of Health and other government agencies are operated in adherence to the principles of economic management as well as performance and quality standards and development and approval of policies for the coordination and integration between all healthcare providing authorities.Over the last few decades, numerous organizations across Saudi Arabia have independently undertaken the task to create documents aimed at guiding clinical decisions, such as guidelines, consensus documents, pathways, and protocols . DespiteTable Important aspects setting our project apart from previous endeavors and aiming to inform similar endeavors worldwide include its focus on extensive engagement with key stakeholders in the Saudi guideline ecosystem, the co-development of evidence-based recommendations with aligned key performance measures, and the implementation of national guideline recommendations in the clinical workflow at the point of care via integrated electronic order sets.As of October 2022, several milestones have been reached including: (i) documentation of the Center\u2019s vision and mission, charter, goals, processes, and policies; (ii) extensive stakeholder engagement with organizations active in the Saudi guideline ecosystem; (iii) confirmation of the SHC National Center for Evidence-Based Medicine as the most suitable entity to host the center following consultation among 19 stakeholder organizations using a RACI (Responsible/Accountable/Consulted/Informed) framework; (iv) based on a data-driven impact/effort analysis, selection of the initial 12 guideline topics as follows: Chronic kidney disease, Dental caries, Community-acquired pneumonia, Cesarean section, Stroke, Sepsis, Acute gastroenteritis in children, Low back pain in adults, Mechanical ventilation, Chronic obstructive pulmonary disease, and Depression; (v) Recruitment of Clinical Leads and multidisciplinary Task Forces for all topics; and (vi) Development of a multi-component dissemination and implementation strategy.Over the upcoming months, work will focus on (i) completing the Center\u2019s first 12 guidelines; (ii) approving the guidelines by the National Center for Evidence-Based Medicine\u2019s Scientific Committee; (iii) disseminating the guidelines via multiple channels including a website, mobile apps, and educational events; (iv) implementing national guideline recommendations at the point of care through localized order sets embedded in the electronic health record at selected pilot sites; (v) finalizing the Center\u2019s internal team and infrastructure; (vi) disseminating guidance on the GIN criteria for giving a seal of approval as national guidelines to those developed by other guideline organizations ; (vii) d"} +{"text": "Stress is defined as the state of threatened homeostasis. It has been associated with dysregulation of the stress system, consisting of the Hypothalamic-Pituitary-Adrenal (HPA) Axis and the Locus Caeruleus-Norepinephrine/Autonomic Nervous Systems (LC-NE/ANS), as evidenced by altered central and peripheral biomarkers of this system of the stress system, as evidenced by altered concentrations of stress-related biomarkers and brain changes in individuals with anxiety disorders, post-traumatic stress disorder (PTSD), and depression . The study demonstrated positive associations between low-normal thyroid function at the 2nd and 3rd trimesters of pregnancy and postpartum with anxiety, depression, and OCD scores. These findings are in close relation with the third article of this Research Topic, the mini-review examining the relations of prenatal maternal stress with thyroid function and neurodevelopment of the offspring, by Anifantaki et al. Indeed, both the HPA and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (THs), mediate several fundamental processes involved in neurodevelopment. It is well established that growth and neurodevelopment of the fetus depend on maternal hormones, especially during the first half of pregnancy. Altered concentrations of both GCs and THs can cause abnormalities in the neuronal and glial structures and functions, with subsequent effects on postnatal neurocognitive function. Experimental studies demonstrate that increased GC concentrations, related to maternal stress, may reduce maternal and, consequently, fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating fetal hormonal concentrations.The study of Konstandi et al. suggest that stress plays a central role in the regulation of drug bioavailability in the body, granted that pharmacotherapy may be a potential threat to homeostasis. Thus, stress may contribute to determining a drug's pharmacokinetic profile, as it regulates various enzymes that catalyze the metabolism of the majority of drugs.One opinion article of the Research Topic summarizes neuropharmacological aspects of stress. Makris et al. critically summarized the existing data on stress system alterations in children and adolescents with Autism Spectrum Disorder (ASD). This review focused on the variations of circadian rhythms of cortisol and alpha-amylase, as peripheral biomarkers of the HPA axis and LC-NE/ANS system, respectively, and on stress system responses to different stressors. This review article also included imaging and immunological findings that have been associated with stress system dysregulation in ASD youth. Finally, the article discussed the possible contribution of early life stress in ASD pathophysiology and the developmental trajectory of the stress system in ASD individuals. Similarly, Payen et al., in their systematic review, analyzed existing data on peripheral biomarkers of the gut and the heart in ADHD, the most prevalent NDD in childhood. The article provided a broader view of stress system components, including task-related heart rate reactivity (HRR) and gut microbiota data in children with and without ADHD. Lo Iacono et al., in their review, summarized evidence on the psychobiological effects of childhood sexual abuse, which has been considered a major traumatic experience in childhood. The authors provided data on specific alterations in the endocrine and immune systems, as well as data on epigenetic modifications related to child sexual abuse.Four articles of the Research Topic focus on peripheral neurobiological measures in children and adolescents. Giannopoulos et al. investigated early life sensorimotor sex/age differences using Electroencephalographic (EEG) recordings to measure muscular and neural acoustic startle response (ASR) in a healthy young population. ASR is a cross-species indicator of sensorimotor and inhibitory mechanisms, showing distinct signature in cognitive aging, sex and psychopathological characterization. Neural ASR was assessed by two different analyses, Event-related Potentials (ERPs) and First-derivative Potentials (FDPs). In this study, the modulation of ASR by PPI and PPF was associated with biological sex and internal/external traits in childhood and adolescence, potentially useful to guide symptomatology and prevention of psychopathology.Finally, the research paper by The articles of this Research Topic highlighted the pivotal role of the stress system in neurodevelopment, either as a contributing environmental factor interacting with a genetic background, or as a major physiological mechanism of adaptation in individuals with neurodevelopmental disorders. Various neurobiological measures of stress have been analyzed and discussed by the authors, however, this is only a limited view of the role of the Stress System in the pathophysiology of NDDS. More data are needed to further elucidate and increase our knowledge on the longitudinal role of stress in brain development and in adaptation to everyday and novel/unexpected stressful stimuli.PP wrote the initial draft. AA and GC critically reviewed the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but the underlying medical condition and possible interaction with medical treatments might pose serious safety issues.To review the direct and indirect evidence on the safety of psychotropic drugs in people with COVID-19 and provide practical recommendations for frontline clinicians.An international, multi-disciplinary working group was established with the aim of producing evidence-based recommendations on the management of psychotropic medications in people with COVID-19, following the WHO Rapid Advice Guidelines methodology in the context of a public health emergency. Evidence retrieved was focused on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications. Furthermore, drug-drug interactions between psychotropic and medical treatments used in people with COVID-19 was reviewed and critically discussed by the working group.The analysis of available evidence, although indirect, showed that all classes of psychotropic medications might carry relevant safety risks for people with COVID-19. The working group produced a set of 12 recommendations to support clinicians in the assessment of the anticipated risk of psychotropic-related unfavourable events, and how to practically manage this risk, including when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication.The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.No significant relationships."} +{"text": "As the scale of foundation pit projects of subway stations in Shenzhen becomes larger, and the construction constraints become more and more complex, there is an urgent need for intelligent monitoring and safety management of foundation pits. In this study, an integrated intelligent approach for monitoring and management of a deep foundation pit in a subway station was proposed and a case study based on the Waterlands Resort East Station Project of Shenzhen Metro Line 12 was used for validation. The present study first proposed the path of intelligent foundation pit engineering. Based on geotechnical survey and building information modeling, a three-dimensional transparent geological model of foundation pit was constructed. Multi-source sensing technologies were integrated, including micro electromechanical system sensing technology, Brillouin optical frequency domain analysis sensing technology, an unmanned aerial vehicle and machine vision for real-time high-precision wireless monitoring of the foundation pit. Moreover, machine learning models were developed for predicting key parameters of foundation pits. Finally, a digital twin integrated platform was developed for the management of the subway foundation pit in both construction and maintenance phases. This typical case study is expected to improve the construction, maintenance and management level of foundation pits in subway stations. In recent decades, various advanced technologies, such as artificial intelligence (AI), internet of things (IoTs), digital twin (DT), and machine learning (ML), have been successfully applied in various activities of civil engineering, such as slope stability analysis ,2, geoteFoundation pit engineering, as one of civil engineering branches, needs to adapt to increasingly complex urban environmental conditions and striIn this study, 35 published papers related to foundation pit engineering were collected for knowledge mapping. The input keywords in the Scopus search engine included foundation engineering, foundation pit, foundation excavation, foundation construction, BIM, monitoring and automation. A knowledge map of the relationship between the keywords among those literatures was obtained using VOSviewer, as shown in Based on the keyword relevance analysis atlas of intelligent foundation pit engineering, and the analysis of previous engineering cases, it was found that the research content of intelligent foundation pit engineering is often limited to a certain part of the project. For example, through the establishment of computer in-situ 3D transparent geology of the foundation pit, soil information can be retrieved and managed with high accuracy , and theThis study was based on the project of Waterlands Resort East Station of Metro Line 12, Shenzhen, China. The first intelligent foundation pit integrating \u201ctransparent geology multi-source perception deep learning digital twin\u201d was done through in-situ testing, BIM, multi-source perceptions, ML, and DT. This innovation can significantly enhance the design, operation, and management of foundation pit projects for metro stations.This study was based on the project of Waterlands Resort East Station of Metro Line 12, Shenzhen, China. An overview of the project is shown in Through a geotechnical engineering investigation , on-site engineering geological basic information data was obtained. The three-dimensional geological information and foundation pit engineering structure in the current project were modeled with BIM technology to form a three-dimensional transparent foundation pit engineering infrastructure. Based on the deep foundation pit of Waterlands Resort East Station Project of Shenzhen Metro Line 12, this study carried out six in-situ tests, including a double bridge static penetration test, a three-bridge static penetration test, a pressure meter test, a flat shovel lateral expansion test, a vane shear test and a full flow penetration test. The change laws of the strength, permeability coefficient and mechanical parameters of the stratum soil mass, and the fine division of the soil layer and relevant geotechnical parameters, were analyzed based on the test results. As shown in Through multi-source sensing technologies, including MEMS, BOFDA distributed optical fiber, UAV and MV, a safety monitoring assessment of foundation pit engineering was carried out. MEMS technology is mainly characterized by miniaturization and integration . SensorsOptical fiber sensing technology meets the requirements of high precision, long-distance and long-term measurement. Distributed optical fiber sensor, represented by BOFDA, achieves continuous spatial distributed measurements with accurate measurement results and small errors , and is At present, UAV and MV technoloDue to the depletion of the sensor itself, the measurement accuracy declines after a period of time, which affects the accuracy of the monitoring results. Different from the traditional single engineering monitoring method, this study uses MEMS sensing technology, BOFDA distributed optical fiber sensing technology, a UAV and MV technology to monitor the working parameters of the foundation pit, including but not limited to axial force, stress, temperature and displacement, to give reasonable play to the advantages of various sensors and make up for the shortcomings of various sensors, and ensure the accuracy and reliability of monitoring parameters.Based on the foundation pit project of Waterlands Resort East Station, an intelligent monitoring platform of foundation pit based on deep learning algorithms and BIM was developed.The back propagation (BP) neural network algorithm is composed of three-layer networks of input layer, hidden layer and output layer. Its core idea is to transmit the output error back to the input layer by layer through the hidden layer in some form ,58. BaseThese four neural network models were used to train the axial force, settlement and displacement dataset of the support system of the deep foundation pit over the past one year and then develop prediction models. The reliability of the proposed models was assessed using root mean square error. The proposed models are expected to be used for the early warning and safety assessment of deep foundation pits. By calculating the relative average error, we found these four ML models can accurately predict the axial force, settlement and displacement. Furthermore, the GA-BP algorithm has the best prediction performance due to the smallest error.The intelligent monitoring platform of the foundation pit was constructed using IoTs technology and a three-dimensional geographic information system . Figure At present, the platform has only been used to monitor the key parameters during the foundation pit construction stage. It is necessary to complete the monitoring of the whole life cycle of the subway station project using other platforms. Based on the related research of traditional foundation pit engineering monitoring and management, the platform was developed by the Future Underground City Research Institute of Shenzhen University in conjunction with Jinan Bimu Digital Software Technology Co., Ltd. , which is convenient for enterprise users to monitor and calculate their own projects. Based on the cast modeling platform of Huawei Kunpeng cloud, the platform completes the application and development of BIM graphics and subsequent multi-source heterogeneous data. The parametric model data is uploaded and downloaded through the cast without loss. The platform supports repeated editing and modification of BIM models and can add/delete monitoring equipment models for many times. The real-time synchronization of the platform is conducive to the monitoring and management of the BIM model at different stages, and the reuse of one modeling for many times greatly improves the application value of the model. The platform provides an open cloud computing framework, supports the loading of third-party algorithms, and is used to calculate and analyze the collected data of different monitoring devices online, and predict the future development trend with one click. At the same time, an algorithm back test function is provided to directly compare the predicted value with the measured value. The accuracy of the prediction result is evaluated and the most appropriate algorithm according to the data type is selected. As shown in Based on Waterlands Resort East Station Project of Shenzhen Metro Line 12, this study developed a DT app terminal open platform integrating intelligent construction and management of rail transit foundation pit. Unity3D was used to realize intelligent upgrading of two-dimensional drawings. The platform accomplished the integration of a station building drawing and model, and all current project drawings of the enterprise could be viewed in the start page. The current platform was divided into two parts: intelligent construction and intelligent management.As shown in This app is currently applied only to the integrated intelligent construction and management project of Waterlands Resort East Station Project of Shenzhen Metro Line 12. If it is to be applied to other projects, it needs to import relevant information. At the same time, the compatibility problem of the app still needs to be improved. Currently, it can only be used for mobile phones equipped with the Android system. Different from the traditional DT platform, the app includes three major functions: three-dimensional visualization, full life cycle monitoring and predictive analysis. Three-dimensional visualization breaks the traditional mode of integrating building information through plane drawings, and maps the building model of the physical real world through 3D modeling technology. The information integration of DT from planning and design to construction to operation and maintenance stage ensures the integrity and consistency of data and runs through the whole life cycle of the subway station. The introduction of DT technology provides a basis for predictive decision-making and analysis. The key parameters are monitored by the sensors, and the data collected by the monitoring sensors are analyzed with the help of the deep learning algorithm, and the safety level is predicted at the same time.Augmented reality combines real world information and virtual world information. Through real-time imaging, three-dimensional and other technologies, it projects physical information that is difficult to experience in a certain time and space range of the real world into a real world in the form of virtual information, so as to be directly captured by human senses and achieve a perceptual experience beyond reality. The working principle of AR includes video capture, graphics system, video synthesis, and video output. As shown in Through on-site geological investigation, refined geological information of the on-site soil layer was obtained. Three-dimensional transparent geology was then developed on the BIM platform to facilitate information management of the on-site soil layer and effectively control the construction risk;Through MEMS sensing technology, BOFDA distributed optical fiber sensing technology, laser radar, UAV and machine vision technology, the key parameters of the foundation pit, including but not limited to axial force, displacement, strain, temperature, etc., were obtained. The accuracy and reliability of monitoring data were greatly improved using a variety of monitoring methods and multi-source sensing technology;An intelligent monitoring platform of foundation pit based on BIM of independent intellectual property rights was developed using a cast modeling cloud platform to realize integrated monitoring and management of the foundation pit during construction. Four ML neural network algorithms were used to predict the key parameters of the foundation pit. It was found that the algorithm with the smallest error in the project was the GA-BP algorithm;A DT app terminal open platform integrating intelligent construction and operation and maintenance of rail transit was developed using DT means, which included three major functions: three-dimensional visualization, full life cycle monitoring and predictive analysis. Based on app and augmented reality technology, BIM 3D model, facilities, equipment and other operation and maintenance data were combined with the current real tunnel scenario to realize the DT of subway stations.This study advances a new idea for an integrated intelligent approach for monitoring and management of a deep foundation pit in a subway station, which is divided into four modules: the implementation path of intelligent foundation pit engineering, field investigation and in-situ test, multi-source perception technology, ML prediction algorithm and DT integration of foundation pit construction and operation and maintenance. This innovative idea was implemented in the foundation pit engineering of the Waterlands Resort East Station Project of Shenzhen Metro Line 12. The main conclusions are as follows:At present, the data obtained from the in-situ test reflect the real parameters of rock and soil to the maximum extent. The stability of different types of sensors is different, resulting in high cost and long time-consuming of the monitoring platform with multi-source information fusion. Different from the traditional foundation pit project management scheme, this research achieved the integration of construction, operation and maintenance and management of intelligent foundation pit project through four modules of \u201ctransparent geology multi-source perception deep learning digital twin\u201d, which intuitively displays the soil layer information, monitoring data, prediction results and three-dimensional models of construction and electromechanical, greatly improving the project management efficiency of engineering personnel."} +{"text": "Alcohol is frequently used in association with cannabis, with co-use now perceived as normative with expanding cannabis legalization. Cannabinoid products are increasingly used for a number of medical and recreational purposes, including to enhance alcohol-reinforcing properties or in some cases to substitute for alcohol. Rates of alcohol use disorder (AUD) are higher among cannabis users relative to nonusers, with approximately 60% of individuals with current cannabis use disorder also meeting criteria for current AUD.This research review series approaches cannabinoid\u2013alcohol co-use through the lens of complex interactions between biological, psychological, and environmental factors. Basic science research reviewed in this topic series highlights the role of the endogenous cannabinoid or endocannabinoid (eCB) system in alcohol-related behaviors. The eCB system, which regulates cannabis reinforcement, is also involved in modulating alcohol reinforcement, motivation to consume alcohol, excessive alcohol consumption, AUD,Cannabinoids may reduce harmful effects of AUD, in part, by conferring beneficial effects on the gastrointestinal and immune systems.This translational research series strives to elucidate the cannabinoid\u2013alcohol interactions by synthesizing findings across animal studies as well as human laboratory and epidemiological designs from community and clinical samples. From synapse to policy, the reviews in this series reflect the current state of the science on the reciprocal impact of alcohol and cannabinoids on an individual and the society at large. Several comprehensive reviews summarize findings from preclinical and human studies on the effects of alcohol exposure on the eCB system as a whole34This topic series aligns with the research efforts discerning the shared impact of cannabinoids and alcohol on health undertaken by the Collaborative Research on Addiction at the National Institutes of Health (CRAN) partnership between the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse (NIDA), and the National Cancer Institute. Elucidating effects of cannabis and alcohol co-use on health, policy, and economy is also a key research priority identified by the Cannabis Policy Research Workgroup of the NIDA National Advisory Council on Drug Abuse (NOT-DA-22-003). The empirical literature on cannabis and alcohol co-use has grown fourfold in the last decade alone, reflecting burgeoning interest in this topic. As summarized in the articles in this series, more research is needed to improve our understanding of the mechanisms underlying the functioning of eCBs in relation to alcohol in order to advance the development of eCB-based pharmacological treatments of AUD and related conditions. Clinical data examining the role of specific cannabinoids in alcohol-related human behavior also are critically needed to inform clinical guidelines for individuals engaged in AUD treatment and/or people who drink heavily and co-use cannabis. The authors lend crucial insights and make specific recommendations for future research endeavors on alcohol and cannabis interactions, taking into account between-person and within-person variability across time and contexts. All together, these findings will have important implications for the development of policy concerning alcohol in the context of the changing cannabis sociopolitical landscape."} +{"text": "Currently, there are no ideal medications for treating anorexia nervosa (AN) and bulimia nervosa (BN). This is due to the variety of symptoms from the mental and somatic spheres.Describe the modern methods of psychopharmacotherapy AN and BN.Data from available publications on the topic of psychopharmacotherapy AN and BN, and long-term practical experience of research staff the Department of psychiatry and medical psychology RUDN University, Moscow.Therapy includes antidepressants (AD) - serotonin reuptake inhibitors (SSRIs), antipsychotics and tranquilizers. AD groups of SSRIs reduce most of the symptoms AN and BN - depressive disorders, anxiety, obsessive and compulsive symptoms, episodes of overeating and purifying behavior, suicidal thoughts, and reduce the frequency of relapses. With severe and persistent dysmorphophobia, a high degree of impulsivity, and psychopathic behavior second-generation antipsychotics Quetiapine, Olanzapine, Risperidone and Aripiprazole are used. Benzodiazepine tranquilizers (Lorazepam) are used in small doses and as additional therapy. Data from the European national guidelines for the treatment of AN and BN very different, and the world Federation of societies for biological psychiatry (WFSBP) does not provide specific recommendations at all. There are many reasons for disagreement and lack of specificity regarding drug selection, including the lack of an equally solid evidence base, that reflects the modern state of research on the psychopharmacological treatment of eating disorders.In General, therapy AN and BN should be comprehensive - psychopharmacotherapy, psychotherapy, diet therapy, social rehabilitation. Treatment should be carried out both in the hospital and on outpatient basis and should be decided individually.No significant relationships."} +{"text": "Most passengers and goods in Canada travel by road. The trucking industry is the backbone of the tangible goods economy. However, the health and well-being of this aging workforce is in jeopardy. Recent data reveals that 86% of the truckers\u2019 community are 50 years old and over, 4% are female and 5% are immigrants. Moreover, 75% of the male truckers self-reported one or more health condition . Despite, the high prevalence of risk factors and preventable chronic diseases among truckers, in New Brunswick and elsewhere in Canada, there is a lack of on-the-road accessible lifestyle change programs. Therefore, tailored interventions are needed to appropriately support them adopt healthy behaviors. Using the Re-AIM Framework, we carried out 23 semi-structured interviews to inform the development of tailored educational material. The aims were: to describe the needs and challenges and to design a truckers-sensitive educational intervention. The theoretical foundation of this qualitative study is articulated around concepts extracted from cognitive and behavioural theories . Qualitative analysis of verbatims identified four major themes: Lifestyle challenges, Social and individual representation of healthy behaviors, Health education strategies and communication and Motivational and engagement strategies. Drawing upon these findings we developed tailored educational material and pre-validated them with a small group of professional truck drivers. Our findings informed the development of an educational intervention to support truckers manage and improve their mental health and self-management of chronic diseases. The next step is to implement a randomized clinical trial to test and assess acceptability, feasibility, and effectiveness of our intervention.Improving mental health of professional truck drivers is an urgent public health issue.Format and content of mental health and chronic disease self-management need to be adapted at the cognitive and capacity level."} +{"text": "Peste des petits ruminants virus (PPRV) is an important agent of contagious, acute and febrile viral diseases in small ruminants, while its evolutionary dynamics related to codon usage are still lacking. Herein, we adopted information entropy, the relative synonymous codon usage values and similarity indexes and codon adaptation index to analyze the viral genetic features for 45 available whole genomes of PPRV. Some universal, lineage-specific, and gene-specific genetic features presented by synonymous codon usages of the six genes of PPRV that encode N, P, M, F, H and L proteins reflected evolutionary plasticity and independence. The high adaptation of PPRV to hosts at codon usages reflected high viral gene expression, but some synonymous codons that are rare in the hosts were selected in high frequencies in the viral genes. Another obvious genetic feature was that the synonymous codons containing CpG dinucleotides had weak tendencies to be selected in viral genes. The synonymous codon usage patterns of PPRV isolated during 2007\u20132008 and 2013\u20132014 in China displayed independent evolutionary pathway, although the overall codon usage patterns of these PPRV strains matched the universal codon usage patterns of lineage IV. According to the interplay between nucleotide and synonymous codon usages of the six genes of PPRV, the evolutionary dynamics including mutation pressure and natural selection determined the viral survival and fitness to its host. Morbillivirus, family Paramyxoviridae, and order Mononegavirales (Peste des petits ruminants (PPR) caused by peste des petits ruminants virus (PPRV) is a highly contagious, acute and febrile viral disease of wild and domestic small ruminants, and poses a great threat to the ruminant industry in the world . PPRV waavirales . This isavirales . H and Favirales .The PPR outbreaks can cause high morbidity and mortality, resulting in severe economic losses in the developing countries. Hence, the analysis of epidemic tendency and evolutionary dynamics of PPRV for prevention and control remains particularly important. A Bayesian phylogenetic analysis of all PPRV lineages (I-IV) identified an ancestral PPRV and individual lineages of Nigeria for PPRV and Senegal for lineage I, Nigeria/Ghana for lineage II, Sudan for lineage III and India for lineage IV . In addiThe 45 whole genome sequences of PPRV strains available were downloaded from the National Center for Biotechnology (NCBI) Genbank database, accessed on 1 September 2017 . Based oAs for the nucleotide usage bias at gene levels of the 45 PPRV strains, the normalized information entropy over the frequencies of different nucleotides in a given gene was presented by the below formula :fi is the probability of the specific nucleotide (Fi), and Fi is the total number of occurrences of the specific nucleotide in the target gene . The value of Entropy for nucleotide usage bias ranges from 0 to 1, representing how the dispersed contribution of these four types of nucleotides is: the higher the value is, the more uniform the nucleotide usage is; in contrast, a lower value reflects a more biased usage of nucleotides.where To further compare the nucleotide usage biases in the six coding sequences, the overall nucleotide usage biases, and the nucleotide usage biases at the 1st, 2nd, and 3rd codon positions were estimated by One-way ANOVA method in SPSS 16.0 software, respectively.The relative synonymous codon usage (RSCU) values for the given coding sequences of the PPRV strains were calculated to quantify synonymous codon usage bias without the confounding influence of amino acid usage patterns or the length of different gene samples . Of noteD was introduced into this study is defined as a cosine value of an included angle between A and B special vectors, meaning that the evolutionary distance between gene A and gene B at the aspect of 59 RSCU values, ai is defined as the RSCU value for a specific codon in 59 synonymous codons of gene A, and bi is termed as the RSCU value for the same codon of gene B. Here, the lower the D value is, the higher the extent of similarity of codon usage patterns between gene A and gene B.where http://genomes.urv.es/CAIcal, calculated the CAI for a group of viral sequences using the specific host reference set and included a complete set of tools related with codon usage adaptation. The host reference set required to calculate the CAI can be introduced in the codon usage database of the host. The synonymous codon usage patterns of host as reference, the synonymous codon usage bias with high extent represented the highest relative adaptation to the host, and coding sequences with higher CAI values should be regarded preferred over those with lower ones were selected as the reference set, and the related data was obtained from the Codon Usage Database (The codon adaptation index (CAI) analysis of PPRV coding sequences were carried out depending on the CAIcal server , which wwer ones . The synDatabase .Rij) was intrandXi is the standard deviation of the Euclidean distance between each point (Bi) in the ith group and the centroid (Ai) of the ith group; Xj means the standard deviation of the Euclidean distance between each point (Bj) in the jth group and the centroid (Aj) of the jth group, Tiand Tj standard for the total numbers of points in the ith group and in the jth group, respectively. Mij is the Euclidean distance between the centroids (Ai and Aj) of the ith group and the jth group. The smaller the Rij value is, the stronger the interaction between the two groups.p-value was <0.05. Linear regression was used for modeling the relationship between a scalar dependent variable and one independent variable using the software GraphPad Prism 6 for Windows.One-way ANOVA method was used to compare the means of two or more groups containing numerical response data using the software SPSS 16.0 for Windows, and significant difference can be identified when P < 0.0001). Generally, the nucleotide usage patterns represented the gene-specific compositional trends rather than the similar compositional trends with the overall content of nucleotides analysis also found highly similar extent of synonymous codon usage in viral genes of the three groups (Although the PPRV strains from China (2007\u20132008), China (2013\u20132015) and other countries generally shared a similar synonymous codon usage pattern , the dife groups based one groups . In addie groups . These rOvis aries) cellular machinery. Based on the classification of gene types, a strong significant difference was found (Ovis aries) based on RSCU data for Ovis aries and AAU (Asn) in F gene, UCA (Ser) in H gene, UUG (Leu), UCA (Ser) and AAU (Asn) in L gene, CUA (Leu) and UCA (Ser) in M gene and UCA (Ser) in P gene. These synonymous codons likely mediated and regulated the relevant viral genes translation due to its low corresponding tRNA abundance in the host.The CAI analysis were performed to estimate the correlation between the synonymous codon usage bias and the expression efficiencies of gene samples of PPRV, implying that the strong codon adaptation of the viral genes fit the host indicated that despite the obvious effects of nucleotide usage biases at different codon positions on the overall codon usage bias of PPRV coding sequences, nucleotide usage biases at the first and second codon positions played more vital roles than that at the third codon position in the codon usage bias for the coding sequences . AnotherPreviously, the major bottleneck limiting in better understanding of the genetic features of PPRV was their dependence on nucleotide usage variation. Although nucleotide usage variation can be regarded as evolutionary dynamics of PPRV genome, synonymous codon usage patterns of PPRV coding sequences carry more genetic information, including viral adaptation to hosts, viral gene expression, and effects on the biological functions of viral protein.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Conceptualization: XW, F-yP, and F-qX. Methodology: F-yP, F-qX, XW, and D-rZ. Software: XW and F-yP. Formal analyses: F-yP, D-rZ, XW, and JS. Writing-review and editing: XW, JS, and F-qX. All authors contributed to the article and approved the submitted version.This work was supported by Department of Science and Technology of Gansu Province Nature and Science Fund [21JR1RA141], Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital , Cuiying Postgraduate Student Supervisor Culture Plan [CYDSPY202005], Innovation Foundation for Higher Education Institution of Gansu Province [2020B-022], and Gansu Province Science and Technology Fund [20JR10RA737].The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Rural households are facing severe challenges while adapting to existing and emerging risks of various kinds, including the effects of unprecedented shocks that affect individuals and families in terms of lack of income, reduced consumption and the sale of assets. Health shocks, i.e., unpredictable diseases that undermine people's health status, are the most common unprecedented shocks and the most pressing causes of families falling into poverty. When an illness or injury impairs the health of a family member or causes the income of the family to be reduced or even lost, the family is faces high levels of vulnerability due to the costs of medical treatment as well as the lack of income caused by incapacity for work. Health shocks, together with economic ditto, thus place a heavy financial burden on families and are, de facto, one of the most important factors related to poverty in these regions.Risk adaptation and coping has become necessary activities for families living in rural areas of low and middle income countries, but this is also taking a significant share of their income. Consequently, understanding these risks and related coping strategies is crucial for policymakers. This is also reflected in the Global Development Report entitled Risks and Opportunities, which examines how families can cope with the wide range of risks they face.The focus of this special issue addresses the effects of COVID-19 on rural areas in the Low- and Middle - Income Countries. Several researchers submitted a significant number of high-quality papers for consideration in this special issue, which went through a rigorous peer-review process, with an acceptance rate of 50%. Finally, 16 quality contributions were published, and among them were the following papers:COVID-19's Impact on China's Strategic Emerging Industries: An Observation of Policy Difficulties studies the influence of the COVID-19 on R&D investment and foreign exchange development of China's most important emerging industrial firms.Analysis of Preventive Behaviours of Rural Tourism Hosts in the Face of COVID-19 Pandemic: Application of the Health Belief Model discusses preventive behaviors of rural tourism hosts and the COVID-19 utilizing the HBM model.Investigating the Adoption of Precautionary Behaviours Among Young Rural Adults in South Iran During COVID-19 investigates the factors affecting youth intention and preventive behavior with respect to COVID-19, also using the HBM.Besides of those the issue also discussed the following topics:Social, Environmental and Economic Impact Assessment of COVID-19 on Rural tourism.Dynamic conservation in risk society: A case study of COVID-19 pandemic risk in Kashan Qanat Irrigated Agriculture.Tourism development during the pandemic of coronavirus (COVID-19): Evidence from Iran.The impact of COVID-19 pandemic on food security, and food diversity of Iranian rural households.How do collective efficiency and norms influence the social resilience of Iranian villagers against COVID-19? The mediating role of Social leadership.Impacts of COVID-19 pandemic on micro and small enterprises (MSEs): Evidence from Rural Areas of Iran.Developing a paradigm model for resilience of rural entrepreneurial businesses in dealing with the COVID-19 crisis; application of grounded theory in western of Iran.We hope that the papers presented in this special issue will be useful and stimulating for further understanding of risks, vulnerabilities, and counter mechanisms available to deal with a wide range of health and economic shocks faced by rural households and to properly design and develop social safety nets.https://www.frontiersin.org/research-topics/41035/addressing-the-effects-of-covid-19-on-rural-areas-in-low-and-middle-income-countries-volume-2.Due to the good response from the researchers to this Research Topic, the journal has decided to initiative, the Volume 2 with the same editorial team. Further information can be found at: All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Prefabricated construction is one of the solutions to the problem of balancing environmental improvements with the new buildings in the construction industry. Some work originally done on site is transferred to the front end, and the occupational health risks to industrial workers during the production of prefabricate concrete components are thus aggravated. This study aims to propose a framework to simulate the occupational health risks of workers in prefabricate concrete component plants from the perspective of risk identification, risk assessment, and risk control. Through the following 4 steps, including environmental release monitoring, diffusion and human inhalation mechanism analysis, occupational health risk evaluation, and full-path health risk simulation, this study maps physical entities to virtual reality. The proposed method tends to address the root causes behind occupational health risks, such as the lack of measurement, assessment and prevention criteria, and providing new ideas for theoretical research and innovative practice of HSE management and risk management in the construction industry. Green Building Action Plan released in 2013. In 2018, the Chinese government further made the vigorous development of prefabricated buildings a key task and overall requirement for the future. In 2021, the Chinese government released the Action Plan for Carbon Peaking by 2030, which aims to accelerate the application of prefabricated buildings and the industrialization of construction. Even under the influence of the epidemic, the total building area of new prefabricated building in China reached 740 million square meters in 2021, accounting for about 25% of total area of new construction with more than 500,000 workers employed.The construction industry faces the problem of balancing economic growth and environmental impact. The concept of prefabricated building is an innovative solution to this problem. Compared to traditional forms of construction, prefabricated building has the advantages of increasing efficiency, shortening periods, lowering costs, saving energy, reducing consumption, reducing environmental pollution and sustainability in the production, construction and use processes , 2. TherPrefabricated buildings can be divided into concrete structures, steel structures, bamboo and timber structures according to the type of structure, among which prefabricated internal/external wall panels, prefabricated floor slabs, prefabricated staircases and prefabricated balconies as the main components of prefabricated concrete structures are the most common, accounting for over 90% of the market share . Unlike Occupational Health and Safety Management System Guide in the UK, the Occupational Health and Safety Management System in the US, the Occupational Health Inspection Management Regulations in China, the Occupational Health and Safety Management System General Guide in Australia, the Occupational Health and Safety Management System Guidelines in Japan and the international standard Occupational Health and Safety Management System Requirements and Guidelines for Use. However, the risk regulation system and standards for the assembly construction industry, which lies between manufacturing and construction industry, are still immature and require systematic theoretical research results to support the development of risk evaluation criteria and the control of the overall process.The environmental protection authorities in most country will review the environmental assessment before the project goes into operation. However, the focus is on the impact of the plant's emissions on the external environment, while neglecting the occupational health of workers. For example, although a certain prefabricated concrete (PC) component manufacturer acquired ISO 9001 and ISO 14001 certification and meet the 17 elements of environmental management, there are only a few words of discussion concerning the occupational health of workers. In addition, through the preliminary site survey and visits, some PC component production enterprises, especially the small plants, have problems such as dust, noise and odor, and workers lack the necessary protective measures and awareness of health protection, which exposed them to serious occupational health risks. A series of occupational health-related laws and regulations are enacted worldwide, including the Thus, this article is grounded in the intersection of engineering, environmental, and health management. A logical framework of occupational health risks was formed using risk management concept to identify the full pathway process of environmental release, combined with a personal exposure assessment method to form a simulation model of occupational health risk assessment for the whole process workers. It is also applied to real-life cases to form a complete set of long-term management models of occupational health risks caused by environmental release, providing a new paradigm for research in the field of occupational health risk management.The environmental release in this study refers to the hazardous substances or energy spilling, leaking, emitting or escaping into the external environment in physical or chemical form. The construction phase is long with many upstream and downstream industries, complex construction elements, and huge amounts of construction materials, machinery and energy, thus generating various types of environmental release at all stages of building production, transportation, construction, decoration and renovation . The maiTraditional building products, especially concrete components, are mostly cast on site in an outdoor open environment, and the resulting harmful environmental release are easily dissipated into the atmosphere, so the exposure concentration/intensity of industrial workers is relatively low. The production of PC components is conducted in industrial plants, and the production process produces various harmful environmental release, such as dust, noise and VOCs. Industrial workers have long been in this semi-enclosed space with high environmental release and high intensity, suffering serious potential threat to the health in the short or long term.\u201cOccupational health risk\u201d refers to the possibility of work-related diseases or occupational diseases caused by workers' exposure to occupational hazard factors in the process of occupational activities, and its health damage consequences have specific probability and severity . OccupatOccupational health risk assessment can be divided into qualitative, semi-quantitative and quantitative risk assessment methods. In the 1990's, European and American countries and international organizations successively issued occupational health risk assessment guidelines or norms to assess and manage the risk of hazardous substances in the workplace, For example: ICMM Operational Guidelines for Occupational Health Risk Assessment, Occupational Exposure Limits Evaluation Methodology, New Guidance on Inhalation Risk Assessment, Simple Elements of Chemical Occupational Hazard Classification and Control Techniques, Romanian Risk Assessment Methodology for Occupational Accidents and Occupational Diseases, Australian Guidance on Occupational Health and Safety Risk Assessment Management, International Council on Mining and Metals Occupational Health Risk Assessment Guidance, Risk Assessment Methodology for Occupational Exposure to Toxic Chemicals, ICI Mond Toxicity Index Evaluation Method and so on \u201333. In aThe United States National Institute for Occupational Safety and Health (NOSH) research report indicated that there are as many as 39 categories related to occupational health and safety in the construction industry, such as: sandblasting, blood lead, asbestos, asphalt, carbon monoxide, eye diseases, high temperature and pressure, quartz, skin exposure, noise and so on. At present, in addition to Australia, Sweden, Germany and other countries with good occupational health management, there are still some countries in the world with relatively weak research on occupational health management in the construction industry, and there is still a great room for improvement in occupational health management in the construction industry.Previous research OHSAS and HSE management system as the core, aiming at comprehensive evaluation of the construction industry practitioners of occupational safety and health risks. In fact, multi-source harmful environmental release is one of the causes of occupational health risks. From the perspective of building types, studies mainly focus on traditional building forms and their construction processes, while studies on prefabricated buildings, especially the PC component production are relatively few. In terms of the type of emissions, the vast majority of studies focus on emissions of carbon dioxide and other greenhouse gases that have profound effects on human health and the environment. However, there are few studies on environmental release such as dust, noise and VOCs that pose acute/chronic threats to the health of construction workers. In addition, previous studies lack real-time and long-term monitoring and dynamic optimization of emission sources and their surrounding environment, resulting in the lack of universality of static data obtained from a single measure, and the lack of referential results and conclusions.The Life Cycle Assessment (LCA) can be used to assess the impact on human health of various pollutants emitted from the entire process of product production, with emphasis on a long term and cyclical evaluation concept . Risk MaThe risk identification is divided into three parts through the investigation and literature review to understand the mechanism of environmental release from the perspective of LCA. In the Risk Assessment stage, the occupational health risk assessment method and a simulation model adapted to the PC component production phase are built, so that the risks can be can be quantified and optimized. Finally, the modeled risk assessment system is put into empirical analysis. We will control the risk status of all aspects accurately and put forward policy advice. With the records of the database, the effect of measures on risk reduction are tracked and monitored, and the information is feedbacked to the risk evaluation and risk management system to achieve dynamic risk control .Given that the uncertain factors occur as probabilistic phenomenon, the individual exposure assessment method is used in this study. The individual exposure assessment method is used to simulate the probability of inhalation, exposure and exposure to hazardous environmental release during a worker's long-term work, and thus to assess occupational health risks . It can CDIi denotes the chronic daily inhalation/intake of emission i (mg/kg/d), Ci is the concentration of emission i (mg/m3), IR is inhalation rate (m3/h), ED represents exposure duration (h/d), EF is exposure frequency (d/a), EL is years of exposure, BW is body weight (kg), and AL is average life cycle (years).Where In the available health risk assessment literature, hazardous compounds are usually classified as non-carcinogens or carcinogens . For carCRi denotes carcinogenic risk of emission i, ISFi is inhalation slope factor for emission i (kg\u00b7d /mg), HQi means Hazard Quotient, namely the ratio of the concentration of emission i to its reference concentration RfCi in a given time period, with HQi \u22651 indicates that the emission concentration is high enough to cause chronic non-carcinogenic effects. RfCi symbolizes the reference concentration factor of emission i (mg/m3). ISFi and RfCi are captured in the US Integrated Risk Information System (IRIS).Where DALY) is used to quantify the disease burden and injuries in human populations in the Global Burden of Disease Study and perform a quantitative assessment of health damage (DALY as shown in Equation (4) .YLL denotes the year of life lost. YLD is the year of life lived with a disability. It is a time-based measure that combines the time lost due to premature mortality and the duration of disability caused by illness in survivors.Where According to the three stages of risk management theory, this study builds an occupational health risk framework, starting from the three stages of risk identification, risk assessment and risk control, including research content, technical roadmap and methods, as shown in Identifying the source of environmental release and confirming the emission characteristics. Specifically, it includes the following two contents: (1) Sorting out the current production process and process characteristics of typical prefabricate concrete component plants assembly lines. (2) Determining the type, location and extent of environmental release resulting from operations such as material fugitive, energy consumption and mechanical equipment operation during the production of prefabricate concrete components. Taking PC exterior wall panels as an example, their production contains more than 30 processes such as cleaning the mold, installing reinforcement cages, pouring and vibrating, and spray release agent, etc. The potential harmful environmental release during the process mainly contains dust, noise, and VOCs, as shown in Detection and analysis of environmental release properties in precast concrete components plants includes: (1) Field sampling of dust, VOCs gas and other aerosol substances using cyclone particulate collectors, vacuum sampling pumps, Teflon filter membranes, etc. Samples collected in the field are sent to the laboratory under light-free, low-temperature and dry conditions. (2) The material class and particle size interval of the solids in the filter membrane, and the composition and proportion of the gas in the sampler, respectively, with the aid of gas chromatography/mass spectrometry (GC/MS), according to the standard test method provided by the National Institute for Occupational Safety and Health Research (NIOSH). (3) Toxicological and human potential damage analysis was conducted for all detected substances, and the substances with a large proportion and heavy hazard were finally selected as the final environmental release types .Based on the source emission characteristics, the diffusion and dispersion mechanisms of environmental release are analyzed using spread and dispersion laws as follows: (1) Using monitoring equipment such as laser dust meter, acoustic meter and photo-ionization detector to monitor the emission sources and the surrounding environment at fixed points to obtain real-time data on the change in concentration of dust or gas emissions during the production of prefabricate concrete components and the change in intensity of noise, respectively. (2) Collecting and measuring data on potential influencing factors such as spatial boundaries, wind speed, wind direction, temperature and humidity within the plant during the same production time period using temperature/humidity meters, anemometers and so on. (3) Establish an environmental release propagation/diffusion model, and simulate the transport trajectory, diffusion path and concentration distribution of dust and gas, as well as the propagation distance and decreasing degree of noise, respectively, with Fluent software. (4) Determine the propagation or dispersion pattern of various types of environmental release during the production of prefabricate concrete components.The human intake mechanism of environmental release includes the following four steps: (1) Real-time monitoring of noise intensity and emission concentration data at the ear, mouth and nose of workers of different job types during production operations by requiring workers to wear portable devices. (2) Deploy RFID sensor devices at designated locations to collect and record data on workers' job characteristics, behavioral habits, movement range and other potential influencing factors. (3) Modeling the inhalation/exposure dose of workers to simulate their inhalation, exposure dose, or exposure level to short-lived environmental release under specific constraints. (4) Determine the way of environmental release from human intake during the production of prefabricate concrete components. A number of instruments and equipment are used in these processes, which are highly specialized and sophisticated. The main instruments and equipment mentioned above are shown in On the basis of the risk identification and assessment methods, the simulation model was established to establish the \u201cEmission-Transmission-Inhalation\u201d whole process of worker occupational health risk simulation and evaluation model. The simulation module of each part is established, specifically including: (1) Establish a basic simulation module of prefabricate concrete component production process and emission source location based on building information model. (2) Establish a numerical simulation module based on computational fluid dynamics to simulate the propagation and dispersion of environmental release in component plants. (3) Establish a multi-intelligence-based worker production behavior and health injury simulation module. (4) Create a multiple sources database module containing information on environmental release monitoring, worker health data, emission factors and so on. (5) The application development platform is selected to integrate the above simulation modules and database to build a quarriable, editable and calculable occupational health risk simulation and evaluation model, as shown in Based on the life cycle risk management evaluation method, combined with the above simulation model, the long-term control of occupational health risks caused by environmental release is formed. For the identification of risk control strategies, the target case analysis takes into account the results of risk evaluation and identifies control strategies based on the classification of carcinogenic risk and chronic disease risk respectively. Then, based on the Critical success factors (CSF) analysis method, the key success variables of environmental release risk control are searched from three aspects: emission sources, transmission paths and recipient individuals.Drawing a fishbone diagram to identify, define and develop specific measures included in the above three CSFs, such as reducing dust/gas release due to handling, disturbance or vibration of parts, installing sound insulation and noise reduction equipment, installing sprinkler systems, optimizing ventilation systems, temperature and humidity regulation systems, regular cleaning and decontamination, requiring workers of specific jobs to wear protective equipment, strictly setting daily/yearly working hours for workers of certain special jobs, adopting a job rotation system on a regular basis, etc. Fishbone diagram through critical success factor analysis, the gray correlation algorithm is used to determine the gray correlation between the above measures and to develop the optimal combination strategy. The process is shown in SM is the simulation model, PE is physical entity, VE is virtual entity, SS is service, DB is data, and CN is the connection between the parts.The simulation model contains five key elements as shown in Equation (5), where: PE is the basis for building the simulation model. In the project, a single PC component production machinery and equipment can be regarded as a unit-level PE, which is the smallest unit for function realization; a full set of PC component production line can be regarded as a system-level PE, which can complete the component production task; the whole plant composed of production line, environmental Emission and workers can be regarded as a system-level PE, which is a comprehensive system including material flow, emission flow and information flow, including four parts of human-machine-material-environment, as shown in Equation (6).Physical layer element identification and data acquisition. The accurate analysis of Hp describes the scope of action and behavior of industrial workers in the production process of components, and the data are obtained through RFID and image recognition technologies; Mp describes the operation of production machinery and production lines, and is portrayed and simulated through preliminary research and continuous probability events; Pp describes the production process of PC components, and is built through the material flow model; Ep describes the intensity and propagation law of environmental release, and is measured through sensors and portable devices.Model layer model building and rules making. The establishment of the model layer is the core of the simulation technology. The digital model of this project includes geometric model, behavioral model and rule model, which describes and portrays each physical entity in the production process of PC components from multiple time scales and multiple space scales, as shown in Equation (7).Gv is a 3D model describing the geometric parameters and relationships of PE, with good spatial and temporal consistency with PE, which can be realized by Fluent 3D modeling software with Revit and Auto CAD; Bv describes the real-time response and behavior of PE under the joint action of external environmental impact and internal operation mechanism in different time scales, using a multi-intelligence-based simulation model. Rv describes how physical entities operate, including rules based on historical data, experience based on tacit knowledge summaries, and process flow standards, enabling VE to map the PC component production process and environmental release in real time.Bs). At the same time, the service (Fs) needs of PC component manufacturing enterprise managers for environmental release and worker health risk information acquisition are met through application software and clients, as shown in equation (8).Functional and business module design of the service layer. The service layer is designed to encapsulate various types of data, models, algorithms, and results in the simulation model in a service-oriented manner, to support the operation of the internal functions of the model and to provide functional services .Database establishment and data are interconnected in the data layer. The establishment of the database in the data layer is the key to realize the information linkage and transmission among other layers, mainly including Dp mainly includes physical element attribute data reflecting PE specifications, functions, performance, relationships, etc., as well as dynamic process data reflecting PE operating conditions, real-time performance, environmental parameters, sudden disturbances, etc., which can be collected through testing equipment, sensors and other equipment; Dv mainly includes data related to geometric models, physical models, behavioral models and rule models in VE, as well as simulation data based on the above models Ds mainly includes data related to Fs and Bs .CN) between the above four layers is shown in Equation (10).Inter-layer connection method design. After the above four layers are established, how to connect the layers together is another key technique to realize the proper operation of the simulation model. The connection Integrate the multi-objective model with the simulation model, combine simulation experiments with parallel experiments, and establish environmental release and worker occupational health risk evaluation criteria for PC component production for different products and different types of work , respectively. (2) Determine the number, location and scope of environmental release monitoring points according to the standards, set the concentration/intensity monitoring thresholds for different categories of emissions, and establish a multi-level risk warning system for workers' carcinogenesis and chronic diseases. (3) Compare the monitoring data of several PC component plants, summarize the characteristics of environmental release and workers' health risks, further optimize the monitoring program of monitoring points, thresholds and types of work, and form evaluation standards with high timeliness and universality, and promote and apply them in the whole industry.The occupational health risks of construction industry workers have been much higher than the social average. With the growing scale of prefabricated buildings, the work originally required to be done on site is shifting to the front end, and the health risks of on-site construction workers are shifting to industrial workers in prefabricate concrete component plants.Based on the intersection of engineering, environmental, and health management, this study tries to solve the root problems behind occupational health risks from risk identification, risk assessment, and risk control, the three processes such as the lack of measurement, assessment, and prevention standards. Through mapping physical entities to virtual simulation, feeding back the quantification and optimization results to practical applications, and then expanding individual projects to the whole industry, this study provides new ideas for theoretical research and innovative practice of HSE management and risk management in the construction industry. Firstly, the logical framework of occupational health risk is formed using the concept of life cycle risk management, which provides a new paradigm for the research in the field of occupational health risk management. Secondly, identifying the characteristics of the source of emissions and analyzing the diffusion propagation law and diffusion mechanism to understand the whole path process of environmental release. Afterwards, clarifying the human intake mechanism combined with the personal exposure assessment method that considers uncertainty factors. Finally, the simulation model of occupational health risk assessment for the whole process workers is formed, and finally it is applied to real cases to form a complete set of long-term management model of occupational health risks caused by environmental release.A reasonable risk assessment simulation model and a long-term management model are proposed in this study. In the future, more empirical researches need to be verified in the model to improve the measurement accuracy, refine the human exposure assessment method, and adjust the simulation parameters, and so as to help decision makers to formulate occupational health risk policy. Furthermore, the production of PC components is only one phase of the assembled building industry. Transport, construction and other phases also include a large number of workers whose health risks need to be considered in future studies.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.PC led the overall study. HZ, ZD, and XJ conducted the analysis. HZ, ZD, XJ, PZ, and SZ drafted the manuscript with input from the other authors. All authors contributed to the concept and design of the study, the interpretation of data, revision of the manuscript for important intellectual content, and have read and approved the final version of the manuscript.This research was funded by Jiangsu Natural Science Fund (BK20200782) and Innovation and entrepreneurship training program for college students in Jiangsu Province (202110298026Z).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Studies of the cognitive and behavioral factors of perpetuation and quality of life in patients with somatoform disorders are important for identifying targets for psychological interventions and risk groups .To reveal beliefs and behavior in patients with somatoform disorders associated severity of somatic complaints and poorer subjective well-being.125 patients with somatoform disorders 17-68 years old filled Screening for Somatoform Symptoms , Cognitions About Body And Health Questionnaire , Scale for the Assessment of Illness Behaviour , and Quality of Life Enjoyment and Satisfaction Questionnairie-18 .Severity of somatoform symptoms is higher in patients with catastrophization of bodily sensations, autonomic sensations, belief in their bodily weakness, somatosensory amplification, scanning for bodily symptoms, and disturbances in daily activities due to illness . Adjusting for the severity of somatoform symptoms, subjective well-being was lower in patients with higher belief in their bodily weakness and somatosensory amplification, autonomic sensations, expression of symptoms, and changes in daily activities due to illness .The results suggests that regardless of symptoms severity poorer quality of life in patients with somatoform disorders is associated with beliefs about body and body perception that could be addressed in psychotherapy."} +{"text": "Broadly speaking, psychology is the scientific study of behavior and mental processes, while criminology is the scientific study of crime and criminal offenders. Psychological criminology (or simply as psycho-criminology), which combines the two, is generally concerned with the use of psychological knowledge and skills to explain, describe, and potentially prevent or deal with deviant and criminal behavior Hollin, . More spIn this Research Topic (RT), the focus lies on the application of psycho-criminological approaches and constructs to crime, criminal and civil law, and the influence of law on mental health and behavior. This RT aims to advance our understanding of psycho-criminological mechanisms associated with different criminal behavior in the intersections of mental health and the law. The 10 articles included in this RT explore varied aspects of crime and criminal behavior through the application of psychological concepts and theories to increase our understanding of crime, delinquents and criminal offenders, and their behavior. The highlight of this RT is the range of contribution conducted with six sampling populations, namely Spanish, mainland Chinese, Hong Kongers, Americans, Germans, and Italians. Besides, the collection of these articles addresses the different aspects in the criminal justice system from a psycho-criminological standpoint.Pecino-Latorre et al.. Using a sample of 448 homicides, this article examines the effectiveness and validity of the Action System model to distinguish thematically between the structure of the homicides and to generate a homicide typology in Spain based on the relationships between the modus operandi, and victim and offender characteristics. Four homicide typologies were identified: Expressive, Adaptive, Integrative, and Conservative. Next, Zhu and Shek investigate the effect of individual dimensions and the global positive youth development (PYD) measures on adolescent delinquency, individually; and the underlying mediating effect of life satisfaction. Employing a two-wave longitudinal data collected from 2,648 mainland Chinese adolescents, findings are found to be consistent with the general theoretical prediction of the PYD approach; in which different PYD attributes are inversely related to concurrent and future adolescent delinquency. Moreover, the negative predictions are mediated by the adolescents' life satisfaction. Also recruiting mainland Chinese adolescents, Xiong et al. construct a moderated mediation model to test the mechanisms underlying the relationship between perceived discrimination and proactive and reactive aggression in a longitudinal data of 470 mainland Chinese migrant students (aged 11\u201317). They observed that perceived discrimination fosters negative emotions, which in turns increase reactive aggression. Furthermore, socioemotional support reduces the negative impact of perceived discrimination on reactive aggression by weakening the relationship between perceived discrimination and negative emotions.This RT begins with an empirical study of testing a typology of Spanish homicides by Chan sampled 1,171 young adults (aged 18\u201340) to explore the psychosocial risk factors of risky sexual behavior (RSB) by testing the theoretical propositions of several criminological theories . Relative to females, males possess significantly higher mean levels of general, penetrative, and non-penetrative RSB; and negative temperament, use of alcohol and other drugs, and paraphilic interests. Males and females are generally sharing a similar set of psychosocial risk factors for their involvement in general, penetrative, and non-penetrative RSB. Similarly exploring risky behaviors, M\u00e9ndez et al. explore the different adaptation profiles in adolescents based on their interpersonal risk factors on drug use. Analyzing 1,201 secondary school students (aged 11\u201318 years) in Spain, a latent class analysis generated three different types of adaptation: Maladjusted group, At-risk group, and Adjusted group.In Hong Kong, Acklin and Velasquez argue that Structured Professional Judgment (SPJ) methods can be a corrective approach for unstructured clinical judgment that prone to evaluator bias and suboptimal levels of inter-rater reliability. The authors propose a SPJ model for criminal responsibility evaluations translated from violence risk assessment methodology. Sampling 230 patients in 13 forensic psychiatric hospitals in Germany, B\u00fcsselmann et al. measure the patients' quality of life in forensic psychiatric hospital using the Measuring the Quality of Prison Life (MQPL) questionnaire. They found that the adapted MQPL questionnaire demonstrates good internal reliability and construct validity. The next article by Titze et al. examine the self-reported acculturation processes and associated individual and social factors in a similar sampling population of 235 forensic psychiatric patients with a migration background in 11 forensic hospitals in Germany. The findings indicate that the patients oriented themselves more toward the culture of admission and less toward the country of origin than the reference sample did.Next, Rossetto et al. retrospectively compared 42 readmitted with 48 non-readmitted females in an Italian forensic psychiatric hospital through a minimum of 42 months follow-up (ranges from 3.5 to 10 years). Their findings indicate that readmitted females were positively associated with the presence of substance use disorders and a primary diagnosis on Axis II. The final article of this RT is authored by Brown et al.. They examine the fetal alcohol spectrum disorder (FASD) by proposing a renewed focus on applying and adapting the Risk-Need-Responsivity (RNR) approach to individuals with FASD in criminal justice settings. The authors argue that the use of RNR approach can better determining the needs and interventions in reducing the propensity of offender recidivism.In Italy, With studies conducted in Spain, Mainland China, Hong Kong, the USA, Germany, and Italy, the 10 articles in this RT collectively demonstrate the importance of applying psycho-criminological knowledge and skills to better understand the underlying mechanism associated with different criminal behavior in the intersections of mental health and the law. Having studies from different cultures and jurisdictions have clearly demonstrated that a combined etic-emic approach is arguably more appropriate when studying crime and criminal behavior, and developing culturally sensitive assessments and interventions (Ho and Cheung, The author confirms being the sole contributor of this work and has approved it for publication."} +{"text": "Dear Editor,Tricho-rhino-phalangeal syndrome (TRPS) type I is a rare condition first described by Giedion in 1966. The main characteristics are sparse and slow-growing hair, a pear-shaped nose and coned epiphyses on the medial phalanges of the hands. The hair shafts are thin and miniaturized, as in androgenetic alopecia. There is a down-regulation of the TRPS1 gene in the baldness area, and the decrease of the same protein can impair endochondral cartilage differentiation and cell interactions in the development of hair follicles.Short stature, Legg-Calve-Perthes Disease , shortening of the toes (clinobrachydactyly), dystrophic nails, long philtrum, thin upper lip, and thinning of the distal third of the eyebrows may occur.2TRPS type I often shows an autosomal dominant pattern inheritance, but autosomal recessive inheritance can occur. Type II occurs sporadically, associated with mental retardation and multiple exostoses.The aim of this study is to report the investigation of a case of TRPS in an eleven-year-old girl with mechanical arthralgia in the knees for three years, without morning stiffness, she presented also shortening of the toes and ulnar deviation of the second, third and fifth fingers, bilateral osteochondromas in the supracondylar region, hair rarefaction, and three episodes of convulsive crisis. The neuropsychomotor development was normal. Parents were non-consanguineous and there was no history of repeated abortions. Regarding family history, the father is being treated for epilepsy, and siblings do not have any signs suggestive of genetic syndromes.On physical examination, bilateral hypermobility and deformity of the interphalangeal joints, thickening of the wrists, thinning of the skull, collapse of the nasal bridge, thin upper lip, pear-shaped nose , and higThe cranial tomography showed no changes. The knee radiography revealed a well-defined sclerotic lesion along the medial cortex of the distal diaphysis of the right femur. The patient is undergoing clinical follow-up with the Orthopedics team. The hand radiography showed a widening of the base of the middle phalanx from the second to fifth fingers, bilaterally . The ophThe diagnosis of TRPS type I is attained through typical clinical findings and radiographic findings of coned epiphyses, or the identification of a heterozygous pathogenic variant of TRPS1. For type II, the diagnosis is attained through typical findings of TRPS II and a contiguous chromosome 8 deletion that includes the genes TRPS1, RAD21 or EXT1.Treatment includes supportive measures from a multidisciplinary team .None declared.Evelyn Freitas Rodrigues: Statistical analysis; approval of the final version of the manuscript, design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Lisa Gava Baeninger: Statistical Analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Caroline Romanelli: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "Mindfulness-based interventions have received growing attention over the last years for the treatment of various mental disorders, including schizophrenia spectrum disorders (SSD), demonstrating their transdiagnostic validity. However, no study has examined the relationship of probable mechanisms underlying the therapeutic effects of mindfulness in SSD.The current study examines the relationship between mindfulness, depression, anxiety, and quality of life in individuals with SSD through quantitative measures.A total of 83 participants with SSD were recruited at the in- and outpatient facility of the Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin in Germany. Participants completed the Southampton Mindfulness Questionnaire, Comprehensive Inventory for Mindful Experiences, and Freiburger Mindfulness Inventory, the Depression, Anxiety, Stress Scale, and the World Health Organization Quality of Life Questionnaire. PROCESS analysis examined the relationship between mindfulness and quality of life and the mediating role of depression and anxiety.Indicated a significant positive association between mindfulness and physical health, psychological and environmental quality of life. Depression and anxiety were found to mediate this relationship, with higher depression and anxiety scores being related to lower mindfulness and quality of life. In this relationship, however, depression was found to be the stronger predictor.The findings of this study provide insight into the mechanisms of mindfulness. Initial evidence for the transdiagnostic and process-based clinical relevance of MBIs for SSD has been found and future studies can further explore the role of mindfulness for central therapeutic processes of change by employing longitudinal designs.No significant relationships."} +{"text": "Metamaterials for Wireless Power Transfer is a new open Special Issue of Materials, which aims to publish original and review papers on new scientific and applied research and make great contributions to the finding and understanding of the use of metamaterials for wireless power transfer (WPT) and related fundamentals, characterization, and applications. WPT technology is becoming an important topic for the wireless industry , which hMetamaterials for Wireless Power Transfer includes, but is not limited to, the following: low-frequency metamaterial-based WPT systems, electromagnetic compatibility in metamaterial-based WPT systems, wireless energy harvesting (WEH), theoretical research for metamaterial-based WPT systems, magneto-inductive and resonant waves in WPT systems via metamaterials, programmable metamaterials and metasurfaces for WPT systems, and SWIPT systems based on information metamaterials and metasurfaces.The research interest for the Special Issue"} +{"text": "\u0421ognitive deficit significantly affects the quality of life of patients. Aims of research was detection of cognitive impairments of varying degrees in epilepsy, and as well as studying the results of complex treatment in conditions of University clinic, physical and psychological rehabilitation, cognitive training and VNS included.We studied the features of clinical and psychopathological manifestations of cognitive impairments in patients suffering from epilepsy.The study was attended by 100 patients (35 men and 65 women) who were inpatient care. The following psychodiagnostic techniques were used: the Toronto Cognitive Assessment TorCA, the test of 10 words of Luria, the MOCA test, the M\u00fcnsterberg test, the quality of life scale, the Hamilton scale of depression and anxiety.MCI was observed in 88 % patients, dementia in 12 % . We used non-pharmacological rehabilitation methods for correction of cognitive impairment in epileptic patients with MCI and mild dementia during 3 mounth.. Improving of cognitive function was observed in 48 % patients, stable level of cognitive function - in 36 %, progressing of cognitive imparment - in 16 % patiens with epilepsy.The results of the conducted research indicate the need for further study of the features of cognitive disorders in pharmacologically treatment resistant epilepsy and implementation of training aimed at improving cognitive function and preventing the progression of cognitive impairment in complex treatment of those patients."} +{"text": "In recent decades, numerous studies provided consistent and convincing evidence that the adoption of healthy plant-based dietary patterns is a valuable strategy to reduce the risk of most non-communicable diseases ,2. SeverAmong the most recent areas of research, the potential action of polyphenols in the central nervous system and related diseases, including neurodegenerative disorders, is of major interest . Diet haIn our Special Issue entitled \u201cPolyphenols and Polyphenol-Rich Foods in Neurodegenerative Disorders\u201d, several articles are published that provide further evidence on the potential role of polyphenols in brain health. The study of Al-Musharaf et al. investigOverall, the Special Issue provides interesting insights on the role of certain polyphenols, especially underrated polyphenols such as phenolic acids, and brain health for the prevention of neurodegenerative diseases. Additional studies are encouraged for submission to further explore this research topic and broaden the field of exploration of polyphenols on the benefits for the human brain."} +{"text": "As a research hotspot, deep learning has been continuously combined with various research fields in medicine. Recently, there is a growing amount of deep learning-based researches in orthopedics. This bibliometric analysis aimed to identify the hotspots of deep learning applications in orthopedics in recent years and infer future research trends.We screened global publication on deep learning applications in orthopedics by accessing the Web of Science Core Collection. The articles and reviews were collected without language and time restrictions. Citespace was applied to conduct the bibliometric analysis of the publications.Nature has the highest impact factor in the cited journals. The current hot keywords are convolutional neural network, classification, segmentation, diagnosis, image, fracture, and osteoarthritis. The burst keywords are risk factor, identification, localization, and surgery. The timeline viewer showed two recent research directions for bone tumors and osteoporosis.A total of 822 articles and reviews were finally retrieved. The analysis showed that the application of deep learning in orthopedics has great prospects for development based on the annual publications. The most prolific country is the USA, followed by China. University of California San Francisco, and Skeletal Radiology are the most prolific institution and journal, respectively. LeCun Y is the most frequently cited author, and Publications on deep learning applications in orthopedics have increased in recent years, with the USA being the most prolific. The current research mainly focused on classifying, diagnosing and risk predicting in osteoarthritis and fractures from medical images. Future research directions may put emphasis on reducing intraoperative risk, predicting the occurrence of postoperative complications, screening for osteoporosis, and identification and classification of bone tumors from conventional imaging. As a subset of machine learning, deep learning has broken the limitations of traditional machine learning, and can implement more accurate classification and segmentation of images to extract feature elements , 2. It iMost musculoskeletal diseases in orthopedics require a large degree of help from images. Given the advantages of deep learning in image processing, there has been a growing number of researches on the application of deep learning in orthopedics in recent years . BibliomCurrently, no bibliometric analysis has been conducted to quantitatively analyze the progress and current status of deep learning in this emerging field. Herein, this study aimed to elucidate the research hotspots, key fields, and trends of deep learning applications in orthopedics in recent years by using Citespace, Moreover, the research direction and references for further exploration were shown as well.* OR orthopedic* OR \u201csports medicine\u201d) OR TS = , #2: TS =\u201cdeep learning\u201d OR TS = \u201cconvolutional neural network*\u201d). There is no limit to the publication year. The type of literature was selected as articles and reviews without language restriction. Literature not relevant to this topic was excluded, and duplicate literature was removed by Using Citespace (5.8 R3). Finally, a total of 822 articles were retrieved and exported for records in the format of plain text files. Meanwhile, we also obtained the number of annual publications and the amount of publication of the journal.Since the details of the documents in the Web of Science are more accurate than other databases, such as Scopus, PubMed, Embase, etc. We retrieved all literature from the Web of Science Core Collection. The retrieval was completed within 1 day on March 29, 2022 to reduce changes due to frequent updates to the bibliographic database. The searching strategy was as follows: #1 and #2 (#1:WC = (orthopedics) OR TS = were identified. The number of studies published in each year can help us understand the general trends in the relevant research. Since 2022 has just begun, the number of documents in 2022 cannot show the overall publication situation. Therefore, the analysis only included the publication from 2015 to 2021. As shown in We used Citespace to conduct co-citation analysis of the countries (or regions) and institutions. The country or region distribution map consisted of 56 nodes and 53 links. As demonstrated in A total of 250 authors were involved in the cooperative map . As showSkeletal Radiology (33 times) had the highest number of outputs, followed by IEEE Access (28 times), Scientific Reports (25 times), Computer Methods and Programs in Biomedicine (19 times), Applied Sciences Basel (17 times), Diagnostics (17 times), International Journal of Computer Assisted Radiology and Surgery (15 times), Journal of Digital Imaging (14 times), Medical Image Analysis (14 times), and Sensors (14 times). The co-occurrence analysis of cited journals obtained from Citespace was shown in Lecture Notes in Computer Science (345 times), In Proceedings of The IEEE Conference on Computer Vision and Pattern Recognition (324 times), Medical Image Analysis (287 times), Radiology (280 times), IEEE Transactions on Medical Imaging (274 times), Scientific Reports (197 times), Nature (190 times), Journal of Digital Imaging (185 times), PLoS One (179 times), and American Journal of Roentgenology (149 times).The 822 articles retrieved in this study were published in 308 journals. As shown in A total of 464 nodes and 733 links presenting the co-citation relationship of the references formed the cited reference network in The high-frequency keywords the article can help us understand the main research hotspots of the filed. Keyword co-occurrence analysis was performed by Citespcace. The co-occurrence network of keywords had a total of 265 nodes and 404 links . The higThe clustering of keywords can present the structural system of related research fields. The sixteen different clusters made through Citespace were shown in The strong burst keywords can help us explore the development trends of the filed. We use Citespace's burst function to analyze keywords that have attracted much attention from academia. The burst keywords were shown in This study utilized the principles of bibliometrics analysis and the method of Citespace visualization. In the application of deep learning in orthopedic filed, the annual number of articles, countries (or regions) and institutions, authors and cited authors, journals and cited journals, and keywords were extensively analyzed to reveal the current research hot-spots and trends in this field.Based on an analysis of countries (or regions) and institutions, the USA and China were the two most documented countries, but there was a lack of international cooperation between them. More international cooperation is needed for China to jointly promote development in this field. England, Australia, and Canada had high centrality and publications, suggesting that these countries might play an essential role in bridging research. At the same time, most of the top ten institutions with the most centrality and publications are from China and the USA, but these institutions basically cooperate with other institutions in their countries. Therefore, from the perspective of cooperation networks, we hope that there will be more cooperation between different countries.Through the analysis of the author cooperation network, we found that the top ten authors mainly constituted three cooperative networks. In the cooperation between the two authors in the deep learning field, VALENTINA PEDOIA and Sharmila MAJUMDAR , the most cited literature showed that the improved U-net can automatically segment cartilage and meniscus from MRI . PAUL H As to the analysis of a network of cited authors, the most frequently cited author-LeCun Y believed that deep learning is good at processing high-dimensional data, and can accurately identify and classify targets in image recognition tasks . SimilarAccording to the journals and co-cited journals in Among top ten co-cited references, these references are usually the basis of relevant knowledge fields and play an important role in knowledge structure. For three proceedings papers, Ronneberger O, He KM, and Huang G built new models for deep learning in 2015, 2016, and 2017, respectively, which strengthened the ability of deep learning to process images. These models are deep residual learning, densely connected convolutional networks, and U-net . ArticleKeywords are the cores of a paper that reflecting the concerns of relevant field. By analyzing the high-frequency keywords and strong-burst keywords, we can explore the hot-spots and research trends. The main research hotspots and research trends are as follows:After the first report of deep learning in fracture by Olczak et al. , the numFor upper extremity fracture, deep learning is commonly applied to distal radius fracture and humeral fracture \u201326. Gan In lower limb, hip fractures attracted much attention. Cheng et al. proved that deep learning model can automatically identify femoral neck fracture and trochanteric fracture through pelvic X-rays, with 98% sensitivity and 91% accuracy . Mutasa Moreover, studies showed that deep learning can also help to reveal vertebrae fracture as well. Murata et al. accurately identified vertebral fractures on plain thoracolumbar radiography . UsuallyOsteoarthritis is the most common musculoskeletal disorder, which mainly affects the hip and knee joints with large weight bearings, especially the knee joint. Initially, a proceedings paper showed the use of CNN to analyze Kellgren & Lawrence (K&L) grades based on knee radiographs . Then, TDeep learning is often applied to the classification and diagnosis of diseases. However, with the development of deep learning, this technique will also be applied to perioperative management of orthopedic surgery. Nowadays, deep learning is being gradually explored in the study of orthopedic surgery. Since the visual field in arthroscopic surgery is often affected by different angles of the joint, which requires repositioning in different visual fields, automatic localization under the arthroscopic field of view is urgently needed. Recently, Banach A et al. collected arthroscopic videos and performed deep learning on video sequences at four different knee angles, and the results showed that deep learning performed well in arthroscopic field of view . BesidesFrom the timeline viewer of keywords, we found that the study of fractures and osteoarthritis gradually began to study in-depth from 2016 to 2019. We also paid special attention to the direction of gradual in-depth research after 2019, such as osteoporosis, and bone tumors (osteosarcoma). Osteoporosis often occurs in older or postmenopausal women, and is usually detected because of fractures, thereby screening for osteoporosis may help prevent osteoporotic fractures in many patients. Deep learning can help predict osteoporosis and the possible fracture risk , 51. AltSeveral limitations remain in this study. First, as the literature in the Web of Science Core Collection is constantly updated, and there is currently no uniform regulation on keywords related to the literature, the results of this study may differ from the actual number of documents included. Second, deep learning first appeared in seminars or conferences, and then gradually appeared in journals in the form of article. Since we consider that article has more systematic research, so it is strictly regulated in literature inclusion, which may introduce certain bias to this study. However, it is believed that literature-based visual analysis has undoubtedly laid a foundation for investigators to quickly understand the research hot-spots and development trends of deep learning applied in orthopedics.In conclusion, according to the annual publication curve, the research on the application of deep learning in orthopedics has developed rapidly, and there is a good research prospect. Accordingly, researchers in the field of deep learning and orthopedics may benefit this study. The USA is the country with the largest amounts of articles in this field. University of California San Francisco, the institution with the largest amounts of articles, is also from the USA. However, cooperation between different countries is markedly insufficient. The application of deep learning in orthopedic research has been published in journals of various discipline categories, and multidisciplinary communication conforms to the mainstream of today's world. The current research hot-spots mainly focused on the classification and diagnosis of orthopedic diseases that rely heavily on medical images, such as fractures and osteoarthritis. The application of deep learning to reduce intraoperative risk, predict postoperative risk, screen osteoporosis, and identify, classify, and segment bone tumors may be at the fore-front of the future. At the same time, with the rapid development of deep learning applications in orthopedics, researches in this field will continue to evolve toward multicentric data and more perfect deep learning algorithms.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.CF: investigation, data analysis and visualization, and writing\u2014original draft preparation. XZ, HW, YH, and ZL: investigation and editing. CT: conceptualization, supervision, and writing and revision. All authors have read and agreed to the published version of the manuscript.This work was supported by grant from the National Natural Foundation of China (81902745), Hunan Provincial Natural Science Foundation of China (2022JJ30843), the Science and Technology Development Fund Guided by Central Government (2021Szvup169), Hunan Provincial Administration of Traditional Chinese Medicine Project (No. D2022117), and Clinical Research Center for Medical Imaging in Hunan Province (2020SK4001).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The European\u2013Latin American Consortium towards Eradication of Preventable Gallbladder Cancer, EULAT Eradicate GBC, is collecting high-quality data and samples in four Latin American countries with high gallbladder cancer incidence to build a unique biorepository integrated into a tailored IT platform, to identify, validate, and functionally characterize new risk biomarkers, and to develop prediction models that integrate epidemiological and genetic\u2013molecular risk factors. We decided to develop an application for electronic data collection to facilitate the retrieval of sociodemographic, clinical, lifestyle, dietary, and sample-related information from 15,000 Latin American study participants. The application EULAT eCollect will facilitate the work of study nurses, reduce time spent by participants, limit the use of paper and ink, minimize costs and errors associated with filling out written forms and subsequent digitisation, and support the monitoring of local recruitment rates and data quality. We describe in this article the design and implementation of the EULAT eCollect application, which started with the specification of functional and non-functional requirements, and ended with the implementation and validation of four separate application modules: Socio-Demographic Interview, Sample Information, Case Report Form, and Food-Frequency Questionnaire. We present both general and technical results, and our experience with the free and open-source software, Open Data Kit (ODK), which may be of interest for future related research projects, especially those on personalised cancer prevention carried out in low- and middle-income regions. Gallbladder cancer (GBC) is the most common neoplasms of the biliary tract ,2. GBC tAmong the risk factors associated with GBC, female gender, age, gallstones (cholelithiasis), genetic ancestry, obesity, multiparity, and socioeconomic and educational levels are the most important ,4. The lCurrently, there are no tests that reliably detect GBC early enough to be useful as screening tools ,7. Due tA European\u2013Latin American research consortium towards eradication of preventable GBC\u2013EULAT Eradicate GBC\u2014has been established with funding from the European Union\u2019s Horizon 2020 programme to identify factors related to the development of GBC, to find biomarkers in blood, saliva, urine, and faeces that allow individual risk prediction and early diagnosis of the disease, and to facilitate the development of better primary, secondary, and tertiary prevention strategies . The conThe stated goals of the EULAT Eradicate GBC project can only be achieved through collaboration between European and Latin American researchers, clinicians, governmental authorities, and representatives of cancer-patient societies. We plan to leverage samples and data from European cohorts and registries, and collect and analyze data and samples from 15,000 Latin American participants to build a unique European\u2013Latin American GBC biorepository complemented by a customized IT platform applying a translational and multidisciplinary approach. It is challenging to collect high-quality socio-demographic, clinical, lifestyle, dietary, and sample-related information for this large number of study participants, mainly from low-income regions in four South American countries, which led us to develop a customized computer application to support not only the data-collection process but also the monitoring of local recruitment rates and data quality. The application for electronic data collection in the EULAT Eradicate GBC project (EULAT eCollect for short) was designed to facilitate the work of study nurses by, for example, displaying different questions depending on the characteristics of patients and samples, reduce the time invested by study participants in the interview, which is particularly important for patients in poor health, limit the use of paper and ink, and minimize costs and errors associated with the written completion of forms and subsequent digitisation by medical documentalists. Important requirements for EULAT eCollect were the ability to collect and store data without a stable internet connection, and the secure transfer of data to the storage server when the internet is available.This article describes the process of designing and developing the application EULAT eCollect to facilitate the collection, storage and future analysis of high-quality information from patients and their families. EULAT eCollect consists of four separate modules: Socio-Demographic Interview, Sample Information, Case Report Form, and Food-Frequency Questionnaire. We first present the specification of the functional and non-functional requirements, then the design of the application architecture, and conclude the manuscript with a description of the four implemented modules and the usefulness of EULAT eCollect to monitor recruitment rates and data quality.The process of designing and developing an information technology (IT) infrastructure for electronic data collection was based on typical software engineering methodology . The defEULAT eCollect was designed to support patient-data collection by incorporating the functional and non-functional requirements needed to make it easy and secure for the recruiting personnel. Study participants are interviewed by trained nurses before surgical gallbladder removal at the participating hospitals, or in the participant\u2019s home . After the complete process of informed consent, which includes a detailed description of study objectives and participant rights, clarification of any questions or concerns the potential participant may have, and signing of the consent form, recruitment personnel apply a socio-demographic questionnaire. Interviews are always conducted in a private room to protect data confidentiality.The specification of functional requirements see includedThe non-functional requirements refer to technical aspects of the web application, such as usability, information security, access to and quality of the internet, and the hardware performance . RegardiThe project contemplates collecting, storing, and analysing sensitive information to reach the project\u2019s objectives, which implies a significant challenge of keeping confidentiality and protecting participants\u2019 data. The information collected to improve the prevention and early diagnosis of GBC in Latin America contains sensitive data. Part of the data collected is considered clinical information, and the legislation of the participating countries mandates that this type of information is stored, processed, and used appropriately . AccordiThe application EULAT eCollect for electronic retrieval of patient and sample information was developed and is currently being applied to guarantee standardized data collection at all project recruitment sites. The following complementary activities were also carried out to ensure the establishment of a harmonized project biorepository: development and application of technical operational guidelines, training of recruitment staff in biobanking and biorepository procedures, establishment of a data and sample quality assurance programme, and development and establishment of automated quality control and standardized data-management procedures.EULAT eCollect was organised into four separate modules, taking into account that the ultimate objective of the EULAT Eradicate GBC project is to identify major modifiable dietary and lifestyle risk factors , body size/shape measurements, and reproductive and hormonal factors, and to evaluate possible differences by gender and ethnicity. In a first step, the association between dietary and lifestyle characteristics and GBC risk will be assessed using multiple conditional logistic regression models. Biologically plausible effect-modifiers will then be considered by investigating potential interactions between biomarkers and dietary/lifestyle risk factors. With these goals in mind, the following application modules were considered:Module 1: Socio-Demographic Interview. The development of this module combined our own experience from previous GBC research [research with theresearch .Module 2: Sample Information. The aim of this module was to facilitate the collection of relevant information on different types of samples . The type of samples collected depends on the type of study participant, and our application simplifies the work of staff processing study samples by asking for participant-specific information. The data collected includes transport, processing, and storage conditions, which greatly facilitates the automatic generation of pre-analytical sample quality indicators.Module 3: Case Report Form. This module was developed to collect clinical patient information, the characteristics of resected gallbladder specimens, and treatment information. We tried to incorporate the research interests of all collaborating clinicians, and also took into account the latest guidelines for pathology reporting [eporting .Module 4: Food-Frequency Questionnaire. This module was based on a validation study of a self-administered food-frequency questionnaire for Argentina, Chile, and Uruguay [ Uruguay .The four modules were implemented using the free and open-source software ODK . The widAfter creating an application prototype, EULAT eCollect modules were validated with the help of an R script developed for this purpose, which was used to calculate quantitative and qualitative indicators for the data collected. In June 2021, we analyzed a pilot dataset using both the R script and manually calculated indicators. The few discrepancies were identified and corrected, leading to the final version of EULAT eCollect, which is now fully operational and has been used for almost a year to recruit gallstone and GBC patients in Argentina, Bolivia, Chile, and Peru, with a positive experience so far. A bioinformatics engineer (J.G.D.) was responsible for the technical deployment with the active support of the head of the Biomedical Informatics Laboratory at the Universidad de Talca (S.G.M.). The project coordinator (J.L.B.) and the project manager in Latin America (C.B.P.) were in charge of formulating and verifying the application requirements, with excellent support from the Biobank of the Universidad de Chile during the validation phase. The entire team spent six months creating the application prototype and another two months making the necessary modifications during the validation phase.A fundamental input for the design of EULAT eCollect was the requirements identified and listed in After defining the functional and non-functional requirements for EULAT eCollect, we started its design and implementation. The application was developed under a model\u2013view\u2013controller architecture to separate the views of the data model and the business logic . Figure EULAT Eradicate GBC data can also be collected via a web browser on a desktop or mobile device and to guarantee consistency with the Chilean National Health Surveys. Standard answers were formulated to avoid typing errors and mandatory fields were defined to limit the amount of missing information.After the informed consent, recruitment personnel enter their authentication credentials and select the type of participant. The application EULAT eCollect displays specific questions for four types of participants: (1) cholelithiasis patient, (2) GBC patient recruited before any treatment , (3) GBC patient recruited after treatment, and (4) first-degree relative of a GBC patient (proband) in a family with multiple members affected by GBC.The patient interview is structured into eight to nine sections: (I) basic information, e.g., participant code, recruiter identifier, and type of participant, (II) demographic information, (III) socioeconomic information, (IV) lifestyle factors, (V) individual health history, (VI) family health history, (VII) body measurements, (VIII) physical activity, and (IX) gynaecological information (for women only). In Bolivia and Peru, an additional item on coca-leaf use was included in the interview. Visual aids are used when conducting the interview, especially for questions on lifestyle and physical activity , to stanAfter biospecimen collection, samples are processed, aliquoted, and stored in compliance with all relevant ethical and legal regulations for biomedical research, and to the standardized operating procedures of the EULAT Eradicate GBC research project. The second module of the EULAT eCollect application facilitates the electronic retrieval of sample information from the donation of blood, urine, faeces, and saliva, through transport to the laboratory, to sample processing and storage, enabling the automatic creation of customized sample inventories for shipment, receipt, and further processing, including pre-analytical quality indicators for the different types of stored samples . Recruitment staff collect different biospecimens depending on the type of participant. For example, only saliva is collected from GBC patients who have been cholecystectomised or started chemotherapy. In contrast, cholelithiasis patients donate blood, urine, and faeces before cholecystectomy. After authentication, the staff responsible for sample processing and storage, which may be different from the staff who collected the samples, selects the type of sample in EULAT eCollect, which then displays specific questions depending on the type of sample and previous answers . For exaThis module of the application facilitates the collection of clinical patient and anatomical\u2013pathological gallbladder information, taking into account the research interests of participating clinical partners , particularly in view of future studies on early diagnosis, predictive and prognostic biomarkers, and personalised treatment. To illustrate, information collected on GBC patients includes method of diagnosis, tumor stage, lymph node involvement, presence and location of metastases, histological type of the tumor, and comorbidities, as well as information on surgical procedures and treatment . Central to the design and implementation of this module were the latest guidelines for pathology reporting . The casThe fourth module of EULAT eCollect enables the electronic application of a food-frequency questionnaire validateAn important feature of EULAT eCollect is its usefulness for real-time tracking of patient recruitment in each recruitment site of the EULAT Eradicate GBC project using qualitative and quantitative indicators. Briefly, the forms sent by recruitment personnel to the project\u2019s secure server are processed using R scripts to generate 19 indicators on the number of patients recruited, and on the quality of collected samples and socio-demographic, clinical, and dietary information.Quantitative indicators include the cumulative number of forms collected; stratified by form type ; the number of patients with all forms completed, as pathology reports required to complete case report forms are usually available 3\u20134 weeks after cholecystectomy; the distribution of participants according to participant type at interview , the total number of recruited participants per month; the distribution of participants according to type/s of donated samples ; and the distribution of patients according to anatomy reports . In addition to reports in tabular format , R scripts also generate useful figures that facilitate comparison of the recruitment progress between recruitment sites .Qualitative indicators include the proportion of patients with all forms completed, the proportion of incomplete, non-compulsory fields in the four modules of EULAT eCollect , and the proportion of samples showing deviations from the sample processing protocol. Thresholds were defined and validated for specific indicators and indicators are highlighted in the monitoring reports when thresholds are exceeded.Research on GBC has been largely neglected, as this aggressive disease is relatively rare in most high-income countries. Several South American regions including northeaster Argentina, Bolivia, Chile, and southern Peru, have a high GBC incidence ,4,5. InhDefining functional and non-functional requirements was the first step in designing the application EULAT eCollect. Functional requirements included minimizing interview time, especially for frail study participants, avoiding errors when creating the sample inventory using barcode readers or mobile phone cameras, taking into account the latest pathology guidelines and applying previously validated food-frequency questionnaires. Non-functional requirements comprised the ability to collect data without internet connection and the secure transfer of data, which takes place via HTTPS protocols. Digest authentication with an encrypted form of the password stored on the server is used to secure username and password authentication.EULAT eCollect enables electronic data collection for the EULAT Eradicate GBC project via mobile devices . Once the application is installed, staff recruiting study participants and processing samples can download, fill in, and send the four forms developed for the project. The first module of EULAT eCollect facilitates the recording of the main established and potential GBC risk factors in accordance with the Chilean National Health Surveys. The second module of the application facilitates the electronic retrieval of sample information from biospecimen donation to sample storage, enabling the automatic generation of sample inventories that include pre-analytical quality indicators. A practical feature of the third module of EULAT eCollect is the ability to upload images and PDF files of blood tests and pathology reports for case report forms. Finally, the Food-Frequency Questionnaire embedded in EULAT eCollect allows for efficient collection of comprehensive nutritional information. An important activity in the EULAT Eradicate GBC project is the monitoring of patient recruitment, which is greatly facilitated by the automatic generation of quantitative and qualitative indicators through the EULAT eCollect application.The free and open-source ODK software was chosen for the implementation of EULAT eCollect. ODK provides convenient tools for developing a data-collection system with an integrated database . The fleThe collection, storage and analysis of sensitive information to reach the objectives of the EULAT Eradicate GBC project is a major challenge\u2014confidentiality must be maintained, participants\u2019 data must be protected, and the participating countries have different legislation for the use of sensitive patient data. Therefore, we have paid special attention to information security in the development of EULAT eCollect. The four application modules were built in such a way that the identity of the patients remains anonymous\u2014components of data records that would allow participant identification are replaced by pseudonyms on-site, and only treating physicians know patient identity. In addition, data are transferred via HTTPS protocols for which a key and certificate are generated based on regulatory requirements, firewalls restrict access to the servers where data are stored, and administrative access is limited to the management of the institution\u2019s intranet.The EU-funded project EULAT Eradicate GBC is collecting high-quality data and samples from 15,000 study participants to identify geographic, environmental, lifestyle, ethnic, and molecular differences in GBC risk and prognosis, and to translate the results into optimised GBC-prevention programmes considering the specificities of national health systems. The collection of high-quality information for this large number of participants in low- and middle-income regions is challenging and motivated the design and development of a customized computer application, EULAT eCollect, which we describe in this article.EULAT eCollect can be easily adapted or used directly for electronic data collection in similarly oriented research projects, and we explicitly offer our support in this direction. For example, current and future research projects on the prevention of gastric, colorectal, and biliary malignancies in Latin America could benefit from our experience in designing and implementing the application. Modules 1, 2, and 3 will probably require some modification to take into account established and potential risk factors for the disease under investigation, the type of samples and aliquots collected in the project, and clinical characteristics according to generally accepted guidelines, but Module 4 could be used directly after clarification of data storage. We also offer to share, interested researchers, our list of quantitative and qualitative indicators for monitoring of the participant recruitment."} +{"text": "The skeletal system is generated and maintained by its progenitors, skeletal stem cells (SSCs), across the duration of life. Gradual changes associated with aging result in significant differences in functionality of SSCs. Declines in bone and cartilage production, increase of bone marrow adipose tissue, compositional changes of cellular microenvironments, and subsequent deterioration of external and internal structures culminate in the aged and weakened skeleton. The features and mechanisms of skeletal aging, and of its stem and progenitor cells in particular, are topics of recent investigation. The discovery of functionally homogeneous SSC populations with a defined cell surface phenotype has allowed for closer inspection of aging in terms of its effects on transcriptional regulation, cell function, and identity. Here, we review the aspects of SSC aging on both micro- and macroscopic levels. Up-to-date knowledge of SSC biology and aging is presented, and directions for future research and potential therapies are discussed. The realm of SSC-mediated bone aging remains an important component of global health and a necessary facet in our understanding of human aging. A remarkable proportion of healthcare costs are attributed to skeletal disease . In 1990Fundamentally, the vertebrate skeleton is a remarkably dynamic and complicated organ. Throughout life, nearly every bone in the body continually deconstructs and regenerates itself in order to maintain structural and mechanical integrity . This hiThroughout life, adult stem cells are responsible for replenishing and restoring tissues of the body. Evidently the natural process of aging diminishes the capability of adult stem cells to maintain these systems in a youthful and resilient state. In the skeletal system, aging corresponds to a decline in the regenerative and restorative potential of its progenitor cell population, and through replicative exhaustion, chromatin remodeling, and changes to the intra- and extracellular transcriptional landscape, the skeleton becomes less capable of maintaining its dynamic stability .The foundation for skeletal integrity lies in the cellular progenitors of the skeletal system supplying bone tissue with its building blocks of mature cell types. Significant effort has been made in identifying the bona fide progenitors of bone- and cartilage-forming cells, and indeed much debate remains over the precise cellular identity and definition of such progenitors ,10. A loOnly within the past decade have advances in lineage tracing and cell sorting using multiple surface markers revealed more functionally homogeneous populations of self-renewing, lineage-restricted progenitors of bone, cartilage, and stromal cells that have the unique capacity to effectively reconstitute the skeletal niche in-vivo \u201321. ThesIn search of the transcriptomic identity of SSCs, the apparent features of aging in the skeletal system reveal itself . In agedIn many regards, biological aging itself is a process that is poorly understood. Theories on the causes of aging point towards genomic instability and progressively deleterious epigenetic modifications that produces an aged, unstable cellular phenotype . EvidencThe mechanisms of aging in SSCs remain less clear but are under current investigation, with focus on relating the functional differences between young and aged cells. A summary of gene pathways altered in aged cells and their effect on SSCs and skeletal tissues is provided in Within the skeletal niche, hematopoietic stem cells (HSCs) reside alongside skeletal cell types and share an age-related decline in lineage diversity potential . A hallmLastly, evidence of age-related differences of SSCs in the histone deacetylation protein Sirtuin1 suggests a mechanism for epigenetic control of SSC differentiation . In thisCurrent approaches to treating age-related decline in bone and cartilage health rely almost exclusively on maintaining the balance of bone resorption and production by targeting osteoclast and osteoblast activity . TreatmeDirected application of stem cell therapies in humans remains largely under investigation, but provides an enticing avenue for minimally disruptive, highly regenerative treatment . StudiesAccumulation of senescent SSCs may play a role in age-related skeletal regeneration deficiencies, and indeed in-vivo studies in mice have demonstrated a reversal of age-related bone loss by eliminating senescent cells . RemodelIn general, our understanding of aging among organisms remains elusive. While the role of aging in nature is not clearly delineated, evidence of unusually long lifespans in the animal kingdom, the longest of potentially 300 or more years belonging to the Greenland shark, suggests the potential for expansion of the human lifespan, and the potential to reverse or elongate youthful features of human tissues through targeting of stem cells ,66. MuchIndeed, the loom of aging evades no known animal. Regardless, the prospect of delaying or reversing the effects of aging serves as motivation to understand the systems that generate our bodies. Much progress has been made in recent years to reveal the process by which the skeleton is generated and maintained. The discovery of functionally homogeneous SSC populations identified by a combination of surface markers has therefore unveiled the potential for directed and reliable studies into the nature of the progenitor cells of the skeletal system. Moreover, the complexities of skeletal aging can more readily be elucidated by studying the changes in cellular function and expression profile across age groups. Several studies have already identified key features of SSC aging and its components, but more work is needed to better clarify cellular mechanisms that, in aggregate, generate an aged and dysfunctional skeletal niche, and subsequently an aged and dysfunctional skeletal system."} +{"text": "Historically, the science of Psychology and the practice of psychological assessment in Africa have been influenced by Western ideologies and practices , Frontiers or do not support faculty with the APC. That researchers are often restricted by lack of funding to publish their work in high impact outlets like Frontiers is highly problematic and undermines our collective efforts in overcoming some of the limitations in hegemonic psychological theory, research, and praxis.To diversify the pool of potential contributors, we invited as many Africa-based and Africa-focused researchers and practitioners as possible through the use of: (1) the professional networks of the guest editors; (2) websites of African departments; (3) Africa-based and Africa-focused journals, books, and book chapters; and (4) invitations to individuals whose previous work appeared consistent with the goals of this RT. We invited a total of 269 prospective contributors, out of which 212 were unresponsive, 23 declined our invitation, 20 withdrew, and 14 confirmed their participation. We accepted 15 abstracts and expected additional 2 manuscripts from researchers who requested permission to submit after the deadline for receiving abstracts had elapsed. Of the 17 expected submissions, we received 12 full manuscripts. We accepted seven of these for publication. Unfortunately, the response to this RT was negatively affected by the Article Processing Cost (APC), given that many African universities do not have institutional agreements with van der Merwe et al.), a perspective , development of ethical guidelines for online mental health screening tools (Hassem and Laher), an evaluation of an adaptation to a self-directed format of the Grade 9 Career Guidance Project , and application of approaches to construct validity .The seven (7) papers accepted for publication in this RT were mostly authored by South African and Ghanaian researchers. More recently, Serpell et al. reportedvan der Merwe et al. and van Vuuren et al. provide guidance on how to approach the process of contextualizing assessment tools as well as the factors that influence the assessment process in the African context. For instance, van der Merwe et al identified contextual factors, the school learners' test-taking skills/familiarity and prior learning, and the school learners' cognitive abilities that affect the applicability of the test instrument when imported into other settings. Similarly, van Vuuren et al. raised the concerns of culture and language in the development of psychological tests, highlighting the challenges associated with test adaptation and translation and offered some guidance on how to navigate cultural and language issues in the development, adaptation, and translation of tools assessing intelligence and similar constructs.Together, the work by Hassem and Laher and van Schalkwyk et al. provided guidance on how to contextualize intervention programme or guidelines in the South African context. In this regard, Hassam and Laher presented guidance to researchers on the practical steps required to either contextualize an existing ethical guideline or develop new ones using a two-phase in-depth interview with mental health experts. On the other hand, van Schalkwyk et al. provided evidence via a mixed-methods design to evaluate teachers' support for the use of a self-directed manualised booklet to assist Grade 9 learners to explore their career interests and their knowledge of self. The reliance on teachers' evaluative feedback serves as key approach to assessing implementability of similar programmes. In particular, the assessment of relevance, appropriateness of methods of adaptation, and suggestions for improvements are important standards for evaluating any ethical guidelines.Further, Anum; Khumalo et al.; Tadi et al.) sought to provide evidence of construct validity using different approaches. Tadi et al. employed the theory-consistent group differences approach and LCA to investigate the validity of the dual-continua model among young adults from Ghana, Kenya, Mozambique, and South Africa who completed the Mental Health Continuum\u2014Short Form (MHC-SF) and PHQ-9. Both studies are exemplary as they utilized CFA , LCA, large sample sizes, and cross-national samples to enhance the validity evidence they produced. Finally, Anum employed appropriate developmental changes and theory-consistent group differences approaches to investigate the relative impact of age and socio-economic status (SES) on fluid and crystallized intelligence. He showcased that the type of school attended (private or public) can reasonably be used as a proxy for SES among young children and offered practical steps on the use of appropriate developmental changes approach to construct validity.The last set of studies (Gregory, to examiWe hope that this RT will inspire Africa-based researchers and practitioners to become more conscious of the need to adapt or generate context-responsive assessment tools, show preference for validated versions of tools, and contribute to culturally appropriate guidelines and testing practices in Africa and the Global South.SO developed the first draft. RA, GH, JK, and SO edited and improved it until a final version was agreed upon. All authors contributed to the article and approved the submitted version."} +{"text": "Differentiated thyroid carcinoma (DTC) is on the rise worldwide and ranks first among endocrine cancers . The surMajor efforts have been made to reduce the surgical burden in low-risk tumours and in diagnostic procedures. Other surgical contraventions, such as the role of central neck dissection, especially prophylactically, has been questioned given its risk-benefit ratio; the role of active survival in low-risk DTC; non-surgical interventions such as radiofrequency and thermal ablations are among the studies included in these current Research Topics. Other aspects relate to the use of technology to minimise potential complications and adverse outcomes of thyroid surgery - use of intraoperative nerve monitoring to reduce recurrent laryngeal nerve injury, remote surgical approaches that avoid visible neck scars, and more.After completion of primary treatment, patients with DTC can usually remain healthy and return to their former lives , 4. HoweIn addition to objective factors that have an obvious impact on quality of life, such as postoperative complications, recurrence, etc., subjective quality of life, i.e. patient-centred factors in treatment options for DTC, has become an important topic in recent clinical trials \u20134. This Factors influencing the quality of life of DTC patients include physical and psychological symptoms, self-efficacy and social support , 3. ClosThe more severe the symptoms in DTC patients, the greater the psychological distress, the lower the physical and social functioning and the poorer the overall quality of life . Social The concept of quality of life is currently gaining importance in the evaluation of treatment procedures . When coPhysicians should discuss the expected outcomes after thyroid surgery with patients in order to increase patient satisfaction and quality of life through detailed information.AK, OC and GD: writing and revising the manuscript. All authors contributed to the article and approved the submitted version."} +{"text": "RNA-Seq and mass spectrometry-based studies generate omics data tables with measurements for tens of thousands of genes across all samples in a study. The success of a study relies on the quality of these data tables, which is determined by both experimental data generation and computational methods used to process raw experimental data into quantitative data tables. We present OmicsEV, an R package for the quality evaluation of omics data tables. For each data table, OmicsEV uses a series of methods to evaluate data depth, data normalization, batch effect, biological signal, platform reproducibility and multi-omics concordance, producing comprehensive visual and quantitative evaluation results that help assess the data quality of individual data tables and facilitate the identification of the optimal data processing method and parameters for the omics study under investigation.https://github.com/bzhanglab/OmicsEV, and the source code is released under the GPL-3 license.The source code and the user manual of OmicsEV are available at RNA-Seq and mass spectrometry (MS)-based proteomics provide global measurements of the abundance of genes and their protein products in samples of interest. These measurements are usually stored in quantitative data tables for downstream analysis. The success of an omics study is largely determined by the quality of these tables, which in turn depends on the quality of both experimental data generation and computational methods used to process raw experimental data into quantitative data tables. Omics data processing involves multiple steps, and many algorithms, software, and workflows have been developed for these essential tasks.Optimal selection of tools, algorithms and parameters is critical to ensure reliable and accurate estimation of gene or protein quantification , by grant CPRIT [RR160027] from the Cancer Prevention & Research Institutes of Texas, by funding from the McNair Medical Institute at The Robert and Janice McNair Foundation. B.Z. is a CPRIT Scholar in Cancer Research and a McNair scholar.Conflict of Interest: none declared."} +{"text": "Observational outcomes of recent studies indicate the notion of the gut microbiota's contribution to the host's physiological, immune, neurological, and metabolic health. In dysbiotic conditions, gut microbes could contribute to the development of a wide spectrum of diseases including metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) , 2. HoweIn this regard, the special issue of \u201cGut Microbiota and Gastrointestinal Disorders\u201d appeared highly topical, wherein the aim was to provide novel insights on the central role of the gut microbiota in gastrointestinal disorders and seek innovative therapeutic and predictive applications of selected microbial species.Hu et al. reviewed the genetic, immunological, and microbial risk factors for UC pathogenesis. They enumerated potential microbiome-based approaches to restore and preserve intestinal microbial homeostasis and subsequently resolve UC. In another review, Wang et al. focused on gastrointestinal microbial dysbiosis and its contribution to the development of NAFLD, ranging from steatosis to non-alcoholic steatohepatitis (NASH). In this study, the special association of periodontopathic bacteria, mainly Porphyromonas gingivalis, to the pathogenesis of NAFLD was highlighted through clinical and basic research.Considering the profound influence of the gut microbiota on the development and progression of ulcerative colitis (UC), Tavakoli et al. during the treatment procedure of IBD patients. Observational findings suggested a substantial decrease in microbial diversity of Crohn's disease (CD) patients compared to UC patients. This, in principle, leads to the interdependence of treatment strategy and microbial dynamic comparing CD and UC patients. Although most studies associating the gut microbiota with human health and disease have focused on the analysis of bacterial and archaeal components, the importance of the mycobiota, the microbiota's fungal portion, is now recognized. The analysis of the mucosa-associated mycobiota in CD patients by Olaisen et al. revealed the enrichment of Malassezia and the depletion of Saccharomyces, along with a higher proportion of Candida albicans and Malassezia restricta, compared to healthy controls. Notably, the mycobiota structural differences between the inflamed and proximal non-inflamed ileum within the same individual may contribute to CD pathogenesis. Moreover, the identification of intraindividual and interindividual differences in microbial composition can be utilized as predictive biomarkers. Tian et al. exhibited the abundance of Alistipes and Eubacterium and the impoverishment of Roseburia species in patients suffering from slow transit constipation. The enrichment of fatty acid biosynthesis, butanoate metabolism, and methane metabolism pathways along with microbial alteration might be potential biomarkers for slow transit constipation. Another predicting strategy was provided by Vincentis et al., evaluating the clinical improvement of patients receiving rifaximin therapy. Although inaccurate in predicting gut microbiota alterations, their electronic multi-sensorial systems constituted of e-tongue and e-nose, could effectively predict clinical improvement.The significance of microbial species in the progression and emission of gastrointestinal disorders has led to the evaluation of longitudinal bio-psychological dynamics by Nakajima et al. in C57BL/6 male mice. Nicotine administration prior to the induction of DSS-induced colitis elevated indole concentration in the distal colon and rectum while short-chain fatty acid (SCFA) values presented insignificant differences, compared to the control cohort. The high level of indole concentration, as well as the increased proportion of Clostridioides and Porphyromonas genera, were presented as the underpinning mechanism of DSS-induced colitis suppression following nicotine administration. Similarly, Zhou et al. reported the potential for a ginger extract to attenuate the susceptibility to DSS-induced colitis by preventing weight loss, colon shortening, inflammation, and intestinal barrier dysfunction. Ginger administration to mice models for 4 weeks following antibiotic exposure increased bacterial diversity and the relative abundance of Helicobacter species while decreasing the relative abundance of Peptococcaceae rc4-4.In the context of IBD research, a treatment strategy for dextran sodium sulfate (DSS)-induced colitis was evaluated by Ishikawa et al. for UC patients following triple-antibiotic therapy. This study protocol presented a double-blinded, randomized, placebo-controlled, parallel assignment trial that primarily should evaluate the Total Mayo Score at 8 weeks after the FMT procedure. Furthermore, the comparison of clinical features, microbial structure, and metabolic profile, as well as post-FMT 2-year follow-up constitute other endpoints of this study protocol.Another therapeutic approach for restoring the inherent microbial composition is fecal microbiota transplantation (FMT), which was proposed by Yang et al. assessed the efficacy and safety of FMT combined with biofeedback for mixed constipation. They reported insignificant differences in side effects, yet the combined therapy presented a substantial enrichment in the proportion of probiotic species namely Prevotella and Bifidobacterium. Considering FMT as a stopgap, yet effective and safe, microbiome-based therapeutic strategy for the remission of gut dysbiosis and gastrointestinal disorders, Savigamin et al. presented four primary steps for initiating FMT in developing countries including: 1. Finding a perfect stool donor; 2. Initiating a clinical trial; 3. Establishing a stool standard for use in other research trials; 4. Establishing a clinical center for the transplantation of fecal microbiota. They further discussed and provided insightful suggestions for the first two steps.In conclusion, the studies published in this Research Topic further shed light on the critical contribution of the gut microbiota in the pathogenesis of gastrointestinal disorders and its potential capacity in developing efficient biomarkers and therapeutic strategies. In this field of study, the knowledge gaps to be filled and the bottlenecks to be surpassed include deciphering the contribution of hundreds of as-yet-unknown metabolites and their related signaling pathways to the host's physiological and metabolic health and disease.AN-R wrote the first draft of the manuscript. AY, JO-R, TO, and Y-DW revised the manuscript. All authors read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The COVID-19 pandemic has substantially affected global communities and health systems in both high- and low-income countries. Many nations have been experiencing very high population burdens that implies the importance of strengthening responses systems and mobilizing communities in pandemic preparedness and control. The shortage of resources in LMICs is well-documented prior to COVID-19 and it has been worsened with the surge of COVID-19. In many LMICs, testing capacity remains inadequate, the number of ICU beds is far less than required, access to drug treatments such as dexamethasone is limited, and the supply of therapeutic oxygen and ventilators is insufficient . ImportaZhang studied the experience of public health system construction in China's COVID-19 prevention and identified key lessons for other countries to confront unprecedented pandemic. The paper not only pointed out several advantages of China's public health system construction in response to COVID-19, such as adequate supply of health resources and improved affordability of health care, but also discussed China's deficiencies, including low utilization efficiency of health resources, unequal ability to pay for medical expenses, and late disclosure of virus information in the early stage of the outbreak of COVID-19. Given that Nepal is facing a flood of COVID-19 cases after the lockdown was lifted in July 2020, Rayamajhee et al. provided critical insights on response of the government, highlighting the need to increase testing, tracing, and isolation capacity, and to set up quality quarantine centers throughout the nation to address the rise in COVID-19 infection cases. As cases have continued to fluctuate over a year into the pandemic in Indonesia, Mahendradhata et al. reviewed the current capacity of the healthcare system to respond to COVID-19 and emphasized the need for the Indonesian Government to ramp up the country's healthcare capacity in order to absorb and accommodate the varying healthcare demands during the pandemic. Saha and Gulshan provided a systematic analysis of the overall patterns in terms of number of cases, number of deaths, and impacts of COVID-19 in Bangladesh. The authors also shed light on the underlying causes that resulted in a continuous outbreak while discussing possible measures, effectiveness of the preparedness, implementation gaps, and their consequences to gather vital information and prevent future pandemics. Abd El Ghaffar et al. investigated the situation in some of the COVID-19 screening hospitals in Egypt in terms of inpatient beds, ICU beds, and ventilator utilization rates. Results from this paper, which indicated a shortage of resources, would help policymakers make informed resource reallocation decisions in Egypt, or other developing countries, which suffered from a lack of resources and a weak health system prior to the pandemic. Coumare et al. discussed the challenges and experiences in preparation and responses to the ongoing COVID-19 pandemic at a tertiary teaching hospital situated at Puducherry, India. Tran et al. examined factors associated with the intention to participate in COVID-19 frontline prevention activities among Vietnamese nursing students. The finding suggested that socioeconomic characteristics of participants, their source of COVID-19 related knowledge, and their perception and attitude toward participating in COVID-19 frontline activities were associated with intention to participate. Given resource-scarce settings of most LMICs, these countries are challenged by their limited capacity for manufacturing test kits, limited budgets for equipment and reagents, and scant ability to make competitive bids for global supplies. Gyawali and Mohammad Al-Amin et al. advocated for recognition of the almost insurmountable obstacles that face the implementation of non-pharmaceutical interventions for COVID-19 management in Asian LMICs and called for a global commitment to the equitable distribution of therapeutants and vaccines. Although the World Bank is making available more than $160 billion funding to LMICs to purchase and distribute COVID-19 vaccines, tests and treatment and mitigate the health, economic, and social shocks, and philanthropic organizations such as the Global Alliance for Vaccines (GAVI) have received billions of dollars in donations, much more will be required for LMICs to combat COVID-19 and mitigate the expected economic downturn. In the long term, LMICs will need to develop their own capacity to manufacture and distribute vaccines, as well as strengthen primary health centers to manage the impact of the pandemic.The following studies summarized experience of LMICs in managing the surge of COVID-19 in terms of capacities and responsiveness of health systems and communities. Muhammad Nur Amir et al.. described the workforce mobilization from the National Institutes of Health (NIH) to the other public healthcare facilities within the Ministry of Health (MOH) in the early phases of the COVID-19 pandemic management in Malaysia. The paper demonstrated how this workforce mobilization team efficiently mobilize the healthcare workforce and fulfill requests received for human resource aid, resulting in reduced infected COVID-19 cases throughout the country. Nguyen D. N. et al. provided evidence for reforming the training programs to prepare medical students, a potential task force with the capability to support the stretched health sector, for COVID-19 responses in Vietnam. This study suggested that the training curriculum should include both theoretical approaches as well as other contextual approaches to achieve efficient epidemic control in specific regions. Le et al. illustrated the potential and feasibility of intersectoral collaboration in epidemic preparedness and response at grassroots levels in the threat of COVID-19 pandemic in Vietnam, which ensures sufficient resources for urgent cases and helps to inform a determined response framework.In addition to capacities and responsiveness of health systems and communities to respond to the pandemic, numerous studies have highlighted the importance of strategic planning and resource mobilization to maintain essential health services and maximize human resource capacity to address COVID-19 situation and its associated disruptions. Shewade et al. reported that the estimated COVID-19 deaths in India after adjusting for the coverage and quality of the routine death surveillance may be 5.5\u201311 times the reported COVID-19 deaths. Hence, this study further discussed the routine deaths surveillance in India, the rationale for adjusting the reported COVID-19 deaths for coverage of the routine death surveillance and its implications on the estimated infection fatality ratio (IFR) for India in order to make meaningful and reliable comparisons. Mansab et al. highlighted the disparity in oxygen provision for COVID-19 patients between 26 nations included in the study and suggested that there was an association with higher national mortality rates in those nations that pursued a conservative oxygen strategy. Abbasi-Kangevari et al. sought to determine the priorities of the Iranian public toward the fair allocation of ventilators during the COVID-19 pandemic. Participants stated that socioeconomic factors, except for age > 80, should not be involved in prioritizing mechanical ventilators at the time of resources scarcity. Front-line physicians and nurses of COVID-19 patients, pregnant mothers, mothers who had children under 2 years old had been given high priority.Given the speed and spread of transmission of COVID-19, assessing the effectiveness of epidemiological monitoring and surveillance of the epidemics is critical to control the expansion of the epidemics and avoid the collapse of health care systems. Vo et al. demonstrated how social distancing measure had been implemented in Vietnam and further discussed factors associated with the high compliance of Vietnamese with social distancing measures. Tam et al. discussed the evidence on the effectiveness, and rationale for community mass masking to prevent the COVID-19 transmission in Vietnam. Sun et al. showed that the proper management of inbound travelers from outbreak areas had a significantly positive effect on the prevention and control of the virus and suggested that effective measures taken by Yunnan province may provide an important reference for preventing the COVID-19 outbreak in other regions. As the prevalence of psychological stress among healthcare workers (HCWs) in Vietnam during the COVID-19 pandemic was high, Nguyen P. T. L. et al. sought to understand COVID-19-related, psychological stress risk factors among HCWs, their concerns and demands for mental health support during the pandemic period. The author recommended psychological interventions involving web-based consulting services to provide mental health support among HCWs. Nguyen A. N. et al. assessed the knowledge and practices regarding the prevention of the COVID-19 among the HCWs in Vietnam to identify the ways of disseminating information to maximize the safety of these essential workers. Findings from this study suggested that future education initiatives should centre initially on the COVID-19 virus aerosols with the primary focus on doctors, especially those in emergency and the intensive care departments. In addition to epidemiological and psychosocial interventions, Nguyen H. T. T. et al. described economic recovery solutions implemented by the Vietnam government to manage the fiscal deficit, such as focus on effectively implementing domestic stimulus, use the savings from falling international oil prices to curb the crisis, earn funding from the World Bank WB and the International Monetary Fund, etc.Many articles in this Topic focused on evaluating the effectiveness of epidemiological, psychosocial and economical interventions to prevent the importation, spreading and relieve the impact of COVID-19 pandemic in LMICs. Vietnam has achieved initial results in flattening the curve and slowing the spread of COVID-19 transmission in the community, which is attributable to a high-level adherence with social distancing measures, accompanied with contact tracing, mass testing, and mandatory isolation. Klement pointed out that journalism, politics, and medicine involved within the COVID-19 crisis have maintained a simple narrative and reductionist thinking and emphasized the need for systems thinking during the outbreak. A survey by Raza et al. was conducted to understand knowledge, attitudes, and practices related to COVID-19 among the students in Lahore, Pakistan. This survey showed that most of the students were well informed about COVID-19 and exhibited a proactive approach during the outbreak, suggesting an effective public health campaign of the local government to deliver public health knowledge in the community. Chatterjee et al. focused on highlighting some of the key aspects of digital healthcare during the times of COVID-19 pandemic in South America. This study shed light on the role of Artificial Intelligence and the Internet of Things role in resource optimization along their potential applications like clinical decision support systems and predictive risk modeling, especially in the direction of combating the emergent challenges due to the COVID-19 pandemic. Mat Dawi et al. examined the influence of e-government and social media on the public's attitude to adopt protective behavior and suggested that during the COVID-19 outbreak, public health decision makers may use e-government and social media platforms as effective tools to improve public engagement on protective behavior. Although Nguyen, Nguyen, Le, et al. demonstrated a high level of agreement among the general population toward the importance and necessity of national response measures to combat the COVID-19 epidemic in Vietnam, Nguyen, Nguyen, Nguyen, et al. expressed concern about the impact of fake news on the adherence of national response measures during the lockdown period in Vietnam. In response to fake news, the government had made early predictions and concrete strategies, such as passing a cybersecurity law or establishing official communication channels, which may also have important lessons for other nations in the fight against COVID-19.Several studies have raised important points regarding the impact of perceptions and attitudes toward the COVID-19 crisis on the improvement of both public health and individual well-being and highlighted how digital health care and social media may influence public's attitude during the COVID-19 outbreak. Specifically, Gyawali and Mohammad Al-Amin et al.; Mahendradhata et al.; Rayamajhee et al.; Tran et al.; Zhang). Ensuring sufficient healthcare workforce, training more health providers, and recruiting volunteers would help to increase vaccine availability, distribution, and monitoring. In addition to healthcare workforce capacity, vaccine acceptance and hesitancy remain a significant barrier to increase vaccination rate. Perceptions and attitudes play an important role on the improvement of both public health and individual well-being, which significantly influenced by Internet and social media . Thus, governments could establish awareness-building initiatives using community and mass media to manage inaccurate information about vaccines, lack of information, and lack of trust in the government and pharmaceutical companies. Lastly, governments should consider to increase budgets for COVID-19 vaccine purchase and delivery to scale up COVID-19 vaccination and offer access to all populations; however, this has not been discussed in the collection of papers in this topic.Besides efforts to mitigate pandemics in LMICs from medical staff training and monitoring to system modernization, it is also important to consider potential barriers that arise during the COVID-19 vaccine rollout in LMICs and how to address these difficulties in resource-scarce settings. Recent studies have reported several challenges for vaccination faced by LMICs, including vaccine hesitancy , inadequThe COVID-19 pandemic has challenged the healthcare capacity of many countries. The collection of papers in this topic provides insight on the opportunities and challenges in strengthening health system and community responses to confront COVID-19 pandemic in resource-scarce settings. Lessons learned in terms of strength and limitations from the latest evidence on health sectors and community responses to control the COVID-19 pandemic in LMICs would suggest implications to improve the effectiveness of current policies and facilitate development of new strategies to strengthen the capacity and efficiency of healthcare systems in the fight against COVID-19. Governments will continue to play an important role in responding to the coronavirus pandemic and providing access to care for communities in resource-constrained countries with limited human, infrastructural, and financial resources and that are behind the curve in the spread of the pandemic.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.Research was supported by the Vingroup Innovation Foundation (VINIF) in project code VINIF.2020.Covid-19.DA03. The article processing charge for journal is financed by NUS Department of Psychological Medicine (R-177-000-100-001/R-177-000-003-001/R177000702733) and NUS iHeathtech Other Operating Expenses (R-722-000-004-731).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "This study aimed to identify a set of newborn signal functions (NSFs) that can categorize health facilities and assist policymakers and health managers in appropriately planning and adequately monitoring the progress and performance of health facilities delivering newborn health care in Bangladesh and similar low-income settings.A modified Delphi method was used to identify a set of NSFs and a cross-sectional health facility assessment among the randomly selected facilities was conducted to test them in public health facilities in Bangladesh. In the modified Delphi approach, three main steps of listing, prioritizing, and testing were followed to identify the set of NSFs. Then, to finalize the set of NSFs and its variables, a total of five Delphi workshops and three rounds of Delphi surveys were conducted. Finally, 205 public health facilities located in 41 randomly selected districts were assessed for the availability and readiness of finalized NSFs using the updated tool of Bangladesh Health Facility Survey (BHFS) 2017.Twenty NSFs were identified and finalized, nine of which were categorized as primary NSFs, 13 as basic NSFs, 18 as comprehensive NSFs, and 20 as advanced NSFs. Almost all district hospitals (DHs), Upazila health complexes and maternal and child welfare centres (MCWCs) performed the primary NSFs in the last three months. However, around one-third of the union health and family welfare centres (UH&FWCs) and very few community clinics (CCs) performed them during the same period. The basic, comprehensive, and advanced NSF readiness was inadequate and inappropriate across all types of facilities, including DHs and UHCs.In the absence of internationally or nationally agreed-upon NSFs to measure a health facility's service availability and readiness for providing newborn care, this study becomes the first to identify and finalize a set of NSFs and to incorporate relevant variables in the health facility assessment tool which can be used to monitor the availability and readiness of a newborn care facility. The identified NSFs can also be adapted for the countries with similar contexts and can serve as a standard base to determine a global set of NSFs. In the last decade, commendable progress has been made in improving maternal and newborn health globally. During the Millennium Development Goals (MDG) era 1990-2015), the global neonatal mortality rate (NMR) declined from 36 19 deaths per 1000 live births; the decline in NMR 47%) has been much slower than that of the post-neonatal under-five mortality rate (58%) [990-2015,7% has beConsidering this high burden, the government of Bangladesh is highly committed to achieving the SDG targets of newborn mortality by 2030. In response to the global Every Newborn Action Plan (ENAP), it developed the Bangladesh Every Newborn Action Plan (BENAP) with specific strategies for averting newborn mortality and morbidity. Following up on these commitments, newborn health has been included as one of the priority activities in the fourth health sector program (2016-2022) of Bangladesh, while the operation plan has a separate programme called the National Newborn Health Programme and Integrated Management of Childhood Illness (NNHP&IMCI) for implementing the newborn health interventions targeting the major causes of newborn death in Bangladesh .Since most of these interventions involve specialized and facility-based treatment, a robust health infrastructure is needed to provide the necessary services ,7. ServiEmergency obstetric care (EmOC) signal functions have been used to assess the availability and quality of maternal care . The latA set of signal functions is crucial in planning policy and programs for correctly identifying health facilities that provide newborn services. Acknowledging the necessity and significance, NNHP & IMCI Program of the Directorate General of Health Services (DGHS) has designated the identification of newborn signal functions (NSFs) as a priority task for successful planning and scaling-up of newborn interventions in Bangladesh . This stThis cross-sectional study was carried out from October 2017 to February 2020. It adopted the Delphi method to seek expert consultation and built consensus for identifying the NSFs and their relevant variables as well as adapting the assessment tool. The Delphi method, mainly developed by Dalkey and Helmer at the Rand Corporation in the 1950s, is well adapted for building consensus due to its evident potential for revealing underlying assumptions and searching out new perspectives that can contribute to consensus among different respondents . The DelThree main steps of the Delphi process were followed, with each step being divided into two sub-steps, as illustrated in To identify the leading causes of neonatal mortality, relevant interventions, indicators, and possible functions (skills and resources needed to provide an intervention), a comprehensive desk review of the available literature (both written and unpublished) was undertaken. We develop a list of existing maternal, newborn, and child health strategies, action plans, monitoring frameworks, standard operating procedures (SOPs), and national and global guidelines on interventions/functions to avert major causes of newborn deaths. A group of International Centre for Diarrhoeal Disease Research, Bangladesh researchers systematically reviewed relevant five global and ten national documents from the list. Table S1 in the Besides desk review, a total of six key informant interviews (KIIs) were conducted with Ministry of Health & Family Welfare (MoHFW) program managers and newborn health experts from professional bodies such as Bangabandhu Sheikh Mujib Medical University (BSMMU) and Bangladesh Neonatal Forum (BNF) to identify additional interventions and functions needed to deliver newborn care in a health facility setting. The interviews helped to identify an additional 11 newborn interventions/functions that were added to the primary list of 79 newborn interventions/functions.The National Technical Working Committee for Newborn Health (NTWC-NBH) (established by MoHFW) formed a group of newborn expert panels with a specific Term of Reference (ToR). A total of 48 newborn experts, representing 22 organizations such as the MoHFW, professional bodies, United Nation (UN) agencies, and development partners engaged in newborn health, became part of the newborn expert panel tools: Averting Maternal Death and Disability (AMDD), Health Facility Census (HFC), Service Provision Assessment (SPA), Rapid Health Facility Assessment (R-HFA), Service Availability Mapping (SAM), and Service Availability and Readiness Assessment (SARA) . The 201The variables present in the 2017 BHFS tool (n\u2009=\u200945) and the variables present in the other HFA tools (n\u2009=\u200916) were automatically included in the final variable list. Variables identified from interviews with the newborn Delphi experts were validated before they were included in the final variable list. Project research physicians (PRPs) measured the variables\u2019 construct and content validity by field testing them in seven different public health facilities. The operational definition of these validity measures is described in the published protocol . ContentThe questionnaire adaptation for the 2017 BHFS tools took place in August 2019. A consultative meeting with the stakeholders especially from National Institute of Population Research and Training (NIPORT), visits to the service provision sites for pre-testing the tools, and a day-long questionnaire adaptation workshop elicited the feedback needed to adapt the questionnaires. Based on the feedback, the validated variables were incorporated into the BHFS 2017 tool, and finally, the tool was updated and finalized for the assessment of service availability and readiness of NSFs in Bangladesh. The updated 2017 BHFS had two types of data collection tools as facility Inventory questionnaire and the health care provider interview questionnaire.12 PRPs were recruited for the HFA who received five days of training on the updated BHFS 2017 tool in September 2019, in Dhaka.Four data collection teams were formed, with one data collector on each team assigned the role of a team leader. Data collection was conducted from November to December 2019. On average, data collection took two days for each health facility. And was conducted using paper-based Facility Inventory and Health Care Provider Interview questionnaires. The data collectors interviewed the most knowledgeable person about the facility and its services; if collected from other persons, the information was validated by direct physical observation and/or some facility record review.Two medical doctors monitored the overall data collection process and supervised the team. They conducted periodic visits to ensure the quality of data collection and provide onsite training.To assess the service availability and readiness of the public health facilities for the NSFs, a precision-based sample size was measured. With a 10% error margin, the study aimed to cover maximum variance (50%) as there is no estimate available. The required sample size was 101 public health care facilities, assuming a non-response rate of about 5%. We were able to conduct a cross-sectional facility assessment in 205 registered public health facilities across all eight divisions to provide the most representative results for Bangladesh tools .To analyse each Delphi survey outcome, central tendency (mean) and a measure of distribution (interquartile range (IQR)) were measured. Additionally, the average expert agreement (AEA) for every intervention/function was calculated from the ratio between the frequency of mode and the number of responses in each survey. As experts recommended, consensus and agreement were stable when the AEA value was 50 or more for any intervention/function. Kappa statistics with a >0.75 cut-off were used to report on the construct validity of the newly added variables in the HFA tool. The BHFS tabulation plan was followed to analyse the HFA data.Ethical approval was obtained from the Research Review and Ethical Review Committee (ERC) of icddr, b (PR-17089). Written and informed consent was sought from the health facilities and each participant before the assessment or interviews.Based on the pre-defined cut-off values and scoring guidelines recommended by the newborn Delphi experts, we identified 20 NSFs from the shortened list of 37 interventions/functions for Bangladesh. The summary of the average score for each intervention/function and the cut-off values to identify four categories of NSFs is presented in The AEA of the Delphi experts on newborns was checked based on each category of NSFs on the pre-defined cut-off values supplementation function. Almost all district hospitals (DHs), Upazila health complexes and maternal and child welfare centres (MCWCs) provided IFA supplementation in the last three months, while around one-third of union health and family welfare centres (UH&FWCs) and less than 10% of community clinics (CCs) provided IFA supplementation in the same period.One-fourth of the facilities did not perform hand washing each time before touching the baby. All DHs, MCWCs, and UHCs performed hand washing each time before touching the baby, whereas around half of the UH&FWCs and less than 10% of CCs performed hand washing each time before touching the baby.About 73% of the facilities performed immediate drying. Moreover, all DHs, MCWCs, and UHCs performed the immediate drying of the newborn, while around half of the UH&FWCs and less than 10% of CCs performed this function.About 73% of the facilities performed delayed umbilical cord clamping approximately one to three minutes after birth. All DHs, MCWCs, and UHCs performed delayed umbilical cord clamping approximately one to three minutes after birth, whereas the function was performed by around half of the UH&FWCs and less than 10% of CCs.About 72% of the facilities performed a clean cord-cutting function. Nearly all DHs, MCWCs, and UHCs performed clean cord-cutting. However, around half of the UH&FWCs and less than 10% of the CCs performed this function.About 73% of the facilities performed a single application of 7.1% chlorhexidine to the umbilical cord followed by dry cord care. All DHs, MCWCs, and UHCs performed the single application of 7.1% chlorhexidine to the umbilical cord followed by dry cord care, while only around half of the UH&FWC and less than 10% of the CCs performed this function.About 68% of the facilities performed neonatal resuscitation. All MCWCs, nearly all DHs, and about 93% of the UHCs performed this function.About 72% of the facilities performed early initiation of breastfeeding within one hour. All MCWCs and UHCs performed this function whereas 2% of DHs did not perform this function.About 73% of the facilities performed skin-to-skin care for two hours. While all DHs, MCWCs, and UHCs performed the clean cord-cutting (clean/sterile thread) function, only 53% of the UH&FWC and 10% of the CCs performed this function.Only 58% of all facilities performed tetanus toxoid function. The function was performed by over 80% of the DHs, MCWCs, and UHCs, but by less than one-third of the UH&FWCs.One-third of the total facilities performed suction of newborns. All DHs and nearly all UHCs and MCWCs performed this function, but less than 50% of the UH&FWCs performed it.Only 12% of the total facilities provided oral antibiotics for infections. Across facilities, the performance of this function was lower than 25%, and no CCs performed this function.Only 24% of the total facilities provided injectable antibiotics (intramuscular (IM)) for infections. Besides, none of the UH&FWCs and CCs performed this function.Only half of the total facilities provided antibiotics for premature rupture of the membrane (PROM). Nearly all the DHs provided antibiotics for PROM, while none of the UH&FWCs and CCs performed this function.About 60% of the total facilities provided oxygen therapy. However, only 78% of the DHs, 56% of the UHCs, and 39% of the MCWCs performed this function.Only 35% of the total facilities provided injectable antibiotics (intravenous (IV)) to the newborn. Besides only 78% of the DHs, 56% of the UHCs, and 39% of the MCWCs performed this function.Less than 30% of the total facilities provided phototherapy. Moreover, about 88% of the DHs and less than 10% of the UHCs and MCWCs performed this function.Only 28% of the total facilities provided kangaroo mother care (KMC) for pre-term and low birth weight (LBW) babies. Only 63% of the DHs, 39% of MCWCs, and less than one-third of the UHCs performed this function.Only 37% of the total facilities provided ACS for preterm birth. Only 78% of the DHs and around 50% of the MCWCs and UHCs performed this function.Only 10% of the total facilities performed incubator functions. Only half of the DHs and 2% of the UHCs performed this function, while none of the MCWCs performed this function.Overall, almost all the MCWCs, 90% of the UHCs, and 85% of the DHs performed all primary NSFs, while only 39% of the UH&FWCs and 5% of the CCs performed those in the previous three months of the assessment. Only 5% of DHs performed advanced NSFs.Using the adapted Delphi method, a clear, evidence-based, and low-cost technique combining scientific methods and expert opinion -19, thisIn identifying a set of valid and agreed-upon NSFs, this study followed all relevant steps of a Delphi study including defining consensus. A Delphi study must have a pre-defined meaning of consensus for their study, if not, the credibility of the outcomes will not be considered as valid . VariousThe utilization of RAND-modified Delphi in this study improved the validity and generalisability of the identified NSFs . The resThe identified valid NSFs can capture the service availability, readiness, and functionality of a range of relevant newborn interventions/functions at different facility levels, which can help identify the causes of the high burden in newborn mortality and the recent halt in the reduction in newborn morbidity. In this study, a total of 20 interventions were accepted and 17 were rejected, with a focus on impact, reliability, actionability, priority, and feasibility of data collection during the scoring and ranking process. A similar attempt undertaken in Zimbabwe identified 11 obstetric and newborn signal functions, three of which were for routine newborn care, six for basic emergency newborn care, and two functions for comprehensive emergency newborn care . To finaThese 20 identified NSFs can be captured as part of a health facility assessment survey or as a routine monitoring system by health managers at any health facility level. When reviewing existing HFA tools, we found that most NSFs are not collected through health facility surveys. The 2017 BHFS tool only measured the availability and readiness of one newborn indicator (newborn resuscitation) as part of Basic Emergency Obstetric Care (BEmOC) of public and private health facilities in Bangladesh, which was insufficient to accurately measure the health facility's availability and readiness to provide newborn care and to assess the status of identified NSFs. All these NSFs are not routinely collected or reported in the existing health information system. Having an agreed list of functions made it relatively easy to identify and finalize the list of variables required to measure the service availability and readiness of these functions at a health facility level. The results of the survey conducted by the updated HFA tool contributed to assessing the health facilities for the NSFs and will assist policymakers and health managers in planning and monitoring their performance and progress regarding newborn health services . The preThe HFA of this study revealed that the functionality of NSFs for neonatal infection management such as oral antibiotics, injectable antibiotics (IM), and injectable antibiotics (IV) was poor, especially in primary referral facilities. Infections such as sepsis, pneumonia, tetanus, and meningitis account for about 22% of overall newborn deaths worldwide and around one-quarter of newborn deaths in Bangladesh ,30. The This research study and its findings primarily aimed to influence national policy and programs. From the study\u2019s initiation, the NNHP & IMCI Program of the DGHS was co-leading the study activities with icddr,b . All theTen years have left to achieve the ambitious Sustainable Development Goals (SDGs) of ending preventable neonatal deaths, accelerated efforts are needed to improve access to and quality of care for all mothers and newborns -3. As moThis is the first study to identify widely agreed upon NSFs for Bangladesh by adopting the validated and widely used Delphi methodology to synthesize experts\u2019 knowledge and experiences. The MOHFW of Bangladesh, various associations, academics, and development partners have endorsed the identified NSFs. The existing health facility assessment tool has been updated to test the NSFs in public health facilities for further use. In the future, the updated health facility assessment tool will be used for the national health facility assessment in Bangladesh.This is a resource-intensive and long-time study. It took us longer than anticipated to ensure the participation of numerous Delphi experts during each workshop and survey. Some Delphi experts were unable to participate throughout the whole process.There are currently no internationally or nationally recognized signal functions that are widely accepted and can be used to measure a health facility's service availability and readiness to provide newborn care. We developed a widely agreed-upon set of NSFs that assisted in updating the national HFA tool. The findings of the survey helped to determine whether health facilities are adequately ready to provide newborn health care services. The results contributed to categorizing newborn care health facilities as primary, basic, comprehensive, and advanced. The identification of the NSFs will guide health managers and policymakers towards appropriate planning and adequately monitoring of the progress and performance of health facilities delivering newborn health care in Bangladesh."} +{"text": "Legumes and cereals, which provide different nutrients, are cultivated as coupled crops in most centers of plant domestication worldwide. However, as the only legume domesticated in China, the spatio-temporal distribution of soybeans and its status in the millet- and rice-based agricultural system of the Neolithic and Bronze Ages remains elusive. Here, archaeobotanical evidence of soybeans (n=254), millet (n=462), rice (n=482), and zooarchaeological evidence of fish (n=138) were synthesized to elucidate the phenomenon of coupled or decoupled cereals and legumes in prehistoric China. During the Neolithic and Bronze Ages, soybeans was mostly confined to northern China and rarely found in southern China, serving as a companion to millet. In contrast, fish remains have been widely found in southern China, indicating a continuous reliance on fish as a staple food besides rice. Thus, an antipodal pattern of millet-soybeans and rice-fish agricultural systems may have been established in northern and southern China since the late Yangshao period respectively. These two agricultural systems were not only complementary in terms of diet, but they also exhibited positive interactions and feedback in the coculture system. Consequently, these two systems enabled the sustainable intensification of agriculture and served as the basis for the emergence of complex societies and early states in the Yellow and Yangtze Rivers. Zea mays) in Mesoamerica was accompanied by the common bean (Phaseolus vulgaris) (Triticum aestivum) and barley (Hordeum vulgare) in southwest Asia had a series of companion legumes, including lentil (Lens culinaris), pea (Pisum sativum), chickpea (Cicer arietinum), and broadbean (Vicia faba) (Oryza sativa subsp. indica) in south Asia was associated with the mungbean (Vigna radiata) (Glycine max) seem to be merely associated with broomcorn (Panicum miliaceum) and foxtail millets in northern China, while no companion legumes to rice (Oryza sativa subsp. japonica) have been discovered in southern China.Optimal foraging theory in anthropological studies suggests that energy constraints and nutrient requirements are vital to the origin and evolution of agriculture . As essulgaris) , wheat (ia faba) , and ricradiata) . HoweverGlycine soja) in far eastern Russia, China, Korea, and Japan, a variety of regions have been proposed as candidate sources , Early Yangshao period , Late Yangshao period , Longshan period , and Bronze Age . SubsequBased on the previous investigations on the distribution of millet, rice, and mixed farming sites , the milMylopharyngodon piceus), grass carp (Ctenopharyngodon idella), and crucian carp (Carassius carassius) . Besidesephalus) .In terms of meat acquisition strategies, fishes were clearly an important component of diets in the Yangtze River throughout the Neolithic Age, whereas they seemed to be less significant in the Yellow River . A detaiIn addition to fishes, shellfishes were also regarded as an important source of protein, which was mostly confined to the coastal regions, especially the Liaodong and Shandong peninsula to the northeast and Fujian and Liangguang region to the southeast with hundreds of shell middens existed during 7000\u20135000 cal BP . HoweverGiven that soybeans and fish served as an important source of protein for ancient humans in northern and southern China, antipodal patterns of a millet-soybean and rice-fish agricultural system may have formed in the Neolithic and Bronze Ages. During the Peiligang period , only wild soybeans was discovered along the marginal mountains of the Loess Plateau and Inner Mongolian Plateau , while fDuring the Longshan period and Bronze Age , the soybeans began to spread in four directions . HoweverIn summary, antipodal patterns of a millet-soybeans agricultural system in northern China and rice-fish agricultural system in southern China may have been established since the late Yangshao period , which sustained the nutritional requirement of both starch and protein. To a certain extent, the cultivation and domestication of soybeans in the Yellow River may compensate for the possible lack of protein due to the transition from hunting wild animals to the rearing of livestock. However, the relative abundance of diverse animals and fish species in the Yangtze River may promote ancient humans to continue fishing and hunting rather than reliance on soybeans domestication , and ultIn most centers of origin of agriculture in the world, legumes and cereals have been cultivated as coupled crops except for southern China. Soybeans, generally considered to be domesticated in the middle and lower Yellow River, was mostly confined to northern China and served as a companion to millets. In contrast, fish had been intensively exploited in southern China and rarely recovered from the Yellow River. Thus, since the late Yangshao period , an antipodal pattern of millet-soybeans and rice-fish agricultural systems may have been established in northern and southern China, respectively. On one hand, these two systems are dietary complementation of starch and protein, providing balanced requirements of energy and nutrient; on the other hand, the systems exhibit agronomic compensation that soybeans fix atmospheric nitrogen and improves the soil fertility while millet uses soil nitrogen up, and fish reduce rice pests and rice favors fish by moderating the water environment. Positive interactions in these two systems enabled sustainable intensification in agriculture and provide the basis for the emergence of complex societies and early states in the Yellow and Yangtze Rivers.The original contributions presented in the study are included in the article/HL designed the research. XY and KH assisted the analysis of archaeobotanical and zooarchaeological data. XY and CS contributed to the discussion sections. KH compiled the figures. KH and HL wrote the manuscript. All authors contributed to the article and approved the submitted version.This research was supported by the National Natural Science Foundation of China , and China Postdoctoral Science Foundation (Nos. 2020M670444).www.editage.cn) for English language editing.We sincerely thank Xue Yan, Xiaoqu Zheng, Yuqian Wang and YM for their assistance with data collection. We would like to thank Editage (The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The handling editor YG declared a shared affiliation with the authors KH, XY, HL at the time of review.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Background: As the world prepared for and responded to the COVID-19 pandemic in early 2020, a rapid increase in demand for personal protective equipment (PPE) led to severe shortages worldwide. Acquisition of PPE in the general market was an integral part of pandemic response, along with the safeguarding of hospital supplies. We seek to quantify the difference in cost per unit (CPU) of PPE during the first wave of COVID-19 compared to prepandemic prices. Methods: We performed a retrospective review of market prices for PPE during the first surge of the pandemic in Chicago. Cost of PPE was tabulated and compared with prepandemic prices. The maximum cost per unit (CPU) of PPE was tabulated for each week, and the average cost throughout the pandemic was calculated. Disposable gowns, washable gowns, N95 respirators, face masks, and gloves were included in our analysis. Results: PPE prices were significantly higher during the pandemic compared to prepandemic prices (Figure Conclusions: Market prices for PPE were significantly elevated during the first weeks of the pandemic and remained high throughout the first wave of COVID-19. Multiple factors likely contributed to high prices, including demand shock, disrupted supply chains, and a rush to acquisition by healthcare systems and the general population alike. The impact of COVID-19 on prices highlights the importance of supply chains and national stockpiles for pandemic preparedness.Funding: NoDisclosures: None"} +{"text": "This article presents a brief history of public policies to address sexually transmitted infections (STI) in Brazil. It also discusses deficiencies and challenges to be considered by the country to formulate and implement future policies.STI remains a global public health issue. In 2016, the World Health Organization (WHO) estimated a 376.4 million incidence of curable STI in people aged 15 to 49. There were 127.2 million cases of chlamydia, 86.9 million cases of gonorrhea, and 6.3 million cases of syphilis. In the Region of the Americas, an estimated 29.8 million cases of chlamydia, 13.8 million cases of gonorrhea, and 2 million cases of syphilis were reportedThese estimates indicate a high STI incidence and warrant the WHO global strategy and the establishment of priority measures to achieve STI elimination goals by 2030. This strategy focuses on (i) gonococcal antimicrobial resistance and chlamydial co-infection risk, (ii) congenital syphilis elimination, which requires increased testing and treatment of pregnant women and specific populations, and (iii) human papillomavirus (HPV) infection, with a focus on immunization to eliminate cervical cancer and anogenital wartsThe Pan American Health Organization's (PAHO) Plan of Action for the Prevention and Control of HIV/STI (2016-2021) aims at expediting the elimination of the human immunodeficiency virus (HIV) and STI epidemics as public health issues in the Region of the Americas by 2030In Brazil, acquired syphilis, syphilis in pregnant women, and congenital syphilis cases are compulsorily notifiableBrazilian nationwide-covering STI prevalence studies reveal the scale of the problem. Parturients attended in public maternity hospitals had a 9.8% prevalence of chlamydia and 1.0% of gonorrhea in 2011The publishing of the first Clinical Protocol and Therapeutic Guidelines (PCDT) for Comprehensive Care for People with STI, approved by the National Committee for the Incorporation of Technologies in the Brazilian National Health System (Conitec), in 2015, is noteworthyIn the period 2015-2016, the Ministry of Health's partnership with the Federal University of Santa Catarina and sentinel sites for the elaboration of a gonococcal resistance study (SenGono Project) made possible the first Brazilian gonococcal antimicrobial susceptibility surveillance program. The nationwide surveillance research analyzed gonococcal strains at seven sentinel sites and found high tetracycline, penicillin, and ciprofloxacin resistance in the bacteriaNeisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis, in urethral discharge samples; and herpes simplex virus types 1 and 2, Treponema pallidum and Haemophilus ducreyi, in genital ulcer samples.In 2018, a new phase of the SenGono Project started with installing more collection sites and the inclusion of two new antimicrobials (spectinomycin and gentamicin) in the analyses. Within the SenGono Project, the following are undergoing research: The SenGono Project results led to the publication, on June 17, 2020, of Ordinance GM/MS no. 1.553/2020, by which the Ministry of Health instituted the sentinel surveillance of male urethral discharge syndrome to monitor data in qualified health unitsConsidering the global and national penicillin supply shortage and the difficulties for its acquisition by states and municipalities in the period 2014-2016, the publication of the 'Strategic Actions Agenda for Syphilis Reduction in Brazil' in 2016Following the HPV vaccination inclusion in SUS, the need for monitoring the impact of such immunization on the specific population was perceived. Research on HPV prevalence in Brazil was scarce until thenNeisseria gonorrhoeae to several antibiotics threatens the efforts for controlling this infection. 66% of the 67 countries participating in the Gonococcal Antimicrobial Surveillance Programme have already shown increased clinical and in vitro resistance to broad-spectrum cephalosporins in 2009-2014, and it is the only remaining first-line monotherapy for gonorrhea controlThe fast antimicrobial resistance growth of Treponema pallidumSome challenging goals in syphilis control include eliminating vertical transmission, improving case surveillance, developing more accurate tests to diagnose active syphilis, neurosyphilis, and congenital syphilis, increasing access for the most vulnerable populations, and developing alternative oral drugs and vaccines against ,,Lack of knowledge and fake news on immunization are examples of contributing factors to low vaccination coverage for HPV. Health care integration with schools and communities is central to achieve better indicators since well-informed adolescents are potential communicators of such information to their parentsChallenges and deficiencies persist in the formulation and implementation of public policies in IST in Brazil. In such a scenario, there is a permanent need for (i) strengthening the role of primary health care in comprehensive care to people with STI and their sex partners, (ii) ensuring adequate vaccination coverage against HPV and viral hepatitis A and B, (iii) promoting health information, education, and communication, (iv) expand access to STI testing and treatment, with emphasis on the most vulnerable populations, (v) notify sex partners, and (vi) qualify health professionals' approach to sexual health matters, in addition to screening for asymptomatic, prevention, clinical-laboratory management, and surveillance of sexually transmitted infection cases."} +{"text": "Food microbiology studies the microbiota of food products. It is a very diverse area within the field of microbiology because it deals with microorganisms that may have both beneficial and deleterious effects on food quality and safety, comprising fermentative, probiotic, spoilage, and pathogenic bacteria, moulds, yeasts, and other microorganisms.The survival and growth of these diverse microorganisms is very much influenced by a wide range of environmental factors, which include the hugely diverse composition of the different food matrices.Among the submitted manuscripts that pretty much covered all aspects of food microbiology, eight research articles were selected by external experts to enter this annual special issue of BioMed Research International.Micromeria fruticosa serpyllifolia plants, growing in different regions of Palestine, screening for their antioxidant and antimicrobial activities.Salameh et al. did a comparative study on the volatile oils of Gebru and Sbhatu studied a collection of probiotic lactic acid bacteria (LAB) isolated from Korean Kimchi and Ethiopian spontaneously fermented Teff and evaluated the effect of LAB on the phenolic content of Teff during fermentation.Cordyceps kyushuensis, a parasitic fungus, for their immunomodulatory and antioxidant actions and concluded that these could be considered potential candidates for functional foods and therapeutic agents.The work by Su and coworkers evaluated the water-soluble polysaccharides of Staphylococcus aureus and Acinetobacter baumannii.Hassan and colleagues studied the probiotic properties of lactobacilli isolated from traditional Pakistani yoghurt and evaluated the antimicrobial activity of their bacteriocins against foodborne pathogens, such as Staphylococcus aureus and Escherichia coli resistant isolates, highlighting the public health consequences associated with the consumption of these unhygienic food products.Jaja et al. reported a high-level contamination of meat with Salmonella enterica.The article by Tenea described the role of peptide extracts from native LAB as promising food antimicrobials against Bacillus megaterium-coated diets on the growth, digestive enzyme activity, and gut microbial diversity of Songpu mirror carp.Finally, Luo and colleagues described the beneficial effect of The authors come from nine different countries, one European (United Kingdom) and eight non-European, namely, Ethiopia, Pakistan, Saudi Arabia, South Africa, Nigeria, China, State of Palestine, and Equator.BioMed Research International find this Food Microbiology 2020 special issue of relevance to their research field.We are happy to launch this special issue, which includes eight manuscripts that reported new findings mainly on the antimicrobial and antioxidant activities of food microbiota or their secondary metabolites. We hope that the readers of"} +{"text": "The global aging of the population, combined with shifts in the structure and composition of families, has led to increased attention to the role of family and social relationships in the aging experience. The importance of family in determining healthy aging, however, may largely depend on the social, political, and economic context in which individuals are embedded. Cross-national investigations offer a unique opportunity to understand how family relationships and family caregiving influence health and well-being among older adults by comparing family dynamics across different sociocultural contexts. The HRS-family of surveys, which have been harmonized within the Gateway to Global Aging, provides remarkable opportunities for cross-national comparative analysis. The papers in this session use harmonized data from the Gateway to compare the influence of family on health across different social dimensions in multiple countries from around the world, including examinations of: 1) the impact of grandparenting on health of older adults in Europe and China; 2) psychological well-being among European older adults whose partners receive formal care; 3) the influence of parent-child relationships on health and well-being of older adults in China and the U.S.; and 4) how loneliness among older adults is patterned according to their living arrangements and relationship quality. The discussion will highlight the promises and challenges of cross-national research on families and aging and how harmonized aging data facilitates international comparisons."} +{"text": "This systematic review aimed to analyse the performance of the Integrated Disease Surveillance and Response (IDSR) strategy in Sub-Saharan Africa (SSA) and how its implementation has embraced advancement in information technology, big data analytics techniques and wealth of data sources.HINARI, PubMed, and advanced Google Scholar databases were searched for eligible articles. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols.A total of 1,809 articles were identified and screened at two stages. Forty-five studies met the inclusion criteria, of which 35 were country-specific, seven covered the SSA region, and three covered 3\u20134 countries. Twenty-six studies assessed the IDSR core functions, 43 the support functions, while 24 addressed both functions. Most of the studies involved Tanzania (9), Ghana (6) and Uganda (5). The routine Health Management Information System (HMIS), which collects data from health care facilities, has remained the primary source of IDSR data. However, the system is characterised by inadequate data completeness, timeliness, quality, analysis and utilisation, and lack of integration of data from other sources. Under-use of advanced and big data analytical technologies in performing disease surveillance and relating multiple indicators minimises the optimisation of clinical and practice evidence-based decision-making.This review indicates that most countries in SSA rely mainly on traditional indicator-based disease surveillance utilising data from healthcare facilities with limited use of data from other sources. It is high time that SSA countries consider and adopt multi-sectoral, multi-disease and multi-indicator platforms that integrate other sources of health information to provide support to effective detection and prompt response to public health threats. Despite scientific development to strengthen the health system to protect and promote human health, Sub-Saharan Africa (SSA) continues to be confronted by longstanding, emerging, and remerging infectious disease threats , 2. The Before 1998, most countries in Africa implemented surveillance systems through vertical programmes of specific diseases of national and /or international priority. These included malaria, HIV/AIDS, tuberculosis and vaccine-preventable diseases. Epidemiological data were collected mainly at the health care facility level and in outreach health service settings . This siIDSR functions are categorised into core and support functions. The core functions include identification of cases, investigation and confirmation, registration, case notification/reporting, data analysis and interpretation, response to the situation, communication and provision of two-way feedback, evaluation of the interventions, and preparation for emergency occurrences. The support functions include guidelines, laboratory capacity, supervision, training, resources and coordination at all health system levels . The IDSDuring the past 20\u00a0years, the IDSR framework has been used in 94% (44/47) of the countries in the WHO African region to enhance capacity for surveillance for priority diseases, conditions, and events \u201316. In mOver the years, the IDSR has relied heavily on the routine health management information system (HMIS) implemented at the facility and district levels of the health systems . HoweverThis review was guided by the following overarching question: Does IDSR generate information that drives early detection of and response to infectious disease outbreaks? Specific questions were: (i) Has IDSR improved health data quality and utilisation during its 20\u00a0years of implementation in SSA?; (ii) What are the challenges and opportunities for IDSR to improve early detection and prompt response to infectious diseases in SSA? The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols 2015 checklist . Three dThe review involved two-stage screening, title/abstract screening and full-paper screening. The inclusion criteria were: the study must involve at least one of the SSA countries, clearly describe the evaluation of the IDSR system, focuses on at least one of the IDSR functions and/or systems attributes. The review excluded studies with abstracts without full text, not in English, reviews and newsletters. Two of the authors (IRM and LEGM) extracted eligible articles independently, and any disagreements between them on inclusion or exclusion were resolved by discussion and consensus. The linked descriptive search requests that were developed and search results from each database are presented in Table A total of 1,809 articles were initially identified using the key search descriptors. A large number of articles were irrelevant or duplicate and were excluded. The 498 remaining abstracts were screened further, and 412 were excluded based on the inclusion/exclusion criteria. Of the remaining 86, full-text articles were screened, and 45 studies met the inclusion criteria and hence, were selected for detailed reviews disease control programmes; implementation of standard surveillance, laboratory and response guidelines; improved timeliness and completeness of surveillance data, as well as increased national-level review and use of surveillance data for the response , 15. HowImprovements in IDSR system attributes such as completeness and timeliness of data reporting have been observed in Uganda, Malawi and Ghana , 49, 51.Studies in Ghana, Tanzania, and Zambia have reported that several health facilities lack copies of the IDSR Technical Guidelines for Standard Case definitions; and that laboratories are ill-equipped to provide confirmation of any suspected priority notifiable infectious disease , 25, 60.In terms of IDSR support functions, of the 47 countries in the WHO Africa Region, 94% were implementing the IDSR strategy, and 45 (85%) have initiated training at the sub-national level . Thirty-This review indicates that in most countries, data generated through the routine HMIS, which is the key source of IDSR, are rarely assessed for their quality, analysed and used to support decision-making . SeveralIn Ethiopia, Liberia and Tanzania, assessments of the HMIS have identified some data quality issues and lack of use of the generated data , 60, 75.A few countries have reported analysing and used routine HMIS data at sub-national levels , 74. In For the integrated system to be efficient, it requires strong coordination and communication, a clear organisation structure, adequate resources , 81, andIn SSA, several government ministries, agencies, and academic and research institutions are involved in managing different aspects of the health information systems. The ministries of health run the routine HMIS as the major source of information for decision making and planning. National Statistical Offices are responsible for most of the nation-wide household demographic and health surveys as well as population census . Other kA warning of an impending epidemic can help relevant authorities and communities to prepare and take immediate actions to reduce morbidities and mortalities. Many of the epidemic diseases are highly sensitive to long-term changes in climate and short-term fluctuations in weather. Meteorological data are made available daily by the National Meteorological Agencies, yet they are rarely used to monitor the occurrence of diseases. Meteorological data can be combined with geospatially referenced data, population densities or road networks to generate estimates of environmental indicators relevant to infectious diseases . HoweverIt is critical for a good and efficient surveillance system to incorporate other sources such as mortality data from demographic surveys, environmental data, vital statistics and civil registration, antimicrobial resistance, systematic surveys, meteorological data and research data. In most countries, despite an enormous amount of data generated by these systems, they run in parallel and independently, not well-coordinated, and sharing of information between them is minimal. Each of the existing systems operates its data collection and utilization framework. Moreover, much of the information is generated outside the health sectors \u2013 making it not readily available for disease surveillance purposes. It is a fact that the innovations, including the use of big data and artificial intelligence, could transform infectious disease surveillance and response and complement the existing traditional disease surveillance systems and improve detection and response to epidemics .Laboratories play an important role in the prompt diagnosis of infectious diseases. The findings of this review have shown that IDSR is challenged by inadequate diagnostic capacities at all levels of the health system, especially in terms of staff levels, skill sets and infrastructure. It is critical, therefore, that countries support the efforts to strengthen laboratory capacities for the detection of a wide range of pathogens in relation to the IDSR priority diseases. Moreover, laboratory networking should be encouraged and should involve both national, regional and research reference laboratories. To address the gaps in knowledge, it is important to strengthen the laboratory management information systems (LIMS), recruit adequate staff who are well trained and motivated as well as the need for periodic support supervision of the surveillance activities. The plan by the African Centres for Disease Control and Prevention to establish and operationalize a Regional Integrated Surveillance and Laboratory Network is commended. This network is expected to coordinate and connect the continent\u2019s analytical, surveillance, and emergency-response assets .An effective epidemic intelligence should contain both indicator-based and event-based surveillance. Globally, with the use of information technologies, an event-based surveillance approach is being promoted to complement the traditional \u201cindicator-based\u201d surveillance approach as part of the components of epidemic intelligence . There hThere is growing interest in using digital surveillance approaches to improve monitoring and control of infectious disease outbreaks . HoweverWith the proliferation of information technologies and increased ownership of mobile phones in SSA, there are large amounts of data on social media blogs, chatrooms, and local news reports that may provide governments and other stakeholders\u2019 clues about disease outbreaks time and place daily. Such data are essential raw materials for DDS. Advancements in information technology and information sharing give rise to infodemiology \u2013 defined as the science of distribution and determinants of information in an electronic medium, specifically the internet . To dateCommunity-based surveillance (CBS) is defined as the systematic detection and reporting of events of public health significance within a community by community members . CommuniThe WHO Technical Guidelines on IDSR , 17 highAs part of an effective global response to diseases transmitted between animals and humans , there hIn 2019, the Tripartite organisations \u2013 the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health, and the World Health Organization \u2013 developed the Tripartite Zoonoses Guide (TZG). The aim is to help the countries develop a capacity to address zoonoses in a coordinated manner, linking to existing international policies and frameworks and supporting efforts for global health security. The TZG includes three operational tools to support national authorities: (i) the Multi-sectoral Coordination Mechanism, (ii) the Joint Risk Assessment, and (iii) the Surveillance and Information Sharing operation tools .The emerging and re-emerging infectious diseases in Africa underline the urgent need to integrate public health surveillance systems . As infeThe importance of using both formal and informal data sources for timely and accurate infectious disease outbreak surveillance has been emphasized . EvidencModern technologies such as artificial intelligence and machine learning are widely applied in analysing a significant volume of data to assess the status and forecast future dynamics of diseases , 124. A This review indicates that most countries in SSA rely mainly on traditional indicator-based disease surveillance utilising data from healthcare facilities with limited use of data from other sources. However, the traditional indicator-based disease surveillance approaches face several challenges, including data quality and inefficient early warning systems, because they are less sensitive than event-based surveillance approaches. They most often miss information from populations who do not access health care or do so through informal channels, thus unable to detect new, potentially high-impact disease outbreaks. Moreover, there is a dearth of information on IDSR data quality, analyses that utilise advanced methodologies and use in the detection and response of infectious disease outbreaks in the region. Over the years, data-use and data-process have not been given adequate attention. This analysis indicates that future efforts to address disease surveillance systems should consider data quality, multi-source data analysis and triangulation, data use and data integration. Capacity building for health workers at the national and sub-national levels in data management is critical.This review highlights the untapped opportunities for integrating community-based, digital surveillance through a one health approach that could improve public health surveillance in SSA. It is high time that the region explores and adopts the integration of several surveillance programmes into hybrid systems that combine traditional surveillance data with data from the public health laboratories, community, research settings, search queries, social media posts, and crowdsourcing. Improved performance requires the merging of current gains, strong collaboration from all stakeholders, supervision and regular evaluation of the surveillance system to identify and address challenges as they emerge. The introduction of innovative ways to further strengthen the surveillance and response system in SSA countries is critical to enhancing early detection and reporting of suspected cases of priority diseases, conditions and events.To address the challenges of the IDSR system, there is a need to develop an electronic platform that will combine data from multiple relevant databases such as HMIS, research programmes, laboratory management information systems (LMIS), population-based surveys, digital disease surveillance, sentinel surveillance, OH surveillance and community-based surveillance initiatives to allow their interoperability. The aim is to make optimal use of community, facility and research-based epidemiological information in preparing the community to act before a health emergency happens, as well as to provide high-quality evidence to guide policy development and resource allocation at the national level. With this platform, a continuing analysis and review of scientific publications, social media, routine health data and demographic statistics can be established to feed different decision-making units. Composite and multi-sourced indicators that comprise information from various sources can be generated, analysed and monitored. The goal is to make data readily available and help speed up dissecting the information and putting programmes in place to detect and promptly respond to epidemics. The platform will foster improved utilisation of surveillance data for action and avoid delays in response to emergencies by linking health indicators with other information such as climate data that can add value to inform health risks accurately. A multi-sectoral approach should be used to pursue a common strategic goal of developing a workforce that can support public health surveillance and response."} +{"text": "The COVID-19 pandemic and global lockdown have had drastic socioeconomic and psychological effects on countries and people, respectively. There has been limited access to health care and education. These negative consequences have had a significant impact on the well-being of children and adolescents. Therefore, the EAP and the ECPCP are requesting state, health, and education authorities as well as European pediatric societies and the healthcare professionals that special attention be given to this population and the problems they face as a result of the pandemic. The COVID-19 pandemic has caused unprecedented changes in people's way of life and social relationships. Global public health measures, including a worldwide lockdown, have affected socioeconomics, health care, education, and public mental health . This haTo highlight this issue, provide guidance, and offer strategies for the prevention or minimization of the detrimental effects of the pandemic and associated lockdown on young people, the European Academy of Paediatrics (EAP) and the European Confederation of Primary Care Paediatricians (ECPCP) present this position paper and recommendations directed to state, health authorities, European pediatric societies, and the European healthcare professionals involved in the care of the pediatric population. This statement does not focus on the care of children and adolescents with COVID-19 disease.The course of SARS-CoV-2 infection is rarely severe in children and adolescents \u201310. HoweThe lockdown has also affected the availability of well-child care and the administration of childhood inoculations for vaccine-preventable diseases. Many children, especially those from lower-income households, have not received scheduled routine vaccinations and the overall immunization rate has dropped significantly \u201327. ThisLimited access to mental health services for children and adolescents has resulted in the intensification of preexisting problems and an increase in the prevalence of depression and anxiety disorders \u201330.The new situation has led to weakened communication, deprivation of personal peer relations, lack of physical activity, and reduced sensory stimulation. The consequences of this can include psychological deterioration, anxiety, frustration, stress disorder, adjustment disorders, grief, loss of appetite, and sleep problems , 31, 32.Social distancing and limited interpersonal contact can lead to development delays, impaired social skills, anxiety, and depressive symptoms . The lenThe transference of social activity exclusively to the Internet can result in digital technology overuse, abandonment of other activities, exposure to inappropriate content, and cyberbullying , 47.The prolonged school closures are likely to have detrimental effects on learning outcomes \u201350. In yThe lockdown exacerbates socioeconomic inequalities. In the context of education, this can mean that children from poorer families are likely to have inadequate access to appropriate IT tools, insufficient intellectual support from caregivers, and fewer educational opportunities beyond school. As they do not receive meals at school during the lockdown, these children are also at increased risk of malnutrition , 52. MorFor teachers, the pandemic has been a challenge related to the crisis of competence. Educators have had to develop and improve objective methods of assessing learning progress. Remote education has also weakened teacher-student relationships , 53.The EAP and the ECPCP strongly believe that action is necessary to reduce the negative effects of the pandemic on young people. The following measures are advised:For state, health, and education authorities- Establish a framework on how to mitigate the impact of COVID-19 on children and adolescents needing essential services in a variety of healthcare settings.- Consider strategies to reduce preventable illness during the COVID-19 pandemic in young people with non-COVID-19 diseases and injuries.- Guarantee the staffing, adequate drug, and material supply, especially for personal protective equipment for essential pediatric services.- Implement secure and flexible reopening and maintenance of kindergartens and schools based on the rights of children and adolescents.For European pediatric societies:- Keep members updated in the area of risks for child and adolescent health during the COVID-19 pandemic.- Encourage members to make all possible efforts to maintain curative and preventive high-quality services for children and adolescents.- Initiate and coordinate European-wide surveys regarding the temporary impact of the COVID-19 pandemic on pediatric health services.- Analyze the experiences with telemedicine in the area of pediatric care, screening, follow-up, and drug prescribing.- Support the EAP campaign \u201cVaccinate your child,\u201d to restore routine immunization of children .For the providers in the primary, secondary, and specialized pediatric care- Increase vigilance and diligence about the risks of non-personal appointments when conducting remote health assessments of children and adolescents.- Encourage face-to-face visits when presenting symptoms require them to rule out life-threatening diseases. Provide postnatal care in person wherever possible.- Ensure hygienic measures and personal protection for all staff and patients. Make appropriate adjustments and appointments to avoid crowding in outpatient services. Limit the quantity of accompanying persons.- Communicate personally and in public with caregivers to reassure the trust in essential health services and the unlikely danger of COVID-19 infection in the health care system. Clarify any public misinformation.- Reinforce the capacity of parents and adolescents for self-management and timely presentation in case of alarming signs and symptoms.- Make every effort to maintain essential pediatric health services by facilitating open access to curative services for the acute and the chronic ill children and adolescents.- Maintain preventive health services as well as child checks and vaccinations. Use recall and other motivational reminder systems to catch-up with missed visits.- Increase surveillance and screening for emotional, social, and behavioral disorders and provide age-appropriate guidance at any given opportunity.- Engage to maintain mental health services and social services in the community, with special focus on lower-income households.- Encourage adolescents to discuss non-pharmacological COVID-19 interventions such as social distancing, hygiene, and the use of face coverings. This will enable them to identify and minimize behavioral infection risks, which may be detrimental even in areas with high vaccination rates.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.\u0141D, AM, and AH: study design. \u0141D, IR-W, and GH: data collection. \u0141D, IR-W, GH, ZG, AM, ST, SB, AC, and AH: data analysis and interpretation, manuscript preparation, and critical revision. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Dear EditorWe had a case of Krukenberg tumor (KT) of the right ovary, which extended to pelvic zone M;18*13*10 cm in a 40-year-old virgin woman who had no history of previous cancer. The patient received five courses of chemotherapy before surgery, and because of the chemotherapeutic effect on the ovarian stroma, spindle cells of stroma were plump, hyperchromatic, with mild pleomorphism. The number of signet cells was low, and they were scattered between spindle cells, mostly with eosinophilic cytoplasm. Spindle cell tumors such as pelvic rhabdomyosarcoma (with scattered eosinophilic rhabdoid cells) also gastrointestinal stromal tumor (GIST) with signet ring-like change were in the differential diagnosis in frozen section examination and permanent sections. Because of the increasing use of preoperative chemotherapy in the management of ovarian malignancy, pathologists should be aware of changes in cellular morphology induced by chemotherapy, which may cause problems in tumor typing and grading and the identification of ovarian epithelial tumors or metastatic tumors to the ovary such as breast and lung cancers .Effects of chemotherapeutic drugs on the cellular stroma of the ovary were seen in the literature previously, which can cause apoptotic depletion of follicles . ChemothAge of women at menopause show duration of estrogen deficiency which can cause health problems . The tumThen, correct interpretation requires exact evaluation of the morphology of tumoral cells and stromal cells, patient history, and confirmation of diagnosis with immunohistochemistry such as anti-cytokeratin and anti-histiocytic antibodies."} +{"text": "This study systematically reviewed processes and educational programs for self-management of health and diseases that are the subject of public health attention. This systematic review of the literature (SRL) is relevant to recognizing the characteristics of the educational processes in self-managing chronic diseases in contexts where technology did not play a significant role. Following the PRISMA protocol, the authors independently reviewed full-text articles from several databases using the following criteria: (1) intervention studies evaluating the effects of self-management health programs; (2) educational process of disease self-management; (3) studies that included at least one control group, and (4) peer-reviewed studies. In addition, the Scottish Intercollegiate Guideline Network measurement tool was used to assess the risk of bias in each trial. In the final sample, 38 articles were included. The findings regarding health education methods of self-care, using community-based care and technological tools, are considered fundamental. Among the conclusions, the relevance of the pedagogy that health education processes demand improvement in post-pandemic program effectiveness stands out. Educational processes in public health seek to ensure the populations\u2019 right to health by promoting improved living conditions, welfare, and development . Public Health education interventions have traditionally focused on prescriptions and lifestyle restrictions . This apTherefore, educational actions developed in public health contexts and reported by research mainly focus on disease self-management and the appropriation of self-care skills . MedicalAccess to medical and health education programs include mechanisms to counteract their low participation rates. According to health institutions and research worldwide, low community participation is mainly related to socioeconomic conditions, transition effects over time, and a low level of health experts in educational training . AdditioThe importance of working on the aspects that affect people\u2019s willingness to participate in educational programs and daily, personal, collective activities to control and treat disease is evident. In this regard, improving self-regulation and self-management requires immediate feedback to modify behavior . Thus, tLikewise, health education programs have various innovative educational strategies that focus on the subject and his/her context to facilitate the formative effectiveness of the programs . EducatiOther health education initiatives have reflected on the role of health education professionals to ensure that there are no gaps in access to educational programs . FurtherEducational approaches involving technological tools in training processes in healthcare are in an exploratory phase, given the possibilities of improvement offered by technology . This syThis systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses, or PRISMA, guidelines . To idenOne author performed the initial eligibility assessment by reviewing the titles and abstracts. Then, two authors independently reviewed full-text versions of 92 articles using the following criteria: (1) intervention studies evaluating the effects of self-management health programs; (2) studies including at least one control group; and (3) peer-reviewed studies.Data extraction was performed independently by the authors. The following data were extracted from each study: first author, date and place of publication, study design, population served, analysis of the program effectiveness, EdTech used, and pedagogical strategy. Extracted data were entered into standardized MS Excel files. Any disagreements were resolved by discussion among the authors.The Scottish Intercollegiate Guideline Network (SIGN) measurement tool was used to assess the risk of bias in each study in this review. SIGN was developed in 1993 to improve healthcare quality for populations in Scotland by reducing variation in practice and outcomes by developing and disseminating national clinical guidelines with recommendations for effective practice based on current evidence . This toA total of 3114 records were found in the database search. These search results were imported using Parsifal, and 1428 duplicates and 81 records marked as ineligible by automation tools were removed. A detailed flow chart of the selection process is shown in After the elimination of duplicates, 1605 records were examined. Subsequently, we searched for papers citing any of the initially included studies. However, no additional articles meeting the inclusion criteria were found in these searches. Finally, 38 full-text papers were reviewed.n = 14), Asia (n = 13), North America (n = 8), Africa (n = 3), and Oceania (1). Twenty-five studies involved adults aged between 35 and 60 years, while ten studies reported educational programs for self-management of health and disease with young adult participants between 18 and 35. In a smaller proportion, programs involving follow-up and control of people >65 years (n = 2) and accompanied by health professionals (n = 2) were identified. The general characteristics of the studies are presented in It was identified that, while some articles met the inclusion criteria, they evaluated performances in regular professional training processes in health ,27, leavDisease self-management programs link different pedagogical strategies and learning methodologies developed to contribute to the knowledge and control of chronic diseases. It was highlighted that 16% of the investigations ,34,47,48Similarly, methodologies that allowed discussion and knowledge exchange among patients in collaborative groups in contextual intervention programs were recognized. We also found analyses of patient perception through the accompaniment of a professional or the majoritarian use of qualitative analysis tools. This review showed that 29% of the texts studied ,54,55,57It was emphasized that the analysis of technological tools, which contributed to self-management of diseases, were contemplated where technology was not an indispensable tool for their management, as reflected in 71% of the investigations that do not report the mediation of technology in their educational process. This point becomes relevant for identifying lessons learned and best practices of current educational processes that aim to meet educational challenges during and after pandemics, where technology is the main instrument for transmitting knowledge.According to the SIGN checklist, 18 of the studies ,45,49,55In interpretating the findings, we were careful about generalization due to the number of studies reviewed and their open-access character. However, the results allowed us to answer the guiding research question and identify the educational process characteristics of self-management of health in public healthcare. The results aligned with recent research on the innovation needs of medical and health education programs reported by health institutions and agencies worldwide ,30. The While public health processes aim to prevent diseases, promote and maintain health and quality of life, the above is interpreted as a call to public health and medical and health education to diversify their objectives and educational strategies for the prevention, promotion, maintenance, and monitoring of population health. Doing so aligns with the recommendations of the World Health Organization (WHO). It invites broadening of the clinical and therapeutic perspective of healthcare and health education through strategies that build frameworks of trust, social support, and learning which respond to the needs of individuals and communities for health and welfare beyond the health-illness binomial .Thus, it seems that health education programs continue to emphasize informative actions on the self-management of diseases, leaving at a low priority the training and monitoring of learning and the appropriation of knowledge and skills for self-care and self-management of health in the daily activities of families and communities . Some reThe findings of this review indicate that health education programs in public health face significant challenges in guaranteeing program access, participation, and permanence and improving the effectiveness of the learning processes. The programs studied mainly address objectives for the self-management of diseases, remaining at the level of health maintenance, and lacking educational processes for disease prevention, promoting integral health, and monitoring people\u2019s quality of life and welfare. Some studies emphasized the importance of involving the participants in the design of the educational sessions and using tools, such as dialogue and other interactive methods, to improve participation . Thus, mRegarding technological tools, electronic education has become crucial in the information era and, therefore, it is also incorporated in medical and health education processes. Our results identify that technologies have offered robust mechanisms that support the self-management of health and guarantee a lasting educational experience for people, any time and place , with neThe findings report that educational processes for self-management of health hold promise for public health intervention when technology supports it. This review suggests recognizing and integrating the transformative possibilities of community education methods coupled with the use of technology. In addition, it is relevant to consider the pedagogical character of health education processes to improve the effectiveness of the programs. To this end, it is essential to strengthen the educational training processes for health professionals and structure evaluation goals for the teaching-learning process in these programs. The assessments should cover content, teaching strategies, appropriation of knowledge, and self-management of health in populations. Concerning technologies in the training processes, their functionality and usability, with regard to achieving the expected learning, should be evaluated.The findings regarding health education methods of self-care as part of community-based care and how technological tools are used are fundamental to this review. Consequently, we urge future research to focus on studying the barriers and facilitators that arise when using technological tools as mediators of learning in health education programs, mainly in terms of access to infrastructure, generational gaps, cultural factors, levels of digital literacy, and economic disadvantages .One limitation of this systematic review is language bias, as we only included studies published in English. Therefore, studies published in other languages, such as Chinese and Japanese, were not included in this review. In addition, the review did not include research from grey literature, which could exclude important unpublished pieces produced by non-governmental organizations. Finally, it should be noted that the analyses performed represent a partial view of the phenomenon under study and, therefore, the generalizability of the data is not considered. Despite these limitations, this literature review study increased the understanding of self-management health education processes and identified opportunities for improvement.This review began with the question, \u201cwhat are the characteristics of educational processes of self-management of health in public health care?\u201d. We identified that the most relevant characteristics respond to objectives focused on self-management of diseases, primarily chronic, and mitigating disease signs and symptoms. There is a focus on remedial education for the maintenance of health that is typical of hospital environments, which, in the public health context, is limited. In this regard, institutions and researchers propose innovative medical and health education processes to improve training and contribute to the prevention, promotion, care, maintenance, and monitoring of integral public health.The innovative processes highlight social and community-based learning characteristics that involve peers, caregivers, families, and professionals in training actions. In addition, some initiatives highlight socio-emotional characteristics of education and the need for contextual learning in daily life practices. Finally, there are characteristics oriented around using technological tools in the teaching-learning process as an area of opportunity to improve their effectiveness and increase their coverage.Future research is invited to examine the barriers and facilitators in medical and health education programs using socio-community and technology-enhanced educational strategies. Furthermore, the contributions of innovative processes for public health education toward long-term improvements in self-management of health and diseases should be evaluated. These research needs are especially relevant due to the COVID-19 health crisis because the fundamental medium of knowledge transmission for the formulation and implementation of health education programs, which recognize the health, economic, social, and cultural realities of communities, has become technology."} +{"text": "On physical examination, erythematous papules and pustules were observed on the abdomen , on the sternum, the back, and the lateral surface of the buttocks Pruritic folliculitis of pregnancyb)Polymorphic eruption of pregnancyc)Bacterial folliculitisd)Acneiform eruptionPruritic folliculitis of pregnancy (PFP) was originally described in 1981 by Zoberman and Farmer.3This is the least common pregnancy-specific pruritic dermatosis.In the 1999 study by Vaughan Jones et al., a cohort of 200 women with gestational dermatoses (GD) with a two-year follow-up identified PFP in 14 patients (7%).In 2006, Ambros-Rudolph et al. carried out a retrospective study by analyzing the medical records of 505 pregnant women. PFP was diagnosed in only one patient (0.2%), with a history of eczema in childhood and a family history of atopy in two first-degree relatives. The authors proposed a new classification of GD, introducing the term atopic eruption of pregnancy (AEP) which encompasses PFP, prurigo of pregnancy, and eczema of pregnancy.As described in the literature and observed in the present case, patients respond well to topical treatments based on 5% or 10% benzoyl peroxide and 1% hydrocortisone.Pruritic folliculitis of pregnancy is a rare, benign and self-limited gestational dermatosis that does not interfere with maternal-fetal morbidity and mortality. It is essential that pregnant women be adequately diagnosed and advised, and followed-up with specialized care.None declared.Maria Rita Carvalho de Freitas Amorim: Collection, analysis and interpretation of data; writing of the manuscript; obtaining, analysis and interpretation of data; critical review of the literature and approval of the final version of the manuscript.Flavia Amorim Meira Cavaliere: Critical review of important intellectual content; effective participation in research orientation; intellectual participation in the propaedeutic and therapeutic conduct and approval of the final version of the manuscript.Esther Oliveira Xavier de Brito: Critical review of important intellectual content and approval of the final version of the manuscript.Amanda Nascimento Cavalleiro by M. Mota da Silva: Design and planning of the study; critical review of important intellectual content; intellectual participation in the propaedeutic and therapeutic conduct and approval of the final version of the manuscript.None declared."} +{"text": "Increasing the number of specialized human resources for health is paramount to attainment of the United Nations sustainable development goals. Higher learning institutions in low-and middle-income countries must address this necessity. Here, we describe the 5-years trends in accreditation of the clinical and non-clinical postgraduate (PG) programmes, student admission and graduation at the Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania, highlighting successes, challenges and opportunities for improvement.This was a retrospective longitudinal study describing trends in PG training at MUHAS between 2015\u00a0and\u00a02016 and 2019-2020. Major interventions in the reporting period included university-wide short course training programme to faculty on curricula development and initiation of online application system. Data were collected through a review of secondary data from various university records and was analyzed descriptively. Primary outcomes were the number of accredited PG programmes, number of PG applicants as well as proportions of applicants selected, applicants registered (enrolled) and students graduated, with a focus on gender and internationalization (students who are not from Tanzania).The number of PG programmes increased from 60 in 2015-2016 to 77 in 2019-2020, including programmes in rare fields such as cardiothoracic surgery, cardiothoracic anesthesia and critical care. The number of PG applications, selected applicants, registered applicants and PG students graduating at the university over the past five academic years had steadily increased by 79, 81, 50 and 79%, respectively. The average proportions of PG students who applied, were selected and registered as well as graduated at the university over the past five years by gender and internationalization has remained stably at 60% vs. 40% and 90% vs. 10% , respectively. In total, the university graduated 1348 specialized healthcare workers in the five years period, including 45 super-specialists in critical fields, through a steady increase from 200 graduates in 2015-2016 to 357 graduates in 2019-2020. Major challenges encountered include inadequate sponsorship, limited number of academic staff and limited physical infrastructure for teaching.Despite challenges encountered, MUHAS has made significant advances over the past five years in training of specialized and super-specialized healthcare workforce by increasing the number of programmes, enrollment and graduates whilst maintaining a narrow gender gap and international relevance. MUHAS will continue to be the pillar in training of the specialized human resources for health and is thus poised to contribute to timely attainment of the health-related United Nations sustainable development goals in Tanzania and beyond, particularly within the Sub-Saharan Africa region. Building stronger health systems in paramount to attainment of the United Nations sustainable development goals (SDGs). The World Health Organization (WHO) recognizes six major health systems building blocks including human resource for health (HRH), service delivery, information, commodities, financing, leadership and governance as pivotal components for maturing health systems to reach their full potential \u20133. Of thIn Tanzania, this large and growing demand for HRH is apparent and is driven in part by the recent changes of disease patterns in the country such as the emergency of the new burden of non-communicable diseases (NCDs) \u201311. In aEver since its founding in 1963, the Muhimbili University of Health and Allied Sciences (MUHAS) and its predecessors have produced the largest share of specialized (Master\u2019s degree level) HRH in Tanzania in fields such as internal medicine, obstetrics and gynecology, pediatrics and surgery, and was the sole producer of such specialists in the country before establishment of other medical universities from the late 1990\u2019s. To date, MUHAS is the only university in Tanzania offering training in super-specialized fields of clinical medicine such as cardiology and nephrology. With the existing and growing demand, and in line with its vision, MUHAS needs to continue to play the leading role in producing an increased output of HRH, especially in the diverse specialized and super-specialized fields, without compromising quality.In order to ensure equitable socio-economic development, higher learning institutions have the obligation to maintain narrow gender gaps by fostering unbiased enrolment and training of the specialized healthcare workforce . MUHAS hSince its existence, MUHAS has faced several challenges in providing specialized training to healthcare workers. Notable challenges include limited sponsorship for postgraduate students which contributes to inability of up to 35% of the selected students to register for studies, inadequate number of qualified academic staff where over half of the 313 currently available full-time academic staff are in the junior ranks of Tutorial Assistant and Assistant Lecturer, and limited physical infrastructure for teaching. Here, we describe trends in development and accreditation of postgraduate programmes, student admission and graduation at MUHAS over the past five years. We highlight successes and provide new windows into challenges and opportunities faced by academic institutions in low- and middle-income countries (LMIC) which can inform other similar efforts.This was a retrospective longitudinal study describing trends in postgraduate degree training (Master and PhD) at MUHAS over the past five academic years (2015-2016 to 2019-2020).To date, MUHAS has seven academic units, comprising five Schools; , two academic Institutes; and 11 directorates; . Besides postgraduate programs reported in this article, the University also runs 6 diploma programmes, 1 advanced diploma programme and 15 undergraduate (bachelor) degree programmes. Currently all MUHAS academic units offer postgraduate training with exception of the Institute of Allied Health Sciences. The total enrolment at the University is currently 4423 students, out of whom 1332 are postgraduate students. In the five\u00a0years period under current report, the university undertook two major interventions including training of faculty on curricula development with the aim to increase the number of postgraduate programmes and initiated an online application system with the aim to increase the number of applicants for postgraduate programmes, especially from outside Tanzania.This study was based on review of documents (secondary data) to obtain information on accredited programmes, academic staff available for teaching, applicants for postgraduate programmes, applicants selected, applicants registered (enrolled), students who obtained sponsorship as well as students who graduated at MUHAS between 2015 and 2016 and 2019-2020. The sources of data included postgraduate admission records, records from the Students\u2019 Academic Report Information System (SARIS), graduation books, minutes of academic committee meetings and annual reports from relevant academic and administrative units.Data were analyzed descriptively. Numerical data were summarized in frequencies and percentages and were presented in Tables and Figures. Outcomes of interest in this study were the trends in number of postgraduate programmes, academic staff available for teaching, admission processes , sponsorship for postgraduate programmes, together with graduation . In analyzing the trends in admission and graduation by gender and internationalization, the number of students in the relevant group was divided by total number of students in appropriate category and multiplied by 100, and proportions for individual academic years were presented for each group with error bars indicating standard deviation. Data were analyzed using Prism 4 .The total number of postgraduate programmes at MUHAS has steadily increased from 60 in the academic year 2015-2016 to 77 in the academic year 2019-2020. Major contributors to this increase were the SOM which initiated 10 new programmes and SPHSS which initiated 3 new programmes in the five-year time span. The SON also initiated 3 new programmes in 2019-2020 , registering a 100% increase in the number of its postgraduate programmes, from 3 in the preceding year to 6 in 2019-2020. Other increase was in the SOD, which initiated 1 new programme (Master of Dentistry in Orthodontics) in 2019-2020 , Master of Science and Master of Science-super-specialization . Currently, there are 17 accredited Master of Science-super-specialization degree programmes or subspecialties in various fields of medicine . The SON offers MSc programmes . The SOD offers Master of Dentistry degree programmes and the ITM offers MSc in Traditional Medicines Development which runs for 2\u2009years, recruiting diverse bachelor\u2019s degree holders with background in science and Doctor of Philosophy (PhD). These are distinguished from coursework programmes in having intense research component culminating in a defendable thesis. Apart from the written thesis, other graduation requirements include course credits in research methodology, biostatistics, bioethics and scientific writing (15 for MSc R&P and 30 for PhD), published articles in peer-reviewed journals (2 for MSc R&P and 4 for PhD) and presentations in scientific meetings (2 for MSc R&P and 4 for PhD).Currently, the University has a total of 313 full-time academic staff. Most academic staff are aged 50\u2009years and below (81%) and are in junior academic ranks of Tutorial Assistant and Assistant Lecturer (52%). Detailed description of the academic staff by age, gender and academic rank is provided in Table\u00a0There was a steady increase in the number of applicants for postgraduate degree programmes over the past five years, from 543 in academic year 2015-2016 to 970 in 2019-2020 (79% increase). Similarly, the number of applicants selected to join the various postgraduate programmes increased over time from 470 in 2015-2016 to 853 in 2019-2020 (81% increase), which is concordant with the increase in the number of selected students who registered/enrolled at the university, from 358 in 2015-2016 to 536 in 2019-2020 to purse studies at MUHAS was 62, 79, 68, 127 and 159 in academic years 2015-2016, 2016-2017, 2017-2018, 2018-2019 and 2019-2020, respectively.The total number of students graduating at MUHAS had steadily increased over the past five years, from 200 in 2015-2016 to 357 in 2019-2020 (79% increase). The SOM and SPHSS contributed the largest number of graduates in each of the past five academic years . Here we aimed to describe the trends in initiation of specialized programmes, enrolment and graduation at the Muhimbili University of Health and Allied Sciences (MUHAS), the premier health sciences university in Tanzania. We show that, compared to five years ago, the MUHAS has made noteworthy strides by initiating 17 new specialized and super-specialized degree programmes, increasing student enrolment by 50% and increasing the number of graduating Tanzanian and international health specialists by 79% whilst maintaining a narrow gender balance. Overall, the University graduated 1348 specialized healthcare workers in the five years period, including 45 super-specialists in critical fields. These advances will have significant positive impact in strengthening health systems in Tanzania and Sub-Saharan Africa at large.MUHAS has a notable strength in the large number of specialized degree programmes in health sciences. Over the past five years, this strength has been emphasized by initiating 17 new competence-based and demand-driven programmes. The super-specialized programmes, also known as subspecialties, have been established in collaboration with partnering institutions in-country, including the Jakaya Kikwete Cardiac Institute, Muhimbili National Hospital, Muhimbili Orthopedics Institute and Ocean Road Cancer Institute, as well as universities in South Africa, Australia, United Kingdom, Germany, Sweden, Norway, Canada and USA that provided technical assistance as well as expertise in teaching as visiting scholars, adjunct faculty and through opportunities for international clinical attachments. This model has been used successfully in other countries in Sub-Saharan Africa and has proven to be effective for the transfer of skills to LMIC . The incThe WHO estimates that Sub-Saharan Africa would need to scale up its production of healthcare workforce by 140% in order to meet the international development targets . In the Besides training of Tanzanian healthcare workforce, and in line with the obligation for regional and international integration , 26, MUHNotwithstanding achievements made, there have been several challenges that were experienced over the past five years. Firstly, close to 35% of selected students in each academic year did not register due to lack of sponsor, being called back by employer due to staff shortages and other personal reasons. In addressing this challenge, the University continues to work closely with the Tanzania government through the Ministry of Health\u00a0as well as Ministry of Education, Science and Technology and other stakeholders in advocating for increased sponsorship to postgraduate students. Secondly, the University has inadequate number of qualified academic staff. The University is tackling this challenge by increasing recruitment of academic staff and soliciting scholarship opportunities for training of the junior staff towards PhD. Lastly, with the expansion of programmes and enrolment, the University is currently facing limitation of physical space for teaching. In addressing this challenge, the University is working to expand the physical infrastructure including extension of the dental facility at the SOD which is underway. Furthermore, the University has acquired 3800 acres of land in Mloganzila area, Dar-es-salaam, where a new campus will be built. To date, a 571-bed state-of-the-art hospital has been built in the area and construction of the Centre of Excellence in Cardiovascular Sciences - a research and teaching facility - is near completion. Next in plan is construction of lecture halls, laboratories, student hostels, administrative buildings, library, and other supporting units.Despite challenges encountered, the MUHAS has made significant advances in the past five years by increasing the number of programmes, enrolment, and graduation of specialized and super-specialized healthcare workforce for Tanzania and beyond, whilst maintaining a narrow gender gap. These milestones occurred amidst challenges of inadequate sponsorship, limited number of academic staff and limited physical infrastructure for teaching. The proposed improvements will further cement its leading role in training of the specialized and super-specialized healthcare workforce for Tanzania and Sub-Saharan Africa by enhancing the diversity of programmes, enrolment, gender equity and internationalization thus contribute positively towards timely attainment of the SDGs for Tanzania and the region."} +{"text": "At the launch of this issue, then newly discovered COVID-19 seemed to be faltering, and the collection of papers gathered in this publication was bound to be both a reminder and a relatively final display of domains and aspects of human functioning that were somehow affected by the corona crisis. Meanwhile, the health situation in the world has shown us the full breadth of the impact that the coronavirus has left or still leaves in almost all fields of human behavior. Overall, bibliographic mapping shows that most of the papers, framed within the scientific study of coronavirus and its societal impact, were in the field of medicine and psychology , mental health , and positive and negative affects during the COVID-19 outbreak. Taking a more differential approach, papers dealing with the socio-cognitive factors related to the COVID-19 crisis build the next larger group of the collected articles . The third group includes papers dealing with preventive and protective behaviors, such as adherence to epidemiological recommendations . A final group of studies conferred deals with the way of mitigating psychological distress during the coronavirus crisis. In the following paragraphs we have grouped these studies according to overarching topic, with their main findings summarized.As in the case of other health crises in the human history, our research collection has placed an emphasis on the effects of this pandemic on our emotional and cognitive behaviors, as well as attempts to prevent or mitigate its destructive effects. Indeed, most of the collected papers revealed the affective side of living with the pandemic. These studies cover topics of anxiety Fear of COVID-19, Stress, and Anxiety in University Undergraduate Students: A Predictive Model for Depression Anxiety and Social Support as Predictors of Student Academic Motivation During the COVID-19 The Influence of Personality, Resilience, and Alexithymia on Mental Health During COVID-19 Pandemic (Mehuli\u0107 and Kamenov)Mental Health in Affectionate, Antagonistic, and Ambivalent Relationships During the COVID-19 Pandemic: A Latent Profile Analysis The Relationship Between Quarantine Length and Negative Affect During the COVID-19 Epidemic Among the General Population in China: The Roles of Negative Cognition and Protective Factors .The Moderation Effects of Comparative Thinking Between Gratitude and Negative Affect During the COVID-19 Outbreak Analytic Thinking and Political Orientation in the Corona Crisis Who Believes in COVID-19 Conspiracy Theories in Croatia? Prevalence and Predictors of Conspiracy Beliefs The Relationship Between Perceived Stress and Subjective Cognitive Decline During the COVID-19 Epidemic .Individual Differences Facing the COVID-19 Pandemic: The Role of Age, Gender, Personality, and Positive Psychology vs. non-pharmacological measures differ, which should also be considered when planning communication strategy. These are the studies dealing with the above topics:Lep et al.)One Hundred and Sixty-One Days in the Life of the Homopandemicus in Serbia: The Contribution of Information Credibility and Alertness in Predicting Engagement in Protective Behaviors Boldness Personality Traits Are Associated With Reduced Risk Perceptions and Adoption of Protective Behaviors During the First COVID-19 Outbreak .Trust in Science, Perceived Vulnerability to Disease, and Adherence to Pharmacological and Non-pharmacological COVID-19 Recommendations , it is advised to avoid some self-guided techniques (such as expressive writing) in the context of the COVID 19 pandemic\u2014as suggested by the following studies:Rivera et al.)Autogenic Training Improves the Subjective Perception of Physical and Psychological Health and of Interpersonal Relational Abilities: An Electronic Field Survey During the COVID-19 Crisis in Spain Reduction of COVID-19 Anxiety Levels Through Relaxation Techniques: A Study Carried Out in Northern Spain on a Sample of Young University Students .Effectiveness of Expressive Writing in the Reduction of Psychological Distress During the COVID-19 Pandemic: A Randomized Controlled Trial and three continents testified about the efforts made world-wide to better understand its impact and mobilize inter- and intra-individual resources in combating its negative consequences.We have found commonalities of psychological responses of fear, anxiety, conspiracy, resiliency, and support across countries and cultures. We have also seen strong individual and group differences responding to COVID-19 related stress due to age, gender, and culture. This Research Collection provides examples of the many ways in which evolutionary principles can help advance psychological and behavioral science applied in a pandemic context. The Topic provides scientific evidence of effective coping strategies to protect from stress and negative emotions, such as:- Build trust in science and lower the sense of political helplessness- Increase optimism, cognition, uncertainty tolerance, and social support- Mindfulness, relaxation, and writing to reduce stress.This Research Topic was envisioned as an evidence-based reminder of the times of crisis caused by the new and then little-known coronavirus. By clearly identifying areas of research important for our coping with the pandemic and its effects, this Research Topic has outgrown its primary purpose. It can now be viewed as a tool for generating new valuable research ideas, consolidating the existing findings, and testing future treatment strategies.AV has drafted the article. All authors have contributed to the final revision to the editorial.Part of the effort was supported by United States National Institute of Health AG060608 to YJ.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "World Heritage sites, Biosphere reserves and UNESCO Global Geoparks are three primary categories of UNESCO-designated sites. As irreplaceable sources of life and inspiration, heritage is our legacy from the past, what we live with today, and what we pass on to future generations . StrengtTaking into consideration the interdisciplinary nature of heritage studies, scientists, engineers, managers and relevant stakeholders with diverse knowledge advocate a more cooperative approach to develop comprehensive, yet practical, solutions and applications. Space technologies, including remote sensing, Geographic Information System (GIS), Global Navigation Satellite System (GNSS), along with big data, cloud computation, artificial intelligence, 5G communications etc., provide a new paradigm of scientific and technological innovation, with the potential to transform the way of social production and people\u2019s life.The relevance and performance of space technologies in managing and monitoring heritage sites has already been established. Applications for space technologies in heritage conservation enable innovative solutions primarily in three aspects. First, the core elements of heritage ontology along with surrounding environments can be digitalized to develop seamless virtual representations that help to archive valuable archaeological assets, improve resource management, enable digital forensic studies and data intensive investigations utilizing modern analytical techniques and methods. Secondly, space-air-ground stereoscopic observation enables high resolution monitoring of heritage sites to sense minute changes and perceive historical and ongoing transformations in near real-time providing comprehensive information to develop practical solutions. Third, multisource spatiotemporal data and models can be collected, and integrated into a smart management system.Additionally integrating big data analytics, along with simulation/prediction, virtual reality/augment reality, socio-economic and geo-science process model, enhances the capacity to optimize management countermeasures to ensure sustainable development of these heritage sites. These technological resources also help to promote the Outstanding Universal Value (OUV) of heritage sites through digital communication platforms improving knowledge, education, awareness, and recognition of the OUV, and improving community involvement sustainable conservation of UNESCO-designated sites, ensuring a transformation towards a resilient society.The International Centre on Space Technologies for Natural and Cultural Heritage (HIST) under the auspices of UNESCO was proposed to UNESCO by the Chinese Academy of Sciences (CAS) in May 2007. The proposal was approved by the 35th General Conference of UNESCO in October 2009, and ratified by China\u2019s State Council in April 2011. On 24 July, 2011, the launching ceremony of HIST was held in Beijing. HIST is devoted to developing and utilizing space technologies for the identification, conservation, monitoring and management of UNESCO-designated sites to support UNESCO and its Member States in the implementation of the World Heritage Convention and providing support for the implementation of the UN 2030 Agenda for delivering Sustainable Development Goals (SDGs).Introduction to Space Archaeology (Chinese Version), which is the first book of its kind that reviewed space information technology applications for archaeology and introduced different space information techniques used for archaeology application and discussed the potential to establish a new discipline: Space Archaeology. Another prominent case is that HIST worked with other international scientists to make the discovery of 10 new archaeological sites in Tunisia dating to ancient Rome using Chinese space technology, which won the plaudits from Tunisian Ministry of Culture and Chinese Academy of Sciences. In addition, HIST has also expanded its global network with more than 30 UNESCO Member States and international organizations such as IUCN, ICOMOS, ICCROM. In the past decade, HIST has\u00a0made outstanding achievements, received international recognition and wide praise from UNESCO and other international organizations as well as relevant governments and institutions across the globe.Since its inauguration in July 2011, HIST has played a vital role in assisting UNESCO and its Member States in the conservation of UNESCO-designated sites. It has conducted 70 international conservation projects such as Remote Sensing for Environment of Angkor Site, Monitoring Landscape Evolution and Abnormal Deformations of the pagodas in Bagan World Heritage site, Monitoring and Analysis of Changes in the Forest Cover Loss in Asian Elephants\u2019 Habitats in Sri Lanka, Digital Characterization and Preventive Conservation of the Ming Great Wall with 20 UNESCO Member States, like Cambodia, Tunisia, Italy, Brazil, and strengthened capacity building through cultivating 20 doctoral students from developing countries and training 300 heritage site managers, technicians, researchers and decision-makers from UNESCO Member States. Meanwhile, HIST has pioneered the building of a new discipline-Space Archaeology. One of the landmark achievements is the publication of the Heritage Science, part of Springer Nature, to launch the special issue (article collection) to commemorate its 10th anniversary. This special issue presents the latest academic achievements from HIST researchers and its international partners. It groups a selection of eleven papers to illustrate the uses of space technology in the characterization, monitoring and assessment of heritage sites. These research studies not only highlight the necessity of this technology by emphasizing its benefits in first-hand data collection at macro\u2013micro scales, but also reveals its advantages in sustainable conservation of heritage properties by means of spatiotemporal analysis and scientific findings.Supported by the Bureau of International Cooperation, Chinese Academy of Sciences, HIST has joined hands with As the one of the four ancient civilizations worldwide, the\u00a0Chinese civilization is quite unique and one that has lasted continuously for thousands of years. Cultural heritage sites are witnesses to our history, a mirror to reflect upon our past. Yan et al. utilizedOn site or space-based monitoring and surveillance is the most effective way to evaluate the condition of heritage sites as well as their surrounding environment. For those inaccessible locations , the prominent role of remote sensing for heritage monitoring is essentially important and irreplaceable. Owing to the technological advance of active and passive Earth observation sensors along with intelligent processing chains and the emerging of open-source data , remote sensing has been applied as a systematic observation tool for stakeholders to map drastic or slowly driven landscape changes towards the better management of these sites and their surroundings . In caseThe paradigm of scientific discovery has transformed from statistical modelling to the data-driven and knowledge mining in the era of big data. Considering the transboundary and interdisciplinary characteristics of heritage studies, the potential of big data science in the sustainable conservation and smart management of heritage sites needs to be fully exploited. In Liang et al. , the spaIn general, the digital technology and data aggregation are the foundation for the data-driven knowledge mining. In the smart management of Mount Lushan project, Cai et al. evaluated the performance of digital technologies including oblique aerial photography, 3D laser scanning and 360-degree panorama imaging and synergistically utilized them to integrate all elements into a virtual tourism subsystem. This pilot application is a representative demo to overcome the shortcoming of heritage protection and heritage tourism marketing .Looking forward, future researches on the application of space technologies to heritage conservation will be conducted in six major fields: (a) heritage-related multi-source data access, big data processing and analytic techniques, (b) fine-precise heritage conservation methods; (c) digital heritage technological system based on high and newly emerging technologies; (d) blending and presentation techniques for heritage utilization; (e) the formulation of different standards for heritage property conservation and digital conservation; (f) participatory heritage education, social governance pathways and methods.In the next decade, HIST would like to strengthen partnerships with UNESCO and its Member States and advisory bodies as well as other international organizations to meet strategic demands for the conservation and sustainable development of UNESCO-designated sites. It calls for global stakeholders to make concerted efforts to integrate science, technology and engineering to develop a system of theoretic framework and technological methodology, to further build space archaeology paradigm, to construct an international digital world heritage platform for scientific research and technological application by integrating database, monitoring, evaluation, presentation and decision support, and to establish a whole chain of digital heritage with a mix of data access, processing, analysis, presentation, application and industrialization, thus helping UNESCO and its Member States to achieve heritage-related SDGs."} +{"text": "Religiosity and spirituality are commonly supported and viewed as essential elements of well-being in old and very old age, particularly at end of life. These essential elements often include the exploration of the meaning in life, inner peace, belonging, contentment, and near-end-of-life-completion. The positive outcomes of religious and spiritual beliefs and practices have been well established. However, these experiences and related positive outcomes may not always include a diverse array of older adults. The spiritual care of older adults is becoming more culturally diverse and includes differing perspectives on what constitutes spiritual care, both in approach and practice. This symposium will explore the current state of spiritual care for older adults through a lens of cultural diversity and inter-religious/spiritual perspectives. A focus on the current practices of spiritual care for older adults and future implications will also be considered. Recommendations pertaining to future gerontological inquiry in the importance of spiritual care, as well as diverse approaches within gerontological practice will be highlighted and discussed."} +{"text": "The current increase in the number of publications on the use of artificial intelligence (AI) technologies in neurosurgery indicates a new trend in clinical neuroscience.The aim of the study was to conduct a systematic literature review to highlight the main directions and trends in the use of AI in neurosurgery.Using the PubMed search engine, 327 original journal articles published from 1996 to July 2019 and related to the use of AI technologies in neurosurgery, were selected. The typical issues addressed by using AI were identified for each area of neurosurgery.The typical AI applications within each of the five main areas of neurosurgery were defined.The article highlights the main areas and trends in the up-to-date AI research in neurosurgery, which might be helpful in planning new scientific projects. In the first part of this systematic review : 106), using topic modeling, we determined the main topics featured in publications on artificial intelligence (AI) in five important fields of neurosurgery: neuro-oncology, functional, vascular, spinal neurosurgery, and traumatic brain injury. The second part of the review presented here discusses the main issues addressed by the authors to test and evaluate AI methods.The review was conducted using PRISMA guidelines .The analysis covered journal articles and international conference proceedings that met the following criteria:the publication was an original research article;the publication referred to a disease and/or a treatment directly related to neurosurgery;the authors analyzed the use of AI technology for solving clinical problems of diagnosis, treatment, prognosis, rehabilitation, or prevention of a nervous system disorder;neurosurgery was a potential or actual field of application for the AI technology analyzed in the study.(https://www.ncbi.nlm.nih.gov/pubmed/). The search query was phrased to find all documents, in which the terms \u201cneurosurgery\u201d or \u201cneurosurgical procedures\u201d were coupled with terms related to specific AI technologies in all database fields. The exact and complete query in the PubMed search engine is given below:The literature search for this systematic review was performed with PubMed US National Library of Medicine search engine system OR \u201cneurosurgical procedures\u201d[All Fields] OR \u201cneurosurgery\u201d[All Fields] OR \u201cneurosurgery\u201d[MeSH Terms]) AND .The search results from PubMed were reviewed to select original articles that met the inclusion criteria in this systematic review. The selected articles were classified according to the relevant fields of neurosurgery. The topics in these studies were preliminary outlined by experts and their number was counted. The selection process and the technical tools used in this systematic review have been detailed in Part I.In accordance with the inclusion criteria, 327 papers published between 1996 and July 2019 were selected. A complete list of the 327 publications is presented in the Appendix. Below, we analyze the application of AI technologies in each field of neurosurgery in more detail; typical publications illustrating the study objectives are shown in brackets. Approximately 41% of the selected studies provide examples of using AI technologies in neuro-oncology (see Appendix). Most of data for these works were obtained from medical images as well as from genomic sequencing and histology.The main tasks in neurosurgical oncology attempted to be solved using AI technologies were:segmentation and volumetry of brain structures , 3;noninvasive tissue and molecular genetic differential diagnosis \u20137;predicting complications and treatment outcomes , 9.One of the unconventional AI applications in neuro-oncology was the analysis of research trends in neuro-oncology based on scientific publications. An interesting task to be solved was concerned with the brain shift during neurosurgery. The solution to this problem is of great importance for the developing technologies of intraoperative neuro-navigation. Approximately 19% of articles on the use of AI in neurosurgery address the issues of functional neurosurgery, including epilepsy surgery (see Appendix). The data in these studies were obtained from electroencephalography and electrocorticography, magnetoencephalography, medical imaging , as well as deep brain stimulation, video monitoring of patient\u2019s condition, medical records, biochemical and genetic analyses, wearable devices.Among the typical tasks approached by researchers in these studies, there were:diagnosis of epilepsy, ictal and interictal activity, seizure predictors \u201312;functional tractography ;search for epileptogenesis biomarkers ;patient selection for epilepsy surgery ;predicting outcomes of epilepsy treatment ;Parkinson\u2019s disease diagnostics ;study of functional compensatory mechanisms in patients with Parkinson\u2019s disease ;study of movement disorders in Parkinson\u2019s disease ;electrophysiological identification of postural tremor and voluntary movements with essential tremor ;detection of targets, planning and modulating of deep brain stimulation ;prediction of postoperative side effects ;predicting the outcomes of microvascular decompression in hemifacial spasm ;search for electrophysiological correlates of neuropathic pain ;diagnosis of neuropsychiatric disorders ;research of episodic and semantic memory mechanisms ;speech-based identification of hemisphere dominance ;detection of the epileptogenic focus and segmentation of brain structures .This section of neurosurgery is characterized by a greater variety of research tasks as compared with neuro-oncology. Predominantly, attention was paid to epilepsy and movement disorders. The principal source of data was the electrical activity of the brain as recorded not only from the scalp, but also from the cortex and deep brain structures including specific neural ensembles. Using intracranial microelectrodes, researchers were able to directly measure the electrical activity in the brain and then analyze that in studies on memory and speech. Research in vascular neurosurgery accounted for 14% of the entire pool of retrieved publications on AI in neurosurgery (see Appendix). Most of the data were retrieved from medical images followed by the data from medical information systems, bedside monitor recordings, electroencephalography, stereolithography, blood tests, and social/demographic questionnaires. A non-typical source of data in this field was a study on environmental pollution.The key tasks of the above studies were:identification of patients with aneurysms ;diagnosis of unruptured aneurysms ;risk factors and risk assessment for aneurysm rupture and spontaneous intracranial hemorrhage ;risk assessment for cardiac disorders after aneurysmal subarachnoid hemorrhage ;predicting outcomes of ruptured aneurysms ;predicting ischemia after aneurysmal subarachnoid hemorrhage ;grading the severity of intracranial vascular stenosis ;diagnosis of atherosclerotic plaques ;predicting a persistent decrease in blood pressure after carotid stenting and angioplasty ;risk assessment for stroke after carotid artery stenting ;predicting perfusion deficiency ;segmentation of blood vessels and arteriovenous malformations ;predicting adverse events and outcomes of treatments for arteriovenous malformations ;definition, classification, and segmentation of intracranial/intracerebral hemorrhage ;discovering the genesis of intracranial hematomas ;predicting an increasing volume of hypertensive intracerebral hematoma ;risk assessment for intracerebral hemorrhage ;predicting functional outcomes of intracerebral hemorrhage ;predicting consciousness impairment in hemorrhagic stroke .Despite the substantially smaller number of publications as compared to neuro-oncology, the field of vascular neurosurgery earned a fairly wide range of AI applications. Most of these tasks can be summarized as (i) diagnosing pathological vascular formation and (ii) predicting complications and treatment outcomes. The use of AI in the field of spinal neurosurgery was discussed in 8% of the publications (see Appendix). The main sources of data in this area were medical images , as well as the data obtained from limb motion sensors. Special data were derived from video recordings of the surgeon\u2019s movements, as well as articles from the US National Library of Medicine. The main tasks addressed in this area of research included:prediction of complications ;prediction of treatment outcomes ;hospital discharge options ;transformation of images into different modalities ;segmentation of bone tissue and the spine ;grouping of patients and interventions for spinal deformation surgery ;assessing the motor function in patients with cervical spine disease and lumbar stenosis of the spinal canal , 54;assessing the foot drop in lumbar radiculopathy ; visual predicting the long-term use of opioids after surgery ;predicting the development of osteoporosis .The unusual research in this category included two studies on predicting changes in the intracranial pressure in patients during spinal surgery and predicting the surgeon\u2019s actions during the intervention , 60. In 8% of the selected studies, AI was used for issues of neuro-traumatology (see Appendix). The reported data were extracted from medical images , electroencephalography, patient monitoring devices , clinical examinations, eye movement recordings, and genetic studies.With a relatively small pool of AI-associated articles, traumatic brain injury is an area with multiple data sources and quite a few challenging problems related to prognosis. The main objectives of the analyzed studies were:assessing the severity of traumatic brain injury ;diagnosis of impaired consciousness ;quantitative assessment of intracerebral changes ;search for biomarkers of traumatic brain injury ;prediction of secondary injuries, classification of adverse events and complications ;predicting outcomes, searching for prognostic factors ;evaluating autoregulation of cerebral blood flow ;noninvasive assessment of intracranial pressure . About 10% of the studies on AI application in neurosurgery were concerned with general issues relevant to a number of neurosurgical conditions or non-specific for any disease. In these studies, medical imaging data, electrophysiological data, and other sources described above were used. For example, an analysis of infectious complications in patients in the neuro-intensive care unit.Non-standard sources of data in this area included photographs of patients\u2019 faces, information from smartphone , and texts of scientific publications. In the above studies, both traditional approaches to classification and prediction and the most recent methods were used. Thus, almost the entire spectrum of modern AI technologies was involved in these studies.According to our literature review, the majority of data concerning the use of AI technologies in neurosurgery come from neuroimaging, genome sequencing, invasive and non-invasive biosensors, and medical information systems (including unstructured data). Along with that, much less attention has been paid to the AI-based analysis of medical texts .Current technologies of text analysis allow one to explore the content of medical records, highlight relevant information, and test scientific hypotheses. AI technologies can not only extract data from medical texts but also create diagnostic and predictive models based on this data . An archImportantly, electronic medical libraries represent an invaluable source of \u201cbig\u201d data for research tasks. Today, generalization and critical assessment of research results using the criteria of evidence-based medicine are carried out by experts who write systematic reviews and meta-analyses . As a ruToday, a common limitation of AI-assisted research in neurosurgery is a relatively small sample size compared to the \u201cbig data\u201d that has been processed by machine learning in other branches of science and industry. This data insufficiency calls into question the scalability of AI-powered solutions, even though it performs well in isolated studies. That is why research projects using AI technologies are beneficial and productive for medical research organizers who own the resource of big data.In our opinion, when planning research using AI technologies, it is important to adhere to the principles of evidence-based medicine, which ensure the scientific validity of the obtained results and, therefore, increase their benefit to patients. Research planning and the choice of methodology are of fundamental importance and should be adequate to achieve the study objective while minimizing potential biases. In addition, technologies for analyzing large amounts of data can, to a certain extent, compensate for the methodological limitations of research in neurosurgery .With a wide range of tasks demonstrated in this review, the application of the AI technologies can be reduced to two major areas \u2014 research and clinical practice.In research, the AI potential involves its ability to extract a lot of useful information and knowledge by making this extraction most efficient and by reducing the time of investigation. This approach overcomes the limitations of traditional mathematical statistics, which test hypotheses using much fewer data.In clinical practice, AI can be instrumental in solving tasks of medical activities automation, i.e. accelerating, simplifying, and increasing the reliability of diagnosing diseases, making clinical decisions, and predicting possible complications and outcomes of medical interventions. Thus, AI is expected to bring an economic effect by reducing human labor costs and the time for decision-making in medicine.A good understanding of the AI technologies perspectives justifies the efforts to develop and test these methods in research and clinical medicine. The term \u201cartificial intelligence\u201d can be intuitively understood as \u201ca machine capable of thinking\u201d, and in the context of medicine \u2014 literally \u201ca robotic doctor\u201d. Neuroscience has not yet reached the understanding of human intelligence, and AI technologies have not come close to creating an \u201cartificial brain\u201d. At present, the methods united by the concept of \u201cartificial intelligence\u201d, solve rather traditional and pragmatic tasks, but using entirely novel technologies. Calculations based on AI methods, like the results of traditional statistical analysis, are interpreted by a medical doctor. Despite the similarity between the principles of mathematical algorithms and human intellectual activity, the AI methods cannot yet imitate consciousness, conscience, reflection, and other abilities of the human mind, which allow the doctor to make informed and responsible decisions. Like robotic navigation systems, microscopes, and linear accelerators, AI technologies are new tools in the doctor\u2019s arsenal. Today, they have the potential to become routine, but, for now, they cannot replace a clinician. This work includes a large number of publications reflecting major trends in using AI in neurosurgery without addressing the issues of efficacy, safety, or economic feasibility of specific technologies under specific conditions. Thus, the authors limit their scope to stating the facts of using AI methods in various tasks without assessing the quality of these studies.To date, research using artificial intelligence technologies has been carried out mainly in five major areas of neurosurgery: neuro-oncology, functional, vascular, and spinal neurosurgery, and the area of traumatic brain injury. The main sources of data in these studies were neuroimaging, genome sequencing, biosensors, and medical records. The use of artificial intelligence is becoming a global scientific trend in neurosurgery, therefore, an assessment of their efficacy, safety, and applicability in the clinic is highly important."} +{"text": "Mycobacterium tuberculosis DNA in a cutaneous fragment, through polymerase chain reaction, the diagnosis of gummatous tuberculosis was confirmed, probably secondary to hematogenous dissemination from an intestinal focus.As the treatment of infectious and parasitic diseases improved, the prevalence of these conditions declined. However, with the expansion of the use of immunobiologicals, opportunistic infections have emerged, especially under atypical presentations. The present study reports the case of a patient treated with infliximab for Crohn's disease, who presented diarrhea, weight loss, abdominal pain, fever, and subcutaneous erythematous nodules that evolved with spontaneous fluctuation and ulceration. With the finding of alcohol-resistant bacilli and Immunobiologicals were introduced in the 1990s to treat inflammatory bowel diseases.A 26-year-old female patient was diagnosed with Crohn's disease (CD) due to stomach enterorrhagia and abdominal colic. After therapeutic failure with prednisone, mesalazine, and azathioprine, infliximab 5\u202fmg/kg was initiated. Despite the initial improvement in symptoms, she gradually worsened. After 14 months on infliximab, she maintained an active disease and weight loss, in addition to daily feverish peaks. She presented three subcutaneous erythematous nodules on the posterior region of the right thigh, of approximately 3\u202fcm in diameter, without fluctuation or drainage. Subsequently, these lesions ulcerated, with well-defined edges and a necrotic background . HistopaYersinia pseudotuberculosis was raised. The treatment with gentamicin and ceftriaxone was ineffective, with the onset of a new erythematous cutaneous nodule on the left thigh, which revealed the presence of AAFB on histopathological examination (Mycobacterium tuberculosis by the rapid molecular test, confirming the diagnosis of gummatous tuberculosis. Computed tomography of the chest showed nonspecific nodules, and pulmonary involvement was not ruled out. Treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol was instituted for six months. The ulcerated nodules healed completely after the third month, with no recurrence after one year of follow-up.Due to the characteristics of the granulomas, the hypothesis of infection with mination and geneCutaneous TB accounts for approximately 1% of the cases of the disease.6Gummatous tuberculosis is rare and affects mainly immunosuppressed and malnourished children. It is characterized by subcutaneous erythematous nodules, which evolve with intense central necrosis, fistulization, and ulceration. It results from the acute hematogenous spread of a primary outbreak during periods of bacillemia. The tuberculin test is usually negative. Histopathology shows extensive necrosis, formation of loose granulomas, and high bacillary load. Molecular techniques also contribute to the diagnosis.None declared.Lucas Campos Garcia: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Everton Carlos Siviero do Vale: Approval of the final version of the manuscript; drafting and editing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Maria de Lourdes Ferrari: Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases.Lauro Damasceno de Carvalho Faria: Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases.None declared."} +{"text": "This Special Issue on Development of Laser Welding and Surface Treatment of Metals contains as many as twenty-two research articles mainly related to the application of lasers, but also on other welding processes that may be competitive to laser technologies under specific conditions. Despite the introduction of lasers for material processing in the 1960s, the continuous development of laser devices also leads to the development and expansion of laser technology applications. This Special Issue is a compendium of knowledge in the field of fusion welding, the manufacturing of surface layers and coatings with increased wear resistance and tribological characteristics, as well as corrosion resistance and the characterization of coatings and surface layers. The topics of the presented research articles include aspects related to laser welding (eight articles), especially technological conditions, the properties of different types of joints, and analytical and numerical aspects of modelling the laser heat sources. The second dominant issue concerns laser cladding and laser surface treatment of different ferrous and nonferrous metallic and composite materials (six articles). In addition, there are interesting results of the study of fusion welding under forced cooling of the deposit or underwater conditions (four articles), results on the characterization of wear resistance coating produced by different technologies that can be competitive for laser cladding (three articles), and an original study on local strengthening of the thin-walled structure by laser treatment (one article). This Special Issue provides very wide and valuable knowledge based on theoretical and empirical study in the field of laser and fusion welding, laser and related coating technologies, characterization of coatings, and wear phenomena. Striving for sustainable development as well as limiting the harmful impact on the environment, including the reduction in COructures ,2,3.Therefore, new materials are being developed with higher mechanical properties, higher wear resistance and thus higher operating parameters. The conventional welding methods and technologies usually do not provide satisfactory results in applications such as joining and cladding of modern materials, e.g., high strength steel, nonferrous metals and alloys, composite materials, and nanostructured and hybrid materials ,5,6,7,8.The main disadvantages of typical methods of welding and cladding such as conventional arc or plasma arc methods are excessive heat input and the relatively large volume of the molten pool. This leads to overheating of the material, internal stresses and deformations, and unfavorable grain growth or dissolution of the reinforcing phase particles, e.g., carbides or nitrides. Therefore, the attention of researchers and industry is focused on the search for methods of joining and processing materials that ensure a minimum thermal effect on the material and the ability to precisely control the amount of heat and the thermal cycle of the process ,11,12,13One of the dynamically developed areas of material processing technology in recent years is laser material processing technology. In the area of joining materials, laser welding shows several advantages because it provides high-power densities and low diameter of the laser beam spot, and thus high penetration depth, high welding speed, and low, precise, and controllable heat input. The above features are particularly important for the joining of modern and advanced alloys such as ultra-high-strength steels (UHSS), advanced high-strength steels (AHSS), modern stainless duplex and super duplex steel, nonferrous metals, and light metals, e.g., titanium and aluminum alloys ,15,16,17Another area of laser beam application that is currently being intensely developed is the shaping of the properties of surface layers and the production of coatings for enhanced wear characteristics such as corrosion resistance, tribological properties, abrasive resistance, thermal and mechanical fatigue resistance, and resistance to impact load ,6,7,8,18In the area of surface treatment and cladding, the laser beam as a heat source is also advantageous. The most significant advantages include low and controllable heat input, and thus limited thermal impact on the substrate, reduced internal stresses, minimized distortions, high solidification and cooling rates, low penetration depth, and low dilution of the clad layer by the substrate material. Low heat inputs and related high cooling rates during laser processing are beneficial in many applications of surface treatment and cladding as they provide high quality clads and surface layers. Usually, surface layers are characterized by superior metallurgical bonding and a fine-grained and refined microstructure, which are decisive for providing superior tribological characteristics, high abrasive or erosion wear resistance, and corrosion or fatigue resistance ,8,18.It is worth noting that laser-made clads and surface layers show higher functional properties compared to surface layers made by plasma arc (PTA) or conventional arc cladding processes, even if the same additional materials are applied. This is due to intense grain refinement caused by very fast cooling and solidification of the molten pool, typically an order of magnitude higher than plasma (PTA) and conventional arc cladding ,12.Thanks to the advantages mentioned above, lasers are used in different processes of surface treatment such as laser surface hardening (LSH), melting (LSM), shocking (LSS), texturing (LST), alloying (LSA), cladding (LSC), remelting (LSR), and surface deposition (LSD), and in additive manufacturing processes such laser metal deposition (LMD) or selective laser sintering and melting (SLS/SLM) .2 and solid-state rod type Nd:YAG laser generators used for the last few decades, new generations of solid-state lasers are currently available such as high-power diode lasers (HPDL), disk lasers, and fiber lasers [2 gas lasers and disk lasers, as well as fiber lasers [Continuous development of laser generators and related improvement of laser radiation and laser beam characteristics enable further development in the field of laser material processing, including laser welding and laser surface treatment. In addition to the gaseous COr lasers ,15,16,17r lasers ,17,18. There has also been significant progress in the design and construction of fiber generators in the last decade. Modern fiber lasers are also beneficial due to their compact design, high wall plug efficiency, low beam divergence, and possibility to focus the beam into a very small spot, even at relatively high power . MoreoveAnother interesting example of dynamic development in the field of material processing technology is hybrid processes. According to the definition, the hybrid process combines at least two different machining processes which must be carried out simultaneously and in the same processing area . In the case of welding, the laser beam is often combined with the arc, e.g., laser + GMA , laser + GTA (gas tungsten arc) or laser + PTA (plasma tungsten arc). Such combinations of two different heat sources allow taking the advantages of both welding methods. The laser beam is responsible for deep penetration of the material, while the arc processes provide additional heat and material to fill the gap. Consequently, it is possible to weld at high speed and ensure the correct shape of the weld at high depth. Hybrid processes are also being developed in the field of surface treatment and coating applications, ensuring higher functional parameters or the possibility of producing coatings with special properties ,18.The Materials and Methods should be described with sufficient details to allow others to replicate and build on the published results. Please note that the publication of your manuscript implicates that you must make all materials, data, computer code, and protocols associated with the publication available to readers. Please disclose at the submission stage any restrictions on the availability of materials or information. New methods and protocols should be described in detail, while well-established methods can be briefly described and appropriately cited.-Study of technological conditions of laser welding, investigation of test joints properties ,24,25,26-Analytical and numerical models of heat sources of laser beam and arc welding processes ,20,22,23-Study of laser cladding and investigations of the coating\u2019s properties and tribological characteristics ,31,32,33-Study and development of fusion welding processes, investigation of properties of the deposit produced under forced cooling or underwater conditions ,35,36;-Study of cladding, surfacing, and thermal spraying processes of wear-resistant coatings, characterization of the coatings ,38,39;-Study of application of local strengthening of the thin-walled structure by laser treatment .This Special Issue, entitled \u201cDevelopment of Laser Welding and Surface Treatment of Metals\u201d, is a complementary and valuable resource of knowledge in the following fields:In the work presented by Wang et al. , plates Kik presenteIn the second article, Kik presenteThe study presented by G\u00f3rka was focu2 laser welding of lap joints of low-carbon structural steel. They determined hardness profiles and weld geometry for the welds produced at different parameters. They also provided detailed analysis of the metallographic structure of fusion zone (FZ) and heat-affected zone (HAZ), as well as a quality assessment of the tested joints. The laser welding process was also investigated by Danielewski and Skrzypczyk . They prThe study presented by Landowski et al. concerneThe results of the study presented by Pa\u0144cikiewicz et al. also conAnother study on laser welding was presented by Tofil et al. . They coThe topic of laser surface treatment and cladding begins with Lisiecki\u2019s article on the s4C particle on the microstructure and chosen properties was investigated and determined. A highly interesting study on laser surface modification of an aluminum alloy by boron carbides was carried out by Sroka et al. . The fibAnother interesting study on laser cladding was performed by Li et al. . In theiThe next study, presented by Majkowska-Marzec et al. , is relaA comparative study of laser and plasma cladding was presented by Czupry\u0144ski et al. . The coaAnother study on the effect of laser treatment on tribological properties was presented by Lubas et al. . They an2C-WC carbides across the coating. The thematic series on laser surfacing and cladding ends with the article presented by Lisiecki and \u015alizak on hybriAnother very novel and interesting subject related to arc welding processes was presented by Szczucka-Lasota and Szymczak et al. ,35. The Some manuscripts dealt with other arc processes and technologies, but the presented solutions were very innovative. An example of a highly interesting subject was presented by Tomk\u00f3w et al. . They inThe study presented by Mician et al. was relaThe second study presented by Czupry\u0144ski was focuThe next article provided by Czupry\u0144ski presenteAnother original issue was presented in the study by Kapustynskyj et al. . They foThis Special Issue was very successful due to the valuable articles that were submitted, the wide variety of topics and research problems that were undertaken, and in-depth analysis of the state of the art in different fields of laser and related processes. This Special Issue contains a significant number of research articles ; however, the entire number of manuscripts submitted to this Special Issue was half that higher. Unfortunately, some of the manuscripts have not gone through a very rigorous review process. Such a large interest and quantity of articles shows the importance of the issue and themes. It should also be emphasized that each research article in the field of materials processing is the result of tedious, long-term, and interdisciplinary research, usually conducted by a team of scientists. The topics of the articles were mainly focused on laser welding, laser cladding, and laser surface treatment, as well as related processes of fusion welding and manufacturing of coatings. The wide range of experimental, numerical, or analytical study conducted and presented by 58 authors, representing 19 academic or research centers and 3 industrial centers from 5 countries and 16 cities, proved the topicality and importance of this Special Issue."} +{"text": "Artificial intelligence (AI), together with robotics, sensors, sensor networks, internet of things (IoT) and machine/deep learning modeling, has reached the forefront towards the goal of increased efficiency in a multitude of application and purpose. The development and application of AI requires specific considerations, approaches, and methodologies. This special issue focused on the applications of AI to environmental systems related to hazard assessment in Urban, Agriculture and Forestry. A total of ten papers were published in this special issue, with topics ranging from reviewing the current climate-smart agriculture approaches for smart village development to the iThe development of smart villages in Europe requires a framework to secure sustainability based on climate-smart agriculture. As argued by Adesipo et al. , these cOne of the detrimental effects of reduced green infrastructure is the contamination of waterways and water networks. The study by Lu\u010din et al. proposedFor agricultural systems, novel digital technologies were applied for farm animal welfare assessment based on weather information and cow data to predict milk productivity and quality through supervised machine learning . The modClimate change effects include the increased incidence, number and severity of climatic anomalies such as heatwaves and bushfires. These climatic anomalies have a specific impact on viticulture and winemaking, specifically with bushfires producing smoke contamination on leaves and berries, which are later passed to the wine through the fermentation process. These have been investigated in two studies focused on implementing digital technologies and machine learning modeling using low-cost electronic noses and nearFinally, low-cost electronic noses and near-infrared spectroscopy were also implemented to assess the infestation of insects in plants and the insect-plant interaction . This st"} +{"text": "Zienkiewicz and Zienkiewicz). Because of the vital role of lipid metabolism in photosynthetic organisms, exploring lipid processes is very important for engineering crops to obtain better agronomic traits including productivity, nutrition, stress tolerance and resilience.Lipids are the essential building blocks of cellular membranes, and they play fundamental roles in numerous biological activities such as photosynthesis, protection, environmental and cellular communication, and storage of carbon and energy. Lipid metabolism is a dynamic and complicated process that includes lipid biosynthesis, transport, accumulation, turnover, and excretion, acting to regulate plant development and tolerance to various environmental stresses. Understanding how lipid metabolism regulates the development and growth in response to adverse conditions raises many interesting questions. Communication between membrane and storage lipids has been observed during the progress, for example, membrane degradation accompanied by lipid droplet (LD) accumulation. Recently, autophagy has been connected with lipid metabolism in plants and algae under stress conditions . As the major reservoir of cellular carbon and energy, TAG is packed in LD, a dynamic organelle at the center of cellular metabolism. The review also compares the LD degradation in plants and algae , while Liao et al. show the roles of two rice acyl-CoA-binding proteins, OsACBP4 (plasma membrane and ER) and OsACBP5 (apoplast), in the intra- and extracellular transport of acyl-CoA esters, respectively leaves ; together with the specificities of extraplastidial acyltransferase enzymes, the olive OeFAD2-2 and OeFAD2-5 regulate the oleic/linoleic acid ratio in the mesocarp of olive cultivars . The Research Topic also highlights the significance of lipid metabolism in environmental stress response and tolerance that catalyzes the biosynthesis of very-long-chain fatty acid (VLCFA) in Citrus sinensis , reduces water loss and ion leakage and increases tolerance to drought and salt stress ; Arabidopsis phospholipid:diacylglycerol acyltransferase 1 (AtPDAT1) promotes the activities of acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT) and acylCoA:lysophosphatidylethanolamine acyltransferase (LPEAT) and improves resilience to heat and cold exposure . In Vaccinium corymbosum L., cv. Duke (Duke blueberry), intermittent warming treatment of the fruit regulates its lipid metabolism such as increases in phosphatidylcholine, linoleic acid, and oleic acid, which enhances the low-temperature tolerance in the fruit . In the roots of maize, integrated lipidomic and transcriptomic analyses reveal the membrane lipid remodeling and gene regulations under saline-alkaline or cold stress , which are applicable for engineering the crop for better performance under these stress conditions.This Research Topic includes 10 original review and research articles, with a special focus on lipid metabolism in crops. The review by nd algae . Lookingectively . Other cultivars (Hern\u00e1ndolerance . In ArabThe collection of articles in this Research Topic demonstrates the significance of lipid metabolism in various biological processes and the findings will contribute to engineering agronomic traits of crops for the increasing demand for food and bioproducts.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Objectives: To assess the quality of health facility documentation related to maternal deaths at health facilities in Afghanistan.Methods: Analysis of a subset of findings from the 2016 National Maternal and Newborn Health Quality of Care Assessment in Afghanistan. At each facility, maternity registers were reviewed to obtain data related to maternity caseload, and number and causes of maternal deaths in the year preceding the survey. Detailed chart reviews were conducted for up to three maternal deaths per facility. Analyses included completeness of charts, quality of documentation, and cause of death using WHO application of International Statistical Classification of Disease to deaths during pregnancy, childbirth and the puerperium.Key findings: Only 129/226 (57%) of facilities had mortality registers available for review on the day of assessment and 41/226 (18%) had charts documenting maternal deaths during the previous year. We reviewed 68 maternal death cases from the 41 facilities. Cause of death was not recorded in nearly half of maternal death cases reviewed. Information regarding mode of birth was missing in over half of the charts, and one third did not capture gestational age at time of death. Hypertensive disorders of pregnancy and obstetric hemorrhage were the most common direct causes of death, followed by maternal sepsis and unanticipated complications of clinical management including anesthesia-related complications. Documented indirect causes of maternal deaths were anemia, cardiac arrest, kidney and hepatic failure. Charts revealed at least eight maternal deaths from indirect causes that were not captured in register books, indicating omission or misclassification of registered deaths.Conclusion: Considerable gaps in quality of recordkeeping exist in Afghanistan, including underreporting, misclassification and incompleteness. This hampers efforts to improve quality of maternal and newborn health data and priority setting. The World Health Organization defines maternal death as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes . MaternaMaternal mortality in Afghanistan has significantly declined from 1,600 deaths per 100,000 live births in 2002 to 638 dDespite these challenges, the Ministry of Public Health (MoPH) in Afghanistan remains committed to reducing preventable maternal mortality and has set a national target for mortality reduction , consideMaternal death surveillance and response (MDSR) is widely implemented in low- and middle- income countries, as one strategy to identify and address health system weaknesses contributing to maternal deaths . In AfghHowever, while national guidelines for maternal and neonatal death surveillance and response exist, authorities acknowledge that maternal death audits have been poorly performed in Afghanistan and gaps exist in the quality of reported data , 15. BeyPrevious studies in Afghanistan have assessed accuracy and validity of maternity care records and quality of cesarean section-related documentation, but none have examined the availability and completeness of documentation of maternal deaths , 17. We National Maternal and Newborn Health Quality of Care Assessment, a cross-sectional health facility assessment conducted in 2016. The assessment was designed to examine health facility readiness for basic and comprehensive emergency maternal and newborn care, and assess quality of routine antenatal care, childbirth and postpartum care, and management of selected obstetric and newborn complications , and a random sample of facilities with fewer than five births per day (n = 149). The sample size for low-volume facilities was calculated to provide a representative sample of the 1,736 public facilities with < five births per day, with a 10% margin of error, 5% alpha error, design effect of 1.5 due to stratification of facility types, and 5% oversampling for potential inaccessibility due to geography or insecurity. In addition, 20 private health facilities were purposively selected to provide a snapshot of care at private sector facilities in all regions of the country.The Data collection was conducted by 32 female doctors and midwives trained on assessment objectives, data collection techniques and research ethics. Data collection methods for this paper included use of a facility inventory and record review tool to verify caseload, availability of relevant data and guidelines, as well as review of patient's folders or mortality charts. Data collection at health facilities with an average of at least five births per day was completed between May 14th, and August 3rd, 2016. Data collection at health facilities that averaged fewer than five births per day was completed from November 5, 2016, to January 5, 2017. At each facility, maternity registers were reviewed for information on the maternity caseload and number and causes of deaths in the year preceding the survey. Detailed chart reviews were conducted for up to three maternal deaths per facility; charts were requested for the three most recent maternal deaths in the previous year. For each chart, data collectors extracted information on client characteristics, location and mode of childbirth, timing and causes of death, and newborn outcomes. Data collectors reviewed charts for any information on factors contributing to maternal death and noted if women experienced any of the following: delayed arrival to health facility, delayed transfer to appropriate level of care, delay in care due to lack of supplies, delay in care due to absence or non-attendance on part of the health professional, delay in correct diagnosis . All datData was exported from CommCare to Excel for cleaning and analysis. We used visual inspection and descriptive statistics methods to analyze quality of documentation and completeness of charts, and case review methods to classify causes of death using WHO Application of ICD-10 to deaths during pregnancy, childbirth and the puerperium (ICD-MM coding). Facility types were defined as follows: (1) Specialized, Regional, and Provincial Hospitals; (2) District Hospitals (DHs) with an average of five or more births per day; (3) DHs and Comprehensive Health Centers (CHC) with an average of fewer than five births per day; and (4) Basic Health Centers (BHC), Sub Health Centers (SHC), Family Health Houses (FHH), and other primary health care facilities.The 2016 Afghanistan National Maternal and Newborn Health Quality of Care Assessment protocol was approved by the ethical review boards of the Afghanistan Ministry of Public Health (361533) and the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland . Written permission for data collection was also obtained from the in-charge of each facility.Review of maternity registers showed an average number of 194 births per month at public facilities and 67 births per month at private facilities in the Afghan calendar year preceding the assessment (April 2015 \u2013 March 2016). An average of 175 antenatal care visits per month were reported at public and 107 antenatal care visits per month at private facilities . Of publSpecialized, Regional, and Provincial Hospitals which reported an average of more than 8500 births per year , recordeWe reviewed patient charts for 68 women from 41 facilities , who died from direct or indirect causes related to the pregnancy, childbirth or clinical management. Seventeen charts did not record the age of the woman who died and 21 did not indicate gestational age. In more than half (39) mode of birth was not recorded. Seventeen did not record timing of death in relation to childbirth . Approximately half of the charts reviewed (35 of 68) recorded cause of death .Of the 51 charts with the woman's age recorded, four were <20 years old, 31 were between the age of 20 and 35 years and 16 were over 35 years of age. Of the 52 charts with birth location recorded, most (46) were facility births, whilst four women gave birth at home, and two women on the way to the health facility. Mode of birth was only recorded for 29 cases: 18 women gave birth vaginally and 11 by cesarean section. Fourteen women were referred from lower level health facilities and private sector to higher levels of care. Of the 51 charts with timing of death recorded, 33 were deaths occurring postpartum, 13 intrapartum and 5 antepartum.The review of patient's charts showed that the main causes of mortality were obstetric hemorrhage (17), hypertensive disorder, preeclampsia and eclampsia (16), amniotic fluid embolus (2), unanticipated complication of management such as anesthesia (2), sepsis (1), and ectopic pregnancy (1). Fifteen charts indicated no indirect causes of maternal death, while 37 did not record any information on indirect causes. The causes of death listed in 16 cases reporting indirect causes were cardiac, respiratory, liver and kidney disorders (9), anemia (4) and anemia with heart and kidney disease (2), and shock (1) . SixteenThe 68 maternal mortality charts reviewed included 59 singleton pregnancies and 9 twins . Of the Fifty-five of the 68 maternal mortality charts reviewed included information on factors contributing to maternal deaths . Thirty-Our study shows remarkable weaknesses in quality of documentation and record keeping, at both public and private facilities in Afghanistan. We found glaring gaps in completeness of recordkeeping. Critical information on characteristics of deceased were missing in nearly half of the records. Our results are in line with other studies from Afghanistan that have indicated that quality of medical record keeping is extremely low , 17, 22.Charts reviewed suggest that the most commonly reported direct causes of maternal deaths were obstetric hemorrhage, eclampsia, and abortions; fewer cases were recorded on maternal sepsis and complications of anesthesia. Hence, urgent effort is needed to first address these immediate causes of death for many women, while putting in longer-term efforts to strengthen the health system and working on social determinants that lie outside the realm of the health sector, in a multifaced approach , 3. As pAccurate classification of causes of maternal mortality is vital for decision making and provision of care; otherwise there could be misclassification and under-identification of maternal deaths at facilities, where a woman of reproductive age may die in a medical or surgical ward with an undiagnosed obstetric complication . For proNotably, reliability of facility level data will become even more important when frontline clinicians accurately record clinical activities and related outcomes in charts. Information on the medical records can be used to improve health service quality , 27. MorThe private health sector in Afghanistan is dynamic, rapidly expanding, and largely unregulated . Very feIn Afghanistan, the poor quality of medical records, lack of knowledge and skills, staff turnover, lack of coordination, the culture of blame and inadequate resources are barriers to conducting effective death reviews , 31, 32.Providing targeted refresher training on clinical record keeping, improved compliance by health care providers, staff support and fostering a culture of secrecy and professional protectionism, and non-punitive responses on medical errors, and strong leadership at national level and at lower levels of governance will lead to accuracy, reliability and completeness of medical records , 22, 31.There are some examples of successful large-scale implementation of MDSR in low- and middle-income countries, including in Malaysia, Sri Lanka and India. Evidence suggests that such implementation requires considerable efforts to identify and address maternal deaths and associated factors . In counMDSR remains a vertical intervention in Afghanistan, operated in parallel to the country's disease surveillance system. A study in Ethiopia has emerged the importance of MDSR embedment within the existing disease surveillance system as a routine practice rather than a stand-alone system, with a greater supervisory support to improve the reporting and response mechanism .There are considerable methodological shortcomings of surveys to measure maternal mortality in Afghanistan, exacerbated by the fragile context. Efforts should be redirected to improve access to and quality of routine maternal health data to obtain real time-insights, with increased longer-term investment in civil registration and vital statistics .The use of electronic medical records (EMR) in Cameroon and Malawi has shown an increase in completeness and accuracy of medical records , 36. A sOur study is not without limitations. It was designed to assess the quality of broader maternal and newborn health services. Therefore, only three most recent patients' charts per facility were reviewed, not all deaths in the previous year, so data on case characteristics and causes of death cannot be considered representative of all maternal deaths in Afghan health facilities. The private-sector snapshot provided only a limited picture of maternal mortality in private health facilities in Afghanistan and cannot be compared with nationally representative data from public health facilities. Despite these limitations, our study shines a light on the deplorable quality of record keeping and documentation of maternal health outcomes, and highlights challenges in relying on facility records for estimations of maternal mortality.Our study identifies considerable concerns with regard to the quality of record keeping in Afghanistan. These encompass under reporting, misclassification, and incomplete documentation. Improvements in record-keeping and health management information systems are critical to improve maternal and newborn health outcomes. Improving the quality of maternal and newborn health data requires robust political support and investment at various levels to support real-time clinical and political decision making and priority setting. This paper serves as a call to improve documentation and analysis of causes of maternal deaths amidst insecurity in Afghanistan, and to systematically improve accountability for coordinated, data-driven efforts to address factors associated with preventable maternal mortality.Data is available from the principal investigator or upon reasonable request or signature of a data use agreement.The studies involving human participants were reviewed and approved by the ethical review boards of the Afghanistan Ministry of Public Health (361533) and the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland (6799).FM served as co-trainer for the 2016 Afghanistan National Maternal and Newborn Health Quality of Care Assessment, wrote the first draft of this manuscript, led data analysis, interpretation and revision of this article. TvdA contributed to the writing and revision of the manuscript. JS served as a study advisory board member and contributed to the review and revision of the manuscript. HT served as principal investigator, led the data analysis, and contributed to the interpretation of study findings and revision of the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "People with substance use disorders may be at a greater risk of contracting COVID-19 infection and developing medical complications. Several institutional and governmental health agencies across the world developed ad hoc guidance for substance use disorder services and care of individuals misusing substances. We aimed to synthesise the best available recommendations on management and care of people with or at risk of substance use disorders during the COVID-19 pandemic from existing guidelines published in UK, USA, Australia, Canada, New Zealand, and Singapore.th 2021). We summarized the extracted data as answers to specific clinical questions.We systematically searched existing guidelines and websites from 28 international institutions and governmental bodies in the context of the COVID-19 pandemic (May 4We organised the available recommendations from 19 sources in three sections. First, we focused on general advice and recommendations for people who misuse alcohol or drugs during the COVID-19 pandemic, the design of contingency plans, safeguarding issues for children and families of service users and advice to the public, patients, and carers. Then, we summarised specific guidelines for people who use illicit drugs and related services, such as opioid substitution treatment and needle and syringe programmes. Finally, we provided a synthesis on specific recommendations for services supporting people who misuse alcohol and key topics in the field, such as management of alcohol detoxification and safe transition between supervised and unsupervised consumption.Available guidance reflected different approaches, ranging from being extremely cautious in providing recommendations other than generic statements to proposing adaptation of previously available guidelines to confront the challenges of the COVID-19 pandemic. After the early phase, guidance focused on reduction of infection transmission and service delivery. Guidance did not provide advice on infection prevention via vaccination programmes and service access strategies tailored to individuals with substance use disorders.The online version contains supplementary material available at 10.1186/s12888-022-03804-7. The corPeople with SUD may be more susceptible to developing COVID-19. They may have a higher burden of comorbid medical and mental health conditions, be less likely to be tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and live in social conditions which make it difficult to comply with home isolation \u201310. PeopGovernmental health agencies across the world have rapidly developed additional guidance on treatment services, with adaptations to national legislation and policies, to try and meet the specific needs of patients with SUD during the COVID-19 pandemic . HoweverTo aid the busy clinicians in rapidly accessing reliable sources of existing guidelines in this area, we systematically searched and synthesised the best available guidance of both governmental and non-governmental agencies in the UK, USA, Australia, Canada, New Zealand, and Singapore, focusing on treatment of SUD during the COVID-19 pandemic and its aftermath.th 2021:Governmental institutions: Public Health England (PHE), Centers for Disease Control and Prevention (CDC), US Department of Labor, Singapore Ministry of Health (SMH), Health Canada (Government department), Australian Government Department of Health, Substance Abuse and Mental Health Services Administration (SAMHSA), and Canadian Society of Addiction Medicine (CSAM).Professional bodies: Royal College of Psychiatrists (RCPsych), Royal College of Nursing (RCN), Royal College of Physicians (RCP), American Psychiatric Association (APA), Singapore Psychiatric Association (SPA), Singapore Medical Association (SMA), Canadian Psychiatric Association (CPA), Royal Australian and New Zealand College of Psychiatrists (RANZCP).Health Technology Agencies (HTA): The National Institute for Health and Care Excellence (NICE), Healthcare Improvement Scotland.International agencies: World Health Organization (WHO), Inter-Agency Standing Committee (IASC), UNICEF, European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).Scientific societies: The National Association of Psychiatric Intensive Care and Low Secure Units (NAPICU), RCPsych with British Geriatric Society and European Delirium Association, Massachusetts General Hospital Psychiatry, World Psychiatry Association (WPA), British Association of Psychopharmacology (BAP), Scottish Health Action on Alcohol Problems (SHAAP).A multidisciplinary team within the Oxford Precision Psychiatry Lab systematFurther sources were hand-searched from the references of each website. Given that summarising data from primary studies was beyond our scope, we did not search reference databases . Nonetheless, should we come across a particularly relevant publication, either supporting or in disagreement with available recommendations, we included it to better outline the context of a specific question. A search on Google was also completed using keywords relevant to COVID-19 , substance and alcohol use disorders and related treatments , and guidelines . Queries or disagreements were resolved by discussion with a third researcher (AC), and the team collaborated with international experts in the field to keep the guidance global, focused, and comprehensive. We incorporated the feedback of clinicians and mental health professionals, and the final synthesis of guidelines was grouped in a questions and answers format for ease of consultation, with key sentences highlighted in bold. The recommendations were classified as \u201cGeneral advice and recommendations\u201d, when applicable to the whole population potentially accessing healthcare services due to substance or alcohol misuse, or \u201cspecific guidelines\u201d when tailored to distinct sub-groups of service users. Finally, we appraised the identified recommendations according to type of source organisations and institutions , international agencies, scientific societies).n\u2009=\u200911, 58%%) were from governmental institutions , healthcare technology agencies (n\u2009=\u20092), professional bodies (n\u2009=\u20092), and scientific societies (n\u2009=\u20091). The identified sources focused on promoting telepsychiatry in routine care, providing detailed recommendations on how to deliver digital assessments to abide by the social distancing requirements. Moreover, available guidance emphasised the potential benefits of digital services, such as an increased level of anonymity for consultancy services, though inevitably some services require face-to-face interaction. A blended or mixed approach was thus recommended, such as in-person assessments delivered for people with a moderate level of dependence. Where possible, an increased level of flexibility was prompted in the provision of take-home treatments.We collected recommendations from 19 sources, \u201334 of whThe full guidance is reported in Table We have summarised the available guidelines published in English-speaking countries on several key topics relevant to the management of people with substance or alcohol use disorders and misuse of drugs or alcohol during the COVID-19 pandemic. Identified sources were primarily from governmental institutions. Available guidance reflected several changes to standard practice and care that occurred due to the impact of the COVID-19 pandemic on substance and alcohol use disorders treatment services. Key changes in recommendations focused on the role of telepsychiatry and increased flexibility in dispensing take-home treatments.Identified guidelines widely promoted the use of digital consultations and telepsychiatry to maintain social distancing when delivering substance and alcohol use services whilst minimising perceived social isolation. The social distancing restrictions in several countries prompted a rapid implementation of telehealth and the dissemination of digital mental health practices at an unprecedented pace . TeleheaIn the early phase of the COVID-19 pandemic, detoxification services needed to adapt the management and delivery processes of their activities. However, these changes to usual practice came with some drawbacks. Service disruptions and unmet support needs have been recorded as a direct result of the impact of the COVID-19 pandemic , 38, 39.In some cases, the initial adaptation of policies and recommendations to the COVID-19 pandemic significantly deviated from usual care. For instance, in the UK requirements for opioid substitution therapy prescription were relaxed. Drug testing was suspended as a requirement for buprenorphine prescription and, in the case of methadone, limited to individuals without a clear history of opioid use and tolerance and known patients with evidence that opioids have been used in the previous 24\u00a0h . In-persAs the pandemic has progressed, focus has shifted from immediate management and reduction of transmission to prevention via licensed COVID-19 vaccines. A key area of concern is vaccine hesitancy, in those with mental health difficulties more generally, and specOur work has some potential limitations. The search process was restricted to English language sources to synthesise available guidance from a list of English-speaking countries. The recommended resources in this paper are primarily limited to the UK and USA, whilst laws and policies regarding the treatment of and resources for people with SUD may differ between countries. For instance, this is indeed the case with regards to the treatment of opioid use disorder. Nonetheless, given the global nature of the COVID-19 pandemic, international collaborators have produced translations of our synthesis of guidance in several foreign languages and adapted it for local use , 13. SinSubstance and alcohol misuse services had to rapidly and profoundly change to limit disruptions for service users and, where possible, continue the treatments previously in place. At the same time, the demand for services increased. More than 8 million adults in the UK are drinking at high risk, and a surge in the number of people addicted to opiates seeking help have been recorded . Mental In the initial phase of the COVID-19 pandemic, regulatory agencies and professional bodies quickly provided guidance to address urgent issues. This rapid response was inherently based on limited evidence and resulted in several different approaches. Some sources of guidance were more conservative and limited to generic recommendations, whilst others suggested temporary amendments of pre-COVID-19 guidelines. Since then, a vast volume of scientific literature has been published on COVID-19, which present the opposite challenge of quickly synthesising available evidence. Future guidance should shift focus from acute restrictions to longer term management, such as the implementation of a comprehensive vaccination programme with equitable access and managing the mental health consequences of COVID-19. To do so, guidelines should source their recommendations from the growing body of literature by leveraging newly developed frameworks to provide up-to-date syntheses of the available evidence .Additional file 1.Additional file 2."} +{"text": "As of early May 2021, there have been more than 4.67 million cases of coronavirus disease 2019 (COVID-19) and nearly 126,000 deaths reported in Africa.American Journal of Tropical Medicine and Hygiene.To understand COVID-19 knowledge, attitudes, and practices and their impacts on health, nutrition, and education, the Africa Research, Implementation Science, and Education (ARISE) Network conducted a telephone survey at six sites in Burkina Faso, Ethiopia, and Nigeria between July and November 2020.,,There have been wide variations in the levels of knowledge of COVID-19 symptoms and modes of transmission among adolescents, adults, and healthcare workers. Although the level of knowledge of common symptoms and the perception of personal risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were relatively low among adolescents, prevention approaches were commonly practiced.These surveys revealed many worrisome findings. The majority of adolescents had greatly decreased communication with family and friends, were no longer attending school because of closures, could not continue their education during the pandemic, and anticipated not being able to catch-up with what they missed after the pandemic.In addition to the adverse effects on education and food security, the survey found partial or complete interruptions in the delivery of basic maternal and child healthcare services, including pediatric immunization services, vitamin A supplementation, and access to preventive nutrition services and malnutrition treatment.Although these studies had several limitations, including differences in consent processes between countries (in-person informed consent was required in Ethiopia but not elsewhere), a lack of generalizability beyond the study communities, variations in sampling frameworks across the study locations, and the availability of completed surveys only from willing individuals with mobile telephones, there were also several strengths. Diverse samples of the general population in rural and urban areas were recruited across three countries, there was a focus on the impact on adolescent health and education, and data were disaggregated by age and sex. Additionally, mobile telephone surveys represent a potentially low-cost strategy for data collection in contrast to in-person household surveys.This three-country telephone survey revealed varying levels of knowledge of COVID-19 symptoms and how this disease is transmitted, although most adults and healthcare workers reported using effective preventive measures. However, the more concerning findings were related to the negative adverse effects of the COVID-19 pandemic on routine health services, access to education for adolescents, and food security and dietary diversity. The short-term impacts of undernutrition and impaired access to basic healthcare for children, adolescents, and adults are likely to be substantial. These problems are likely to be further exacerbated by the ongoing second wave of the pandemic, which appears to be more severe in sub-Saharan Africa. The combination of food insecurity leading to undernutrition and major challenges regarding completing education may have long-term negative effects on adolescents and younger children who may be greatly impacted by food insecurity and reduced dietary diversity in terms of their future health, nutritional status, and potential for economic development."} +{"text": "The Omnibus Budget Reconciliation Act (OBRA) of 1987 included provisions for the Preadmission Screening and Resident Review (PASRR) program, which requires states to create and maintain systems to assess persons with serious mental illness (SMI) seeking NH care. The prevalence of SMI in NHs is increasing, and little is known about the effectiveness of the PASRR program intervention. We conducted 20 interviews with state and national PASRR stakeholders, including assessors, hospital discharge planners, mental health advocates, geriatricians and geriatric psychiatrists. Interview data were triangulated with state provided materials on PASRR collection and implementation. Based on these interviews, we identified four themes: 1) variation in the implementation of federal PASRR legislation across states and jurisdictions, 2) the need for investment in professional development and workforce capacity, 3) lack of usefulness of PASRR in ongoing care planning, and 4) the need to consider the role of age, race/ethnicity, and stigma on quality of care for NH residents with SMI. Stakeholders agree that PASRR legislation was well intentioned, but also expressed concern regarding the completion of PASRR as an issue of compliance versus meaningful assessment. More work is needed to determine how best to develop and support the care needs of people with SMI, while being mindful of the original goals of deinstitutionalization that prompted OBRA passage. In order to assess the impact of the PASRR program on quality of care and mental health outcomes, further research should take an evaluative approach through meaningful use of PASRR data."} +{"text": "IUCrJ.Henry Chapman and Xiaodong Zou have recently been appointed as Main Editors of IUCrJ. Henry Chapman, who was already a Co-editor of IUCrJ, will succeed the late John Spence in leading the journal section on Physics and Free Electron Laser Science and Technology. Xiaodong Zou will lead a new section on Electron Crystallography, which will act as a home within the IUCr journals for high-quality, high-impact papers in this field. We are assembling a team of Co-editors to work with Xiaodong Zou and details of this section will be provided in the next issue of IUCrJ.Henry Chapman of the Center for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, and Xiaodong Zou of the Department of Materials and Environmental Chemistry, Stockholm University, have recently been appointed as Main Editors of Henry Chapman is a physicist who is a world leader in exploiting modern high-brightness X-ray sources for high-resolution structure determination and imaging of soft matter or biological systems. His work in developing experimental methods and analysis for coherent diffractive imaging of non-periodic objects includes the first experimental demonstration of X-ray ptychography, as well as his pioneering work in serial femtosecond crystallography. His international status in these FELS fields also includes his association with multiple world-class high-brightness coherent X-ray source developments around the world. Henry completed his PhD in 1992 at The University of Melbourne, Australia, for which he was awarded the Bragg Gold Medal from the Australian Institute of Physics. He explored lensless X-ray imaging at Stony Brook University , and first demonstrated X-ray flash imaging while at Lawrence Livermore National Laboratory in California where he also contributed to the development of extreme ultraviolet lithography. He joined DESY and the University in Hamburg in 2007 as a founding director of the Center for Free-Electron Laser Science. He was awarded the Leibniz Prize of the German Research Foundation (DFG), the Roentgen Medal, and an honorary doctorate of Uppsala University, and is a Fellow of the Royal Society (FRS).Xiaodong Zou is a leading expert in electron crystallography and porous materials. Her research interests have been developments of electron crystallographic methods and design of novel porous materials. She is one of the pioneers in establishing electron crystallography as an important technique for accurate atomic structure determination of unknown 3D crystals. Her group has demonstrated the power of electron crystallography in studying complex structures including zeolites, metal-organic frameworks, pharmaceuticals and proteins. Professor Zou has also made key contributions in design, synthesis and applications of novel zeolites and metal-organic frameworks. Xiaodong is a full professor in structural chemistry and deputy head of the Department of Materials and Environmental Chemistry, Stockholm University. She received her BSc in Physics at Peking University in 1984, and PhD in structural chemistry at Stockholm University in 1995. One of her main research interests is method development for accurate atomic structure determination of nano-sized crystals by electron crystallography. Her group has solved a number of complex structures of zeolites and mesoporous crystals by transmission electron microscopy. She is also working on synthesis, structure determination, topology analysis and applications of inorganic open-framework materials and metal-organic frameworks. She has received several prestigious awards given by the Royal Swedish Academy of Sciences. She is an elected member of the Royal Swedish Academy of Sciences (KVA), member of the Royal Swedish Academy of Engineering Sciences (IVA), Fellow of the Royal Chemical Society (FRCS) and council member of the International Zeolite Association."} +{"text": "Healthy ageing has become a popular topic worldwide. We investigated the role of sleep, leisure activities, and socioeconomic inequalities in relation to cognitive decline, wellbeing, and quality of life in data from the English Longitudinal Study of Ageing (ELSA), Chinese Health and Retirement Longitudinal Study (CHARLS), and Japanese Study of Aging and Retirement (JSTAR), national representative samples of England, China and Japan, respectively. We found an inverted U-shaped association between sleep quality and memory in English adults and a positive dose-response association in Chinese older adults (Brocklebank). In another examination, we found that younger English individuals playing games had lower quality-of-life than older participants who game, and this association is more pronounced for widowed individuals than others (Almeida-Meza). Cognitive impairment and dementia represent significant challenges worldwide. In a cross-country investigation, we found that the prevalence of MCI was twice as great in England compared with Japan, but that the two nations differ slightly across socioeconomic correlates (Gireesh). In another cross-country comparison between England and China, we found that the rate of memory change appeared socioeconomically patterned, primarily by education and area-based characteristics , with a more substantial impact on rural China inequalities compared to England (Cadar). Our results indicate more robust educational and geographical disparities in China and increased occupational impact among English and Japanese participants. Our findings highlight the imperative need for policy interventions and tailored strategies to protect those particularly disadvantaged in England and China."} +{"text": "Mortality burden in South Africa since the mid-1990s has been characterized by a quadruple disease burden: HIV/AIDS and tuberculosis (TB); other communicable diseases (excluding HIV/AIDS and TB), maternal causes, perinatal conditions and nutritional deficiencies; non-communicable diseases (NCDs); and injuries. Causes from these broad groupings have persistently constituted the top 10 causes of death. However, proportions and rankings have varied over time, alongside overall mortality levels.To provide evidence on the contributions of age and cause-of-death to changes in mortality levels in a rural South African population over a quarter century (1993\u20132018).Using mortality and cause-of-death data from the Agincourt Health and Socio-Demographic Surveillance System (HDSS), we derive estimates of the distribution of deaths by cause, and hazards of death by age, sex, and time period, 1993\u20132018. We derive estimates of life expectancies at birth and years of life expectancy gained at age 15 if most common causes of death were deleted. We compare mortality indicators and cause-of-death trends from the Agincourt HDSS with South African national indicators generated from publicly available datasets.Mortality and cause-of-death transition reveals that overall mortality levels have returned to pre-HIV epidemic levels. In recent years, the concentration of mortality has shifted towards older ages, and the mortality burden from cardiovascular diseases and other chronic NCDs are more prominent as people living with HIV/AIDS access ART and live longer. Changes in life expectancy at birth, distribution of deaths by age, and major cause-of-death categories in the Agincourt population follow a similar pattern to the South African population.The Agincourt HDSS provides critical information about general mortality, cause-of-death, and age patterns in rural South Africa. Realigning and strengthening the South African public health and healthcare systems is needed to concurrently cater for the prevention, control, and treatment of multiple disease conditions. Ongoing characterization of mortality and disease patterns is required in different settings in order to set locally relevant health and development priorities, identify critical elements for strengthening of health systems, and determine the focus of health services and programmes. During the first half of the twentieth century, populations in high-income countries moved from periods of high, fluctuating mortality rates dominated by epidemics of infectious diseases, famines, and wars to periods of progressive reductions in mortality rates and the emergence of degenerative diseases as the major causes of morbidity and death . They suIn South Africa, overall mortality levels were declining, and life expectancy was steadily improving from the 1960s until the early 1990s . From thThe dramatic increases in overall mortality and reductions in life expectancy from the mid-1990s to the mid-2000s were driven mostly by increases in mortality caused by the HIV/AIDS epidemic and lack of treatment programmes ,23\u201325. AWe used mortality and cause of death data collected from 1993 to 2018 as part of annual updates of vital events of the population of the Agincourt Health and Socio-Demographic Surveillance System (HDSS) in rural northeast South Africa ,28. SimiThe most probable cause-of-death was generated using the InterVA-5 probabilistic model (version 5.1) . For eacUsing the person-year file, we estimated the hazards of death by age, sex and time-period using logistic regression models . ThereafWe split the calendar years into the following time periods: 1993\u20131997, 1998\u20132000, 2001\u20132003, 2004\u20132007, 2008\u20132010, 2011\u20132013, 2014\u20132016 and 2017\u20132018 to contextualize the dynamics of the HIV epidemic and the rollout of prevention of mother-to-child transmission (PMTCT) and antiretroviral treatment (ART) services. Where possible, we compared the indicators of mortality and cause-of-death trends from Agincourt with South African national indicators generated from publicly available datasets as a way of assessing the generalizability of our findings. We compared estimates of life expectancy at birth from the Agincourt HDSS with estimates of life expectancy at birth for South Africa obtained from the World Bank data archive . We alsoAll analyses have been conducted using Stata version 14.1 .A total of 17 934 deaths were recorded in 2 210 631 person-years of follow-up in the Agincourt HDSS surveillance population over the period 1993\u20132018. Panel (a) of Trends in mortality levels in children under the age of 5 years show progressive increases between 1993\u20131997 and 2001\u20132003 and decreases thereafter (Panel (b) of Trends in life expectancy at birth exhibit a similar pattern to trends in overall mortality for both males and females (Panel (d) of Panel (d) of Owing to the significant contribution of HIV/AIDS and TB to the mortality profiles of the Agincourt HDSS population in the last two and a half decades, Building on the finding that cardiovascular diseases have progressively gained prominence among the leading causes of death, A clear understanding of the levels and patterns of mortality and diseases in different sub-populations is continuously needed in order to formulate and implement locally relevant policies and programs to improve population health. However, effective responses to this need for populations in the most resource-poor settings are hampered by a lack of comprehensive, reliable, population-based data on health risks, exposures, and outcomes. One of the viable alternatives to addressing this lack of data has been the establishment of HDSSs in some resource-poor settings. HDSSs enumerate populations in geographically well-defined areas and prospectively collect detailed information on the core components of population change as well as complementary information on health, social and economic indicators . In thisUnlike prior research ,30,54,55While there have been impressive reductions in mortality levels in Agincourt since 2007, the COVID-19 pandemic that has been underway in South Africa since March 2020 may well induce some reversal through both direct and indirect mortality, the latter resulting from reduced provision and utilization of health service for NCDs, HIV/AIDS, TB, antenatal care and vaccine-preventable diseases in children under 5\u00a0years . The extA previous study showed broad similarity in major cause of death categories despite low agreement of cause attribution at the individual level between the causes of death in the South African national data that are determined from death notification forms (Form BI-1663) completed by clinicians or death reports (Form BI-1680) completed by authorised traditional leaders when clinicians are not available, and causes of death in the Agincourt HDSS population determined from verbal autopsies using the InterVA model . The strThis study has a number of limitations. First, the sensitivity of our findings to different computer-based models for assigning causes of death other than the InterVA model, such as Tariff and InSi61Our findings show that the population in Agincourt, a rural area of South Africa adjacent to southern Mozambique, has experienced significant shifts in mortality levels and the associated contributions of age and various causes of death over a quarter century of tremendous health, population and social change. The findings also illustrate that the general mortality and cause of death transition experienced in the Agincourt area largely reflects the mortality, age, and cause of death transition experienced in South Africa, although the magnitudes may differ from one setting to the other. Most importantly, the mortality and cause-of-death transition presented in this paper highlights the increased importance of CVD and other chronic NCDs as leading causes of death in recent years as more people living with HIV/AIDS access ART and attain prolonged survival. Therefore, there is a need for realigning and strengthening of the public health and healthcare systems in South Africa to concurrently cater for the prevention, control, and treatment of multiple disease conditions."} +{"text": "The aim of the present study was to provide an overview of gingival crevicular fluid (GCF) bone turnover markers (BTMs) concerning the physiology of orthodontic tooth movement (OTM) and assess their potential contributions to regulating bone remodeling, that could prove useful in designing future approaches to modulating orthodontic tooth movement.Multiple electronic databases were searched up to October 1st, 2020. Randomized controlled trials (RCTs), controlled clinical trials, observational studies of prospective and retrospective designs, and cross-sectional studies reporting on levels of BTMs in GCF were eligible for inclusion. The quality of the included RCTs was assessed per the revised Cochrane risk of bias tool for randomized trials (RoB 2.0), whereas the risk of bias of the included cohort studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool.Five RCTs, 9 prospective cohort studies, and 1 cross-sectional study fulfilled the inclusion criteria. The risk of bias was deemed as high for the RCTs and 4 of the prospective studies and moderate for the rest of the studies. The following biomarkers for bone formation were assessed: bone alcaline phosphatase (BALP), alcaline phosphatase (ALP), and osteocalcin (OC). For bone resorption, the following BTMs were assessed: deoxypyridinoline (DPD) and pyridinoline (PYD), N-terminal telopeptide (NTX), osteopontin (OPN), and tartrate-resistant acid phosphatase (TRAP). The follow-up period ranged mainly from baseline to 45 days, although one study had an expanded follow-up period of up to 16 months. The results of the included studies comparing different BTMs were heterogeneous and qualitatively reported.Current evidence continues to support the potential for BTMs to provide clinically useful information particularly for adjusting or standardizing the orthodontic stimulus. The present systematic review has retrieved studies of high, overall, risk of bias, and has unveiled a substantial clinical and methodological heterogeneity among included studies. Further data of the relationships between the clinical assays and the physiological or pre-analytical factors contributing to variability in BTMs\u2019 concentrations are required.CRD42020212056.The online version contains supplementary material available at 10.1186/s13643-021-01860-w. Orthodontic tooth movement (OTM), as a biological process, encompasses a series of histological and biochemical reactions ; these lA reflection of these phenomena can be found in the gingival crevicular fluid (GCF) of moving teeth, with significant elevations in the concentrations of its components. The noninvasive nature and the convenience of repetitive sampling of GCF are considered of great importance for identifying the periodontal changes followed by orthodontic force application .There are three main methods of collecting GCF: (a) the gingival washing technique, which consists of perfusing the GCF with an isotonic solution of fixed volume; the fluid collected represents a dilution of crevicular fluid, containing cells and soluble constituents, as plasma proteins; (b) insertion of capillary tubes, with specific diameter, into the entrance of the gingival crevice; the fluid then migrates into the tube by capillary action. (c) The most common method, however, of collecting GCF is with the use of absorbent sterilized paper strips. The paper strips are inserted into the gingival crevice and left in situ for 5 to 60 s to allow the GCF to be adsorbed by the paper .Several substances can be collected from GCF and are considered biomarkers. The term \u2018biomarker\u2019 depicts a substance that is measured and evaluated objectively as an indicator of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention .Numerous protein or protein derivative biomarkers are released during bone remodeling by osteoblasts or osteoclasts and are generally described under the term of bone turnover markers (BTMs) . BTMs laBTMs have been studied for over 30 years, and they are separated into two groups: markers of bone formation , osteocalcin (OC), and bone alkaline phosphatase (BALP)) and markers of bone resorption and N-terminal telopeptide of type I collagen (NTX)) . HoweverIn orthodontics, biomarkers related to bone turnover may introduce new possibilities for understanding bone growth and remodeling. Knowledge of the ongoing process occurring in periodontal tissues during orthodontic and orthopaedic therapies can lead to proper choice of mechanical loading with the aim of shortening the period of treatment and avoiding adverse effects associated with orthodontic treatment .The aim of the present study was to provide insights into possible GCF BTMs concerning the physiology of orthodontic tooth movement and assess their potential contributions to regulating orthodontic processes that could prove useful in designing future approaches to modulating orthodontic tooth movement.The latest (2021) Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were adopted throughout the process of the present systematic review , 10.Participants (Population):orthodontic patients of any age and sex.Intervention: any type of removable or fixed orthodontic appliance resulting in OTM.Comparisons: any control group was accepted ).Outcomes: quantitative and qualitative analyses of bone remodeling biomarkers detected in GCF; measurement units were nanograms per microlitre (ng/\u03bcl), international units per microlitre (IU/\u03bcl), units per milligram (U/mg), picograms per millilitre (pg/ml), and milliunits per sample (mU/sample). Receptor activators or mediators not considered as exclusive bone remodeling biomarkers were excluded. Follow-up: All observation periods were accepted.Study design: Any study design was considered eligible for inclusion in this review, including randomized clinical trials (RCTs), non-randomized or quasi-randomized controlled trials, and prospective and retrospective studies.Exclusion criteria: animal and in-vitro studies, case reports or studies reporting less than 5 patients, studies including patients with systemic disorders affecting periodontal and orthodontic therapy, preclinical studies/ abstracts/ letters to editors/ narrative reviews, insufficient/unclear information not allowing data extraction, and no author response to inquiry email for data clarification.Detailed search strategies were developed and appropriately revised for each database, considering the differences in controlled vocabulary and syntax rules by the last author (DK). No language or publication date restrictions were applied.The Cochrane Central Register of Controlled Trials (CENTRAL) ;MEDLINE (PubMed) ;Ovid MEDLINE ;Ovid Embase ;LILACS On October 1st, 2020, we updated and searched the following electronic databases to find reports of relevant published studies:The search strategy of all databases is shown in Additional files http://www.clinicaltrials.gov), the multidisciplinary European database (http://www.opengrey.eu), the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis databases (https://about.proquest.com).In order to further identify potential articles for inclusion, grey literature was searched in the register of clinical studies hosted by the US National Institutes of Health , who were not blinded to the identity of the authors of the studies, their institutions, or the results of their research. Study selection procedure comprised of title-reading, abstract-reading, and full-text\u2013reading stages. After exclusion of non-eligible studies, the full report of publications considered by either author as eligible for inclusion was obtained and assessed independently. Disagreements were resolved by discussion and consultation with the third author of the review (IS). A record of all decisions on study identification was kept.The first two authors (LK and IG) performed data extraction independently and in duplicate. Disagreements were resolved by discussion with the last author (DK). Specifically designed Excel collection forms were used to record the desired information. Data extraction was piloted in five random included papers between the two first authors. The following data were collected: author/title/year of study, design of study, number/age/gender of patients recruited, type of orthodontic treatment, method of GCF collection, tooth site of GCF collection, control group, observation period (follow-up of patients), changes of biomarkers in GCF, biological consequence, and clinical significance.If stated, the sources of funding, trial registration, and publishing of the trial\u2019s protocol was recorded. This information was used to aid assessment of heterogeneity and the external validity of the included studies. In case of missing data, it was attempted to contact the corresponding author. Studies without enough data for meta-analyses were kept in the systematic review, but excluded from the meta-analyses.The methodological quality of all included studies was assessed by the first two review authors (LK and IG) independently and in duplicate. For interventional, randomized controlled trials (RCTs), the Risk of Bias 2.0 tool was used . For intMeta-analyses would have been conducted if included studies reported similar interventions and comparable outcomes in homogeneous population (i.e. in the case of limited heterogeneity). For continuous variables, mean differences and standard deviations would be used to summarize the data from each study. For dichotomous data, number of participants with events and total number of participants in experimental and control groups would be analyzed. Regarding meta-analysis for dichotomous data, risk ratios and their 95% confidence intervals (Cls) would be calculated. For continuous data, mean differences and 95% Cls would be calculated.2 test and the I2 statistic.Clinical and methodological heterogeneity were assessed by examining the characteristics of the studies, the similarity between the types of participants, the interventions, and the outcomes as specified in the inclusion criteria for considering studies for this review. Statistical heterogeneity would have been assessed using a ChiReporting biases arise when the reporting of research findings is affected by the nature or direction of the findings themselves . PotentiAs no sufficient data existed, subgroup analyses based on study characteristics or sensitivity analysis based on the risk of bias were not conducted.We anticipated that some of the included studies presented data from repeated observations on participants, which could lead to unit-of-analysis errors. In such cases, we followed the advice provided in section 9.3.4 of the Cochrane Handbook for Systematic Reviews of Interventions : we woulIn total, 1051 studies were identified from the electronic searches as relevant. After exclusion of all duplicates and assessment of the title and abstract of the reports, 64 studies were considered eligible for inclusion in this review. Out of the 64 studies, another 49 studies were excluded after full-text assessment, leaving 15 studies fulfilling the inclusion criteria , according to the Newcastle-Ottawa Quality assessment scale , alcaline phosphatase (ALP), and osteocalcin (OC).The following biomarkers for bone resorption were assessed: deoxypyridinoline (DPD) and pyridinoline (PYD), N-terminal telopeptide (NTX), osteopontin (OPN), and tartrate-resistant acid phosphatase (TRAP). The follow-up period ranged mainly from baseline to 45 days. One study had an expanded follow-up period of up to 16 months and alcaline phosphatase (ALP)\u0392ALP was examined in one study . AlthougOsteocalcin (OC)OC was assessed in 4 out of 55 studies , 26, 29.Deoxypyridinoline (DPD) and pyridinoline (PYD)DPD was evaluated in two studies , 29. AccN-terminal telopeptide (NTX)NTX was investigated in 2 out of 5 studies , 26. AlfHowever, in the Isik et al. study, NTX values were found to be below the detection limit with a few readings which showed large variations between subjects and stages of tooth movement .Osteopontin (OPN)OPN was investigated in 4 studies , 21, 22.Tartrate-resistant acid phosphatase (TRAP)TRAP was detected only in one study . In the The aim of the present systematic review was to provide an updated summary of the available evidence regarding the collection of biomarkers in GCF, so as to guide and facilitate future research projects. The included studies demonstrated high heterogeneity, regarding methodological, clinical, and statistical issues. Clinical heterogeneity among studies included considerable variations in participants as well as in interventions , whereas the diversity in the measurement units of the biomarkers indicated considerable methodological heterogeneity. The aforementioned forms of heterogeneity precluded the possibility for a valid meta-analysis.The inclusion criteria for most of the studies were good general health, no history of antibiotic therapy during the previous months or anti-inflammatory drug use within 1 month before GCF collection in periodontally healthy nonsmokers. One week to 1 month prior to GCF collection, the participants underwent a session of professional supra- and sub-gingival scaling and also received repeated oral hygiene instructions , 27.Most studies evaluated the biomarkers in GCF samples before, during, and after canine distalization in cases of first premolar extractions , 27, 29 Isolation of the sites of GCF collection (most often with cotton rolls),Method of GCF collection ,Depth insertion of paper strips,One single or repeated measurements,Time that paper strips remain inside the gingival sulcus (e.g. 30 or 60 s),Time slot of the day for the collection,Incubation solution which was used for the GCF sample ,Biochemical assay used for the analysis of biomarkers .There was no agreement between the studies regarding GCF sample collection and management. Several differences were identified during the following stages:The fluctuation of the levels of biomarkers in GCF is suggestive of underlying intricate biological remodeling processes in bone and periodontal tissues related to OTM . MechaniThe increase of these pro-inflammatory cytokines results in chronic leukocyte recruitment and tissue destruction and seems to play a crucial role in periodontal remodeling during tooth movement, preventing pathological destruction of the bone and PDL . The amoIn the past two decades, there has been significant interest in the development of noninvasive oral and systemic diagnostic biomarkers by large-scale protein analysis. Whole saliva, parotid secretions, and GCF samples have been collected for diagnostic biomarker discovery. The notion to use GCF as a source of diagnostic biomarker is not uncommon; however, the possibility of using a panel of independent disease-related proteins has recently emerged. In this respect, the ability to highlight a large number of proteins with local tissue/cell specificity and to define their relative levels in health versus disease have become of major interest.The use of BTMs for the monitoring of treatment requires a baseline assessment with a repeat measurement at some defined point during orthodontic treatment. In order to do this effectively, it is important to assess the expected level of alteration. Thus, it is important to monitor treatment effect in the individual, the imprecision of the measurement, as well as the intra-individual variability which may be influenced by factors such as timetable of sampling, fasting status, adherence to instructions, etc..Some limitations do exist in the present review. Ideally, only randomized trials with control groups would be included in this review. However, due to the scarcity of available studies in the field, non-randomized designs were also considered for eligibility. Inter-rater reliability during data extraction was not tested; nevertheless, this has probably low impact as consensus was reached with the last author, when needed. The lack of blinding and generally the methodological heterogeneity in the included studies may have also introduced uncertainty in the results. However, the main strength of this review is that it gathers information about GCF collection and BTM values so that the future studies can be conducted under standardized conditions, with the sole purpose of using BTM in regulating orthodontic tooth movement.The diversity in expressing the released quantities and the use of different units hindered this review. To allow unequivocal interpretation and comparison between different studies, it is recommended to express quantitative release data in standardized units. The use of internationally agreed decision limits and target values for these markers requires that measurements are universally comparable. Standardization and establishment of a reference system for the BTMs is the route to achieve this , 37.The limits for detection/quantification of each analyzed eluate are essential for the interpretation of the results, and should therefore always be mentioned. Compounds that could not be detected, may still have been released, but in concentrations below the detection limit. It would thus not be correct to assume that they are not released in the GCF.Contamination may lead to false-positive detection of compounds, and great care should be taken to avoid any contamination. All studies should report if the necessary measures were taken in order for contamination from saliva to be avoided.In summary, the available studies relating BTM changes after an orthodontic stimulus are promising. Based on the results of this literature review, several guidelines for standardization may be suggested:Too often, the materials and methods failed to mention necessary information about the GCF collection procedure. Information such as the volume of incubation solution, the percentage of solvent in case of dilutions, the pH of the solution, and the brand of paper strips should be always stated.As BTMs may show significant responses to the orthodontic treatment, their response to treatment may allow the best choice of a possible future chemical or pharmacological agent. They may also help with the proof of principle and help establish the mechanism of action. This could potentially alter the actual orthodontic treatment modalities.Current evidence continues to support the potential for BTMs to provide clinically useful information particularly for adjusting or standardizing the orthodontic stimulus, and in the future for modulating the orthodontic tooth movement. The present systematic review has retrieved studies of high, overall, risk of bias, and has unveiled a substantial clinical and methodological heterogeneity among included studies. Further data of the relationships between the clinical assays and the physiological or pre-analytical factors contributing to variability in BTMs\u2019 concentrations are required.The review protocol was specified in advance and registered at PROSPERO , No. CRD42020212056.Additional file 1. PRISMA 2020 for Abstracts Checklist.Additional file 2. PRISMA 2020 Checklist.Additional file 3 Search strategy, MEDLINE/PubMed, assessed as up to date: 01.09.2020.Additional file 4. LILACS, Cochrane Library, MEDLINE, and Embase search strategies.Additional file 5. List of excluded studies."} +{"text": "A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems. A group of morphologically and functionally related brain structures receiving and interpreting stimuli associated with satisfaction, positive feeling, and addiction is commonly defined as the brain reward system (BRS). This system consists of subcortical mesolimbic structures, such as the nucleus accumbens (NAc), ventral tegmental area (VTA), amygdala (Amg), striatum (Str), and septum (Spt). It also includes several meso-corticolimbic regions, such as the hippocampus (Hip), prefrontal cortex (PFC), para-hippocampal, entorhinal, and motor function-related cortical areas . NAc is NAc contains predominantly small and medium-sized spiny neurons (MSNs) ,8. AmongEach part of NAc, namely shell and core, has different molecular characteristics considering the type of released neurotransmitters and their receptors. Levels of neurotransmitters, such as dopamine (DA), serotonin (5-HT), and norepinephrine (NE) are different in the two parts of NAc ,13. WhilIn humans, the concentration of NE is different in various portions of NAc. Tong et al. reported three-fold higher concentration of this neurotransmitter in the caudomedial portion than in its caudolateral part, and 12-fold higher in the caudal fragment compared to the rostral . DA leveApart from the internal functional specialization within NAc, high concentrations of NE and DA in the same area may suggest an interrelationship between both neurotransmitter systems and their reciprocal modulatory function upon controlled processes. On the other hand, the 5-HT content is higher in the shell compared to the core, although its utilization is greater in the latter . High leThe degree of morphological differentiation of neurons in NAc, their molecular characteristics, as well as the development of their spino-dendritic system determine the optimal adaptation of this brain structure to the integrative function which it plays within the BRS.A functionally important feature of NAc is its extensive system of connections with numerous brain areas. These can be divided into structural levels of cortical, hemispheric subcortical, diencephalic, and brain stem areas b. This hSignificant differences in the topography of connections between the two parts of NAc can be explained by their functional diversity 2,3,4].,3,4.2,3,The target areas of projections originating from the shell are limbic structures, such as extended Amg (Amgex), Spt, basal forebrain (BF), ventral pallidum (VP), and diencephalic areas involved in the regulation of vegetative and limbic functions, such as lateral preoptic area (LPa), lateral hypothalamus (LHTh), and lateral habenular nucleus (LHn) ,3,4. TheThe NAc core is a source of efferent projections targeting areas of the basal ganglia related to the limbic and motor systems, e.g., VP, external and internal parts of globus pallidus . Neurons located in the core also project to pars reticulata of substantia nigra (SNpr) ,6,30.Altogether, both parts of NAc have extensive ascending and descending connections which allow this nucleus activity to be coordinated with several cortical areas related to the association, limbic and projection functions 27]. Th. Th27]. The role of NAc as an important integrating center in the elaboration of behavioral reactions of the limbic, motor and vegetative systems is possible due to projection pathways using several neurotransmitters, of which DA, Glu and GABA could be considered as of primary importance, although serotoninergic and noradrenergic projections also contribute to the specific NAc functions.Numerous studies indicate a crucial role of receptors representing all the main neurotransmitter systems in physiological and pathological processes in NAc ,42,43,44The sources of dopaminergic projections that reach the NAc shell and core are VTA and SN, two mesencephalic structures involved in functioning of the limbic and motor systems, respectively ,46,47. WThe DA released in NAc affects many physiological processes. The level of this neurotransmitter increases in this brain area with the reward approaching, which reflects the awaiting state for its achievement. DA in NAc has also a positive effect on motivation for reward-achievement behaviors and reward-driven learning. Finally, it enhances learning of prediction errors, important in planning new adaptive behaviors . RegulatThe modifying effect of DA on synaptic plasticity is based on changes in receptors\u2019 activation and on the stimulating or inhibiting character of their response, changing the probability of neurotransmitter release and cell excitability, as well as on triggering synaptic potentiation or depression . LocatedOne of the most important functions of DA in NAc is its modulatory effect on the processes of short- and long-term homeostatic synaptic plasticity ,60. HoweApart from the essential physiological functions, the dopaminergic system plays fundamental role in development of addiction which isGlutamatergic projections terminating in NAc originate from Hip, Sub, Amg, thalamus (Th), VTA, and from the mPFC and prelimbic cortical areas ,72,73,74Action of Glu on NAc is associated mainly with the development of LTP ,80. HoweActivation of different types of glutamatergic receptors in NAc induces the development of dendritic spines in the MSNs. During maturation, they go through the stage of \u201csilent\u201d synapses with NMDARs, but not AMPARs . Later oAs mentioned before, the mechanism of drug addiction is associated with the modification of iGluRs , which is based on changes in their number and function . First-tAltogether, the role of glutamatergic projection in the functioning of NAc involves various types of receptors, although the contribution of AMPARs and NMDARs is probably the most significant. Changes in the expression of these receptors correlate with morphological modifications of the spino-dendritic system, contributing to the development of synaptic plasticity and playing an important role in the processes of both short- and long-term synaptic potentiation.The main target of GABA-ergic projection from NAc is pallidum (predominantly VP) ,32,98. OThe role of GABA-ergic projection and relevant receptors, necessary for the functioning of NAc and the whole BRS, have been raised in several excellent publications ,42. AmonSome evidence suggests the presence of functionally diverse GABA pools in the axonal endings of neurons in NAc . Newly sThe GABA-ergic receptors play an important role in controlling Glu release in NAc . The parGABARs also play a significant role in the regulation of mechanisms related to the consequences of alcohol consumption. The reinforcing effect of ethanol in the NAc\u2019s shell can be modulated by activation of GABAARs and GABABRs, together with 5-HT3 receptors . InteresFurthermore, GABARs play a crucial role in the regulation of addiction processes induced by psychostimulant drugs. For example, activation of GABAARs, but not GABABRs, modulates the reinforcing effects of morphine in NAc . The GABAdditionally, the GABA-ergic system in NAc is involved in alleviating the effects of stress and emotions. Activation of the GABABRs in NAc ameliorates spatial memory impairment after stress exposition , and exeIn summary, GABA-ergic receptors in NAc have important regulatory functions associated with direct inhibition of other cell populations and controlling the release of several neurotransmitters. Regulation of NAc activity via GABA-ergic receptors enables precise control of processes occurring in the BRS.Large projections originating from the small population of neurons concentrated in the raphe nuclei complex deliver 5-HT to the BRS. This monoamine neurotransmitter is involved essentially in all physiological processes controlled by NAc. The 5-HT function in this brain area depends on the dynamic balance between other neurotransmitters\u2019 systems and concentrations of the relevant neurotransmitters. One of the important functions of 5-HT in NAc is its role in motivation. This function is closely related to the facilitating activity of DA. Impairment of interactions between the serotoninergic and dopaminergic systems may result in anhedonia, lack of motivation, and finally in depression . InteresAnother important function of 5-HT in NAc is the regulation of prosocial interactions and behaviors, which is closely related to the rewarding effect of such interactions . AdditioThe role of 5-HT in NAc is also associated with the reinforcing effect of ethanol. This effect is further enhanced by DA release, which leads to an increased reward experience and impulsivity. In combination with some drugs, such as mephedrone, 5-HT and DA can increase the susceptibility to alcohol abuse, due to their increased release in NAc and mPFC . The incThe serotonergic system has a complex influence on NAc. This is due to the large number of receptors, their distribution on many types of cells, and to the use of several neurotransmitters. Among different types of receptors, at least two representing the 5-HT2R group play an important role in control of addiction mechanisms. Taking into account the fact that development of addiction is associated with an increase in DA released in the NAc, it has been suggested that the role of these receptors is based on a regulation of the DA concentration . They caApart from the aforementioned agonists and antagonists of the serotonergic receptors, other drugs such as partial agonists of serotonergic receptors, inhibitors of the 5-HT transporters and multiple neurotransmitter uptake inhibitors also act on the serotonergic system ,145. TheIn addition to all the above-mentioned functions, 5-HT also plays a regulatory role in the metabolic processes in NAc, leading to an increase in glucose blood levels . StudiesAlthough stimulation of different types of 5-HT receptors in NAc can enhance the effect of some addictive substances such as alcohol, stimulation of other types of receptor in this brain area leads, paradoxically, to a lower likelihood of addiction in response to the other psychostimulants ,126. TheNE, as one of the most important brain neurotransmitters, is also represented in the BRS. Its sources are neurons localized in TegB, mostly in LC. Extensive projections of this relatively small population of neurons allow the distribution of NE to almost all brain regions. Under stressful and rewarding stimuli, NE is released in NAc and mPFC . The amoAnother study has shown that cocaine administration enhances the release of NE, DA, and 5-HT in NAc . The dynIn addition to the abovementioned functions, increasing evidence points to NE involvement in the mechanism of alcohol addiction. Karkhanis et al. reported that chronic early-life stress resulting from social isolation has an impact on the behavioral risk of alcoholism manifested by a greater tendency to alcohol self-administration . This coAltogether, NE via its action in NAc, as well as in other BRS structures, regulates a wide spectrum of physiological processes and plays a role in the development of addiction. Moreover, cooperation with other neurotransmitters, such as DA or 5-HT, determines the NE action upon NAc and its regulatory role in these processes.NE plays a role in several processes, such as concentration of attention, wakefulness, drug addiction, and psychostimulants relapse. Action of this neurotransmitter within NAc is based mainly on its interaction with the \u03b11-adrenergic receptor (\u03b11AR) . A rare In summary, the release of neurotransmitters in NAc is precisely adjusted to the cause of activation, the goal to be achieved, and the origin of the activated projection. The action of a neurotransmitter depends on its concentration in NAc and its binding to specific receptors. The important role of neurotransmitter receptors the NAc functioning is related to changes in their expression level, subunit composition, and externalization or displacement within the plasma membrane or outside the synapses. The cooperative effect and synergistic action of receptors representing different neurotransmitter systems are critical for motivation, learning, and addiction.The proper functioning of the BRS requires cooperation among all morphological elements of brain tissue. Structural and functional relationships occurring between neuroglia and neurons form the basis not only for processes of motivation and reward-aimed behaviors, but also for the development of addiction and mental diseases . As can 2+ ion-dependent signaling pathways [Astrocytes are an important element of the brain tissue involved, together with neurons, in the regulation of reward and addiction mechanisms . An impopathways ,162. As pathways . Finallyad libitum. On the other hand, an increase in the dendritic spine density correlates with compulsive seeking behavior [Interesting data about the role of microglia in NAc come from animal studies. Microglia activation has been reported in mice fed with a high-caloric chocolate cafeteria diet . Apart fbehavior . In casebehavior . This reOligodendrocytes, like other neuroglial cell subpopulations, play an important role in the BRS, both in physiological conditions and pathology. Their role in myelin metabolism is important for the functioning of the brain tissue. Through controlling myelin metabolism, oligodendrocytes can influence the plasticity processes related to transmission efficiency of excitatory stimuli along the neuronal fibers. Consequently, myelin metabolism seems to be a good indicator of the BRS status during stress or anxiety. Down-regulation of myelin genes and oligodendrocyte-specific genes in NAc and PFC was recorded after four weeks of stress exposure in mice . SimilarAnother important issue represents myelination disorders and changes in myelin synthesis, resulting in impairment of the brain function observed in the course of some mental illnesses. The major depressive disorder (MDD) is associated with changes in the myelin content in several brain regions, but in particular in structures of the limbic system, including NAc . FurtherResults of a postmortem study showed myelination impairment in several brain areas, including NAc, after chronic cocaine abuse . DysreguTo conclude, neuroglia participates in a wide spectrum of processes occurring in NAc and other areas of the BRS. Its role includes modulation of synaptic transmission and signaling pathways within tripartite synapses, as well as regulation of energetic metabolism by astrocytes. It also takes part in the regulation of the BRS activity, through the release of inflammatory mediators by activated microglia. Finally, these cell populations regulate myelin metabolism, expression of oligodendrocyte-specific proteins and, consequently, the efficiency of stimuli conduction along the neuronal fibers. The modifying effect of neuroglia upon the BRS activity (including NAc) involves both physiological processes and a wide spectrum of pathologies associated with addiction, neurodegeneration, and mental illnesses. Further studies on the role of neuroglia in these processes are needed.In the 1980s, Mogenson and colleagues formulated a hypothesis that NAc functions as an interface between the limbic and motor systems . More reDifferences in functioning of the two parts of NAc have previously been reported ,186,187.The core of NAc is involved in responses to motivational stimuli , impulsiLike other brain regions, NAc undergoes characteristic morphological and functional changes during ontogenesis. At the subsequent stages of development, changes in the cellular structure, formation of connections with other brain areas, along with development of neurotransmitter systems and signaling pathways, as well as development of structural and functional plasticity, occur ,201. NumThe action of the above-mentioned factors at different stages of ontogenesis results in development of behavioral disorders and mental dysfunctions either during adolescence or in adulthood. This could be a consequence of an impairment in functioning of the endocrine system , disturbances in the functioning of neurotransmitter systems , as well as changes in the expression of neurotrophic factors and transcription factors ,207,208.During early development, due to an incomplete development of endocrine regulatory mechanisms, stress hormones (glucocorticoids) may be harmful to immature NAc, and induce abnormal behavioral responses ,210. DefAdolescence is the period in NAc development characterized by the final formation of connections, shaping balanced functional relations between neurotransmitter systems, as well as stabilization in the production level of neurotrophic factors and balanced gene expression. In addition, the development of hormonal maturity related to the HPA axis, both in terms of controlling stress reactions and achieved sexual maturity, is important for the functioning of the reward system during that period. Despite these changes, during adolescence there is a greater susceptibility to stressful and aversive stimuli than in adulthood . This caThe susceptibility of NAc to the harmful effects of addictive substances during development can be illustrated by the effects exerted by nicotine. Exposure to this commonly consumed psychostimulant has been linked to NAc impairment. The most important research includes the effects of early exposure to nicotine and its long-term consequences, the effects of nicotine withdrawal during development and adolescence, and mechanisms shaping the reward feeling triggered by nicotine during development. It has been shown that exposure to nicotine already in the fetal period affects the expression of genes of growth factors, death receptors, and some kinases related to the regulation of cell death or survival in adolescence . MaternaNicotine withdrawal has different effects on the functioning of NAc in adolescence as compared to adulthood. Studies have shown that discontinuation of nicotine in juveniles causes less side effects than in adults . This maThere are premises indicating involvement of different mechanisms triggering the reward and satisfaction feelings at various ages . These cAdolescence is a period of development associated with intensive learning, gaining various types of experience, as well as developing a responsiveness to stressful stimuli resulting from action of environmental factors and social interactions . All of Chronic juvenile (pre- and adolescent) stress of different nature has a significant impact on development of many brain areas, including NAc and the prefrontal cortex, important for shaping of the reward processing and the executive functions. Disturbances in the functioning of these areas resulting from impact of stressful stimuli on the immature structures may manifest in psychopathological symptoms during development and in adulthood, and sometimes may lead to the development of mental illnesses .Some evidence indicates that early-life adversity experiences like poverty, chaotic environment, maternal separation or poor parental care may significantly contribute to dysfunction of the BRS . They maThe plasticity processes occurring during adolescence in the shell and core of NAc not only have different dynamics but also reveal a different involvement in rewarding and aversion effects, thus emphasizing the functional differentiation of both parts of this nucleus . Some auOverall, the presented data indicate the complex character of the NAc function in the rewarding or aversive responses. This implicates the existence of different regulatory mechanisms depending on the situational context of the shaped reaction, which are disturbed in the course of such pathological processes as addiction, stress, depression or mental disorders.The importance of dendritic spines in the NAc neurons results not only from their involvement in synaptic transmission and plasticity, shaping motivational behavior and reward feeling, but also from their role in the development of addiction. Morphology of dendritic spines in NAc, predominantly bearing excitatory synapses, is determined by processes that occur both in the prenatal and postnatal period . The devDrugs of abuse, such as cocaine, change the number and structure of dendritic spines in NAc ,44,246. In summary, both external and internal stimuli can initiate morphological changes in dendritic spines in NAc and other regions of the BRS. The importance of dendritic spine modifications results from their involvement in the synaptic transmission and neuroplasticity processes. These modifications are accompanied by activation of signaling pathways contributing to an increase in efficiency of synaptic transmission, which enables specific behavioral reactions. The modifications occur not only in physiological processes, but also in pathological processes, such as addiction, mental, and neurodegenerative diseases.Growing evidence shows the relationship between stress, taken psychostimulants, and some mental disorders and changes in the synapto-dendritic system of the reward-involved brain structures ,44,89,95Some addictive substances can also induce molecular changes in the BRS. Cocaine and morphine induce a decrease in content of Homer1 protein and postsynaptic density of protein 95 (PSD95) in the BRS ,262. TheA recent study found a correlation between drug addiction and dysregulation of the circadian rhythm of sleep and wakefulness . These dFurther research on the molecular basis of plasticity mechanisms in the spino-dendritic system in the BRS is warranted, since it might contribute to a better understanding of the causes of numerous pathological processes and to the development of new and more effective therapies.The main role of neurotransmitter transporters in the CNS is removal of the appropriate mediators from the synaptic cleft . TherefoFrom a practical point of view, the effects of inhibition of the individual transporters are of great importance, on the one hand affecting the dynamics of psychopathological disorders such as depression, anxiety, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD), and addiction . On the DAT plays an important role in eliminating DA from the synaptic space, ensuring physiological homeostasis in the neurotransmitter system . By inhiBahi et al. reported the crucial role of DAT in ethanol-seeking behavior, as well as acquisition and retrieval of ethanol contextual memory in mice . ConsequApart from the receptors, Glu transporters also play an important role in the efficiency of synaptic transmission in NAc . Their fActivity of GABA-ergic neurons and release of GABA have a significant impact on the activity of projection neurons and, thus, indirectly on the concentration of DA in NAc . This prExpression level of vesicular GABA transporter (vGAT) and vesicular glutamate transporter 2 (vGlut2) in NAc of the adolescent and adult rats after ethanol exposure shows a characteristic ontogenetic pattern with lower vGlut2/vGAT ratios in adolescents compared to adults . The preAs shown by studies performed in mouse experimental models, chronic unpredictable mild stress is often associated with development of major depression . During Results of a recent study have shown that SERT deletion contributes to the protection against the development of behavioral sensitization by increasing serotonergic neurotransmission, which is accompanied by dendritic remodeling of the MSNs in NAc . These rResults of the study by Verheij and Karel have shown that changes in NE content do not have a decisive influence on the enhancement of cocaine intake in the SERT knockout rats . In the Studies on the mechanisms of reward, stress, depression and addiction involve animal knock-out models of serotonin and dopamine transporters ,285,286.The dopamine transporter (DAT) is responsible for removing the neurotransmitter from the synaptic cleft to the presynaptic terminal. The DAT ko mice show symptoms resulting from the increased DA content . The useSome authors emphasize the importance of brain-derived neurotrophic factor (BDNF) for proper functioning of connections between structures of the BRS, such as VTA, NAc, and PFC ,292,293.The relationship between changes in BDNF expression and altered functioning of the limbic system\u2019s structures has been documented in several mental disorders such as depression, schizophrenia, and drug-induced addiction ,298,299.Data presented in this review show a wide range of NAc functions, not only under physiological conditions but also in pathological processes. The unique role of NAc among the structures of the BRS is a consequence of: (1) a widely distributed hierarchical system of connections with other brain regions, (2) cooperation with the limbic and motor functional systems in regulating the state of consciousness and behavioral reactions, and with the vegetative system, in coordinating metabolic, endocrine, and autonomic nervous systems functions, (3) cooperation among several neurotransmitter systems, (4) well-developed morphological and functional plasticity processes enabling control of the short- and long-term synaptic enhancement, and (5) supportive role of the NAc neuroglia in physiological and pathological processes.Changes in NAc functioning contribute to the development of several CNS diseases, such as depression, schizophrenia, and AD. In all these cases, the NAc dysfunction should be analysed in the context of its hierarchical connections with the other CNS structures and functional systems, impairment of the neurotransmitter systems and neuroplasticity processes. Further research on the structure and function of NAc will provide relevant information, useful not only for a better understanding of the mechanisms regulating motivation processes and striving for reward-achievement but possibly also for the development of effective therapies for some CNS diseases."} +{"text": "In recent years, cardiovascular disease (CVD) continues to be the leading cause of global disease burden. Extensive efforts have been made across basic, translational, and clinical research domains to curb the CVD epidemic and improve the health of the population. The successful completion of the Human Genome Project catapulted sequencing technology into the mainstream and aroused the interests of clinicians and scientific researchers alike. Advances in single-cell RNA sequencing (scRNA-seq), which is based on the transcriptional phenotypes of individual cells, have enabled the investigation of cellular fate, heterogeneity, and cell\u2013cell interactions, as well as cell lineage determination, at a single-cell resolution. In this review, we summarize recent findings on the embryological development of the cardiovascular system and the pathogenesis and treatment of cardiovascular disease, as revealed by scRNA-seq technology. In particular, we discuss how scRNA-seq can help identify potential targets for the treatment of cardiovascular diseases and conclude with future perspectives for scRNA-seq. Cardiovascular disease (CVD), primarily ischemic heart disease and stroke, remains the leading cause of mortality and morbidity across the world . Recent With the completion of the Human Genome Project and the rapid development of sequencing technologies, there has been a growing interest in single-cell genomic and transcriptomic studies. Single-cell sequencing investigates biodiversity and heterogeneity at a single-cell resolution . Since iIn contrast, single-cell RNA sequencing (scRNA-seq) is used to detect the mRNA level of individual cells . In the Compared to adult hearts, embryonic and neonatal cardiac tissues are easier to digest and isolate single cardiomyocytes with higher viability. The lineage and heterogeneity of various cells in the process of cardiac development can be comprehensively analyzed by scRNA-seq . In 2016In addition, scRNA-seq contributes to the identification of factors responsible for the spatial development of the heart. Recently, uniquely expressed genes responsible for the development of the cardiac conduction system were identified in an embryonic mouse . SimilarAs for human vascular cells, scRNA-seq can comprehensively provide mRNA information of each cell in the heart and blood vessel in disease states, which can enable the discovery of new therapeutic targets for CVDs . In a moBecause of the large size of intact adult cardiomyocytes, researchers have used nuclei extracted from myocytes for scRNA-seq, so-called snRNA-seq. Coming to blood vessels, In addition, smooth muscle cells were reported to transition to macrophage- and fibrochondrocyte-like cells during atherosclerosis, a phenomenon regulated by the retinoic acid pathway . RecentlIn recent years, cardiovascular cells differentiated from human embryonic stem cells or hiPSCs have provided a new source of cells for repairing or regenerating the injured heart. Transplantation of cardiovascular cells was found to improve wall stress, cardiac metabolism, and contractile performance in a porcine heart model of MI . Geneticin vitro and the complexity of differentiated cardiomyocyte subsets are still unsolved questions is the basis for the development of scRNA-seq and spatial RNA sequencing (spRNA-seq), the latter two can offer transcriptional information at a single-cell level or near single-cell level . In addiscRNA-seq provides a powerful tool for studying cell heterogeneity, tracking cell dynamics, and subsequently finding new therapeutic strategies for CVDs. It has, thus, opened a fresh chapter in the field of modern cardiovascular research. With constant improvement in scRNA-seq technology and the combination of multiomics and spatiotemporal analysis, scRNA-seq will play a greater role in the field of cardiovascular research. In particular, the comprehensive study and analysis of genomics, epigenomics, and transcriptomics at the single-cell level holds promise for the elucidation of gene regulatory mechanisms at a single-cell resolution, contributes to individualized therapy of CVD in clinical practice, improves therapeutic efficacy and clinical outcomes, and facilitates the practice of precision medicine."} +{"text": "ABSTRACT IMPACT: As scientific research is trending towards greater interdisciplinary and collaboration in order to meet the challenges of contemporary science, which has led to increased recognition of the importance of Team Science, this study will promote team science research within NJ ACTS Consortium as well as across the country. OBJECTIVES/GOALS: The objective of this study is to assess the feasibility of using the NIH Reporter database for developing and tracking team science metrics within the CTSA-funded NJ ACTS Consortium, which consists of RU, PU, and NJIT. The NIH Reporter database provides detailed information on single-PI and multiple-PI R01 grants funded by NIH. METHODS/STUDY POPULATION: 58 multi-PI projects and 344 single-PI projects are currently funded within the NJ ACTS consortium. We will use information from the database on funding levels, institutional composition of projects , numbers of publications, impact factors of publications, and funding supplements obtained to quantify and track NIH R01 Team Science activity in the consortium. RESULTS/ANTICIPATED RESULTS: Preliminary analysis suggests that it will be both feasible and efficient to use the NIH reporter database to develop Team Science metrics and to augment information in the database with information on PI characteristics such as department/center/school/university, academic discipline, and rank/tenure status, as well and detailed composition of research teams, such as the mix in terms of senior and junior scholars. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study will make an important contribution to this movement by demonstrating the feasibility of using the publicly available NIH Reporter Database to quantify the level and success of Team Science in the form of single-PI and multiple-PI R01 grants funded by NIH, which represent extremely important Team Science activities at universities."} +{"text": "The outbreak of COVID-19 has posed a huge threat to global health and economy. Countermeasures have revolutionized norms for working, socializing, learning, and travel. Importantly, vaccines have been considered as most effective tools to combat with COVID-19. As of the beginning of 2021, >200 COVID-19 vaccine candidates, covering nearly all existing technologies and platforms, are being research and development (R&D) by multiple manufacturers worldwide. This has posed a huge obstacle to the quality control and evaluation of those candidate vaccines, especially in China, where five vaccine platforms are deployed in parallel. To accelerate the R&D progress of COVID-19 vaccines, the guidances on R&D of COVID-19 vaccine have been issued by National Regulatory Authorities or organizations worldwide. The Center for Drug Evaluation and national quality control laboratory in China have played a leading role in launching the research on quality control and evaluation in collaboration with relevant laboratories involved in the vaccine R&D, which greatly supported the progression of vaccines R&D, and accelerated the approval for emergency use and conditional marketing of currently vaccine candidates. In this paper, the progress and experience gained in quality control and evaluation of COVID-19 vaccines developed in China are summarized, which might provide references for the R&D of current and next generation of COVID-19 vaccines worldwide. Consequently, >200 companies and institutions quickly put together plans for the research and development (R&D) of COVID-19 vaccines, covering almost all technology platforms available for preparing vaccines.3 Currently, COVID-19 vaccines from 19 developers have entered phase III clinical trials, and 12 related vaccines have been approved for conditional marketing or emergency use worldwide , quality control system, analytical methods, and qualification/validation data and validation data for assays used to evaluate critical vaccine qualities, such as purity, identity, and potency for all stages of manufacturing should be clarified and provided.40 While promulgating the technical guidelines for the R&D of COVID-19 preventive vaccines, China has formulated the technical guidelines for the pharmaceutical research of COVID-19 preventive mRNA vaccines to address and meet the growing interest in the R&D of new mRNA vaccines.37 These technical guidance documents have played an important role in the development and approval of vaccines for emergency responses globally. However, most of the above guidelines are based on the existing experience in vaccine development, which need to be updated and revised in a timely manner based on new data and trends arising from the research on the produce, quality control, preclinical, and clinical trials related to COVID-19 vaccines.To guide and standardize the R&D of COVID-19 vaccines, global health organizations or regulatory authorities, including WHO, NMPA of China, FDA of the United States, EMA of the European Union, and PMDA of Japan, have issued a framework for the evaluation of clinical studies and guidelines related to emergency use of COVID-19 vaccines Table .34\u201345 AsIn addition, in view of the emergence of new problems and challenges, it is necessary to formulate contingent technical guidelines that can be tested quickly and adopted for standardization. For example, WHO and FDA are currently developing guidelines on testing the impact of mutant strains on the efficacy of protection of vaccines. Relevant departments in China are also working on preparing supplemental guidelines and policies to assist and streamline responses to rapidly evolving situations during pandemics.Countries all over the world had to rush to come up with countermeasures to mitigate the impact of the COVID-19 pandemic. Companies and institutions scrambled for the development of vaccines. The resulting tight R&D time lines, adoption of numerous platforms for the development of vaccines, participation of multiple enterprises, and inadequate scale-up, as well as production facilities severely impacted the setting up and implementation of standards to guide the development of COVID-19 vaccines through the various stages of R&D and production. For instance, in China itself, currently, there are >50 R&D enterprises working on five different vaccine platforms. Among the candidates being studied and developed, 17 products have entered clinical trials. Standardization of the various processes developed by many companies posed a huge challenge to the Chinese regulatory authorities. To address this, the Chinese Center for Drug Evaluation (CDE) has released multiple publications on guiding principles for vaccine development, recommendations on methods, and the statutory standards for the quality control at each step of R&D. Furthermore, the national laboratory of China, National Institutes for Food and Drug Control (NIFDC), worked closely with several laboratories conducting research on vaccines to establish a series of quality control and reference standards for the purposes of evaluation, which provide valuable support for vaccine development.The purpose of recommending guidelines for vaccine quality is primarily to ensure the safety and effectiveness of vaccines. To aid the rapid development of vaccines for emergency use, parameters related to quality control and their specifications should, at the minimum, include the basic requirements of safety and effectiveness, while keeping in mind the urgency in rolling out vaccines for epidemic prevention and control. In view of the limited data generated during the R&D of quality control methods for new vaccines, some leeway should be permitted on the condition that specifications are continuously improved and validated in the subsequent R&D efforts.In terms of quality control methods and specifications, China has set forth technical requirements on key items like viral strains, cells, purified bulk, and final bulks to final lots for vaccine production by each platform. These form part of the quality control effort and require registration of related products that are specifically used in the development of vaccines from any of the five technical platforms.For a variety of cell lines involved in the production of COVID-19 vaccines, the relevant international guidelines were closely integrated with the Chinese pharmacopoeia, in order to formulate comprehensive recommendations on the quality control measures for the processes using cell lines in the production of vaccines. The numbers of new methods available for monitoring a range of parameters related to cell cultures for guaranteeing the quality have surged recently. For instance, a variety of methods for detecting contamination and misidentification of cell lines like multiplex polymerase chain reaction (PCR), DNA barcoding, and STR mapping are now available for rapidly identifying problems and quality issues with cell lines. In particular, the newly established methods for the rapid detection of exogenous contamination (such as the Touchdown PCR detection method for mycoplasma) not only guarantee the safety of the vaccine, but also solve the problem of lack of cell detection technology, which can save considerable time for vaccine R&D, while providing strong support for the quality of production processes during technical reviews.For vaccines made up of recombinant protein Fig. , the tar37 The quality control of the mRNA bulk targets steps like mRNA identification, mRNA sequence length, sequence integrity and accuracy, etc. Research for enhancing the quality of nanoparticles should focus on optimization of encapsulation rate, particle size distribution, surface charge, stability and immunogenicity, etc. Biological activity of the final products should be demonstrated in vitro, as well as in vivo tests.For vaccines based on mRNA technology Fig. , there i46 it also puts forward relevant requirements for vaccine design. For example, the rationale for the selection of the target antigen(s), encoded proteins and the inflammatory nature of the given mRNA, the quality, quantity and bias of the immune responses cell phenotype), biostability, etc. should be clarified.In addition, in the general guideline for RNA vaccines newly formulated by WHO in 2020,One of the key challenges in COVID-19 vaccine development that remains unaddressed is the drafting and acceptance of criterion for the evaluation of the efficacy of vaccines by all stake holders. In the early stages of COVID-19 vaccine development, NIFDC of China successfully prepared and established the SARS-CoV-2 neutralizing antibody (NtAb) standard, created the pseudovirus detection method as a substitute for tests involving use of live SARS-CoV-2 and ACE2 transgenic mice models for in vivo testing of the efficacy and safety of the vaccine. It is mandatory for the emergency use vaccines to provide data related to the use of these standards and methods in the preclinical studies before entering the clinical trials, leading to their subsequent approval for emergency use.47 In addition, the preparation of serum has also helped some vaccine development companies to establish a vaccine antigen detection method.SARS-CoV-2 recombinant RBD protein was used to immunize goats and rabbits to successfully prepare several anti-goat and anti-rabbit sera against the virus. The highly potent sera were distributed to several Chinese manufacturers of SARS-CoV-2 inactivated vaccine, which solved the technical bottleneck of identification of the virus specifically and detection of exogenous virus-related factors.For the first generation of coronavirus vaccines being developed and approved for emergency use, in vivo efficacy testing remains the main rate-limiting step for licensure. The traditional methods for establishing the efficacy of the vaccine rely on the collection of blood samples for the detection of antibodies 1 month after immunization. Based on the results from previous research, it is proposed that both the inactivated and recombinant protein vaccines should be tested for binding antibodies 14 days after the administration of the first dose of vaccine. After successful demonstration of the required titer of antibodies, the candidate vaccine for emergency use can successfully complete the registration requirements in the first attempt and quickly enter the clinical trial.Many R&D enterprises that developed inactivated vaccine and recombinant protein vaccine adopted their own antigen detection methods, which make it difficult to compare the active content of vaccines across the manufacturers. Recently, a team of scientists extensively screened monoclonal antibody libraries to obtain antibodies suitable for establishing a double antibody sandwich ELISA-based kit for the universal detection of antigens, which showed good correlates between vaccines developed from different platforms and different systems (unpublished date). Such a kit would be used for the evaluation of the in vitro efficacy of recombinant protein vaccines and inactivated vaccines.48Elicitation of neutralizing antibodies is one of the main measures of vaccine pharmacodynamics during clinical trials. Plaques reduction and microcytopathic methods are the gold standards for the detection of NtAb at present. But, the application and popularization of these methods are greatly limited due to the need of live virus. In the early stage of the outbreak of COVID-19, Wang et al. constructed the SARS-CoV-2 pseudovirus using the VSV pseudovirus system and established the pseudovirus neutralization method. This method of detection of neutralizing antibodies offers several advantages like objectivity, sensitivity, and accuracy. Most importantly, there is no need for a P3 laboratory for performing tests using this method. Consequently, it has been used in many vaccine R&D enterprises and institutions, solving the key issue of detection of NtAb evoked by COVID-19 vaccine, and providing strong technical support for ensuring effectiveness of the process of evaluation for the vaccine.49Animal models are key tools for evaluating the amount of protection conferred by vaccines in preclinical studies. Using CRISPR/Cas9 knock-in technique, Sun et al. constructed a transgene mouse model that could express human ACE2 (HACE2) receptor. Compared with wild-type C57BL/6 mice, both young and old HCE2 mice maintained higher viral loads in the lungs, trachea, and brain during nasal infection. At the same time, increased interstitial pneumonia and cytokines were observed in SARS-CoV-2-infected HCE2 mice. At present, this model is being used in the preclinical pharmacological evaluation of several vaccines, providing a crucial tool for evaluating the ability of vaccine to confer protection against viral challenge.51 Synchronous R&D of the vaccine by different manufacturers helped establish, authenticate, and validate the processes and methods for QC during preclinical and clinical immunogenic evaluation of vaccines produced by different manufacturers,60 which ensured the accuracy and comparability of vaccine, and aided the marketing and application of EV71 vaccines.61Standard materials are yardsticks for ensuring the safety, effectiveness, and produce consistency of the vaccines. The use of rational, reliable, stable, and uniform standard materials is necessary to ascertain that the internal, as well as external regulatory QC requirements are met. These attributes also play a role in the evaluation of vaccines of different kinds originating from different regions or institutes involving various methods used for their appraisal. Such as enterovirus 71 (EV71) vaccines, methods for QC and establishment of standard reference materials for EV71 vaccines were done in the early stage of development to guarantee accurate evaluation of vaccines.Compared to EV71 vaccine, which was developed using only one technical platform, the establishment and application of standard materials for COVID-19 vaccines that have been developed from multiple platforms would be more challenging. Given the importance and need for unifying protocols for ease of comparison of different COVID-19 vaccines, the guiding principles on establishment and use of standards could greatly reduce the burden and challenges, surrounding approvals for these new vaccines.62 This standardized reference also plays an important role in assuring adequate QC measures for vaccines developed from different platforms and by different manufacturers. Importantly, it provides a reference point for comparison of NtAb titers evoked by different vaccines. WHO established the first WHO international standard for anti-SARS-CoV-2 immunoglobulin in December 2020, and it was assigned an international unitage of 250\u2009IU/ampoule. The standard was a result of an international collaborative effort with laboratories from all over the world participating in the calibration of the standard, leading to a uniform international standard for the estimation of antibody titers.63NtAb response is a key measure of immunogenicity and efficacy of vaccine. To assist in the evaluation of the efficacy of COVID-19 vaccines during the R&D stage, Hou et al. employed convalescent sera of COVID-19 to develop a national standard for SARS-CoV-2 NtAb with an assigned unitage of 1000\u2009U/ml.64 Therefore, RBD protein content is the key of the whole virus inactivated vaccine and other forms of recombinant protein vaccines developed using various expression systems. Presence of correctly folded RBD ensures efficacy. To establish a uniform reference to quantify effective components in vaccine, Liang et al. selected a CHO-expressed RBD antigen that had a moderate antigen activity from different candidates. This RBD protein was distributed to 11 labs for collaborative calibration. The results indicated that this candidate standard showed good parallelism and linearity with inactivated antigen and S or RBD antigens produced from CHO cells, yeast, Escherichia coli, or sf9 cells, which demonstrated that this candidate standard could be used as a uniform antigen standard for inactivated or recombinant vaccines. The standard is expected to provide a uniform benchmark for the quantification of effective components in vaccine.RBD is a universally accepted active domain of SARS-CoV-2 vaccine.The outbreak of COVID-19 has been catastrophic for human health, and its epidemiology posed a great challenge for global regulators and vaccine industry. In order to promote the R&D of vaccines and ensure the safety and effectiveness of vaccines, global regulators have formulated a series of guiding principles for the R&D of this new vaccine, including quality control, evaluation, and licensure. Among them, China is facing the biggest challenge due to the complicated and diverse vaccine R&D situation. In China, as a part of the national supervision system for vaccine development, CDE and NIFDC have played a leading role in launching the research on QC and evaluation at the earliest stages in collaboration with relevant laboratories involved in the vaccine R&D, which supported and accelerated the process of conditional marketing and emergency use of different vaccines with high quality.In this process, the Chinese National Regulation Authority believes that the establishment of national and international unified evaluation methods and standards is extremely important for the QC and evaluation of these new vaccines. So, QC and evaluation methods, including psedovirus-based NtAb detection method, and NtAb standard, were rapidly developed, established and used in the quality control and evaluation of COVID-19 vaccines. Those accomplishments relied on the close communication and collaboration between Chinese regulatory authorities and international organizations , and the close cooperation among institutions with supervisory roles in China, and the direct communication among supervisors and manufacturers. These works unified projects, methods, and standards for QC of vaccines using same platforms to great extent, which ensures the consistency, comparability, and objectivity of quality control and evaluation of different kinds vaccines or same kinds vaccines developed by different manufactures.66 More innovative technologies and ideas, such as research on heterologous prime-boost strategy of combining different vaccine candidates, next-generation vaccines capable of evoking more potent and effective immune responses against mutants, monovalent or multivalent vaccines, and the monitoring for tendency of the virus mutation should be studied if it can help mitigate these issues. At the same time, how to constantly adjust the standards and technical requirements of vaccines according to the changing situation, so as to ensure the safety and effectiveness of vaccines is a common challenge faced by global regulatory agencies. Active and close international cooperation and exchange is the only way to solve the problem to better prevent and control of the epidemiology of SARS-CoV-2 worldwide.Recently, COVID-19 inactivated and adenovirus-vectored vaccines have been approved for marketing. However, there has been variability in their protective efficacies, which needs to be further investigated. Furthermore, the recent variants documented in South Africa and Brazil might escape the protective immune responses elicited by these vaccines."} +{"text": "Nucleic acids underlie the storage and retrieval of genetic information literally in all living organisms, and also provide us excellent materials for making artificial nanostructures and scaffolds for constructing multi-enzyme systems with outstanding performance in catalyzing various cascade reactions, due to their highly diverse and yet controllable structures, which are well determined by their sequences. The introduction of unnatural moieties into nucleic acids dramatically increased the diversity of sequences, structures, and properties of the nucleic acids, which undoubtedly expanded the toolbox for making nanomaterials and scaffolds of multi-enzyme systems. In this article, we first introduce the molecular structures and properties of nucleic acids and their unnatural derivatives. Then we summarized representative artificial nanomaterials made of nucleic acids, as well as their properties, functions, and application. We next review recent progress on constructing multi-enzyme systems with nucleic acid structures as scaffolds for cascade biocatalyst. Finally, we discuss the future direction of applying nucleic acid frameworks in the construction of nanomaterials and multi-enzyme molecular machines, with the potential contribution that unnatural nucleic acids may make to this field highlighted. Nucleic acids demonstrated very unique properties and advantages to be used for constructing nanomaterials and scaffolds of multi-enzyme systems. For example, the structures of nucleic acids are well determined by their sequences, which allows straightforward control of their structures by customized sequence design . The feamachines . In recemachines . Hopefulin vitro and in vivo are summarized and discussed. A perspective on future development and application of novel nucleic acid frameworks in building nanostructures and multi-enzyme systems is provided in the end, with the potential contribution of unnatural nucleic acids highlighted.In this review article, we start from a brief introduction of the molecular structures and properties of natural and unnatural nucleic acids. Then the approaches and recent progresses on fabricating and applying complex nanostructures and multi-enzyme systems with nucleic acid scaffolds de novo synthesis of DNA and the invention of polymerase chain reaction (PCR) technology for exponential amplification of DNA have already laid the technical foundations for large-scale preparation of DNA, which is the prerequisite to extensively use DNA as a structural material has greatly expanded the genetic alphabet . Introduormation . Moreovereagents .in vivo replication, transcription, and even translation , and the ssDNA was then reverse transcribed from the RNA by HIV reverse transcriptase, which was recruited by HTBS effector staple proteins , four-way junction (4WJ), kink-turn motif, hairpins, pseudoknot, C-loops, right-angle motifs, tetraloop-receptors, paranemic motifs, and kissing loops, which can be directly employed in the design and construction of RNA nanostructures . Early emedicine . Mao andmedicine . Hermannmedicine . Since tmedicine . With inmedicine . In anotmedicine .in vivo construction and application of nanostructures more feasible. Geary et al. designed RNA tiles fabricated with a single-stranded RNA, and these RNA tiles can self-assemble into hexagonal lattices , for the treatment of triple negative breast cancers (TNBCs) . AlternaEfforts have also been made to fabricate RNA and DNA structural units together to produce novel RNA-DNA hybrid materials that possess characteristics, properties, and functions of both RNA and DNA. For example, Hermann and co-workers reported a self-assembled RNA-DNA hybrid polygonal nanostructure, the formation and stabilization of which were highly dependent on the binding of the DNA aptamer integrated in the nanostructure with its ligand AMP . Afonin in vivo production of RNA nanostructures via co-transcriptional assembly has also been demonstrated by several groups, which suggested the potential use of RNA as a scaffold material for organizing functional molecules in living cells. For example, Delebecque et al. assembled programmed RNA scaffolds in vivo, and applied them to guide the spatial organization of proteins , which mimicked peroxidase , which was composed of AMP and Ce3+ . The NCP3+ . Other t3+ 20 oligonucleotide, was attached to the surface of the DNA tile in between these two enzymes, and behaved as a swinging-arm that facilitated hydride transfer between G6PDH and MDH 20 oligonucleotide had an obvious negative impact on the catalytic activity. Later, they expanded this work to the construction of an artificial 2D enzyme network of G6PDH and lactate dehydrogenase (LDH), in which the enzymes were immobilized on the nodes of a wireframe DNA origami grid, and the cofactor NAD+-coupled duplex swinging arms were immobilized halfway between each pair of G6PDH and LDH and a malic dehydrogenase (MDH) were co-immobilized on a DNA double-crossover tile scaffold, and a NAD and MDH and xylitol dehydrogenase (XDH) of xylose metabolic pathway on DNA origami nanostructures with different distribution patterns of protein binding sites Ngo et . While Xin vitro construction of multi-enzyme systems, presumably due to the fact that RNA is not as stable and cheap as DNA. However, there are some examples of using RNA scaffolds for the in vivo construction of multi-enzyme systems, taking advantage of easy in vivo production of RNA via transcription and efficient co-transcriptional assembly of RNA nanostructures, which will be introduced in next section. Unnatural nucleic acid scaffolds have also not been used for the construction of multi-enzyme systems yet, since the efforts on the development of efficient tools to produce, amplify, and manipulate them, including unnatural nucleic acid polymerases, although already fruitful, are still in progress. The great potential of this field will be discussed in the end of this article.There is barely any example of using RNA scaffolds for the via in vivo construction of multi-enzyme systems with key enzymes in the metabolic pathways cells. After being expressed in the cells, the zinc finger protein-fused enzymes spontaneously assembled onto the scaffold plasmid. They then optimized stoichiometric ratios of the enzymes and intervals between the enzymes for higher L-threonine production. With the optimal system, the production time of L-threonine was reduced by over 50%, and the growth rate of the host cells was also enhanced, presumably due to reduced accumulation of toxic intermediates. Chen and coworkers reported the application of similar strategy on spatial modulation of pathway enzymes for improved production of N-acetylglucosamine in Bacillus subtilis (in vitro or in vivo by simply fusing enzymes with TALE proteins and immobilizing them onto a DNA scaffold with multiple TALE binding sequences. Zhu et al. reported the in vivo construction of TALE-based multi-enzyme system for the synthesis of indole-3-acetic acid (E. coli (Whole cell biocatalysts have been broadly used in bioindustry for the production of valuable chemicals, and their catalytic efficiency can be significantly improved pathways . Biomacr ligands . Many of ligands (Lee et ligands . Plasmidsubtilis (Liu et subtilis . The zinsubtilis (Conradosubtilis . TALEs asubtilis . Taking tic acid . In this(E. coli . After oin vivo construction of multi-enzyme systems have been reported yet, mainly due to the lack of efficient and user-friendly methods for in vivo production and assembly of singles-stranded nucleic acid components, as well as methods for in vivo immobilization of enzymes of interest site-specifically onto these nanostructures. Sliver et al. pioneered an effort to construct multi-enzyme systems in vivo based on RNA nanostructures (in vivo constructed 2D RNA scaffolds for enhanced pentadecane and succinate production (Up to now, not many examples of applying complex nucleic acid nanostructures for ructures . RNAs wioduction .in vitro and in vivo.In the past decades, a variety of elegant artificial structures based on nucleic acids have been designed and constructed, and some of them have found broad application in the construction of elegant nanomaterials or as highly programmable scaffolds for multi-enzyme systems. In this article, we started from the introduction of basic characteristics and properties of natural and unnatural nucleic acids, which demonstrated the uniqueness and superiority of nucleic acids to be used as structural materials. The progress in the development of polymerases for the efficient synthesis of nucleic acids with unnatural moieties, which are essential for broader application of unnatural nucleic acids, was also discussed. We then summarized representative approaches in the application of DNA, RNA, and unnatural nucleic acids for the construction of various artificial nanostructures, ranging from simple one or two-dimensional structures to complicated 3D origami nanostructure assemblies. In the end, we reviewed the construction of multi-enzyme systems using nucleic acid structures as scaffolds, as well as the application of these multi-enzyme systems for efficient catalysis of cascade reactions, both de novo synthesis technology, will facilitate the acquirement of more and better oligonucleotide sequences to be used as components for the construction of nucleic acid nanostructures in the future (Rapid development of DNA and RNA nanotechnology has enabled the construction and broad application of various nucleic acid nanostructures. However, more efforts still need to be made to make the procedures and the computational programs for the design and construction of complicated nanostructures more robust and user-friendly . Recentle future .in vitro or in vivo. However, these systems are still far from perfect, and a lot of efforts need to be made to further improve their performance. For instance, new chemistry may be developed to achieve efficient site-specific immobilization of the enzymes onto the scaffolds and precise control of the orientation of the enzymes, which is obviously very important for the accessibility of substrates or intermediates to the active sites. Smarter nucleic acid nanostructures may also be designed for better regulation of the stoichiometric ratio and relative positions of the enzymes based on their kinetic parameters to achieve optimal overall catalytic performance. Development of better computational tools to assist the design, assembly, and behavior simulation of versatile nucleic acid nanostructures will also greatly promote these efforts (in vitro, complex DNA origami nanostructures are rarely used as scaffolds for in vivo construction of multi-enzyme systems. Most of the nucleic acid scaffold-based multi-enzyme system constructed in vivo are still simply based on the immobilization of DNA-binding protein elements on linear double strands of DNA. Further exploitation of methods for constructing complicated nucleic acid nanostructures in vivo and combining these nanostructures with well-designed nucleic acid-binding proteins may lead to much better scaffolds for in vivo assembly of highly programmable multi-enzyme systems, and facilitate the engineering of cellular metabolic pathways.In order to immobilize and organize two or more enzymes for efficient catalysis of cascade reactions, multi-enzyme systems have employed various materials to fabricate the scaffolds, including inorganic materials, organic frameworks, and biological materials. Among those, nucleic acid has proven one of the most promising scaffold materials. Numerous artificial structures have been constructed with nucleic acids, and many of them are already well suited for the construction of multi-enzyme systems for efficient catalysis of cascade reactions efforts . Despitein vitro application of unnatural nucleic acids, the efforts on construction of semi-synthetic organisms have opened the gate for in vivo application of unnatural nucleic acids (in vitro and in vivo.Although natural nucleic acid frameworks have already been broadly used in the construction of nanomaterials or as the scaffolds of multi-enzyme systems, there still remain many challenges in the construction and application of better nucleic acid scaffolds that fulfill the requirements of more programmable and robust nanostructures or multi-enzyme systems. For example, the number of nucleobases in natural DNA and RNA is quite limited compared to the number of amino acids in protein, which results in limited sequences, structures, and designability of DNA and RNA. Moreover, natural nucleic acids have low tolerance against nuclease degradation and reduced stability under various chemical or physical conditions, which restricts the application of nucleic acid nanostructures or multi-enzyme systems with nucleic acid scaffolds in biological solutions or harsh environments. The fast development of unnatural components has provided a generous toolbox for the structural and functional expansion and augmentation of nucleic acids, and thus offered a great potential for the design and construction of better nucleic acid-based nanostructures and multi-enzyme scaffolds. As mentioned above, newly developed unnatural base pairs are already able to pair, replicate and transcribe as efficiently as natural base pairs . The intic acids , so we c"} +{"text": "Rates of suicide are elevated in middle- and late-life, yet studies focusing on suicidal ideation and behavior in older adults are limited compared to research in younger adults. The studies included in the present symposium offer valuable findings on suicide in older adults across the span of late-life. Owsiany et al. focus on age differences between older and younger adults in the association between anxiety symptoms and suicide risk. In Heisel et al., an online intervention is assessed for improving the outcomes of psychological well-being and suicide risk in older adult men who are transitioning into retirement during the COVID-19 pandemic. Crnek-Georgeson and Wilson reviewed the link between retirement patterns and psychological effects, including suicidal behaviors, among older adults. Additionally, this review includes recommendations for policy makers and employers in an effort to assist older adults with the transition into retirement. Utilizing baseline data from the Helping Older Adults Engage study, Fenstermacher et al. research the association between volunteering and suicidal ideation in a predominantly lonely older adult sample across the span of late-life. Together, these studies provide foundation for future research on suicide in late-life to build upon. Future studies should continue to focus on risk and protective factors for suicide in older adults and aim to improve screening and intervention for suicidal thoughts and behaviors in this population. Yeates Conwell, M.D., Director of Geriatric Psychiatry and Co-Director of the Center for the Study and Prevention of Suicide at the University of Rochester Medical Center, will serve as discussant."} +{"text": "Internally Displaced Persons (IDPs) in the camps face many reproductive health challenges. They should meet their needs timely to save their lives. This paper outlines a systematic review to discuss the challenges of reproductive health management in the camps of internally displaced persons.For this research, electronic databases including PubMed, Science Direct, Scopus, Pro Quest, Google Scholar and Cochrane Library till January 1, 2020 were searched. A threestage screening process was used for the selection of literature due to PRISMA checklist. Finally, a thematic synthesis approach was applied to analyze the data.In total, 133 articles were identified; 11 articles met the inclusion criteria for entering the process of final analysis. The findings were demonstrated in six main categories of availability and accessibility of reproductive health services, sexual and gender-based issues, human rights, social and cultural issues, coordination and collaboration, and mental health issues. The remarkable result of this study highlighted that the main challenges are lack of access to health services, violence against women and lack of household education.Results of this systematic review present valuable advice for policy makers and managers to prepare and respond effectively and timely to reproductive health challenges of internally displaces persons. Disaster preparedness plans and contingency plans for maintaining and developing reproductive health in IDPs camps are recommended. Every year, millions of people around the world miss their homes as a result of conflicts and disasters and become internally displaced within their own countries . A totalInternally Displaced Persons (IDPs) have the same health needs as non-displaced people. Women accounted for around half of the IDPs in 2010 . They arReproductive health is a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity, in all matters related to the reproductive system and to its functions and processes . Many stThe purpose of this systematic review study is to determine the reproductive health challenges of IDPs in disasters and emergencies.Search strategy and selection criteria: Six electronic databases were searched to identify studies from published and grey literature on productive health problems and challenges of IDPs. The populations of interest were persons who had been internally displaced. The search was done on January 1, 2020 and not limited to a specific time frame. The bibliographic databases searched were PubMed, Scopus, Science direct, ProQuest, Cochrane Library for English literature and Google Scholar for Persian ones. The search terms adopted include: AND AND AND (Disasters). Reference listings of identified articles were also independently hand-searched for more specific articles. The numbers of articles/abstracts generated from the various databases are indicated in Study screening and selection: A three-stage screening process was undertaken for the selection of literature for the study. Initially, the authors conducted independent searches based on the search strategy. Secondly, title and abstract of founded articles were screened independently by the authors to assess their eligibility for inclusion in the review. This stage was conducted using the inclusion and exclusion criteria. Finally, the available full texts of the selected articles were reviewed to confirm that the studies met the research question of this review. The process for selecting and reviewing the articles has been indicated in Inclusion and exclusion criteria: All the studies with different study designs and methodologies that reported the reproductive health challenges of IDPs were included. Studies with no data on the scope of the research question of this review were excluded alongside books, guidelines, peer-review and online articles and reports. Also, the articles that whose full texts were not available or were in other languages other than English and Persian were excluded. Furthermore, time, age and sex were not factors considered for exclusion in this study.Data extraction: The full texts of eligible studies for this review were independently screened and summarized according to designed forms for descriptive and thematic analysis. Information about the author, country in which the study was carried out, study year, study design, objectives and key study results were extracted from the descriptive analysis. Another form was applied for extracting the challenges of reproductive health in IDPs and categorizing them. Finally, the manuscript was evaluated by PRISMA checklist.The screening process yielded a total of 133 citations/abstracts (Stage 1). The duplicated studies were removed, and of 119 studies after reviewing the titles and the abstracts, a total of 90 of these were rejected because they were not relevant to reproductive health challenges of IDPs, or the study populations were done in either refugees or unrelated populations (Stage 2). A total of 29 articles were left for the full-text review (Stage 3). Subsequently, 18 studies were discarded because they did not meet the inclusion criteria .Descriptive results: By reviewing the eleven included articles, it was declared that the largest numbers of papers were from Africa (36%), followed by Asia (18%) and United States (18%). Other studies were from Europe and South America. The descriptive analyses of the most important included articles in this study are summarized in Analysis: Classification of reproductive health management challenges of IDPs in disasters are shown in The database search yielded 101 papers . Of thesThe 11 included studies reported on reproductive health management in IPDs focusing on lack of access to certain services , violencThe main challenges were described and categorized in the field of reproductive health management in the humanitarian settings for IDPs at this stage. Availability and accessibility of reproductive health services, sexual and gender-based issues, human rights, social and cultural issues, coordination and collaboration, and mental health issues were the main categories 22,23).,23.22,23This review identified a limited evidence base on the main IDPs challenges of reproductive health management in the humanitarian settings with available studies covering divergent settings. Available studies revealed that there are many fundamental challenges to IDPs reproductive health management ,21.Availability and accessibility of reproductive health services: The first important challenge in this category was lack of access to certain services (services \u201316. Lackservices \u201327, but services . Neglectservices ,17,19, uservices ,14,17, pservices , 17 and services , 15\u201318 mA woman has many reproductive health needs, through the different stages of reproductive life such as access to a full range of family planning services, safe abortion care, and prenatal, delivery and postnatal care . ReproduThere are some health concerns of women and infants in disasters . UnplannSexual and gender-based issues: In disasters and emergency situations, overall levels of violence increase (increase . Women aincrease . Communiincrease and inteincrease .Human rights: Some studies mentioned that women in IDP camps suffer diminished human rights and dignity ( dignity . This is dignity . Nationa dignity . Humanit dignity . Also, S dignity .Social and cultural issues: Lack of household education is one of the main reproductive health management challenges of IDPs in disasters. Most of the studies had focused on this issue (is issue ,15,19,20is issue . Disasteis issue . To asseis issue . Therefois issue .Women in IDP shelters suffer from reproductive health challenges and their activities are mainly influenced by cultural taboos and community beliefs . The heaCoordination and collaboration: One of the challenges was lack of adequate standards for managing the reproductive health. One of the active roles of the government and humanitarian assistance organizations is to provide adequate standards of living and social security for IDPs. This is in complete agreement with previous studies ( studies . Minimum studies \u201350. Deve studies . Also, mMental health issues: Mental disorders after disasters reported in previous studies. Depression especially in women are recognized as a common mental disorder. Post disaster suicide-attempt rates and depressive disorders are higher in internally displaced population (pulation . Violencpulation , and accIn general, IDPs in camps face with many reproductive health challenges. In this systematic review, we provided a comprehensive discussion and summarized all aspects of these challenges. Developing disaster preparedness and contingency plans, estimating the immediate reproductive health needs using the MISP, increasing the knowledge of women about their rights, and addressing the mental and psychosocial needs are important approaches to decrease these challenges. Also, planning for gender-based violence prevention, developing referral programs, using female officers in the IDP camps, creating standards of living and social security for IDPs and increasing the access to a full range of family planning services are some recommendations to decrease the reproductive health management challenges of IDPs in disasters."} +{"text": "The quality of meat and dairy products can be evaluated from the perspective of the farmer seeking high yields and profits or the consumer for whom sensory characteristics are the most important, although health and ethical aspects, such as animal welfare and the environmental impact of the production system, are increasingly becoming concerns worldwide. Animal nutrition is one of the most important environmental factors that significantly influences the quality of meat, milk, and other dairy products; therefore, emphasis is often placed on improving the quality of feed. A main target for improving the nutritional characteristics of meat and dairy is the enhancement of lipid quality, which can be achieved by increasing the content and improving the composition of beneficial fatty acids (FAs)\u2014n-3 polyunsaturated FA (PUFA) and conjugated linoleic acid (CLA)\u2014and decreasing the n-6:n-3 PUFA ratio. Factors such as the forage:concentrate ratio, dietary fat supplements, pasture, etc. have a crucial effect on dairy and meat quality. Some studies have shown that meat and dairy from ruminants grazing on pasture are enriched with bioactive substances of natural origin like phenolic compounds, fat soluble vitamins, terpenes, and lipid components. These animals are also able to consume increasing amounts of by-products or \u2018unconventional\u2019 animal feedstuffs, which can improve the health-giving properties of products. In addition, dietary manipulations favouring polyunsaturated FA in dairy and meat lipids increase the risk of lipoperoxidation, which can be efficiently prevented by the use of antioxidants in the diet. Furthermore, the search for biomarkers that link the composition of animal products to livestock feed has become a target of scientific research; these biomarkers allow for traceability from farm to fork, based on the herbivore diet and geographical origin. In this context, the Special Issue \u2018Better Animal Feeding for Improving the Quality of Ruminant Meat and Dairy\u2019 aims to provide an integrated analysis of the major aspects of the nature and composition of ruminant meat and dairy and the effect of better animal feeding on the improvement of nutritional and sensory qualities and functional properties beneficial to human health. This Special Issue comprises seven valuable works of original research on product quality; four studies were conducted on pasture-based systems , two on alternative feedstuff-based systems , and one on conventional concentrate-fed animals .Of the articles on pasture-based systems, three compared grass-fed regimes with conventional concentrate-fed regimes. Serrapica et al.\u2019s study onIn the Mediterranean region, high amounts of by-products are available that can be used as alternative feedstuffs for ruminants, lowering feed costs, and enhancing farm sustainability, while reducing the environmental impact of livestock production. Monllor et al. determinIn the last paper of this Special Issue, Barahona et al. studied In summary, the Special Issue provides evidence that production systems based on grass and forages produce healthier products with better sensory attributes, thereby promoting the consumption of healthier foods. At the same time, as suggested by several authors, high amounts of by-products can be used as alternative feedstuffs for ruminants, enhancing farm sustainability while improving the health-giving properties of products."} +{"text": "The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergency involved Italy as the first European country. Meanwhile, China was the only other country to experience the emergency scenario, implementing public health recommendations and raising concerns about the mental health of the population. The Italian National Institute of Health [Istituto Superiore di Sanit\u00e0 (ISS)] reviewed relevant scientific literature in mental health to evaluate the best clinical practices and established the collaboration with the WHO, World Psychiatry Association, and China to support the public health system in a phase of acute emergency. This process permitted the definition of organizational and practical-operational Italian guidelines for the protection of the well-being of healthcare workers. These guidelines have been extensively disseminated within the Italian territory for maximum stakeholder utilization. Starting from February 2020, Italy was the first European country facing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergency. On March 8, 2020, several Northern Provinces of Italy were placed under lockdown, and on March 10, 2020, at 00:30, any movement of people across the whole Italian national territory was forbidden, unless motivated by compelling reasons of health or work. All Italian people suddenly experienced confinement at home, physical distancing, while simultaneously receiving dramatic news from all media concerning the pandemic evolution and hospital emergencies, with potential negative impacts on the mental health of the people, as shown in a recent German study ] consequently elaborated specific guidelines for COVID-19 diagnostic and care procedures, particularly for individuals in the autistic spectrum and/or with intellectual disabilities, to optimize the management of sharp changes in the living and working environment and daily routine of such individuals. The main areas addressed by the ISS guidelines included strategies to promote the training of professionals, reorganize clinical and care activities through the development and maintenance of remote interventions, scheduled interventions in the presence, and patient management in the long-term facilities.Finally, frontline health workers found themselves exposed to biological risk factors, social isolation from family members, and subsequently, intensified challenges of recovery from physical and emotional distress . Only China, at that time, was devoted to face the COVID-19 pandemic and its consequences on the mental health of the people. The ISS researchers reviewed relevant scientific literature in mental health to evaluate the best clinical practices. We established the collaboration with the World Psychiatric Association Action Plan 2021\u201323 Working Groups on Intellectual Developmental Disorder and Autism Spectrum Disorder, consolidating a working group that formulated advice to tackle mental distress for people with intellectual disability and autism spectrum disorder, SIDiN (https://www.iss.it/en/rapporti-iss-covid-19-in-english/). This ISS report is freely available and has been extensively disseminated within the Italian territory for maximum stakeholder utilization. The report provides guidelines to organize the roles and activities of workers, ensure training , promote material in support of interventions, and monitor psychological well-being such as individual support strategies, monitoring of reactions related to discomfort, activate psychological and psychiatry support, psychological, psychiatric, and psychopharmacological interventions (as shown in The Research Coordination and Support Service of the ISS collaborated with the Nottingham Ningbo GRADE Center and researchers of the Shanghai University of Traditional Chinese Medicine, and Children's Hospital of Fudan University to translate and adapt the aforementioned guidelines for an Italian context, with consideration of contextual and cultural differences. The translation of Chinese guidelines has been useful in the preparation of the organizational and practical-operational guidelines for the health workers report \u201cInterim guidance for the appropriate support of the health workers in the SARS-CoV-2 emergency scenario,\u201d developed by the ISS Mental Health and Emergency Working Group COVID-19, which is accessible on the institutional ISS website (via an e-meeting organized by the WHO working in Ethiopia on Mental Health and COVID-19. This document describes an evidence-based process that can be taken as an example for future international collaborations to support the public health systems.The collaboration between Italy and China, established in a phase of acute emergency, has been fundamental as a basis for the definition of Italian guidelines dedicated to public mental health and promotion of the well-being of health workers, whose protection is a key component of public health measures in addressing the COVID-19 epidemic . The proMLS: conceptualization and funding acquisition. MLS, FS, GG, and JX: writing the original draft preparation, writing the review and editing. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Dear Editor,Pure Neural Leprosy (PNL) is a form of leprosy characterized by neural involvement without any skin lesions.M. leprae and the diagnosis of tuberculoid leprae with PNL was made. Antibodies against phenolic glycolipid-1 antigen (anti-PGL antibody) were negative. A therapy based on a combination of three drugs associated with prednisone 25\u202fmg and gabapentin 300\u202fmg (2 cp/die) was started with improvement of symptoms.A 78-year-old man, a professional missioner in the Philippines and Papua New Guinea, has presented sensory loss of left foot and pain of left hand present over a period of 4 years. A physical examination revealed dorsal flexion deficit of the left foot, superficial paraesthesia, and dysesthesia of toes associated with impaired deep sensitivity. In addition, he presented paraesthesia and dysesthesia to the IV and V fingers of the left hand. The left ulnar nerve was palpable and enlarged on the left elbow and no cutaneous lesions were found. The research of Acid-Fast Bacillus (AFBs) in the nasal swab and the slit skin smears from earlobes and left elbow was negative. Motor and sensory action potential of the left ulnar nerve, left peroneal nerve, left anterior and posterior tibial nerves are suggestive of mono-neuritis multiplex. Magnetic Resonance Imaging (MRI) of the left elbow showed the enlarged ulnar nerve partially damaged by entrapment within the fibro-osseous tunnel. Neurosurgery allowed the debridement of the ulnar nerve and, at the same time, the scraping of the perineural tissue. ZN stain and PCR of the scraping were positive for the presence of To the best of our knowledge, this is the first case of PNL diagnosed through scraping, ZN staining, and PCR test. Scraping is a technique that allows obtaining a clinical specimen rubbing a part of the body, in our case myelin sheaths of a nerve. The surface is scraped with a 15 Bard-Paker blade held at a right angle to the incision. Upon scraping, perineural tissue is obtained and examined by ZN staining and PCR test. Traditionally, diagnostic criteria for the diagnosis of PNL consist of nerve tissue samples obtained out of a nerve biopsy, analysis of PCR, and measure of anti-PGL-1 antibody levels.None declared.Ilaria Trave: Conception and planning of the study; elaboration and writing of the manuscript; approval of the final version of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Alberto Cavalchini: Conception and planning of the study; elaboration and writing of the manuscript; approval of the final version of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Gianfranco Barabino: Conception and planning of the study; elaboration and writing of the manuscript; approval of the final version of the manuscript; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Aurora Parodi: Conception and planning of the study; elaboration and writing of the manuscript; approval of the final version of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "In 2021, NIH funded six high-priority research networks designed to develop resources to support and advance the study of emotional well-being (EWB) and its core components. These research networks aim to advance the field by facilitating transdisciplinary research in the social, behavioral, psychological, biological, and neurobiological sciences. The National Institute on Aging (NIA) co-sponsored the RFA, and provided funding for NEW Brain Aging, because of the central importance of EWB to health trajectories across the adult lifespan. In this presentation, Dr. Simmons, Chief of the Individual Behavioral Processes Branch within the NIA Division of Behavioral and Social Research (BSR), will discuss how EWB research fits within NIA priorities. She will then facilitate open discussion about NIA and BSR\u2019s vision for the EWB \u2018network of networks,\u2019 the synergy of NEW Brain Aging with other members of the larger network, and the opportunities these networks will provide for investigators interested in EWB."} +{"text": "The National Health and Aging Trends Study (NHATS) is a nationally representative sample of Medicare beneficiaries aged 65 and older. From 2011 through 2020, annual in-person interviews have collected data in many areas, including health, environment, wellbeing, cognition, and function. With a decade of follow-up, including replenishment samples, NHATS is an ideal setting to investigate trends and trajectories of aging. Aging is heterogeneous and understanding the myriad of factors and functions that impact health and wellbeing is critical to developing interventions and care to promote health and wellbeing. Considering a multifactorial, wholistic approach to aging will provide a deeper understanding to create an impact. This symposium features pivotal research conducted using NHATS data, while highlighting overall strengths of the dataset for future research. The first presentation of this symposium investigates the factors that define cognitive profiles associated with dementia diagnosis over a period of five years. The second presentation investigates the role engagement in personally meaningful activities play in cognitive, emotional, functional, and health-related outcomes in older adults. The third presentation investigates the association between sleep medication use and fall risk among older adults with and without dementia. The session concludes with an investigation of end-of-life communication in persons with dementia and hearing impairment."} +{"text": "Nipah virus (NiV) first emerged in 1998 in Malaysia, causing an outbreak of respiratory illness and encephalitis in pigs. Pig-to-human transmission of NiV associated with severe febrile encephalitis was described, and it was thought to occur through close contact with infected animals. The first outbreak was reported in India in Siliguri, West Bengal in 2001 followed by Nadia, West Bengal and adjoining areas of Bangladesh in 2007, where an intermediate animal host was not identified, suggesting bat-to-human and human-to-human transmissions. Although it is extremely difficult to document the spillover event and ascertain crossing of trans-natural boundaries by bats and bringing new viruses in an unexposed population, efforts for source identification are important to understand the epidemiology of disease. As the disease transcends beyond one species and has shown to infect humans, it therefore requires the \u2018One Health approach\u2019 in which multiple sectors coordinate and work together to achieve better public health outcomes.We summarize the re-emergence and response of the Nipah virus outbreaks (NiVD) in Kerala, India, about 1800 kms away, a decade later in 2018 and 2019. The paper recapitulates involvement of various stakeholders from the Ministry of Health and Family Welfare, Directorate of Health Research, Indian Council of Agricultural Research, State Health Department, State Animal Husbandry, District Administration, and multidisciplinary response mechanism during the NiVD outbreaks of 2018 and 2019.Information was collected from the Press Information Bureau (PIB), media/weekly alerts from the Integrated Disease Surveillance Programme (IDSP), news articles from print and electronic media, newsletters, advisories from the National Centre for Disease Control (NCDC), Disease Outbreak News (DON), World Health Organization (WHO), and published papers from various stakeholders.The evidence of NiV in humans and bats, with samples collected from the outbreak sites, was laboratory confirmed. The multidisciplinary response mechanisms during the 2018 outbreak helped in further understanding the importance of the One Health approach for systemic and streamlined response utilizing existing surveillance systems. This was of utmost help in the subsequent outbreak of the disease that occurred during 2019, wherein there was no documented spread of disease from the index case and no mortality was observed. This success reiterates the need for institutionalizing the involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases, using the One Health approach. Nipah Virus (NiV) belongs to the family paramyxovirdae genus Henipavirus with a broad host range. NiV was initially identified to be responsible for outbreaks of febrile respiratory illnesses among veterinary stock. Selected species of bats are being increasingly recognized as reservoir hosts for viruses that can cross species barriers to infect humans, other domestic, and wild mammals. NiV infection in humans causes a range of clinical presentations, from asymptomatic infection to acute respiratory infection and fatal encephalitis .Fruit bats of the Pteropodidae family are the natural host of NiV . The infWe summarize the re-emergence of the Nipah virus disease (NiVD) outbreaks (2018 and 2019) in Kerala, India about 1800 kms away, a decade later from the previous ones West Bengal (2001) and adjoining areas of Bangladesh (2007). We also recapitulate the systemic and combined efforts of various stakeholders, including Central as well as State authorities, for effective and timely management of these recent outbreaks. The steps taken by all the stakeholders to mount an effective response led to successful containment of the outbreak and prevented its spread to other neighboring districts and states, limiting it to a localized event. This success also reiterates the need for involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases and dealing with them using the One Health approach. The One Health approach aims to establish an inter-sectoral coordination mechanism at National, State, and District levels, and utilizes the existing surveillance systems of various stakeholders to detect early warning signals of impending outbreaks for timely and effective public health response; also, it facilitates sharing of relevant information within the stakeholders for taking necessary action.After reports of an emergence of NiVD cases in Kerala in (2018 and 2019), a multi-disciplinary Central team was deputed, at the direction of the Union Health Minister, to review and respond to the situation of the NiVD in Kerala. Multi-disciplinary central teams were deployed at the sites to provide assistance to the local state authorities in investigating and responding to both the outbreaks; they consisted of public health experts, microbiologists, neurologists, and other infectious disease experts. These experts came from several organizations, including the National Centre for Disease Control (NCDC), Delhi and Calicut, Emergency Medical relief (EMR), MoHFW Delhi, All India Institute of Medical Sciences (AIIMS), Delhi, National Institute of Mental Health and Neuro-Sciences (NIMHANS), Bangalore, and National Institute of Virology Pune (NIV). Experts from the National Institute of High Security Animal Diseases (NIHSAD), Bhopal were also involved, along with the local Animal Husbandry Department 56.5Figure 1 and Table 1.As the state had a very recent experience in dealing with the NiVD outbreak, resulting in an already existing network of inter-sectoral coordination in 2018, an available set of guidelines and an expert team of doctors with past experience were already at hand for handling the outbreak of 2019 . The varThe first outbreak of NiVD was reported in India in District Siliguri, West Bengal in 2001 (66 probable cases and 45 deaths) followed by an outbreak in District Nadia, West Bengal and adjoining areas of Bangladesh in 2007 (5 probable cases and 5 deaths). As any intermediate animal host was not identified, bat-to-human and human-to-human transmissions were suggested 9.The unusual event apparently started with the death of a 26-year-old male resident of Block Perambra at the PHC-Changaroth on 5 May 2018, who was clinically diagnosed with viral encephalitis at the Government Medical College Hospital, Kozhikode on 4 May 2018. Two weeks later, two members of the same family reported with similar symptoms, deteriorated rapidly and died while in treatment at a private tertiary care hospital. Then, a cluster of three cases of viral encephalitis was reported from the same area. Subsequently, six more persons succumbed to similar symptoms, including a staff nurse of the taluk hospital involved in treatment of the primary/index case. All the affected cases were found to be epidemiologically linked with a confirmed case/death. Laboratory testing of throat swabs, urine, and blood samples collected from four suspected patients was conducted by the National Institute of Virology, Pune; three of the four reported deaths were confirmed positive for NiV by real-time polymerase chain reaction (RT-PCR) and IgM Elisa for NiV, and thereafter many more. A total of 19 cases and 17 deaths were reported through 3 June 2018 1112. The11On 30 May 2019, a 23-year-old male resident of Vadakkekara Village, Paravur Block, Ernakulam District, Kerala, having fever with altered sensorium, was referred to a private hospital at Eranakulam. A throat swab, CSF, blood, and urine samples were collected. The samples tested positive and were confirmed for NiV by NIV Pune. A total of 330 contacts were traced and samples from all the 13 suspected cases were tested and found negative for NiV 16. ErnakFor early detection, monitoring, and response to epidemic-prone disease outbreaks (including NiVD), the Government of India is doing surveillance through the Integrated Disease Surveillance Program (IDSP) and providing technical and financial support to all states under the National Health Mission (NHM). The NiVD guidelines for case definitions and contacts, advisories for healthcare personnel, information for the general public, treatment guidelines, sample collection, and transport guidelines were framed by IDSP and NCDC 19.The District Rapid Response Teams, along with the central multidisciplinary team, investigated the outbreaks in 2018 and 2019. House to house active case searching and contact tracing was done. Nipah cell of the state was established for contact tracing and ensuring home quarantine. Control rooms were set up at the State Headquarters and District Headquarters. Core committee daily review meetings were held under the chairmanship of the State Health Minister and District Collectors. Central teams reviewed the treatment procedure, infection control practices, use and availability of personal protective equipment (PPE), and availability of drugs, particularly in the designated hospitals 56.5Standard contact, droplet, and airborne precautions were emphasized during patient care and aerosol generating procedures to prevent human to human transmission while managing probable/suspected or confirmed cases of NiVD . To cont23The NiVD outbreak in 2018 was a major event with a very high case fatality rate (CFR), as characteristic of NiVD; however, the subsequent outbreak can be termed as a minor event. The primary cases in both outbreaks could have been infected by an accidental spillover from NiV infected bats or food sources contaminated by their secretions. However, in the 2018 outbreak, the initial spillover event may have been amplified by person-to-person transmission in the hospital settings, as subsequent cases were either close family contacts or hospital contacts. These two episodes are likely to be isolated/localized incidents.The unexpected sudden death of an otherwise healthy young male during the 2018 outbreak could have generated early warning signals only if such unusual events were reported diligently. As all the cases were epidemiologically linked to the index case, , subsequent infection/mortality could have been prevented if the infection control practices and BMW management practices at various levels of healthcare centers were stringently followed. Thus, adequate quantities of PPE and other logistics were ensured in the district at the earliest. Standard precautions and safe BMW practices were also emphasized while handling the deceased, patient specimens, used PPE, linen, clothing of patients, cleaning, and waste disposal activities at all levels of healthcare centers.Lack of an upgraded virus testing laboratory in the state, especially for dealing with BSL-3 or 4 pathogens, poses an additional burden of sample transportation with biocontainment precautions and delayed response during such outbreak situations . The neePteropus giganteus bats were found positive for NiV by RT-PCR [Pig-to-human transmission of NiV associated with severe febrile encephalitis has been described in past NiVD outbreaks . Human-ty RT-PCR .Pteropus sp were positive for anti-NiV IgG antibodies. As per genetic analysis of NiV conducted by ICMR- NIV (Pune) and NIV , a distinct cluster of NiV sequences suggested the circulation of a new genotype (I-India) in South India, which is different from the Bangladesh and Indian northeast NiV strains [During the 2019 outbreak, one rectal swab sample (out of 141 swab samples of bats) and 3 bat visceral organs (out of 92 bats) were found positive for NiV. Interestingly, 20.68% (12/58) of strains . No clinIn absence of a clearly identified primary source of infection to the index/primary case, many unscientific and misleading reports on the possible transmission of disease from fruits, such as mangoes, lychees, dates, bananas, etc., created fear and trepidation in the community . Due to The establishment of strong surveillance and multidisciplinary response mechanisms during the 2018 outbreak was of utmost help in mounting a systematic and organised response rapidly and effectively during the 2019 outbreak, preventing significant human transmission and mortality.The clinical care of patients with suspected or confirmed highly pathogenic infectious diseases is a real challenge for healthcare facilities . A separThe conventional clinical diagnostic procedure required for confirmation of highly infectious disease requires advanced biocontainment laboratories, high-end (and costly) instruments, an expert technician for operation and result interpretation, and longer turnaround time. The technical advancements in research and translation to development of PoCT facilities must be encouraged, which will elevate the clinical diagnostic scenario in resource-limited settings.As per the ensuing bat breeding season, NiVD advisories must be issued to clinicians in affected areas for high index of suspicion and appropriate infection control practices both in public and private sectors . The timPrint and electronic media, social activists, community leaders, and nongovernment organizations play an active role in early case reporting, social mobilization, and the raising of public awareness, which is essential in the rapid control of any outbreak. To prevent the spread of false information, officers must be designated to give authentic information to the media. Correct information helps in managing panic amongst the general public, which can otherwise affect the containment efforts of authorities. A grassroots approach to public health was exercised with success in the NiVD outbreak through consistent public health messages delivered at the community level and steered at the state level, with strategic co-ordination by central government and collaboration with local government .The district, subdistrict, and block-level administrations, along with elected people\u2019s representatives, should be involved in discussions not only during outbreaks, but also prior to the season, to highlight the possibility of an outbreak from endemic- and epidemic-prone diseases. Possible prevention measures can be discussed at routine intersectoral monthly meetings chaired by district or sub-district administrators, leading to better coordination and cooperation at the community level .As spring is the probable breeding season for bats and the preliminary observations with regards to time of occurrence of both events is May\u2013June, this indicates a higher probability of the presence of the virus among bats, and therefore a spillover, during breeding season . FurtherWhen NiV infections are suspected, standard contact and droplet precautions and infection control practices must be promptly strengthened to avoid spillovers in healthcare facility settings, both public and private. Further, in view of emerging NiV infection in the last decades in newer areas, countrywide strengthening of existing disease surveillance systems and multidisciplinary response mechanisms is necessary to enable rapid detection of rare zoonotic diseases, such as NiVD, as is the institution of appropriate control measures with One Health strategy."} +{"text": "The myth of a \u201ctypical\u201d mitochondrial genome (mtDNA) is a rock-hard belief in the field of genetics, at least for the animal kingdom . The firThe present Special Issue is an attempt to set and assess the state-of-art of mitochondrial genomics, with special reference to the suitability of mtDNAs for phylogenetic inference. The work by Formaggioni and colleagues opens thOvis nivicola) using the well-exploited mitochondrial gene cytochrome b.Furfaro and Mariottini ,9 demonsTheileria parva are identified using mitochondrial single nucleotide polymorphisms in the work by Mwamuye and colleagues [Unio crassus from Eastern Europe is unraveled by Kilikowska and colleagues [Crassostrea angulata is addressed by Chiesa and colleagues [Arrenurus (Micruracarus) novus by means of morphology interwoven with the sequence of mitochondrial genes cox1 and cytb at different life stages.Several example of mtDNA-based population genetics are provided. Different strains of the cattle protozoan parasite lleagues ; the poplleagues using onlleagues . Converslleagues provide Aedes, who found a strong and consistent incongruence between nuclear and mitochondrial phylogenetic inference , whose disentanglement is thoroughly discussed. Finally, Xia [Mitochondrial phylogeny and comparison with nuclear data is the main purpose of the work by Zhao and colleagues on two slly, Xia reports Pseudocercospora fijiensis (Ascomycota: Pezizomycotina), as well as the phylogenetic reconstruction of the family Mycosphaerellaceae, providing clues for multiple invasions on introns within mitochondrial genes. Conversely, Johansen and colleagues [Stichodactyla haddoni, that shows group I introns harboring expressed open reading frames and supernumerary genes, and challenges current views of the Actiniidae taxonomy.Furthermore, new complete mtDNAs are hereby reported. Arcila-Galvis and colleagues present lleagues present Concluding, the present Special Issue highlights the effectiveness of mitochondrial-based analyses in different fields of evolutionary biology, on one hand, while highlighting future, promising perspectives of research in the field of mitochondrial genetics, on the other hand, a field where unexpected is expected and the exception is the rule."} +{"text": "Nodularia douglasiae, while the other was N. nipponensis.We determined the complete mitochondrial sequences of female-transmitted (F) mitogenomes of two unionid specimens from the Lake Biwa system, Japan. Their gene contents and orders agreed with those of the typical F mitogenome of freshwater mussels. Molecular phylogenetic analysis using 20 previously identified partial COI and seven (five previously identified and two newly determined) whole mitogenome sequences revealed that one of the two mitogenomes was that of Nodularia species in Japan: Nodularia douglasiae and N. nipponensis , the former occurring on Kyushu and Honshu Islands in the area along the Sea of Japan, and the latter being endemic to northern Honshu and Hokkaido. Before the new classification, however, two subspecies were recognized in Japan under the name, Unio douglasiae Gray, 1833: Unio douglasiae nipponensis Martens, 1877 and Unio douglasiae biwae Kobelt, 1879, with the latter endemic to the Omi Basin (Lake Biwa and adjacent area) on Honshu and the former occurring widely in Japan with the exception of the Omi Basin are burrowing, filter-feeding bivalves. They occur in lakes and rivers worldwide but are now declining in many countries , under the registration numbers LBM-1300014505 and 1300014533. Genomic DNA was isolated from foot muscle tissue, and sequenced using Illumina MiSeq and HiSeq X Ten sequencers (Illumina). The resultant reads were assembled using CLC Genomic Workbench . Contigs were annotated by alignment with the two female (F)-transmitted mitogenomes of N. douglasiae (LC496352 and NC_026111) . The phylogenetic positions of the two mitogenomes indicated that one was that of N. nipponensis , while the other was the new N. douglasiae. This result demonstrated that there are two mitogenome lineages of Nodularia in the Omi Basin, unlike the previous classification hypothesis of Kondo (U. douglasiae biwae).The resulting supermatrix tree containeof Kondo , which r"} +{"text": "Objective: The efficacy and safety of adjunctive magnetic seizure therapy (MST) for patients with schizophrenia are unclear. This systematic review was conducted to examine the efficacy and safety of adjunctive MST for schizophrenia.Methods: Chinese and English databases were systematically searched.Results: Two open-label self-controlled studies (n = 16) were included and analyzed in this review. In these studies, the Positive and Negative Syndrome Scale (PANSS) total scores and Brief Psychiatric Rating Scale (BPRS) total scores significantly decreased from baseline to post-MST , without serious adverse neurocognitive effects. Mixed findings on the neurocognitive effects of adjunctive MST for schizophrenia were reported in the two studies. A discontinuation rate of treatment of up to 50% (4/8) was reported in both studies. The rate of adverse drug reactions (ADRs) was evaluated in only one study, where the most common ADRs were found to be dizziness and subjective memory loss .Conclusion: There is inconsistent evidence for MST-related adverse neurocognitive effects and preliminary evidence for the alleviation of psychotic symptoms in schizophrenia. Schizophrenia is a severely disabling psychiatric disorder affecting ~1% of the population worldwide . The ecoECT is the most effective treatment for individuals suffering from schizophrenia , 23 and MST is a novel neurotherapeutic intervention that induces therapeutic seizures based on high-frequency rTMS \u201334. MST To date, no systematic review on the efficacy and safety of adjunctive MST for schizophrenia has been published. Therefore, the target of the current study was to investigate the efficacy and safety of MST as an adjunctive therapy in schizophrenia.PICOS criteria. Participants: adult subjects with a diagnosis of schizophrenia based on any standardized diagnostic instruments. Intervention vs. Comparison: treatment as usual (TAU) plus MST vs. TAU plus ECT (RCTs); MST added to TAU . Outcomes: in this systematic review, the primary outcome was the improvement of psychotic symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS) or Brief (PANSS) . Key secTwo investigators (XYZ and XHY) independently searched English and Chinese databases from the date of inception until October 6, 2021 for studies on adjunctive MST for schizophrenia using the following search terms: (\u201cmagnetic seizure therapy\u201d[Mesh] OR magnetic seizure therapy OR MST) AND . Similarly, two independent investigators (XYZ and XHY) evaluated whether the potentially relevant studies fulfilled the inclusion criteria of this systematic review, and the senior author (WZ) was consulted in case of any differences of opinion.Two investigators (XYZ and XHY) independently extracted data from each included study. Any discrepancies in data entry between the two investigators (XYZ and XHY) were discussed, and the senior author (WZ) was consulted as needed. We contacted the first and/or corresponding authors to acquire any missing information as necessary. The quality of each included RCT and open-label prospective trial was evaluated by two independent investigators (XYZ and XHY) using the Cochrane risk of bias and the As shown in n = 16) (The characteristics of the two open-label self-controlled studies (n = 16) , 21 are n = 16) , and then = 16) and a flThe Cochrane risk of bias was not used because no RCTs were included in this systematic review. The NOS scores of the two self-controlled studies , 21 werePs<0.05). In Jiang et al.'s study , but no such decrease was found using the MATRICS Consensus Cognitive Battery (MCCB), Trail Making Test (TMT), Stroop Test or Verbal Fluency using the Controlled Oral Word Association Test (COWAT), and Montreal Cognitive Assessment (MoCA) ( > 0.05) .In both studies, discontinuation of MST for any reason was reported for 50% (4/8) of the participants , 21. TheThis article is the first systematic review on the efficacy and safety of MST as an adjunctive therapy for schizophrenia. Only two open-label self-controlled studies , 21 wereThis systematic review shows there is preliminary evidence for the antipsychotic effects of MST in schizophrenia and negligible neurocognitive adverse effects. As reported in the two included studies , 21, theAs for other neurotherapeutic strategies, such as tDCS, DBS, or ECT, the main objective in investigating MST is to monitor the effects on neurocognition. The findings of this systematic review are that MST has little to no adverse neurocognitive effects, supporting the findings of an early study . HoweverThis systematic review is limited for the following reasons. First, only two open-label self-controlled studies , 21 withThere is inconsistent evidence for MST-related adverse neurocognitive effects and preliminary evidence for the alleviation of psychotic symptoms in schizophrenia. RCTs with an optimal sample size need to be performed on the use of adjunctive MST for schizophrenia to confirm and extend these findings.The original contributions presented in the study are included in the article/X-YZ and X-HY selected studies and extracted the data. WZ reviewed all the data and helped mediate disagreements. X-YZ, WZ, and D-BC wrote the first draft. All authors contributed to the interpretation of data and approved the final manuscript.This study was funded by the National Natural Science Foundation of China (82101609), Scientific Research Project of Guangzhou Bureau of Education (202032762), Science and Technology Program Project of Guangzhou (202102020658), the Science and Technology Planning Project of Liwan District of Guangzhou (202004034), Guangzhou Health Science and Technology Project (20211A011045), Guangzhou science and Technology Project of traditional Chinese Medicine and integrated traditional Chinese and Western medicine (20212A011018), China International Medical Exchange Foundation (Z-2018-35-2002), Guangzhou Clinical Characteristic Technology Project (2019TS67), science and Technology Program Project of Guangzhou (202102020658), and Guangdong Hospital Association (2019ZD06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "OBJECTIVES/GOALS: The University of Rochester CTSI Research Education Hub is designed to: 1) connect the local research community with essential internal and external educational resources; 2) create a community of inquiry and collaboration across the translational science workforce pipeline within the university. METHODS/STUDY POPULATION: The Research Education Hub (RE-Hub) utilizes the university\u2019s widely used Learning Management System (LMS), Blackboard, and accessible to anyone at the university with a BlackBoard account. The RE-Hub greets users with an overview, an introduction of key local faculty experts in relevant research methodologies, and links to institutional research programs and helpdesks. Users are provided with curated educational resources organized by topic areas including, but not limited to, research methodology, statistical analysis, and grantsmanship. Discussion boards were created for users to ask general research questions and to connect with others in the translational research community. RESULTS/ANTICIPATED RESULTS: The RE-Hub was designed in Fall 2019 with the purpose of increasing utilization of university resources, including workshops, seminars, methods forums and consultation resources to improve translational science at the university. The RE-Hub was designed to be flexible and responsive to the changing needs of the local research community. User feedback will be used to identify improvements in the organization and content of the RE-Hub. Future improvements will include additional topic areas that span translational competencies, additional materials added to existing topic areas, and facilitation of better collaboration and integration of career development programs and grantsmanship resources. DISCUSSION/SIGNIFICANCE OF IMPACT: The Research Education Hub provides the University of Rochester translational science research community with a space to explore educational resources, to interact with colleagues and ask research related questions, and to help develop and/or improve other educational programs at the university."} +{"text": "Although polyhydroxyalkanoates were discovered over 100 hundred years ago, and have been used for many applications , the majTo solve these bottleneck barriers, large members of research institutes and industries have contributed their endeavors in this developing field. Other than polyhydroxyalkanoates, semi-synthesized polylactic acid (PLA) has become another bulk commercialized biopolyester with acceptable unit cost and promising material properties . Other nMoreover, the diversity of bio-monomers has increased in recent years . In addiNduko and Taguchi have provided insights into the history for the development of lactate containing polyesters/oligomers, and the applications of variable lactate containing polyesters/oligomers (as macromonomer building blocks). Relating to the use of non-food feedstocks in the bioproduction of polyesters, Sun et al. and Moriya et al. present their updated studies on the microbial production of poly(3-hydroxybutyrate) from a broader-range of non-food substrates. Relating to the microbial production of medium chain-length polyhydroxyalkanoates, Scheel et al. reported a fermentation protocol which can be applied to control the copolymer composition to exhibit increased flexibility and elasticity in a series of medium chain-length poly. Harada et al. present a study on the microbial production of medium chain-length poly by application of an engineered polyhydroxyalkanoate synthase, which significantly improved the 3-hydroxyhexanoate (3HHx) fraction in the copolymers. Dartiailh et al. studied the effects of monomer composition on the thermal and mechanical properties of medium chain-length polyhydroxyalkanoate synthesized by Pseudomonas putida cultured with different substrates.In this Research Topic, a number of experts contributed their updated research outcomes or opinions regarding the strategies to improve the microbial production of polyester. From the perspective of microbial production of novel lactate containing polyesters and oligomers, It is hard to forecast the future of polyester industries, but we believe biopolyesters will have a promising future, based on: the availability of renewable and sustainable bio-feedstocks to support the bioproduction of polyesters; consumer demand for biodegradable and bioassimilatable materials based on renewable biopolymers; industries and research institutes that are eager to develop renewable and degradable polyester products; and the increasing application of advanced biotechnologies and materials science techniques that are being applied in this field.Enjoy reading!"} +{"text": "Waste electronic and electrical equipment (e-waste) consists of used and discarded electrical and electronic items ranging from refrigerators to cell phones and printed circuit boards. It is frequently moved from developed countries to developing countries where it is dismantled for valuable metals in informal settings, resulting in significant human exposure to toxic substances. E-waste is a major concern in Africa, with large sites in Ghana and Nigeria where imported e-waste is dismantled under unsafe conditions. However, as in many developing countries, used electronic and electrical devices are imported in large quantities because they are in great demand and are less expensive than new ones. Many of these used products are irreparable and are discarded with other solid waste to local landfills. These items are then often scavenged for the purpose of extracting valuable metals by heating and burning, incubating in acids and other methods. These activities pose significant health risks to workers and residents in communities near recycling sites. E-waste burning and dismantling activities are frequently undertaken at e-waste sites, often in or near homes. As a result, children and people living in the surrounding areas are exposed, even if they are not directly involved in the recycling. While toxic substances are dangerous to individuals at any age, children are more vulnerable as they are going through important developmental processes, and some adverse health impacts may have long-term impacts. We review the e-waste situation in Africa with a focus on threats to children\u2019s health. How to safely dispose of waste products coming from human activity is a global problem. Often in countries without adequate regulation, wastes are simply discarded. Most countries put wastes into landfills, but without adequate control landfills stink, leachate coming from the landfill can contaminate water and methane escaping from degradation of organic material contributes to climate change. In addition, landfills often attract vermin than can cause and spread disease. In many poor countries, people\u2014including children\u2014scavenge landfills for items of value, increasing risk of injury, infection and exposure to dangerous substances. Incineration is an alternative to landfills, but if incinerators are not operated with appropriate controls, they release toxic metals and dioxins that have the potential to cause significant harm to human health ,2. The harm to the environment is made worse when the discarded material is not readily degradable, as is the case with plastics that now contaminate land, lakes, streams and even the ocean. About eight million metric tons of plastics enter the oceans each year . HazardoThe term electronic and electrical waste (e-waste) refers to \u201celectrical or electronic equipment, which is waste, including all components, subassemblies, and consumables, which are part of the equipment at the time the equipment becomes waste \u201d. E-wastIn 2019, the world generated an estimated 53.6 million metric tons (Mt) of e-waste, or an average of 7.3 kg per person . FurtherThe value of the raw materials in global e-waste is estimated to be 57 billion USD, with iron, copper and gold contributing the most . In someE-waste includes many substances that are dangerous to the health of humans and the environment if released in an unsound manner. E-waste recorded in 2019 contained as much as 50 tons of mercury and 71 kt of brominated flame retardants . The impWhile there is significant exposure risk to all individuals who are involved in informal e-waste recycling childrenPeer-reviewed publications within the past 15 years related specifically to e-waste in Africa were assembled based on searches on academic research publication databases including PubMed, Science Direct, and Google Scholar. Publications, governmental and regulatory agency reports, and guidelines, were obtained through formal and informal sources. Keywords used to search the literature were: e-waste in Africa, WEEE in Africa, used electronic equipment in Africa, African e-waste management, e-waste regulations and guidelines in Africa, health effects of e-waste chemicals in Africa, African children\u2019s exposure to e-waste chemicals and impacts, countries exporting e-waste to Africa, and African countries most affected by e-waste. Tsydenova and Bengtsson reviewedLandfills in African countries containing e-waste have shown elevations of many different potentially hazardous metals . Soils aE-waste is recognized as a resource as it contains valuable materials . HoweverThese methods result in severe air pollution containing many toxic substances around e-waste recycling areas. Particulates and other air pollutants are inhaled by workers and nearby residents. In addition, chemicals escape and may contaminate dust, soil, and water in communities around dump sites leading to additional routes of exposure, such as dermal contact and consumption of contaminated food and water . E-wasteLead: Lead is a well-known neurotoxin . Ho. Ho11]. The care and management of e-waste in African countries is either poor or non-existent. The management of e-waste in African countries is a major contributing factor to high levels of pollution and hence the adverse effects on humans, animals, and the environment . Few AfrOn the Ban of the Import into Africa and the Control of Transboundary Movement and Management of Hazardous Wastes within Africa, was set up in 1991 to ban the importation of toxic substances from developed countries into African countries. The East Africa Communication Organization (EACO), formed in 2012, has developed working groups to address e-waste issues in its member nations. EACO has held a range of regional conferences and has produced several reports and strategies addressing e-waste management, awareness, and the status of e-waste in member nations. EACO also aims to train national representatives in better e-waste management, facilitating interventions, and the development of more reliable regional and national statistics. At a national level, the e-Waste Association of South Africa (eWASA) was formed in 2008 to establish sustainable and environmentally friendly ways of managing e-waste. Its members include electronics manufacturers, importers, and retailers. eWASA has struggled to affect the import of e-waste in South Africa. One reason for this is that e-waste and its economic benefits have been championed by business-people who may not consider or be aware of short- and long-term health impacts due to exposure of inappropriately recycled e-waste [The Bamako Convention, e-waste . At the e-waste . In Marc e-waste . Other S e-waste . Interventions targeting e-waste are desperately needed in African countries. At international and regional levels, interventions need to target the illegal importation of e-waste, including the better training of inspection officers and better management techniques, without depriving recyclers of their source of livelihood. The International Labor Organization (ILO) has produced strategies on ensuring the safety of e-waste workers that can be adapted to African contexts . At natiAwakening environmental awareness, increased environmental regulation and associated disposal costs in developed countries in the 1970s and 1980s led to incidents of uncontrolled transboundary movements of hazardous wastes and, at times, intentional dumping in developing countries, including in the African region. In response, the global community adopted the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and Their Disposal on 22 March 1989 and entered into force in 1992. The main objective of the Basel Convention is the protection of human health and the environment against the adverse effects resulting from the generation management, transboundary movement, and disposal of hazardous and other wastes.E-waste can fall under several entries in the annexes to the Basel Convention. In 2019, the \u201cBan Amendment\u201d to the Basel Convention entered into force, prohibiting the transboundary movement of hazardous wastes controlled under the convention destined for final disposal operations from parties listed in Annex VII (Organization for Economic Co-operation and Development (OECD), the European Commission countries and Liechtenstein) to all other States. The Ban Amendment also prohibits transboundary movement of hazardous wastes controlled by the convention except for those considered or defined as hazardous by the national legislation destined for reuse, recycling, or recovery operations. The entry into force of the Ban Amendment has significant political weight, acting as a flagship of international efforts to ensure that those countries with the capacity to manage their hazardous wastes in an environmentally sound manner take responsibility for them, while still allowing parties wishing to receive wastes required as raw materials for recycling or recovery industries. The Basel Convention was followed by other important conventions designed to deal with hazardous wastes, as outlined in The Bamako Convention is a treaty of the African countries to ban the import into Africa and to control the transboundary movement and management of hazardous and radioactive wastes within Africa. The need for the Bamako Convention was based on the realization that many developed nations were exporting toxic wastes to Africa. This convention was adopted in Bamako, Mali in 1991 and came into effect in 1998 . The majOstrava DeclarationLegal status: Legally bindingAdoption: 13\u201315 June 2017Entry into force: 15 June 2017Parties: 53 Member States of the WHO European Region (as of July 2021)Objectives: to improve outdoor and indoor air quality as one of the most important environmental risk factors in the region through actions towards meeting the WHO air quality guideline values in a continuous process of improvementScope: to shape policies and actions on environment and health, support the implementation of effective evidence-based policies and advance actions on environment, health, and well-being in the WHO European Region (as of February 2021)Key provisions:Improve air quality for all by ensuring access to safe drinking water, sanitation, and hygiene. Minimize the adverse effects of chemicals. preventing, and eliminating the adverse effects of waste management and contaminated sites. Strengthen adaptation to and mitigation of climate change. Build environmentally sustainable health systemsThe Basel, Rotterdam, Stockholm, Bamako Conventions, and the Ostrava Declaration are multilateral environmental agreements, which share the common objective of protecting human health and the environment from hazardous chemicals and wastes. Meanwhile, membership of any of the above conventions is not universal and compliance for some countries remains a challenge. For example, while most European countries have signed the Basel Convention, there is evidence that some 352,474 metric tons of e-waste are shipped from EU countries to developing countries each year . Therefoadvocacy including awareness raising and campaigns; knowledge and best practice sharing; and the development of a joint intervention model for the implementation of e-waste work at the country level [In 2018, the E-waste Coalition, a group of international organizations working globally and supporting national governments to address the e-waste challenge more effectively and across health and environment, climate and development agendas, signed a letter of intent. The E-waste Coalition has three core functions: ry level . As a mery level . The pilThis article proposes that actions can be taken at the local, national, regional and international levels to combat hazardous exposure to e-waste. At the local level, the health sector can play an important role by working with other sectors, such as labor, education, policy and environment, identifying specific needs within e-waste-affected communities, educating local communities on the health risks of exposure to e-waste and communicating methods to reduce exposure where possible, recognizing and monitoring health effects of exposure to e-waste and prescribing appropriate solutions. At national, regional and international levels, governments and policy-makers need to ratify appropriate conventions, such as the Bamako and Basel Conventions, that regulate and restrict the transboundary movement of hazardous waste, including e-waste, and implement World Health Assembly Resolution 69.4 on the role of the health sector in the Strategic Approach to International Chemicals Management towards the 2020 goal and beyond. At the regional level, countries need to work together to develop more robust data, build capacity and train those responsible for identifying illegal e-waste exports and to ensure that restrictions on transboundary movement of hazardous waste are enforced. National governments need to develop and implement effective waste management legislation that addresses hazardous waste, such as reducing the use of the most hazardous components in electronic and electrical equipment and encouraging safer and more efficient methods of recycling, develop health-related targets and actions for current and future e-waste policies and conduct research on e-waste and its potential health effects in a variety of contexts and locations, and to evaluate the efficacy of interventionsAt national and international levels, the health sector can play an important role by advocating and lobbying policymakers to incorporate strong health protection measures into national waste management policies and new electronics manufacturing initiatives. Across all levels more research is needed to monitor exposure to e-waste, to better understand the health outcomes associated with e-waste and to implement, and provide evaluation, of e-waste interventions. Research is key to providing national governments and international conventions with evidence of the dangers of e-waste exposure, the urgent need for greater regulation and informing effective legislation and controls. At the local level the health sector should be informed and empowered to raise awareness of the risks of e-waste recycling and prescribe appropriate solutions, work with communities at the primary health-care level to educate and engage key agents and implement and monitor the success of interventions that aim to reduce e-waste exposure.E-waste is a global problem due to the desire of people to have the latest electronic device, the rapid development of new devices and the short lifecycle of many electronic devices, such as computers and mobile phones. While almost all electronic and electrical items contain valuable materials, especially metals such as copper, the cost associated with extraction of these valuable materials from most devices in a safe manner and then disposing of the remainder often exceeds the value of the materials that are extracted. This has made recycling of electronic equipment questionably cost effective in most developed countries, leading to illegal exportation to and exploitation of less developed countries that do not have stringent safety regulations. At the same time the informal recycling of e-waste has provided necessary income for many people in developing countries. Workers, nearby residents and especially children living in or near the sites of informal e-waste recycling are being exposed to a variety of dangerous chemicals that impact cognitive function and increase the risk of many different diseases, including respiratory diseases and cancer. African countries have tried to address these problems through the Bamako Convention and a number of regional interventions, but lack of national action, legislation and enforcement has resulted in serious harm to e-waste workers, nearby residents and especially to the health of children. Stronger action and awareness are needed at international, regional, national and local levels to ensure that the health of people, especially children, and the environment is protected from hazardous chemicals found in e-waste."} +{"text": "Infections are a major cause of premature death. Fast and accurate laboratory diagnostics of infectious diseases is a key condition for the timely initiation and success of treatment. Potentially, it can reduce morbidity, as well as prevent the outbreak and spread of dangerous epidemics. The traditional methods of laboratory diagnostics of infectious diseases are quite time- and labour-consuming, require expensive equipment and trained personnel, which is crucial within limited resources. The fast biosensor-based methods that combine the diagnostic capabilities of biomedicine with modern technological advances in microelectronics, optoelectronics, and nanotechnology make an alternative.The modern achievements in the development of label-free biosensors make them promising diagnostic tools that combine rapid detection of specific molecular markers, simplicity, ease-of-use, efficiency, accuracy, and cost-effectiveness with the tendency to the development of portable platforms. These qualities exceed the generally accepted standards of microbiological and immunological diagnostics and open up broad prospects for using these analytical systems in clinical practice directly at the site of medical care provision .A wide variety of modern biosensor designs are based on the use of diverse formats of analytical and technological strategies, identification of various regulatory and functional molecular markers associated with infectious pathogens. The solution to the existing problems in biosensing will open up great prospects for these rapidly developing diagnostic biotechnologies. The most terrible tragedies of mankind in recent centuries have been associated with the outbreaks and spread of pandemic infections that have claimed hundreds of millions of lives. Despite the obvious success of the global health care system, the risk of epidemics of known, new, and recurring infections remains a serious threat to the world\u2019s population. The bacterial and viral infectious diseases with the fecal-oral mechanism of infection claim about 2 million lives annually. The recent outbreaks of Ebola, Zika, Dengue, Middle East respiratory syndrome, severe acute respiratory syndrome, and H5N1 influenza, as well as the increasing resistance of bacteria to antimicrobial drugs, increase the urgency of searching for new effective diagnostic tools aimed at early and rapid detection of pathogens .With broadening our knowledge on the complex biochemical processes underlying the pathogenesis of infectious processes, it has become necessary to develop more sensitive and highly specific diagnostic strategies. They are based on the identification of molecular markers, profiling of microorganisms without cultivation, enrichment, and isolation of pure cultures. These methods will become ideal analytical tools for controlling pathogenic microorganisms and make a basis for identifying the relationship between molecular structures and biological processes , 4, 5.Classical microbiological and immunoserological methods, as well as modern diagnostic platforms such as ELISA and chemiluminescence analysis, PCR, flow cytometry, and mass spectrometry (MALDI) adopted in recent decades, prevail when accurate verification of infectious agents is needed in centralized laboratories of medical hospitals and centers. However, these diagnostic tools require expensive equipment, long testing times, and qualified personnel, and are not always available for small hospitals, especially under limited economic resources and the decentralized infrastructure of medical facilities , 6, 7.The biosensor technologies that have emerged over recent years and are actively developing serve as innovative platforms for analyzing biomarkers of the infectious process have a high potential to become affordable, fast and reliable in operation, highly specific and sensitive tools for timely and true diagnosis of bacterial and viral diseases , 9. The In the global practice of infectious disease diagnostics, the point-of-care strategy is becoming increasingly important, based on modern molecular diagnostic technologies, including laboratory testing by the medical personnel at the patient\u2019s bedside or self-monitoring of certain laboratory parameters by patients at home , 9.The diagnostic platforms-precursors of this innovative strategy include qualitative and semi-quantitative test systems for identifying specific antigens and antiStreptococcus pneumoniae and Legionella pneumophila urinary antigens with the LFIA method. This has increased the popularity of the universal technology that is equally effective in the sandwich analysis format for both high-molecular antigens of microorganisms and antibodies to them in biosubstrates and low-molecular analytes .According to the definition of IUPAC , biosensThe idea of developing biosensors appeared more than half a century ago, and putting it into practice started , 35. TheIn the modern world, a considerable growth of interest is observed in biosensor technologies, which are rightly considered to be one of the rising trends in the scientific and technical sphere , 38\u201340. Structurally, biosensors are a complex consisting of three main functional segments:a bioreceptor (a biosensing component) with the elements on the sensor plate for recognizing target analytes (target molecules) contained in the biosubstrates;a transducer operating on physical and chemical principles ;an electronic device for signal processing, recording, and displaying data in a convenient form for the researcher .The analysis of the literature demonstrates interest in the development and use of these analytical devices in ecology, toxicology, agriculture, biosafety, and medicine, including the clinical diagnosis of infectious diseases and septic conditions. Over the decades of the development of the biosensing technology, a large number of structurally different sensors and attempts to systematize them have been proposed , 41\u201343.Currently, the biosensor classification is based on the nature of the biochemical component used, the analytical tasks to be solved, the type of signal transducer, the intended application field, and the generated signal. The technical strategies conditioning the ways of further detection (transduction) of the signal/event determine the basic principle of differentiation of the analytical devices , 44.According to this principle, in one of the proposed IUPAC classifications , all bio2 are immobilized on a solid sensor substrate (matrix) by covalent binding or biotin-avidin interaction. They serve for selective binding and identification of target analytes (ligands) in biological fluids [The recognition elements (bioreceptors) are common to all types of biosensors used in biomedical diagnostics: immunoglobulins (antibodies), enzymes , nucleic acids \u201347, micrxtracts) , 49\u201351.When designing highly sensitive biosensors, the correct choice of the matrix and conditions for immobilization of bioreceptors is of key importance. When using non-covalent binding, the receptor is retained on the sensor substrate of the transducer due to electrostatic, van der Waals, or ion interactions that hold the biomolecules fairly firmly. The main advantage of this type of immobilization is that the matrix does not affect the biological properties of the receptor , 26. WitThe new-generation devices more often comprise nanomaterials, the unique catalytic efficiency and adsorption properties of which are ensured by the optimal physical and chemical characteristics of the sensor substrate surface , 40, 54.The mechanism of transmitting a ligand-receptor interaction signal and its transduction is another important functional element of biosensors. Transmission is carried out with electrodes and graphite pastes , 56, 57.The principle of operation of bioreceptors can also be represented as three consecutive stages: recognition of the target ligand in the biosubstrate by a specific bioelement located on the touch panel; transduction of information about the biochemical reaction into the form of an electrochemical signal; transduction of this signal into a form convenient for reading or processing by the researcher , 55, 56.For example, in the biosensors, where the enzymes immobilized on the sensor plates serve as a recognition element, the substrates from the biomaterial in the presence of catalysts enter a biochemical reaction with them. The resulting product is determined with the aid of an electrode that transduces the biochemical reaction into an electrochemical signal, the magnitude of which is proportional to the amount of substrate in the studied biomaterial , 57, 58.In recent decades, the key task of interdisciplinary research into the design of modern biosensors has been to improve the parameters of close interaction of biochemical and physical functional elements in order to increase their sensitivity, selectivity, and reduce the detection limits of target analytes , 59, 60.The progress in the development of biosensor diagnostics of bacterial and viral infections has been achieved mainly due to modern improvements in the methods used for the identification of specific markers , 61\u201364.Escherichia coli or Staphylococcus aureus) integrated on the sensory substrate assimilate target organic compounds from biosubstrates , they themselves acting as a sensitive mechanism [Together with the already used analytical devices, where immunoglobulins and enzymes in the form of bacterial homogenates are applied as bioreceptors, in recent years, whole-cell microbial biosensors have been introduced, in which live natural or engineered microorganisms and its relationship with the patterns of metabolism and growth of microbes were described. These fundamental studies were confirmed in subsequent years by studying the role and structure of DNA and other reporter genes, such as xylE and tfdA, which are currently used actively as a biophysical model for environmental research [The use of reporter genes to identify factors that trigger genetic response in living microorganisms was proposed in the middle of the last century , 35 whenresearch , 66, 67 E. coli, S. aureus, Pseudomonas aeruginosa, and Staphylococcus epidermidis) with concentrations ranging from 102 CFU/ml. Besides, this sensor enabled the differentiation between live bacteria and dead ones.Liu et al. reportedS. aureus, where a bacteriophage with a detection range of 4\u00b7108 CFU/ml was used as a receptor [Another group of researchers proposed a biosensor design for highly sensitive and rapid identification of receptor .Further improvement of microbial biosensors has been due to the emergence of regulatory biosensing associated with advances in molecular genetic technologies and the discovery of new mechanisms for detecting various extracellular and intracellular signals, as well as their subsequent optical and electrochemical transduction , 69, 70.With the development of modern technologies in infectious disease diagnostics and epidemiology, label-free biosensors have become increasingly more widespread. They enable screening of intermolecular interactions and cellular reactions, provide detailed information about the selectivity of bacterial exotoxins and the specificity of antimicrobial agents, the interaction of antigen with antibody, as well as the kinetics of the inflammatory process, immunological and serological reactions , 73.Currently, there is a wide range of analytical devices for analyzing biospecific ligand-receptor interactions in label-free biosensors. In these highly sensitive and functional systems, the binding reactions of the target analyte to the bioreceptor can be studied without the use of any enzyme, radioactive, or fluorescent labels , 74, 75.This type of biosensor requires only one recognition element, which simplifies the analysis scheme, reduces its duration, and the cost of reagents. The current generation of label-free biosensors allows quantitative measurements of biomolecular reaction products in real time, which makes it possible to perform continuous data recording that enables kinetic monitoring of the parameters of the recognition process in ligand-receptor interactions , 78.An important advantage of using label-free biosensors is that the target analytes are detected in their natural form, without labeling or chemical modification, which means that they can be saved for further analysis .In recent decades, numerous studies have been conducted to develop new types of receptors , 68, 73 The optical, (piezo)electrical, or (micro)mechanical transducers are among the promising methods for recognizing ligand-receptor interaction signals in label-free biosensors used for the diagnosis of various infectious diseases. These biosensing methods are enhanced by surface plasmon resonance (SPR) , surfaceThe biosensors with optical transducers, considered as the main tools for signal perception, are one of the most powerful detection and analysis tools widely used in biomedical research and practical medicine , 88, 89.Due to a variety of detection methods using optical transducers in label-free biosensors, the authors of the review limited themselves to the devices that have proved successful in the detection of infectious disease pathogens. The cutting-edge technologies in the design of label-free optical biosensors with the focus on the diagnosis of bacterial infections are associated with the development of modern methods of transduction and new recognition elements (molecular-imprinted polymers) , 90\u201392 .Among the modern technologies used for the clinical diagnostics of bacterial and viral infections, the development of electrochemical methods of optical biosensing based on nucleic acids presents interest. The recognition elements used in these types of analytical devices include DNA, RNA, PNA, and aptamers. For example, nowadays the sensor technology of DNA hybridization based on electrochemical (impedance spectroscopy) and optical methods which recognizes the complementary target DNA chain of a pathogenic microorganism is gaining popularity, , 93, 94.The appearance of aptamer-based biosensors (aptasensors) and recombinant nucleic acids as recognition elements has resulted from the development of new technologies and advances in synthetic aptamer biology , 40, 48.For example, in a recent study by Sheng et al. , they reS. aureus, selected as the target pathogen for their aptosensor in food and water. The quantitative assessment of ligand-receptor interaction in the proposed biosensor variant was performed with specific fluorescent dyes for nucleic acids (Sybr Gold and Sybr Green I). It is noteworthy that rapid detection of the pathogen did not require special sample preparation .The authors demonstrThese modern innovations make optical biosensors more versatile than other types of sensor technologies , 74, 76.In optical biosensors, the use of the transduction method based on the surface plasmon resonance effect and the phenomenon of total internal light reflection is common , 84, 90.If gold (or silver) is sprayed on a hydrogel plate, then another phenomenon occurs associated with the presence of free electrons in this metal(s), which are exposed to the alternating electric field when illuminated. These electrons can collectively vibrate and resonate, adjusting to the frequency of incident light M. tuberculosis biomolecules and non-tuberculosis CFP10 and MPT64 mycobacteria, which, among numerous mycobacteria antigens, interact most strongly with related anti-CFP10 and anti-MPT64 antibodies on the immunosensor matrix.Among the family of optical label-free biosensors, SPR is one of the most accessible, developed, and most successfully used technologies in recent years for the diagnostics of infectious diseases and septic conditions. This is due to the high sensitivity and versatility of this type of sensors, which also allow real-time detection and direct measurement of the kinetics of molecular ligand-receptor interaction , 80. ForThe only drawback of optical label-free biosensors that use prismatic light refraction and SPR effects is their relatively large size, which is incompatible with mobile use in the point-of-care mode , 81. TheM. tuberculosis, mycobacterial proteins, and IFN-\u03b3 cytokine as the most important markers in the early diagnosis of tuberculosis.Label-free optical biosensors have been consistently used for characterization and screening of molecular interactions in clinical laboratories. For example, Golichenari et al. presenteThe majority of modern biosensors intended for the detection of infectious pathogens are based on electrochemical conversion of the signal. These sensors are based on measuring changes in the current, electrochemical potential, and impedancemetry as a means of conversion of biochemical reactions , 47, 85.The advantages of these devices include portability and simple measuring equipment. Together with their cost-effectiveness, high sensitivity, and large linearity detection range, the electrochemical sensors are capable to work with small sample volumes. Moreover, the result is not affected by sample turbidity, unlike the optical methods based on spectroscopic transduction , 100.The analysis of the research results published in recent years has shown that the development of molecular biology methods with the aid of nanotechnology opens up broad prospects for designing new biosensor platforms with highly efficient, highly sensitive, and highly selective detection of molecular infectious biomarkers.Medical biosensors as a new type of diagnostic tools are at the initial stage of their development. However, the first decades of practical application of these analytical devices in healthcare have shown their absolute attractiveness and prospects for detecting bacterial and viral pathogens. The development and implementation of biosensor technologies in clinical laboratory practice is a modern non-alternative strategy for reducing infectious diseases in the regions with a low level of healthcare, where cheap and highly effective diagnostics can play a key role in timely verification of pathogens. The development of inexpensive and affordable analytical devices for clinical diagnostics with lower detection limits for pathogens is necessary due to the importance of diagnosing infectious diseases at the preclinical stage. In this regard, successful experiments in designing and using biosensors for the detection of spore and uncultivated bacteria with an assessment of their viability pose interest , 87, 101This review focuses on a large group of biosensors that are more available and do not need labels for the reproduced signal, but have rather complex transduction systems. However, the future is for simpler and more portable diagnostic analytical systems that do not require complex conversion platforms (surface plasmon resonance and surface Raman spectrometry) and can detect multiple pathogens simultaneously on the base of multiplex analysis. Such biosensors will be able to solve the global problem of effective control of infectious diseases.Modern trends in the development of biosensor medical technologies are associated with the development of new materials for designing transducers and conditions for more effective ligand-receptor interaction. The prospects for expanding the practical applications of biosensor technologies are related to clinical diagnostics which meets the requirements of personalized medicine, and are equally attractive for doctors and patients, particularly when verifying pathogens of infectious diseases.in vivo metabolites, drugs and molecular markers of the infectious process will soon play a leading role.Moreover, one of the key modern trends in the development of clinical laboratory diagnostics is non-invasive testing, which does not involve blood sampling. In this regard, highly sensitive, miniature, and portable medical biosensors with their capability to continuously monitor"} +{"text": "Dear Editor,Psoriasis is a chronic, immune-mediated and complex inflammatory disease. The immunopathogenesis of the disease involves interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and specific interleukins (ILs) that coordinate the interaction between inflammatory cells and keratinocytes.IL inhibitors represent a new group of biological agents with greater specificity for the treatment of psoriasis, as they selectively target inflammatory pathways.Ustekinumab is a fully human monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit, shared by cytokines IL-12 and IL-23.43) in patients with no history of recurrent infections and no secondary causes.Benign constitutional neutropenia is an asymptomatic condition characterized by mild chronic neutropenia of 13, Psoriasis Area and Severity Index (PASI) of 12.9 (3.A 44-year-old dark-skinned male patient started follow-up at a dermatology referral service 10 years ago due to severe psoriasis, without joint involvement. He had a previous diagnosis of familial constitutional leukopenia 17 years ago, with a mean leukocyte count of 2600\u00a0mm of 12.9 and, conAfter undergoing the initial tests before starting the immunobiological treatment, which were all within the normal range, treatment with ustekinumab 45\u00a0mg was introduced, with the induction phase taking place in weeks 0 and 4 and then every 12 weeks, associated with calcipotriol, twice a day. The patient showed significant lesion improvement after12 weeks, with residual macules only and currently with PASI 0 . The patEvidence indicates that neutropenia during therapy with ustekinumab is rare, and when it occurs it is mild; therefore, periodic monitoring is recommended.None declared.Jessica Vianna Starek: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis and interpretation of data; critical review of the literature; critical review of the manuscript.Mariana Reis and Rocha Dultra: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.Cristina Santos Ribeiro Bechara: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.Juliana de Morais Fernandes Krakheche: Approval of the final version of the manuscript; design and planning of the study; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "For years, restrictive cardiomyopathies have remained poorly understood and resulted in significant morbidity and mortality. These cardiomyopathies are often difficult to diagnose and can be considered orphan diseases that often lack definitive therapies. In the last several years, however, exciting innovation and treatment, particularly in the field of amyloidosis, has spiked new interest and hope for patients and families affected by these diseases.In this issue, we aim to provide a comprehensive update to our readers regarding restrictive cardiomyopathies and also focus on two of the most common restrictive cardiomyopathies, amyloidosis and sarcoidosis. This issue is of special interest to us as guest editors because we both treat patients with these specific conditions, and we appreciate the opportunity to share answers to many clinically relevant questions through the reviews written by experts in the field.The terminology and classification of restrictive (and infiltrative) cardiomyopathies often leads to much confusion. In the introductory article, Drs. Imad Hussain, Smitha Narayana Gowda, and Hyeon-Ju Ali abate the confusion in their broad overview of the definition and classification of restrictive cardiomyopathy (RCM), defined as a heterogeneous group of diseases that cause increased myocardial stiffness leading to impaired ventricular relaxation and severe diastolic dysfunction. While it is the least common type of cardiomyopathy, it can be a diagnostic challenge given varied pathogenesis, clinical presentation, and diagnostic evaluation. In this review, they provide an overview of the rarer etiologies of RCM (excluding amyloidosis and sarcoidosis) and their diagnostic and treatment approaches.The next reviews focus on amyloidosis. Dr. Daniel Judge and colleagues provide a comprehensive overview of the epidemiology, genetics, and prognosis of transthyretin amyloid cardiomyopathy (ATTR-CM). This is an underdiagnosed disease characterized by pathologic accumulation of extracellular protein arising from unstable TTR tetramers. The authors break down the two distinct forms of ATTR-CM, hereditary and wild-type, and summarize the most common genotypes and their phenotypic heterogeneity. In addition, they give an overview of high-risk clinical features and factors that help predict prognosis.Following the ATTR-CM discussion, Dr. Kelty Baker reviews the epidemiology of light chain amyloidosis, the staging systems, and the concomitant prognostication that is critical in determining the appropriate treatment.Dr. Ahmad Masri and colleagues then review the clinical, imaging, and electrocardiographic clues that should raise suspicion for cardiac amyloidosis. They provide a simplified diagnostic workup algorithm to ensure an accurate diagnosis. The evolution of the noninvasive diagnosis of cardiac amyloidosis has significantly influenced our understanding of disease prevalence, presentations, and outcomes. However, clinical recognition of clues and red flags remains the most important factor in advancing the care of patients with cardiac amyloidosis.Multimodality imaging is becoming the crux of recognizing and diagnosing cardiac amyloidosis. Dr. Mouaz Al-Mallah and colleagues highlight the role of several known and innovative cardiac imaging techniques\u2014including echocardiography, cardiac magnetic imaging, and nuclear imaging\u2014that aid in the evaluation of cardiac amyloidosis.Treatment options used to be limited; however, the last decade has seen significant advances in disease-modifying therapies. Drs. Jignesh Patel and Lily Stern provide an excellent overview of current and experimental treatments for both light chain and ATTR amyloidosis.After these excellent review articles that keep us up to date on present diagnosis and treatment of cardiac amyloidosis, Dr. Barry Trachtenberg explores where the field is heading and what the future might hold for therapeutics and diagnostics. This topic includes the goal to develop anti-fibril therapies that will be safe and effective at removing deposited amyloid fibrils and restoring organs to their pre-amyloid state, as well as the potential for genetic editing to cure variant ATTR even before patients develop clinical signs of the disease.While several landmark studies have been done in amyloidosis, cardiac sarcoidosis is an emerging landscape for well-designed clinical trials. Several areas remain unexplored, particularly in the pathogenesis, genetics, newer imaging modalities, biomarkers, and treatment. Research and innovation are definitely needed in this area. The last two reviews of our special edition focus on this orphan condition.Cardiac sarcoidosis (CS) is a widely underdiagnosed yet clinically significant form of granulomatous myocarditis associated with significant morbidity and mortality. Clinical presentation ranges from clinically silent disease to cardiomyopathy or sudden cardiac death. Diagnosis of CS remains challenging due to the lack of sensitivity of any single diagnostic method, underscoring the importance of elevated clinical suspicion and the use of multimodality imaging to guide diagnosis and treatment. In this review, Dr. Yogita Rochlani and her colleagues discuss the epidemiology, pathogenesis, clinical features, and diagnosis of this clinically evasive disease.Sarcoidosis is a heterogeneous disease with various treatment indications, pulmonary and extrapulmonary. In this review, Drs. Ilias Papanikolaou, Emmanouil Antonakis, and Aggeliki Pandi provide a state-of-the art review on treatment indications and various agents whose use is supported by clinical trials.We are grateful for the opportunity to compile this special edition and provide you with a current overview of restrictive cardiomyopathies in general, with an added focus on the two specific cardiomyopathies. Clearly, the last decade has been exciting, particularly in the arena of cardiac amyloidosis. We anticipate additional advances that will come with new innovations in bioinformatics, imaging modalities, and drug development.Methodist DeBakey Cardiovascular Journal express our thanks to Dr. Trachtenberg and Dr. Kassi for their enthusiasm and dedication in curating this issue on infiltrative and restrictive cardiomyopathies.The editorial team of the Barry Trachtenberg, MD, is a cardiologist specializing in cardio-oncology, cardiology, heart failure, and transplantation cardiology. He is board certified in internal medicine, cardiovascular disease, echocardiography, and advanced heart failure and transplant.Dr. Trachtenberg received his BS degree from the University of Pennsylvania and attended medical school at the University of Texas-San Antonio. A native Houstonian, he completed his residency in internal medicine at Baylor College of Medicine prior to his cardiology training at the University of Miami School of Medicine.His clinical experience includes heart failure and heart transplantation, mechanical support pumps, cardiomyopathies, cardiac amyloidosis, and cardio-oncology. He has contributed to many publications related to advanced heart failure, cardio-oncology, amyloidosis, and ventricular assist devices.Dr. Trachtenberg is a member of the Amyloidosis Working Group of the International Cardio-Oncology Society of North America and serves on the Cardio-Oncology Council of the American College of Cardiology. He serves as the Heart Failure chair for the Texas Chapter of the American College of Cardiology. Currently, Dr. Trachtenberg is a heart failure/transplant cardiologist at Houston Cardiovascular Associates and a member of the Houston Methodist DeBakey Heart & Vascular Center and Methodist J.C. Walter Transplant Center.Mahwash Kassi, MD, is an advanced heart failure and transplant cardiologist at the Houston Methodist J.C. Walter Jr. Transplant Center and the Houston Methodist DeBakey Heart & Vascular Center. An assistant professor of cardiology at the Houston Methodist Academic Institute and Weill Cornell Medical College, she also is an assistant clinical member of the Houston Methodist Research Institute.Dr. Kassi received her medical degree from Aga Khan University in Karachi, Pakistan. She completed fellowships in cardiology at Houston Methodist Hospital and in advanced heart failure and transplant at Mayo Clinic, Rochester, Minnesota, in 2017.Her clinical interests include inherited and inflammatory cardiomyopathies, particularly cardiac sarcoidosis. She has numerous publications in peer-reviewed journals and her research interest includes computational fluid dynamic modeling in patients with left ventricular assist devices, for which she received the Texas A&M Presidential Award. In addition, Dr. Kassi is leading research efforts in cardiac sarcoidosis."} +{"text": "Coronaviruses in wild and domestic animals have a long history of spillover between species . These examples emphasize the need for wider mobilization of veterinary skills and expertise within national and international task forces in countering SARS-CoV-2 transmission and future epidemics.At national and international levels, veterinary professionals, their representative associations and animal health regulatory bodies have played roles in protecting the public\u2019s health during the COVID-19 pandemic due to their knowledge and first-hand experiences with animal coronaviruses. The United States Agency for International Development\u2019s Emerging Pandemic Threats, the Pandemic Preparedness for Global Health Security (PREDICT) project, was managed by the School of Veterinary Medicine at the University of California, Davis, and was headed by wildlife veterinarians. Through this project, bio-surveillance of SARS-CoV-2 in animals and humans was conducted. The program underscores the significance of veterinarians and their capacities in coronavirus surveillance and control. Another example of the human-animal-ecosystem endeavor is the establishment of the World Organisation of Animal Health (OIE) \u201cAd Hoc Group on COVID-19 at the Human-Animal Interface.\u201d The Group is led by Dr. William Karesh, president of OIE\u2019s Working Group on Wildlife, and joined by collaborating groups to identify research priorities, assess and disseminate surveillance information, and provide guidance on veterinary services that are COVID-19-relevant in animal health and veterinary public health. In Ireland, veterinary epidemiologists work with medical and research colleagues of the National Public Health Emergency Team\u2019s modeling advisory group to counter COVID-19 (Ferri and Lloyd-Evans http://www.primate-sg.org/covid-19). As a precaution against COVID-19 spillover, the IUCN Group recommends biosecurity measures to prevent and control coronavirus transmission from humans to wild great apes, including guidelines on physical distancing, mandatory use of medical masks and various bans on visitation. Further examples of veterinarians researching, producing and following statements can be found at the Center for Disease Control, COVID-19 Safe Industry Plan for Zoos and Aquariums by the Australia Zoo and Aquarium Association, and OIE guidelines to prevent spillover of coronavirus around humans, terrestrial and aquatic animals (www.cdc.gov/coronavirus) Species Survival Commission (SSC) and the Wildlife Health Specialist Group collectively produced \u201cGuidelines for Working with Free-Ranging Wild Mammals\u201d, among other risk assessments and preventive measures for care of captive wildlife. The IUCN SSC recommends that during the COVID-19 pandemic, no great ape reintroductions or translocations should take place . In addition, the US Centers for Disease Control and Prevention (US-CDC) co-funded the development of a Field Epidemiology Training Programme for Veterinarians (FETPV) in Indonesia in 2017 which helps Indonesia to gatekeep against emerging animal coronavirus epidemics. Current surveillance systems were found to be inadequate in a number of countries when COVID-19 emerged. Surveillance for infectious agents in farmed animals and wildlife is both underfunded and often inconsistent, with reduced interest in disease during inter-epidemic periods. There have been strong calls for enhanced wild animal surveillance to determine the extent and nature of the threats posed and for appropriate action to be taken , and in turn, EID prove to be very costly, both monetarily and environmentally have provided veterinarians with insights into ways to address the COVID-19 pandemic and also to prevent future spillovers. Transmission of coronaviruses between species and adaptive changes have occurred on many occasions and appear to have accelerated in the past 20\u00a0years. Anthropogenic factors such as biodiversity loss, environmental degradation and inappropriate farming and selling practices, though contending at contribution levels, must be investigated and addressed to reduce and mitigate future spillover and pandemics (Roche et al. Veterinarians\u2019 expertise and knowledge, particularly experiences in epidemics that involve multiple hosts, primary, secondary and evolving pathogens, can improve One Health approach to this disease and other emerging diseases (McNamara et al."} +{"text": "Bile duct cancer (BDC) has been identified as a highly aggressive cancer arising from epithelial cells of the bile duct, including intrahepatic, perihilar, and extrahepatic . TogethePalliative chemotherapy with cisplatin and gemcitabine (GEM) has been the standard of care for patients with unresectable cancers since 2010 and no breakthrough progress in this challenging disease in the era of targeted therapy and immunotherapy , clinicaIn recent years, scientists have established many omics profiles to reveal underlying mechanisms and networks in cancer. This omics-based approaches can be used and integrated for further basic and clinical research. Chang et al. reviewed the integration of genomics, epigenomics, transcriptomics, proteomics and metabolomics in BDC and provided the views of the application of omics in tumorigenesis, identification of prognostic factors, and investigation of novel targets for current and future drug development .TP53 encoding p53 protein, the guardian of the genome [One famous tumor suppression gene, e genome , has beee genome .Emerging evidence demonstrated that miRNAs regulate tumor responses to chemotherapy and targeted therapy. Huang et al. provided an overview of the current knowledge about the miRNA-mediated regulatory mechanisms underlying drug resistance among BDC, discussed the application of miRNA-based therapeutics to BDC, and provided the basis for innovative treatment approaches . Pan et Based on the comprehensive reviews and studies of various aspects in BDC from this special issue, to elucidate the successful strategy to overcome GEM resistance and innovate future novel treatment could be envisioned. All the efforts on BDC will help clinicians and researchers to beat such tough disease in the future."} +{"text": "Brassicaceae plants are of great interest for human consumption due to their wide variety and nutritional qualities. Of the more than 4000 species that make up this family, about a hundred varieties of 6\u20138 genera are extensively cultivated. One of the most interesting aspects is its high content of glucosinolates, which are plant secondary metabolites with widely demonstrated anti-oncogenic properties that make them healthy. The most relevant Brassicaceae studies related to food and melatonin are examined in this paper. The role of melatonin as a beneficial agent in seedling grown mainly in cabbage and rapeseed and in the postharvest preservation of broccoli is especially analyzed. The beneficial effect of melatonin treatments on the organoleptic properties of these commonly consumed vegetables can be of great interest in the agri-food industry. Melatonin application extends the shelf life of fresh-cut broccoli while maintaining optimal visual and nutritional parameters. In addition, an integrated model indicating the role of melatonin on the organoleptic properties, the biosynthesis of glucosinolates and the regulatory action of these health-relevant compounds with anti-oncogenic activity is presented. N-acetyl-5-methoxytryptamine) is an indolic bioamine derived from tryptophan as a precursor in its biosynthesis. Since its discovery in 1958 in the pineal gland of cow .,65.Elongnstrated . An overnstrated , and thaA. thaliana, Chinese cabbage seedlings and broccoli florets, the promoting role in glucosinolate biosynthesis has been demonstrated. Melatonin treatments induce the accumulation of total aliphatic and indole glucosinolates, increasing specific glucosinolates, including GER, GRA, GBS and NGBS, among others to know better the effects of melatonin on primary metabolism, specifically on the photosynthetic, respiratory and carbohydrate transformation pathways ; (ii) to form a better understanding of the regulatory mechanism of melatonin on glucosinolate metabolism ; (iii) to know the possible effect of melatonin on mineral, dietary fiber and vitamin composition in plants and cabbages; (iv) postharvest, to better understand the effect of melatonin on the metabolism of ethylene and other plant hormones in broccoli; and (v) to study the effect of melatonin in other postharvest products of the Brassicaceae family such as cauliflower, Romanesco, kohlrabi, red cabbage and leafy vegetables."} +{"text": "Gryllus bimaculatus) during storage. Four antioxidants and two packaging methods were used. The effects of different antioxidants and packaging methods on composition of fatty acids, contents of free fatty acids (FFA), peroxide value (PV), and thiobarbituric acid reactive substances (TBARSs) value of deep fried Gryllus bimaculatus were analyzed during 150 days of storage. The composition of fatty acids changed and the content of FFA, PV, and TBARs value also increased with the extension of storage time, indicating that the lipid oxidation dominated by oxidation of unsaturated fatty acids could occur in deep fried Gryllus bimaculatus during storage. In the same storage period, the total content of FFA, PV, and TBARs value of samples treated with antioxidants and vacuum-filling nitrogen packaging were lower than those of controls, suggesting that antioxidants and vacuum-filling nitrogen packaging have noticeable effects on inhibiting lipid oxidation and improving the quality of deep fried crickets, and dibutyl hydroxyl toluene (BHT) was found as the most effective antioxidant in this study. The results may provide a reliable reference for processing of deep fried edible insects.This study aimed to investigate the effect of processing methods on inhibiting lipid oxidation of deep fried crickets ( Insects are a biological group with the largest number of species, huge biomass, fast reproduction capability, and high food conversion rate on earth. Insects are highly nutritious, containing a large amount of high-quality proteins, high levels of unsaturated fatty acids, and high levels of essential trace elements, such as iron and zinc . AlthougBrachytrupes membranaceus, Gryllus similis, Gryllus bimaculatus, Gryllotalpa orientalis, and Acheta domesticus . These studies demonstrated that different degrees of lipid oxidation and decomposition may occur in edible insects during processing and storage, which are similar to other animal foods. Lipid oxidation is an important factor, influencing the quality and shelf-life of animal foods.Compared with other meat products, such as pork , beef 33, and goPhyllanthus emblica polyphenols have activities such as scavenging free radicals and anti-lipid oxidation [Phyllanthus emblica polyphenols (PEP), were used for the investigation in this study. The analysis results of free fatty acids content and PV value show that the antioxidant effects of BHT and TBHQ are better than that of ET and PEP, while the antioxidant effects of BHT, ET, and PEP are better than that of TBHQ in the analysis results of TBARs, in which the most effective antioxidant is BHT. Although some studies have reported that the antioxidant effects of some natural antioxidants in meat products are equivalent to BHT [Antioxidants inhibit the oxidation of lipids by scavenging the peroxide reaction matrix, complexing metal ions, reducing the concentration of active oxygen and blocking the dehydrogenation of fatty acids ,42. Syntxidation . Therefot to BHT , and evet to BHT , the antGryllus bimaculatus, four antioxidants were added to the palm oil used for deep frying, and the non-vacuum sealed packaging and vacuum-filling nitrogen packaging methods were used. Besides, the composition of fatty acids, contents of FFAs, PV, and TBARs value of samples that were treated with different methods during 150 days of storage were analyzed. The results showed that the contents of UFAs decreased, while the contents of SFAs increased. Meanwhile, the total content of FFAs, PV, and TBARs value increased during 150 days of storage, indicating that the lipid oxidation dominated by oxidation of UFAs could occur in deep fried Gryllus bimaculatus during storage. Additionally, at the same storage time, there were significant differences in the contents of UFAs and SFAs, as well as the total content of FFAs, PV, and TBARs value of samples treated with different methods. The total content of FFAs, PV, and TBARs value of samples treated with antioxidants and vacuum-filling nitrogen packaging were lower than those of the control, suggesting that antioxidants and vacuum-filling nitrogen packaging could significantly inhibit the lipid oxidation in deep fried Gryllus bimaculatus, which is an effective method to improve the quality and shelf-life of deep fried crickets, and BHT was found as the most effective antioxidant in the present study.In order to study and inhibit lipid oxidation in deep fried"} +{"text": "Chronic kidney disease (CKD) is a serious public health problem worldwide, leading to a series of physical and psychological comorbidities, in addition to costly treatments, lifestyle and dietary restrictions. There is evidence that mindfulness-based interventions (MBIs) offer complementary treatment for people with chronic illnesses, including CKD, with the aim of improving overall health, reducing side effects and treatment costs. This review aims to investigate the MBIs impact on people with CKD undergoing hemodialysis, and to identify the methodological quality of the current literature in order to support future studies.We ran searches in five databases in July 2020. The papers were selected and evaluated by two reviewers independently, using predefined criteria, including the Cochrane Group's risk of bias tool and its recommendations (CRD42020192936).Of the 175 studies found, 6 randomized controlled trials met the inclusion criteria, and ranged from 2014 to 2019. There were significant improvements in symptoms of anxiety, depression, self-efficacy, sleep quality, and quality of life (n=3) in the groups submitted to the intervention, in addition to physical measures such as blood pressure, heart rate and respiratory rate (n=1).MBIs can offer a promising and safe complementary therapy for people with CKD undergoing hemodialysis, acting on quality of life and physical aspects of the disease. For Embase, the search was carried out with the filter \"all fields\", Web of Science was filtered by \"topic\" and Scopus through \"title, abstract and keywords\". For the other databases, no filter was used. The reference lists of the included studies was also analyzed in order to identify a possible flaw in the original search. The articles included in the search had no definition of an initial period and were extracted until July 2020.The research included keywords indexed in Health Sciences Descriptors (DECS) and Medical Subject Headings (MeSH Terms) such as: Renal Dialysis; Dialysis; Chronic Kidney Failure; Peritoneal dialysis; Chronic Kidney Failure; Nephropathies; Mindfulness; Mindfulness Meditation; Mindfulness-Based Intervention; MBI; Mindfulness Based Stress Reduction; MBSR; Mindfulness Based Cognitive Therapy; MBCT; Mindful Eating. The synonyms present in each keyword listed were included in the search. The choice of adding synonyms to the search strategy was applied in order to unify the key used in the different databases and expand the search. All potentially eligible studies were reviewed, regardless of primary outcome or language.We included only MBI studies in people with chronic kidney disease, over 18 years old on hemodialysis treatment, and written in English. Systematic reviews and meta-analyses, MBI together with other interventions, incomplete texts and themes other than the objective of the study were excluded.All citations retrieved from electronic databases were imported into an Excel spreadsheet. Two reviewers (BNR and MFR) analyzed independently and blindly, where the researchers first selected the titles and abstracts, and then the full texts, applying the inclusion and exclusion criteria established in the protocol.Data from the included studies were independently extracted by the same two reviewers using a standardized form. The extracted data included: main author, year of publication, design, participants , inclusion criteria, information about the intervention and control group , post-intervention follow-up evaluations, evaluation measures and main results.The methodological quality of the included studies was independently assessed by the same two reviewers using The Risk of Bias 2 (RoB 2) tool, in its updated version for ECRs (and its variation for ECRs in crossover format)-,,We found 175 potential studies in the database searches. After removing 77 duplicate studies, we coded 98 titles and/or abstracts. Following the application of the exclusion criteria showed that 49% of the participants were married, 50% lived with a family and 46% used psychiatric medications. Four studies described comorbidities associated with CKD, with hypertension and diabetes being the most prevalent-,The six clinical trials involved a total of 264 participants with CKD and a mean age of 57.34 years (\u00b1 9.8), ranging from 15 to 63 participants among the studies. Except for the study by Nejad et al. (2018),,,-,,Most of the studies evaluated used well-established protocols such as mindfulness-based stress reduction (MBSR),Two studies adapted the MBSR protocol to be performed through videoconference and in groups (tMBSR), the first and the last face-to-face meeting and the rest were online-,,The practices described in the cited studies ranged from body scanning practices, conscious breathing, raisin practice, gentle arm movement, mindfulness in daily activities and self-compassion, in which participants were invited to adopt a gentle and non-judgmental attitude to respect for experience throughout practices. In addition to the practices carried out in the weekly meetings, most studies encouraged participants to practice at home and keep records over the weeks,Thomas et al. (2017)Since this review aims to investigate the impact of interventions based on mindfulness and chronic kidney disease in a broad way, the outcomes found throughout the studies were described as a majority, being mental health outcomes such as depression, anxiety and self-efficacy, physical measures of fatigue, pain, sleep, blood pressure, sympathetic activity, respiratory rate, and psychosocial measures of quality of life See .,,Three studies associated the effects of MBIs on anxiety and depressionSolati et al. (2019)Gross et al. (2017),Two studies assessed sleep quality. The authors used different scales to assess this outcome. Gross et al. (2017)Park et al. (2014)Two studies assessed quality of life using different scales. Solati et al. (2019),,,,,,,The quality of the studies was measured using The Risk of Bias 2 (RoB 2), in its updated version,,In the domain referring to the measurement of outcomes, all studies cited the psychometric properties of the instruments used, as well as the justification for implementing the adopted measures. Only two studies did not have enough information about the outcome and whether the intervention could have been interfered from the responses,,,,,,,,..) The attrition rate was described in two studies, being 13% for each group,,,MBIs have grown worldwide as a complementary therapy in the treatment of chronic diseases, including CKD,,,,The results of the six studies are encouraging for the domains of mental health, physical measures and quality of life. There were significant improvements in the symptoms of anxiety, depression, greater self-efficacy, sleep quality and quality of life in the groups submitted to the intervention-,In addition to psychological and psychosocial stressors, the presence of comorbidities associated with CKD, such as hypertension, is very prevalent in people with CKDThis review enabled a broad understanding of the impacts of MBIs on CKD patients undergoing hemodialysis and employed a rigorous methodological strategy to research and evaluate the literature on this topic. Two reviewers were involved in the screening and evaluation of studies eligible for inclusion, with in-depth discussions regarding the proposed evaluations, and with the help of a third reviewer, when necessary. The methodological quality of the studies was carefully assessed according to the recommendations in the Cochrane Manual (Cochrane Collaboration 2020)The fact that MBIs originate from ancient Eastern traditions, and the resource constraints for translations in languages \u200b\u200bother than English, may have biased our findings. In addition, the low methodological quality of three studies together and the general heterogeneous nature of the evaluations/outcomes of the analyzed papers made it impossible to carry out a quantitative meta-analysis.,,,,,,,Reilly-Spong et al. (2015)In some studies, the authors used instrument subscales to assess their secondary outcomes, such as the item related to pain inserted in the SF-12,,,Although most of the papers evaluated used MBIs based on well-established protocols and certified mindfulness instructors, two studies did not specify the information on the protocol base of the program adopted, making it difficult to generalize the resultsFuture studies involving MBIs in patients with CKD should be carried out on larger scales, and with the implementation of robust methodologies; examine both physical and psychological measures, quantitatively or qualitatively, in order to further explore the clinical implications of interventions in this population. The sociodemographic characteristics, disease stages and associated comorbidities, sample stratifications, and issues regarding the necessary adaptations for the application of appropriate MBIs to the hemodialysis context, whether individually, in groups or online.Although the evidence is limited, this review indicates that MBIs may offer a promising, safe and non-invasive complementary therapy for patients with CKD on hemodialysis, specifically in relation to mental health, quality of life and the physical aspects of the disease. The implementation of these interventions must consider the certification of instructors and details of the protocols, ensuring their reliability. The potential impacts of MBIs for people with CKD require studies with higher methodological quality, clarifying the feasibility of different formats of interventions presented, and long-term evaluations."} +{"text": "BACKGROUND: Host factors expressed by individual past medical history of hypertension, stroke, and myocardial infarction may have a relationship with colorectal cancer.METHODS: As part of the Japan Collaborative Cohort Study (JACC Study) for the Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho), we conducted a follow-up study of 110,792 Japanese inhabitants aged 40-79 years to reveal the relationship of past medical history of hypertension, stroke, and myocardial infarction at the baseline in 1988-1990 with colorectal cancer death for about 10 years up to the end of 1999.RESULTS: Past medical history of hypertension associated with an increased risk of female rectal cancer when analyzing all cancer cases with adjustment for age, body mass index, and exercise . Past medical history of myocardial infarction was also an increased risk for female rectal cancer . Females who had a medical history of stroke had increased risk of rectal cancer without statistical significance.CONCLUSION: There was a positive association of past medical history of hypertension and myocardial infarction and an increased risk of rectal cancer in women. These common risk factors may contribute to the positive association between the above circulatory diseases and colorectal cancer.We reported a positive association between past medical history of hypertension and colorectal cancer in a case-control study in early 1980,Therefore, we conducted a cohort study to reveal the relationship in the Japan Collaborative Cohort Study (JACC Study) for the Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho).3,4 Briefly, the study population was 110,792 Japanese inhabitants aged 40-79 years at 45 study areas in 1988-1990. Subjects completed a self-administered questionnaire including past medical history of hypertension, stroke, and myocardial infarction. A response to the medical history questions was selected from four alternatives such as \u201chave never suffered from the disease\u201d, \u201chave suffered from the disease with present treatment\u201d, \u201chave suffered from the disease with treatment\u201d, and \u201chave suffered from the disease without treatment\u201d. Therefore, subjects with positive medical history of hypertension, stroke and myocardial infarction were defined as those who had suffered from hypertension, stroke and myocardial infarction, respectively, irrespective of past and present treatment.The study population, procedures for conducting the baseline survey using a self-administered questionnaire, and follow-up methods in the JACC Study have been described previously.5 by verifying computer-stored data in the Ministry of Health, Labour, and Welfare with permission. A diagnosis of colon cancer was defined by code C18, while rectal cancer was C19 and C20, in the above classification.5The follow-up survey was conducted using population registries in local municipalities to determine the vital and residential status of the cohort in each area. All subjects that moved out of the study areas were treated as censored subjects. All deaths that occurred in the cohort were ascertained by death certificates from local public health centers in the study areas with the authorities\u2019 permission from the Director-General of the Prime Minister\u2019s Office . The causes of death were coded according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision2, and no answer) and exercise for all colorectal cancer cases and cases except for those who had died within the first two years of the follow-up period. Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared provided in the self-administered questionnaire at the baseline.The risk of colorectal cancer was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs) estimated by the Cox proportional hazards model. Sex-specific HRs were computed after adjustment for age in all colorectal cancer cases and cases except for those who died within the first two years of the follow-up period. Sex-specific HRs were also computed after adjustment for age, body mass index (BMI) and for cases except for those died within the first two years of the follow-up period . Past medical history of stroke and myocardial infarction had a positive association with female rectal cancer, although there was no statistical significance. Past medical history of hypertension, stroke, and myocardial infarction also showed a positive association with male colon cancer, although none were not statistically significant. There were no other significant relationships among past medical history of hypertension, stroke, and myocardial infarction with colorectal cancer death by sex or site of cancer (colon/rectum).Sex-specific HRs and 95% CIs of colon cancer and rectal cancer adjusted by age, BMI and exercise are shown in 1,2 The present study showed a positive association between past medical history of hypertension and female rectal cancer. Females who had a medical history of hypertension had an increased risk of rectal cancer. This result supports the idea of the presence of common risk factors between colorectal cancer and hypertension. Obesity and physical inactivity are risk factors for hypertension.6 Obesity7,8 and physical inactivity8,9 are also risk factors for colorectal cancer. However, the risk of rectal cancer still existed when BMI and exercise were adjusted. Therefore, there may be common risk factors other than BMI and exercise involved in the link between hypertension and rectal cancer deaths. Females who had a medical history of myocardial infarction also had increased risk of rectal cancer when BMI and exercise were adjusted. Females who had a medical history of stroke had increased risk of rectal cancer without statistical significance. This may be accounted for by hypertension, as myocardial infarction and stroke are both closely related to hypertension.There are no consistent epidemiologic reports on the relationship between past medical history of hypertension and colorectal cancer.10 We proposed this hypothesis because the average value of plasma homocysteine of patients with colorectal cancer was significantly higher than of healthy controls in a clinical case-control study.10 Except for folic acid deficiency, oxidative stress may contribute to the relationship. We have already reported that higher levels of serum oxidized low-density lipoprotein, which is believed to play a role in the development and progression of atherosclerosis,11 were associated with risk of colorectal cancer as part of the JACC Study.12 Therefore, our findings that past medical history of hypertension and myocardial infarction increased the risk of female rectal cancer could be a secondary association due to folic acid deficiency and /or oxidative stress.There is a hypothetical correlation between circulatory diseases and colorectal cancer, shown in There is a major limitation in interpreting the present results. As we conducted a cohort study, some of the subjects who did not have a medical history of hypertension at the time of the baseline questionnaire survey may have developed hypertension and then subsequently colorectal cancer during the follow-up period. Therefore, the relationship between past medical history and colorectal cancer death might have been underestimated.There were no consistent results by sex or site of cancer (colon/rectum) in our study. These differences should be carefully addressed by considering factors other than folic acid deficiency and /or oxidative stress, such as hormonal background.The present investigators involved, with the co-authorship of this paper, in the JACC Study and their affiliations are as follows: Dr. Akiko Tamakoshi (present chairman of the study group), Nagoya University Graduate School of Medicine; Dr. Mitsuru Mori, Sapporo Medical University School of Medicine; Dr. Yutaka Motohashi, Akita University School of Medicine; Dr. Ichiro Tsuji, Tohoku University Graduate School of Medicine; Dr. Yosikazu Nakamura, Jichi Medical School; Dr. Hiroyasu Iso, Institute of Community Medicine, University of Tsukuba; Dr. Haruo Mikami, Chiba Cancer Center; Dr. Yutaka Inaba, Juntendo University School of Medicine; Dr. Yoshiharu Hoshiyama, Showa University School of Medicine; Dr. Hiroshi Suzuki, Niigata University School of Medicine; Dr. Hiroyuki Shimizu, Gifu University School of Medicine; Dr. Hideaki Toyoshima, Nagoya University Graduate School of Medicine; Dr. Shinkan Tokudome, Nagoya City University Graduate School of Medical Science; Dr. Yoshinori Ito, Fujita Health University School of Health Sciences; Dr. Shuji Hashimoto, Fujita Health University School of Medicine; Dr. Shogo Kikuchi, Aichi Medical University School of Medicine; Dr. Akio Koizumi, Graduate School of Medicine and Faculty of Medicine, Kyoto University; Dr. Takashi Kawamura, Kyoto University Center for Student Health; Dr. Yoshiyuki Watanabe, Kyoto Prefectural University of Medicine Graduate School of Medical Science; Dr. Tsuneharu Miki, Kyoto Prefectural University of Medicine Graduate School of Medical Science; Dr. Chigusa Date, Faculty of Human Environmental Sciences, Mukogawa Women\u2019s University ; Dr. Kiyomi Sakata, Wakayama Medical University; Dr. Takayuki Nose, Tottori University Faculty of Medicine; Dr. Norihiko Hayakawa, Research Institute for Radiation Biology and Medicine, Hiroshima University; Dr. Takesumi Yoshimura, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan; Dr. Akira Shibata, Kurume University School of Medicine; Dr. Naoyuki Okamoto, Kanagawa Cancer Center; Dr. Hideo Shio, Moriyama Municipal Hospital; Dr. Yoshiyuki Ohno, Asahi Rosai Hospital; Dr. Tomoyuki Kitagawa, Cancer Institute of the Japanese Foundation for Cancer Research; Dr. Toshio Kuroki, Gifu University; and Dr. Kazuo Tajima, Aichi Cancer Center Research Institute."} +{"text": "The immature immune system at birth and environmental stress increase the risk of infection in nursing pigs. Severe infection subsequently induces intestinal and respiratory diseases and even cause death of pigs. The nutritional and physiological conditions of sows directly affect the growth, development and disease resistance of the fetus and newborn. Many studies have shown that providing sows with nutrients such as functional oligosaccharides, oils, antioxidants, and trace elements could regulate immunity and the inflammatory response of piglets. Here, we reviewed the positive effects of certain nutrients on milk quality, immunoglobulin inflammatory response, oxidative stress, and intestinal microflora of sows, and further discuss the effects of these nutrients on immunity and the inflammatory response in the offspring. During gestation and lactation, maternal nutrition is a predominant factor to regulate the growth and immunity of piglets , 2. SincMaternal infection or inflammatory exposure during pregnancy impairs the innate response of newborns and increases their susceptibility to infection . During As indigestible carbohydrate, dietary fiber (DF) is partially or completely fermented by microorganisms in the large intestine, which could be categorized into insoluble and soluble fiber . InsolubBifidobacterium) of sows has been reported to activate the immune system and prom of sows . A recen of sows . Similar of sows .Chitosan oligosaccharide (COS) has good water solubility and performs antioxidant , anti-inSugar peat pulp (SBP) contains large amounts of soluble fibers such as pectin and dextran . FeedingEnterobacteriaceae in sow feces at delivery and the number of Escherichia coli in piglet feces at weaning (Seaweed extracts (SWEs) mainly consists of seaweed polysaccharide (SDP), laminarin, and fucoidan . Supplem weaning . These b weaning .Lactobacilli and decrease the abundance of Bilophila spp in intestine. Importantly, IL-10 and TGF-\u03b2 levels were increased in piglets, which avoids over-activated immune system in piglets , derived from the cell wall of Saccharomyces cerevisiae, has been used as a prebiotic for a long time . Recent diarrhea .Besides soluble fiber, insoluble dietary fiber also plays a crucial physiology role in sow. Insoluble dietary fiber accelerates gastrointestinal motility, reduces constipation and increases satiety of sows . Wheat bHowever, excessive level of dietary fiber could negatively affect total tract nutrient digestibility in pigs . As soluDuring late pregnancy and lactation period, sows require more nutrients and energy for fetal growth and milk synthesis. Oil supplementation in sow diets could prevent excessive mobilization of body reserves , shortenTLR-4, TLR-9 and MyD88) in the ileum is rich in long-chain n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory effects both in vitro is rich in monounsaturated fatty acids , as wellIt is worth noting that high fat-induced obese sows have lower number of live-born piglets , piglet During late pregnancy,rapid fetal development increases the metabolic burden and induces systemic oxidative stress of pregnant sows .Severe oVitamin E, one of the most effective antioxidants, could directly react with free radicals and stimulate the expression of antioxidant enzyme genes, like GSH-Px and CAT . In addiForsythia suspensa extract (FSE) is a medicinal herb extract that mainly consists of forsythiaside A, forythialan A, phillyrin and phillygenin. FSE has been shown to perform antioxidant and liver of neonates . Furthermore, administration of HMSeBA decreased the gene expression of IL-1\u03b2, IL-6 and IL-8 in placentas and IL-6 serum concentration in neonatal piglets. Therefore, HMSeBA supplementation in sows during late pregnancy increased the antioxidant capacity of piglets and reduced maternal and fetal inflammation is incorporated into selenopsroteins and subsequently prevent intestinal inflammation by alleviating oxidative stress . In addiammation . Similarammation . MoreoveTaurine (Tau), a metabolite of methionine and cysteine, have anti-inflammatory and antioxidant properties , 117. TaOxidized \u03b2-carotene (OxBC) is a complex mixture produced by complete and spontaneous oxidation of \u03b2-carotene. The addition of OxBC (8 mg/kg) to the perinatal diet (G85-L21) improved the litter weight and individual body weight of the weaned piglets. This might be due to OxBC increased the immune status of sows, which further affect the growth of piglets. This is evidenced by decreased levels of cytokines (TNF-\u03b1 and IL-18) and increased levels of immunoglobulin in colostrum .In this section, we describe some other nutrients which are advantageous to regulate the immunity and inflammation of piglets when supplemented in sow diets such as rare earth elements, lysozyme, and yeast nucleotides etc Table\u00a03.Christensenellaceae and Ruminocococaceae) and decreased abundance of opportunistic pathogenic bacteria (Proteus and Campylobacter) were also found in the intestinal tract of piglets (Rare earth elements (REEs) includes 15 elements such as lanthanum (La) and cerium (Ce) . In addi piglets .campylobacter in the feces (Lysozyme (LZM) is a natural antibacterial enzyme found in the tears, saliva and milk of mammals . Previouhe feces .Nucleosides could promote the growth and development of intestinal epithelial cells . The addSpray-dried plasma (SDP) is a protein-rich feed additive that contains immunoglobulins, peptides, glycoproteins and other active ingredients . PreviouDietary fiber regulates inflammatory and immune response in the offspring by modulating the maternal intestinal microflora and milk immunoglobulin content. The antioxidant substances could directly react with the free radicals and enhance the maternal antioxidant capacity, thereby indirectly reducing infection in the offspring. The oil and fat products not only provide adequate energy to sows, but also supply functional fatty acids to alleviate infection and enhance the immune function in the offspring by exerting the anti-inflammatory and anti-oxidant effects. In summary, maternal nutrition intervention is an effective way to regulate the inflammatory response and immunity in the offspring.in vitro cell experiments are required to clarify the potential mechanism. Lastly, whether the metabolites of these nutrients were involved in the regulation of immunity and inflammation in the offspring is still unclear and require more research.In this review, we mainly focus on the positive effects of nutrients in the regulation of immunity and inflammatory response of sows and piglets during pregnancy and lactation. It worth noting that these effects would be affected by timing and/or dosage of nutrient supplementation. Moreover, it is well known that excessive addition of fat usually has a negative effect on pigs. The toxic effects of excessive addition of other products, such as vitamin E and selenium are alsoQL, SZ, and MR initiated the idea, the scope, and the outline of this review paper. QL, SY, XZ, XL, ZW, YQ, WG, MR, and SZ studied and analyzed all of the publications cited in this paper and were involved in the manuscript preparation. SZ and MR conducted the final editing and proofreading. All authors contributed to the article and approved the submitted version.This study was financially supported by the National Natural Science Foundation of the P.R. of China (No. 31872364 and No. 31802067), Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515010440), Science and Technology Program of Guangzhou (No. 202102020056), Anhui Provincial Science and Technology Major Special Project (201903a06020002).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Carbon-based nanomaterials have been increasingly used in the design of sensors and biosensors due to their advantageous intrinsic properties, which include, but are not limited to, high electrical and thermal conductivity, chemical stability, optical properties, large specific surface, biocompatibility, and easy functionalization. Therefore, the final aim of this Special Issue is to share new data concerning the novel exploitation strategies of these nanomaterials in order to support the development of improved (bio)sensing tools. Focus is mostly placed on the usage of graphene but also on carbon dots and carbon nanotubes, as well as on the preparation and characterization of new (nano)composites. The tailoring of the (bio)sensor surface is the common approach of the different reported schemes when optimizing the (bio)sensor design. Simulation tests are also performed .The research community has shown rising and commendable interest in searching for and applying greener synthesis methodologies, with different studies ,3,4 explMoreover, for those researchers seeking an overview of the state of the art of the use of carbon-based nanomaterials for (bio)sensors\u2019 development, three review papers targeting different topics are included in this Special Issue. Pan et al. revised,The incorporation of carbon-based nanomaterials, independent of the detection scheme and developed platform type , has demonstrated a major beneficial effect on the sensitivity, specificity, and overall performance of (bio)sensors. Consequently, carbon-based nanomaterials have brought about a revolution in the field of (bio)sensors with the development of increasingly sensitive devices."} +{"text": "OBJECTIVES/GOALS: Hepatitis B and C virus causes inflammation of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. The aim of this study is to generate a modeled estimate of changes in hepatitis B and C prevalence, and future sequelae, that accounts for recent mass migration to the European Union stemming from 50 high-emigration countries. METHODS/STUDY POPULATION: Total migrant population from 2013-2017 was obtained from the Eurostat population database. Demographics including country-of-origin, sex, and age distributions were used to determine migrant contributions to HBV and HCV prevalence where available. Undocumented migration estimates were obtained from the Institute of Migration database. Country-of-origin HBV and HCV prevalences were obtained for the select 50 country-of-origin nations from the Polaris Observatory and from systematic reviews. Disease progression was estimated using HBV and HCV outcome data for total populations from treatment guideline publication from the European Association for the Study of the Liver. RESULTS/ANTICIPATED RESULTS: Between 2013 and 2017, a total of 11,030,786 documented migrants born outside the EU arrived to the 30 nations. Germany, United Kingdom, and Spain received the greatest influx of persons and the majority of migration stemmed from countries in West Asia, the Middle East, and Africa. A significant proportion of total migration was driven by conflict-related crisis in Syria, and East and North Africa. The most significant increases in estimated total hepatitis case numbers, national prevalence increases, and future sequelae were seen in Germany and Sweden. DISCUSSION/SIGNIFICANCE OF IMPACT: Mass migration has significantly changed HBV and HCV disease burden in Europe over the past 5 years. Consequently, long-term outcomes of cirrhosis and HCC are also expected to increase. These increases are likely to disproportionally impact individuals of the migrant and refugee communities. HBV and HCV surveillance and management programs must strategically focus on individuals from high-burden age cohorts and nations. Screening and treatment would aid WHO elimination efforts while benefiting both the vulnerable individuals and host nations through reduction of morbidity, mortality, and associated healthcare expenses."} +{"text": "One of the distinctive strengths of WLS is the availability of Henmon-Nelson IQ scores on all participants while in high school, followed by prospective collection of data through cognitive batteries of varying size and sophistication. Launched in 1993, the initial longitudinal cognitive testing included 8 abstract reasoning items followed by the administration of larger cognitive batteries in 2004 and 2011 comprised of a 10-item word recall test, digit ordering task, phonemic and category fluency, as well as repeated and new items from the WAIS-R similarities task first administered in the 1993 survey. In 2018, with R01 funding from NIA, the scope of cognitive testing expanded significantly and includes administration of a phone-based cognitive screening measure, and a comprehensive in-person neuropsychological assessment for individuals identified at risk for dementia targeting a range of cognitive domains, including memory, language, attention, visuospatial abilities, and executive functioning."} +{"text": "The pandemic profoundly affected the care of older adults in long term care communities (LTCC) across the world. More than one third of pandemic deaths were linked to nursing homes. Most nations and states had strict guidelines on visitation, with many, especially in the United States, totally prohibiting visitation for over an entire year. Well-intentioned measures to protect through isolation caused a profound ethical tension between safety and self-determination. The aim of the project was to examine this dilemma using a case study and the Madison Collaborative Ethical Reasoning in Action Framework. Eight key questions of fairness, outcomes, rights, responsibilities, character, liberty, empathy, and authority were applied in the context of federal and state mandates in the US and Australia. Results highlighted issues of ageism, paternalism vs empathy, regulatory vs family authority, a focus on short-term outcomes while forfeiting long-term outcomes, community responsibilities to the resident trumped individual resident rights, the potential loss of community character in lieu of basic care provision, a loss of personal freedoms, and the emphasis of physical well-being over holistic well-being. The results of this analysis can inform future policy and provide lessons learned for the future."} +{"text": "The advances in the field of gene therapy have significantly improved the possibility for nucleic acids as highly promising agents for the treatment of both inherited and acquired human diseases. Substantial progress has been made in the development of different types of nucleic acids, including plasmid DNA, mRNA, microRNA, small interfering RNA, and antisense oligonucleotides. Nevertheless, despite the immense pharmacological potential of these molecules, the successful clinical application of genetic material-based strategies remains dependent on the generation of safe and effective delivery systems that have the ability to overcome the numerous biological barriers associated with the gene delivery process. Up to now, the large majority of gene therapy clinical trials have been based on the use of viral vectors, namely due to features such as high levels of transduction, or the efficient and stable integration of exogenous DNA into the host genome. However, several drawbacks have been associated with viral vectors, such as immunogenicity, carcinogenesis, the size limit of exogenous DNA, and the difficulty of large-scale production. Non-viral gene delivery systems have the potential to overcome these limitations, allowing not only a safe but also efficient gene delivery process into the target cells.The aim of this Special Issue was to highlight the current progress in non-viral gene delivery systems. Six original papers and six review articles were published.The publication by Guan and Chen et al. focused Mart\u00ednez-Negro and Junquera and coworkers developeOn the other hand, Saher and Zain et al. evaluateIbaraki and Seta et al. used a nNagachinta and de la Fuente et al. aimed toThe potential of cell penetrating peptides (CPPs), also recognized as protein transduction domains (PTDs), to be used as non-viral gene delivery systems was the focus of the review article by Taylor and Zahid . In thisRoma-Rodrigues and Fernandes et al. providedpiggyBac (PB) transposon, one of three transposon systems and Tol2), namely the diverse roles of PB in gene delivery and strategies to improve its performance. This work highlights the potential of PB, which promotes the chromosomal integration of the delivered transgenes, to overcome the referred limitations associated with non-viral gene delivery systems.On the other hand, Sato and Nakamura et al. reviewedCarvalho, Cordeiro and Faneca presenteCarballo-Pedrares and Rey-Rico et al. performeOn the other hand, Aulicino, Capin and Berger focused Egorova and Kiselev et al. develope"} +{"text": "Most brain diseases are fatal with no effective therapeutic solutions currently available, contributing to major health issues globally. One of the major obstacles in overcoming the pathologies of these diseases is the existence of the blood-brain barrier (BBB), which physically separates the brain and the bloodstream . The BBBIn the past decades, various strategies including drug modification, novel delivery systems, transiently opening the BBB by physical or chemical methods and bypassing the BBB through intracranial or intranasal delivery have beein vitro and in vivo, and the application of nanoparticles for treating various brain diseases.This Frontiers Research Topic brings together contributions in new advancements in the mechanisms of the BBB regulation, the development of novel nanoparticles with the capability to be traced Wang et al showed that microRNAs (miRNA) could either inhibit or enhance the expression of tight junction molecules, thereby directly regulating the BBB. In addition, miRNAs affected the structure and function of brain endothelial cells, including the cytoskeleton, channels and transporters of brain endothelial cells. Furthermore, miRNAs also targeted inflammation molecules and other molecules often used in the crosstalk between brain endothelial cells and the other cells of the neurovascular unit. The profound effect of miRNAs on BBB function and integrity makes them a promising target for treatment of brain diseases. Additionally, improvement of brain vascular function may benefit the treatment of brain diseases. In the article by Zhu et al, the authors developed amorphous selenium nanoparticles (A-SeQDs) for treating chronic isocarbophos poisoning through the protection of endothelial function. They showed that A-SeQDs inhibited inflammation while increasing oxygen saturation, leading to sodium hydrogen exchanger 1-dependent reduction of endothelial apoptosis. Consequently, isocarbophos-induced vascular dysfunction was inhibited.Brain diseases are often associated with a dysfunctional often disrupted, BBB . Therefoin vivo drug monitoring. Chung and Zhang developed a novel colloidal stable and non-toxic fluorescent probe, an iron oxide and carbon dot-based nanoparticle, to deliver chemotherapeutics for killing of cancer cells. This new type of nanoparticle was low in toxicity and able to respond rapidly for quantitative imaging. Transparent cranial implants provided a possibility for chronic brain imaging, thereby facilitating brain research. Halaney et al analyzed the optical properties of a ceramic, nanocrystalline Yttria-Stabilized Zirconia (nc-YSZ)-based transparent cranial implant. The optical properties of the implant were critical to the design of optical systems for imaging the brain and for interpreting imaging outcomes.The development of nanoparticles with the capability for imaging is critical to disease diagnosis and Ngowi et al summarized the unique properties of nanoparticles for diagnosis and treatment of brain diseases, including brain tumor, ischemic stroke, amnesia, and amyotrophic lateral sclerosis. The small size of nanoparticles, usually less than 100\u00a0nm, enables them to cross the BBB for delivering therapeutics and diagnostic probes to the brain parenchyma. In addition, nanoparticles can be modified for improved solubility, bioavailability and specificity of conventional drugs. To accelerate clinical translation, the authors highlighted the importance of determining the toxicity and bioaccumulation of nanoparticles in clinical settings. Khan et al discussed the application of various nanoparticles in treating Alzheimer\u2019s disease (AD). They focused on the formulation of nanoparticles employed for this purpose, including organic, lipid-based, as well as metallic nanoparticles. The authors contended that the development of nanoparticles with multi-therapeutic capacities would be the research direction of future AD nanomedicine. Finally, in this special issue Li et al summarized the application of nanomedicine in AD and Parkinson\u2019s disease by focusing on the pathogenic targets of nanoparticles, such as oxidative stress, protein fibrillation, and inflammation.Nanoparticles have been employed to transport therapeutic agents to the brain, providing a safe and effective approach to improve brain drug delivery . Ngowi e"} +{"text": "According to the cognitive discrepancy theory, although the discrepancy between actual and desired social resources may result in loneliness, Perlman and Peplau (1998) suggested that cognitive processing and attributional style also impact the interpretation of social information. Previous empirical research investigating predictors of loneliness have not assessed a wide range of cognition and attribution factors, so this study filled this gap by examining how protective and exacerbating , and experiences of age-based discrimination) factors influence and moderate the experience of loneliness cross-sectionally and longitudinally using a sample of 3,345 Americans aged 50 years and older from the 2008 and 2012 waves of the Health and Retirement Study. Optimism , mastery , purpose in life , depression , control constraints , negative SPA , and experiences of ageism were significantly related to loneliness cross-sectionally and longitudinally, respectively. Optimism buffered the negative impact of poor functional social resources on loneliness cross-sectionally while control constraints, negative SPA, and experiencing ageism exacerbated the relationship between low functional social resources and loneliness cross-sectionally. None of the protective or exacerbating factors modulated the relationship between functional social resources and loneliness longitudinally. These findings have important implications for the development of interventions that target loneliness. Targeting maladaptive cognitions may be particularly effective in reducing loneliness."} +{"text": "Scientific Reports 10.1038/s41598-021-82844-7, published online 15 February 2021Correction to: The Acknowledgements section in the original version of this Article was incomplete.\u201cWe are grateful for the constructive comments received from Andrzej Baranski, Sanjeev Goyal, Agne Kajakaite, Byungkyu Lee, Georgia Michailidou, Rebecca Morton, Nikos Nikiforakis, Daniele Nosenzo, Wojtek Przepiorka, Ernesto Reuben, and Marie Claire Villeval as well as the participants of the 2019 Winter Experimental Social Sciences Institute at NYU Abu Dhabi, International Meeting on Experimental and Behavioral Social Sciences at the University of Utrecht and the participants of the Networks and Time speaker series at Columbia University. We also thank the anonymous reviewer for generous comments that helped improve the paper.\u201dnow reads:\u201cWe are grateful for the constructive comments received from Andrzej Baranski, Sanjeev Goyal, Agne Kajakaite, Byungkyu Lee, Georgia Michailidou, Rebecca Morton, Nikos Nikiforakis, Daniele Nosenzo, Wojtek Przepiorka, Ernesto Reuben, and Marie Claire Villeval as well as the participants of the 2019 Winter Experimental Social Sciences Institute at NYU Abu Dhabi, International Meeting on Experimental and Behavioral Social Sciences at the University of Utrecht and the participants of the Networks and Time speaker series at Columbia University. We also thank the anonymous reviewer for generous comments that helped improve the paper. This work was supported by the NYUAD Center for Interacting Urban Networks (CITIES), funded by Tamkeen under the NYUAD Research Institute Award CG001 and by the Swiss Re Institute under the Quantum Cities\u2122 initiative.\u201dThe original Article has been corrected."} +{"text": "For more than 40 years, under the leadership of four editors and two publishers, The International Journal of Aging and Human Development (IJAHD) has featured multidisciplinary scholarship related to aging processes and older adults. With the publication of eight issues a year, with over 800 pages of scientific content, the IJAHD places emphasis upon psychological and social studies of aging and the aged. However, the Journal also publishes research that integrates observations from other disciplines that illuminate the \"human\" side of gerontology. A more recent focus includes midlife development, as well. About half (47%) of the publications in the IJAHD are from international colleagues. This presentation will discuss tips for both international and US-based scholars for ensuring timely reviews and positive decisions for manuscript submissions, including such areas as key words, suggesting unbiased reviewers, formatting, writing mechanics, clearly-articulated methods, and a sound theoretical basis."} +{"text": "To evaluate the clinical and histopathological effects of natural extracts in the treatment of oral ulcers induced in animal experimental models.We carried out a search in the Medline, Scopus, WoS and Embase databases from the start of the databases to December 2020, and also made a manual search of the references. The search and selection were carried out by two researchers independently. The inclusion criteria were: experimental studies in animal models, in english, which complied with the study object.Jasminum grandiflorum, Ficus deltoidea, curcumin and Bixina orellana provoked a significantly greater reduction in the size of the ulcer. Extracts of Salvatora persica, Musa acuminate, Ganoderma lucidum mycelia and Bixina Orellana, as well as preparations of Kouyanqing Granule and curcumin, were able to reduce levels of pro-inflammatory cytokines and increase the expression and serum levels of growth factors and anti-inflammatory cytokines. Extracts of Piper sarmentosus, Cannabis sativa and Bletilla striata provoked a reduction in the severity of the histological inflammation. No significant differences were observed compared to controls in the treatments with extracts of Cannabis sativa, Aloe barbadensus Miller and Malva sylvestris in reducing the area of the oral ulcers.A total of 705 articles were identified. After selection by title, abstract and full text, 19 articles were finally included. Natural extracts of Most of the natural extracts described in this review presented a positive clinical and histological effect on the cicatrisation of oral ulcers induced in animal models. Key words:Recurrent aphthous stomatitis, oral ulcer, plants, herbs, extracts, medicine, treatment. An oral ulcer is defined as a tissue loss that alters the epithelium and the underlying connective tissues . Its aet-Review protocolThe systematic review protocol was registered in the international prospective register of systematic reviews (PROSPERO) of the National Institute for Health Research database (www.crd.york.ac.uk/prospero), reference code number CRD42020209352. This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline .-Search strategyA search was carried out in the MEDLINE, WoS, SCOPUS and EMBASE databases. A manual reference search was also carried out. The database search strategy is detailed in -Selection criteriaThe inclusion criteria were: experimental studies in animal models; in english; available from the beginning of the databases until december 2020; studies that aimed to evaluate the effect of natural extracts in the treatment of oral ulcers.in vitro studies; studies to evaluate effect of natural extracts on other pathologies of the oral mucosa.The exclusion criteria were: reviews, clinical trials, case series, case reports; published in other languages; human or -Study selectionAll the references identified were exported to the Mendeley\u00ae reference manager to facilitate the elimination of duplicates. The articles were reviewed by two authors independently ; when necessary, a third author (SW) resolved conflicts. Articles were selected first by title and abstract and then by full text, using the Rayyan tool.-Data extractionTwo data extraction Tables were prepared with the following information: first author and year of publication; total number of subjects and animal species; distribution of the experimental groups; method of induction of oral ulcers in animal model; type of treatment applied cont.; n-Risk of biasTwo authors independently assessed the risk of bias of the articles finally included. A third author resolved conflicts (ES). The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guideline was usedA total of 705 articles were obtained; 47 were selected by title and abstract, and 19 articles were finally included by full text -48. All -Extracts usedGanoderma lucidum and IL-6 in tissues, and the excessive release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). It has been shown that lack of sleep can activate the hypothalamus pituitary adrenal (HPA) axis . KYQG ha placebo . Extractdiflorum , Bixina orellana , Musa acorellana ,40, Blet striata , curcumi striata , Ficus dlization ,31,44,47lization , less selization , and betlization ,44 and 1gel used . Extractix (ECM) . Cannabiix (ECM) . Freeze-ix (ECM) . It is aJasminum grandiflorum, Bletilla striata, Ficus deltoidea, curcumin, Bixina orellana, Chamomilla recutita and Musa acuminate provoked a positive effect in ulcer contraction, re-epithelialization, and serum levels of molecules that promote repair or accelerate the healing rate. No significant differences from the control groups were observed with the use of treatments based on cannabidiol, Aloe Vera and Malva sylvestris in the area of the oral ulcers.Extracts of"} +{"text": "Antimicrobial resistance (AMR) is a global public health concern because of its fast spread. India, one of the world\u2019s top consumer of antibiotics and second most populated country has its unique constraints of social, cultural and economic strata. The continual self-medication, use of antibiotics for the growth promotion in animals, and accumulation of residual antibiotics in the environment challenge the implementation of AMR containment policy. Hence, the present review attempts to delineate the influence of antibiotics abuse on the human, animal and environmental health under the realm of one health. It was based on the literature search using public databases to highlight the rapid surge in the burden of AMR in India affecting various sectors and/or ecosystems in India. It was found that the irrational and overuse of antibiotics in different sectors have led to the emergence of extended antimicrobial resistance wherein the environment acts as a reservoir of antibiotic resistance genes (ARGs); completing the cycle of contamination and recontamination. There are efforts by government policy makers to reduce the burden of AMR in the country to reduce the health risks, through the One Health approach. Parallel efforts in educating healthcare professionals, strict legislation for pharmacies and pharmaceutical companies should be prioritize. At the same time surveillance of newly emerged AMR pathogens, prioritising research focusing on AMR, and awareness camps or programs among the local population is critical while addressing the consequences of spared of AMR in India. Discovery of the antimicrobial agents in the early twentieth century was a breakthrough to safeguard the public health from the microbial infection. Propensity of these compounds to kill pathogens influenced the discovery of novel antimicrobials. However, since the 1970s, soon after the discovery of the fluoroquinolones, no major antibiotics have been introduced , 3. The Bacteria are ubiquitous in nature; thriving in soil, water and air and, interconnectedness of ecosystems, featuring human, animals and environment collectively indicates that the burden of AMR is multifaceted in nature . AntibioblaNDM-1 and associated controversy necessitated the policymakers to initiate the development of AMR containment-related policies for India in 2011 . Mo. MoAcineectively . Thus, rc health , 29.Fig.E. coli or Salmonella species. Furthermore, there have been molecular investigations suggesting extended-spectrum beta-lactamase (ESBL)-producing and colistin-resistant E. coli from the poultry [The ever-increasing demand of animal-based food products compelled the producers to increase the usage of antibiotics and growth-promoting factors in the animal feed. The higher usage of antibiotics aids the better health of animals and also enable industries to abandon the responsibilities of maintaining hygiene and sanitation. Such ill-usage of antibiotics in the animal feed leads to bioaccumulation which was supported by observed traces of antibiotics in animal-based food products . Majorit poultry . Moreove poultry . The ant poultry . MoreoveStaphylococcus aureus have been isolated from the animals suffering from mastitis [Vibrio species and members of family Enterobacteriaceae [MDR strains like Vancomycin-resistant mastitis . Furthermastitis , 36. Mormastitis . Similarmastitis . Excessimastitis , 17. Stueriaceae , 17. Preeriaceae . Additioeriaceae \u201317, 33.The finding of antimicrobial-resistant microorganisms in humans, poultry, cattle and fishes reveal possible transmission and sharing of such microorganisms and antibiotic resistance genes (ARGs) between these organisms. However, the underlying mechanism of transmission and establishment of AMR is not well understood . Thus, ablaNDM-1, blaOXA-48, blaCTX-M and mcr-1 genes [NDM-1 genes are responsible for the development of drug resistance in pathogens and also provide an advantage to evolve as a superbug [Sewage plants receiving untreated or inadequately treated hospital and industrial effluents are a potential reservoir of AMR and ARGs. Discharge of untreated sewage into the rivers is a another major factor contaminating the river and facilitating the spread of AMR. Recent studies from India have indicated that the hospital waste carries significantly higher proportion of antibiotic residues, particularly the traces of broad-spectrum antibiotics . In the -1 genes \u201343. blaNsuperbug . Similarsuperbug , 41. Thesuperbug .blaNDM-1 were monitored during the seasonal pilgrimage on the bank of Ganga. The authors reported a 20-fold increase in prevalence during the pilgrimage [Acinetobacter, Corynebacterium and Brevibacterium which was isolated during the event show higher antimicrobial resistance [Corynebacterium godavarianum, a novel bacterium isolated during the Kumbh Mela 2015, was found to confer resistance against an array of antibiotics supporting the observed increase in antimicrobial resistance during the mass bathing event [India is a country of festivals involving several cultural events during the year, one such event is the Kumbh Mela. It is considered as the world\u2019s largest mass gathering event attracting millions of pilgrims for the duration of three months , 46. Thelgrimage . Similarlgrimage , 50. Antng event .Neisseria meningitidis serogroup W135 in 1968, 1987, 2000 and 2001, H1N1 pandemic in 2009, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, etc. Additionally, such a large participation also elevates the risk of stampedes or crush injuries, hence necessitates intensive planning and preparedness of the event to minimize the risk to the public health [India is one of the\u2009~\u2009184 countries that take part in Hajj pilgrimage at the Mecca, Saudi Arabia. Participation of pilgrims from these diverse countries has been associated with the morbidity and mortality at the event. In past, the Hajj has witnessed the burden of communicable diseases like, c health \u201354. Massc health , 52, 55.c health , 52. ThuThe striking observations of threatened humans, animal husbandry and fishery and, environment health due to growing antimicrobial resistance raise a serious concern Fig.\u00a0. Self-meTo address the ever-growing challenge of antimicrobial resistance and to safeguard public health, officials keep on upgrading the local policies by following the strategies outlined by WHO. The controversies related to the NDM-1 drew the attention of policy makers to initiate the National Policy on Containment of AMR in 2011 . The MinSimilarly, to safeguard the animal health, Food Safety and Standards Authority of India (FSSAI) has developed norms for the rational use of antibiotics. The FSSAI has banned the use of several antibiotics that could harm the fisheries and those used in the seafood processing . FurtherThe irrational and overuse of antibiotics in different sectors of India i.e., humans, food, animals and environment are responsible for the ever-increasing antimicrobial resistance (AMR), however, it has received little attention compared to its drastic impacts. Mitigation of the growing antimicrobial resistance would require strategies focusing on the one health approach. Initiative of the Indian government such as NAP-AMR policy along with the continued surveillance, awareness camps, and cross-continental research and training would enable combating the issue of AMR. Initiatives like designated AMR repositories by the Department of Biotechnology, Government of India at the National Centre for Cell Science, India would be helpful to generate and validate the emergence of AMR-related data in different sectors of India."} +{"text": "The Coronavirus disease 2019 (COVID-19) outbreak in Ghana is part of an ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The first two cases of COVID-19 were confirmed in Ghana on 12th March 2020. COVID-19 was consequently declared a Public Health Emergency of National Concern, triggering several response actions, including enhanced surveillance, case detection, case management and contact tracing, closure of borders, suspension of international flights, ban on social gatherings and closure of schools. Preparedness and response plans were activated for implementation at the national, regional, district and community levels. Ghana's Strategic approaches were to limit and stop the importation of cases; detect and contain cases early; expand infrastructure, logistics and capacity to provide quality healthcare for the sick; minimise disruption to social and economic life and increase the domestic capacity of all sectors to deal with existing and future shocks. The health sector strategic frame focused on testing, treatment, and tracking. As of 31st December 2020, a total of 535,168 cases, including 335 deaths (CFR: 0.61%), have been confirmed with 53,928 recoveries and 905 active cases. All the regions have reported cases, with Greater Accra reporting the highest number. The response actions in Ghana have seen high-level political commitment, appropriate and timely decisions, and a careful balance of public health interventions with economic and socio-cultural dynamics. Efforts are ongoing to intensify non-pharmaceutical interventions, sustain the gains made so far and introduce COVID-19 vaccines to reduce the public health burden of the disease in GhanaNone declared The Coronavirus disease 2019 (COVID-19) outbreak in Ghana is part of an ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2).6Most infections are asymptomatic, or patients present with mild symptoms, but some progress to a severe Acute Respiratory Distress Syndrome (ARDS), which is likely to precipitate a cytokine storm.The droplets may fall onto surfaces, and people could become infected by touching contaminated surfaces and touching their faces afterwards.Spread is highest during the initial three days after symptoms, but the spread is possible before the onset of symptoms and from asymptomatic individuals.22th of January 2020, several measures were instituted in Ghana as part of preparedness for COVID-19.th March 2020 and the confirmation of first two cases in Ghana on the 12th of March 2020 led to the declaration of COVID-19 as a Public Health Emergency of National Concern by Minister for Health, triggering a series of emergency preparedness activities to prevent and protect against COVID-19 in Ghana. This report provides an overview of preparedness and response to COVID-19 pandemic in Ghana over the period January to December 2020.Following the declaration of COVID-19 a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) on the 30Preparations were initially health sector driven and included infrastructure, equipment, logistics and human resource capacity development and enhancement, public education and sensitisation, public and stakeholder engagements. There were press releases and media engagements to solicit the media's support, collaboration, and participation in providing updates and information to the public. Key activities for preparedness included the training of healthcare workers on the disease based on existing knowledge. Training also focussed on surveillance using developed case definition on COVID-19, Infection Prevention and Control for diseases spread by droplet infection and the appropriate use of Personal Protective Equipment (PPE).At the regional and district levels, preparedness and response plans for public health emergencies were revised, and Public Health Emergency Management Committees (PHEMCs) were activated. Rapid response teams were also activated and trained. The National Technical Coordinating Committee (NTCC) and the Emergency Operations Centre (EOC) were activated at the National level. The NTCC was constituted by Ministries, Departments and Agencies with a direct role in the response. The membership of the NTCC also included international organisations such as the WHO; Research institutions such as the Noguchi Memorial Institute for Medical Research and School of Public Health at the University of Ghana. The EOC was the operational arm of the NTCC and had four thematic areas- Surveillance, Laboratory, Case Management and Risk Communication. The NTCC was responsible for coordinating the preparedness and response for COVID-19 with the EOC leading in the implementation of preparedness and response plans at the national level. At the regional and district levels, the respective PHEMCs and Rapid Response Teams (RRTs) played the roles of the NTCC and EOC, respectively. All regions and districts activated their respective RPHEMCs and District Public Health Emergency Management Committees (DPHEMC) with daily meetings.Other preparedness actions were the development of case definitions for COVID-19 based on the WHO recommendations. Ghana adopted an extremely sensitive case definition to reduce the risk of missing a case. A health declaration form was adapted from the Ebola Virus Disease (EVD) form for use at all points of entry (PoEs). Appropriate testing kits were also provided to facilitate confirmation of COVID-19 cases in Ghana. The procurement of other logistics such as PPEs was also undertaken. Additional measures implemented as part of preparedness for COVID-19 included the use of thermal scanners and non-contact thermometers at POEs, the introduction of health declaration forms at POEs, restrictive entries (non-entry from countries with more than 200 cases), and ban on government officials from travelling.The Government of Ghana's response was driven by three key principles: All of Society Approach, All of Government Approach, and Data and Science.nd March 2020; a partial lockdown in the Greater Accra and Greater Kumasi Metropolitan areas from 30th March 2020 for three weeks; the banning of social gatherings including religious activities and funerals, and the closure of schools.Initial response actions to the confirmation of COVID-19 in Ghana were the closure of borders to neighbouring countries and suspension of international flights from 22th of April 2020; and EI 164 on 15th June 2020. These provided the legal basis for restricting movements and social gatherings and mandatory wearing of face masks, among other measures. The response was also driven by a political framework based on the involvement of all ministries and agencies across all levels of governance from the community, through the districts, regions, to the national level. At the national level, the health sector, in collaboration with other sectors whose function impact on the response, together with development partners , activated the national public health emergency plan Limit and stop the importation, detect and contain the virusSlow down and manage community spreadProvide adequate medical and psychosocial care for COVID-19 casesStrengthen Governance, Coordination and Accountability of COVID-19 ResponseMinimise the impact of COVID-19 on Social & Economic LifeIncrease Domestic Capacity and Self-Reliance including building and strengthening capacity for health research and InnovationsGhana's response actions harnessed the appropriate legal framework, including the Public Health Act 2012 (Act 851) of 2012, which grants powers to the Minister for Health in Public Health emergencies; the Imposition of Restrictions Act 2020 (Act 1012); Executive Instrument (EI) 68 of 2020 on the 17The coordination of the COVID-19 pandemic response at the national level was subsequently elevated to the Presidency with daily emergency operation meetings chaired by His Excellency the President of Ghana with the Vice President, entire Cabinet, and a team of experts in attendance. Leadership by the President provided assurance, a sense of ownership and commitment at the highest level in preparedness for the pandemic response in Ghana. An Inter-Ministerial Presidential Taskforce on COVID-19 was set up chaired by the President of Ghana. The President initiated a whole-of-government approach including Ministries of Health, Information, Interior, Communication, Education, Local Government, Trade and Industries, Environment and Sanitation, Environment Science and Technology, and Aviation. Each ministry was assigned specific tasks in the national COVID-19 response effort. The President appointed a Coordinator for COVID-19 at the Presidency and established a command centre for COVID-19.A team of public health experts, medical laboratory scientists and expert Physicians were involved in the rigorous assessment and review of data to inform decision and policy. Processes were started for early and frequent engagements with institutions such as the Schools of Public Health, the Ghana Academy of Arts and Sciences, Professional Groupings including the Ghana Medical Association, Non-Governmental Organisations (NGOs) and Civil Society Organisations (CSOs) such as Occupy Ghana.At the time of confirmation of the first two cases of COVID-19 in Ghana, only two laboratories, the Noguchi Memorial Institute for Medical Research (NMIMR) and the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) could test for COVID-19. This presented challenges to the response with increasing numbers of suspected cases requiring testing leading to a backlog of samples. An aggressive drive to increase the capacity of the existing laboratories to test was instituted. This included recruiting additional staff and the institution of 24-hour workdays for the laboratories to reduce the backlog. In addition, other laboratories within and outside the health sector, such as the Veterinary Services Department laboratory came onboard to support testing and reduce the waiting period between sample collection and testing. Private laboratories were also assessed and accredited to provide testing for COVID-19 that further increased the capacity for testing and significantly reduced the waiting time. Thus, from two testing laboratories in April 2020, the number of laboratories capable of PCR testing for COVID-19 increased to 16 [4 private all in Greater Accra and 12 Public facilities ; Ashanti ; Volta ; Northern , Western (Veterinary Services Department Laboratory), Upper East . Six GeneXpert sites for SARS-CoV-2 testing were initially established with two functional at Cape Coast Teaching Hospital and Effia Nkwanta Hospital. Other GeneXpert facilities yet to be operational are Sunyani, Bolgatanga, Wa Regional and Sefwi Wiawso Municipal Hospitals. Thirty-two more sites were identified and are to be equipped to provide GeneXpert testing services for COVID-19.The laboratory component of the response also saw a significant increase in the human resource capacity for PCR testing in Ghana. Biomedical scientists and other laboratory staff received training from the NMIMR and the KCCR to provide PCR testing services. A laboratory network was also established at the national level, with a Coordinator appointed to oversee the work of the network, including the management of logistics for sample collection, transport and testing.Laboratory testing policy, guidelines and job-aids were developed, and staff were trained on them for immediate use. Real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) has been the mainstay of diagnosis and laboratory confirmation. Initially, testing was based on case definition, testing of close contacts, enhanced contact tracing (community screening). Prioritised testing of suspected cases, contacts, exposed health workers, students and at-risk groups was later adopted as part of the laboratory response strategy. The testing policy required initial PCR and double exit testing to assess recovery and discharge from the caregiving pathway. Following the revision of the National discharge and recovery policy, the mandatory exit testing was stopped. The pooling method was adopted initially but was suspended when the test positivity rate increased. Rapid diagnostic testing at Kotoka International Airport (KIA) using Immuno-fluorescent assay technology was introduced as part of measures to re-open KIA. Part of the laboratory response measures included evaluating the Rapid Diagnostic Test kit by the Food and Drugs Authority (FDA) in collaboration with the Noguchi Memorial Institute for Medical Research (NMIMR). At the end of December 2020, a total of 70 test kits had been evaluated. All 70 kits did not meet the set criteria for acceptability and use in Ghana for COVID-19 testing.Surveillance was a key component of the preparedness phase for COVID-19 in Ghana. It remains a useful component of the response phase. It includes routine surveillance through case definitions, enhanced surveillance and contact tracing to ensure early case detection and management. At the onset of the outbreak globally but before the recording of the first two cases of COVID-19 in Ghana, the working case definition adopted was:Suspected Case: A person presenting with fever (>38\u00b0C) or a history of fever and symptoms of respiratory tract illness, e.g., cough, difficulty in breathing AND in the last 14 days before symptom onset, a history of travel to China or any other affected countryORAND in the last 14 days before symptom onset, close contact with a person who is under investigation or confirmed for 2019-nCoV.A person with fever (>38\u00b0C) or a history of fever and symptoms of respiratory tract illness, e.g., cough, difficulty in breathing Confirmed Case: A suspected case with laboratory confirmation of 2019-nCoVFollowing the confirmation of cases in Ghana and the subsequent establishment of community spread in Ghana, the case definition was appropriately amended as:Suspected Case: A person presenting with fever (>38\u00b0C) or a history of fever and symptoms of respiratory tract illness e.g., cough, difficulty in breathing OR other symptoms such as loss of sense of smell, loss of sense of tasteORAND the last 14 days before symptom onset, close contact with a person who is under investigation or confirmed for COVID-19A person with fever (>38\u00b0C) or a history of fever and symptoms of respiratory tract illness e.g., cough, difficulty in breathing or loss of sense of taste and/or smell Confirmed Case: A person with laboratory confirmation of SARS-CoV-2 with or without symptomsst and 22nd March 2020, 105 were positive for COVID-19 . Mandatory quarantine ceased temporarily when international flights were banned but was resumed when the government approved evacuations which lasted till 1st September 2020.The overall objective of surveillance was to limit and stop the importation of cases among foreign travellers and reduce the local spread of the disease. Several activities were implemented as part of surveillance measures, including training of port health and other PoE staff , closure of all borders and introduction of mandatory quarantine. Mandatory quarantine for 14 days was enforced during the early phase of the pandemic in Ghana. This involved initial laboratory testing, daily monitoring for signs and symptoms of COVID-19 and exit testing at the end of the 14-day quarantine. Out of the 1,030 passengers who were quarantined upon arrival at KIA on the 21Development of surveillance and contact tracing guidelines, standard operation procedures (SOPs), and job-aidsTraining of health staff on the implementation of the guidelines and SOPsEnhanced contact tracing Use of call centres and toll-free emergency phone linesRegional Rapid Response Teams were trained, provided with enablers and rendered operationalContact tracing was decentralised and was conducted by district teams with the support of regional and national level teamsSurveillance Outbreaks Response Management and Analysis System (SORMAS), an open-source online mobile e-Health system that processes disease control, outbreak management procedures, disease surveillance, early detection of outbreaks and also software for management for epidemiological data, was deployed and scaled up nationwide for real-time electronic data collection and transmissionA barcode system to link surveillance and laboratory data was developed and implementedAdditional measures implemented to aid detection and containment of cases were the:th of March and 31st December 2020, the surveillance system confirmed 55,168 cases of COVID-19 from a total of 672,364 tests performed, giving a positivity of 8.2%. Among these were 705 cases recorded among international arrivals at the Kotoka International Airport. A total of 335 deaths were reported among the confirmed cases of COVID giving a case fatality rate of 0.61%. Ghana recorded the first major wave of COVID-19 cases between June and August 2020 with the 2nd of July 2020 recording the highest number of cases in a day (774). The trends in COVID-19 cases reported in Ghana between the 12th of March and the 31st of December 2020 are shown in Between the 12st of December 2020. The regions reporting the most cases were the Greater Accra, Ashanti, Western, Eastern and Central Regions. The Greater Accra region alone accounted for more than 50% of the reported cases. The North East Region recorded the lowest number of cases,22. The cumulative COVID-19 cases by region from 12th of March 2020 to 31st December 2020 is as shown in All 16 regions had reported cases of COVID-19 as of the 31st of September 2020. As part of measures to ensure the safe opening of the airport and to reduce the risk of COVID-19 transmission at the airport, the following measures were undertaken:Re-configuration of infrastructure to ensure adequate physical and social distancingLogistics for hand hygieneInstallation of operational booths for Port Health staffInstallation and establishment of an electronic data collection system for the health declaration form (HDF) and network connection of the HDF with the testing laboratory at the KIAWorkshops for airline operators on the guidelines on COVID-19 safety for international travelsSimulation exercises on planned passenger flow for airport re-openingRecruitment of additional staff such as nurses, doctors, disease control officers and clinical psychologists to strengthen their capacityEstablishment of a laboratory at KIA to conduct COVID-19 testing using immune-fluorescent antigen technologyEstablishment of a holding area for COVID-19 positive casesProvision of ambulances to transfer confirmed cases to designated treatment centresThe closure of the airport to international travel was the initial response to the pandemic in Ghana. After months of closure, the Kotoka International Airport (KIA) was re-opened on the 1Other activities implemented at KIA included completing the Electronic Health Declaration, an inspection of PCR test results from the country of origin for arriving passengers, temperature checks and disclosure of COVID-19 test results, isolation and transfer of COVID-19 Positive cases and contact tracing for passengers arriving at KIA.For three weeks, the Enhanced Contact Tracing strategy was adopted to ensure early case detection and establish the extent of community spread, especially in high burden regions and partial lockdown areas in the Greater Accra and Greater Kumasi regions. Teams were trained, resourced, and deployed to test, track and link cases to care. All identified and traced contacts of confirmed cases during the lockdown period were contacted and tested for COVID-19. Approximately 150,000 tests were undertaken during the lockdown period. Multisector contact tracing teams involved national security, immigration, and health workers. Heat maps were developed, and these provided evidence of community spread.Risk communication and social mobilisation was a key thematic area in Ghana's preparedness and response strategy. The Ministry of Information led this thematic area in collaboration with the Health Promotion Division of the Ghana Health Service and the National Commission for Civic Education, among others. Several strategies were adopted as part of risk communication and social mobilisation. At the highest level, regularly scheduled broadcasts by the President of the Republic were employed to update the public on measures implemented by the government in response to the outbreak. These broadcasts by the President were also used to announce health policy initiatives and other critical non-health government interventions. The broadcasts by the President of the Republic were very insightful, and the origin of the now popular expression \u2018Fellow Ghanaians\u2019, which was a call to action by all, can be traced to those Presidential updates.In addition to Presidential broadcasts, regular press briefings were part of the risk communication and social mobilisation strategies. The Ministry of Information, the Ghana Health Service, and other stakeholders provided the general public with scheduled media briefings. Subject matter experts and partners, including the Ghana Medical Association, Academia and the Ministry of Communications, were active participants in the press briefings at various points in time. One key message from such briefings was the refrain \u2018the virus only moves when people move\u2019, which helped emphasise the critical role of all Ghanaians during the critical lockdown period. Parliamentary briefings by the Minister of Health and/or Director-General of the Ghana Health Service were also implemented as part of the communication strategy.The risk communication strategy also included developing and disseminating key messages on COVID-19 to the general population. Public education on COVID-19 across regions, districts and at the community level using traditional and social media have been key components of the risk communication strategy. Other strategies employed included the broadcast of COVID-19 related messages on screens at PoEs, media engagements providing information on the disease and its prevention, media monitoring to identify challenges and misinformation on COVID-19, tour of media personnel to PoEs to provide them with a clear understanding of the operations of the Port Health Unit of the GHS and the engagement of other key stakeholders such as the National and Regional Houses of Chiefs.Ghana adopted two main approaches towards case management. The first approach was isolating persons with COVID-19 at designated treatment centres , all Teaching Hospitals, all Regional Hospitals, and some District Hospitals). The second approach was home isolation for asymptomatic and mild cases with no underlying medical conditions such as diabetes mellitus or hypertension.Development of case management protocols, guidelines, and job-aidsStaff training on the protocols and guidelines and capacity building, including infection prevention and controlExpansion of infrastructure for holding suspected cases and isolation of confirmed cases in all health facilitiesExpansion of isolation centres and provision of equipment, PPEs, medication, and consumablesInclusion of clinical psychology services for patient supportRe-assignment and deployment of selected staff of teaching hospitals with expertise in critical areas like intensive care and acute medicine to various treatment centres to facilitate the care of critically ill patients.In preparation for case management and care of the sick, the following were put in place to provide healthcare and appropriate health interventions for persons with COVID-19:Case containment was a critical component of the Case Management strategy. Various activities were implemented to ensure containment, which is key to reduce the risk of disease spread.All health facilities were directed and supervised to establish and operate designated holding rooms for suspected cases of COVID-19.Metropolitan, Municipal and District Assemblies (MMDAs) partnered with the Ghana Health Service to provide quarantine facilities in their respective districtsThe national policy and guidelines on quarantine made provisions for mandatory and self-quarantine under supervision. Provisions for mandatory quarantine were enforced when conditions for self-quarantine could not be met.Public-Private partnerships were used to secure more facilities for quarantine and isolation (with designated Isolation centres such as Pentecost Convention Centre (PCC), TUC (buildings in Accra and other regions), and the Ghanaman Centre of Excellence in Prampram)Designated Treatment Centres included Tema General hospital, Ga East Municipal Hospital, Greater Accra Regional Hospital, Korle-Bu Teaching Hospital, Kumasi South, Komfo Anokye Teaching Hospital, Frimpong Boateng Medical Centre, and the Nyaho Medical Centre) Newly constructed Ghana Infectious Diseases Centre (100 bed capacity) at Ga East Municipal Hospital, AccraThe following were some critical components of measures aimed at case containment in Ghana's response to COVID-19:The National Ambulance Service supported the response by providing ambulances at vantage locations, including the Kotoka International Airport, to transport suspected and confirmed cases. The drone delivery services were also employed in the delivery of test samples.The health system also set out to ensure prompt linkage to care for schools. To improve school health efficiency and quality, the schools were linked with the District Health Management Teams (DHMT) and nearest health facilities. All senior high schools were supported to establish or upgrade their infirmaries, and these were linked to health facilities in the respective districts. Training of heads of schools, teachers and school health staff was undertaken.A strategic effort was initiated for incremental procurement and stockpiling of essential supplies of PPEs. Measures were also started for local production of PPEs. More PCR machines, laboratory testing kits, infection prevention and control logistics such as hand washing facilities and equipment were procured and distributed. An active drive was initiated to expand infrastructure by identifying and converting facilities such as Ga East hospital to a treatment centre. Other facilities used as treatment centres were the Debrah Ward at 37 Military Hospital, University of Ghana Medical Centre (UGMC) and Frimpong Boateng Medical Centre in the Ashanti region. With these measures, the bed capacity for case management, which was 13 , now increased to about 1,000 beds, including Intensive Care Units (ICUs) and High Dependency Units (HDUs).involvement of private health facilities in the management of public health emergencies saw significant improvement as several private health facilities and laboratories have been accredited and licensed to provide COVID-19 testing and manage cases to complement the efforts of government facilities.The private sector support of Ghana's response extended to establishing the first Ghana Infectious Disease Centre (GIDC) at the Ga East Municipal Hospital. This well-equipped centre was constructed and furnished with funds solely from the private sector and handed over to the Government of Ghana to manage COVID-19 cases. This was a useful addition to Ghana's COVID-19 response and had the potential to be used to manage any future outbreaks of infectious diseases.Non-governmental organisations were also involved in the public education drive for COVID-19, including the development and dissemination of information on COVID-19 safety and the provision of billboards and other communication media. The private sector contributed significantly to the Ghana COVID-19 National Trust Fund established by the government to provide a channel for resources from the non-governmental sector to be pooled in support of the government's efforts towards COVID-19 response. Resources mobilised by the Fund have been useful in the COVID response supporting several activities, including procurement of personal protective equipment and other essential logistics.A team led by the Ministry of Health's Policy Planning Monitoring and Evaluation Directorate mobilised resources for Ghana's COVID-19 response. One major activity of this team was developing a COVID-19 Strategic Plan and Budget (2020\u20132024) with an estimated budget of over 600 million USD. The plan's development involved all relevant stakeholders and included the thematic leads from the laboratory, surveillance, case management, infrastructure, risk communication and social mobilisation. This plan was the basis of the development of the first Project Appraisal Document for the World Bank, for which an initial amount of 100 million dollars was raised to cover all the thematic areas.During the outbreak, mentorship and partnership with academia and other experts were also established. Furthermore, retired clinical and public health experts were engaged to provide technical support to the COVID-19 response. The retired consultants were also involved in monitoring, mentoring and evaluation of the response. Outputs from the engagements informed policy decisions.The government of Ghana instituted several social interventions as part of the response efforts for COVID-19. Among the many social interventions were:Provision of food to some residents in the Greater Accra and Greater Kumasi areas:During the lockdown in Greater Accra and the Greater Kumasi Areas in March and April 2020, the government provided hot meals to about 400,000 vulnerable individuals and homes.The meals were distributed at designated points within the cities, such as the Efua Sutherland Children's Park in Accra. In addition, the government also provided dry food packs for some 470,000 families.25Absorption of Water bills and Subsidy on Electricity bills:The government absorbed the water bills for all consumers for six months from April 2020. In addition, public pipe-borne water stands and water tanker distribution services were provided. The government also provided a 50% rebate for all consumers of electricity and provided free electricity for customers on the lifeline tariff for nine months from April to December 2020.26Tax exemption and other social interventions for healthcare workers: as part of response measures, the government also exempted payment of tax on the employment emoluments of healthcare workers from April 2020 to December 2020. In addition, healthcare workers working directly in the COVID-19 response classified as frontline healthcare workers received a 50% of their basic pay as a top-up to their monthly earnings from April to December 2020. Frontline healthcare workers were also provided insurance cover of up to 350,000 Ghana Cedis per worker. In addition to these, free transportation was provided for some healthcare workers in Accra, Kumasi, Tema and Kasoa.27Despite the many useful actions undertaken as part of health sector preparedness and response to the COVID-19 pandemic in Ghana, several challenges were identified. Key among these challenges were sporadic shortages of PPEs, geographical limitations in testing for COVID-19, delays in receipt of COVID-19 tests, lack of staff to manage treatment centres and shortage of COVID-19 laboratory reagents. The shortage of PPE was addressed through the increased procurement of PPEs and the streamlining of the distribution of PPE through a sub-committee of the NTCC, the Commodities Sub-committee. This sub-committee was also instrumental in addressing laboratory reagent challenges. On staffing challenges, staff training to provide critical care services was undertaken in addition to the secondment of specialised clinical care staff from teaching hospitals to treatment centres. The expansion of laboratory testing services to include private laboratories improved the turnaround time for sample processing to about 48 hours compared to several weeks during the early phases of the pandemic, causing a reduction in the pressure brought to bear on the main testing sites, NMIMR and KCCR. The expansion of laboratory testing services also improved geographic access to COVID-19 testing, although a significant proportion of testing laboratories are in Accra. Some of the interventions to alleviate the pandemic's adverse social and financial challenges, like distribution of food during lockdown, had operational challenges resulting in dissatisfaction.The numerous useful lessons from Ghana's response to the COVID-19 pandemic must be further studied and integrated into routine preparedness planning in Ghana. Key issues such as multisectoral collaboration, high-level political commitment, mobilising whole of government and society, private sector involvement and continuous engagement of the general population are useful, and high impact approaches for pandemic response and management of other public health emergencies.Emerging and re-emerging infections pose major threats to global health security. The COVID-19 pandemic has demonstrated the need for adequate and updated preparedness, with the availability of minimum core capacity for preparedness and response to epidemics. It is always difficult to predict when and where the next pandemic will emerge. Pandemic management and complex public health emergencies require multiple disciplines, sectors, and government apparatus. Additionally, good governance and leadership are crucial for effective, efficient, and successful management of pandemics and other complex public health emergencies, and Ghana's experience has demonstrated this."} +{"text": "According to Brown and Cai, Thyroid hormones (THs) have been considered \u201cthe first developmental morphogen ever discovered\u201d . This asXenopus tropicalis metamorphosis, both the cross-talk of THs and glucocorticoids and the intestinal morphogenesis are explored using state-of-the-art functional genomic and developmental biology approaches by Buisine [This article collection highlights the role of THs in different tissues, taking into account data from classical and novel models. The work of Esposito et al., gave an insight on the evolution of THs signalling comparing the homologies of the available sequences of TPO, DIOs, and THRs. Thus, their study supports the hypothesis of the evolutionary adaptation of a functional thyroid hormone signaling in non-vertebrate chordates . Nittoli Buisine and Shib Buisine , respectThroughout these articles the roles and mechanisms of action of THs are covered in different fields of interest including non-mammalian models. Taken together, these contributions should be of wide interest for both scientists of fundamental fields and physicians for translational approaches."} +{"text": "On July 15, 2021, the Secretary of Health of Honduras (SHH) was notified of an unexpected number of mucormycosis cases among COVID-19 patients. SHH partnered with the Honduras Field Epidemiology Training Program, the Executive Secretariat of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), Pan American Health Organization (PAHO), and CDC to investigate mucormycosis cases at four geographically distinct hospitals in Honduras.Mucormycosis is a severe, often fatal disease caused by infection with angioinvasive molds belonging to the order Mucorales. Risk factors for mucormycosis include certain underlying medical conditions and the use of certain immunosuppressive medications ,Given the severe outcomes associated with mucormycosis, clinicians should remain vigilant for this disease during the COVID-19 pandemic, including in immunocompetent patients. Early mucormycosis diagnosis is possible, even in resource-limited settings ("} +{"text": "Venous thromboembolism, a complex disease combining deep vein thrombosis (DVT) and its most dangerous complication, pulmonary embolism (PE), strikes millions of people worldwide. For example, in the United States only, DVT develops in up to 600,000 individuals annually, and 100,000\u2013180,000 deaths from VTE are estimated each year .Studies in the field of venous thrombosis cover several aspects of the disease. Discovery of the mechanisms of thrombosis initiation and propagation could help prevent its development in individuals at risk. Exploration of the routes of thrombus resolution is essential to reduce deleterious effects of the formed clot. Finally, search for specific biomarkers is necessary for both verification of the diagnosis and, importantly, prediction of the probability of thrombosis. A review by Anghel et al. in this issue Journal presents a set of previously known as well as novel biomarkers of venous thrombosis and discusses their potential benefits and limitations in diagnosis and building the treatments strategy for DVT .Separate mechanisms of DVT in certain pathological conditions are relatively well understood. For example, the role of tissue factor in cancer-related DVT has been established . Howevervasa vasorum and receives oxygen and nutrients from the blood inside the vessel. Blood flow stagnancy results in limited supply of oxygen and local hypoxia of both endothelium and subendothelial layers, which leads to formation of reactive oxygen species (ROS) [Venous wall does not contain es (ROS) . An impoes (ROS) . In thises (ROS) . AuthorsAccording to the currently predominant concept, PE develops when a thrombus or its part gets dislodged from the site of initial formation and travels all the way to the lungs where it occludes branches of the pulmonary artery. However, clinical evidence suggests that in many cases, clots in the lungs are observed in the absence of primary thrombosis elsewhere. Porembskaya et al. discuss an alternative scenario, in which systemic prothrombotic and proinflammatory milieu could mediate the development of thrombi in lungs in situ independently of DVT . AccordiThe coverage of VTE-related topics would be incomplete without its clinical aspects. Patel et al. present a comprehensive analysis of existing approaches for diagnostics and prediction of VTE . The artIt is known that pulmonary hypertension (PH) is frequently observed and serious complications of PE . A studyIn conclusion, this Special Issue presents new data and state-of-the-art overview of major aspects of venous thrombosis, such as its development, resolution, diagnosis, and potential biomarkers. This information may be useful to both basic scientists and clinicians dealing with this debilitating and life-threatening disease."} +{"text": "Linguistic phenotypes of individuals with Fragile X (FXS) and Williams (WS) syndromes exhibit various degrees of pragmatic impairment, involving difficulties in social communication and in adapting to conversational principles. The goal of the present study was to explore syndrome-specific pragmatic profiles of adults with FXS and WS based on the assessment of the observance of Gricean maxims of conversation. The participants were 12 Spanish-speaking adults (6 FXS/6 WS), without a diagnosis of ASD, whose extensive naturalistic conversations were transcribed and coded with the CHILDES/TALKBANK tools and the PREP-CORP pragmatic protocol. Violations of the maxims of conversation were analyzed, and indexes of cooperation and conversational response were obtained. Both groups showed reduced verbal production and repetitive dysfluencies; prominent features in the FXS profile were higher proportion of non-contingent language, perseverations of topic and form, and impulsive conversational responses; in the WS profile, salient characteristics were higher proportion of tangential utterances, reformulations, and conversational responses reflecting overly literal interpretation. Pragmatic profiles of violation of conversational maxims reflect specific communication skills impaired in adults with FXS and WS and raise the need for assessment and intervention methods that specifically address their social communication abilities. Fragile X syndrome (FXS) and Williams syndrome (WS) are neurodevelopmental genetic disorders characterized by specific phenotypical profiles of relative strengths and weaknesses in the neurocognitive domain, including intellectual disability and a range of behavioral problems ,2,3,4,5.FXS is the most common identified cause of inherited intellectual disability. It is caused by the mutation of the Fragile X Mental Retardation gene (FMR1) at the chromosome Xq27.3 and the consequent lack of the Fragile X Mental Retardation Protein (FMRP), which is predominantly expressed in neurons [WS is a rare neurodevelopmental disorder caused by the heterozygous deletion of 25\u201327 genes at chromosome 7q11.23, which has a complex genomic architecture, and its multisystemic phenotype is characterized by mild to moderate intellectual disability, cardiovascular disease, and distinctive facies .As expected for an X-linked disorder, males with FXS tend to exhibit more cognitive and behavioral problems relative to females with FXS, and most of the research on FXS has targeted males . ConversThe phenotypical outcomes have implications for language profiles in both syndromes, which present within-syndrome and cross-syndrome differences. Within-syndrome analyses typically display uneven profiles of relative strengths and weaknesses. In parallel, cross-syndrome analyses reveal profiles with shared and syndrome specific features ,9,10,11.Despite marked differences in social orientation, FXS and WS share asynchronous profiles of pragmatic weakness that arise in social communication contexts ,10,11. HPragmatic skills have been investigated independently in both syndromes or in contrast with other neurodevelopmental disorders, such as Down syndrome, in search for specific profiles , but to Pragmatic impairment was primarily considered a symptom of autism in early studies, although it was soon differentiated from autism and included, within the Language Development Disorders, as a Semantic-Pragmatic Disorder (SPD) when it occurred \u201cwithout autism\u201d . SPD wasFinally, it was included in the latest version of DSM-5 as the diagnostic category of \u201cSocial (Pragmatic) Communication Disorder (SPCD)\u201d . SPCD isIndividuals with FXS and WS exhibit pragmatic difficulties in social interaction and communication, including problems in maintaining a conversation topic, perseveration, repetitive language, impulsivity, and inappropriate responses . ResearcNarrative skills are a crucial aspect of social communication and provide a means for investigating aspects of the microstructure and macrostructure of discourse as it is produced in natural contexts. Those aspects of narratives have been addressed in several studies of individuals with WS or FXS alone or compared with other populations with neurodevelopmental disorders, such as Down syndrome, revealing specific weaknesses in macrostructure aspects ,34,35,36Even more scarce are the studies on conversational discourse both in FXS and in WS. In one of the first conversational analyses of males with FXS, Sudhalter et al. reportedIn addition to perseverative speech, individuals with FXS exhibit tangential language, defined as personal and highly idiosyncratic associations of words, phrases, or topics that are not pertinent to the thread of conversation . DysflueIn contrast with FXS, social cognition of adolescents with WS was described initially as a strength, as they showed awareness of listener needs, engagement to the listener, and affective expression in narratives . Their cSubsequent analyses of conversations of individuals with WS indicated that more than 25% of the utterances were inappropriate, which in half of the cases were due to problems of expressive syntax and semantics and insufficient quantity of information provided . Social Pragmatic difficulties in social interaction and communication are often described as autistic symptoms in individuals with intellectual disabilities of genetic origin ,50. AutiAutistic symptoms in FXS might then differ from those of non-syndromic ASD . Social Individuals with WS were initially characterized by a profile of hypersociability and were thus considered to represent the polar opposite of autism in the social and communicative domain . Only inASD comorbid diagnosis in neurodevelopmental disorders may have clinical utility to characterize phenotypic variability, although it is partially based on pragmatic impairments that are not clearly differentiated from those also observed in FXS without autism. If RRB-like features are not present, a more accurate characterization of pragmatic impairment in many individuals with intellectual disability of genetic origin might be provided by DSM-5 diagnosis of Social (Pragmatic) Communication Disorder (SPCD) .The assessment of the pragmatic profile in individuals with intellectual disability is frequently oriented to comorbid diagnosis of ASD, especially in the case of FXS. Therefore, it is based in many cases on instruments designed for autism screening, such as the ADOS-2, ADI-R, Autism Screening Instrument for Education Planning (ASIEP-3), Social Communication Questionnaire (SCQ), and the Social Responsiveness Scale (SRS-2) ,73,74,75Oral language sample analysis is considered the most valid procedure for pragmatic evaluation , such asTaking into account the scarcity of studies on pragmatic impairment and of instruments for its assessment in neurodevelopmental genetic syndromes, the present study had two main objectives: (1) to explore the pragmatic profiles of adults with FXS and WS based on analyses of conversations; (2) to determine the feasibility of the PREP-CORP protocol for assessing pragmatic features in speech corpora.-Maxim of quality (MQL): truthfulness and adjustment to world reality.-Maxim of relation (MRL): non-related, tangential, and perseverations of topic.-Maxim of quantity (MQT): redundant, vague, excessive, and reduced utterances.-Maxim of manner (MMN): repetitions, reformulations, perseverations of form, and alterations of the syntactic order.-AVI of cooperation: aggregate index of violations of all the maxims.-AVI of conversational response: incomprehension, literal interpretation, impulsivity, and echolalia.The PREP-CORP protocol includes a section that allows the coding and quantification of the observance of Grice\u2019s cooperation maxims in conversational utterances. Consequently, the specific objectives of the study were focused on calculating aggregate violation indexes (AVIs) and conducting between-group and within-group comparisons of the following maxims and types of violations:Analyses were expected to yield within-syndrome differences in the types of violations of conversational maxims; and also, cross-syndrome comparisons were expected to show profiles with overlapping and syndrome-specific conversational features.The conversational speech samples were elicited from two groups of Spanish-speaking participants: 6 adult males with FXS and 6 adults with WS . The total size of the speech samples collected was 71,859 words . The participants belong to a larger sample from the SYNDROLING Project . InclusiThe transcripts were coded using the PREP-CORP Pragmatic Evaluation Protocol , adapted(a)Maxim of Quality (MQL)*INV: and what are you working on here nowadays?*PAR: on nothing.%xepr:$i5:MQL:IMP(b)Maxim of Relation (MRL)*INV: (that cap) do you know which team it belongs to?*PAR: of basketball.%xepr:$i5:MRL:TNG:ICOM:LIT(c)Maxim of Quantity (MQT)*INV: why she was called so?*PAR: she was called so.%xepr:$i5:MQT:RUT:ECH(d)Maxim of Manner (MMN)*INV: what happened to the wolf and the stones?*PAR: and then what else? (.) and then (.) and then something else (.) and then something else (.) and then something else yet (.) and then something else yet about stones.%xepr:$i5:MMN:REP:PER_FThe following are examples of PREP-CORP coding for each of the maxims:Speech samples were collected in spontaneous dyadic conversations with an experienced researcher using audiovisual recordings .A certain degree of standardization was introduced by the researcher prompting common topics to all participants, in line with the procedures developed by Abbeduto et al. . The topt-test for independent and related samples. In addition to significance tests, estimates of the magnitude of the observed effects were calculated according to criteria and procedures provided by Ellis [r family (based on correlations), and d family (based on mean differences). Although d is recommended to generalize the impact, r is considered a more flexible and ecologically valid statistic when the sample is small. Therefore, a multiple perspective using both r and d was adopted [In order to control for the differences in grammatical complexity and lexical diversity, mean length of utterances in words (MLUw) and number of different words (NDW) were calculated for both groups. The frequency of the different types of violation of the maxims was also calculated using the CLAN software from the CHILDES project. In order to control for the differences in the size of the transcripts, violation indexes (VI) were calculated: frequency of each type of violation per thousand words. The sum of the VIs provided aggregate violation indexes (AVIs) of each maxim. In turn, the four AVIs were added to obtain an AVI of cooperation (AVIofCOOP), as a global pragmatic measure. An AVI of conversational response (AVIofCONRES) was also calculated from the optional tags. The between-group and within-group differences in the VIs and AVIs were analyzed using the Student\u2019s by Ellis . There a adopted .t-tests, were not statistically significant: MLUw ; NDW .Differences between the two groups on the previous control variables of grammatical complexity (MLUw) and lexical diversity (NDW), assessed with t-test comparisons. The FXS group presented a significantly higher proportion of violations than the WS group in the maxim of relation (MRL) and, specifically, in the topic perseverative utterances (PER_T). Concerning the types of violation of the maxim of manner (MMN), the FXS group presented a significantly higher proportion of violations in perseverations of form (PER_F), while the WS group presented a significantly higher proportion of violations in reformulations (REF). No significant between-group differences were observed in the aggregate measure of violation of the cooperation (AVIofCOOP).t = \u22123.229; p = 0.023; d = \u22121.986; r = \u22120.704) and NRL < PER_T ; in the WS group, NRL < TNG and NRL < PER_T .In the types of violations of the MRL , within-group comparisons yielded the following statistically significant differences: in the FXS group, NRL < TNG , VUT > EVP , and RVP > EVP and in the WS group, RUT < VUT and VUT > EVP .In the types of violations of the MQT , within-group comparisons yielded the following statistically significant differences: in the FXS group, RUT > EVP and REP > ORD and in the WS group, REP > ORD , REP > PER_F , REF > ORD , REF > PER_F , and ORD > PER_F .In the types of violations of the MMN , within-group comparisons yielded the following statistically significant differences: in the FXS group, REP > REF ; MQL < MQT ; MQL < MMN . In the WS group, within-group differences were MQL < MQT , MQL < MMN , MRL < MQT , and MRL < MMN .t = \u22122.352; p = 0.041), IMP , and ECH . Within-group differences were found only in the FXS group between ICOM > LIT and IMP > LIT .t = \u22123.827; p = 0.008; d = 2.44; r = 0.77).The sum of the VIs resulted in a global measure of conversational response (AVIofCONRES) for each syndrome: FXS group and SW group . These differences were statistically significant as a significant marker of the speech disorder of individuals with WS, which has been explained considering the cognitive and linguistic demands of the narrative and conversational tasks, in terms of language processing and planning . ReducedBetween-syndrome comparisons of the global index of violation of conversational cooperation in the FXS and the WS groups yielded no statistical differences. However, the present study found some similarities and a number of important differences in their profiles of pragmatic impairment. In both groups, violations of the maxims of quantity and manner were particularly high, while violations of the maxim of quality were less frequent. These findings may suggest an asynchrony between the pragmatic profiles and the underpinning lexical and grammatical skills. The inadequate use of language in conversation, with regard to the informative needs of the interlocutor, might not be consistent with the relative strengths observed in the lexical and grammatical levels, especially in WS ,9,10,11.The most striking difference between the profiles was a significantly higher index of violations of the maxim of relation in the adults with FXS, which indicates that their utterances tended to be more inappropriate or non-contingent. More specifically, regarding the contextual relevance, participants with FXS produced more tangential utterances and, above all, more topic perseverative utterances. These findings are consistent with the results of Roberts et al. indicatiDespite the fact that violation of the maxim of manner reached similar levels in both groups, prominent differences were also observed concerning the types of violation. On the one hand, perseveration of form was significantly higher in the FXS group, which confirms a great tendency to topic and phrase perseveration as the most salient feature of conversational discourse in people with FXS, as it had been observed in previous studies ,41,43. IThe analysis of the conversational response also revealed differences between the FXS and the WS groups, and it was significantly more impaired in the FXS group, also showing a more differentiated within-syndrome profile. In both syndromes, impulsivity and incomprehension were the more frequent characteristics of inadequate responses, accounting for more than 70% of the index, while participants also exhibited a tendency to an overly literal interpretation of utterances. Such pragmatic difficulties in processing syntax and semantics in context have been commonly observed in atypical populations, including FXS, WS, and ASD, and have been linked to theory of mind and metapragmatic deficits, which may reflect a failure to integrate a situation model including the speaker\u2019s intent and the rest of the communicative context ,98,99. QThe participants with FXS showed a much higher index of impulsivity, which is associated with ADHD and considered part of the core behavioral phenotype of the syndrome ,103. ResResponses indicating incomprehension of the conversation topic were also significantly more frequent in the participants with FXS, which could suggest an area of weakness, as it was observed in early communication by Roberts et al. using a Echolalic responses were significantly higher in the FXS group, albeit far less frequent than self-repetitions, which is consistent with previous studies indicating a profile of low proportion of echolalia in individuals with FXS vs. high proportion in ASD ,109. TheThe results of the present study show that individuals with FXS and WS without a diagnosis of ASD may exhibit different degrees and profiles of pragmatic impairment ,86, and It is important to acknowledge several limitations of the present study. The sample size was small and did not control for gender differences, for which reason the objectives were defined as exploratory. The consequent lack of statistical power and of adjustment for multiple comparisons may have influenced the assessment of differences. However, the conversational sample sizes were adequate and could have partially compensated for this limitation, as can be noted in the effect sizes. Different settings in which the speech samples were taken and the very different age ranges may have affected the results. The focus on group means\u2019 differences and similarities rather than individual differences is also a source of limitations. Stojanovik et al. found stAdult participants with FXS and WS in the present study showed violations of all the maxims of conversation to varying degrees, which may have an impact on their pragmatic skills. The profiles of cooperation resulting from the assessment of such pragmatic impairment using the PREP-CORP shared some characteristics, including reduced verbal production (maxim of quantity), repetitive dysfluencies (maxim of manner), and similar degree of violation of the maxim of quality. Syndrome-specific features were also observed: in the FXS profile, higher proportion of non-contingent language (maxim of relation) and perseveration of topic and form (maxims of relation and manner); in the WS profile, higher proportion of reformulation (maxim of manner). Conversational response showed increased levels of impulsivity, incomprehension, and echolalia in FXS. Thus, both profiles presented different degrees and forms of pragmatic impairment in the absence of a diagnosis of comorbid ASD, which raises the need for assessment and intervention methods that specifically address the social communication skills of adults with FXS and WS."} +{"text": "The Research Centers in Minority Institutions, (RCMI) Program was established by Congress to address the health research and training needs of minority populations, by preparing future generations of scientists at these institutions, with a track record of producing minority scholars in medicine, science, and technology. The RCMI Consortium consists of the RCMI Specialized Centers and a Coordinating Center (CC). The RCMI-CC leverages the scientific expertise, technologies, and innovations of RCMI Centers to accelerate the delivery of solutions to address health disparities in communities that are most impacted. There is increasing recognition that the gap in representation of racial/ethnic groups and women is perpetuated by institutional cultures lacking inclusion and equity. The objective of this work is to provide a framework for inclusive excellence by developing a systematic evaluation process with common data elements that can track the inter-linked goals of workforce diversity and health equity. At its core, the RCMI Program embodies the trinity of diversity, equity, and inclusion. We propose a realist evaluation framework and a logic model that integrates the institutional context to develop common data metrics for inclusive excellence. The RCMI-CC will collaborate with NIH-funded institutions and research consortia to disseminate and scale this model. The National Academies report, titled \u201cRising Above the Gathering Storm: Energizing and Employing America for a Brighter Economic Future\u201d, noted that, in order for the United States (U.S.) to maintain global leadership and competitiveness in science and technology, it must: 1) invest in research; 2) encourage innovation; and 3) grow a strong, talented, and innovative science and technology workforce [ invest i encourag grow a sThis paper provides evidence of the impact of the National Institutes of Health (NIH) investments in the Research Centers in Minority Institutions (RCMI) Program, and, the premise that the RCMI Coordinating Center (RCMI-CC) is well positioned to evaluate, disseminate and scale NIH\u2019s Diversity, Equity and Inclusion (DEI) initiatives.The NIH has long recognized that achieving diversity in the biomedical and behavioral research workforce is critical to ensuring that the best and brightest minds have the opportunity to contribute to the achievement of our national research goals. The RCMI Program was established in 1985 in response to committee report language (House Report 98-911) attached to H.R. 6028, the Departments of Labor, Health and Human Services, and Education and Related Agencies Appropriation Act, 1985, to \u201cestablish research centers in those predominantly minority institutions which offer doctoral degrees in the health professions or the sciences related to health\u201d ,11. SubsThe Department of Health and Human Services (DHHS) action plan to reduce racial and ethnic health disparities and the Despite long-standing efforts by the NIH and other entities across the biomedical and behavioral research landscape to increase the number of scientists from underrepresented groups ,16, GintThe COVID-19 pandemic added to the urgency, by uncovering glaring health inequities and the devastation of structural racism on the health of African Americans, Latinx, Native Americans, Native Hawaiians, and Pacific Islanders .At its core, the RCMI Consortium embodies the trinity of diversity, equity, and inclusion (DEI). The central role of the RCMI Consortium in addressing the NIH-linked objectives of workforce diversity and health equity was highlighted in three keynote presentations delivered at the RCMI Translational Science 2017 Conference in Washington, DC. During the opening plenary keynote, NIH Director Dr. Francis S. Collins, recognized the RCMI community as the brain trust to help develop novel solutions on health disparities . During An analysis of 18 RCMI Centers with active awards between 2002 and 2015 documented RCMI impact, as published in our seminal paper, titled: The Research Centers in Minority Institutions (RCMI) Translational Research Network: Building and Sustaining Capacity for Multi-Site Basic Biomedical, Clinical and Behavioral Research . This puSimilarly, RCMI Clinical Research Centers (CRCs) at Charles R. Drew University, Howard University, Meharry Medical College, Morehouse School of Medicine, University of Hawaii at Manoa, and University of Puerto Rico Medical Sciences Campus collectively enrolled over 16,000 diverse research participants between 2008 and 2016. There was broad representation across health disparity populations, including three quarters women; almost half were Black or African Americans; one third were Hispanics. Native Hawaiians, Whites, Asians, and Native American/Alaska Native were also represented in these clinical research studies. These clinical research centers also supported the training and career development of over 600 new clinical and translational research scholars over the same time period ,24,25. TThis manuscript will describe how the RCMI Consortium will build on its track record by developing and implementing consortium wide data collection processes and evaluation framework that will serve as a best practice for NIH DEI initiatives.The overarching purpose of this work was to understand how a context-based evaluation framework can serve as a blueprint for establishing data standards and common metrics for inclusive excellence (IE). We explored how the centralized data model of the RCMI Consortium can support the evaluation of the RCMI U54 Centers, and ultimately to disseminate and scale the RCMI DEI model.We hypothesized that the RCMI Consortium of institutions and the communities they serve provide a context-based and health equity-centered lens for a realist evaluation (RE) framework of IE.Rationale: Despite the urgent need for diversity in NIH-funded institutions, data confirm that institutional cultures lacking the necessary elements of inclusion and equity consistently send the message that certain groups do not belong in science ,27,28,29The theoretical framework of the RCMI Consortium is the Community of Practice and Stakeholder Engagement model ,33, whicThe RCMI-CC goals include evaluating the RCMI U54 Centers and the RCMI Consortium. The RCMI-CC integrates the Community of Practice and Stakeholder engagement in its needs assessment as described in the methods section. Given the diversity of research resources across the RCMI Consortium institutions, we propose the realist evaluation (RE) framework ,35,36, wThe Community of Practice Stakeholder-Engagement Framework ,46 is a Current NIH diversity programs lack the evidence for a standardized DEI evaluation framework . This prWith funding support, the RCMI-CC will collaborate with NIH-funded research networks, such as the Clinical and Translational Science Award (CTSA) and Institutional Development Award (IDeA) consortia, to disseminate and scale the adoption of the RCMI DEI model across various institutional contexts, from research-intensive to resource-limited settings ,38,39,40We have implemented a centralized RCMI database for baseline and longitudinal RCMI investigators data collection. We are also integrating the open-source central data repository, Dataverse , to sharThe needs assessment was conducted between 18 September and 11 December 2019, and designed to define the priorities, and identify resource gaps, for each RCMI U54 Center. Each U54 Center identified areas of expertise, and opportunities to strengthen its Center\u2019s capacity for inter-institutional research collaboration, by prioritizing access to the following resources: research studio/investigator development; biostatistics expertise; bioinformatics expertise; community engagement expertise; human subjects recruitment expertise; letters of support; finding collaborators ; technology transfer; institutional review board; samples/biorepository/laboratory methods; industry clinical trials; NIH multi-site studies; collaborative pilot project funding; RCMI Program National Conference; minority health and health disparities research training; national research mentoring network resource.The organization of the RCMI Consortium, its stakeholders, and governance are shown in For example, the Administrative Core Consortium includes the RCMI-CC Contact PI Steering Committee Chair and all the U54 Centers principal investigators/program directors. The Evaluation Consortium resides within the Administrative Core of each RCMI U54 Center and the RCMI-CC. The Community Engagement Core Consortium, Investigator Development Core Consortium, and Research Infrastructure Core Consortium are similarly configured to include the directors from the respective cores and the RCMI-CC MPIs.The objective of the stakeholder engagement was to: (1) develop a theory-based evaluation protocol, agree on common metrics, and standardize data collection process; (2) engage RCMI Centers directors in a continuous process improvement and sharing of best practices on investigator development, community engagement, resource sharing, and collaborations, relevant to their respective U54 Center goals and scientific activities; (3) agree on a process to monitor and share outcomes annually. We conducted two full days of Consortium-wide research retreat and strategy sessions followed by breakout sessions. The strategy and breakout sessions were followed by full day workshops for the respective Consortium Core leaders. The workshops were conducted during the RCMI Annual Scientific Conference, with full participation of all 21 active U54 Centers. Each Core Consortium provided direct input to the RE logic model being developed by the Tracking and Evaluation Consortium.We used a modified Delphi method , where tGiven that evaluation, common metrics, and data standardization are goals of this work, we referenced evaluation programs, as well as lessons learned from the CTSA program ,51,52,53To maximize the potential for improved inter-institutional engagement and collaboration, the RCMI-CC established a centralized database to support research collaboration and data collection across the RCMI Consortium. The searchable database can be used for finding investigators, and groups with specific areas of expertise, as well as search publications ,38,39. TCapitalizing on a centralized research-centric system to track productivity is essential to streamline the process for tracking research productivity and inter-institutional collaborations, especially when working with large research networks such as the RCMI Consortium. Using the centralized database as a systematic approach to track productivity at various levels yields consistent, objective, and standardized results across all the RCMI U54 Centers. Two of the most used key performance indicators (KPI) to assess scientific productivity are the number of publications and the number of awarded grants, both of which are routinely (quarterly) captured by the RCMI-CC centralized database. By harnessing the power and capabilities of the underlying relational database management system (RDBMS) of the centralized database, the RCMI-CC will be able to produce a quantitative representation of research activities (publications and grants) over time, at the individual (researcher) level as well as at the institution and consortium levels. In addition to the number of corresponding publications/awards, the centralized database captures other data elements such as: (1) How relevant the concepts of publications to the overall topic? (2) How long ago the publications were written? (3) Was the person the first or senior author, and how many other people have written about the same topic? The data can also identify shifts in research focus over time or reveal gaps in research productivity. The centralized database provides visualizations and timelines that show the dates of publications, top concepts, and concept clouds to emphasize keywords that make a person\u2019s research unique, illustrating changes in the primary topics over time. Other visualizations display cluster and radial graphs of authors, co-authors, and co-authors of co-authors. The graphs illustrate the proportional number of a person\u2019s publications and a proportional number of publications that they share with co-authors.In addition to the centralized database, we are also implementing an open-source central data repository, Dataverse , to sharThe 21 RCMI grantee institutions are located across 12 States, the District of Columbia, and Puerto Rico . Each RCThe results of the needs assessment showed that all (100%) RCMI U54 Centers prioritized community engagement expertise. Other prioritized resources were: 94% letters of support; 89% pilot project funds; 83% access to biostatistics expertise; bioinformatics expertise and finding collaborators for multi-PI research funding opportunities and publications; 78% investigator development research studios, NRMN resources, RCMI Annual Conference, and health disparities training; 72% technology transfer and innovation; 67% human subjects resource/institutional review board. These results bolster the DEI focus of the RCMI Evaluation framework and will be prioritized for common data elements in the logic model. The priorities identified in the needs assessment are included as data elements in the research resources and knowledge resources, which are inputs for the RE logic model. The needs assessment also show that RCMI Consortium members are interested in collaborations with RCMI and non-RCMI investigators. The dissemination and implementation of the RCMI DEI evaluation framework will benefit from this robust collaboration capacity. The fostering of collaboration among young and early investigators, seasoned investigation internal and external to each U54 RCMI, and bi-directional relationship between academic and community partners underscore the RCMI Program\u2019s commitment to inclusion and community focused priorities that impact health outcomes.The centralized database includes existing active, and newly registered investigators. The newly registered investigators were on-boarded between January through 22 April 2021. This sample is from scientific abstracts accepted for presentation at the 2021 RCMI Annual Conference. Our group published the paper titled \u201cUsing a Virtual Community to Support Early-Stage Investigators Pursuing Grant Funding\u201d . This woThe RE logic model\u2019s inputs, activities, outputs, outcomes, community and health equity impact will track the four pillars that drive sustainable interventions see 34,35,3,335,36. Influence of the external environment including at the agency, state, region, or national policies may be standardized where feasible for purposes of comparative analysis.In this article, we present the design and RE logic model for a context-based evaluation framework of IE, by developing a systematic process with common data elements that align with the inter-linked goals of workforce diversity and health equity. We demonstrate that the mission, goals, and track record of the RCMI Program positions it to develop and standardize common data elements relevant to IE. The RCMI-CC centralized database and Dataverse open-source data-sharing model support collaboration capacity, and support users to disseminate and scale the model. The RE places our study in the larger context of NIH DEI initiatives. The logic model, common data elements, and data standardization will serve as a blueprint for adapting the model to diverse NIH-funded institutions, from research intensive to resource limited settings. The NRMN use case demonstrates the capacity of the RCMI Consortium to support national initiatives on DEI. The RCMI-CC governance and evaluation objectives support future collaboration that can disseminate and scale the RE model. By developing baseline common data elements that can apply across institutions, as well as investing in the Dataverse platform for secure and privacy protected data sharing, the RCMI-CC is establishing a RE grounded logic model for transparent and comparative evaluation of IE at RCMI Centers as well as across NIH funded institutions, regardless of the institution size, resources, public, or privately funded. The RE logic model and common data elements serve to establish a transparent and accountable process to collect and refine baseline data that will support DEI and IE processes and outcomes.This work aligns with the commitment and statement of NIH Director Collins, who declared, on 1 March 2021, that NIH stands against structural racism in biomedical research: \u201cto those individuals in the biomedical research enterprise who have endured disadvantages due to structural racism, I am truly sorry. NIH is committed to instituting new ways to support diversity, equity and inclusion, and identifying and dismantling any policies and practices at our own agency that may harm our workforce and science\u201d. Adding action to words, he announced a new NIH initiative called UNITE, unveiled a website on Ending Structural Racism , and issThe evaluation framework and common metrics represent the first step in the RCMI DEI blueprint for IE. A next step is to complete the implementation of the model in coordination with RCMI U54 Centers. The next step will include establishing benchmarks for publication and research excellence outcomes, that incorporates the RE logic model resource inputs. Our goal is to standardize outputs, based on the baseline data that will populate the RE logic model (anticipated completion in 2022). We will publish this work, to support dissemination and scaling in collaboration with NIH research consortia, including CTSA, NRMN/DPC, and IDeA programs. In addition, we are exploring innovative data collection and analysis methods by leveraging the EQ collaboratory , to engaThis work confirms our hypothesis that the RCMI Consortium context-based and health equity-centered evaluation of IE can serve as a blueprint for NIH DEI initiatives. As the NIH embarks on efforts to address structural and systemic racism, DEI initiatives should prioritize context-based evaluation and common data elements that transparently track and publicize individual, institution, as well as system level outcomes. The RCMI Consortium welcomes a bidirectional outreach and collaboration with NIH-funded institutions and research consortia, as we seek to collectively engage and support the best and the brightest underrepresented investigators in biomedical research."} +{"text": "The number of older adults who live in long-term care (LTC) is expected to increase worldwide. The COVID-19 pandemic has caused serious consequences in Canadian LTC homes, while homes in China and Japan reported minimal infection and death rates in residents. The differences in LTC policies may be one of the contributors. The purpose of this literature review was to identify elements of the LTC policies that might have impacted COVID-19 outcomes in LTC homes in Canada, China, and Japan. A scoping review was conducted following the framework proposed by Arksey and O\u2019Malley. Scholarly articles and grey literature published between January 2015 and June 2020 were identified in six databases, four in English , one in Chinese (CNKI), and one in Japanese (CiNii), using MeSH terms for LTC and health policy. Grey literature was identified using Google. Data were extracted, summarized and common themes identified through content analysis. A total of 52 articles and 26 grey sources were included in the review based on determined inclusion criteria. They were research articles, reviews, government or association reports, policy briefs, policy documents, and guides. Four common themes of challenges emerged: caregiver workforce, service provision, funding, and physical environments. Three sub-themes were identified for caregiver workforce and service provision. Differences in COVID-19 consequences in LTC homes in the three countries seem to be related mainly to the challenges with the caregiver workforce and the lack of funding. The result suggests Improvements of LTC policies are required, especially in Canada."} +{"text": "In addition to cancer-related death, malignant progression also leads to a series of symptoms and side-effects, which would detrimentally affect cancer patients' the quality of life, adversely influence their adherence to treatments, and, therefore, negatively affect their long-term survival. Acupuncture and electroacupuncture (EA), as two classic treatment methods in traditional Chinese medicine, have been widely employed to cure various diseases. Recently, the clinical application of acupuncture and EA in cancer patients has received great attention. In this review, we summarized the clinical application of acupuncture and EA in alleviating the cancer symptoms, reducing the cancer treatment-related side-effects, and relieving the cancer pain. The symptoms and side-effects discussed in this review include fatigue, insomnia, chemotherapy-associated dyspepsia syndrome (CADS), pain, xerostomia, and anxiety and depression. The underlying mechanisms of the therapeutic effects of acupuncture and EA might be related to the regulation of the mitochondrial function, coordination of the activity of the nervous system, adjustment of the production of neurotransmitters, and alleviation of the immune responses. In conclusion, acupuncture and EA have been proved to be beneficial for cancer patients. More research, however, is required to clarify the potential mechanisms behind acupuncture and EA for widespread adoption in clinical application. Carcinoma is the leading cause of global morbidity and mortality, so cancer prevention and treatment have become the key research topic in the medical field. In addition to death, the progression of cancer is also accompanied by a series of symptoms and side-effects that is caused by not only cancer itself but also cancer-related therapies, such as surgery, chemotherapy, radiotherapy, etc. These symptoms and side-effects will severely impact the life quality and treatment adherence of cancer patients, and, therefore, adversely affect their long-term survival. Recently, complementary and alternative medicine (CAM), including acupuncture, deep breathing exercises, massage therapy, meditation, naturopathy, and yoga, has been increasingly adopted by cancer patients for seeking relief from cancer-associated symptoms Acupuncture has been defined as the insertion of fine needles into specific acupuncture points (acupoints) in the human body. In Eastern Asia, acupuncture has been widely employed to treat various diseases for over 2,500 years. Notably, the benefits of acupuncture in treating various diseases have been gradually recognized by Western society. For example, the World Health Organization (WHO) and the National Institutes of Health (NIH) released a report on acupuncture in 2003, suggesting more than 100 types of diseases and conditions could be treated by acupuncture Electroacupuncture (EA) is developed around the mid-1900s and is a modified approach of acupuncture that applying weak electronic currents through the needles after conventional acupuncture procedure. Although it is still controversial, EA has been shown to achieve similar or even better effects compared to acupuncture. Moreover, the efficacy of acupuncture mainly depends on the manipulation technique of the acupuncturist, but EA can be practiced more reproducibly and is more suitable for both basic and clinical research. In this review, we introduced the effects of acupuncture and EA on cancer-related symptoms and side-effects, the possible mechanisms behind acupuncture, and the hindrance against the wide application of acupuncture and EA in cancer-related treatment.Cancer and cancer treatments are frequently associated with a lot of symptoms and side-effects including fatigue, insomnia, chemotherapy-associated dyspepsia syndrome (CADS), radiation-induced xerostomia (RIX), pain, vomit and nausea, cognitive impairment, distress, anxiety, depression, etc. Because some of those symptoms and side-effects are tightly related, we mainly discussed the therapeutic potential of acupuncture and EA in some of those symptoms and side-effects in this review.Cancer-related fatigue (CRF) has been recognized as one of the most common cancer-related side-effects The effective treatment options for CRF are limited, consisting of non-pharmacologic interventions like physical activity and psychosocial and mind-body interventions. However, a recent clinical trial, including 302 breast cancer outpatients, showed that acupuncture could significantly relieve CRF Insomnia, also called sleeplessness, is recognized as the most prevalent sleep problem worldwide. The reported prevalence of insomnia in cancer patients is up to 50%, which is three times higher than that in the general population Chemotherapy is routinely employed in combination with radiotherapy, surgery, hormone therapy, or immunotherapy for treating many types of cancers. Despite the effectiveness in reducing tumor burden, chemotherapy also unavoidably raises many irreparable side-effects, such as chemotherapy-associated dyspepsia syndrome (CADS). CADS is defined as a collection of gastrointestinal symptoms after receiving chemotherapy, including early satiety, anorexia, diarrhea, nausea, and vomiting Acupuncture has been commonly employed in China to treat gastrointestinal symptoms for thousands of years and the possible mechanisms behind might be through the altering acid secretion, GI motility, and visceral pain Pain is the most common symptom of cancer and is reported in 90% of cancer patients at various progression stages Acupuncture and EA have been widely employed to relieve non-malignant acute and chronic pain Salivary glands are significantly sensitive to radiation therapy and will be irreversibly damaged at doses higher than 50 Gy Anxiety and depression are common complications of cancer, influencing cancer patients' quality of life, their adherence to treatment, and their survival Although many efforts have been made to understand the effects of acupuncture and EA in the treatment of cancer-related symptoms and side-effects, the mechanisms by which acupuncture and EA achieve therapeutic benefits remain largely unknown. The main focus has been on investigating the mechanisms of the analgesic effects of acupuncture and EA. In the early 1970s, Han's group, for the first time, strongly suggested the involvement of central chemical mediators in the analgesic effect by acupuncture. They transferred the cerebrospinal fluid of acupunctured donor rabbits into recipient rabbits and achieved analgesic effects in recipients The studies on mechanisms of acupuncture and EA for treating other cancer-related symptoms and side-effects are limited. A previous study has shown that EA can improve chronic fatigue by reducing mitochondrial oxidative stress and increasing ATP synthesis Table 1). We also simply introduced the potential mechanisms involved in the therapeutic effects of acupuncture and EA (Table 2). Given that the actual mechanisms of acupuncture and EA remain largely unknown, more basic and clinical studies are needed to endorse the broad clinical application of acupuncture and EA in the treatment of cancer-related symptoms and side-effects.This review summarized the application of acupuncture and EA in cancer patients for improving cancer-related symptoms and side-effects, such as fatigue, insomnia, chemotherapy-associated dyspepsia syndrome (CADS), radiation-induced xerostomia (RIX), anxiety and depression, and pain ("} +{"text": "Cochrane Cameroon is the fourth geographical group of Cochrane in sub-Saharan Africa, following Cochrane South Africa (1997), Cochrane Nigeria (2006) and Cochrane Kenya (2021). All are part of the Cochrane Africa Network, formally established in 2017. Cochrane Cameroon is based in the Centre for Development of Best Practices in Health, at the Yaound\u00e9 Central Hospital in Cameroon, and is the base of the Francophone hub of Cochrane Africa [June 30Cochrane is a not-for-profit international network aiming to have evidence at the heart of health decision-making world-wide. Cochrane does not accept commercial or conflicted funding which is vital for generating authoritative and reliable information, unconstrained by commercial and financial interests. Cochrane Cameroon responds to the needs to expand evidence-based decision-making and Cochrane activities to French speaking Africa and to aIn collaboration with Cochrane Africa, Cochrane Cameroon will continue to support the production of high-quality systematic reviews, make relevant Cochrane evidence accessible (through translation of plain language summaries and evidence assessments), advocating for evidence (by raising awareness and stakeholder engagement) and contributing to the sustainability of the network (by supporting mentors and mentees). In recognition of the need to enhance health equity by involving stakeholders and end-users in priority setting , CochranConclusion: this letter is an open invitation to researchers, health care providers, journalists, policymakers, and consumers in the region to visit our website and engage meaningfully in the production and use of high-quality locally relevant and accessible health evidence."} +{"text": "The growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme.This Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0\u201319 years , age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme.The SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas.SALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments. Childhood cancer is of increasing public health concern, as approximately 35,000 new cases are diagnosed yearly in children and adolescents in Europe, and about 500,000 European Union citizens are childhood cancer survivors, with complex needs for medical and psycho-social care . AlthougThe experience of cancer during childhood and adverse somatic or mental health conditions may also have consequences for social and family life and for socioeconomic achievement later in life. Previous research has shown that childhood cancer survivors are at increased risk of several adverse socioeconomic and social outcomes, including scholastic difficulties, such as requiring special education or attending learning disability programmes, lower levels of attained education and lower income than their peers . There aThe current evidence is limited by methodological shortcomings. Most previous research is based on self-reported information from surveys and are thereby susceptible to non-participation, which might have affected the outcomes. Further, many studies included survivors of only one or a few specific childhood cancer types, did not involve repeated measurements of social and socioeconomic outcomes throughout the life-course or suffered from substantial loss to follow-up. Further limitations of previous studies include insufficient sample size of survivors and short follow-up. The mechanisms that lead to adverse social and socioeconomic conditions, especially in vulnerable subgroups of survivors, are still poorly understood , 26, andThe Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme was initiated to address these gaps and enrich understanding of the impairments and social and socioeconomic difficulties that survivors of childhood cancer may face during their life-course. This Nordic research programme is a collaboration among the Danish Cancer Society Research Center, the Finnish Cancer Registry and Karolinska Institutet in Sweden.In 2020, Denmark, Finland and Sweden had populations of 5.8, 5.5 and 10.3 million, respectively . The NorThe welfare systems of the three countries are largely comparable. Citizens are entitled to an education free of charge, from primary schooling, which is compulsory, to advanced tertiary educational levels . AdditioIn general, all citizens of the Nordic countries have equal access to government-subsidized primary health care services provided by general practitioners and specialised health care in hospitals or provided by specialist physicians. Out-of-pocket expenses and reimbursement schemes vary, however, in the three countries \u201338. The As childhood cancers are a heterogeneous group consisting of very different diseases, survival and developments in survival over time differ widely by cancer type . Since tCurrent therapy for some malignancies is highly intensive, and, while survival has gradually increased, the risk of treatment-related acute toxicity and late effects may also be increasing. The aim of many current protocols is to identify subgroups of patients for whom the intensity of therapy can be reduced to decrease toxicity.Collaborative clinical trials to standardise childhood leukaemia treatment protocols in all Nordic countries began in 1981 , 40, 43,The SALiCCS research programme is a Nordic register-based cohort study of social and socioeconomic consequences in long-term survivors of childhood cancer in Denmark, Finland and Sweden. SALiCCS is based on the Nordic research programme Adult Life after Childhood Cancer in Scandinavia (ALiCCS), which investigates late effects of cancer therapy in children to better understand the risk and mechanisms of treatment-induced somatic disease . Data frThe main objectives of the SALiCCS research programme are:to ascertain hospital contacts for mental disorders in childhood cancer survivors;to examine how survivors of childhood cancer transition from childhood to adulthood by determining the following social and socioeconomic conditions and attainments: scholastic achievements, attained educational level and educational delays, income, employment, occupational position and professional attainment, leaving the parental household to live independently, cohabitation with a partner, getting married and founding a family; andto assess the socioeconomic burden of childhood cancer and treatment on survivors by determining the uptake of social security benefits, such as unemployment benefits, social assistance, sickness allowance, disability pension and rehabilitation benefits.The SALiCCS research programme is based on a registry-based matched cohort design. Denmark, Finland and Sweden have civil registration systems with numerous national administrative registries \u201347 that The infrastructure of the population-based registers in the Nordic countries, with longstanding, high-quality, comprehensive health, socio-demographic and socioeconomic data, are an ideal, unique basis for large-scale epidemiological studies of childhood cancer survivorship. None of the Nordic countries, however, has a sufficiently large population to provide adequate statistical power for a detailed assessment of social and socioeconomic outcomes in childhood cancer survivors in a life-course perspective, particularly not for determining the underlying mechanisms of adverse social and socioeconomic outcomes and identifying particularly vulnerable groups of survivors. Combination of data from several Nordic countries is required for such purposes. As the Nordic countries have longstanding, largely standardised diagnostic and treatment procedures and similar welfare systems, it was considered reasonable to combine data on childhood cancer survivors across Nordic countries.The SALiCCS core population comprises all five-year survivors of a first childhood cancer diagnosed at ages 0\u201319 years in Denmark (1971\u20132008), Finland (1971\u20132009) and Sweden (1971\u20132011) .The cancer diagnoses were classified according to the International Classification of Childhood Cancer, in which tumours are classified into 12 major diagnostic groups and detailed subgroups according to the nomenclature of the International Classification of Diseases \u2013 Oncology \u201369.We established two independent comparison groups. We randomly sampled five population-based comparisons per survivor from the populations of Denmark, Finland and Sweden from the national population registries. Survivors and population comparisons were individually matched by year of birth, sex and country of residence for somatic and mental disorders and the respective discharge diagnoses. We obtained information on prescribed drugs from the nationwide prescribed drug registries, whereby prescription data from Finland was limited to contraceptive medications, antidepressants, pain killers, and psychiatric drugs.Apart from diagnostic data from the national cancer registries, clinical and treatment information was overall sparse. The Finnish Cancer Registry included limited and non-validated treatment information on surgery, radiotherapy and chemotherapy (with incomplete coverage). The treatment information is given on binary level for curative, palliative or unknown intention . For DenWe collected basic socio-demographic and socioeconomic information for the biological and adoptive parents of the childhood cancer survivors, the population comparisons, and the sibling comparisons. Furthermore, to account for the increasing number of reconstituted families in the Nordic countries, we also defined the \u201csocial parents\u201d for the Danish and Swedish SALiCCS populations, for whom we collected the same socioeconomic and socio-demographic information as for biological parents. In Denmark, social parents were defined as individuals living at the same address with the index person the year before the reference year, at least 16 years older and not a full or half sibling of the index person. In Sweden, social parents were defined as individuals registered by Statistics Sweden as a parent or guardian in the same household in which the index person was defined, the year before the reference date. Social parents could be identified from 1980 onwards in Denmark and from 1990 onwards in Sweden. Corresponding information was not collected for the Finnish SALiCCS population. The SALiCCS research programme has been approved by Statistics Denmark, the Regional Ethical Review Board in Stockholm, Sweden , Findata (Dnro THL/5543/14.06.00/2020) prolonging the former approvals by the National Institute for Health and Welfare and Social Insurance (KELA) and Statistics Finland (TK-53-394-17) in Finland. For the European Union General Data Protection Regulation (GDPR), the SALiCCS project is listed in a local archive (2018-DCRC-0044) at the Danish Cancer Society Research Center, which provides an accurate, updated overview of ongoing projects and of ongoing research projects involving personal data under the GDPR. The 2018-DCRC-0044 replaces the former notification from the Danish Data Protection Agency.The SALiCCS research programme is conducted in compliance with the requirements of the GDPR and other applicable laws in the respective countries, as well as the respective procedures at Statistics Denmark, the Danish Cancer Society Research Center, Karolinska Institutet and the Finnish Cancer Registry. All data have been stored, linked and pooled and are analysed at a secure remote platform at Statistics Denmark, with controlled remote access only for individually approved SALiCCS project members. Personal identification numbers were replaced by pseudonymised ID numbers, and the key code is kept only by the original register holders or at the respective statistical institutes. All the results of the statistical analyses will only be presented as aggregated data.The core SALiCCS population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as the second comparison group. The distribution of diagnostic characteristics differed only slightly in Denmark, Finland and Sweden Table\u00a02.The SALiCCS core population is defined by individuals who survived the five-year survival point. To describe this population, the survival probabilities of all children diagnosed with cancer in Denmark, Finland and Sweden, their population comparisons and siblings are shown in This SALiCCS core population will serve as the basis for individual studies of the objectives of the SALiCCS research programme, as outlined in section 1.3. Additional inclusion and exclusion criteria may be applied to the core population in individual SALiCCS studies, which may be restricted to specific time periods, depending on the respective research objectives and register coverage.The growing number of survivors of childhood cancers diagnosed at a young age, with many years of life ahead, indicates the increasing clinical and public health relevance of investigating the long-term social and socioeconomic consequences of the cancer diagnosis and the life-saving treatment. Some previous evidence points to higher risks of impaired social functioning and adverse socioeconomic outcomes in adult life. Nevertheless, additional research is urgently required to fully understand the long-term social consequences of a diagnosis of cancer in childhood, to identify vulnerable survivors at particular risk for adverse social and socioeconomic impairments in adulthood and ultimately to provide scientific knowledge for evidenced-based survivorship care that addresses not only somatic late effects but also psychosocial impairments.Data linkage among various population-based registries in Denmark, Finland and Sweden gave us the unique possibility of setting up the largest, most comprehensive population-based research initiative on the social and socioeconomic consequences of childhood cancer so far, comprising more than 21,000 five-year childhood cancer survivors and two independent comparison groups. The large number of survivors will enable detailed analyses, allowing for identification of vulnerable subgroups in terms of e.g. diagnostic or socio-demographic characteristics. Use of high-quality population-based register data with high coverage, virtually no loss to follow-up and no self-reporting or non-participation allows reliable estimation of the social and socioeconomic outcomes with minimal risk of bias in countries with similar welfare systems and generally equal access to education and other services. Particularly valuable strengths of the SALiCCS research programme include annual information on social and socioeconomic outcomes, facilitating the study of trajectories and enabling a comprehensive long-term follow-up, as well as the availability of detailed information on hospital contacts, allowing stratified analyses by somatic or mental late effects. A limitation of the SALiCCS research programme is the lack of comprehensive and three-countrywide information on cancer treatment and other relevant clinical characteristics such as subtype of disease and tumour stage or grade. Such information would have been of considerable value for assessing the underlying mechanisms leading to adverse social and socioeconomic conditions, and to identify survivors of childhood cancer that are particularly vulnerable to adverse outcomes. For instance, especially cranial radiation therapy has been associated with various somatic late effects, including long-term neurocognitive impairment, as well as with adverse educational attainments, higher risk of unemployment and low income . UnderstThe novel findings resulting from this research programme may serve as a basis for recommendations on interventions for vulnerable subgroups of survivors. Such recommendations may not be limited to the Nordic countries, with their extensive welfare systems, but may also be applicable to other countries, especially within Europe.jeanette@cancer.dk), the Principal Investigator of the SALiCCS research programme, for further questions about data access.The data that support the information of this article were accessed remotely on a secure platform at Statistics Denmark. Pseudonymised individual-level data were obtained from national registry holders after ethical approval (where applicable) and secrecy assessment. According to Danish, Finnish and Swedish laws and regulations, individual-level sensitive data can only be made available for researchers who fulfil legal requirements for access to personal sensitive data. Please contact Jeanette Falck Winther , Findata (Dnro THL/5543/14.06.00/2020) prolonging the former approvals by the National Institute for Health and Welfare and Social Insurance (KELA) and Statistics Finland (TK-53-394-17) in Finland. For the European Union General Data Protection Regulation (GDPR), the SALiCCS project is listed in a local archive (2018-DCRC-0044) at the Danish Cancer Society Research Center, which provides an accurate, updated overview of ongoing projects and of ongoing research projects involving personal data under the GDPR. The 2018-DCRC-0044 replaces the former notification from the Danish Data Protection Agency.FE and JW developed the concept and outline of the manuscript. All authors contributed to the acquisition and preparation of data. FE, LF, HM, NM, L-MM-H, MF, and JW developed the strategy for the descriptive analysis and presentation of the study population. FE, LF, HM, and JW drafted the manuscript. All authors provided critical feedback, critically reviewed the manuscript for important intellectual content, and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.This work was supported by NordForsk under grant 76111, the Danish Childhood Cancer Foundation under grant 2016-0293, Aarhus University under fellowship 43239402, the Swiss National Science Foundation under grant P2LUP3_175288 , the T\u00f8mrermester J\u00f8rgen Holm og Hustru Elisa F. Hansens Mindelegat under grant 20088 and the Swedish Childhood Cancer Foundation under grant PR2020-0130. The funding sources had no involvement in the content or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The invasive behavior of glioblastoma is considered highly relevant for recurrence. However, the invasion zone is difficult to visualize, typically lies outside the resected and irradiated area, and is protected by the blood brain barrier, posing a particular challenge for treatment. We present biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes in patient derived orthotopic xenografts (PDOX) and corresponding patients.1H-MR spectroscopy and imaging . Tissue obtained at surgery was transplanted orthotopically into immune-compromised mice. Longitudinal follow-up was performed by 1H-MRS/I (14.1T) on the injected and the contralateral side. The PDOX, the corresponding contralateral side, and the original human tumors underwent RNA-sequencing.Patients with suspected glioblastoma were enrolled (NCT02904525) and underwent 1H-MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel analyses of the patients\u2019 tumors. Associations between the metabolite profiles and the combined transcriptome of the xenografts and the host, reflected molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling.The temporal changes of the metabolite profiles characterized the kinetics of invasive growth of PDOX, and were patient specific. Comparison of in vivo monitoring of progression in the non-enhancing tumor infiltration zone and provides insights into the remodeling of the extracellular matrix that is essential for cell-cell communication and regulation of cellular processes. The changes of the structural and biochemical properties of the extracellular matrix are of importance for the biological behavior of the tumors and may be subjected to therapeutic targeting.Integrating metabolic profiles and gene expression of highly invasive PDOX allows"} +{"text": "Background: The social isolation of older people is a growing public health concern. The proportion of older people in society has increased in recent decades, and it is estimated that ~40% of the population will be aged 50 or above within the next few decades. This systematic review aims to summarize and renew knowledge of the effectiveness of existing interventions for alleviating social isolation of older adults.Methods: Relevant electronic databases, including Cochrane Library, CINAHL, SCOPUS, and Web of Science, were searched by a systematic evaluation method. Eligible randomized controlled trial (RCT) studies were published between 1978 and 2021 in English or Chinese. The primary and secondary outcomes were social isolation and loneliness. The quality of the included RCTs was scored by the Cochrane risk-of-bias tool to assess their quality. Two independent reviewers extracted data, using a standardized form. Narrative synthesis and vote-counting methods were used to summarize and interpret study data.Results: Twenty-four RCTs were finally included in this review. There was evidence of substantial heterogeneity in the interventions delivered. The overall quality of included studies indicated a low-to-medium risk of bias. Eighteen of 24 RCTs showed at least one dimension effect on reducing social isolation. The interventions with accurate targeting of clients in social and public places had more obvious effect. The interventions in which older people are active participants also appeared more likely to be effective. In addition, group intervention activities and individual intervention interviews were effective in improving structural social support; mixed intervention, and group intervention on training support significantly improved functional social support.Conclusions: This study suggests that group and mixed intervention targeting of older adults could be helpful for alleviating social isolation problems. The use of modern technology for remote services could also present good results. More well-conducted RCTs of the effectiveness of social interventions for alleviating social isolation are needed to improve the evidence base. Especially as the debating results of remote interventions, further research in this field should be conducted. Social isolation is a major threat to the health of older adults. There are many risk factors in social isolation in old age, including the lack of family members, rare or no daily communication with friends, depression, and a solitary lifestyle , CINAHL databases, SCOPUS, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform (WANGFANG). Another search retrieved social isolation and/or loneliness in the review and has been included in the study of the reference literature; retrieval from the University of Southern California Social Work Institute database, evidence-based medicine research center of Lanzhou University, and Population Research Institute of Southwestern University of Finance and Economics. Contacts were made with scholars within the network of the authors to obtain information about ongoing studies. Search words used were as follows: older/elder/senior/aged/geriatric, isolation/isolate/isolated, lone/loneliness/alone/solitude/solitary, social support/network/relations, psychosocial intervention, treatment/therapy, clinical trial, explanatory trial, pragmatic trial, and randomized controlled trial. Search terms used were as follows: (isolation/isolate/isolated) or or and (older/elder/senior/aged/geriatric) and or . The search terms in different databases were slightly different. Therefore, we also searched through the reference lists of systematic review articles on social isolation.According to the research topic and summary, two researchers (FT and CLY) made a preliminary identification of study criteria. The third researcher (FF) read the abstract of the indeterminate literature and determined the specific discussion about the disagreement. A pair of independent raters selected abstracts for full review based on inclusion/exclusion criteria. Two independent reviewers extracted data, using a standardized form. Due to the heterogeneity of different outcome indicators , meta-analysis is not suitable for use. According to the analysis method of the three previous evaluations older adults over 50 years of age with no mental illness or cognitive impairment; (ii) the purpose of the intervention was to alleviate social isolation or loneliness; (iii) the results of social isolation intervention were reported; (iv) there were randomized controlled trials but no drug trials; and (v) the paper was written in Chinese or English. Exclusion criteria for the study: (i) study samples aged younger than 50 years; (ii) not used a randomized controlled trial (RCT); (iii) drug intervention was used; and (iv) outcomes reporting only on loneliness but no social isolation.Because of the heterogeneity of the intervention types and results of the trial, quantitative analysis of data was not used in the review, so the method of narrative synthesis was applied to analyze the effect of interventions. In the quality evaluation of open randomized controlled trials, we chose not to use the Jadad standard Berger, as this About 746 items were found in the related research, with 452 duplicates removed, 268 of the studies excluded as they did not meet the selection criteria. Two studies were excluded because of high-bias risk. Twenty-four studies were eventually included .A total of 24 randomized controlled trial studies were included with a total of 4,078 subjects, each involving 26\u2013708 cases. Of all the studies, there were only two studies from mainland China : The Evidence Reorganization, Conversion, and Enlightenment Research of Evidence-based Social Work Intervention on Long-term Care of older adult.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Introduction: Melodic intonation therapy (MIT) is one of the most studied speech and language therapy (SLT) approaches for patients with non-fluent aphasia, although the methodological quality of the studies has been rated as low in previous reviews. The aim of this study is to update current evidence on the possible efficacy of MIT for the treatment of non-fluent post-stroke aphasia.Methods: A systematic review and meta-analysis. We selected randomized clinical trials (RCT) that included adult patients over 18 years of age with non-fluent post-stroke aphasia, whose intervention was MIT vs. no therapy or other therapy. We excluded non-RCT studies, mixed populations including patients with aphasia of non-stroke etiology, studies with no availability of post-stroke aphasia-specific data, and incomplete studies. Three sections of communicative ability were analyzed as outcomes: functional communication, expressive language (naming and repetition), and comprehension.Results: We identified a total of four eligible RCTs involving 94 patients. Despite the heterogeneity in the psychometric tests employed among the trials, a significant effect of MIT on functional communication was found . In addition, a positive effect of MIT on expressive language (repetition) was found . No significant effects on comprehension measurements were found, despite a lack of significant statistical heterogeneity.Conclusion: This systematic review and meta-analysis shows a significant effect of MIT on improving functional communication and on repetition tasks. Future larger RCT specifically addressing those outcomes should provide the definite evidence on the efficacy of MIT on post-stroke aphasia recovery.Systematic Review Registration:PROSPERO-URL https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020144604. Aphasia is a disorder that is the result of an injury to the brain areas that control the production and understanding of language as well as its components . Aphasia is common after stroke, with an estimated frequency of 30 and 34% for acute and rehabilitation settings, respectively . TherefoA Cochrane meta-analysis published in 2016 showed the effectiveness of SLT for post-stroke aphasia as compared to no therapy, in terms of better functional communication, reading, comprehension, writing, and expressive language . To dateMelodic intonation therapy is a widely used therapy in clinical practice, and therefore, it is necessary to understand whether there is evidence of its efficacy. MIT has been proposed mainly for patients with significant defects in language production, poor verbal agility, poor repetition of sentences, exaggerated prosodic pattern of sentences, and relatively preserved auditory comprehension \u20138. PatieThe mechanisms underlying the effects of MIT on aphasia recovery are not well-known, although it seems to stimulate brain plasticity by promoting the neuroplastic reorganization of language function, the activation of the mirror neuron systems, the utilization of shared features of music and language (such as pitch and rhythm) reflecting common or associated processing pathways, and improving the patient's motivation and mood . Indeed,A systematic review published 8 years ago reviewed the literature on the effect of musical elements in the treatment of patients with neurological language and speech disorders . The autOur aim is to update current evidence on the possible efficacy of MIT for the treatment of non-fluent post-stroke aphasia in adult patients on functional communication, expressive language, and comprehension.This systematic review and meta-analysis is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations for systematic reviews and the Cochrane guidelines for systematic reviews , 20. TheOur PICO question to guide the systematic review was formulated as follows: in adult patients over 18 years of age with non-fluent aphasia due to ischemic stroke, does the MIT, as compared to no therapy or other therapy, improve functional communication, expressive language (naming and repetition), and comprehension?http://clinicaltrials.gov/), and Clinical trials results . We also performed a manual search of reference lists in other prior systematic reviews on the same topic as well as in guidelines to identify further potentially eligible studies.The following databases were searched: Cochrane Central register of Controlled Trials (CENTRAL), PUBMED, EMBASE, Clinical trials gov. . Duplicate records were deleted. Those separate reports from the same study were linked and evaluated as a single study. Studies analyzed in previously published systematic reviews were manually included when not obtained by the database search . Only puThe evaluation of study eligibility was performed by two authors (AHM and CPA) with the supervision of the review coordinator who identified all potentially relevant articles. After examining the titles and abstracts, clearly irrelevant reports were discarded and the full text of potentially relevant reports was reviewed.The following information was included in the data collection form: eligibility of the study and/or the reason for exclusion, study design, study duration, allocation and blinding process, possible sources of bias, total number of participants, study setting, diagnostic criteria, age, sex, relevant comorbidity, dates of the study, total number of intervention groups, specific interventions, outcome definitions, time-point of reported outcomes related to stroke onset, number of participants allocated to each study group, number of outcomes in each study group, missing data (lost to follow-up), summary data for each intervention group and outcome .For the analysis of the extracted data, we used the Review Manager 5 software .The quality of the included studies and the risk of bias of each study were evaluated following Cochrane Collaboration recommendations available in the Cochrane handbook of systematic reviews of interventions: sequenceUnder the coordination of the principal investigator, the entire team participated in this stage. Publication bias was assessed with the help of funnel plots. The results of the data analysis were imported into the GRADEpro Guideline Development Tool .Three areas of communicative ability were analyzed as outcomes: functional communication, expressive language (naming and repetition), and comprehension.The main outcome was improvement in language skills or in functional communication constructs as measured by a formal evaluation with validated tools including the Boston Diagnostic Aphasia Examination (BDAE) , the AacI2 test. Sensitivity analyses were performed for each diagnostic tool to better identify possible sources of heterogeneity.Collected data for each outcome were mean and standard deviation after the treatment period as well as the number of participants in the experimental and control groups. Standardized mean difference (SMD) was the summary statistic chosen, given that it allowed for the comparison of various psychometric scales. Data were analyzed on a random-effects basis. Results were summarized as standardized mean differences (SMD) and 95% confidence intervals (CIs), and the results from tests evaluating the same outcome were pooled in forest plots for a more comprehensive analysis of the global effect across studies. Heterogeneity across the studies was evaluated considering clinical reasoning and statistical measurements such as the chi-squared and the Finally, we used the GRADE approach to rate the quality of evidence, and we summarized the results in an evidence profile using the GRADE Pro tool.Our search for articles in the databases produced a total of 226 results. After removing duplicates, 88 articles remained. The abstracts of these articles were analyzed, and 40 potentially eligible studies remained. Of those 40 studies, six studies were selected for full-text evaluation. Two were excluded: one for being a topic review and the Van der Meulen et al. conducteVan der Meulen et al. also useHaro et al. was a raThe risk of bias assessments are summarized in This systematic review and meta-analysis, compared to the 2016 Cochrane review which included only one RCT on MIT involving 27 patients, providesResearch on post-stroke aphasia faces two main challenges that limit the internal validity of this study: (1) scarcity of published studies that meet the high standards of well-designed clinical trials, leading to a low number of included studies for the present meta-analysis; (2) heterogeneity in outcome measurements. In this meta-analysis, four randomized clinical trials were included and only two of them, conducted by the same research group, used the same endpoints. Due to the heterogeneity in the outcome measurements of the included studies, in those studies in which several outcomes were described, the most appropriate test for each of the outcomes considered in this review was chosen. Thus, for the functional communication outcome, the ANELT test was chosen over the Sabadel for the Van der Meulen et al. and Van Functional communication represents the ability to successfully communicate in daily interactions, which should be the main goal for patients with post-stroke aphasia to ensure their social reintegration. However, less than half of clinical trials on SLT have focused on functional communication . In receSLTs can be considered complex interventions per the definition of the Medical Research Council Framework for the Development and Evaluation of RCTs for Complex Interventions . Post-stThe main limitations we faced were the small sample sizes in those trials as well as the heterogeneity in outcome measurements that prevented a pooled analysis. Nevertheless, we were able to show an effect of MIT on the CAL measurements and in the repetition tasks. Despite the randomized design of all the included trials and the lack of high-risk of bias, none of the clinical trials were sufficiently powered to demonstrate the efficacy of MIT. Therefore, the quality of evidence is moderate.In conclusion, this systematic review provides updated evidence on the efficacy of MIT in improving functional communication and repetition in post-stroke non-fluent aphasia. Future larger RCT specifically addressing those outcomes should provide the definite evidence on the efficacy of MIT on post-stroke aphasia recovery.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.AH-M and BF: conception of the work, acquisition, analysis and interpretation of data, draft of the manuscript, and approval of final version to be published. CP-A: acquisition, analysis and interpretation of data, draft of the manuscript, and approval of final version to be published. JS-C: analysis and interpretation of data, draft of the manuscript, and approval of final version to be published. ED-T: conception of the work, interpretation of data, and approval of final version to be published. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The Care Ecosystem (CareEco) model is a telephone-based dementia care program providing standardized, personalized and scalable support and education for caregivers and persons living with dementia (PLWD), medication guidance, and promotion of proactive decision-making. It has demonstrated improvement in quality of life for PLWD and reduced unnecessary healthcare expenditures. We initiated a pragmatic, embedded randomized pilot trial of an adapted CareEco model for nurses who provide high-risk care management and are embedded in primary care practices within a large healthcare system. Outcomes include feasibility of collecting emergency department visits, usability and acceptability of the intervention by nurse care managers, caregiver strain, behavioral symptoms of dementia and healthcare expenditures. Challenges of implementation include engaging key care management leaders, adaptation of the CareEco training modules for nurses, identification of primary caregivers, training and reinforcing knowledge and skills of the nurses, embedding clinical assessments into care manager workflows and integration with the EMR."} +{"text": "Objective: To investigate the impact of the severity of age-related hearing loss (ARHL) and tinnitus, presence of ARHL and/or tinnitus, and physical frailty on the health-related quality of life (HRQoL) and domain-specific HRQoL in Chinese community-dwelling older adults.Design: This was a cross-sectional study of a community-based cohort.Participants: We evaluated Chinese older adults aged \u2265 58years.Measurements: The severity of HL and tinnitus were measured using pure-tone audiometry and the Tinnitus Handicap Inventory (THI), respectively. Physical frailty was measured using the five-item Fried scale. HRQoL was assessed using the Assessment of Quality of Life-8-Dimension (AQoL-8D) multi-attribute utility instrument (35 HRQoL items and eight domain-specific HRQoL subcategories). Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic (Model 1) and health-related (Model 2) and psychosocial (Model 3) confounders.Results: Age-related hearing loss severity was an independent determinant of senses in the physical dimension of HRQoL after adjusting for all covariates. Tinnitus severity was significantly associated with HRQoL and with independent living, senses, and pain in the physical dimension after adjusting for demographic and health-related covariates and was still associated with independent living and senses after adjusting for all covariates. The presence of ARHL and/or tinnitus was significantly associated with independent living and senses in the physical dimension after adjusting for all the covariates. Physical frailty was an independent determinant of HRQoL, independent living, and pain in the physical dimension and with mental health, happiness, and coping in the psychosocial dimension after adjusting for demographic and health-related covariates. The association with HRQoL, independent living, and pain in the physical dimension, and with happiness and coping in the psychosocial dimension remained significant after adjusting for the covariates. Depressive symptoms, social dysfunction, and a number of comorbidities were critical determinants of psychosocial HRQoL.Conclusion: Physical frailty has a stronger and more profound effect on HRQoL, particularly on independent living and pain in the physical dimension and on happiness and coping in the psychosocial dimension. Domain-specific HRQoL should be considered in the management of patients with ARHL with tinnitus and physical frailty.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT2017K020. Age-related hearing loss (ARHL) is the most common chronic disorder of the sensory system . PhysicaThe severity of ARHL and tinnThe negative effect of the severity of ARHL and tinnitus and the presence of ARHL and/or tinnitus on HRQoL varies according to the assessment instruments used and confounders , 16. OveThe older population has more complex multimorbidity due to the overlap among physical frailty, comorbidity, and chronic physical and mental health diseases . PhysicaThis study aimed to determine whether these associations were different and independent of demographic, health-related, and psychosocial factors. We hypothesized that the association of physical frailty with HRQoL and specific domains in community-dwelling older people is different from that of ARHL with tinnitus.In total, 429 community-dwelling Chinese older adults (age \u226558 years) were recruited from our previous cross-sectional cohort study on ARHL with tinnitus and general health . The numAll the participants underwent cognitive function, hearing and tinnitus severity, QoL, and comprehensive geriatric assessments. The inclusion criteria were: permanenHealth-related quality of life was assessed using the 35-item Assessment of Quality of Life (AQoL-8D) self-report questionnaire. The questionnaire covers three physical and five psychosocial dimensions . The senThe severity of ARHL and chronic subjective tinnitus was assessed using pure-tone audiometry and the Tinnitus Handicap Inventory (THI), respectively. The pure-tone average (PTA) in the better ear was calculated using the.5-, 1-, 2-, and 4-kHz thresholds. The participants were then divided into four groups based on their hearing levels .Tinnitus was classified into three categories by severity . The patients were also scored based on the presence of ARHL and/or tinnitus .Cognitive performance was assessed using the global cognitive screening test; Mini-Mental Status Exam (MMSE); and normative z-scores of the neuropsychological test battery, including executive or attention, language, and memory domains , 25. Phy2). The medical questionnaire included self-reported smoking, alcohol intake, and chronic comorbidities ; adjusted for covariates in Model 1 and other health covariates (Model 2); and adjusted for covariates in Model 2 and psychosocial factors, including social dysfunction, depression, and neuropsychiatric symptoms (Model 3). These models were run for low HRQoL scores and then separately for each low domain-specific subscore, which was used as a dependent variable. All the statistical analyses were performed using SPSS version 18.0, and P < 0.05 was considered statistically significant.Continuous variables were expressed as medians and quartiles, and non-normally distributed variables were tested using the Kolmogorov\u2013Smirnov test. Meanwhile, categorical data were expressed as proportions and compared using the Patient characteristics stratified by ARHL, tinnitus, and the presence of ARHL and tinnitus are shown in The results of the multiple logistic regression models on the relationships between the severity of ARHL and high HRQoL (low scores) or low subscores in the physical dimensions of HRQoL are shown in For the physical dimensions, after adjusting for all the covariates in Model 3, absence of ARHL and subclinical ARHL were significantly associated with a higher probability of better HRQoL in senses domain. Meanwhile, mild ARHL showed a marginal association. In Model 3, physical frailty had no effect on senses, while social dysfunction was associated with significantly worse senses. Lack of physical frailty and pre-physical frailty were associated with significantly higher probability of independence and less pain after adjusting for all the covariates . Other iAge-related hearing loss severity showed no significant association with all the five psychosocial dimensions . No physThe results of the multiple regression models on the relationships between tinnitus severity and HRQoL or physical dimensions of HRQoL are shown in Among the five psychosocial dimensions, depressive symptoms were independent risk factors for worse psychosocial dimensions, and social dysfunction was an independent risk factor for worse mental health, happiness, and relationship. Tinnitus severity was not directly associated with the psychosocial dimensions . AbsenceThe relationships of presence of ARHL and/or tinnitus with HRQoL or physical dimensions of HRQoL in the different multiple regression models are shown in p = 0.076, respectively) and relationships after adjusting for the covariates in Model 2 and in relationships after adjusting for all the covariates in Model 3. Depressive symptoms were the major determinant of all the five psychosocial dimensions, and social dysfunction was an important determinant of mental health, happiness, and relationships. Age, education level, smoking, and CVD were also independent risk factors for mental health after adjusting for all the covariates.The presence of ARHL and/or tinnitus was not associated with any of the five psychosocial HRQoL domains . Those wThe impact of the presence and severity of ARHL and tinnitus, ARHL, tinnitus, and physical frailty on the HRQoL and its specific domains in community-dwelling older adults is yet to be clarified to date. This study found an association of ARHL severity with the senses domain of HRQoL, and the association remains significant after adjusting for demographic, health-related, and psychosocial covariates. Tinnitus severity is negatively associated with HRQoL and with three physical dimensions, but the association is no longer significant for HRQoL and pain after adjusting for all the covariates in Model 3. The presence of ARHL and/or tinnitus is only significantly associated with independent living and senses, and the association remains significant after adjusting for all the covariates. The severity of physical frailty is significantly associated with worse HRQoL (high scores) and independent living and pain (high subscores), and the associations remain significant after adjusting for all the confounders. Moreover, the severity of physical frailty is also significantly associated with the psychosocial domains of mental health, happiness, and coping, and the association is only decreased for mental health after adjusting for the psychosocial covariates in Model 3. The use of a multidimensional HRQoL questionnaire and the three models, with successive adjustments for different covariates, provided original information on these relationships.These results extend our understanding of the association among the severity of ARHL , 9, tinnThe effects of age-related auditory disorders (ARHL and tinnitus) on the specific domains of HRQoL were significantly different from those of physical frailty. Previous studies have indicated that ARHL, tinnitus, and the presence of ARHL and/or tinnitus were significantly associated with physical function , frailtyOur study also showed that psychosocial factors, such as social dysfunction and depressive symptoms, were independent determinants of the psychosocial dimensions of HRQoL. In a large cross-sectional population-based study of individuals aged >19 years, hearing loss with tinnitus had a significant impact on all five dimensions of HRQoL . In contSeveral studies have shown that frailty, including physical frailty, is significantly associated with worse HRQoL in the community-dwelling older people , 14. AmoAside from ARHL, tinnitus, physical frailty, education level, BMI, alcohol intake, disability in basic activities of daily living, multicomorbidity, chronic diseases, cognition, and depressive symptoms also influence HRQoL , 26, 35.To our best knowledge, this cross-sectional study is the first to report the different effects of the severity of ARHL, tinnitus, and physical frailty, and the presence of ARHL and/or tinnitus on overall HRQoL and its specific domains. The use of a multidimensional HRQoL instrument, in combination with several self-report and objective covariates, in the assessment improved the robustness of the data collected. However, there are also some limitations to this study. First, participation was voluntary, which could have led to selection bias. Second, the cross-sectional design limited the analysis of causal relationships. For example, ARHL and tinnitus are associated with depressive symptoms , 29, 34 In conclusion, ARHL severity is an independent determinant of senses, while tinnitus severity is an independent determinant of independent living and senses in physical HRQoL. Physical frailty is an independent determinant of overall HRQoL, of independent living and pain in the physical dimension, and of happiness and coping in the psychosocial dimension.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by the Ethics Committee of Huadong Hospital, Fudan University. The patients/participants provided their written informed consent to participate in this study.QR, ZY, and ZH conceived and designed the study. QR wrote the article. WZ, JR, RZ, MZ, XH, and ZY conducted the investigation and data analysis. All authors contributed to the article and approved the submitted version.This study was supported by the Medical Science and Technology Support Project of Shanghai Science and Technology Commission (Grant Nos: 18411962200 and 20Y11902300), Shanghai Municipal Key Clinical Specialty (Grant No: shslczdzk02801), and the National Key Research and Innovation Project (2018YFC2002000).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Royal Society Open Science [We introduce the Life Sciences New Talent collection, comprising invited papers which showcase emerging fields of cross-disciplinary life sciences research and some of the exciting work funded by the Royal Society. The collection is part of a series of commissioned New Talent collections originally started with the Chemistry New Talent collection which ha Science .Royal Society Open Science, commissioned this collection with the aim of expanding the breadth of these New Talent collections to showcase early career investigators in the Life Sciences.We, the Editors of the Biochemistry, Molecular & Cellular Biology, and Genetics & Genomics sections of The papers published in this collection were invited from recent awardees of a Royal Society University Research Fellowship (URF) , Sir HenParamecium bursaria, opening the door to the investigation of its nascent endosymbiotic relationship with a green algae partner [We have enjoyed reading and preparing these manuscripts, which highlight the extraordinary breadth of new talent in the UK Life Sciences research community. Yulia Yuzenkova, a Royal Society URF at Newcastle University, reviews the fast-developing field of non-canonical RNA capping, highlighting the prevalence of this RNA modification across the domains of life . Lu-Ning partner . Michael partner . Benjami partner .Wolbachia bacterial strains in populations of the mosquito Anopheles gambiae in Guinea\u2014findings that identify further candidate strains that might be used in the future for malaria biocontrol strategies [Helge Dorfmueller, a Sir Henry Dale Fellow at Dundee University, contributes a review of recent developments in the understanding of Group A Streptococcus pathogenesis and the implications for vaccine development . Kok-Lunrategies . Christorategies .At the time of writing, we also hope to include the following contributions to our New Talent collection: Andrew Hitchcock, a Royal Society URF at the University of Sheffield, and colleagues review the state of our understanding of the catalytic function, substrate recognition and regulation of two key enzymes which are critical to the final stages of (bacterio)chlorophyll biosynthesis. Benjamin Steventon, a Sir Henry Dale Fellow at the University of Cambridge, reviews the current state-of-the art in the study of pattern formation in static and motile cellular environments, looking ahead to challenges and the approaches that may surmount them. Maria Christophorou, a Sir Henry Dale Fellow at the Babraham Institute, reviews citrullination and its consequences for cell physiology. Joe Grove, a Sir Henry Dale Fellow at the Centre for Virus Research, Glasgow, surveys processes of viral entry to cells and mechanisms of inhibition by antibodies.https://royalsocietypublishing.org/topic/special-collections/life-sciences-new-talent [We hope that readers of the journal will explore this collection and find something of interest. These papers are all curated at w-talent ."} +{"text": "Colorectal carcinoma is a highly prevalent and heterogeneous gastrointestinal malignancy. The emergence of organoid technology has provided a new direction for colorectal cancer research. As a novel-type model, organoid has significant advantages compared with conventional tumor research models, characterized with the high success rate of construction and the high matching with the original tumor. These characteristics provide new possibilities to study the mechanism of colorectal carcinogenesis and improve the treatment effects. The present literature would mainly summarize the characteristics of tumor organoids and the up-to-date technique development of patient-derived organoids (PDOs) and application in colorectal cancer. Colorectal cancer (CRC) is a highly prevalent and incurable tumor in the population, which is recognized as the third riskiest cancer of death worldwide and the second most deadly cancer in the United States . There aRegarding traditional models in CRC research, APC(Min/+) mice are mainly used to study the effect of the interaction between APC and other related genes and pathways on the origin and progression of intestinal adenomas , 7. Adenin vitro. It has apparent advantages, such as simple operation, fast proliferation, short culture cycle, high success rate, high reducibility to the physiological properties of tumor tissues, and self-renewal ability.In addition, cell lines, patient-derived xenograft (PDX), and tumor organoids were created for studies of each stage of CRC. However, the limitation of cell lines and PDX lies in their loss of heterogeneity of CRC genes, which was inaccurate in the study of advanced CRC , 10. Duein vitro in 2009 , which promotes the proliferation of cancer cells. Noggin protein, a bone morphogenetic protein (BMP) inhibitor, regulates cell differentiation and prevents bone metastasis in CRC. R-spondin1, a Wnt pathway activator, promotes proliferation and metastasis of cancer cells. Prostaglandin E2 (PGE2) and nicotinamide both provide nutritional support to the organoid that maintains long-term activity. Two more compounds, A83-01 (TGF-\u03b2 inhibitor) and SB202190 (p38 inhibitor), are both often used to inhibit the migration of cancer cells and help maintain the stability of the tumor organoid and growth factors that regulate signaling pathways are all necessary for culture. After preparing the required organoid materials, the culture process Figure\u00a02organoid . Furtherorganoid , 28.Up to the present day, there are still some challenges in the construction of organoids. In terms of the extracellular matrix, there are shortcomings such as high cost, complex specific composition, poor controllability, and limitations in the application. Besides, the tumor organoid after tissue implantation into Matrigel by digestive enzymes contains only epithelial cells and lacks mesenchymal cells, immune cells, and other non-cancerous cells, while the proliferation and differentiation of tumor tissues are affected by the microenvironment containing epithelium and mesenchyme , and theIn conclusion, materials and techniques for the construction of CRC organoids still need to be optimized and constantly upgraded and created to better satisfy the practical needs of clinical implementation.in vitro culture conditions. In 2011, the team of Sato along with collagen as the core material, which can compensate organoids for the ability of personalized treatment assessment to some degree.Nevertheless, incomplete replication of the models for the biological environment of the intestine as the limitation of models may not be conducive to the development of organoids in CRC; the current research , 40 idenin vivo experiments by verifying in vitro that PDOs are highly concordant with the genes and histological properties related to the source tumor and to better guide clinical use of drugs and personalized treatments by uncovering the diversity of tumor responses to drugs. Initially, van de Wetering et al. , microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and sawtooth-like pathway . Therefoet al. , especially high (MSI-H), occurs inextricably with DNA mismatch repair (MMR) gene silencing, commonly MLH1, MSH2, MSH6, and PMS2 . In contmutation and abnomutation , often tmutation verifiedf Takeda establishf Takeda that 90%V600E as well as MLH1 mutation organoids and successfully modeled the characteristic lesions related to serrated colorectal adenocarcinoma, such as infiltrative growth of serrated tissue with mucus cap, and detected an increased frequency of CpG methylation, which verified that the serrated pathway activation has a strong correlation with BRAF V600E, MSI, and CIMP. It can be supposed that the organoid can still maintain high fidelity to the CRC environment, which provides a piece of important evidence for extensively studying the molecular pathways of CRC in the future.As unique colorectal carcinogenesis pathways, both CIMP and the serrated pathway are relevant in most cases. CIMP, generally interpreted as CpG island methylation, inhibits the normal transcription of genes and thus downstream genes for their normal expression. It is mostly positively expressed in serrated colorectal adenomas, often occurring in collaboration with both BRAF mutations and MSI . The LanIn summary, CRC organoids are competent to recapitulate the relationship between genes and signaling pathways and validate the complexity, diversity, and association between pathway mechanisms of oncogenesis. Applications of tumor organoids can promote research in predicting the development of CRC prognosis based on genetics and in innovating oncology drugs to regulate the interaction among pathways.Due to the phenomenon of tumor heterogeneity, the response of tumors induced by different pathways to drugs may also differ, so the development of various antitumor drugs is inseparable from the study of tumorigenesis and development mechanisms. Furthermore, the preclinical, experimental stage is necessary to ensure that the efficacy of drugs in clinical applications can still achieve the expectation in basic research, which requires the support of a majority of suitable models. On the one hand, CRC PDOs can be used to establish a biological sample bank and preserve the heterogeneity of CRC, providing abundant preclinical models that can be used to predict drug response and efficacy; on the other hand, organoids can be functional in estimating the effect of drugs on genes or signaling pathways referring to the mutation characteristics of colorectal oncogenes and screen out suitable anti-CRC drugs referring to patients\u2019 clinical\u2013pathological data.et al. and programmed cell death-ligand 1 (PD-L1) are popular immunotherapeutic targets in CRC . By incuUp to now, as the concept of personalized medicine is gradually kept in mind, the space for organoid technology continues to grow. The use of CRC organoid culture technology has broadened the horizons of diagnosis and treatment of CRC and reminds us to target more breakthroughs in medical healthcare and drug selection of CRC.Major progressions of organoids from 2009 to 2020 are supplemented in JL, XH, BZ, and WT conceived of the study and participated in its design and coordination and helped to draft the manuscript. JL, XH, LH, JH, DL, LL, YD, LZ, BZ, and WT made a significant contribution to the work about the analysis, writing, and interpretation. All authors contributed to the article and approved the submitted version.This research was funded by the Guangxi Clinical Research Center for Colorectal Cancer (Guike: AD19245197); Research Basic Ability Improvement Project for Guangxi Young College Teachers (2021KY0087); Innovation Project of Guangxi Graduate Education (YCSW2021133); Guangxi Medical University Autonomous Region-level College Student Innovation Training Project (202110598177); Guangxi Natural Fund Facial Project (2021JJA140081); Guangxi Medical and Health Appropriate Technology Development and Promotion Project (S2021016); and The project of improving the basic ability of scientific research of young and middle-aged teachers sponsored by the Education Department of Guangxi Zhuang Autonomous Region (2021KY0086).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Background: Dance interventions are considered beneficial for older patients with mild cognitive impairment in many aspects. We conducted a comprehensive systematic review and meta-analysis to assess the effects of dance on different aspects of this population.Methods: A systematic search of PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Embase, American Psychological Association PsycInfo, ProQuest, Scopus, Cumulative Index to Nursing and Allied Health Literature, the Chinese BioMedical Literature Database, the VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data database was performed. Two reviewers independently assessed the study quality.Results: Fourteen studies were retrieved from the databases for analysis. The pooled results showed that dance interventions significantly improved global cognition , rote memory , immediate recall , delayed recall and attention . No significant improvement was found in executive function, language, depression, anxiety, dementia-related behavioral symptoms, motor function, and quality of life.Conclusion: Dance interventions benefit most aspects of cognitive functions. The evidence for the effects of dance on psycho-behavioral symptoms, motor function and quality of life remains unclear. More trials with rigorous study designs are necessary to provide this evidence. The Lancet reported that approximately one-fifth of the older population, aged over 65 years, experience MCI was first proposed by Reisberg et al. , to descThe intervention methods for MCI can be pharmaceutical or non-pharmaceutical. Current reviews have found that acetylcholinesterase inhibitors used to treat Alzheimer's disease (AD) have proven ineffective in the MCI treatment group , lifestyle, emotions, and social functions, thereby improving the quality of life (QOL) of the research subjects ; to establish a general summary of the existing literature; and to provide a basis for follow-up studies in this field.This work adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and was prospectively registered with the International Prospective Register of Systematic Reviews (CRD42021230159).RRID:SCR_004846), Web of Science, the Cochrane Central Register of Controlled Trials , Embase , American Psychological Association PsycInfo , ProQuest , Scopus, Cumulative Index to Nursing and Allied Health Literature, the Chinese BioMedical Literature Database, the VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data. To ensure the comprehensiveness of the included studies, we used combinations of Medical Subject Headings and free text words without language restrictions from inception to November 12, 2020. We also retrieved the reference lists of all eligible studies and other relevant studies using alternative approaches . The complete search strategy is provided in We searched the following electronic bibliographic databases: PubMed ; dance not limited to the frequency or duration of the intervention; dance performed under the guidance and supervision of trained professionals or by the participants themselves.We defined dance intervention by the following principles: systemic movements of the body that are needed to be observed and imitated, are focused on physical flexibility and expression of emotion, and are accompanied with music.Including but not limited to drug treatment, regular therapy, and educational programs.At least one measure of cognitive function , motor function , psycho-behavioral symptoms , and QOL.Studies that included the following tests were included in the review: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess the global cognition level; Trail Making Test Parts A (TMT-A) mainly to evaluate rote memory of patients; Trail Making Test Parts B (TMT-B) primarily to assess executive function; Logical Memory I (LM-1) and Rivermead Behavioral Memory Test (RBMT) to measure immediate recall; Logical Memory II (LM-2) to assess delayed memory; the Symbol Digit Modalities Test (SDMT) or Test of Everyday Attention (TEA) to assess attention; the Boston Naming Test (BNT) to assess the language function in patients with cognitive impairment.Studies that included the following tests were included in the review: Psycho-behavioral symptoms evaluated using Neuropsychiatric Inventory (NPI) to assess the 12 behavioral disorders occurring in patients with dementia such as delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities; degree of anxiety mainly measured by the Hospital Anxiety and Depression Scale (HADS); the Geriatric Depression Scale and HADS to test depression.Studies that included the following tests were included in the review: Berg Balance Scale (BBS) to evaluate balance; the Timed Up and Go (TUG) test to test functional mobility.Studies that used the following two scales for QOL evaluation were included in the review: Quality of Life in Alzheimer's Disease (QOL-AD) and the 36-item Short Form Health Survey (SF-36).Studies that were randomized controlled trials (RCTs) or quasi-experimental trials were included in this review.Two reviewers worked independently to identify studies that met the inclusion criteria briefly by screening the abstracts. If the abstract did not provide sufficient information, the full text was obtained to determine the study's eligibility for inclusion in this review. Any disagreements were resolved after discussions with a third reviewer (JYC). We excluded studies for which complete information could not be obtained despite our best attempts.RRID:SCR_014001) and NoteExpress.For each eligible study, information about the first author's name, country, number of participants, age, male to female ratio, control group intervention, intervention characteristics , and outcome measures were extracted using a self-designed standardized form . Two revTwo reviewers independently assessed the study quality according to the Cochrane Handbook for Systematic Reviews of Interventions to perform the meta-analysis. Since all data were continuous, we selected the mean difference (MD) with 95% confidence intervals (CIs). When different scales were applied to measure the same outcome, we used the standardized mean difference (SMD). Heterogeneity in the included studies was tested by the Cochrane Q statistic and quantified by the IUsing the search strategy, 1,534 articles were identified from 12 databases . After en = 7) Yi, , USA , and other studies described their dance interventions as choreography, poco-poco dance, and standard dance-based aerobics format. The poco-poco dance course was guided by experienced professionals who gradually increased the difficulty and intensity of the dance both for acceptance and safety. BAILAMOS\u00a9 program was professionally guided based on the BAILAMOS\u00a9 guidebook. The researchers constantly adjusted the dance content in conjunction with the difficulty of the steps and safe limit of each of the participants. The dance used props (Velcro bracelets of different colors) to help participants remember their movements. Chinese square dancing, which originated in China, involves a variety of dance forms, but is also easy to learn. Dance rug is a modern aerobics game that is simple and easy to operate, allowing participants to learn at home without outside guidance. Yangko is a traditional Chinese folk-dance form. This dance mainly involves the twisting of various parts of the body; this unique form of exercise has particular advantages.The data for the risk of bias in the included studies is provided in P < 0.00001; Twelve studies examined the effects of dance interventions on global cognition. Analysis of global cognition at the end of the intervention demonstrated a significantly higher post-intervention global cognition level in the dance group than in the control group. The pooled SMD showed a statistically significant increase in global cognition , we performed a sensitivity analysis. When we excluded the four quasi-experimental trials . Another study .Two studies were pooled for the BNT results. One study illustrated that a structured modular ballroom dance intervention can improve language among older people with MCI . However, another trial . Four studies . One study . Another study .Eight studies compared the dance intervention group with non-dancing controls to evaluate the effectiveness of dance intervention on depression in 577 older adults. Two trials . In contrast, another RCT .Two studies . Another study indicated that a 48-week ballroom dance program could improve these symptoms in older people with MCI . However, both studies demonstrated no significant differences in dementia-rated behavioral symptoms between the two groups.Two . Another RCT .Two studies . However, one RCT . One study .QOL scores were available for 136 participants from three trials. Two trials . Furthermore, we performed a descriptive analysis for those results of the meta-analysis with more significant heterogeneity (>50%).The aggregate results of MMSE and MoCA evaluations showed that the dance intervention group was better than the control group in terms of overall cognition, and the results were durable and stable when sensitivity analysis was performed. Dance intervention as an aerobic exercise maintains the integrity of cerebral vessels by providing blood, oxygen, and nutrients and influences cognition by increasing brain-derived neurotrophic factor levels and synapses, promoting the growth and survival of neurons , Nursing science, a key discipline project of Jiangsu Province during the 13th Five-Year Plan period (sjy [2016] No. 9), Project Studies on Construction of Core Competency Model and Development of Assessment Tool for Nurses of Hospice Care supported by NSFC (72004099), and Project Comparative study on hospice care mode between China and Canada (2017SJB0295) supported by Philosophy and Social Science Foundation of universities in Jiangsu Province.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Area Agencies on Aging (AAAs) have played an important and well-documented role in meeting the nutritional and wellness needs of older adults during COVID-19. To better understand the continued impact of COVID-19 pandemic on AAA services, partnerships, and clients, the National Association of Area Agencies on Aging surveyed the nation\u2019s 618 AAAs in February 2021, with a 27% response rate. As a result of COVID-19, most AAAs reported both increased numbers of new clients and needs of existing clients; three-quarters of AAAs developed new external partnerships; and over half are implementing strategies to address equity and inclusion regarding their services and clients. Nearly 80% of AAAs are involved with COVID-19 vaccine outreach and delivery, from scheduling appointments to administering the vaccine to homebound clients. We will describe these and other transformations of services, partnerships, and client needs; discuss challenges and opportunities; and provide examples and video vignettes from AAA directors."} +{"text": "Social isolation and loneliness are detrimental risk factors to older adult\u2019s physical and psychological well-being and quality of life. Given the current situation of the COVID-19 pandemic, social isolation has risen. Social isolation affects younger adults as well and may increase the chances of depression and anxiety. In this study, we tested the acceptability and feasibility of an Intergenerational Bonding (IGB) Program with older and younger adults. Participants include students aged 19-29 at the University of Nebraska at Kearney and older adults above the age of 60 residing in the community. First, we surveyed younger and older adults to determine their interest level in participating in an IGB Program. Both groups of participants rated their interest in different activities. The most popular activities among both groups included engaging in conversations, board games, and an exchange of skills. Neither of the groups was in favor of participating in free housing opportunities or sports-related activities. Response rates were high in young adults but low in older adults, due to lack of trust. Then, in a pilot study, we measured the feasibility and acceptability of the IGB Program. Older adults residing in independent dwellings, assisted living environments, nursing homes and members of community groups were invited to participate in the intergenerational program. Response rates of older adults were low. Further, establishing collaboration with institutions such as nursing homes was not easy despite initial interest. Building trust and working with community activity group facilitators would be beneficial in recruiting older adults."} +{"text": "While the US-Mexico border region has had increasing restrictions due to coronavirus 2019 (COVID-19), the economically and socially integrated region continues to facilitate necessary movement between the two countries. Binational partners representing universities, government, and health delivery worked together to develop a COVID-19 Virtual Seminar for the US-Mexico Border Region, which consisted of weekly sessions in Spanish designed to better facilitate communication and collaborative systems between border states. In total 835 participants registered for the virtual seminar with attendance ranging from 394 in Session 1 to 269 in Session 6. From evaluation surveys (n\u2009=\u2009297), organizers observed a large plurality of healthcare professionals, followed by students, researchers, and government employees. The seminar\u2019s contribution to increasing collaborative and communication systems identified major needs in the region surrounding surveillance and monitoring; increased resources for migrant shelters to control outbreaks; an increase in personal protective equipment; tracking binational cases. Coronavirus-19 (COVID-19) has had a major impact on population health and health systems across the globe, with the WHO reporting approximately 108.2 million cases and over 2.3 million deaths globally [The US-Mexico border region stretches for approximately 2000 miles along the southern end of the US and most northern area of Mexico. It consists of the US states: California, Arizona, New Mexico, and Texas; and the Mexican states: Baja California, Sonora, Chihuahua, Coahuila, Nuevo Leon, and Tamaulipas. The interdependence of the two countries has continued manifest into a tightly woven region that shares economic, cultural, social, and behavioral ties, regardless of the increased politicization of the border region in recent decades . OverallIn order to better facilitate communication and collective action to monitor and prevent COVID-19 across border region, the US-Mexico Border Health Commission, the University of Arizona, and El Colegio de la Frontera Norte established a virtual seminar series. The series conducted in Spanish shared the state of COVID-19 along the border region, public health prevention efforts, and actions taken by every state government to mitigate the impact of the virus. The seminar series was specifically designed for health personnel and providers, academics, students, among others interested in the topic. The overall objectives of the seminar series to promote information exchange, enhance monitoring processes, identify mutual issues,and promote discussions surrounding solution-based approaches.The COVID-19 Virtual Seminar Series for the US-Mexico Border Region was designed as six weekly 90-min sessions with experts in the field invited to present for approximately 20\u00a0min. The formAll sessions were conducted in Spanish using Zoom with only presenters having permission to share video and audio, while participants had access to a chat feature for questions, reflections, and/or comments on the seminar. Participants were asked to register prior to sessions. All registered participants were able to attend all sessions, given they were subsequently were notified and provided information for every weekly session. At the conclusion of the seminar series, registered participants received an online evaluation form. As no personal or identifiable information was collected, and the investigators are reporting the findings of an open public seminar, US-Mexico Border Health Commission exempted from review.As seen in Table Surveillance and monitoring of suspicious and positive cases, along with tracking of contacts to decrease the spread of the virusIncreasing the diagnostic capacityAcquiring of supplies including personal protective equipment for essential workers and healthcare workers.Strengthening and standardizing of mental health care programsControlling the outbreaks among vulnerable populations specifically, indigenous communities and migrant farm workersIdentification and tracking of cases, as well as exchange of information at the binational level, particularly to address the transmission through binational cases.The last seminar brought together decision-makers across the region to discuss issues across states in the US-Mexico border region, along with collaborative efforts to increase surveillance and control of COVID-19. Identified challenges discussed across the US-Mexico border region:As seen in Table Given the fluidity of the border region, both in crossing of people, goods and services, the Virtual Seminar highlighted the importance of continued communication and collaboration in impeding the epidemic in the US-Mexico border region. As most countries around the world, the US and Mexico, were not an exception to the unpreparedness in addressing the magnitude of this pandemic.In 2011, an infusion of resources was distributed to states across the US and Mexico through the US-Mexico Border Health Commission, which was establish and approved by both federal governments for prevention efforts and public health emergencies , 8. ThesIn addition, there still lacks a cohesive effort by border states to collectively define binational cases. As such, there is an opportunity to recommend at the very least the importance of revisiting collective binational surveillance efforts at both federal and state levels, regardless of political affiliation. These cases that move seamlessly back and forth across the international boundary need to be properly and promptly addressed to curve current pandemics along the border region. This also has critical implications for contact tracing\u2014improved implementation of communication and surveillance systems can immediately identify binational cases through contact tracing to rapidly mitigate community spread on both sides of the border. In addition, this can be extended to migrant shelters and communities that have seen consistent outbreaks, and are in urgent need of additional resources to combat COVID-19 transmission. Lastly, the Operational Protocol for Binational Communication and Coordination between Mexico and the United States on Disease and Outbreak Notifications should be updated, implemented, and serve as policy for improving practice in communication sharing and forging opportunities for collaboration with the current pandemic and future events that require early detection and response."} +{"text": "With the application of engineering management in smart city construction under Industry 4.0, the intelligent design of urban street landscape has attracted extensive attention. Affected by the low intelligent level of traditional landscape design, the existing urban landscape composite system has difficulty in meeting the needs of smart city construction. Therefore, this paper proposes the construction of street landscape big data-driven intelligent decision support system based on Industry 4.0. Based on the complex network theory, this paper analyzes the structure, links, nodes, driving forces, and functional requirements of urban street landscape and then puts forward the construction content and implementation method of urban street landscape intelligent decision support system. The system consists of four aspects: intelligent infrastructure, service, protection and maintenance, and management and evaluation system. Its implementation not only reflects the cooperation and effective application of intelligent technology in each stage of street landscape construction, but also provides reference for the application of engineering management in other fields under Industry 4.0. Based on the connectivity provided by the Industrial Internet of Things (IIoT) and the use of a variety of digital technologies such as cloud computing, big data, and artificial intelligence, Industry 4.0 is proposed as a new stage of industrial maturity , 2. ThesAs an important part of smart city construction, landscape architecture is also facing opportunities and challenges brought by the intelligent process. Smart gardens changing the construction, operation, and management modes of traditional gardens can effectively improve the efficiency in landscape garden industry, realizing the normalization, standardization, digitization, networking, and intelligence of garden construction . The typIn the construction of urban street landscape intelligent system, \u201curban street\u201d refers to the urban road equipped with sidewalks, municipal utilities, and various buildings on both sides in the overall length or most sections. As one of the subsystems under the future urban open complex giant system, the nature, function, form and structure of urban street are more complex than traditional urban road. Urban street serving as the most basic public urban space focuses on the citizens' life and humanized experience, which facilitates the interpersonal communication and interactions via emotional sustenance as well as playing an irreplaceable role in shaping the urban charms and vitalizing the economic development , 10.Relying on the complex network theory and \u201cInternet +\u201d thinking, the smart landscape cooperates with new-generation information technologies such as Internet of Things, big data cloud computing, mobile Internet, remote sensing, and information intelligent terminal, obtains time-domain advantages, and responds quickly to social and natural activities carried in the landscape space. Integrating the spatial domain of modern ecological landscape into the large database achieves the intelligent connection between scattered social activities and needs of human beings, nature and landscape space for the interactive perception, and cognition and communication and improves the utilization and sharing rate of various scattered landscape resources, thus promoting the intelligent construction, service, and management of landscapes , 12.The design of intelligent street landscape systems shall be based on the comprehensive consideration of user needs, greening landscapes, and basic street functions, through the Internet of Things, web services, and virtualization technology. The basic attributes, characteristic parameters, status, and other information of various street landscape elements are dynamically and intelligently sensed and accessed in real time, to build street space intensively. Through processing the information perceived by the landscape intelligent system, data collection, integration, analysis, processing, and feedback are realized under the mapping of landscape resources in urban streets. On the premise of ensuring the basic functions of the road, people's travel safety, life, and social security should be guaranteed, which provides conditions for the scientific, rapid, comprehensive, and visual development of urban street landscape design and management.The construction of intelligent systems for urban street landscape based on complex network theory and the integration of smart landscape concept into the traditional urban street landscape indicate further improvement, which shall meet the requirements for intensive intelligent spaces, multiple interactive experience, and green ecology of energy conservation , 14.In order to cope with the multiple landscape needs under the complex system of urban streets, the intelligent street landscape system based on the complex network realizes the intelligent supply-demand matching of street landscape space services from the three levels of landscape facilities Internet of Things, service Internet, and user Internet.The construction of street landscape intelligent system mainly involves four aspects: intelligent infrastructure, intelligent service, intelligent protection and maintenance, and intelligent management and evaluation.Intelligent infrastructure is the physical layer and the foundation of street landscape intelligent systems. The infrastructure of street landscape intelligent systems shall proactively provide the information and services desired in addition to the basic functions and be available to correlate with other facilities and even users for the formation of a complete intelligent network featuring information interaction and function linkage, thus completing the virtualization and service-oriented information interaction and functional linkage of the intelligent information system.Information infrastructure is the basis of intelligent street landscape, covering the electric information screen shown in Data cognition is the core of intelligent street landscape development. The data infrastructure is used to collect and integrate street landscape data, achieving the intelligent street landscape construction by providing the users and managers with comprehensive and intuitive information based on the integration and analysis of multisource data (basic/business/service databases).Basic database clarifies the spatial location and surrounding environment of urban street landscape for the precise positioning of smart landscape. Business database has multiple subdatabases covering the special data, system planning and management, monitoring management, and industry management available for the precise and whole-process collection of street landscape data. Service database can provide the popular science knowledge about smart street landscape for the public and facilitate the review of various urban green spaces and scenic spots by potential travelers .Based on the ecological requirements of the street landscape intelligent system construction, ecological observation of the street is an effective measure to achieve this goal. Using RFID (radio frequency identification) technology, the real-time update of spatial ecological information of street landscape can be realized, and the location of vegetation, structures, and buildings can be monitored online. Special sensors and wireless sensor networks for street landscape ecological observation can effectively realize real-time data acquisition and transmission. Real-time monitoring of the street green space ecosystem can help with maintenance and management of the green landscape. Furthermore, the obtained ecological econometric characteristic data can aid in the formation of quantitative analysis results of the street landscape space, resulting in better landscape and ecological effects from green space maintenance and management, The service object of the intelligent street landscape systems is the streetscape users. The construction of intelligent service system is based on Internet functions, which can realize the dynamic matching of the user's needs. From the perspective of users, in the process of system construction, our goals and demand motivation can be evaluated, and the service content can be derived dynamically.In terms of qualitative or quantitative data, managers could be provided with genuine feelings, opinions, and suggestions generated by the public in the service experience. With the help of dynamic characteristics analysis of smart infrastructure, a reliable method for demand forecast management is provided. Thus, public involvement can be achieved, and the quality of the service improves continuously .Network service platforms are the basis for intelligent service and the guarantee for intelligent linkage with other service facilities. The construction of portals serving the public shall cover various services such as bus routes, e-maps, traffic notices, travel tips, and road service calls. In addition, the construction of mobile-based network service platforms shall also be emphasized to ensure the real-time content update and provide mobile users with street information services based on the shared portal resources.Basic street services are mainly the traffic, lighting, and other necessary basic services. For instance, the smart parking management system achieves the real-time monitoring of parking spaces and the intelligent guidance about available parking spaces based on the information inquiry of parking lots and spaces through various intelligent terminals such as smart phones. The construction of public transportation system shall ensure the timely release of bus information and certain functions in combination with the special bus signal system for important bus corridors and the intelligent bus stations. The streets with heavy traffic flows shall be equipped with smart toilets, which are available for the information inquiry of location and real-time usage through various intelligent terminals . In addition, the intelligent lighting system subject to the independent sensing, timing, voice control, or remote control of intelligent terminals shall also be arranged for the smart control of landscape lighting in different areas , Figure The intelligent terminals and multilanguage terminals for self-service navigation shall be arranged to facilitate the inquiry of street and surrounding-area e-maps and tour route planning as well as the scenic spot/plant introduction using QR code/RFID technologies .An interactive information system shall be established to provide life, service, business, and medical information for citizens, with various network service platforms serving as the channels for street information release, covering the street information, real-time road conditions, toilet usage, spare parking spaces, restaurant usage, and other basic information; climatic information and health information such as negative oxygen ion content in key areas Figures Personalized services available at various network service platforms can meet the street use demands of different people , for insCompared with the traditional consulting/complaint services, the services provided through the intelligent system are more convenient and efficient, and multiple channels are available for the public. The intelligent system of linkage service can achieve the unified receipt and instant feedback/response to consultations and complaints from telephones and network terminals.In order to improve the user experience, a multimedia experience center focusing on historical districts shall be constructed using multiple technologies for the display of historic landscapes, original natural features, and historical changes. The 3D panorama/reality enhancement display technology and 360\u00b0/720\u00b0 real-life photos or videos can be utilized to create the virtual blocks for digital virtual tours that are available at portals and terminal devices , 21.Intelligent protection and maintenance are the function expansion of the user Internet based on the Internet of Things of landscape facilities. Dynamically generate landscape maintenance needs based on smart infrastructure, and dynamically match landscape maintenance needs with landscape maintenance services through the Internet of Things technology. Realize the informatization and intelligence of the protection and maintenance process, provide visual guidance on daily maintenance process and key technology, and the responsible personnel and stages could be specified for the real-time recording of maintenance process and information .Green space protection and maintenance are the key to intelligent protection and maintenance, covering the digital recording, monitoring, and control of boundaries and green resources including the main plants and facilities. The important spots and key facilities shall be equipped with 3D scenes for inspection and comparison via intelligent terminals, mainly involving the plant irrigation and fertilization, pest and disease and freezing damage management, and intelligent cultivation.Environmental monitoring and intelligent irrigation system can provide effective services for intelligent plant irrigation and fertilization management. The digital data processing of soil nutrients can maximize the effects of water-saving and precise irrigation, scientific management, and low-carbon maintenance , 24. TheThe GPS positioning and FRID technologies shall be adopted for the control of plant diseases and pests, with the dynamic tracking system established to ensure the dynamic protection and monitoring of green plants as well as help technicians locate the areas of pests and diseases at first time. The implementation of \u201cprevention-first\u201d principle by each institution responsible for plant management and protection targeting the necessary early warning of pests and diseases within all periods can greatly reduce the prevention costs and probability of large-scale pests and diseases . Early wThe intelligent technology-based seedling planting and cultivation shall make full use of the IoT and spatial information integration technologies. The partitional measuring of regional soil quality, hydrological conditions, and microclimate factors at the stage of planting planning provides the definite data basis for breeding and rapid formulation of cultivation schemes. At the same time, a tree full cycle database shall be established for plant tracking and data sorting in the whole process, as well as the records of seedling archives, tree transplantation, and maintenance information. Intelligent cultivation can effectively prevent the challenges faced by the traditional seedling cultivation .Both natural heritage and cultural heritage involve heritage protection and maintenance, including ancient and famous trees and cultural relics. For the ancient and famous trees, the high-definition photos shall be obtained based on the precise coordinate positioning via monitoring and RFID technology in addition to the normal maintenance measures, and mastering relevant detailed information will facilitate the data calling, plant protection, document management, maintenance, and rejuvenation monitoring. Digital modeling based on the growth environment of ancient and famous trees also facilitates the accurate analysis of protection measures Scientific and comprehensive management measures are an important prerequisite for realizing the sustainable development of streetscapes. Quantitative evaluation mechanism is an effective objective to judge the effectiveness of streetscapes.How to effectively integrate various scattered landscape management resources and coordinate various quantitative evaluation parameters to achieve the best match between street landscape management and demand is the key problem. Hence, quantitative data-driven evaluation and control system is ultimately conducive to the continuous optimization of landscape effects.The comprehensive and scientific management shall take account of internal office work, gardening business, street security, and other related factors.Office automation (OA) system can improve the overall efficiency of internal office work, covering process management, e-mail, document management, document circulation, approval management, working calendar, notice announcement, personal information maintenance, conference management, and attendance management.In terms of the gardening business management, video monitoring, RFID, and infrared sensing technologies shall be adopted for the real-time perception of changes in street green resources, infrastructure, and traffic flows, as well as the automatic collection, adjustment, and update of street landscape data. The real-time monitoring of street landscape can achieve precise management and prevention against vandalism and damage caused by natural disasters.Street security cannot be neglected considering the special traffic function of urban street with public spaces. The construction of integrated street control platform makes the daily operation monitoring and emergency command and dispatching possible, providing basic support for navigation and guidance based on the location services of GIS and satellite positioning systems . NowadayThe evaluation of self-diagnosis by intelligent evaluation system aims to provide reference for further development. Moreover, reasonable performance evaluation can not only measure the achievements of street landscape construction and find out the existing problems, but also provide important guidance for the continuous improvement of street landscape intelligent system.Establishment of the complete, scientific, and effective evaluation system shall be based on the existing urban gardening standards, with the relevant street smart landscape indicators integrated into the system by means of spatial layers, forms/tables, document uploading, and image attachments for real-time computing and result judgment/analysis , Table 1How to manage, digitize, and integrate information from scattered roads efficiently and precisely, in order to realize the effective distribution and dynamic overall grasp of the streetscape service capabilities.How to coordinate the relationship between the geographic space, data flow, time distribution, hardware network, and user needs of the streetscape intelligent system, in order to realize the spatial mapping between complex streetscape resources and intelligent system service capabilities .Intelligent technology refers to a specific technology or method used in the construction of an intelligent urban streetscape system. Internet of Things, spatial information integration, virtual reality and visualization technology, digital technology, etc. can solve the following problems in the construction of streetscape system under the condition of urban complex giant system:Emergence of the most representative IoT technology in the intelligent process has led the transformation of information age into an intelligent era. The all-inclusive IoT technology involving radio frequency identification (RFID), infrared sensor, and sensor-laser scanner solves numerous urban problems via interconnection of things after the Internet-based information connection .Spatial information reflects the spatial distribution characteristics of geographic entities, and the spatial information integration technology involving remote sensing (RS), geographic information system (GIS), and global positioning system (GPS) can reflect the topographical features of all sites more concretely and objectively at the macro level and achieve precise quantification and data digitization for in-depth research and analysis .VR technology integrates multiple techniques features in good experience of immersion, interaction, and conception, covering the real-time 3D computer graphics, 3D wide-angle (wide-field) display, tracking of the viewer's head/eyes/hands, tactile/force feedback, stereo effects, network transmission, and voice input/output .The basic process of digitization involves the transformation of all complex and changeable information into measurable data, digital data modeling for binary code conversion, and input into the computer for unified processing . At presTo achieve the successful construction of street landscape intelligent systems, the mutual mapping of complex system and complex network of street landscape needs to be realized. Therefore, the above intelligent means must be implemented combined with the actual stages of street landscape construction in practice.The early stage of planning and design provides direct guidance for the mid-term construction and post-management of landscape construction. The application of intelligent means such as the Internet of Things, virtual reality, and visualization technology at the planning and design stage can realize more scientific and rational street landscape design.In terms of on-site investigation, the traditional investigation methods have large workload and large error, and most of them are completed on the basis of on-site inspection and surveying and mapping, combined with the existing data. In addition, the traditional street design focusing on-site plane lacks the 3D-space and humanized thinking in terms of vertical design, construction scale, and detailed design. On the contrary, the intelligent landscape construction can realize the targeted integration of IoT and spatial information technologies into the site survey, with the precise positioning of street location and surrounding land uses utilizing the IoT sensing nodes ; moreoveThe construction quality directly affects the smooth implementation of the preliminary design and the cost of later maintenance and management. Due to the problems of inaccurate calculation of quantities, unconstrained construction, and limited professional quality of most construction personnel in traditional garden construction, there are often some deficiencies in construction quality compared with the expected effect.The intelligent street landscape construction can ensure the rational resource allocation and construction efficiency through the in-depth survey of on-site environmental factors using the sensing and RFID systems of IoT technology and the corresponding construction schemes and regulations. The application of spatial information integration technology and sensing system makes precise and rapid data positioning based on construction drawings possible at the stage of fixed point setting-out. The multispace model using VR technology enables the construction personnel to understand the design intention in an intuitive manner during construction, thus ensuring the realization of design effects. The application of IoT sensing system upon project acceptance for data measurement and quantitative analysis of engineering effects, combined with the direct data transmission to the auditor's mobile devices using mobile Internet technology, guarantee the strict project acceptance , Figure Conservation management can maintain and guarantee the landscape effects after gardening construction. The traditional plant cultivation and conservation have certain shortcomings, e.g., unsatisfactory professional quality of management personnel and conservation measures of low technical contents.The intelligent plant cultivation and conservation integrating IoT technology ensure the effective improvement of conservation efficiency and effects with reduced cost. In order to make proper use of local conditions, the sensors shall be used to measure environmental factors at the cultivation stage, and the original manual sprinkling shall be replaced by the sprinkling/drip irrigation system with time-frequency sensors to detect the soil moisture and facilitate the intelligent control . In termApplying intelligent means in urban street landscape design and integrating street landscape intelligent system into smart city construction can actively promote urban development. Procedures starting from scheme design and project construction to maintenance management, technology introduction, and formulation of comprehensive and effective strategies are the key to the successful construction of street landscape intelligent system based on complex network. In addition, the construction of street landscape intelligent system also provides a platform for public participation and governance. The public can easily and quickly obtain information through such intelligent systems and use improved consultation/complaint services to give timely feedback to managers, which indicates that public participation has been significantly improved , 38, 39."} +{"text": "Cancers, experts in this field will review the current approaches for diagnosing and managing patients with the spectrum of GI cancers, and suggest innovative solutions fit for the diagnosis and the management of these cancers in light of the new challenges and abundance of innovations [Gastrointestinal (GI) cancers remain high on the list of the leading causes of death worldwide; however, the recent emergence of new and ongoing global healthcare threats, such as the COVID-19 pandemic, has led to a temporary reduction in elective endoscopic procedures . InnovatThe SI is a showcase of a fine collection of articles that underpin the continuing research and innovation approaches in GI endoscopy. In the Global Burden, Risk Factors, and Trends of Esophageal Cancer : An AnalIn another paper of this SI, Verra et al. present their work on a robotic-assisted colonoscopy platform with a magnetically actuated soft-tethered capsule . Almost The SI is not short of high-quality reviews in the field of GI endoscopy. Finocchiaro et al. provide their elaborate and highly pictorial revision on the current and future perspectives in training simulators for GI Endoscopy . ConventA high-quality negative screening colonoscopy was related to diminished CRC incidence and mortality for up to 17.4 years . HoweverAlso, in this SI, Marlicz et al. aimed at providing a timely review of robotic gastroscopes and related technologies supporting professional skills in clinical practice . Authors"} +{"text": "A substantial scientific advance has recently been made in the elucidation of the molecular mechanism by which unusually folded, self-associating tau proteins drive the neuropathology of several common types of human neurodegenerative disease. This group consists of about ~25 different, invariably lethal age-related tauopathies that include prominently, Alzheimer's disease (AD), argyrophilic grain disease (AGD), chronic traumatic encephalopathy (CTE), corticobasal degeneration (CBD), Parkinson's disease (PD), Pick's disease (PiD), and progressive supranuclear palsy (PSP) as well as familial British dementia, familial Danish dementia, primary age-related tauopathy, and several other more rare tauopathies. Normally neuron-abundant microtubule-associated protein tau (MAPT) proteins are involved in the organization and stabilization of the internal microtubule system of brain cells and are involved in the maintenance of overall neuronal shape, cytoarchitecture, and synaptic organization. Each of the tauopathies are defined by the progressive accumulation in the brain of MAPT proteins as complex, multi-component fibrillar aggregates, and their incidence and prevalence correlate strongly with the degree of dementia , The Brown Foundation, Joe and Dorothy Dorsett Innovation in Science Healthy Aging Award; the Louisiana Biotechnology Research Network (LBRN) and NIH grants NEI EY006311, NIA AG18031, and NIA AG038834 (WJL).The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "The majority of nursing home (NH) residents have Alzheimer\u2019s Disease or Related Dementias (ADRD). However, the association of ADRD prevalence and NH quality is unclear. The objective of the current study is to understand the association of NH characteristics, including the proportion of ADRD residents, with the prevalence of NH complaints as an indicator of quality of care and quality of life. We merged data from the ASPEN Complaints/Incident Tracking System with national NH data from the Certification and Survey Provider Enhanced Reports, the Minimum Data Set, the Area Health Resource File, and zip-code level rural-urban codes in 2017. Three groups of NHs were created, including those whose proportion of residents with ADRD was in the top decile ) and those whose proportion of ADRD residents was in the lowest decile ). Bivariate results revealed high-ADRD NHs had higher percentages of Medicaid-paying residents, were less likely to be for-profit and chain-affiliated, had lower staffing hours and lower percentages of Black, Hispanic, and Asian residents. Using NHs in the middle deciles as reference, negative binomial regression models showed that having a low proportion of ADRD residents was significantly associated with higher numbers of total complaints (p<.001) and substantiated complaints (p<.001), whereas having a high proportion of ADRD residents was significantly associated with lower numbers of substantiated complaints (p=.001). The findings suggest the proportion of residents with ADRD in NHs is associated with quality, as measured by complaints. Policy implications of these findings will be discussed."} +{"text": "The present review summarizes the data on the cerebellar dopaminergic system including its involvement in associative and projective circuits. Furthermore, this study also briefly discusses the role of the cerebellar dopaminergic system in some neurologic and psychiatric disorders and suggests its potential involvement as a target in pharmacologic and non-pharmacologic treatments.In the central nervous system (CNS), dopamine (DA) is involved in motor and cognitive functions. Although the cerebellum is not been considered an elective dopaminergic region, studies attributed to it a critical role in dopamine deficit-related neurological and psychiatric disorders . Data on the cerebellar dopaminergic neuronal system are still lacking. Nevertheless, biochemical studies detected in the mammalians cerebellum high dopamine levels, while chemical neuroanatomy studies revealed the presence of midbrain dopaminergic afferents to the cerebellum as well as wide distribution of the dopaminergic receptor subtypes (DRD In the mammalian cerebellum, the neurotransmitter systems traditionally involved in the synaptic and extrasynaptic interactions may include the excitatory glutamatergic system and noradrenaline (NA); as a result, until now, the functional role of dopamine (DA) in the cerebellum has been widely disregarded.In studies using histofluorescence , mainly by means of the serotonergic receptors 5-HT2+ elevation , which can regulate the threshold of regenerative cycles of Ca2 adrenergic subtype receptor revealed a significant presence of selective dopamine transporter ligands (DAT-Ls) , the synaptic vesicles transporter of monoamine neurotransmitters such as DA, NA, 5-HT, and histamine (HIS) makes use of direct antisera against DA and of -DA in the contralateral caudate nucleus and decreasing such release in the ipsilateral caudate nucleus. Moreover, the electrical stimulation of the fastigial nucleus increased only the release of [3H]-DA in the ipsilateral caudate nucleus , Milardi et al. carried The interconnection studies conducted with invasive methods in non-human mammals, and the analyses carried out in humans by means of tractographic neuroimaging methods highlight the presence of relevant interconnections of the cerebellum with the traditional dopaminergic areas of the brain. Moreover, this may likely suggest double direct functional DA interactions between the cerebellar dopaminergic system described in this review and the traditional DA cell groups system of the CNS . In addiThough several studies suggested an involvement of the cerebellum in dopaminergic related neurologic and psychiatric disorders as PD has been found animal model, increases in the DA level and its metabolites in the anterior cerebellum and as well as a decrease in the caudate-putamen have been detected during PD remains unclear , and VMAT2 produced downstream changes in neuronal activity in the frontal cortex (Schutter et al., 8-A10; Ikai et al., The present review extensively evidenced the available morphological, chemical, and functional data on the existence of a cerebellar dopaminergic system in mammals including humans, which consist of extrinsic fibers which originate mainly from the midbrain cerebellar dopaminergic nuclei (AIn addition, this review evidenced the presence of direct dentate-SNpc and dentate-VTA interconnections (Milardi et al., Finally, we suggest that the cerebellar dopaminergic system and its interconnections may represent an ideal candidate for innovative non-invasive treatments such as electrical or magnetic stimulations in neurological and psychiatric disorders (Demirtas-Tatlidede et al., PF designed the study, performed the experiments and the analysis of the experimental data, and participated in the writing of the manuscript. PL and DG shared the study project and participated in the writing of the manuscript. GB, ABi, SBe, JB, SBi, and ABr participated in the writing of the manuscript. GG, MG, and GA performed the analysis of the experimental data, participated in the writing of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "With the increasing number of people with neurodegenerative disease world-wide, novel directions and paradigms are sought to understand disease-specific neuronal death and to offer novel therapeutic strategies to patients. The ability to transform a differentiated cell into a pluripotent state and to differentiate again to a defined target cell type , identifying the limitations of these approaches, including the variable genetic backgrounds, off-target effects of genetic corrections or targeting, the lacking cellular maturity, and the heterogeneity of differentiation techniques. This latter point is further detailed by Ghaffari et al. whom provide an impressive deep-dive into the different means of differentiation of specific neuronal and glial subtypes in detail, and compare and contrast IPSCs and direct conversion. Despite these challenges, the use of patient-derived tissue is strongly recommended in disease-modeling and preclinical ALS studies for drug discovery and development .In the context of ALS and Frontal Temporal Dementia (FTD), Guo et al. summarize the disease-specific phenotypes in patient-derived IPSC-derived neurons and the variability between reports . The importance of how a gene may cause disease and whether that mechanism remains present in iPSC-derived neurons is also of relevance in the context of the regulation of the gene SNCA, encoding for the protein alpha-synuclein, in Parkinson's Disease . Piper et al. describe in-depth the different ways SNCA may genetically cause disease, as well as how SCNA may be regulated. The authors stress the importance of the understanding of temporal and cell type-specific regulation of SNCA in disease, and in disease-models .With the epigenetic markers of cellular maturity lost when cells are converted to iPSCs , this Research Topic's contributions span the increased understanding of pathophysiology, testing of novel therapeutics, and the transplantation of cells as a potential therapeutic.Naphade et al.). They found that MMPs' endogenous inhibitors are decreased in HD cells and are elevated by TGFb treatment , illustrating a potential new direction for HD therapeutic strategies. Rindt et al. used a similar technique to assess the potential of the pre-mRNA repair of mutant Huntingtin, and also identified a beneficial response in HD-derived IPSC neural models . Subsequnetly, Masnata and Cicchetti describe the evidence for seeding of the Huntingtin protein in in vitro cultures of HD, including by IPSC disease modeling, and find sufficient evidence to suggest that this occurs, prompting the conclusion that in vivo assessment is now needed to further assess this (Masnata and Cicchetti). Al-Gharaibeh et al. transplanted IPSC-derived neural stem cells as a potential therapeutic into the striata of aged HD model mice (YAC128) and observed a striking protective effect on pathology and behavior in these animals , indicating the potential for neuronal replacement therapy in HD.Naphade et al. used patient-derived, isogenic, and control-corrected IPSCs to generate neural stem cells to assess the role of matrix metalloproteinases (MMPs) and their inhibitors in HD . They delineate what constitutes an iNeuron, describe the benefits of each stage of differentiation per neurological disease, discuss whether generating subtype-specific iNeurons is critical to the disease-related features of these cells, and subsequently explain the biomedical potential and limitations of the use of these cells . In addition, Omais et al. summarize an alternative potential cells to model neurodegenerative disease; adult neurogenesis in the olfactory bulb .To understand the potential and limitations of the use of non-primary neurons, Drouin-Ouellet et al. summarize the use of inducible neurons (iNeurons), which are derived from direct differentiation from somatic cells (Han et al. Open Science refers to the transparency of the research and is illustrated by Open Lab Notebooks Durcan, and the sharing of resources, including patient-derived stem cell lines (Gan-Or et al., To accelerate the discovery and development of novel therapeutic strategies for patients, the Montreal Neurological Institute has adopted an \u201cOpen Science\u201d model, as described by The author confirms being the sole contributor of this work and has approved it for publication.KS is employed by company Staats Life Sciences Consulting, LLC."} +{"text": "Ecological science focuses on the structure and function of the natural environment. However, the study of ecological environments primarily focuses on single-element research and lacks a comprehensive perspective. To examine ecological environmental trends on different scales, the present paper selected Yunnan Province as the study area. Chemical oxygen demand, rocky desertification, forest coverage, natural disaster data and spatial analysis methods were used to obtain the ecological environmental characteristics of each county and construct a comprehensive evaluation method of the ecological environment. The present paper revealed that the environmental capacity in Yunnan Province was at a moderate level, the ecological environment fragility was remarkable, the significance of the ecological environment was very high, natural disasters occurred frequently, and spatial differentiation between ecological environments was obvious. The province may be divided into three functional areas: the comprehensive-balanced area, the efficiency-dominated area and the environment-dominated area. Central Yunnan was a key development zone and the main area for the manufacturing and service industries, which were built as a modern industrial system in Yunnan Province. The ecological environment in northwestern Yunnan and southern Yunnan is of high significance, and this region was an ecological environment protection area that was important area for the construction of the modern agricultural system in Yunnan Province. To achieve sustainable development of the ecological environment, the spatial characteristics of the ecological environment must be determined at the county scale. The development of the world economy has exacerbated problems with the ecological environment since the 1990s. Scholars believe that the cost to the ecological environment of achieving economic growth is increasing, which has led to serious deterioration of the ecological environment that continues to intensify. The ecological environment has become a focus of political and academic concerns. Considerable ecological environment research was performed in the last 30 years, and this field has grown rapidly in the last 20 years. Research results are primarily published in journals, dissertations, conference papers and monographs. Research on the ecological environment is systemic and represents an important basis for the development of sustainable resource utilization, economic and social planning and ecological environment protection.Research on the ecological environment primarily focuses on analyses of the water environment, atmospheric environment, soil environment, engineering technology, environmental protection technology, policy guidance, and industry technical guidance and determining solutions to typical regional ecological environment issues . Many reIt is evident that recent developments in the geotechnologies of GIS and remote sensing have had a substantial impact on ecological environment research in the second decade of the 21st century and provided spatial data and associated information to enable further understanding of ecological systems . Remote Remote sensing and GIS have ensured their continuing input and significance in the field of ecological environments . SatelliResearch indicated significant spatiotemporal heterogeneity between economic development and the ecological environment . EcologiWater environmental capacity is defined as the maximum amount of pollutants that a water body can hold and still meet water quality standards , 59. WatResearch on the fragility of the ecological environment began in the 1960s. Research on ecological fragility has been a hot topic ever since 2000, and there were more empirical studies than theoretical studies. Studies in the early period used the city as the data unit. After 2000, a boom of theoretical reviews and initial signs of comprehensive research appeared, and the Grid GIS came into being. In response to requests from governments to show how the environment provides challenges and opportunities for human development, Global Environmental Outlook: Environment for Development gave the concept of vulnerability a central place. Vulnerability is the outcome of multiple stressors and multiple actors in multiple contexts that may occur at various spatial and time scales . Eco-envThe ecological importance showed spatial heterogeneities across and within the regions. Protected area zoning has become an effective tool in recent decades to divide regions into different zones with different protection and development strategies, and it has considerably contributed to biodiversity conservation and the harmonious coexistence of multiple activities . For theThe study of ecological risk assessment started in the 1970s. Ecological risk assessment is a powerful tool for quantifying ecological risk. Ecological risk assessment calculates the possible ecological damage arising from exposure to one or more pollution components . PresentResearch results on the ecological environment are not uncommon. However, this research is basically performed in a specific area and specific year. Therefore, the results reflect only the basic situation of the local area in that year and primarily focus on the study of a single element of the ecological environment. These studies are static. Therefore, the temporal and spatial changes in the ecological environment are difficult to identify. The present paper selected Yunnan Province as the research area to perform a spatial analysis of the ecological environment. The geographical environment of Yunnan Province is highly fragmented, and a single-element evaluation cannot provide a comprehensive explanation of the spatial differentiation characteristics of the environment. In light of the current status of research focusing on a single element of the ecological environment, such as environmental capacity, which can identify the water quality and water pollution status of an area, fragility reflects the sensitivity of the regional ecological environment to the outside world. Significance identifies locations for ecological environment protection, and hazards provide early warnings for earthquake prevention and disaster reduction. The present paper used Yunnan Province as the spatial scale. Focusing on ecological environment theory, this paper constructs a comprehensive evaluation system of the ecological environment and explores the spatial differentiation characteristics of the ecological environment in Yunnan Province to provide a spatial and practical basis for ecological environment research.This paper combines environmental capacity, fragility, significance, hazards and GIS and innovatively proposes a comprehensive research method. Section 2 shows the calculation process for the comprehensive research method. Section 3 presents the application of this method in the study of the ecological environment in Yunnan Province. Section 4 provides suggestions for the sustainable development of the ecological environment in Yunnan Province. Section 5 presents the conclusion.2, the area of Yunnan Province accounts for approximately 4.11% of the area of China, and mountain areas account for more than 84% of the total area of Yunnan. The total population was 48.3 million in 2018, which accounted for approximately 3.46% of the country. The population density was 121.8 people/km2, and the GDP was 1,788,112 million yuan, which accounted for approximately 2% of the GDP of China. Yunnan Province is located in the Chinese frontier area and has the second largest forest area in China. It is an important area for maintaining the stability of the overall ecological environment of China. The forests in this area are mostly distributed in the source area of the river system and the upper and middle reaches of the river basin. The quantity, quality and distribution of the forest are closely related to the ecological environment of a partial area or the entire river basin. The concentrated distribution areas of forests represent the last habitats of the main wild animal and plant resources in Yunnan. As a typical representative border region in China, the supporting capacity of the ecological environment has changed significantly with the development of the economy in mountainous areas, and regulating the deterioration of the ecological environment foundation has become increasingly difficult. Future prospects are not optimistic. Ecological environmental protection has significant benefits in the contemporary era and for future generations. As a source of large rivers in southwestern China, Yunnan Province should place greater emphasis on the ecological environment. Therefore, the maintenance function and social value of the ecological environment in Yunnan Province are far greater than the economic value of these environments. Environmental protection and development in this area must be considered from the perspective of ecological security of the entire river basin and country and the sustainable development of the social economy.As shown in Major Function-Oriented Zone Planning in Yunnan Province (http://www.yn.gov.cn/zwgk/). The soil erosion and rocky desertification data were obtained from the Report on the State of Yunnan Provincial Environment (http://sthjt.yn.gov.cn/hjzl/). The ecological protection data were obtained from the List of Natural Reserves in Yunnan Province (http://sthjt.yn.gov.cn/zrst/). The earthquake and debris flow data were obtained from the Yearbook of Disaster Reduction in Yunnan Province (http://yndzj.gov.cn/yndzj/sy1/index.html), Yunnan Earthquake Prevention and Disaster Reduction Bureau, Department of Ecology and Environment of Yunnan Province. Relevant data were standardized.Chemical oxygen demand (COD) and ammonia nitrogen capacity data for rivers were obtained from the Humans are the main body in the ecological environment, and other living creatures and nonliving objects are a complex of environmental elements . Traditional single-element assessment methods for the ecological environment focus more on analyzing the spatial and temporal distribution characteristics of a single element. Under diversified social development, ecological environment research has obvious comprehensive and holistic characteristics, and the interaction between basic elements of the ecological environment and their associated influence is becoming increasingly obvious. Combined with the objective requirements of developing scientific concepts, ecological environment research aims to overcome the limitations of traditional single-element assessment methods. This paper innovatively constructs a multielement comprehensive evaluation method and emphasizes the possibility of coordinating the balance of the internal system with the external environment.According to the special geographical environment of Yunnan Province, the following comprehensive evaluation system model of the ecological environment is proposed:L) = environmental capacity index (E)+fragility index (Y)+significance index (P)+hazard index (DH).Comprehensive evaluation index system of the ecological environment ((1) Water environmental capacity index system. Japanese scholars proposed the concept of environmental capacity, and the term is rarely used by European and American scholars. Chinese research on environmental capacity began in the 1970s. Environmental capacity is the maximum load of pollutants that the environmental system can accommodate within a certain time frame, and it is the upper limit of the carrying capacity according to the resource and environmental conditions at the development scale. This paper calculated the water environmental capacity using COD and ammonia nitrogen data for the river section at the county level in Yunnan.Ecod is the environmental capacity of COD (t/a), Ccod is the concentration of COD (mg/L), qcod is the amount of COD flowing into the river (t/a), En is the environmental capacity of ammonia nitrogen (t/a), Cn is the NH3-N concentration (mg/L), qn is the amount of NH3-N flow into the river (t/a), Q is the average water volume (t/a), and \u03b1 is the water resource utilization coefficient, which has a value of 0.4.(2) Fragility index system. Scholars determined that sensitivity and instability were the most important characteristics of ecologically fragile areas. The fragility of the ecological environment means that the ecological environment is affected by external interference and factors beyond its own adjustment range. Therefore, the ecological environment shows varying degrees of sensitivity to external interference. The ecological environmental fragility coefficient of Yunnan Province was calculated using the following formula:Y is the ecological environment fragility coefficient, Pi is the dimensionless value of the i-th index, and Wi is the weight value of the i-th index.(3) Significance index system. Ecological significance is an evaluation index for dividing restricted and prohibited development zones within the main functional zone of the province. Many scholars evaluated the importance of ecosystems by analyzing their composition and quantitative service value within a certain national space. Based on the area of nature reserves above the provincial level, this paper calculated the proportion of ecologically important areas in each county.Pi is the ratio of the assessment of regional biodiversity protection areas and ecologically important areas, Ni is the area of an important ecological environment, and Ti is the total area of the region.(4) Hazard index system. The single-element evaluation of natural disaster risk is thorough, and the method of risk assessment shifted from qualitative analysis to comprehensive quantitative evaluations that combine natural and social science. This paper used Graham\u2019s method to evaluate natural disasters.Di is the single-element risk index of natural disasters, Li is the average probability of occurrence of disasters, Ei is the time of recipient affected by the disasters, and Ci is the possible loss caused by disasters.\u03bb is the disaster index weight, and Di is the disaster risk index.(5) Comprehensive ecological environment evaluation index system. Using 124 counties as the basic geographical unit, a comprehensive value measurement algorithm was adopted after standardizing the water environmental capacity index (E), fragility index (Y), importance index (P) and hazard index (DH). The score range of each indicator was no more than 10.Ki is the index weight, and Ai is the index score.https://desktop.arcgis.com/zh-cn/) data show that the water environmental capacity in Yunnan may be divided into 5 levels, which are shown in Based on the minimum value of the remaining amounts of COD and NH3-N in the river section of each county in Yunnan, the results of the study showed that the ecological environment capacity was moderate in Yunnan Province, with 91 counties above the moderate level and 33 counties below the low level. Using the natural classification method, the results using Arcview Hazardous area: Gengma, Midu, Yao\u2019an and Ludian, with an area of 8,730 km2, which accounted for 2.24% of the total area. Earthquake disasters and landslides and debris flows occurred in Gengma and Midu. The earthquake disasters in Yao\u2019an and Ludian were very obvious in recent years. (3) Generally hazardous area: Yuxi, Chuxiong, Zhaotong(except Ludian), Honghe, Pu\u2019er, Baoshan, Lincang, Dehong, Dali, Lijiang and partial areas of Diqing, covering an area of 142,397 km2, which accounted for approximately 36.51% of the total area. Earthquakes and debris flows occur in Zhaotong. Landslides and debris flows are seen frequently in Honghe, and earthquake disasters often occur in western Yunnan Province.As seen in As shown in Comprehensive-balanced area: Baoshan, Xishuangbanna, Qujing, Nujiang, Pu\u2019er and Lincang. The natural geographical environment in these areas was good, and the ecological benefits and the environmental quality were relatively balanced. With a water environmental capacity of more than 6500 (t/a), Nujiang, Pu\u2019er and Lincang are rich in water resources and have a high water environment capacity. Baoshan and Xishuangbanna have abundant biodiversity and higher stability of surface vegetation, and the ecologically important regions account for 21.04% and 13.62% of the whole area, respectively, which indicates that these cities have the highest ecological significance.Efficiency-dominated area: distributed in the central Yunnan urban agglomerations, including Kunming, Qujing, Yuxi and Chuxiong. This type of area had the most developed economy, high resource utilization efficiency, relatively high technical level, good cultural environment, and ecological benefits that exceeded the environmental quality. Economic development created pressure on the ecological environment. Kunming (with a GDP of 520.69 billion yuan), Qu Jing (with a GDP of 201.34 billion yuan), Yuxi (with a GDP of 149.30 billion yuan) and Chuxiong (with a GDP of 102.43 billion yuan) are economically developed regions in Yunnan Province, and the economies of these cities ranked first, second, fourth and sixth in Yunnan in 2018, respectively. Kunming, Qujing, Yuxi and Chuxiong are neighboring areas, and these cities form the central Yunnan urban agglomeration. The GDP of the central Yunnan urban agglomeration accounted for 54.46% of the GDP of Yunnan Province, which made it the economic growth pole of Southwest China. The ecologies of Kunming, Qujing, Yuxi and Chuxiong showed limited fragility and strong resistance to external interference. The rapid development of urbanization and industrialization led to a backward environmental quality. The water environmental capacities of Chuxiong and Yuxi were relatively low. The water environment capacity of the Dianchi Lake Basin in Kunming is extremely low. Therefore, maintaining ecological benefits and improving environmental quality are key points for constructing ecological civilizations in Kunming, Qujing, Yuxi and Chuxiong.Environmentally dominated areas primarily included Wenshan, Dehong, Lijiang, Diqing, Honghe, Dali and Zhaotong. With good natural environmental quality, the sustainable development of these cities was dominated by environmental quality, moderate natural resource utilization rates, and low ecological benefits. The energy consumption per 10,000 yuan of GDP in these areas was not high, the proportion of the secondary industry was low, the proportion of the primary and tertiary industries was large, the GDP per capita was low, and the utilization rate of ecological resources was insufficient. These areas have many biodiversity-protected areas, and the ecological environment was important. The water environmental capacity was greater than 3500 t/a, the ecology was moderately fragile, and vegetation recovery was difficult, as shown in From the perspective of the overall ecological environment, the ecological environment foundation of Yunnan Province was relatively good. However, due to the complexity of the mountainous geographical environment, challenges remain in improving the ecological environment of certain areas. An evaluation of the four indicators of environmental capacity, ecological fragility, ecological importance and natural disaster hazard indicated obvious spatial differences, with the ecological environment in the northwest and southwest areas of Yunnan Province being relatively good and the northeast and central areas of Yunnan relatively weak.Ecological science is the study of the structure and function of the natural environment. The present paper used the relevant principles of ecology to address the current situation of single-element research on the ecological environment, constructed a comprehensive evaluation method of the ecological environment from the perspective of system theory, focused on the prefectural scale, and examined the ecological environment and spatial differentiation characteristics of Yunnan Province. This research has certain theoretical significance and provides a theoretical perspective and practical basis for the construction of ecological civilization space in Yunnan Province. Based on the overall ecological environment, the ecological environment foundation of Yunnan Province was relatively good. However, the geographical environments of mountainous areas are very complex. The environmental capacity, ecological environmental fragility, ecological environmental importance and natural disaster hazards indicators were evaluated, and we found obvious spatial differences, with the ecological environment in the northwestern and southwestern regions of Yunnan being relatively good and that the northeastern and central regions of Yunnan Province being relatively weak.This study found that Yunnan had a moderate environmental capacity, a relatively fragile ecological environment, high ecological environment importance, and frequent natural disasters. The ecological environment had obvious spatial differences, which were divided into three functional areas: comprehensive-balanced area, efficiency-dominated area, and environment-dominated area. Ecological environmental research provides an important basis for the formulation of sustainable economic and social development plans and ecological environmental protection countermeasures. Although the ecological environment was mildly fragile in central Yunnan, this area is a key development zone and the main area for the manufacturing and service industries, which were built as a modern industrial system in Yunnan Province. The ecological environment in northwestern and southern Yunnan is of high significance, and this region is an ecological environment protection area and an important area for the construction of the modern agricultural system in Yunnan Province. According to the environmental capacity, the water quality of Shangri-La, Jingdong, Yongshan, Qiaojia, Tengchong, Baoshan, Dali, Lincang and Pu\u2019er was good and the water pollution in Kunming Dianchi Lake was serious. According to the environmental fragility analysis, the ecological environments of Deqin, Shangri-La, Weixi, Weixin, Zhenkang, Gengma, Mojiang, Honghe, Hekou, Maguan, Wenshan, Malipo, Xichou, Qiubei, Guangnan and Luoping were most obviously affected by external influences. According to the significance analysis, the key areas of ecological environment protection in Yunnan Province included Deqin, Shangri-La, Weixi, Gongshan, Ninglang, Yuanmou, Tengchong, Zhenkang, Yongde, Cangyuan, Jinghong, Mengla, Honghe, Hekou, Luquan, and Funing. These locations had the most ecological environmental protection zones. The hazard analysis identified areas with frequent natural disasters and hidden hazards in Yunnan Province. For example, mudslides were more likely to occur in Dongchuan and earthquakes were more likely to occur in Ludian and Yao\u2019an. Ludian experienced an earthquake in 2014, and Yao\u2019an experienced an earthquake in 2009. Hazard research results have important reference value as disaster warnings.As a hot research field, the ecological environment has obvious comprehensive and systematic characteristics. A comprehensive evaluation system for the ecological environment was constructed as an exploratory research method, and it showed regional characteristics. Particular emphasis should be placed on the selection of indicators for different research spaces in the future.A number of methods are used in environment-dominated areas, including a new round of ecological civilization construction plans, the construction and improvement of a dynamic monitoring network for vegetation coverage, strict implementation of forestland reserves, promotion of forest planting and grassland planting, and scientific development of aboveground and belowground spaces to realize potential land uses and increase surface vegetation coverage. Wenshan, Dehong, Lijiang, Diqing, Honghe, Dali and Zhaotong could gradually improve the level of ecological benefits by enhancing the level of technology and management and increasing the utilization rate of ecological resources.From the perspective of ecological environmental protection, the comprehensive-balanced area could set goals for sustainable economic and social development. Qujing should actively develop its light industry and service industry to prevent hidden dangers caused by the rapid development of highly energy-consuming industries. Baoshan, Xishuangbanna, Nujiang, Pu\u2019er and Lincang could earnestly implement the target responsibility system and accountability system of environmental protection and actively perform paid use of pollution discharge rights and trading pilots. This work would emphasize that the development and protection of the comprehensive-balanced area should work together to improve environmental quality and capacity.The resource-environment dependence path of economic development in efficiency-dominated areas is obvious, and the carrying capacity of the ecological environment hinders the speed of economic and social development. By promoting economic and social development transformation through \"reform\", Kunming, Yuxi, and Chuxiong are capable of breaking through the restriction of the ecological environment on economic and social development to change the traditional resource-dependent development model and transfer the mode of production to promote economic transition and realize the transformation of economic and social development and the ecological environment from \"investment\" to \"reform\".The comprehensive-balanced area, efficiency-dominated area and environment-dominated area should thoroughly implement sustainable development, fully promote law-based governance of the ecological environment, adhere to promoting environmental development, strengthen efforts to promote the ecological environment legal system, and create a good social atmosphere for protecting the ecological environment. The monitoring function of grassroots environmental protection organizations should be supported to provide guarantees for the sustainable utilization of the ecological environment.S1 Data(RAR)Click here for additional data file."} +{"text": "Over the past 60 years, evidence has accumulated on the fundamental role of supportive social relationships in individual health and longevity. This paper first summarizes the results of 23 meta-analyses published between 1994 and 2021, which include 1,187 longitudinal and cross-sectional studies with more than 1,458 million participants. The effect sizes reported in these meta-analyses are highly consistent with regard to the predicted link between social support and reduced disease and mortality; the meta-analyses also highlight various theoretical and methodological issues concerning the multi-dimensionality of the social support concept and its measurements, and the need to control potential confounding and moderator variables. This is followed by an analysis of the experimental evidence from laboratory studies on psychobiological mechanisms that may explain the effect of social support on health and longevity. The stress-buffering hypothesis is examined and extended to incorporate recent findings on the inhibitory effect of social support figures on fear learning and defensive reactions alongside evidence on the effect of social support on brain networks that down-regulate the autonomic nervous system, HPA axis, and immune system. Finally, the paper discusses the findings in the context of three emerging research areas that are helping to advance and consolidate the relevance of social factors for human health and longevity: (a) convergent evidence on the effects of social support and adversity in other social mammals, (b) longitudinal studies on the impact of social support and adversity across each stage of the human lifespan, and (c) studies that extend the social support framework from individual to community and societal levels, drawing implications for large-scale intervention policies to promote the culture of social support. Evolutionary biologists did not anticipate the continuing rise in life expectancy in high-income countries they are cared for and loved, (b) they are esteemed and valued, and/or (c) they belong to a network of communication and mutual obligation. Both Cobb and Cassel considered that social support protects people by buffering the health consequences of life stresses.In 1976, two seminal reviews were published on the concept of social support and its effects on health and mortality .Two electronic databases (Scopus and Web of Science) were searched for meta-analysis studies using the following combination of terms: and . The electronic searches were restricted to studies published in English with adolescent or adult human participants. They had to include at least one measure of social support as independent variable and at least one outcome measure of longevity/mortality/health/disease as dependent variable. Additional complementary search strategies were used by checking cross-references between the meta-analyses and relevant systematic reviews.A total of 23 meta-analyses published between 1994 and 2021 complied with the inclusion criteria. They were checked to ensure that they followed the PRISMA protocol and that the final list of primary studies across the 23 meta-analyses did not include duplicate studies or participants. The 23 meta-analyses covered 1,187 non-duplicate primary studies with more than 1,478 million participants. Six meta-analyses used correlation as effect size measure, and the remaining 17 used proportion ratios . In the six meta-analyses with effect sizes based on correlation see , the outThe 23 meta-analyses displayed in the three tables obtained highly consistent results, with significant effect sizes confirming the association between social support and individual health/longevity (regardless of the type of outcome measure). However, as also observed in these tables, the strength of the association depends on numerous factors, including type of effect size, type of outcome, type of social support, and type of moderator variable. In this section, the results are discussed in relation to the type of effect size and type of outcome. The impact of the social support measures and moderator variables are discussed in the following two sections.strong, consistently positive relationships between social support and health outcome measures. They stressed the need for further refinement of social support measures in future research. It is also noteworthy that the most recently published meta-analysis also used correlation as effect size measure across five continents, used functional and structural measures of social support, analyzed multiple moderator variables, and obtained markedly higher effect sizes .The six meta-analyses in The 10 meta-analyses in post-partum depression , and the heterogeneity of effect sizes for primary studies, weakening, or extinguishing the strength of a true association. However, both problems can be addressed and evaluated by applying meta-analysis methodology.Examination of the social support measures listed in the three tables illustrates the conceptual and methodological diversity described in the Introduction. Twenty-six different social support measures are reported, including: quantitative and qualitative social support; received and perceived social support; enacted social support; network social support; material, informational, and emotional social support; social engagement; and social integration. Only two of these meta-analyses used the recommended functional-structural classification , six structural measures , and a combination of both types of measure. Among the structural measures, the complex measure of social integration was the most highly predictive of the mortality risk, with an effect size of 1.91, whereas living alone was the least predictive, with an effect size of 1.19. Among the functional measures, perceived social support and loneliness were the most predictive measures, with effect sizes of 1.35 and 1.45, respectively, whereas received social support did not even reach statistical significance.The relevance of perceived social support as a predictor of health and longevity is confirmed in five additional meta-analyses in In general, these data show that the measures that best reflect the multidimensionality of the social support concept are the most accurate predictors of a reduced risk of disease and mortality.Correlational studies are based on a non-randomized selection of participants. Evidently, people cannot be randomly assigned to groups for social isolation or divorce. In both cross-sectional and longitudinal studies, the non-randomized selection of participants involves the presence of third variables that can make the association spurious. It is well-known that age, socio-economic status, or physical and mental health at the initial evaluation can influence health status and longevity. Age is by far the most important risk factor for many chronic diseases and disabilities or substantive . In meta-analyses, the influence of these variables is evaluated and controlled by means of sub-group analysis and meta-regression. Overall effect sizes are usually adjusted for the influence of these variables (covariates) or reported separately for specific sub-groups of interest. The evidence provided by the 23 meta-analyses remains consistent after controlling for confounders and mediators, thereby conferring convergent validity to the predictive role played by supportive social relationships in health and longevity. However, while confounding variables may reverse the causal pathway between social support and longevity, and moderator variables can modify its strength, other variables affecting the causal pathway play a different role acting as mediators between social support and outcome. This is the case of psychobiological mechanisms and, in particular, of the variables involved in dampening the stress response according to the stress-buffering hypothesis.Multiple pathways may link social support with health and longevity. Informational and instrumental support, including financial and material assistance, can help individuals to cope with health problems. Likewise, integration within a supportive social network can prevent health problems by providing positive health role models and reinforcing healthy behaviors , and ending in autonomic, endocrine, and motor effectors whose function is to protect the organism from the threat (fight-or-flight response). The result is a state of maintained or intermittent activation of physiological and endocrine responses that can, over the long term, compromise the normal functioning of the organs involved and increase the risk of disease and mortality. Two neurobiological subsystems are especially relevant in the above sequence: the hypothalamic-pituitary-adrenocortical (HPA) axis and the sympathetic-adreno-medullar (SAM) axis. Activation of both axes in response to a stressor increases the circulation of glucocorticoids (cortisol) and catecholamines in the bloodstream to allow energy to be released for the fight-or-flight response, even after the stressor has disappeared.According to the stress-buffering hypothesis, social support is beneficial for health and longevity because the presence of a bond with social partners attenuates or eliminates the adverse consequences of prolonged HPA and SAM activation. This hypothesis was first formulated by Bovard , 1962 anExperimental investigation of the stress-buffering hypothesis in humans has been particularly intensive over the past two decades. The experimental tasks have usually employed laboratory-based stressors, such as public speech, threat of mild electric shock, or exposure to painful stimuli. In children, the tasks may consist in natural stressors such as vaccination injections or exposure to clowns or toys and comparing with control pictures . The first three studies used the standard startle probe paradigm to confirm that attachment figures elicit a genuine positive emotional response that is not confounded by familiarity or undifferentiated emotional arousal in comparison to faces of strangers or known people or neutral objects. The results obtained demonstrate that in comparison to faces of strangers and neutral objects, social support faces, either presented alone or paired with control faces, act as safety signals with the following capacities: (a) to inhibit their own fear conditioning and fear of social rejection (the other) as the two main ancestral fears. Likewise, the main safety signals with capacity to inhibit fear and defense reactions are also other people: attachment and loved figures.The brain structures at the core of the defense motivational system are two subcortical areas within the temporal lobes: the amygdala and the bed nucleus of stria terminalis . Knowledge of these structures derives from animal and human studies on defense reactions and fear conditioning LeDoux, . The amyProlonged activation of the defense system leads to a cardiovascular and autonomic imbalance in which the sympathetic tone is high and the parasympathetic tone is low, a condition associated with increased morbidity and mortality , which stimulates production of adrenocorticotropic hormone (ACTH) by the anterior pituitary and its release into the general circulation. The ACTH then stimulates the production and release of glucocorticoids (cortisol) by the adrenal cortex, whose main function is the mobilization of energy to cope with environmental challenges. Brain control of the HPA axis uses the same structures as those involved in cortical and subcortical regulation of the cardiovascular system: orbitofrontal and medial prefrontal cortex, anterior cingulate, amygdala, and bed nucleus of stria terminalis . The results highlighted the emotional component of social support, principally from family and friends, which is identified as love. Love is embedded in the first and most cited definition of social support proposed in 1976: on Cobb, , describon Cobb, . ImportaNevertheless, research on social support and longevity needs to incorporate recent developments within the field that are helping to expand evidence on the link between social support and health/longevity, to advance knowledge on its underlying neurobiological mechanisms, and to translate this knowledge into the design and implementation of large scale preventive public health interventions that increase the culture of social support. These new developments derive from three different perspectives: the evolutionary, the life span, and the systemic.Mama's last hug (de Waal, Recent comparative studies between human and non-human social mammals have demonstrated that measures of social support and integration in non-human social mammals are strong predictors of health and survival, as observed in humans, with odds ratios between 1.23 and 1.72 (Snyder-Mackler et al., de Waal, , primateThe developmental approach to the stress buffering hypothesis adopted by Gunnar and Hostinar represenThe systemic approach to social support and longevity, recently defended by Holt-Lunstad et al. , 2015 anLoneliness, the perception of social isolation, is reaching epidemic proportions among the elderly in developed countries and is expected to increase further over the next few decades Cigna, . Social The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "This study examined the association between age and preparedness for the continuation of COVID-19. The moderation effects of three types of social support, namely, emotional, financial, and instrumental assistance were also tested. Using a sample of 443 adults in Dallas county which has the most confirmed cases in Texas, results of multiple linear regressions showed that compared to those aged between 18 and 64, older adults aged 65 and reported better preparedness for the continuation of COVID-19. Receiving emotional, financial, and instrumental assistance were respectively more important for older people to get better prepared than for younger adults, which is consistent with the socioemotional selectivity theory. Our findings directed attention to the strengths and resilience of older adults during COVID-19 from a life course perspective and highlighted the importance of social support and social relationship in their post-disaster recovery and ongoing preparedness."} +{"text": "Increasing attention is growing towards advanced multiscale metamaterials and nanostructures, due to recent developments in nanoscience and nanotechnology. Smart nanoscale systems with unconventional features are attractive subjects for many applications, such as electronic, optical and magnetic devices, involved in many areas such as aerospace and mechanical engineering, medicine, biology and sound and heat control. The modeling, characterization and synthesis of innovative materials and structures are, thus, needed to explore new challenging scientific applications.The Special Issue (SI) Multiscale Innovative Materials and Structures provides new insights concerning the modeling and realization of advanced nano-reinforced materials, carbon nanotube-based systems, tensegrity structures, periodic lattices and multiscale composites. Theoretical and experimental outcomes collected in the SI provide original and significant contributions in the field of nano-composites, nano-systems and nano-devices.The first work of the SI deals wiIt is our hope that the works collected in Multiscale Innovative Materials and Structures will provide scientific community with novel and significant contributions to the topic."} +{"text": "Chest X-rays (CXR) and computed tomography (CT) are the main medical imaging modalities used against the increased worldwide spread of the 2019 coronavirus disease (COVID-19) epidemic. Machine learning (ML) and artificial intelligence (AI) technology, based on medical imaging fully extracting and utilizing the hidden information in massive medical imaging data, have been used in COVID-19 research of disease diagnosis and classification, treatment decision-making, efficacy evaluation, and prognosis prediction. This review article describes the extensive research of medical image-based ML and AI methods in preventing and controlling COVID-19, and summarizes their characteristics, differences, and significance in terms of application direction, image collection, and algorithm improvement, from the perspective of radiologists. The limitations and challenges faced by these systems and technologies, such as generalization and robustness, are discussed to indicate future research directions. The rapid spread of the COVID-19 worldwide developed into a global pandemic, leading to a large-scale medical system burden and economic crisis. The detection and diagnosis of COVID-19 rely on the positive results of the reverse transcription-polymerase chain reaction (RT-PCR); however, false-negative results may occur due to the influence of various factors such as low viral load . HoweverHerein, the application, existing problems, and possible solution of machine learning and artificial intelligence systems based on medical images are introduced, such as diagnosis and classification, treatment decision-making, curative effect evaluation, prognosis prediction, and other relevant aspects for patients affected by COVID-19. By conducting a rapid review of published studies and the existing experience of DL and AI in COVID-19 radiological examinations, the aim of this article is to evaluate the feasibility and the effectiveness of available COVID-19 diagnostic tools, which may be helpful to develop better intelligent models by medical experts and technical researchers.A combination of three group of keywords including disease, imaging examinations, together with algorithm technology was used to search for articles in four databases: PubMed, Web of Scicence, Elsevier/SD, and IEEE; all types of research were evaluated, including case reports, original research, clinical guidelines, and systematic reviews. Through reading abstracts and reviewing the references of included studies, the published studies were finally screened and classified. We set the criteria for inclusion and classification. Only research written in English was included; preprints that were not peer-reviewed were excluded. The application and effectiveness of these systems were discussed from the perspective of radiologists. Although the types and development of algorithms were not the focus of this review, they were not excluded Chest X-ray and CT are widely used to diagnose and screen COVID-19 patients from suspected patients and make differential diagnosis from patients with other lung diseases ,7,8. QuaAlthough CT was recommended in the diagnosis of COVID-19 at different stages of the disease in mainland China, the British Society of Thoracic Imaging and the American College of Radiology currently recommend CXR as the first line of COVID-19 imaging ,16. As aDL and AI systems can extract massive amounts of valuable clinical decision information by analyzing medical images and clinical data from COVID-19 patients, thus revealing the great potential for the use of chest X-rays and CT for quantifying the lesions and assessing progression and related medical indicators. Zhang et al. used quaA large number of clinical parameters and imaging data, which are generated during the diagnosis and treatment of COVID-19 patients, can be compared and correlated through DL and AI systems. Zhang et al. selectedThe effectiveness of DL and AI systems in diagnosing COVID-19 is a basic condition for clinical application and is often compared with the diagnostic performance of radiologists. Murphy et al. used datIt can be seen from these studies that the detection and diagnosis performance of AI models based on COVID-19 CXR or CT images is similar to that of experienced radiologists and may help improve the reliability of physicians\u2019 diagnoses, especially for junior radiologists and nonradiologists.Objectively quantifying the degree of disease by the percentage of COVID-19 lesions in the lung parenchyma is currently the most important application of AI in the evaluation of the COVID-19 patient, which can contribute to evaluating and monitoring the progression of the disease. In order to further analyze the clinical and radiological characteristics that lead to critical illness, it is necessary to develop artificial-intelligence-assisted models to estimate clinical prognosis. Shan et al. used theAlthough numerous studies report the efficacy evaluation and prognosis prediction of COVID-19 based on imaging, there are relatively few studies on imaging risk factors for poor prognosis of COVID-19 ,34. ReseDL and AI systems can be used to monitor and quantify disease progression and understand the time evolution characteristics of COVID-19 lesions, reducing the subjectivity of radiologists in comparing chest CT images before and after treatment. They are also conducive to accurate treatment. Although there are currently many studies focusing on the evaluation of the radiology and clinical physiological outcomes of recovered COVID-19 patients ,36, therMany biological data have been accumulated with the spread of the COVID-19 epidemic and numerous infected patients generating epidemic contact history, clinical data, laboratory examinations, and imaging data. Researchers have constructed various multimodal DL and AI systems from different angles to fully mine the information contained therein, and then transform the data into reliable and referable information in the diagnosis and treatment of COVID-19 . Li et aDue to the lack of standard requirements for datasets, there are significant differences in the dataset sources used by different studies and the image scanning conditions of each medical center or database. Researchers studied the performance of various algorithms under different data sources. Shiri et al. used ultThe most common use of deep learning and artificial intelligence based on medical images is for diagnosing and evaluating COVID-19 patients. In addition to using medical image data , DL and After the COVID-19 outbreak, data-driven DL and AI research made a breakthrough in the field of medical imaging. These studies all claimed that these algorithms could diagnose or predict COVID-19 based on CXR and CT images. Although some medical centers or medical imaging alliances have disclosed some COVID-19 dataset resources Table 2Table 2, With increasing research on the application of AI systems in COVID-19, there are increasingly more studies using similar methods.Partial code access of COVID-19 DL and AI models based on radiology images were listed in The construction of a highly standardized database is essential to improve the accuracy and generalization of the model. In addition, the development of DL and AI algorithms greatly depend on the close communication between engineer, radiologist, and clinicians, and strengthened multidisciplinary communication and cross-complementation. The establishment of multilabel and/or hierarchical classification technology evaluation and benchmark solutions will greatly promote the prevention and control of infectious diseases.Since the outbreak of COVID-19, numerous researchers worldwide have extensively studied how to quickly and correctly diagnose COVID-19 and evaluate and control the condition. Machine learning and artificial intelligence with high reliability and huge potential in various applications were adopted by numerous healthcare providers. From multiple angles, this article introduced studies that explored DL and AI technologies based on medical imaging data so as to solve the troubles and challenges encountered in reality and directly point out the limitations of current studies. Overcoming these challenges may lead to significant progress in the use of artificial intelligence technology to combat COVID-19 and future epidemics."} +{"text": "Caregivers with diverse backgrounds make up an important part of the landscape of caregiving in the US. Their unique experiences have been traditionally under-researched in the field of social sciences and underrecognized by society. To further understand the impact of race, ethnicity, class, gender and sexuality onto caregiving, the National Alliance for Caregiving (NAC) and the AARP Public Policy Institute commissioned an in-depth analysis of the dataset collected from the Caregiving in the US 2020 study, which segments populations based on ethnic and sexual identity, geographic location, and income level. Utilizing survey interviews with 1,392 caregivers in the US, this study found differences amongst the African-American, Latinx, and Asian American-Pacific Islander populations in relation to age, time spent caregiving, ADL/IADLs, caregiving strain and intensity, receipt of formal and informal support, and financial impact. In consideration of the distinct challenges presented by diverse caregiving throughout the lifespan, this presentation will also feature results from a 2020-2021 Diverse Elders Coalition and NAC commissioned study on the unmet caregiving needs in diverse communities. 11 virtual listening sessions were held with 400 caregivers of color, including American Indian/Alaska Native caregivers, and LGBTQ caregivers across the nation. Presentation attendees can expect to learn new insights into the experiences of diverse caregivers, while also gaining a fresh understanding of informal and formal support preferences with a multicultural lens. Finally, this presentation will provide recommendations to further prioritize the needs of historically marginalized caregivers in policy and practice."} +{"text": "Noncommunicable diseases and injuries (NCDIs) are the leading causes of premature mortality globally. Ethiopia is experiencing a rapid increase in NCDI burden. The Ethiopia NCDI Commission aimed to determine the burden of NCDIs, prioritize health sector interventions for NCDIs and estimate the cost and available fiscal-space for NCDI interventions.We retrieved data on NCDI disease burden and concomitant risk factors from the Global Burden of Disease (GBD) Study, complemented by systematic review of published literature from Ethiopia. Cost-effective interventions were identified through a structured priority-setting process and costed using the One Health tool. We conducted fiscal-space analysis to identify an affordable package of NCDI services in Ethiopia.We find that there is a large and diverse NCDI disease burden and their risk factors such as hypertension and diabetes (these conditions are NCDIs themselves and could be risk factors to other NCDIs), including less common but more severe NCDIs such as rheumatic heart disease and cancers in women. Mental, neurological, chronic respiratory and surgical conditions also contribute to a substantial proportion of NCDI disease burden in Ethiopia. Among an initial list of 235 interventions, the commission recommended 90 top-priority NCDI interventions for implementation. The additional annual cost for scaling up of these interventions was estimated at US$550m (about US$4.7 per capita).A targeted investment in cost-effective interventions could result in substantial reduction in premature mortality and may be within the projected fiscal space of Ethiopia. Innovative financing mechanisms, multi-sectoral governance, regional implementation, and an integrated service delivery approach mainly using primary health care are required to achieve these goals. Noncommunicable diseases (NCDs) are the leading cause of premature mortality in lower- and middle-income countries (LMICs), accounting for 60% of deaths . InjurieNoncommunicable diseases and injuries (NCDIs) have become a major public-health problem in Ethiopia, resulting in 44% of total annual mortality . EthiopiSDG 3.4 requires countries to commit to reducing premature mortality from NCDs by a third, through prevention and treatment .Despite commitment pledged by countries in the 2011 UN political declaration on the Prevention and Control of NCDs (UN high-level meeting), progress to combat NCDs has so far been slow, particularly in regards to populations living in extreme poverty ,11. To cNCDI disease burden: We retrieved data on NCDI disease burden and the concomitant risk factors from the Global Burden of Disease (GBD) Study, complemented by a systematic review of published literature from Ethiopia. We searched the following databases using a mix of search terms: Global Burden of Disease/IHME, PubMed, Cochrane, HINARI, Google Scholar, EMBASE, The World Bank, WHO Regional Databases and local journals, including grey literature. We included articles published from 1990 to December 2017 that had clear objectives and methodologies and addressed the major NCDIs and their risk factors. We summarised the evidence for each NCD, injury and risk factor. Where several prevalence studies of similar populations were found, we used a weighted average. In this review, community- and institution-based studies and some hospital-based studies were used to show population prevalence, whilst mortality studies and hospitalisation studies were used to indicate disease severity and outcomes.Priority setting process: Following identification of the major NCDIs in Ethiopia, interventions were selected and prioritised in a four-step process. Firstly, priority-relevant evidence from national and international studies was collected, critically reviewed, and supplemented with expert judgements. Secondly, this evidence, along with the WHO principles, was used to prioritise interventions, ranking them in three categories , not targeting the worse off in health and low FRP.entions) . The WHOentions) . Thirdlyentions) . Fourth,Estimation of costs and fiscal space: Cost by intervention was estimated using OneHealth Tool version 4.5 using the software's default data on cost of drugs and supplies and the default population model for Ethiopia Study, complemented by a systematic review of published literature from Ethiopia. The GBD data showed that in 2017 44.4% of total mortality in Ethiopia was due to NCDIs .Our review of studies of common NCDs and their risk factors in Ethiopia revealed a large and diverse burden that varies according to socioeconomic factors and 2. TThe burden of common NCDIs such as hypertension and diabetes (3.2%\u20138% of the adult population) was high, as was the burden of less common but more severe NCDIs such as rheumatic heart disease and cancers in women ,43\u201363. HCancer, especially breast and cervical cancer, is a staggering public-health problem in Ethiopia. There were an estimated 65,000 cancer cases in Ethiopia in 2015, based on projections from the population-based cancer registry in Addis Ababa, and it was estimated that two-thirds of the cancers occurred in women . These fMental, neurological and substance-use disorders in Ethiopia account for 25.6% of all years lived with disability (YLD) in 2017, affecting nearly 30% of the Ethiopian population at any given time \u201371. In aFurthermore, injuries \u2014 particularly road traffic accidents, falls and interpersonal violence - accounted for 8% of total DALYs lost in Ethiopia in 2017 \u201375. The Economic impact of NCDIs: For individuals and their households, NCDs can have devastating long-term economic consequences. A systematic review of the economic effect of NCDs on households in LMICs showed that NCDs placed a substantial economic burden on patients and their families in all socioeconomic strata, particularly in the poorest sector of the population. Direct medical expenses for drugs, diagnostics, outpatient visits and hospitalisation were the major components of out-of-pocket (OOP) costs (P) costs . The cosP) costs . A lack P) costs .There is a shortage of resources for health care in Ethiopia, with a per capita expenditure of US$33 in 2016/2017 . ReliancPriority setting for essential interventions for NCDIs: A task faced by many LMICs is identification of high-priority interventions for NCDIs and fair prioritisation of introduction or scale-up of these interventions. The gap between health requirements for NCDIs and economically feasible provision is a substantial challenge for LMICs, and likewise for Ethiopia. Health care for chronic diseases has largely been neglected, in comparison with interventions that prevent, diagnose and treat malnutrition, infection and maternal and childhood diseases.After establishing the major NCDI conditions in Ethiopia, the Commission identified an initial list of 235 potential health-sector interventions for implementation or scaleup in the Ethiopia health system. The commission used the WHO Consultative group on Equity and Universal Health recommendations to prioritize NCDI interventions: cost-effectiveness, fair distribution (priority to the worse-off) and FRP . EvidencAdditionally, multi-sectoral interventions designed to reduce population-level behavioural and environmental risk factors are available in the commission's report . Many ofEstimated health impact of NCDI interventions: The Commission made a conservative estimate that, if fully implemented, the Highest Priority Package for NCDI services could raise life expectancy at birth from 64.4 to 65.2 (i.e. by 0.8 years), and avert approximately 41,000 premature deaths by 2030 , the Commission estimated that by the end of the first five-year period (2023), there will be US$2.40 extra per capita for NCDI services from the government budget. However, in a best-case scenario of GDP growth of 7%, total government health expenditures of 6% of the GDP and NCDI expenditure 30% of the total health expenditure, there would be an extra US$4.50 for the toppriority package of NCDI services. The potential fiscal space per capita in this best-case scenario approximates the estimated per capita cost of US$4.70 (needed in the year 2023) for the recommended top-priority NCDI services. The three variants for possible targets and budget expansion paths for total (THE) and government health expenditures (GHE) that would be compatible with a commitment to move towards UHC are illustrated in Recommendations from the Ethiopia NCDI commission: Ethiopia is facing a substantial burden from NCDIs such as ischaemic heart disease, stroke, diabetes, major depressive disorders, cancer and chronic respiratory diseases, the incidence of which is increasing at an alarming rate system in Ethiopia is mainly organised around acute care delivery. In recent years the concept of chronic care has been introduced in PHC facilities through HIV service delivery, from which several implementation lessons could be learned for the delivery of NCDI services. These lessons include implementing decentralised care in the PHC, a multidisciplinary approach to care through task-shifting and task-sharing, simplification of protocols and guidelines, use of standardised essential drugs and diagnostic packages, laboratory networking, harmonised recording and reporting systems and facilitated referral mechanisms. The main strategies for prevention, treatment and care of HIV/AIDS are early detection and monitoring of risk factors, population-based interventions, a care continuum, regular monitoring of treatment adherence and psychosocial interventions. These are well-established strategies for chronic care, which could inform NCDI services. Investment in a health-system approach to NCDIs should be the way forward, as fragmented, disease-based approaches will not enable the country to respond to these emerging health problems. Substantial constraints are anticipated across each of the six key health-system components during NCDI services integration and scale-up in Ethiopia. Governance and technical support for NCDIs should be devolved and capacitated at the regional level in order to ensure appropriate decision-making and implementation of NCDI initiatives. Furthermore, the wide-ranging risk factors and the impact of NCDIs on Ethiopian society, as well as the fact that prevention and control of NCDIs require the involvement and commitment of the government and all stakeholders, including the community, call for the establishment of a national multisectoral committee on NCDIs chaired by the Prime Minister or Deputy Prime Minister, in order to guide and organise NCDI efforts. The Ministry of Health has a critical leadership role in spearheading the government's commitment. A summary of the Commission's recommendations is presented in Box 1.Box 1: Key recommendations by the National NCDI commission.Policy, planning and oversight Establish a national multisectoral committee on NCDIs, chaired by the Prime Minister or Deputy Prime Minister, to guide and organise NCDI effortsStrengthen the NCD Prevention and Control Unit at federal levelEstablish NCD Prevention and Control Units at regional levelProtect the implementation of public-health policies for NCDI prevention and control against interference by vested interests through comprehensive legislation and enforcement of national laws and regulations.FinanceAllocate an increased percentage of gains from economic growth to health; rapidly move government spending on health towards 5% of GDPMobilise additional resources, including improved efficiency, improved taxation and sin taxes , and specifically consider tax on sugar-sweetened beveragesMove towards allocating 30% of total government spending (GHE) to NCDIs by 2030Plan for reduced external funding (at least in relative terms), as the country develops economically and transitions to the status of lower-middle-income countryReduce out-of-pocket to a maximum of 20% of total health expenditureHarmonise community-based health insurance, and if possible social health insurance, with public health-sector prioritiesDevelopment of partners for engagement in generating evidence and supporting implementation of costeffective and equitable interventions for NCDs and injuries, based on national needs, in order to maximise the effectiveness of aidService integrationStrengthen the health system at all levels, emphasising primary care, and finance the national set of NCDI services, interventions and health promotion, focusing on prevention and early detection, as well as curative, rehabilitative and palliative careLow-resource countries such as Ethiopia can prevent and manage NCDs and injuries by integrating a high-priority package of interventions into existing platforms; the package's interventions should be cost-effective, target the worse-off and provide financial risk protectionImplement scale-up of health personnel as planned in HSTP, with a special emphasis on the resources needed for NCDI servicesImprove the training of health workforces and the scientific basis for decision-making through NCD-related research and partnershipsDevelop, train and implement the top eleven clinical guidelines for NCD and injury services Strategic information, target-setting, monitoring and evaluationStrengthen integrated national surveillance systems for NCDIs, including vital registration systems capable of reporting cause of death, cancer registers and risk-factor monitoringRefine existing NCDI indicators and expand to include other priority NCDIs in future revisions of HIS in order to monitor the epidemiology and service coverage of NCDIsTrack results of NCDI interventions by monitoring and reporting on the attainment of the 9 national targets .Mobilise and track domestic and external resources for NCDI prevention and control. Improve NCDI subaccounts in next round of National Health Accounts report.Education and advocacy: Achieving global as well as local commitment and action against NCDIs requires sustained advocacy. Alongside actions directed at changing social, environmental and economic conditions that impact health, mobilising the public and educating them on a healthy lifestyle will substantially contribute to the prevention of NCDIs. Advocate for improved NCDI resources and services.There is shortage of well-trained health professionals in Ethiopia, where there are only 0.96 per 1000 population, which is far less than the 4.45\u2030 recommended in order to meet the SDG health targets. Besides the shortage of human resources, inadequate knowledge and skill in NCDI case management are among the expected challenges for the health workforce during decentralisation of NCDI services. The shortage will be more pronounced in terms of staff attrition, with trained staff with their NCDI skills leaving institutions, leading to compromised case management and inconsistent completion of client-NCD risk-assessment forms, which may exacerbate the long-term monitoring of NCD risk factors. Even though the general provision of health-care professionals relative to the population is low, recent studies suggests that there is much to be gained by improving the efficiency of health facilities in Ethiopia ,90. A stGeneration of sufficient resources is critical to the delivery of health-care services. The fiscal-space analysis conducted by the Commission demonstrates that with more commitment from the government, attainment of 30% coverage of high-priority interventions is possible in the best-case scenario. In addition to economic growth, there are other ways of increasing fiscal space for government health expenditure to 5\u20136% of GDP. They include increased mobilisation of domestic resources, intersectoral reallocation and efficiency gains. As for increased mobilisation of domestic resources, particularly important options to be considered are improved taxation and other forms of revenue collection, including increased taxation of tobacco and alcohol . Such anThe NCDI burden in Ethiopia is increasing and is expected to grow at an alarming rate in the next couple of decades. A targeted investment in cost-effective interventions could result in substantial reduction in premature mortality and may be within the projected fiscal space of Ethiopia. Innovative financing mechanisms, multi-sectoral governance, regional implementation, and an integrated service delivery approach mainly using primary health care are required to achieve these goals."} +{"text": "Saccharum officinarum, Saccharum spontaneum, and other wild relatives. Sugarcane breeding programmes are broadly categorized into germplasm collection and characterization, pre-breeding and genetic base-broadening, and varietal development programmes. The varietal identification through the classic breeding programme requires a minimum of 12\u201314 years. The precise phenotyping in sugarcane is extremely tedious due to the high propensity of lodging and suckering owing to the influence of environmental factors and crop management practices. This kind of phenotyping requires data from both plant crop and ratoon experiments conducted over locations and seasons. In this review, we explored the feasibility of genomic selection schemes for various breeding programmes in sugarcane. The genetic diversity analysis using genome-wide markers helps in the formation of core set germplasm representing the total genomic diversity present in the Saccharum gene bank. The genome-wide association studies and genomic prediction in the Saccharum gene bank are helpful to identify the complete genomic resources for cane yield, commercial cane sugar, tolerances to biotic and abiotic stresses, and other agronomic traits. The implementation of genomic selection in pre-breeding, genetic base-broadening programmes assist in precise introgression of specific genes and recurrent selection schemes enhance the higher frequency of favorable alleles in the population with a considerable reduction in breeding cycles and population size. The integration of environmental covariates and genomic prediction in multi-environment trials assists in the prediction of varietal performance for different agro-climatic zones. This review also directed its focus on enhancing the genetic gain over time, cost, and resource allocation at various stages of breeding programmes.Sugarcane is a C4 and agro-industry-based crop with a high potential for biomass production. It serves as raw material for the production of sugar, ethanol, and electricity. Modern sugarcane varieties are derived from the interspecific and intergeneric hybridization between The genetic architecture was incorporated into the kinship matrix by assigning the suitable weight to the markers identified through genome-wide association studies (GWAS) and additionally improved by removing the duplicate trait-specific markers associated with the same , Canal Point, Florida, and the Indian Council of Agriculture Research (ICAR)-Sugarcane Breeding Institute, Coimbatore, India. About 1,002 accessions and 3,345 accessions of Saccharum species clones were used in the development of breeding lines in sugarcane genome-wide association studies in germplasm and identification of elite accessions with more number of desirable genes/trait-specific accessions; (ii) hybridization between elite accessions with noble S. officinarum clones or commercial sugarcane varieties; (iii) identification of true interspecific hybrids through genomic/cytoplasmic/5S rRNA/Inter Transcriber Spacer specific markers; (iv) optimization of the training and testing populations at each generation or back cross programmes which generally requires 3\u20134 generations of backcrossing/crossing with commercial sugarcane varieties; (v) genomic prediction model building and retraining of the genomic prediction models to optimize and predict the genotype with the highest Genomic Estimated Breeding Value (GEBV) for utilization in the next generation of backcrossing or crossing. The genomic prediction model could also be able to help in the swift development of genetic stocks in pre-breeding and genetic base-broadening in sugarcane.Pre-breeding, a bridge between crop improvement and plant genetic resources, provides an opportunity for introgression of desirable genes with minimal linkage drag and enhances the adaptability of the cultivars , site regression model (SREG), shifted multiplicative model (SHMM), genotype regression model (GREG), and completely multiplicative model (COMM), are used for partitioning of the G \u00d7 E interactions into more than one factor interactions. The repeatable G \u00d7 E factors in multi-environment trials are estimated through single dimension based statistical models such as ANOVA and regression approaches. The ANOVA based statistical model partitioning the G \u00d7 E interactions into the main effect of genotypes, environments and their interactions as fixed effects/variables and residuals/error components as random variables sandy soils have high discriminative powers in differentiating the environments and genotypes size, composition and design of training and validation populations, (ii) plot size for breeding experiments varies with stages of breeding programmes, such as parental selection, early and advanced testing, and (iii) the number of replications within and across the environments (Lorenz and Nice, The genomic selection in the early stages of segregating the population is a trade-off between the cost of genomic selection and trait heritability and family size. The phenotypic selection in a large segregating population with highly heritable traits is highly efficient, whereas low heritable traits, such as yield in a large segregating population, require the molecular markers to assist in the selection of desirable plant types. Further, yield measured on the single plant basis in segregating population is inaccurate in most of the crops (Heslot et al., The recurrent selection procedure is effective in augmenting the frequency of favorable alleles in the breeding population. The marker- or genomic-assisted selection helps to reduce the number of breeding cycles and the number of individuals evaluated in each selection cycle. The marker-assisted recurrent selection scheme aims at gene pyramiding after identifying the QTL (Servin et al., The multi-environment trials are the final phase of cultivar identification and need robust statistical analysis with optimum resource allocation. The resource allocation depends on the number of replications, locations, number of test entries, etc. An adequate number of replications are required for each location to control the microenvironment variations and experimental design such as Alpha design, which is very efficient in accounting for the micro-environment variation (Gonz\u00e1lez-Barrios et al., The unbalanced design or sparse testing refers to the multi-environment trials where all the genotypes are not tested in all environments and sparse testing saves the resources. Unbalanced sparse testing with an appropriate genomic prediction model enhances the prediction accuracies and saves the resources (Endelman et al., Saccharum germplasm with genome-wide markers captures the total genomic diversity of gene bank and assists in the formation of core germplasm and genomic prediction to identify the genes associated with cane yield, CCS, and tolerances to biotic and abiotic stresses. The genomic selection in pre-breeding and genetic base-broadening programmes helps in the precise introgression of genes into the parental clones and genomic-assisted recurrent selection is useful in augmenting the favorable alleles in the population. The genomic prediction for characterization of parental clones for their general and specific combining ability leverage the breeders in selecting the elite parents and progenies combined with favorable alleles for cane yield, CCS, and tolerances to biotic and abiotic stresses. The integration of environmental covariates into genomic models predicts the better performing varieties for target environments and deployment of varieties. Genomic selection is an evolving science; appropriate genomic models and breeding strategies strengthen the prediction accuracies and enhance the genetic gain in sugarcane.Sugarcane is a C4 crop with a great potential for high biomass production and a major source of raw material for sugar production and bioenergy. Its crop improvement has many bottlenecks such as the long cycle of breeding duration, complex polyploidy, high degree of heterozygosity, narrow genetic base, and fewer basic germplasm utilized in pre-breeding and linkage drag during wide hybridization and limited financial and manpower resources. The genomic selection schemes are highly helpful in reducing the duration of breeding cycles, population size, and selection of desirable parents and development of varieties. The characterization of CM conceptualized, wrote, and reviewed the draft. KA wrote, revised, provided inputs on molecular markers, SNPs, genomic selections, and resource allocations. CA, GS, PV, HM, RV, GH, GA, and BR provided inputs on molecular markers, genomic schemes, and resources allocations. All authors read and approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Insects are crucial for ecosystem functions and services and directly influence human well-being and health. Insects are among the most diverse classes of the animal kingdom, and therefore it is not surprising that they contain an immense degree of virus diversity, which remains largely unexplored. Until recently, investigations of insect virus diversity were focused on insect species of economic, veterinary, or medical importance. The deployment of high-throughput sequencing technologies has allowed for studies of virus diversity in a wider range of insect species and has led to an explosion in the discovery of new viral sequences in insect hosts, both from known virus groups and from entirely novel families. These studies have, in turn, inspired a re-assessment of the evolutionary relationships among, and taxonomic classification of, insect viruses. It is now clear that further studies of the biological effects of viruses on their insect hosts are required to understand the impact of diverse insect viromes on their host\u2019s physiology, reproduction, and the potential of host insects to be viral vectors.Acheta domesticus) [Neohydatothrips variabilis) [Scathophaga furcata) [Aedes aegypti) from the Amazon basin [Apis mellifera) [Andrena spp.) [Varroa destructor mites, which are closely associated with both Western and Eastern honey bees [Diabrotica undecimpunctata and D. virgifera) [Matsumuraeses phaseoli, an important legume pest, were also presented [The aim of this Special Issue was to invite research articles focusing on recent advances in virus discovery and the elucidation of virus diversity in insect hosts. The published papers illustrated the effectiveness of high-throughput sequencing approaches for the comprehensive analysis of virus communities, identification of novel virus variants, and discovery of novel viruses. This includes the discovery of previously unknown RNA viruses in house crickets (esticus) , soybeaniabilis) , termiteiabilis) , dung flfurcata) , mosquiton basin , hematopon basin , honey bllifera) ,8,9 and na spp.) , and evectively) . Reportsrgifera) and a beresented .V. destructor and honey bees (A. mellifera) [Sequence data on the novel viruses identified in high-throughput sequencing studies could be a starting point for further analysis of virus\u2013host interactions. Notably, some of the published papers already present such analyses, including the investigation of viral inter-species transmission between wild and managed honey bees and betwllifera) , and anallifera) ."} +{"text": "Emerging Topics in Life Sciences entitled \u2018Current Topics in Stem Cells and Regenerative Medicine\u2019 brings together expertise from a collaborative organisation known as the Mercia Stem Cell Alliance (MSCA). The alliance was established initially by Professors Sue Kimber (University of Manchester) and Jon Frampton (University of Birmingham) just over 10 years ago and now has multiple regional centres of excellence across the Midlands and North West of the UK, including Aston University, University of Chester, Keele University, Manchester Metropolitan University, Lancaster University, University of Leicester, University of Liverpool, Liverpool John Moore's University, Loughborough University, University of Nottingham, University of Oxford, University of Sheffield, University of York. Many of these centres have contributed reviews to this issue. The MSCA also partners with industrial and clinical organisations, including the NHS, and is active in bringing stem cells and regenerative medicines to a meaningful translational endpoint (see: http://www.msca.manchester.ac.uk/).This special issue of The concept of using cell spray technologies to deliver stem cells to the CNS in the treatment of neurological trauma and pathology, e.g. following spinal cord injury, has been described and discussed by Chari and co-workers (Keele University) [The reviews published in the special issue cover key areas in stem cell biology and regenerative medicine, from aspects of basic stem cell research through to the use of stem cells and tissue engineering to model human pathophysiology and for drug development through to clinical applications of adult stem cells and other regenerative medicines. Dogan and Forsyth (Keele University) have reported how epigenetic mechanisms influence telomerase activity, which plays an essential, although not fully understood role in regulating pluripotent stem cell proliferation, differentiation, tissue repair and cancer . Walczakversity) (Universversity) . The neeversity) (Universversity) . Finallyversity) (RJAH OrEmerging Topics in Life Sciences and Portland Press for inviting the reviews, which have been written in such a manner that they are broad in outlook, whilst deep in content. One of the main objectives of the MSCA is to help basic researchers and translational scientists learn and work together, both to increase our fundamental understanding of the molecular and cell biology that underpins this exciting field and also to successfully develop new stem cell therapies. Hence, it is hoped that the special issue will provide a useful resource to many current and next generation investigators as they progress in their careers in stem cell research.We are grateful to"} +{"text": "Dear EditorA 27-year-old female patient presented with a six-month history of a persistent and painful nodule on the chin. She referred occasional purulent exudate. There was no history of fever or systemic symptoms. Several courses of oral antibiotics had been ineffective. In the extraoral examination she presented an erythematous nodule with an important surrounding retraction . UltrasoOCF is the result of an abnormal canalization originating from chronic periapical infection. Usually, bacterial infection from the dental pulp drains into the oral cavity. However, when the inflammatory process is severe and long-standing, it may destroy the alveolar bone, spread to the surrounding soft tissue, and eventually drain to the skin.The diagnosis of OCF is usually made based on panoramic radiograph and computed tomography that show the damage of the alveolar process. However, these tests require considerable time and money to perform and may have side effects. Skin ultrasonography is a noninvasive and emerging technique with proven usefulness in localized lesions.Skin ultrasound is a safe and accessible tool for the diagnosis of OCF. The characteristic image of a hypoechoic sinus tract enhanced by color Doppler enables its diagnosis. Hence, neoplastic lesions are rapidly discarded, and many inappropriate treatments are avoided.None declared.Arcadi Altemir-Vidal: Approval of the final version of the manuscript; study conception and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Maribel Iglesias-Sancho: Approval of the final version of the manuscript; study conception and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Monica Quintana-Codina: Approval of the final version of the manuscript; study conception and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "The AGEC Accreditation Handbook and Self-Evaluation Guide has been revised several times since the first drafts were produced in 2016 and 2017. The Handbook contains information for accreditation applicants, AGEC reviewers, and members of the Board of Governors responsible for administering AGEC policies and procedures. It includes the accreditation standards, eligibility for accreditation, timelines, and self-study and site visit guidelines. It is the central document for the AGEC accreditation process. Handbook revisions, drawn from the experience of accrediting programs, have been for the purposes of clarifying expectations and simplifying the application process. This presentation highlights modifications included in the 2020 Handbook, which simplify the self-study outline and site visit guidelines, and the 2021 modifications, which clarify the \u201cMapping Course Matrix\u201d (displaying AGHE competencies covered in program courses) and add an \u201cAssessment Matrix\u201d for measuring acquisition of the competencies and improving the program as needed."} +{"text": "Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common dose-limiting side-effect of taxane-based chemotherapy, causing progressive and often irreversible pain/sensitivity in the hands and feet. Prevention/treatments for CIPN are not well-developed and urgently needed. Limb cryocompression during chemotherapy has demonstrated promising early data of preventing/reducing CIPN severity. Currently there are no medical devices available that are dedicated to the specific requirements of CIPN prevention. As part of our ongoing development of a dedicated CIPN-prevention limb cryocompression system, this study documents the design & development of the wearable arm wrap, a central component of the system, from initial concept to a trial-ready prototype. A collaborative and multidisciplinary approach was adopted to address the complex and high-risk nature of this SME -centered medical device design & development process. The complementary collaboration unites multidisciplinary expertise spanning the scope of the project. Alongside the clinical, academic, and design & development expertise, the integration of commercial expertise is imperative to promote the market viability, and ultimate success, of the development. As the global leading experts in scalp cooling specializing in the prevention of chemotherapy-induced alopecia, UK-based SME Paxman Coolers Ltd is optimally positioned to support the commercial and regulatory dimensions. Development and adoption of a novel mixed-methodology (HudPAX) facilitated the integration of evidence-based and user-centered techniques to optimize the design & development approach and ensure integration of all critical design inputs. Alpha prototypes were designed through evidence-based approaches, with data from existing clinical trials utilized to determine the preliminary design inputs, alongside 3D ergonomic data. Investigations utilized computer-aided design, rapid prototyping, additive manufacturing, sketch modeling, and fast ideation. User-based approaches facilitated stakeholder-feedback through expert focus groups, informing further design & development and projecting the design into the next stage, Beta prototyping, for use in large-scale efficacy trials and upscaling manufacturing. This paper demonstrates a novel mixed-methods approach, which promotes cross-sector multidisciplinary collaboration, to address the complex multi-layered challenges posed by an early-stage medical device design & development process. Chemotherapy-induced peripheral neuropathy (CIPN) is a common debilitating and dose-limiting non-hematological toxicity of taxane-based chemotherapy. Symptoms of CIPN include paresthesias, dysesthesia and pain in the hands and feet, which can be persistent and irreversible even several years after completion of chemotherapy \u20133. A metAt present, dose modification of the chemotherapy itself remains the most successful approach for the management of CIPN, and symptomatic pharmacological treatment is limited to pain killers. Prevention/treatment for CIPN are not well-developed and urgently needed. Several potential neuroprotective agents have been tested in clinical trials but none have proven effective . RecentlInspired by scalp cooling for preventing chemotherapy-induced alopecia (CIA) , limb crLimb cryocompression during chemotherapy, has demonstrated potential for decreasing the incidence of CIPN \u201319. CryoDue to the emerging scientific and efficacy evidence, there is an imminent demand for a limb cryocompression device, designed specifically for use during chemotherapy infusion for the prevention of CIPN, and this is currently in development. The pilot studies by Bandla et al. facilitated data gathering of user requirements and design inputs for development of a CIPN-specific cryocompression device to facilitate enhanced treatment efficacy . The devIt is acknowledged that the design and development of medical devices is a complex, multilayered and high-risk process, with pitfalls including stringent regulation and commercial challenges. Between 80\u201390% of new product launches fail and the complex challenges specific to medical device development are likely to increase the failure rate further . Small MSelection of the optimal design methodology ensures progress through the complex, collaborative and stringent process of medical device design and development. An optimized methodology promotes collaboration across different disciplines and perspectives, and ensures that user needs are comprehensively identified through means suited to the context of the product being designed. An extensive range of design and development methodologies exist that companies can adopt during product development processes, however there is no standard method, and guidance is lacking on the selection and application of the appropriate methodologies for medical device design and development . Due to This study documents the design & development of an arm cryocompression wrap from a concept to a trial-ready prototype using the HudPAX approach. Prototype development is essential to managing individual expectations within a project, aiding tangible feedback and justifying the cost and time invested in their development. This study explores the Alpha prototyping stage. The Alpha prototype is the initial attempt at designing and fabricating the product to meet the Product Requirements Specification; the Beta prototype development follows on from this and incorporates the design refinements found in Alpha development and implements them into production. This study generated an Alpha prototype of CIPN-prevention cryocompression arm wraps as a medical device in the feasibility, pre-clinical stage, addressing the complex challenges posed, through a mixed-methods approach.- The Double Diamond process, by the Design Council: a strategic and incremental process encompassing four stages; Discovery, Define, Develop and Deliver ;- Reflective Practice, by Donald Schon: Promoting the reflection on our actions in design so as to engage in a process of continuous learning ;- Design Science: an evidence/outcome-based methodology used to bridge the practice\u2013academia divide by developing actionable knowledge that is grounded in evidence ;- Design Thinking: This user-based approach is a procedure for investigating potential product-users wants and needs, that culminates in a design brief identifying an opportunity for developing a new product .The research method designed and applied in this study supports the delicate balance within the project, between the distinct needs of medical device design, commercial feasibility and the stringent regulatory control. In addition, it ensures a comprehensive range of design inputs (user requirements) are successfully gathered and addressed through design outputs. This approach, named HudPAX , integraIntegration of the design principles of the Double Diamond process with Design Science (evidence-based approach) and Design Thinking (user-centered approach), through the mixed-methods HudPAX approach, promoted the establishment of an iterative design process which successfully led to the selection of an initial concept for pre-clinical prototyping.The HudPAX method was developed in-line with the scope of medical regulatory standards, to ensure resulting medical devices are fully compliant with international regulations and to ease the eventual regulatory approval processes. ISO 13485:2016 is the Regulatory Quality management system for medical devices, and the incremental milestones defined by ISO 13485:2016 act as a core element within the HudPAX process, to which all other methods tether.This study concentrates primarily on the feasibility stage, Phase 1 (Discover) and Phase 2 (Define) . There iThe HudPAX research method is designed specifically to address the challenges associated with a collaborative, SME-centered, cross-sector medical design and development project, providing an optimized approach for academic and industrial collaboration. Tools including regular reviews, reports and quarterly board meetings help assess progress and ensure that the needs of all stakeholders are continually addressed.Design inputs and initial user requirements were gathered from previous pilot clinical studies, conducted by the Singapore team, to investigate the safety and feasibility of cryotherapy devices in preventing CIPN. These proof-of-concept studies investigated two cryotherapy modalities using existing class-I cooling devices designed for generic injury and therapeutic purposes. The cryotherapy modalities tested were continuous-flow cooling , and cryocompression . Pilot studies involved healthy volunteers first, to investigate safety, tolerability and optimal parameters, and subsequently studied in cancer patients undergoing chemotherapy for efficacy in preventing CIPN \u201319. ThesDesign inputs were gathered from various stakeholders including the healthy volunteers and patients who participated in the study and, nurses and bioengineers who administered the cryotherapy. Design inputs gathered through the Design Science/evidence-based approach included scientific and clinical data which set the parameters for prototyping. Observations were made on the safety (discomfort or cold burns), temperature tolerability (intolerance to cooling and compression), therapeutic efficacy and comfort (fit and ease of use over extended duration of usage). These observations were made for both intra-cycle and over multiple cycles of chemotherapy.Global medical device regulations are very similar and invoke a patient-protective, risk-based system where each device is classified into 1 of 4 categories. The higher the perceived risk, the more stringently the regulations are applied up to the highest risk where a full design dossier review is required.With the exception of the Regulatory Quality management system (ISO 13485:2016), which forms the core of the HudPAX method, integration of regulatory standards is strategically limited during early-stage feasibility investigations of medical product design, in order to permit the full exploration of ideas to ensure the eventual selection of the optimal design. In accordance with the management system, regulatory standards should be fully addressed and applied in the later development stages where IEC 60601-1 was assessed for general requirements for basic safety and essential performance;- IEC 14971 was assessed for applications of risk management to medical devices;- IEC 62366 was assessed for applications of usability engineering to medical devices.Safety and usability testing is considered in all aspects including, but not limited to:While integration of regulatory standards is not required at this feasibility stage of the investigation, awareness of relevant impending regulations is important to ensure a smooth transition to the next development stage and to optimally position the development for eventual regulatory compliance. Regulatory standards which have been considered during this feasibility study include:This study documents the design & development of an arm cryocompression wrap from a concept to a trial-ready prototype. The mixed-methods HudPAX approach promoted the strategic implementation of multiple complementary research methods, through the process of input gathering, ideation and prototyping and designing for manufacture, ultimately producing an Alpha prototype and facilitating a user-centered focus group study.Design inputs were generated based on clinical evidence, which was gathered from over 400 cycles of cryotherapy using the two modalities: continuous-flow cooling, and cryocompression \u201319. ThesThe HudPAX method integrates a well-established commercial product design & development framework, the Double Diamond design process, an incremental ideation approach to explore the full range of potential concepts. With the evidence-based design inputs as a foundation, Phase 1 (Discover - Research) and Phase 2 (Define - Ideate) were explored , primariAn initial design concept was selected by the team, where ergonomic aspects were explored. The ergonomic foundation of this design was adjustability which allows the wraps to fit a wide variety of users' arm types/sizes, tightening it to different contours, and loosening if patients experience discomfort or sensitivity to the cold, in addition it provides easy removal for toilet breaks or in emergencies. The arm wrap will cover a large portion of the arm, hence many variables were to be addressed including: finger, palm and wrist size, forearm girth and arm length. Design mechanisms were used to allow for the required levels of adjustability including Velcro\u00ae and flaps for extending or reducing individual zones of the arm wrap. This development phase also involved the analysis of: suitable materials, exploration of potential manufacturing methods, testing, technical requirements (including flow rates and cooling efficiency), safety, regulatory standards, comfort, and aesthetics.The ergonomic design concept was implemented in the initial designs , 5 whereApart from evidence-based ergonomic inputs, the initial designs also included considerations of the optimal therapeutic parameters (best tolerable temperature and pressure ranges), based on pilot clinical trial efficacy data \u201319. FeatBased on the knowledge, from our pilot studies, that the forearm is able to tolerate lower temperatures than the fingertips, a feature of thermoregulating different zones was investigated through a concept which utilized three separate cooling bladders per arm .Further exploration led to a concept with a single bladder which utilized a bottleneck design to reduce flow and adjust temperature incrementally from low, medium and high , through zones based on our clinical data on temperature tolerability . This siThe initial concept was then selected for pre-clinical investigation . PrototyThe prototypes were created for a focus group testing with users and stakeholders , 9.The developed Alpha prototypes were presented to a stakeholder focus group to gather user-centered and ergonomic based feedback. The user-centered focus group study was conducted at the Clinical Research Facility, Leeds teaching hospital, Leeds, UK and involved healthcare professionals and patient and public involvement (PPI) groups. Engagement of PPI groups ensures that patients, public and caregivers are actively involved early on in the medical device design process and their insights and perspectives are taken into account. This user perspective also aims to mitigate any possible oversights at an early stage in the medical device development process.The focus group, consisting of 12 healthcare professionals and PPI group members, acknowledged the unmet clinical need and appreciated the concept of a wearable device to prevent CIPN. Participants were informed on the usability aspects of the wrap design including compression and cooling aspects, correct fit, intravenous cannula monitoring, ease of removal, optional pressure on the cannulated arm and instructions for use. Participants were encouraged to try on the prototype wraps alongside examples of existing non-CIPN specific cooling devices. The following user-centered development aspects were explored:The focus group appreciated the idea of an intravenous cannula site window providing visual access to the healthcare professionals to monitor any extravasation or adverse reactions that might occur during the chemotherapy infusion. At the same time, this allows for the cannulated arm to receive the benefit of cryotherapy. The placement and size of the intravenous cannula site window in the Alpha prototype was suggested to be modified to fit cannulation practices in the UK, as the earlier placement was catered to practice in Singapore, based on the pilot clinical trial evidence. This highlighted a key user-centered design aspect to be taken into consideration. Using these key inputs, we applied the data from the focus group to develop a concept prototype including multiple adjustable flaps throughout the wrap, as shown in The focus group suggested incorporation of a design feature for the intravenous feed to fit through the wrap without dislodging the cannula. This would allow for the healthcare professionals to remove the wrap without removing the cannula to facilitate toilet breaks.The focus group considered the reusability of wraps and a suitable biocompatible material which would allow for disinfection and reuse over different chemotherapy cycles and in different patients.The Velcro\u00ae flaps were reported to be simple, easy and convenient to use, especially for quick wrap and unwrap during toilet breaks. The focus group was comfortable with the fit of the prototype wraps which catered to various sizes of arms and ease of adjustability. They also indicated that there was sufficient \u201cbreathing\u201d space around the palm area to allow fingers movement during the extended period of application. A concern was that the wrap may be too long for smaller sizes of arms. The group also considered the weight of the device exerted on the patient's limbs as a factor of comfort through the entire duration of cryotherapy.The next stages of prototype development will involve the production of functional or proof-of-concept prototypes which allow the retention and flow of liquids and air pressure, thus allowing the evaluation of fluid dynamics, temperature control, pressure and temperature tolerability. The feedback gathered in this study was adopted as design inputs into the design development process. This further led to the developed Following on from this feasibility study, in phase 2 and phase 3 of the methodology, the design for manufacture becomes a more dominant consideration. In phase 2, we collaborate with several manufacturing companies with different specialist areas to make Alpha prototypes and low-volume prototyping for validation testing and clinical trials. Considerations include the materials, methods and the costs associated with one-off or low-volume manufacture. The later stages will increase the focus on the design for manufacture, specifically regarding tooling, where rapid tooling and hard tooling will be considered depending on volumes, quality and constraints for both the external limb-wrap and the internal coolant-containing-bladder. Due to the many parallels between this device and Paxman's established scalp cooling device, the existing industry expertise and infrastructure for prototyping, supply and material usage provides a readily-available framework which can be adopted and modified to the unique requirements of this project.For the manufacture of the internal bladder for the functional prototype, Radio-Frequency (RF) welding has been selected. RF welding uses high frequency electromagnetic energy to generate heat, thus bonding sheets of plastic together . TechnicThis study documents the design and development of arm wraps as a central component of a CIPN-prevention limb cryocompression system. Using the HudPAX method, design input requirements were gathered from existing clinical pilot studies, and design outputs were developed in an iterative process, with user-centered approaches providing vital stakeholder feedback and propelling the development into its next stage. This research demonstrates the importance of cross-sector multidisciplinary collaboration, mixed-methodology adaptation and the integration of stakeholder consultation, in addressing these challenges, particularly with SME-centered developments where resources and research and development infrastructures are limited.Development of a Beta prototype - based on the findings of this study, generating a near-final design for use in the subsequent clinical trials;A healthy volunteer trial to determine safety will be conducted using the Beta prototype;A clinical trial in cancer patients undergoing chemotherapy will be conducted, to prove efficacy;Regulatory approval will be obtained;The \u201cdetailing and final prototype\u201d stage in collaboration with industry will finalize the product;The final product will be launched to an international market, through Paxman's existing infrastructure.Our ultimate aim is to generate a complete four-limb cryocompression system for CIPN prevention, which can be utilized by patients worldwide, alongside the existing Paxman scalp cooling system. The roadmap of milestones to ensure the continuation of this successful development includes:The method adopted in this project was developed to address the complex and high-risk nature of SME-centered medical device design & development projects and supports the equilibrium between the distinct needs of medical device design, user needs, commercial feasibility and stringent regulatory standards. The complex challenges encountered within medical device development demands a multidisciplinary approach; in which experts from all fields of relevant research collaborate to address unmet clinical needs. In this project, early-stage clinical trials generated the evidence-based inputs and ensured the feasibility of the potential solution. The subsequent ideation phase engaged the expertise of designers and engineers, who utilized the scientific evidence to generate potential concepts. Qualitative assessment of the concepts, from users, was then essential to progress the development into the next stages, where opinions and motivations are explored. This fundamental communication between Design Science and Design Thinking methods is the foundation for establishing early success in medical device design & development.As we have explored in this paper, medical device design & development is complex. The development process needs to be adaptable and multifaceted to ensure the commercial viability. A crucial consideration for any development, during the discovery phase (Phase 1 - Research), is a market analysis to assess the market for existing products, state-of-the-art technology and industrial feasibility. A comprehensive literature review identified key commercial aspects including market size, freedom to operate, problem definition, user behavior, opportunities and needs, together with the integration of academic aspects.Ultimately this development aims to achieve MDSAP approval, which is medical device compliance encompassing HC, FDA, ANVISA, EC, ATG and PMDA, and represents six different medical device markets: Australia, Brazil, Canada, Europe, Japan and the United States. Regulatory approval for additional markets will also be strategically pursued. Utilizing the existing knowledge and infrastructure available from the commercial partner, the future challenges associated with obtaining regulatory compliance, which commonly account for new medical devices' market failure, will be mitigated.Approximately 30,000 patients in the UK, and 1 million worldwide, can be affected by CIPN annually. Scalp-cooling prevents CIA, which occurs alongside CIPN and therefore the market already exists. Collaboration with Paxman Coolers Ltd integrates into the project an existing route-to-market with the synergies facilitating improved productivity and economies-of-scale to be achieved. Limitations specific to this CIPN prevention device include the additional medical time required to attach/detach/monitor the therapy; the additional space required for the device within hospital/clinics; and also potential low adoption of the therapy due to current low-level awareness amongst patients of CIPN as a side-effect of chemotherapy. Identification and consideration of potential limitations by the multidisciplinary team and stakeholders, at this feasibility stage, facilitates early mitigation.Medical requirements; Technical requirements; Stakeholder and user requirements; Regulatory requirements; Multidisciplinary team varied expectations; Commercial viability; and Market awareness and accessibility.This paper has addressed the challenges posed by early-stage medical device design & development, including the following challenge areas: Through the development of a limb-hypothermia arm wrap Alpha prototype for CIPN prevention, cross-sector collaboration has united multidisciplinary expertise from clinical, academic and commercial backgrounds, with the combined regulatory and market-awareness knowledge providing a strong foundation which proves central to the development's ultimate viability.Development and implementation of a mixed-methodology has promoted a flexible approach addressing the complex design challenges and optimized to the cross-sector needs and expectations of the collaborating partners. This mixed-methodology has also demonstrated the equal importance of evidence-based and user-centered inputs, primarily for setting the clinical and technical parameters and secondly for integrating user requirements. Our work highlights the necessity for stakeholder consultation in the early stages of medical device development, specifically when multiple user-types (nurses/patients) exist, to ensure user-inputs comprehensively reflect the user-needs. Continuation of the mixed-methods approach will propel the device through the next stages of the development including Beta prototyping, clinical trials and eventual market launch.The original contributions generated for the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by School Research Ethics and Integrity Committee (SREIC), University of Huddersfield, UK. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.JB, EU, PB, RP, RS, and AB contributed to the conception and design of research. JB and AB contributed to the implementation of the research, acquisition, and interpretation of data. JB, EU, JC, and AB drafted the manuscript. PB, RP, and RS revised the manuscript critically and for important intellectual content. All authors read and approved the final manuscript.JB and PB are employed by Paxman Coolers Ltd. RP partially owns Paxman Coolers Ltd. EU, RS, and AB have received research or travel funding from Paxman Coolers Ltd. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This work was supported by Paxman Coolers Ltd., UK. The funder was involved in the commercial design decisions as this project is a commercial product design and development , but the academic and research team independently made decisions for data collection, analysis, interpretation of data, the writing of this article and the decision to submit it for publication."} +{"text": "Despite being among the most common psychiatric disorders worldwide, and a leading cause of disability including work and school absences, anxiety disorders have been relatively under-represented in recent research of novel pharmacologic agents, compared to major depressive disorder (MDD) and schizophrenia. Panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD) are commonly treated with either medications and/or psychotherapy, while specific phobias (SP) are usually treated with behavioral therapy alone. While there is support for certain forms of psychotherapy to treat anxiety disorders, there remains concern about lower efficacy of psychotherapies compared to medications , and incThe purpose of this Research Topic was to collect original papers and review articles exploring promising novel medications on the pipeline for anxiety disorders, primarily GAD, PD, SAD and SP, after first reviewing the current state of psychopharmacological treatments available. The topic aimed to explore more unique pathways for targeting treatment response in anxiety disorders, including the glutamate system, neurosteroids, the hypothalamic-pituitary-adrenal (HPA axis), neuropeptides, cannabinoids, and phytochemicals.Lijffijt et al. reported a protocol for a randomized, placebo-controlled proof-of-mechanism trial of a n-methyl-d-aspartate (NMDA) receptor antagonist lanicemine for 24 adults with symptoms of post-traumatic stress disorder (PTSD) ]. The study was included in this Research Topic despite being a trial on participants with PTSD symptoms because of its potential application to anxiety disorders. In the protocol, participants are to receive 5 days of intravenous (IV) injections of lanicemine or placebo and be monitored with anxiety-potentiated startle and CAPS scores. Lijffijt et al. are building upon previous research of another NMDA antagonist, ketamine, which has also been tested using IV infusions in patients with treatment-resistant depression , and its interactions with GABA, the primary CNS inhibitor, in anxiety disorders. Building from an overview of circuitry and receptor pathways, and a review of preclinical research describing the role glutamate plays in anxiety, Nasir et al. then describe the current state of glutamatergic and GABAergic drug research in anxiety disorders. The GABA modulators discussed in the paper, most of which are clinically used as anticonvulsants , have limited support due the absence of larger, randomized, double-blind, placebo-controlled trials, with the exception of pregalabin, which was approved for GAD in Europe in 2006 , SSRIs, and benzodiazepines may normalize hyperactivity of the HPA axis. Tafet and Nemeroff cite evidence that these antidepressants may modulate glucocorticoid receptors in the brain and benzodiazepines may have an inhibitory effect on corticotrophin releasing factor (CRF). Taken together, the findings support an expansion of research beyond serotonin and norepinephrine and may spur exploration of novel agents targeting the HPA axis directly.Understanding stress response and hormone regulation may provide further clarity about newer pharmacological treatments, and Garakani et al., along with other authors, presented an overview of the current state of treatment of anxiety disorders, which is discussed above, followed by a review of novel pharmacologic treatments for PD, GAD, SAD, and SP. Several serotonergic agents that were originally investigated for depression have been studied and showed potential, but these trials did not lead to FDA approval and there are limited ongoing investigations. There are also trials of psilocybin and lysergic acid diethylamide (LSD) for anxiety but primarily in those with life-threatening diseases (like cancer) , 18. Ket cancer) . Studies cancer) , 21, andTaken as a whole, the Research Topic did in fact show both promises and disappointments in the research of novel pharmacotherapeutics for anxiety disorders. As expected, the pathways and novel compounds hypothesized to treat anxiety were hampered by lack of efficacy (perhaps due to poor study design), small sample sizes or other mitigating factors. With any hope, this Topic should not discourage ongoing exploration beyond serotonin, norepinephrine and GABA, and instead bolster the efforts to expand on our understanding of the complex neurobiological pathways of anxiety and how to translate this work into novel agents that perhaps can complement the ongoing research into psychotherapeutic treatments of anxiety.AG wrote the original draft of the manuscript. AG, RF, and JM contributed to critical manuscript revisions. All authors reviewed and approved the final draft of the manuscript and made substantial contributions to this study.JM disclosures: In the past 5 years, JM has provided consultation services and/or served on advisory boards for Allergan, Boehreinger Ingelheim, Clexio Biosciences, Fortress Biotech, FSV7, Global Medical Education (GME), Impel Neuropharma, Janssen Research and Development, Medavante-Prophase, Novartis, Otsuka, and Sage Therapeutics. JM was named on a patent pending for neuropeptide Y as a treatment for mood and anxiety disorders and on a patent pending for the use of ezogabine and other KCNQ channel openers to treat depression and related conditions. The Icahn School of Medicine (employer of JM) was named on a patent and has entered into a licensing agreement and will receive payments related to the use of ketamine or esketamine for the treatment of depression. The Icahn School of Medicine is also named on a patent related to the use of ketamine for the treatment of PTSD. JM was not named on these patents and will not receive any payments. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The Acute Life interventions Goals and Needs Program (ALIGN) is an inter-professional team of medical and social work providers dedicated to offering time-limited intensive ambulatory care to the most complex, high cost, high needs older patient population at Mount Sinai Hospital in NYC. During the 2020 COVID19 pandemic, ALIGN pivoted to focus on emergency planning actions. Such actions included language and culturally concordant goals of care discussions with patients and family, completion of electronic Medical Orders for Life Sustaining Treatment, reassessment of patient\u2019s social determinants of health, determination of adequate access to food, medication, and emotional support to those alone and isolated, and assistance with video telemedicine. ALIGN\u2019s model of care has shown how adaptable this program and others were during the height of the pandemic."} +{"text": "The regulation of ROS and RNS levels is indispensable to preserve cellular homeostasis. Low ROS and RNS levels stimulate immune responses, cell proliferation, apoptosis, differentiation, and stress-responsive pathways. High ROS and RNS levels damage lipids, proteins, and DNA [S-transferases) can neutralize ROS directly or with the help of metal cofactors [N-acetyl cysteine and lipoic acid) act as cofactors for some enzyme systems or neutralize the production of free radicals by transition metals [Knowledge on the plants that express the greatest concentration of antioxidant molecules of interest,Pedoclimatic conditions and cultivation stages that make most of their levels available in plants,Extraction methods that can properly maximize their recovery,The potential preventive and/or therapeutic effect of each chemical class of antioxidants,Pharmaceutical delivery systems that allow for the full advantage of their actions in the body.Oxidative stress happens when the levels of reactive species made from oxygen and nitrogen exceed the body\u2019s antioxidant capacity. Exogenous agents and endogenous processes generates-links) . Antioxis-links) . Some en and Zn) . The ant and Zn) . The secn metals . In recen metals ,9,10. Fon metals . Moreoven metals . UnfortuThis work comprises original research papers and reviews on antioxidant molecules in food, the agricultural practices that maximize their levels in plants, the potential preventive effects of selected classes of antioxidant molecules, their potential use in functional foods, and the pharmaceutical delivery systems that maximize their potential activity when used as supplements. Finally, the recovery of food antioxidants from food waste is discussed, considering the need to reduce waste to protect the environment as an issue of primary importance ."} +{"text": "Atherosclerosis is a chronic and progressive inflammatory disease of the arteries initiated by the functional and structural alteration of the endothelial layer responsible for promoting the subendothelial retention of modified low-density lipoproteins (LDL), which in turn generate an active proinflammatory state in which environmental factors, such as oxidizing agents, growth factors, cytokines, monocyte-macrophages and smooth muscle cells (SMCs), work in cooperation to promote the formation of plaque. Despite substantial progress in the prevention, diagnostics, and treatment of atherosclerosis, it remains the leading cause of mortality worldwide, approximately resulting in 18.6 million deaths in 2019 [This Special Issue contains a selection of research articles and reviews written by experts in the field, focusing on the molecular biology of atherosclerosis, the impact of different risks factors and the mechanisms by which they can influence the development of this disease.As briefly mentioned above, atherosclerotic disease arises as a consequence of the subendothelial retention and modification of LDL, sparking an inflammatory state and promoting the formation of fatty streaks, the earliest visible signs of atherogenesis. There is extensive evidence that increased plasma levels of proatherogenic lipid species are causally associated with atherosclerosis, and that lipid-lowering therapies can substantially reduce the lifetime risk of cardiovascular disease . In thisAnother important event contributing to the development of atherosclerosis is the recruitment of circulating monocytes to the vessel wall, their transendothelial migration and their phenotypic polarization towards proinflammatory macrophages that acquire the capability to rapidly secrete a wide range of inflammatory mediators, influencing the development and extent of atherosclerosis. Wu et al. investigated the molecular mechanisms involved in mononuclear cell (MNC) activation and endothelial dysfunction in atherosclerosis, suggesting that circulating fatty-acid-binding protein 4 (FABP4) is capable of altering monocyte cell adhesion and endothelial functions via the upregulation of ERK/JNK/STAT-1 signaling and the downregulation of the eNOS and SDF-1 pathways. Consistently, they also showed that the inhibition of FABP4 attenuates the effect of oxLDL on monocyte adhesion to ECs through the downregulation of the integrin pathways in MNCs and human coronary endothelial cells (HCAECs). Nevertheless, the paper by Chang et al. demonstrates that the selective inhibition of the C-C chemokine ligand (CCL4), an inflammatory chemokine highly expressed in atherosclerotic patients, is able to restore the endothelial adhesive properties and reduce the activity of metalloproteinase-2 and -9, as well as the production of TNF-\u03b1 and IL-6 in stimulated macrophages through the nuclear factor NF-\u03baB pathway. In the context of vascular inflammation and atherosclerosis, the role of neutrophils has been underappreciated for many years; more recently, however, neutrophils have emerged as important contributors to atherosclerosis due to their ability to release neutrophil extracellular traps (NETs). In this regard, it has been demonstrated that NETs are present in the atherosclerotic plaques of both human and animal models, where they induce endothelial cell dysfunction and apoptosis, oxidative stress and the oxidation of high-density lipoproteins; thus, reducing their capability to promote cholesterol efflux from foam cells ,4. Da SiThe health benefits of acetylsalicylic acid (ASA) and diminazene aceturate (DIZE) have also been investigated with respect to the atherosclerotic plaque development and phenotype. Acetylsalicylic acid (ASA), also known as aspirin, was first successfully synthesized in 1899 and widely used to reduce pain, fever and inflammation until the 1970s, when it became the cornerstone of therapy for the secondary prevention of cardiovascular events by the virtue of its antithrombotic properties ,6. In thThe review by Giglio et al. provided a clear overview of the molecular effects of novel nutraceuticals, hypolipidemic agents and hypoglycemic drugs on atherogenesis. Siew and colleagues provided valuable insight into the advances, applications and potential pitfalls of the CRISPR/Cas9 system in the context of atherosclerosis. An interesting interaction between the endothelial cells of coronary arteries (CA) and internal thoracic arteries (ITA) upon coronary artery bypass grafting (CABG) surgery was proposed by Shishkova et al. to explain the molecular mechanism underlying the increased resistance of ITA grafts to atherosclerosis and restenosis."} +{"text": "Da Costa et al., Druege et al., Mhimdi and P\u00e9rez-P\u00e9rez proposed AR formation as the default state of root development in plants, highlighting that root initiation from non-root tissues might be considered as an ancestral trait, as ARs are formed by default in lycophytes and ferns. According to the same authors, in many angiosperms, AR formation seems to be repressed through mechanisms that maintain competent cells in a quiescent state. Activation of competent cells is triggered by environmental conditions to which the cuttings or intact plants are exposed, like exogenous auxin treatment, wounding, waterlogging, or light exposure and mineral nutrition determining the activation of a complex network of signaling, metabolic, and transport pathways formation. The first is known as the induction phase, in which high auxin levels are required for reprogramming of competent cells toward root development, which is further linked to other biochemical changes genes, on the control of auxin or jasmonic acid conjugation, and the PIN, AUX/LAX, and ABCB genes, on the control of auxin transport.The articles of Aux/IAA and ARF genes that encode auxin signaling repressors and their target auxin response factors respectively. Downstream, genes of transcription factors (TFs) from the GRAS, SHORTROOT (SHR), SCARECROW (SCR), WUSCHEL RELATED HOMEOBOX (WOX), LATERAL ORGAN BOUNDARIES-DOMAIN (LOB) and APETALA2/ETHYLENE RESPONSIVE ELEMENT BINDING (AP2/ERF) gene families, control the auxin-dependent establishment of the AR founder cell and the new root apical meristem, the maintenance of the quiescent center (QC) and subsequent establishment and differentiation of the AR primordium . A coordinated change of expression of genes controlling the modulation of the cell wall, such as EXTENSIN and CYS ENDOPEPTIDASE genes, may probably also be involved (Li). Even though these reviews present different perspectives, they stay in line to each other in pinpointing to the core function of plant hormone crosstalk on regulating AR formation, within a process involving a hierarchy of transcription factors, that is linked to epigenetic modulation events, with reactive oxygen species (ROS) also being involved as messenger molecules.Important molecular factors that determine auxin signaling are specific Vilasboa et al. highlight the capacity to efficiently modulate redox conditions though high activity of SOD and soluble GPRX, as the main factor defining AR ability in Eucalyptus. The role of phenolic compounds acting as synergistic or antagonistic in AR formation has long been known, and its role as a species-dependent parameter was also highlighted by Vilasboa et al.The involvement of enzymes from ROS-scavenging mechanisms, and phenolic compounds working as a non-enzymatic antioxidant system, have been investigated across a diversity of plant species during the AR formation process. The activity of ascorbate peroxidase (APX), superoxide dismutase (SOD), and catalase (CAT) have been associated with improved rooting ability . The importance of ROS on AR formation was also explored by studying the involvement of the alternative oxidase (AOX), a key enzyme in the alternative respiratory pathway, using semi-hardwood cuttings .Within the different ROS molecules, the focus has been given to HAbarca suggested the epigenetic control of miR160/167-modulated auxin signaling, the TARGET OF RAPAMICINE (TOR) and possibly RETINOBLASTOMA-RELATED (RBR) dependent metabolic and auxin control of the cell cycle, and the non-cell autonomous regulation of WOX11/12 expression by CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) peptides, as three molecular checkpoints for the age-related decline in AR induction. In their original article, Pizarro and D\u00edaz-Sala compared hypocotyl cuttings excised from Pinus radiata seedlings with different ages to identify genes that control the cell wall-plasma membrane-cytoskeleton continuum in the basal stem, in relation to rooting competence. The RECEPTOR-LIKE KINASE (RLK) and MECHANOSENSITIVE CHANNEL (MSC) genes, as well as genes encoding downstream regulators of the small GTP-binding protein family, were associated with rooting competence, probably via acting on the control of cell wall sensing and membrane disturbances during the essential cellular reorganization .The loss of rooting capacity with plant aging , a major problem in breeding and propagation of many tree species, has also been investigated. Regarding the relevant literature, Bannoud and Bellini, Abarca).Despite all the research carried out and the information achieved in the last years, the mechanisms underlying maturation-induced rooting recalcitrance and environmentally mediated rooting, as well as several other aspects of the AR formation process, are still far from being fully understood . The work of UD was funded by the German Federal Ministry of Food and Agriculture (BMEL) based on a decision of the Parliament of the Federal Republic of Germany, granted by the Federal Office for Agriculture and Food .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "At Robert Koch Institute\u2019s Department of Infectious Disease Epidemiology, approaches for applying the principles of evidence-based public health (EBPH) have been particularly successfully implemented in the Immunization Unit and in the Unit for Healthcare-associated Infections, Surveillance of Antibiotic Resistance and Consumption. Furthermore, both units participated in the international Project on a Framework for Rating Evidence in Public Health (PRECEPT) which has been funded by the European Centre for Disease Prevention and Control (ECDC).The Immunization Unit hosts the Executive Secretariat of the German Standing Committee on Vaccination (STIKO). In 2011, STIKO has adopted a new Standard Operating Procedure (SOP) for the development of vaccination recommendations. Main aim was to provide a methodological framework to guide this process by applying the principles of EBPH. The SOP comprises ten consecutive steps, starting with a prioritization process of relevant topics, and ending with the publication of the recommendation and a related paper on the scientific background. Following the principles of EBPH, systematic reviews and meta-analyses are performed to address key issues. The methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group is a core element of the SOP and is used to assess the quality of evidence on vaccine efficacy/effectiveness and safety, including population effects. In addition, STIKO has started to use Evidence-to-Decision Tables to support the decision-making process. Since 2012, ten recommendations on new vaccines or revisions of previous recommendations have been successfully developed using the SOP, accompanied by publication of background papers and of the respective systematic reviews in peer-reviewed journals .At the Unit for Healthcare-associated Infections, Surveillance of Antibiotic Resistance and Consumption, the EBPH approach has been used to perform systematic reviews on the burden of healthcare-associated infections . As an eThe latter review was part of the PRECEPT project. PRECEPT defined a methodology for evaluating and grading evidence in public health, with a particular focus on infectious disease epidemiology, prevention and control, taking different domains and question types into consideration . The met"} +{"text": "Empirical data regarding Covid pandemic impact on the Nevada Adult Protective Services (APS) Program clients, casework, and staff was gathered and analyzed as part of a multi-faceted program evaluation. Key findings include: 66% of the staff agreed or strongly agreed that the pandemic made their jobs more challenging. Respondents reported Covid-related challenges faced by clients, the program, and themselves as social workers serving older and vulnerable adults. Adverse client impacts observed included increased social and emotional isolation, loss of housing, exacerbation of symptoms of mental illness, necessary services being cut from clients subsequent to testing Covid positive, and fear and reluctance to allow needed visiting service providers, such as home health aides, into their homes. We will discuss the implications of the findings on APS services and clients, and on related health and human services designed to promote the wellness and independence of older and vulnerable adults."} +{"text": "The public health emergency response workforce has experienced unrelenting pressureduring the past decade. Countries in the Western Pacific Region have responded tosignificant outbreaks of avian influenza, Zika virus disease, Middle East respiratorysyndrome, vaccine-derived poliovirus, measles and the coronavirus disease 2019(COVID-19) pandemic, as well as natural disasters; they also supported the response toEbola virus disease in West Africa during 2014\u20132016. . are a keyactivity for strengthening health security by developing vital technical expertise inthe existing workforce. (In 2019, we interviewed public health emergency response experts on topics that includedworkforce support. The experts discussed the challenge of inexperience and noted that anemergency response surge workforce was frequently based on availability rather thanappropriate skills and experience. (To support the technical and leadership needs of the surge workforce during the COVID-19pandemic in Australia, the Public Health Association of Australia and the AustralasianEpidemiological Association rapidly established a pilot mentorship programme for surgeresponders, in which mentors provided both professional and personal support to menteesremotely. (The Australian mentorship programme supported front-line pandemic surge response workersat a time of great need. The main recommendation of the evaluation was to design apurpose-built programme for supporting emergency response workers. (Fig.\u00a01.A similar programme in the Western Pacific Region, based on the experience of theAustralian programme, (Such a support programme could be used in public health emergency response both locallyand globally. It could increase the effectiveness of the workforce, add to professionalknowledge, provide less experienced responders with skills and reduce stress andburn-out. (The first objective of the WHO Global Strategy on Human Resources for Health is tooptimize the quality of performance and the impact of the workforce. ("} +{"text": "Dear Editor,Papio papio), the name Baboon syndrome (BS) was suggested for these cases.In 1984, Andersen et al.This is the report of a 56-year-old male patient complaining of lesions on the inguinal and axillary regions that were slightly pruritic and not associated with other systemic symptoms. He reported a two-day use of paracetamol, exclusively, and a condition identical to the current one in previous exposures. Upon physical examination, well-delimited, erythematous, wine-colored lesions were observed, without signs of excoriation, with a bilateral and symmetrical distribution on the axillary, inguinocrural, gluteal regions, and lateral aspect of the thighs, including the popliteal region . HistopaTherefore, the clinical, dermatological, and histopathological data allowed the diagnosis of paracetamol-induced SDRIFE. The lesions disappeared within a few weeks after drug discontinuation and the use of topical corticosteroids.In 2011, Miyahara et al.5The pathogenesis is not completely understood, but, as in allergic contact dermatitis, the picture suggests a delayed hypersensitivity reaction mediated by T cells. A greater density of eccrine sweat glands in skinfold regions would explain their restricted or predominant manifestation in intertriginous locations, where the excretion of the sensitizing drug would precipitate the dermatosis. Treatment involves suspicion and interruption of the drugs being used. Topical or systemic steroids can speed up resolution. Case reports and identification of the triggering drug are useful from a instructive and epidemiological viewpoint.None declared.Joana Alexandria Ferreira Dias: Approval of the final version of the manuscript; design and planning of the study; critical review of the literature.Luana Moraes Campos: Approval of the final version of the manuscript; critical review of the manuscript.Juliano Vilaverde Schmitt: Approval of the final version of the manuscript; collection, analysis and interpretation of data; critical review of the manuscript.Silvio Alencar Marques: Approval of the final version of the manuscript; drafting and editing of the manuscript; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "The United States of America reports almost double the number of cancer cases relative to India that has a much larger overall population. Accurate insights into such differences in cancer rates may be provided by a better understanding of the genetic and lifestyle influences on tumor growth, progression, heterogeneity, and the underlying stressors that prompt pre-clinical dormant lesions to progress into malignant tumors, as well as by synchronizing the cancer surveillance protocols in the two countries. Toward this goal, an Indo-American Cancer Consortium was conceived. The consortium brings together global transdisciplinary teams of basic cancer researchers, oncologists, epidemiologists and surveillance experts who are well equipped with the experience, diagnostic and therapeutic tools, infrastructure and collective resources. The participating institutes include Government and non-Government organizations: Manipal Academy of Higher Education, Saroj Gupta Cancer Centre and Research Institute, and Tata Memorial Centre in India, and the Mayo Clinic Cancer Center, and University of Kentucky Markey Cancer Center in the United States. The genesis of the consortium dates back to 2017. In person visits of Markey Cancer Center teams and Mayo Clinic faculty to the cancer research institutions in India, and joint cancer conferences held in 2017 and 2018 provided strong motivation to formalize the interactions by founding this Consortium. Facilitated by monthly planning meetings beginning mid-2020 and a first retreat in December 2020, held virtually due to COVID-19 travel restrictions, the consortium has been regularly organizing various interactive sessions. These include fortnightly research presentations by faculty and trainees of participating institutions, invited guest lectures from other institutions, and a quarterly mini-symposium in topical areas of cancer. Concerted efforts to mentor the next generation of scientists saw the introduction of didactic courses in basic cancer biology, translational oncology and epidemiology, for Masters, Ph.D., Pharm.D., and MD students offered by Markey Cancer Center faculty; a certificate Program in Precision Medicine: Oncology Genomics; and a virtual tumor board to guide oncologists on treatment options for precision oncology. These activities led to organic multidisciplinary collaborations involving teams of oncologists, basic scientists, pharmacists, pathologists, and epidemiologists focused on research projects. When the travel restrictions are lifted, there will be an exchange of basic science and clinical faculty and students across the participating institutions to further foster and strengthen the partnership in cancer research and training. The consortium initiatives, supported by the parent institutions and a CRDF-Global-NCI Cancer Research Training Travel Award to exchange knowledge and enable technology transfer, have already resulted in joint peer-reviewed publications. Thus, through its multi-faceted research, education, training and outreach programs, the consortium will build infrastructure, expand capacity and strengthen global cancer research leadership and healthcare at the participating institutions.The significance of collaborative team science cannot be overstated. Unlike the days when scientists worked in silos, and laboratory bench findings were rarely translated to the clinic, the era of team science in the last few decades have underscored the value of interdisciplinary teams of investigators with diverse expertise to tackle critical questions of clinical relevance. Such an approach is particularly essential in cancer care, where, for instance, intricate details about the genetic mutations in the patient\u2019s tumor requires the combined expertise of basic and translation scientists as well as clinicians, to not only select the precise treatment for the patient but also maintain a readily available backup strategy in case the tumor develops therapeutic resistance.Cancer is the second leading cause of mortality worldwide. According to GLOBOCAN, there were an estimated 19.3 million new cancer and about 10 million cancer deaths worldwide in 2020 . In the Strategies to improve the impact of cancer research for patients have been widely discussed in India and United States over the past several decades. One confounding factor that restraints progress is the complexity of the disease associated with significant biological heterogeneity among cancer patients with diverse genetic predisposition, lifestyle, and environmental factors. Another impediment is the translation of basic research findings imposed by structural, financial and logistic limitations in facilitating interactions and workflow from the laboratory to the clinic. Some of these issues can be addressed by cohesive multi-disciplinary teams of basic and translational scientists and oncologists working together through multi-institutional cooperation to develop bench-to-bedside projects complemented by epidemiology data and community outreach efforts. Such teams are likely to be more effective in motivating scientific and administrative policy decisions that positively impact patient care. Based on this ideology, the Indo-American Cancer Consortium was formed by academic institutions in India and the United States. These institutions include Manipal Academy of Higher Education (India), Markey Cancer Center, University of Kentucky (USA), Mayo Clinic Cancer Center (USA), Saroj Gupta Cancer Centre and Research Institute (India) and Tata Memorial Centre (India).This is the first collaborative initiative involving multiple government-supported and non-government cancer centers from India and the United States. The purpose of this consortium is to develop meaningful collaborations among the participating faculty of the cancer centers in key areas of cancer research and treatment, education, and community outreach activity. The partnership is expected to bring together stakeholders with interest in basic cancer biology, translational and precision oncology, cancer prevention programs and public health policy related to cancer. The consortium has identified several thematic areas to allow physicians, scientists, health care workers, and trainees to work together toward the common agenda of cancer research, education, and healthcare. The research collaboration of the cancer centers leverages each institution\u2019s strengths to develop premier research programs focused on key types of cancers that are most prevalent in the United States and India. Even though the interactions are primarily academic, the participating institutions have entered into a mutually acceptable confidentiality agreement to protect intellectual property. Any exchange of research materials is conducted under separate inter-institutional Material Transfer Agreements. This format enables the collaborations to jump-start without initial impediments, and a more involved Memorandum of Understanding (MoU) is developed based on the scope of each project.Working together, the cancer centers in the consortium form an integrated interdisciplinary network. Strong inter-institutional cooperation, cutting edge research concepts and state-of-the-art research infrastructure provide an excellent environment for translational and clinical research, as well as for mentoring of MSc, PhD, PharmD, and MD trainees and junior faculty. The consortium focuses on three themes: Theme 1, Cancer Biology; Theme 2, Translational Oncology; and Theme 3, Cancer Epidemiology, Surveillance, and Community Outreach, and brings together over 30 faculty with active research programs in basic science, clinical and translational research, and public health sciences related to cancer. The consortium faculty are chosen for each theme using criteria that include the strength of their research programs, history of mentoring domestic as well as international students and postdoctoral fellows, activity in co-publishing with other program faculty, and most importantly, passion to facilitate multidisciplinary training in global cancer research.The research aims incorporate plans to: (1) Identify critical signaling molecules, pathways, and mechanisms (Basic Sciences); (2) Discover new compounds and repurposed drugs that target key proteins involved in treatment resistance and discover biomarkers for treatment response ; (3) Develop new or repurposed drugs, or combine existing drugs for clinical trials ; (4) Enhance cancer surveillance and conduct cancer disparities research to promote cancer prevention behaviors . These aims support the objectives of: (a) Mentoring the next generation of medical oncologists interested in academic careers in cancer to become active participants in interdisciplinary cancer research; (b) Enhancing the academic and clinical success of clinicians, scientists, and research faculty; (c) Providing life science, cancer biology or pharmacy track students the requisite didactic training in the basic science of cancer and translational science of cancer biology and epidemiology including opportunities for interaction with clinicians/oncologists; (d) Strengthening global cancer research leadership and mentorship at the participating institutions.Prior visits of Markey Cancer Center teams and Mayo Clinic faculty to the cancer research institutions in India, and the intellectually stimulating breast cancer conferences organized jointly by the Markey Cancer Center, Manipal Academy of Higher Education and Tata Memorial Center in 2017 and 2018 provided the impetus to formalize the interactions by founding the Indo-American Cancer Consortium. The consortium activities started in mid-2020 and were facilitated by monthly virtual planning meetings. These interactions led to the first retreat in December 2020, held virtually due to COVID-19 travel restrictions, that provided an overview of the structure, organization, and programs at each of the participating cancer centers, an introduction to faculty research programs, and the consortium action plan. Since then, the consortium has been regularly organizing the following events:i) Research presentations by faculty and students of participating institutions (oncemonthly). ii) Thematic mini-symposium (occurring quarterly). iii) Featured seminar series with invited guest speakers (once monthly). iv) Didactic courses in: (1) Basic Cancer Biology, and (2) Translational Oncology andEpidemiology, for Masters, Ph.D., Pharm.D., and MD students. v) Certificate Program in Precision Medicine: Oncology Genomics for faculty atparticipating institutions; vi) Virtual tumor board meetings and discussions on tumor next-generation sequencingdata to guide oncologists on treatment options for Precision Oncology. vii) Multidisciplinary team collaborations \u2013 small group meetings involvingoncologists, basic scientists, pharmacists, pathologists, and epidemiologists todevelop focused research projects. viii) Scheduled exchange of faculty and students next year to further strengthen thepartnership in cancer research and training.The impact of the consortium is already apparent in the number of MSc, PhD, PharmD, and MD students from Manipal Academy of Higher Education, Saroj Gupta Cancer Center and Research Institute, and Tata Memorial Center registered for academic credit in cancer biology, epidemiology and therapy courses offered by the Markey Cancer Center; a CRDF-Global-NCI Cancer Research Training Travel Award to train consortium scientists from India at cancer centers in the United States; and joint research publications -10. The"} +{"text": "Following publication of the original article two errobold.The incorrect and correct information is listed below; the changes are shown in Abstractsignificant decline in sharp-curettage , and a decline in the duration of hospitalization of patients admitted for PAC .The implementation of PAC strategy in Kinshasa referral hospitals has resulted in the utilization of WHO recommended uterine evacuation method MVA , a Plain English summarysignificant decline in sharp-curettage , and a decline in the duration of hospitalization of patients admitted for PAC .The implementation of PAC strategy in Kinshasa referral hospitals has resulted in the utilization of WHO recommended uterine evacuation method MVA , a Abstractnon-significant decline in sharp-curettage , and a decline in the duration of hospitalization of patients admitted for PAC .The implementation of PAC strategy in Kinshasa referral hospitals has resulted in the utilization of WHO recommended uterine evacuation method MVA , a Plain English summarynon-significant decline in sharp-curettage , and a decline in the duration of hospitalization of patients admitted for PAC .The implementation of PAC strategy in Kinshasa referral hospitals has resulted in the utilization of WHO recommended uterine evacuation method MVA , a"} +{"text": "Aging in Latin America is occurring rapidly, in a context of high levels of poverty and inequality. This symposium is focused on population health and the heath-disparities found in some of Latin America\u2019s largest middle-income countries, Mexico, Brazil, and Colombia. This symposium contains presentations on different health-related issues affecting older adults, which can have further implications for wellbeing, health, and disease risk. The papers in this symposium examine a variety of health-related dimensions and disparities among older Latinos that include physiological functioning, cognition, and oral health. Using the Mexican Health and Aging Study (MHAS), Sheehan investigates the associations between personal and familial educational attainment on sleep quality. Also using MHAS, Milani. Using data from the Brazilian Longitudinal Study of Aging, Farina examines the relationship between race and cognition. Garcia uses data from the Colombian Survey of Health, Well-Being, and Aging to study the relationship between Motor Cognitive Risk Syndrome (MCRS) and cognition and frailty. Using the same dataset, Osuna examines variation in oral health in Colombian older adults and the impact this has on their wellbeing. Results indicate which population subgroups in Latin American have increased risk for poorer health and which dimensions of health have gender, race and socioeconomic disparities. The findings highlight the importance of understanding the conditions under which Latin American older adults are aging and the implications this can have in the future."} +{"text": "In parallel, Bangladesh Medical Research Council (BMRC) has announced the launch of \u2018Bangladesh Cancer Genome Atlas (BCGA) project with support from the ICGA teams. Teams from United States - National Cancer Institute (NCI) office of TCGA and Centre for Global Oncology, Institute of Cancer Research, London, United Kingdom are interested in extending their collaborations to these large-scale initiatives by acting as knowledge partners.The Cancer Genome Atlas (TCGA) is a landmark cancer genomics program that molecularly characterized over 20,000 primary cancer and matched normal samples spanning 33 cancer types. On similar lines, the establishment of an nd TCGA conference and workshop in India was organised with the theme of \u2018Towards Team Science for Multi-omics Studies in South Asia\u2019 on December 3\u20135, 2020. Over 1,500 delegates comprising of onco-clinicians, basic researchers, bioinformaticians, geneticists, translational researchers, big-data and machine-learning scientists, bioethicists and regulatory experts from across the globe attended the event. The conference agenda focused on the vision, design and plans of the ICGA project with regards to common standard operating protocols (SOPs), operations, logistics, bioethics, policy and governance models. More importantly, conference sessions were planned around the central theme of building a culture of team science for undertaking mega-cancer research projects in India and neighbouring countries. Experts from the globe deliberated on the latest technical aspects of data/biospecimen/multi-omics studies and applications of Precision Oncology in clinical cancer management.With this background, an online version of the 2 Over the last 15 years, The Cancer Genome Atlas (TCGA) program has characterized over 20,000 primary cancers and matched normal samples across 33 cancer types. By networking interdisciplinary researchers from across the world, TCGA has generated a massive 2.5 petabytes of genomic, epigenomic, and transcriptomic data. These data, not least through their publicly availability, have already led to significant and potential translatable benefits in the diagnosis, treatment, and prevention of cancer. The importance of the project and its participants was recently recognized with the prestigious 2020 American Association of Cancer Research \u2018Team Science Award.\u2019There are an estimated 800,000 new cancers cases in India each year and, recTo this end, the \u2018Indian Cancer Genome Atlas (ICGA)\u2019 was initiated in 2020 by forming a national consortium of government agencies, cancer hospitals, academic institutions, and private sector partners in India, led by the Council of Scientific and Industrial Research (CSIR). The ICGA will be a long-term collaborative effort between cancer scientists, basic researchers, onco-clinicians, data scientists, and technology providers to facilitate precision medicine and improve translational cancer research in India.The ICGA\u2019s mission is to create an indigenously developed, open-source, comprehensive database of multi-omics profiles of all possible cancers in Indian populations. The goal is the genomic, transcriptomic, epigenetic, and proteomic characterization of Indian cancers using advanced, next-generation multi-omics technologies. High quality meta-data of cancer patients and their biospecimens will be carefully and ethically collected from across the country. After standardized multi-omics profiling, data will be curated and analyzed in clinicopathological contexts, with the curated databases open-sourced to the Indian and global cancer research communities. To facilitate the uniformity, sanctity, and integrity of the meta-data and biospecimens collected from across India, a pan-India consortium of partners will operate as a \u2018hub-and-spoke\u2019 model in the form of the not-for-profit ICGA Foundation.-National Cancer Institute\u2019s (US-NCI) TCGA has formally agreed to serve as a knowledge partner and will provide technical, operational, troubleshooting, and quality assurance expertise to the ICGA. The Institute of Cancer Research (ICR), UK has formally agreed to help generate and analyze the data and share the data in real-time in a public database.The USAst TCGA conference organized in 2019 in India with the theme of \u201cMulti-omics Studies in Cancer: Learnings from The Cancer Genome Atlas (TCGA)\u201d. In addition to discussing the global trends in multi-omics research, the conference proceedings were focused on the need for developing a national mission program for multi-omics profiling of Indian cancer. These discussions laid the foundation of the ICGA project.The 1nd TCGA 2020 conference was organized in a virtual and online format to discuss these five main domains of the ICGA project. Highlighting governmental support for the conference and the ICGA, the Hon\u2019ble Dr Harshavardhan presented the conference keynote address. In his keynote address, Dr. Jean Claude Zenklusen shared his experiences of the genesis and implementation of TCGA and highlighted the need for a multi-disciplinary team approach for success of the ICGA.With this background, the 2There was strong multidisciplinary interest in the conference, with over 1500 delegates representing basic science, translational and clinical research, genomics, bioinformatics, biostatistics, and computational science and biology from academia, clinical medicine, industry, and governmental agencies. Delegates attended remotely from 36 countries around the world.The event was held over three days: (1) a one-day hands-on pre-conference workshop, where TCGA experts mentored attendees on various aspects of TCGA data mining; (2) conference presentations discussing global trends in multi-omics cancer research, particularly with respect to the technical aspects of clinical multi-omics studies and applications of precision oncology in the clinic; and (3) a full day of discussion between key ICGA stakeholders on the vision, design, and implementation of the ICGA with regards to common standard operating procedures, operations, logistics, and governance models. The conference sessions were planned around the central theme of building a culture of team science for undertaking mega-cancer research projects in India and neighboring countries.nd TCGA conference laid the foundation for the ICGA, and there was a wide consensus that the ICGA consortium will unite diverse expertise in cancer research in India and beyond. Given the high prevalence of breast cancer and unanswered questions around clinicopathological features of the disease in Indian women, the ICGA will begin its efforts with the large-scale multi-omics profiling of breast cancer patients in India. With this focus, the ICGA will develop and validate all protocols and ethical guidelines for subsequent sharing with the entire consortium to ensure uniform data generation and quality. It is anticipated that the economy of scale of the meta-analysis of all cancer data generated in India will help deliver cost-effective cancer research and accelerate bench-to-bedside translation to significantly positively impact the overall cancer burden in the country.The 2In an encouraging development, and motivated by the ICGA project, the Government of Bangladesh has also announced the creation of a Bangladesh Cancer Genome Project (BCGP) modeled on the TCGA and ICGA programs. This partnership will see two parallel large-scale cancer genomic projects span the Indian sub-continent to cover large populations in South Asia.nd TCGA 2020 Conference brought together the global cancer research community through a common goal to accelerate multi-disciplinary, collaborative, and nationwide initiatives in South Asia, which promises to transform clinical cancer research across the region. The 3rd TCGA Conference in 2021 will report progress on the ICGA and BGCP projects. Overall, these efforts are anticipated to deliberate on the emerging trends in precision oncology in the developing world.The 2The conference proceedings were partially funded by Bajaj Auto Ltd and DBT-Wellcome Trust India Alliance.The authors have no conflicts of interest."} +{"text": "Personal stories provide insight into the experience of illness as it intersects with one\u2019s identity. Prior studies by the first author examined identity as manifested in personal accounts of U.S. World War II veterans with and without dementia. The current study examines identity as revealed through written memoirs of middle-aged and older adults who have aphasia, from a cross-section of North American, European, and Australian cultures. The abrupt onset of stroke and associated aphasia, and the subsequent path toward re-engagement in life with an often-chronic communicative impairment, provide a unique window into the nature and evolution of the identity of the writer. The written modality offers an opportunity for reflective formulation that is not afforded to the memoir-writers in their verbal expression. Nineteen memoirs and biographical accounts of individuals with aphasia from a range of primarily individualistic cultures were examined for content reflective of the identity of the author, focused on post-stroke phases of restitution and quest. Primary authors were people with aphasia or rarely their close family member. Some were professional editors, poets or authors. Gender and life backgrounds were varietal. Manifestations of personal identity, its reinforcement, and its evolution were evidenced in: the provision of lessons learned from living with aphasia; content of letters exchanged with friends; engagement with family in life and recovery; fictional and poetic expression; spiritual insight; renewed or altered occupational pursuits; and comments on facing one\u2019s mortality. Findings hold implications for the cross-cultural practice of narrative medicine with the older adult population."} +{"text": "The National Institutes of Health (NIH) recognizes that, despite HIV scientific advances, stigma and discrimination continue to be critical barriers to the uptake of evidence-based HIV interventions. Achieving the Ending the HIV Epidemic: A Plan for America (EHE) goals will require eliminating HIV-related stigma. NIH has a significant history of supporting HIV stigma research across its Institutes, Centers, and Offices (ICOs) as a research priority. This article provides an overview of NIH HIV stigma research efforts. Each ICO articulates how their mission shapes their interest in HIV stigma research and provides a summary of ICO-relevant scientific findings. Research gaps and/or future opportunities are identified throughout, with key research themes and approaches noted. Taken together, the collective actions on the part of the NIH, in tandem with a whole of government and whole of society approach, will contribute to achieving EHE\u2019s milestones. Stigma and discrimination are human rights and public health issues in the United States and worldwide. They are among the most ubiquitous and consequential challenges to successful HIV prevention, treatment, and care \u20134. HIV-rRecognizing that preventing and reducing HIV-related stigma is a critical part of fighting the HIV pandemic and a key aspect of ending the HIV epidemic in the United States, the National Institutes of Health (NIH), an agency under the U.S. Department of Health and Human Services (HHS), designates HIV-related stigma research as a cross-cutting research priority in its HIV research program. This article discusses the NIH\u2019s approach to, and investment in, this priority area and its relevance to the Ending the HIV Epidemic: A Plan for America (EHE) initiative .The mission of the NIH is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.Within that mission, NIH has a robust and structured HIV research program that strives to advance rigorous and innovative research to end the HIV pandemic and improve the health of people with, at risk for, or affected by HIV across the lifespan .NIH has a significant history of supporting HIV-related stigma research across its Institutes, Centers, and Offices (ICOs) as a fundamental and cross-cutting research priority. Below is a brief overview of HIV-related stigma and discrimination research efforts NIH ICOs are leading and undertaking.Stigma is a key research area within the NIH HIV Research Program as stated in the FY 2021 \u2013 2025 NIH Strategic Plan for HIV and HIV-Related Research and as rThe Lancet on developing a research agenda to address stigma and global health ) , 12.Journal of the International AIDS Society (JIAS) a series of papers examining the state of the science and identifying the key gaps in measurement, methods and intervention research [In 2013, NIMH and partners published in the In 2016, the White House Meeting on HIV Stigma was convened by the NIH Office of AIDS Research (OAR), the National Institute of Mental Health (NIMH) and the Office of National AIDS Policy (ONAP) . The meeBMC Medicine in 2019. The 2017 workshop also helped inform the design and launch of FIC\u2019s new grant program in 2018, Reducing Stigma to Improve HIV/AIDS Prevention, Treatment and care in Low- and Middle-Income Countries (LMICs) (PAR-18-732 and PAR-19-326), which encourages multi-level intervention and measurement research, as well as the examination of HIV comorbidities/coinfections and intersectionality [In 2017, FIC and NIH partners hosted a three-day workshop in 2017 entitled \u201cThe Science of Stigma Reduction: New Directions for Research to Improve Health .\u201d Sixty ionality .In 2018, NIMH and NIH partners released the PRISM three RFAs (RFA-MH-19-410/411/412), Promoting Reductions in Intersectional StigMa (PRISM) to Improve the HIV Prevention Continuum . This RFIn 2020 and to date, NIH continues its investments in HIV-related stigma research and spearheading such key activities as the NIH OAR and NIMH sponsored 3-phase virtual workshop on HIV-related intersectional stigma and discrimination held in 2020 , its ongIn 2020, the National Institute on Drug Abuse (NIDA) and NIMH issued two RFAs (RFA-DA-21-001/002), under the title \u201cReducing Stigma Related to Drug Use in Human Service Settings.\u201d These RFAs supported early stage, domestic intervention trials or pre-intervention research to reduce stigma in the context of HIV prevention and care .The Office of the NIH Director (OD) is the central office at NIH for its 27 Institutes and Centers (ICs). The OD is responsible for setting policy for NIH and for planning, managing, and coordinating the programs and activities of all the NIH components. OD program offices include the OAR among others within the OD\u2019s Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI).NIH has 27 ICs, the majority of which have dedicated HIV research investments. ICOs undertake HIV research activities both independently and in partnership with other NIH ICOs and non-NIH stakeholders.The NIH OAR is an Office in the NIH OD within DPCPSI . OAR oveOAR actively initiates and develops cross-collaborations with stakeholders to inform and advance HIV prevention and treatment science, including the assessment of the impact of stigma on efforts to address HIV. The OAR has championed an HIV-related stigma research agenda, which has more than doubled since FY2015, with expanded research across the ICOs. OAR collaborates closely with HHS agencies including the Centers for Disease Control and Prevention (CDC), HRSA, Indian Health Service (IHS) and Substance Abuse and Mental Health Services (SAMHSA), as well as other strategic federal and bilateral partners such as the President\u2019s Emergency Plan for AIDS Relief (PEPFAR) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) to expand the impact of HIV-related stigma research. These collaborations involve strategies to measure and monitor stigma both nationally and internationally, sharing of plans and activities to address stigma among underserved populations, and discussions about how to fill gaps in the HIV-related stigma and discrimination research agenda. OAR seeks input from, and collaborates with, academic institutions and community members through dynamic listening sessions conducted across the U.S., and recently in international settings. The overall purpose of these listening sessions is to increase engagement with a diverse set of stakeholders representing various organizations, groups, populations, and individuals from the research, public health, and HIV-affected communities in order to enhance the framing of emerging, or unaddressed, issues to initiate new approaches and solutions. HIV-related stigma has been a recurring theme across listening sessions in all settings in recent years. In addition, focused conversations with local community constituents involved with HIV programs and services have provided a range of perspectives that contribute to building an extensive HIV stigma research portfolio. The OAR has also conducted HIV-related stigma scientific briefings as part of a series it conducts for NIH science staff on prescient HIV issues and research topics.The NIH HIV-related stigma research portfolio includes projects currently underway that support the EHE initiative goals to drive HIV incidence down by 75% by 2025 and 90% by 2030 . These iThe NIH Office of Behavioral and Social Sciences Research (OBSSR) was estaOver the course of the HIV epidemic, research-informed knowledge about HIV, early public disclosures of HIV status, destigmatization efforts by public figures, and community-driven advocacy campaigns collectively have contributed to both changes in HIV-related stigma and behavior changes , 29. HisThe NIH Office of Research on Women\u2019s Health (ORWH) serves a-OD-20-048) to facilitate the inclusion of U3 women and rigorous research on questions relevant to the health of women, including populations of women that experience stigma and health disparities or are otherwise socially or medically vulnerable [ORWH supports multidimensional, intersectional approaches to understanding and mitigating HIV-related stigma, as stigma manifests differently across cultural contexts and social settings. In the U.S., a disproportionate number of women diagnosed with HIV are members of ORWH-defined understudied, underrepresented, and underreported (U3) populations, including rural women, transgender women, women living at/near/below the poverty line and Black and Latina women \u201336. Recolnerable .2019\u20132023 Trans-NIH Strategic Plan for Women\u2019s Health Research [EHE will require the inclusion of women as a matter of scientific rigor, health equity, and policy planning. The Research describeThe NIH Sexual and Gender Minority Research Office was established in 2015 to coordinate, support, and help develop NIH-wide research and related efforts that advance the health of sexual and gender minorities (SGMs) . Many diSGMs are also disproportionately affected by certain health conditions and diseases . There aThese issues highlight the urgent need to improve existing paradigms and develop novel strategies to tackle health-related concerns and disparities stemming from or exacerbated by stigma related to HIV and SGM status and achieve health equity for all SGMs. There are significant data and training gaps on HIV stigma in SGM populations. This could be addressed, at least in part, through expanded collection of data on sexual orientation, gender identity, and sex (particularly with regard to intersex people and people with differences in sex development) in HIV-related stigma research, as well as in relevant research efforts in HIV and stigma individually. There is a concerning dearth of HIV, stigma, and HIV-related stigma research focusing on those SGM subgroups currently most affected by HIV . There is also a need to adapt and create stigma measures focused on and appropriate for members of the SGM community, incorporating their input wherever possible. In addition, SGM-specific cultural competency training for those who conduct research in HIV stigma-relevant fields and/or who provide healthcare to SGMs is crucial for avoiding further stigmatization and encouraging engagement in both areas by SGM people. Finally, SGMs comprise a highly diverse and heterogeneous community. Intersectional research that incorporates individual and structural factors is necessary to attend to the many dimensions that may contribute to or help ameliorate the impact of HIV stigma in SGMs. Pursuing these opportunities could greatly improve the health and well-being of SGM people facing HIV stigma. SGMRO is taking a leadership role in educating the NIH ICOs on these issues, promoting HIV-related stigma research through OD-level SGMRO initiatives, and in partnering with other ICOs in this important area.The Offices discussed above are noteworthy for their involvement and investments in HIV-related stigma research. These and other activities and partnerships are taking place among and across the OD offices. One example of this is the NIH Office of Disease Prevention (ODP) . HIV-relNIMH mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. The NIMH Division of AIDS Research interest in HIV-related stigma research and discrimination has been shaped by NIMH\u2019s emphasis upon basic behavioral and social science research, and NIH OAR\u2019s emphasis upon ending the HIV pandemic and improving health outcomes for people living with HIV , 51. NIMNIMH-funded research has advanced stigma models, measurement, mechanisms of action and interventions. A groundbreaking HIV stigma model led by Turan and colleagues is not only recognized in the HIV stigma research field, but it is also being adapted and applied to other health-related stigmas . A greatIn 2018, NIMH aimed to harness new tools and frameworks that move beyond a single focus on HIV stigma to examine HIV-related intersectional stigma and discrimination. A new funding opportunity announcement, \u201cPromoting Reductions in Intersectional StigMa (PRISM) to Improve the HIV Prevention Continuum (RFA-MH-19-410/411/412)\u201d was launched, which resulted in eight research awards funded by NIMH and NIH partners . NIMH alFICs mission is to support and facilitate global health research conducted by U.S. and international investigators, to build partnerships between biomedical research institutions in the U.S. and foreign countries, and to train the next generation of scientists to address global health needs . Over thAdditionally, it is also widely recognized that stigma is a global phenomenon and affects individuals across geographic locations, cultures, social structures and health statuses with the same effects on PLWH. Recognizing this need to break the cycle of HIV transmission by counteracting stigma, FIC initiated a new program, \u201cReducing Stigma to Improve HIV/AIDS Prevention, Treatment and Care in Low and Middle- Income Countries (R21)\u201d in 2017 to stimulate research to develop interventions to reduce HIV-related stigma and its impact on the prevention and treatment of HIV and on the quality of life of PLWH . To dateGiven the similarities between some LMICs and high-burden U.S. settings targeted by EHE initiative, and the similarities among stigma-related issues across global contexts, the research and research capacity building portfolio initiated for HIV-related stigma in LMICs can offer valuable lessons to the stigma research community in the U.S. and inform the EHE efforts. Over the past few years, FIC has collected case examples of interventions developed abroad that have been successfully transferred from LMICs to the U.S., with a focus on understanding the scientific processes by which these interventions have been adapted. In October 2020, FIC hosted a webinar titled \u201cTransferring HIV and Stigma Reduction Interventions from LMICs to the U.S.,\u201d which provided the scientific community with lessons learned from abroad, frameworks for intervention transfers, and key barriers and facilitators to HIV stigma-reduction research and implementation . The actThe National Heart, Lung, and Blood Institute's (NHLBI) mission is to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals. One of its strategic vision seeks to advance translational research and optimize clinical and implementation research to improve health and reduce disease for all, including stigmatized populations of PLWH and across the translational spectrum of HIV comorbid diseases . To addrCardiovascular healthcare disparities in vulnerable, underserved populations of PLWH worsen when they suffer from stigmas related to individual factors and social determinants. The intersections of multiple marginalized identities and multiple social positions of disadvantage affect the health of Blacks, Indigenous people, and people of color (BIPOC) who are also sexual and gender minorities , 101. AsAlthough HIV, mental illness, and physical disability health status intersect with other forms of stigma related to social identities such as race, gender, and sexuality \u2013110, litThe National Institute of Allergy and Infectious Diseases (NIAID) mission is to support basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. Its HIV research priorities include development of new HIV prevention, treatment, and cure products and strategies . The HIVSeveral key HIV prevention studies have illuminated the fact that HIV-related stigma is a powerful motivator for behavior, even in the more controlled setting of clinical trials. The results of the VOICE trial (MTN 003), which was testing Truvada daily oral pills, Tenofovir daily oral pills, and Tenofovir vaginal gel used daily in women for use as PrEP made very clear that HIV-related stigma played a significant role in participant behavior in the trial . One reaNIAID funds HIV clinical trial networks and the Centers for AIDS Research (CFAR) focused on Improving of HIV treatment, prevention, and cure . These nEunice Kennedy Shriver National Institute of Child Health and Human Development. Leads research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all [The for all . In 2020 for all . In addiScientific findings of NICHD HIV stigma research address our U.S. populations of interest through several different areas, including disclosure, family planning, healthcare transition, and technology. As willingness to disclose HIV status is often negatively associated with misconceptions about HIV transmission and stigma, interventions to support caregivers and families with the disclosure process address such barriers . RelatedFuture directions for NICHD HIV stigma research will continue to leverage several ongoing research programs and networks to improve HIV health outcomes among NICHD populations of interest. For example, the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) is the only domestic, multicenter research network devoted to the health and well-being adolescents and young adults at risk of and with HIV. Intended to support coordinated research efforts amongst investigators, community-based partners, and youth and young adults, the ATN develops, implements, and adapts its research agenda to respond to the HIV epidemic in the United States, including the role of stigma in HIV transmission. NICHD will continue to utilize such programs and databases to further its work in the area of HIV-related stigma research.The mission of the National Institute of Dental and Craniofacial Research is to improve dental, oral, and craniofacial (DOC) health . Across It is clear that unmet dental needs are a common challenge among people living with HIV, and the likelihood of an individual having an unmet dental need seems to increase with time since HIV diagnosis . Among oAcross the healthcare system, there is immense need for structural, social, and behavioral approaches that maximize the uptake of currently available tools for the prevention and treatment of HIV. Stakeholders in the dental community have long recognized potential roles for dental care providers in reducing the burden of HIV, though research and clinical practice have been slower to realize that vision. In an effort to advance research in this area and accelerate improvements in clinical practice, NIDCR has developed a new initiative to support research on how to optimally engage the dental workforce in meeting the unique needs of individuals living with or at risk of contracting HIV . Each ofNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) mission is to conduct and support medical research and research training and to disseminate science-based information on diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders, and obesity. Several health conditions addressed by the mission of NIDDK are associated with stigmas that often have negative impacts on psychosocial, educational, professional, and healthcare outcomes . Most noHow stigma associated with HIV impacts the development, exacerbation, and effective management and treatment of CCCs within NIDDK\u2019s mission remains poorly understood and needs to be better elucidated. There are several significant areas that could be explored. For example, stigmas often interact and, as discussed above, CCCs may be associated with specific stigmas of their own. Moreover, research focused on specific vulnerable populations needs to address how rather societal stigmas interact with the stigmas associated with HIV and CCCs. Understanding these pathways is a critical component of EHE, since PLWH with poorly managed CCCs may have poor patient engagement related to viral load monitoring and adherence to antiretroviral therapy. For example, NIDDK issued a research announcement with a focus on how societal factors, environmental barriers, and/or stigmas intersect with food insecurity and/or interventions for food insecurity in the context of CCCs, especially in vulnerable populations such as racial or ethnic minorities, sexual or gender minorities, sex workers, unaccompanied youth, older people, people with disabilities, rural residents, or people living alone .The National Institute on Drug Abuse\u2019s mission is to advance science on the causes and consequences of drug use and addiction and to apply that knowledge to enhance individual and public health including efforts to improve the prevention and treatment of substance use disorders . Stigma NIDA recognizes that drug use-related stigma is common in healthcare, social service and other settings related to HIV prevention and care and the drug use field has long acknowledged the presence of stigma as a barrier to adequate participation in prevention and care services, including those directed at HIV. Stigma in human service settings and self-stigma among PWUD can lead to insufficient access to substance use disorder treatment and harm reduction, as well as insufficient access to screening and care for co-occurring disorders such mental illness and HIV . ProvideStigma and Global Health conference that identified gaps in disease-associated stigma research and FIC-led program announcements to stimulate new research [NIDA is committed to informing and assisting EHE and other public health efforts through developing HIV stigma reduction interventions; supporting pilot, feasibility, implementation, and other studies; and testing new or adapted interventions to reduce stigmas that impede the effective provision, uptake, and utilization of HIV care and prevention services . The Insresearch . NIDA alThe National Institute on Minority Health and Health Disparities leads scientific research to improve minority health and reduce health disparities HIV/AIDSNIMHD understands that stigma related to HIV, race/ethnicity, and SGM status ultimately contributes to and maintains HIV disparities through its manifestations at the structural and individual levels; and it is a barrier to the prevention, care and treatment of HIV. NIMHD-funded stigma research has focused on the impact of intersectional stigma and other social determinants of health as they relate to HIV prevention, care and treatment for our populations of interest. We have also focused our attention on patient-clinician interactions and stigmatizing attitudes and beliefs held by health care providers; and interactions of cultural attitudes. In addition, NIMHD supports measurement research on SGM-related constructs, including intersectional and structural stigma and discrimination.NIMHD is focusing future research on interventions to prevent HIV in health disparity populations in geographic areas with high rates of new infections. Future directions for NIMHD include research initiatives that focus on the role of structural stigma and discrimination in causing and sustaining health disparities; as well as interventions to reduce stigma and discrimination.The National Institute of Nursing Research\u2019s mission is to promote and improve the health of individuals, families, and communities . This brLove, Sex and Choices which follows the lives of five women navigating relationship scenarios against a text messaging control [NINR supported the development and clinical trial of a digitally-delivered, private HIV education intervention that draws on the experiences of African American and Latina women living in urban U.S. cities. Investigators developed and tested a streaming, web-based intervention called control . The int control \u2013149. Ano control . The stu control . The int control .Looking forward, NINR recently awarded several research projects focused on the development and testing of community health worker strategies to improve self-management and durable viral suppression among people living with HIV who are out of care or struggling to maintain daily medication routine leading to viral suppression. The initiative is supported through OAR strategic funds and the research is in a geographically diverse set of EHE jurisdictions . As thisThe ICs discussed above are noteworthy for their involvement and investments in HIV-related stigma research. HIV-related stigma research activities and collaborations are taking place among and across these and other NIH ICs, at times with the involvement of OD offices as well. These partnerships and collaborations have and are strengthening the range and depth of the HIV-related stigma research being conducted at the NIH.Achieving EHE\u2019s goals will require a whole-of-society effort. As part of this, EHE is leveraging\u00a0critical scientific advances in HIV prevention, diagnosis, treatment, and care by coordinating the highly successful programs, resources, and infrastructure of many HHS agencies and offices, including the NIH.Developing and testing adaptations to improve interventions that have demonstrated efficacy in reducing HIV-related stigma and improving HIV outcomes across relevant settings, including health and public health contexts involved in HIV prevention and care services;Developing and testing interventions that address self-stigmas that impede people\u2019s use of HIV prevention or care services;Training healthcare, social service, and other providers during key points in their professional development, including their professional or specialty training to adopt non-stigmatizing approaches;Developing and testing interventions that enable AIDS and other service organizations to address potential sources of stigma and increase their reach of HIV prevention and care;Developing organizational or structural intervention approaches to reducing HIV-related stigma and improve HIV outcomes;Evolving the understanding of and interventions for HIV-related intersectional stigma and discrimination; and,Advancing new approaches to address multi-level factors that foster stigma and impede the use of HIV prevention and care services.Within this effort, it is recognized that HIV-related stigma is a dynamic and ubiquitous factor that must be considered and addressed in its many forms if EHE and other local and national efforts like it are to fully and robustly succeed. Given that HIV-related and other stigmas can occur at the individual, interpersonal, organizational and/or structural levels, and can be intersectional, there is still much to learn and to address. Key approaches the NIH is taking in the name of HIV elimination in the U.S. and around the world that specifically entails foci on HIV-related stigma include:Reducing HIV-related stigma and discrimination in healthcare settings;Improving communication competencies, integration of community voice and leadership, and partnership engagement overall;Taking whole person and whole society approaches;Understanding and addressing the challenges and needs of the stigmatized and those who stigmatize;Recognizing and addressing the impact of socio-structural dynamics and psychological factors driving HIV-related stigma;Improving models, measures, and mechanisms; andUnderstanding HIV-related stigma in context of other social determinants of health.As noted throughout this article, areas and themes needing further research, intervention, and implementation include:In closing, the broad span of the federal government itself has a role in addressing HIV as well as other stigmas and discrimination. Across the federal government, multiple agencies play a role in enforcing federal civil rights protections, providing technical assistance for carrying out the mandates of the American for Disabilities Act and other laws, and developing and disseminating information about civil rights and protections. While some Departments have authority to enforce these protections, nearly all can disseminate relevant information about protecting the rights of persons living with HIV and to take steps to confront and reduce HIV-related stigma.These actions on the part of the NIH, in tandem with the needed whole of government/whole of society approach, will contribute to achieving the EHE milestones and 2030 goal as well as work towards fulfilling the National HIV/AIDS Strategy: Updated to 2020 vision, that \u201cThe United States will become a place where new HIV infections are rare and when they do occur, every person regardless of age, gender, race/ethnicity, sexual orientation, gender identity or socio-economic circumstance, will have unfettered access to high quality, life-extending care, free from stigma and discrimination .\u201d And as"} +{"text": "The cerebroplacental ratio (CPR) is an important index for predicting adverse pregnancy outcomes in small-for-gestational-age and appropriate-for-gestational-age fetuses.To find out whether there is an association between the CPR level and the blood cord gases analysis in appropriate for gestational age fetuses.This cross-sectional study included 347 pregnant women at the gestational age of 37-40 wk. Patients had an appropriate-for-gestational-age fetus confirmed from their first ultrasonography results. Participants were divided into two groups based on their CPR, measured before delivery. Finally, after delivery, arterial blood gas level and the incidence of emergency cesarean section, intrapartum fetal distress and neonatal intensive care unit admissions were compared between the two groups.Fifty-four (15.6%) cases had a CPR below the detection limit of the assay. The incidence of fetal distress, emergency cesarean section, neonatal hospitalization in the neonatal intensive care unit, and pH The third-trimester CPR is an independent predictor of stillbirth and perinatal mortality and morbidity. The role of UA/MCA Doppler and the CPR in assessing the risk of adverse pregnancy outcomes should be evaluated prospectively. The cerebroplacental ratio (CPR) is an important index for predicting adverse pregnancy outcomes in small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) fetuses. The CPR is calculated by dividing the pulsatility index (PI) of the middle cerebral artery (MCA) by that of the umbilical artery (UA) (1).The CPR, which was first introduced in 1987, is recognized as a more sensitive Doppler index to predict perinatal outcomes, as it shows the status of both the placenta and fetus. Doppler indices for CPR measurements include the resistance index, the PI of the UA, and Doppler waveform indices of MCA. However, the CPR is not routinely measured in clinical practice (2).Intrapartum hypoxia is the cause of nearly 10-15% of cases of cerebral palsy. Despite the clinical importance of this condition, antenatal identification of fetuses at risk of cerebral palsy and other hypoxia-related outcomes remains a challenge. Hence, a prediction of fetal blood gas imbalance could be helpful for identifying the associated risks and preventing their consequences. Fetal CPR, measured within 72 hr after delivery, can help identify fetuses that are likely to require obstetric intervention for intrapartum fetal compromise (3).In this study, we aimed to determine the correlation between the CPR and neonatal outcomes in AGA fetuses.This cross-sectional study was conducted from December 2016 to February 2018 on young pregnant women referred to Dr. Shariati Hospital, a referral hospital affiliated to Tehran University of Medical Science, Tehran, Iran.A total of 403 pregnant women were recruited who were at the gestational age (GA) of 37-40 wk and had an AGA fetus according to their first ultrasonography. The exclusion criteria were a history of multiple pregnancies, history of preterm birth, fetal growth restriction, and fetal abnormalities. However, 56 women were later excluded due to a lack of sampling and other limiting conditions.Finally, participants were divided into two groups according to their CPR level, as measured before delivery. After delivery, the arterial blood gas (ABG) level, and the incidence of emergency cesarean section, intrapartum fetal distress and neonatal intensive care unit admissions were compared between the two groups.Color Doppler sonography of the UA and MCA was performed by a perinatologist before delivery via ultrasonography device . The CPR was calculated by dividing the PI of the MCA by that of the UA.The ABG was measured in the hospital's laboratory and the total number of cases who were admitted to the neonatal intensive care unit (NICU) was recorded. Fetal distress was evaluated with FHR monitoring.This study was approved by the ethics committee of Tehran University of Medical Sciences (Code: IR.TUMS.MEDICINE.REC.1396.4301). All patients provided informed consent prior to the study.t test. Differences in the pregnancy outcomes of the two groups were analyzed using the Chi-square test. P Data analysis was performed using Social Sciences statistical package v. 19 . Descriptive analyses were performed including means, and standard deviations. The baseline characteristics of the two groups were compared using the student's In this study, 403 pregnant women who met the inclusion criteria of the study were enrolled. During the study, 56 of these women were excluded .Patients were divided into two groups based on their CPR level (cut-off: 0.67 MOM).Participants in the two groups did not differ significantly in terms of demographic characteristics including maternal age, GA at the time of ultrasonography, and GA at the time of delivery (Table I).The incidences of fetal distress, emergency cesarean section, neonatal hospitalization in the NICU, and pH The results of all variables were different between the two groups. Based on the findings, it can be concluded that a low CPR is associated with a low Apgar score, low pH in the ABG of the neonate, and an increased rate of emergency cesarean section and NICU admission. As a result the third-trimester CPR is an independent predictor of stillbirth and perinatal mortality and morbidity.Numerous studies have shown that a low CPR indicates redistribution of fetal blood flow (brain-sparing) and predicts adverse outcomes in neonates. The abnormal fetal growth velocity, NICU admission, emergency cesarean section for fetal distress, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and even death are some of the adverse fetal outcomes (4-6).Term infants weighing The CPR is a preliminary diagnostic measure of pregnancy complications, which can be compared to the biophysical profile score and UA/MCA Doppler studies. The CPR can be used as an independent tool in evaluating of third-trimester fetuses, regardless of UA and MCA findings (1).Detection of stillbirth in prolonged pregnancies is linked to late placental insufficiency and fetal hypoxemia. Therefore, fetal Doppler monitoring may improve the management of fetal condition, although the literature suggests conflicting results. The CPR can help to detect fetal hypoxemia through two mechanisms of reduced resistance in MCA (brain-sparing effect) and increased placental resistance. The CPR has been shown to be more important than Doppler indices of MCA and UA alone in predicting adverse fetal outcomes, associated with growth restriction and prolonged pregnancy (10-12).There is much literature in this field, discussing the pros and cons of the CPR calculation and its features. A number of studies have shown an association between the CPR and growth rate as well as birth weight .Moreover, some researchers showed that the CPR is a major independent predictor of stillbirth and perinatal mortality, and the CPR has the highest sensitivity in the prediction of both intrapartum abnormal fetal heart rate and adverse neonatal outcomes in prolonged pregnancies .However, some believe that there is no relationship between pregnancy outcomes and CPR in prolonged pregnancies (10).The literature suggests that fetuses with CPRs They revealed that the CPR is a marker of impaired fetal growth velocity and adverse pregnancy outcomes, even in fetuses whose size is considered appropriate based on conventional biometry .The findings of this study demonstrate that a low CPR in AGA fetuses is an important marker of low neonatal pH.The CPR is an important factor in predicting the morbidity and mortality of infants. And a low CPR, even in normal weight fetuses, can be a sign of hypoxemia and placental insufficiency. However, this claim needs further investigation.The authors declare that there is no conflict of interest."} +{"text": "Nanotoxicology, a discipline transpired by the need to assess the human and environmental safety of nanoscale materials, has evolved over the past 15 years into a mature area of toxicology. Early on, nanotoxicology studies established a necessary understanding of dose-response relationships of nanomaterials using typical in vitro toxicology models, provided crucial information on interferences induced by nanoparticles (NPs) in the conventional toxicity assays and how to overcome these, and demonstrated that due to their unique physical\u2013chemical properties, nanomaterials act via different toxicological mechanisms than the bulk counterparts of the same materials. For example, ZnO, known as a water-insoluble compound in bulk form, was shown to exert toxicity through released Zn-ions in the case of ZnO NPs, and the cellular uptake pathways of NPs were discovered to depend on the size, shape, and surface properties of nanoscale particles. As the knowledge on NP toxicity mechanisms and behavior in the environment and organisms has accumulated, nanotoxicologists have acknowledged the need for improved understanding about the NP interactions with biological systems at the molecular level to better predict the potential toxicity of novel nanomaterials and ensure safe and sustainable development of nanotechnology.Accordingly, recent trends in nanotoxicology include incorporation of high-throughput screening approaches to establish structure-activity relationships using libraries of NPs with different properties and in vitro screening assays combined with computational analysis; omics- approaches, including metabolomics, proteomics, and transcriptomics, to discover molecular-level effects of NPs at low, sub-lethal NP concentrations, and method development to include sensitive toxicity assays for early detection of toxic effects. Environmental nanotoxicology is moving towards the direction of enhancing the relevance of testing conditions to these relevant to the environment and organism physiology, because NP toxicity has been proven to depend on the interactions with natural organic matter, anions and cations, the level of pH, and other environmental factors. Another major direction of nanotoxicology which has gained momentum in the recent years is the safety assessment of nanomaterials designed for applications in biotechnology, environmental bioremediation, wastewater treatment, agriculture, and nanomedicine. Thus, nanotoxicology has a substantial role not only in the risk assessment of unintentionally or intentionally produced nanomaterials but also in ensuring successful nanoinnovation across broad applications and enabling safe-by-design approach in nanotechnology.This Special Issue covers a range of topics regarding the latest research trends in nanotoxicology. The collection includes 10 research articles and 5 reviews by authors from 16 countries, spanning four continents, which illustrates the global significance of nano-enabled technology and its safety assessment. It is worth noting that, in addition to guest editors who both are female scientists, most of the lead authors of the papers of this Special Issue are female scientist which is an important tendency in the STEM areas. The topics of the research articles and review papers address both environmental nanotoxicity as well as human health and nanomedicine safety aspects, providing an excellent overview of the current status of these important sub-areas of nanotoxicology.2 nanospheres and TiO2 nanotubes to two freshwater algae with different morphology [2 nano-spheres and nanotubes was different from the toxicity of single exposures and depended on the microalgal species. Aravantinou et al. assessed the long-term toxicity of ZnO NPs to microalgae using a modeled natural water treatment system with a semi-continuous supply of NPs [Scenedesmus rubescens was used as a model due to its presence in municipal wastewater and its potential use for biofuel production. The study showed that low concentration (0.081 mg/L) of ZnO NPs, supplied at lower hydraulic retention time, slightly inhibited algal growth but enhanced the lipid content of S. rubescens, highlighting the need for further studies of NP-biota interactions in environmentally relevant conditions. The importance of considering the presence of natural organic matter in nanotoxicity studies has been well illustrated in the article by Bondarenko et al. who assessed the ecotoxicity of magnetite NPs in a plant and unicellular eukaryotic model, assessing the influence of humic acid on the toxicity of the NPs as well as Fe(II) and Fe(III) ions [Eisenia andrei, to study the toxicity mechanisms of nanoscale zero-valent iron (nZVI).The original research articles regarding environmental nanotoxicology address aspects that have been less explored in the nanotoxicology studies so far, such as combination toxicity and long-term toxicity of NPs. For example, Wang et al. investigated the toxicity of the binary mixture of TiOrphology . They foII) ions . In anotII) ions . DevelopII) ions . They us2 NP toxicity, and specifically clarified the mechanism of cell death caused by the combined exposure to UVA and TiO2 NPs [2 NPs under UVA irradiation in HeLa cells and showed that the abnormal membrane integrity and the ultrastructure of HeLa cells, together with the decreased viability induced by TiO2 NPs under UVA irradiation, were due to cell necrosis rather than caspase-dependent apoptosis.The method development and application of novel omics approaches, which can provide molecular-level information about NP biological effects, were also the focus of research articles regarding the human health and nanomedicine safety. Enea et al. applied an innovative and sensitive approach\u2014metabolomics\u2014to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars of similar ~40 nm diameter, coated with 11-mercaptoundecanoic acid, 24 h after an intravenous administration to Wistar rats . Using aTiO2 NPs . They inSeveral articles in the Special Issue discuss the beneficial properties on NPs and the associated mechanisms as well as safe environmental application of NPs. In their research paper, Sguizzato et al. report on the development of a formulation for caffeic acid cutaneous administration . The nanStaphylococcus aureus (MRSA) and biofilm eradication in clinical settings [Clinical applications of NPs and associated safety concerns have been discussed in three review articles. Mosselhy et al. review recent advances in nanotheranostics focusing on the issue of detecting methicillin-resistant settings . The autsettings . A specisettings . The autIn summary, the article collection in this Special Issue addresses important recent trends in nanotoxicology, both from the environmental and human health safety aspects. The articles illustrate the directions where the toxicity studies of NPs are headed: employing novel and sensitive methods which provide molecular level information about the mechanisms of action of NPs, focusing on the NP-biomolecule interactions, development of biomarkers for early detection of NP toxicity, and guiding safe-by-design strategies for NPs."} +{"text": "Lacazia loboi in the cutaneous and subcutaneous tissues, with the presence of isolated nodular and coalescent keloidal lesions. Malignant degeneration is rare. This case report describes a 64-year-old male patient with JLD for 30-years who showed a change in the aspect of a lesion in the left lower limb. Histopathological examination confirmed the progression to well-differentiated squamous cell carcinoma (SSC). JLD is highly prevalent in tropical and subtropical regions, requiring monitoring concerning the transformation into SSC in long-term lesions.Jorge Lobo\u2019s disease (JLD) is a chronic, granulomatous fungal infection caused by the traumatic implantation of the fungus Lacazia loboi.Lacazia loboi (Jorge Lobo\u2019s disease (JLD) is a chronic granulomatous infection of the skin and subcutaneous tissue, without visceral dissemination, which is caused by the fungus ia loboi . Left inJLD, first described in 1931 by Jorge Lobo in a patient from the Amazon region, is a typical infection in tropical and subtropical areas, more common in men aged 20 to 40 years.5None declared.Arival Cardoso de Brito: Approval of the final version of the manuscript; design and planning of the study; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Maraya de Jesus Semblano Bittencourt: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; critical review of the manuscript.Thain\u00e1 da Silva Gon\u00e7alves: Approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.Renata Henriques Cavalcante: design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature.None declared."} +{"text": "The Support at Home pilot program provided financial support for home care services by middle-income adults with disabilities in San Francisco to support aging in place. This presentation reports the results of the mixed-methods evaluation of the program, which incorporated administrative records, surveys of clients and comparison group members, surveys of informal caregivers of clients, surveys of the care providers hired by clients, and focus groups with clients and with informal caregivers. Outcome measures included the Older People\u2019s Quality of Life Questionnaire, Patient Health Questionnaire-2, an adapted Burden Scale for Family Caregivers, and self-reported falls, emergency department visits, and hospitalizations. Analyses included pre-post chi-squared and t-test comparisons and comparisons of changes between the client and comparison groups. Multivariate regression analyses were conducted to control for demographic differences between the groups. An economic analysis was conducted to learn whether changes in costs associated with medical appointments, emergency department visits, and hospitalizations were greater than the costs of the program, including both voucher and administrative costs. Results indicated statistically significant positive changes in personal stress and financial stress, but not in the composite quality of life score. There also were statistically significant reductions in attendance at medical appointments, falls, emergency department visits, and hospitalizations. The focus group data supported the findings regarding personal and financial stress, and also indicated that clients and their caregivers perceived positive quality of life benefits. The economic analysis indicated substantial cost savings from the program due to reduced use of medical services."} +{"text": "ABSTRACT IMPACT: Development and implementation of a parent navigator program to help parents of justice-involved youth could assist parents in navigating the justice system, improve engagement with court and probation, and ultimately improve outcomes for youth involved in the juvenile justice system OBJECTIVES/GOALS: The goals of the study are to (1) develop a parent-peer navigator program utilizing community-based participatory design; and (2) implement and assess the feasibility of a parent peer navigator program in an urban juvenile justice system. METHODS/STUDY POPULATION: The EPIS framework will guide development and implementation of the navigator program as well as measurement of the implementation process, including measurements of feasibility and acceptability. In the Exploration phase, qualitative interviews with juvenile justice staff, parents of justice-involved youth, and members of the local family advisory board will inform program needs. In the preparation stage, I will work closely with the family advisory board to develop the actual parent navigator program protocol, including a training plan for navigators and their specific roles. I will conduct an open trial in the implementation phase, measuring program feasibility and acceptability among parents, navigators, juvenile justice staff, parents, and youth utilizing mixed methods. RESULTS/ANTICIPATED RESULTS: Results will inform feasibility of implementing the program as well as acceptability of the program based on mixed methods data from parents of justice-involved youth, juvenile justice staff, family advisory board members, and other community stakeholders. Results will potentially inform conduct of a larger scale pilot hybrid implementation-effectiveness study. DISCUSSION/SIGNIFICANCE OF FINDINGS: Development and implementation of a parent navigator program to help parents of justice-involved youth could assist parents in navigating the justice system, improve engagement with court and probation, and ultimately improve outcomes for youth involved in the juvenile justice system."} +{"text": "There has been little focus on designing tailored diabetes management strategies in developing countries. The aim of this study is to develop a theory-driven, tailored and context-specific complex intervention for the effective management of type 2 diabetes at a tertiary care setting of a developing country. We conducted interviews and focus groups with patients, health professionals, and policymakers and undertook thematic analysis to identify gaps in diabetes management. The results of our previously completed systematic review informed data collection. We used the United Kingdom Medical Research Council framework to guide the development of the intervention. Results comprised 48 interviews, two focus groups with 11 participants and three co-design panels with 24 participants. We identified a lack of structured type 2 diabetes education, counselling, and collaborative care of type 2 diabetes. Through triangulation of the evidence obtained from data collection, we developed an intervention called VICKY (patient-centred collaborative care and structured diabetes education and counselling) for effective management of type 2 diabetes. VICKY comprised five components: (1) patient-centred collaborative care; (2) referral system for patients across transitions of care between different health professionals of the diabetes care team; (3) tools for the provision of collaborative care and documentation of care; (4) diabetes education and counselling by trained diabetes educators; and (5) contextualised diabetes education curriculum, educational materials, and documentation tools for diabetes education and counselling. Implementation of the intervention may help to promote evidence-based, patient-centred, and contextualised diabetes care for improved patient outcomes in a developing country. Type 2 diabetes is a global public health problem and an economic burden to nations, particularly developing countries . It contIneffective management of type 2 diabetes has been associated with poor clinical outcomes, which include disease progression, and increased health services utilisation, such as repeated hospitalisations and high all-cause mortality ,6,7. In Patient-centred collaborative care and the use of culturally tailored interventions, including behavioural interventions, can improve diabetes care in low-income countries ,24,25. EThe aim of this study was to develop a theory-driven, tailored, and context-specific complex intervention for the effective management of type 2 diabetes at a tertiary care setting of a developing country.The study was undertaken at the diabetes centre of a tertiary teaching hospital in Addis Ababa, Ethiopia. Diabetes care is provided at the diabetes centre of the hospital by endocrinologists, endocrinology fellows, internal medicine residents, and nurses . Each moThe United Kingdom Medical Research Council (UK MRC) frameworDeveloping a complex intervention involves three steps : (1) ideThe first stage in the development of a complex intervention is to identify an existing, relevant evidence base . We undeIdentification and development of appropriate theory in intervention design is key to understanding the possible processes of change ,44. The We used a co-design panel comprising patients, health professionals, and policymakers at TASH and the Ministry of Health of Ethiopia with a representative of the Ethiopian Diabetes Association and incorporated the findings from the systematic review , interviThe first co-design workshop involved health professionals, policymakers from TASH and the Ministry of Health of Ethiopia, and a professional officer from the Ethiopian Diabetes Association . During We conducted the second co-design workshop with patients with type 2 diabetes . The purWho needs to perform the behaviour?What do they need to do differently to achieve the desired change?When do they need to do it?Where do they need to do it?How often do they need to do it?With whom do they need to do it?A joint workshop was undertaken with a nominated patient, health professionals, policymakers, and a professional officer from the Ethiopian Diabetes Association. The workshop involved examining the defined problem related to the effective management of type 2 diabetes and the selected potential target behaviours during the two separate workshops (workshop I and II). The workshop panel members specified the target behaviours that were agreed upon. In workshop III, the panel members discussed and reached a consensus on the defined problem related to effective management of type 2 diabetes and the selected potential target behaviours at workshops I and II . The criThe co-design panel worked through stage one to stage three of the behaviour change intervention design process . The steThis stage involved four steps 47]. St. St47]. Decide what \u2018intervention functions\u2019 to apply: education, persuasion, incentivisation, coercion, training, restriction, environmental restructuring, modelling, and enablement;Select implementation strategy: fiscal policy, legislation, regulation, environmental planning, communications, service provision, and guidelines development. This stage involves the use of the behavioural diagnosis to: DeciDevelop a detailed intervention plan by selecting from among a range of specific behaviour change techniques (BCTs) . Michie Create the detailed intervention specification covering all aspects of content and delivery of the intervention structured around the chosen BCTs and modes of delivery. The focus of the third stage is to:Appropriate intervention functions, BCTs, and intervention contents were determined through discussion between the co-design panel and the research team and using the APEASE criteria . The APEModelling of a complex intervention helps toIn this study, we operationalised the intervention functions and BCTs into a complex intervention to improve the effectiveness of type 2 diabetes management. The researchers collaborated with the co-design panels in operationalising the intervention functions and BCTs into the mode of care delivery using the BCW framework . We usedWe undertook interviews with 48 participants and two focus groups (n = 11) with patients with type 2 diabetes, health professionals, and policymakers from TASH and the Ministry of Health of Ethiopia comprisiEvidence from the interviews and focus groups we have undertaken, previous findings ,12,13,60Lack of resources, such as medications, laboratory, and diagnostic tests;Lack of continuity of care, such as prolonged follow up clinic visits;Lack of knowledge and awareness of patients about type 2 diabetes and its complications;Lack of self-care activities;Low level of type 2 diabetes education and counselling services;Low competence and experience of health professionals providing diabetes care;Inefficient collaboration among health professionals in the care of type 2 diabetes;Absence of involvement of clinical pharmacists, dietitians or nutritionists, and psychologists in the care of type 2 diabetes.We identified through interviews, focus groups, and co-design workshops that had challenges for the effective management of type 2 diabetes related to:Our findings from interviews and focus groups demonstrated that the problem of the effective management of type 2 diabetes can be addressed through multiple behaviours targeted in a complex intervention. These include: ensuring continuity of care; enabling provision of structured type 2 diabetes education and counselling by competent health professionals; providing collaborative care of type 2 diabetes, involving clinical pharmacists, dietitians or nutritionists, and psychologists in type 2 diabetes care; improving health professionals\u2019 competency, commitment and professional ethics; and improving the referral system of patients with type 2 diabetes between TASH and other health institutions . The co-Provide structured diabetes education and counselling with competent health professionals;Enable collaborative care of type 2 diabetes;Involve clinical pharmacists, dietitians or nutritionists, and psychologists in the care of type 2 diabetes as members of the collaborative care team;Improve health professionals\u2019 competency, commitment, and professional ethics through trainings.During the co-design workshop, the co-design panel prioritised the potential target behaviours, out of which the four potential target behaviours are listed from highest to lowest priority:Similarly, the co-design panel in workshop II identified and prioritised the following potential target behaviours for intervention in descending order of priority.Ensure continuous availability of medications;Ensure continuous availability of laboratory and diagnostic tests;Involve clinical pharmacists, dietitians or nutritionists, and psychologists in the care of type 2 diabetes as members of the collaborative care team;Enable collaborative care of type 2 diabetes;Integrate all type 2 diabetes care services at the diabetes centre.Given the evidence from the interviews, focus groups, and previous findings ,30,61, bThe co-design panels confirmed that there was no involvement of clinical pharmacists, dietitians or nutritionists, and psychologists in the provision of type 2 diabetes care. It was found that there was a profound deficiency of the collaborative care of type 2 diabetes at the diabetes centre of TASH. A collaboratively working care team is more likely to be responsive, efficient, and provide improved care . As multAfter the selection of the potential target behaviours for intervention, the co-design panel in workshop III specified the two target behaviours, namely to enable the provision of structured type 2 diabetes education, counselling, and collaborative care of type 2 diabetes. These details are found in the table of The findings of the interviews, focus groups, and co-design panel workshops indicated the need for the involvement of physicians, nurses, clinical pharmacists, dietitians or nutritionists, psychologists, and peer diabetes educators in the provision of structured diabetes education and counselling with patients or family members (caregivers) to improve the care of type 2 diabetes at TASH. The structured diabetes education involved the education of patients with type 2 diabetes about the condition, its complications, and management and self-care activities .In enabling the collaborative care of type 2 diabetes, physicians, nurses, clinical pharmacists, dietitians or nutritionists, and psychologists would work in coordination with patients and their families (caregivers), administrative bodies of the hospital, and the Ministry of Health of Ethiopia. A collaborative care team would be organised at the diabetes centre of TASH. The duties and activities of each member of the diabetes care team are described in the table of We used the COM-B system to identThe provision of structured diabetes education and counselling at TASH was hampered by a lack of availability and involvement of trained and qualified multidisciplinary health professionals in diabetes education and counselling (C). Insufficient time for the consultation of patients (O) and inadequate space (O) led to a lack of physical opportunity to provide structured diabetes education and counselling about type 2 diabetes. Patient adherence to diabetes educations sessions (O) negatively affected the provision of type 2 diabetes education at TASH. A triangulation of evidence from the interviews, focus groups, systematic review , co-desiTime shortages and inappropriate space (O), poor communication among health professionals (O), lack of commitment and motivation of health professionals and policymakers (M), and absence of policies and guidelines for collaboration (O) contributed to a lack of collaborative care of type 2 diabetes at TASH. We triangulated the findings from interviews, focus groups, the co-design panel workshops, and the research team discussions and performed the behavioural analysis using the COM-B . We analIntervention functions appropriate to the context of TASH and that help to improve the management of type 2 diabetes were determined using the APEASE criteria Table S.We used the BCW mapping We linked the COM-B components of the collaborative care of type 2 diabetes with intervention functions using the BCW mapping After identification of the intervention functions, we evaluated the appropriate policy categories that support the delivery of the intervention functions using the APEASE criteria . GuideliFeedback on behaviour;Self-monitoring of behaviour;Prompt/cues;Salience of consequences;Instruction on how to perform the behaviour;Demonstration of the behaviour;Restructuring the physical environment;Restructuring the social environment;Adding objects to the environment;Goal setting behaviour;Action planning;Social support (unspecified).Behaviour change techniques are active components of an intervention designed to change behaviour that helWe operationalised the identified BCTs and identified modes of delivery for the provision of structured education and counselling with trained diabetes educators and collaborative care of type 2 diabetes and developed a complex intervention . We creaThe complex intervention (VICKY) consisted of five components .The following 13 BCTs were linked to the intervention functions for the target behaviour in the collaborative care of type 2 diabetes .Self-monitoring of behaviour;Prompt/cues;Feedback on behaviour;Instruction on how to perform the behaviour;Restructuring the physical environment;Restructuring the social environment;Adding objects to the environment;Demonstration of the behaviour;Goal setting behaviour;Action planning;Social support (unspecified);Social support ;Problem solving.We used the logic model to link This paper describes a systematic development of a tailored complex intervention to improve the effectiveness of the management of type 2 diabetes in a tertiary care setting of a developing country. To our knowledge, the complex intervention is the first theory-driven and context-specific intervention designed using the first stage of the UK MRC framework and the BCW and co-design approaches for the management of type 2 diabetes in Ethiopia.Our intervention addresses an organisational level intervention that involves multiple stakeholders and multifaceted approaches, such as the training of health professionals, provision of educational materials, collaborative care, and patient involvement in the care process. Multifaceted approaches have been demonstrated to be successful in improving healthcare in resource-limited settings, including SSA ,70,71,72Implementation science offers opportunities to design novel healthcare approaches to ensure the utilisation of resources for evidence-based healthcare delivery in developing countries, including SSA ,77. EffoThe MRC framework guided tThere have been tailored complex interventions ,48 desigWe designed an organisational level intervention to improve the effectiveness of type 2 diabetes management. There is a broad range of evidence internationally in support of organisational interventions to improve the care of type 2 diabetes and patient outcomes ,55,56. SDiabetes care models of developed countries are evidence-based, patient-centred, team-based, and guided by contextually tailored diabetes management guidelines and educational materials, where diabetes education by trained diabetes educators are essential elements of care ,96,97. SOur proposed intervention involves the collaborative care of diabetes, diabetes training of health professionals, and diabetes education by a trained team of health professionals. Evidence also indicates that the diabetes care team needs to incorporate a multidisciplinary group involving physicians, nurses, clinical pharmacists, dietitians or nutritionists, and psychologists ,63,64,65This study has some limitations. We did not include the views of nutritionists or dietitians, psychologists, and laboratory personnel in the intervention design. The intervention was designed at a single healthcare setting, requiring feasibility and piloting prior to evaluation and implementation. Nevertheless, the information obtained can be transferred to other similar settings.This paper indicated the usability and applicability of the UK MRC framework and the BCW to designing tailored and evidence-informed behaviour change interventions in SSA. We developed the UK MRC-guided intervention called patient-centred collaborative care and structured diabetes education and counselling (VICKY) using the BCW. VICKY, which is a tailored intervention to the context of a tertiary care setting of a developing country, is a complex intervention for diabetes management to be tested for feasibility and effectiveness in later phases of this project. This intervention will help to manage diabetes effectively by addressing the current practice gap existing at the hospital, and the country in general. VICKY is a comprehensive diabetes care model co-designed by key stakeholders involving consumers, healthcare providers of various disciplines, and policymakers using multiple evidence sources. This model, if found effective, may serve as a springboard to design similar tailored interventions for other non-communicable diseases in the country."} +{"text": "The European Union Directives stipulate mandatory tests for the presence of any infections in donors and donations of substances of human origin (SoHO). In some circumstances, other pathogens, including fungi and parasites, may also pose a threat to the microbial safety of SoHO.The aim of the two systematic reviews is to identify, collect, and evaluate scientific evidence for the presence of fungal and parasitic infections in donors and donations of SoHO, and their transmission via transfusion and transplantation.An algorithmic search, one each for fungal and parasitic disease, was applied to 6 scientific databases . Additionally, manual and algorithmic searches were employed in 15 gray literature databases and 22 scientific organization websites. The criteria for eligibility included peer-reviewed publications and peer-reviewed abstract publications from conference proceedings examining the prevalence, incidence, odds ratios, risk ratios, and risk differences for the presence of fungi and parasites in donors and SoHO donations, and their transmission to recipients. Only studies that scrutinized the donors and donations of human blood, blood components, tissues, cells, and organs were considered eligible. Data extraction from eligible publications will be performed independently by two reviewers. Data synthesis will include a qualitative description of the studies lacking evidence suitable for a meta-analysis and a random or fixed-effect meta-analysis model for quantitative data synthesis.This is an ongoing study. The systematic reviews are funded by the European Centre for Disease Prevention and Control, and the results are expected to be presented by the end of 2021.The systematic reviews will provide the basis for developing a risk assessment for fungal and parasitic disease transmission via SoHO.PROSPERO International Prospective Register of Systematic Reviews CRD42020160090; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020160090 ; PROSPERO International Prospective Register of Systematic Reviews CRD42020160110; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020160110DERR1-10.2196/25674 Trypanosoma cruzi) [The European Union Directives have set safety interventions to prevent transmission of infections through substances of human origin (SoHO) ,2. The sa cruzi) .Surveillance data on the presence and transmission of pathogens via cells, tissue, and blood are currently collected at the national and European Union levels. However, no such data are yet available for organ transplantations . GloballThe systematic review protocols are registered with PROSPERO ; registration numbers: CRD42020160090, CRD42020160110 ,9. The PWe will employ the FINER approach to test A pilot search demonstrated an adequate number of studies for inclusion in the systematic reviews. The algorithmic search in the PubMed database retrieved 2320 and 1895 publications on the relevant fungal and parasitic infections, respectively. Additionally, the technical expertise of the review team, the time allocation, and the available funding guarantee its successful completion.The research questions are interesting as the systematic reviews aim at providing vital information on mitigating the risk of fungal and parasitic diseases transmission via SoHO. This is significant because fungal diseases kill >1.5 million and affect >1 billion people annually globally , while pThe systematic reviews will confirm or reject the earlier findings and produce new findings on the fungal and parasitic infections transmission risks via SoHO donations or contaminations, which would be used to develop future preventive interventions.There are no ethical concerns regarding the current systematic review processes, as it will be entirely based on evidence accumulation from earlier studies.The research questions are relevant to current scientific knowledge, clinical practices, and health policies.The selection of the information sources was based on the relation of scientific topics to the systematic review research questions and information retrieved from analysis regarding the optimal database combination for biomedical systematic reviews . The revScientific databases for peer-reviewed publications included PubMed, EMBASE, Web of Science, Scopus, Cochrane Library , and CINAHL.Databases for gray literature included JSTOR, OpenGrey, ROAR, ROARMAP, OpenDOAR, GreyNet, British Library, TextRelease, APO, bioRxiv, arXiv, Google Scholar, Infectious Disease Advisor, Healthfinder, and TRIP (Turning Research into Practice).Scientific organization websites for identifying peer-reviewed publications, technical reports, and guidelines containing original data included World Health Organization; European Commission; ECDC; Centers for Disease Control and Prevention (CDC); National Health System, United Kingdom; International Foundation for Care; National Health Information Center; Agency for Toxic Substances and Disease Registry; Food and Drug Administration; Indian Health Services; National Center for Chronic Disease Prevention and Health Promotion; National Center for Emerging and Zoonotic Infectious Diseases; National Center for Health Promotion and Disease Prevention, Veterans Health Administration; National Center for Human Immunodeficiency Virus, Sexually Transmitted Disease, and Tuberculosis Prevention, CDC; National Institutes of Health; National Institute of Environmental Health Sciences; Office of Public Health Genomics, CDC; American College of Preventive Medicine; Robert Koch Institute; Australian Department of Health and Aging; National Notifiable Diseases Surveillance System; and ClinicalTrials.gov.The search strategy was based on the guidelines of the Cochrane Library , while rThe official searching procedure for the gray literature databases and the organizations' websites was accomplished by three members of the review team . Following the selection process, a search for the reference lists of systematic reviews, meta-analyses, technical reports, and guidelines relevant to the research questions will be done. Finally, the reference lists of the eligible publications will be screened to identify any research questions\u2013related publications missed out in the initial searching.The inclusion criteria are set for the types of studies, types of participants, and extracted data items.The review team identified the following types of studies to be included as eligible in the systematic review: (1) peer-reviewed experimental, epidemiological studies of any methodological design and case reports that examined the prevalence, incidence, odds ratios, risk ratios, and risk differences of the presence of the fungal and parasitic infections in SoHO from an infectious donor or contaminated donation to recipients; (2) peer-reviewed in vitro studies that explored the presence of fungi and parasites in SoHO donors and donations, and transmission via SoHO to humans; (3) technical reports or guidelines by any relevant organizations, where eligible peer-reviewed publications and related original data can be detected; (4) articles from any organizations that investigated disease prevention relevant to the research objectives; (5) outputs in any language; (6) no date limits will be applied in the selection of eligible publications; (7) only peer-reviewed conference proceedings will be eligible from the gray literature, as failure to recognize trials reported in conference proceedings may impose a risk of bias in the effect estimates .The type of participants in the eligible studies will be humans. The term \u201csubstances of human origin\u201d refers to blood, blood components, tissues, cells, and organs. As a result, therapeutic and diagnostic products derived from humans will not be included in the systematic review. Therefore, the interventions to be considered will be blood and blood components\u2019 donations and transfusions in humans, and tissue, cell, and organ donations and transplantations in humans.The other data items that will be extracted from the databases include the following: (1) population demographics from eligible studies; (2) number of cases and percentages of fungal and parasitic infections in SoHO donors and donations, and their transmission via SoHO donations; (3) the prevalence of fungal and parasitic infections in SoHO donors and donations, and transmission via SoHO donations; (4) odds ratios, risk ratios, and risk differences of the fungal and parasitic infections among SoHO donors and donations, and their transmission risks via SoHO donations between intervention and control groups ; (5) associations of donor derived SoHO\u2013related fungal and parasitic disease transmission with demographic characteristics of the population and with any other factor susceptible to the infections; (6) diagnostic methods for the transmissions associated with the relevant SoHO donations (not those related to other exposures); (7) medications received by patients before and during diagnosis; (8) follow-up measures including hospitalizations and deaths; (9) risk factors of the fungi and parasitic infections or contaminations in SoHO donors and donations, and transmissions via SoHO donations; (10) type of infection screening tests in SoHO donors; and (11) country and continent of the population of eligible studies.The exclusion criteria will be: studies not identifying the transmission of the fungal and parasitic diseases via SoHO donations; animal studies; in vitro studies; reviews, systematic reviews, and meta-analyses; letters to editors and opinion papers; theses and dissertations; and gray literature besides the published peer-reviewed conference proceedings relevant to the systematic reviews\u2019 research questions.Two members of the review team will select the eligible publications independently. A referee investigator will be asked to decide in case of a disagreement between the two reviewers. The Cohen kappa test will be used to measure the interrater agreement in selecting the eligible publications . A studyAn individual data extraction form (Cochrane Library model) will be The priority of the outcomes of this systematic review are as follows: (1) intervention type ; (2) the association of the presence of fungal and parasitic infections in SoHO donors, donations, and their transmission through SoHO donations with any physiological and demographic characteristics of the populations, including aspects such as environmental conditions; (3) the prevalence of the presence of fungal and parasitic infections in SoHO donors, donations, and transmission via SoHO donations; (4) odds ratios, risk ratios, risk differences, and hazard ratios of fungal and parasitic infections or contaminations in SoHO donors, donations, and their transmission via SoHO donations; (5) cause of the infection in donors or the contamination of donation; (6) the type of screening test of infection and the donor types; (7) hospitalizations and deaths; (8) region (country and continent); and (9) diagnostic method.The review team will use the methodological design of each eligible publication to determine the risk of bias assessment. Three appropriate tools are going to be used: the Cochrane Library tool for the The eligible studies with data not suitable for meta-analysis will be summarized into a qualitative description. In the case of the eligible studies with pertinent data for meta-analysis, a random or fixed-effect meta-analysis model will be used to account for heterogeneity due to differences in study populations, types of infections, interventions, study durations, and other factors. All meta-analyses will be conducted using the RevMan 5.3 software .The prevalence for meta-analysis will be calculated using the following formula Standard errors for the meta-analysis will be calculated using this formula Standard errors will then be used for weighted proportions, and the RevMan 5.3 software will be I2 statistic. The results for heterogeneity will be considered statistically significant at P<.10, while the I2 index interpretations will be made based on earlier guidelines [The 95% CI and heterogeneity between studies will be evaluated using the idelines . Small sidelines . The risidelines . Finallyidelines .The reporting of the eligible publications will be checked independently by two review team members, while a referee will make the final decision in case of a discrepancy between them. The interrater agreement in the evaluation results will be tested using the Cohen kappa test . The 25-Two reviewers will independently appraise the implications and applicability of the findings of the systematic reviews using the GRADE analysis . The GRAThis is an ongoing study. The systematic reviews are funded by the ECDC, and the results are expected to be announced by the end of 2021.The two systematic reviews aim to identify the scientific evidence on transmission risks of fungal and parasitic diseases via SoHO globally. The retrieved evidence would assist an evidence-based risk assessment of the fungal and parasitic transmission through SoHO donations and evaluating the available prevention strategies within the European Union. The study results will be used to create an evidence pool containing the geographical data for transmission risks, genetic, physiological, and demographic characteristics of the infected populations, the infection cause and the type of screening tests for donors, and diagnostic methods of the infections. It is also possible that a meta-analysis of these data will be incorporated, which will further strengthen the evidence-based risk assessment approach.The systematic review process has many strengths. The protocol followed the PRISMA-P guidelines. The searching procedure used robust algorithms with standardized indexing terms to retrieve records that had different words to describe the same concept and information beyond the words in the title and abstract . We willThe systematic review process has limitations too. We excluded gray literature, incorporating a publication bias. Nevertheless, the inclusion of gray literature may itself introduce bias, and one reason to include the gray literature is the absence of peer-review sources . AnotherThese systematic reviews will form the basis for developing a risk assessment of fungal and parasitic disease transmission via SoHO."} +{"text": "In 2019, the Fondazione Italiana Linfomi research team proposed a new project to summarize the evidence on late sequelae after treatment of classical Hodgkin lymphoma and diffuse large B cell lymphoma in long-term survivors (>5 years free of disease). Six systematic reviews were conducted. Clinical research questions focused on the incidence of late toxicities, comparison of toxicities with different chemotherapies, radiotherapies and autologous stem-cell transplantation, and evidence on early detection and long-term follow-up of late sequelae. The six reviews investigated the late impact of treatment on cardiological diseases, secondary neoplasms, metabolic and endocrine, neurological and psychological disorders, preservation of fertility and reproductive status, and the effect of lifestyle and nutrition. The literature search was conducted on Pubmed, Embase, and Cochrane Library databases up to 2020. This project summarized current evidence in order to see which course of action was best applicable for the clinical management of long-term survivors after Hodgkin lymphoma and diffuse large B cell lymphoma, and highlighted the gaps in the field.Advances in diagnosis and treatment of hematological malignancies has boosted attention on optimal follow-up care of survivors after cancer. To collect evidence that could inform the development of an optimal model for Italian hematology centers and the scientific community, Fondazione Italiana Linfomi (FIL) commissioned an analysis of the international follow-up approaches for long-term survivors after classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL). FIL set up multidisciplinary teams, representing all different skills relevant for cancer survivors. They conducted a series of systematic reviews focused on three main aspects: incidence of long-term toxicity; comparison of old or standard therapies and more recent ones; and evidence on specific follow-up approaches. The teams applied this framework to cardiological, endocrine-metabolic, neurological/cognitive, and psychological disorders, secondary cancers, fertility preservation, and lifestyles. Each team conducted comprehensive literature searches on PubMed, Embase and Cochrane Library databases up to 2020. Screening followed the PRISMA statement for reporting systematic reviews. The reviews report the results of this wide project covering the main areas of late toxicity and conditions in the long-term survival of cHL and DLBCL patients and their follow-up. From a clinical point of view, the series confirmed that the evidence on follow-up tended to focus on solid tumors with scant evidence on hematological malignancies. Advances in the diagnosis and treatment of hematological malignancies has boosted attention on the optimal follow-up care of long-term survivors. International medical societies and health authorities have developed follow-up programs to support patients after complete remission to improve quality of life (QOL) and monitor long-term sequelae of cancer treatments. Europe\u2019s Beating Cancer Plan, launched by the European Commission in early 2020, focused on follow-up care, in addition to prevention, early diagnosis, and treatment .The essential components of survivorship care include prevention and surveillance of new tumors or relapses of primary diseases and long-term sequelae, as well as the management of the effects of therapies. Survivorship care requires the collaboration of specialists and primary care providers, ideally in multidisciplinary teams. Several out-patient models have been developed: multidisciplinary survivorship clinics, as for instance those dedicated to the long-term follow up of cancers developed in childhood or adolescence; disease-specific survivor clinics, focused on a given disease, for instance, breast or colorectal cancer; and general survivorship clinics, providing services for a broad spectrum of diseases ,3.To manage future health care needs, cancer survivors require a structured survivorship care plan (SCP). Several organizations who coordinate oncological care have developed them\u2013for instance, the American Society of Clinical Oncology . SCPs ofIn 2013, the UK National Health Service (NHS) promoted a document called \u201cLiving with and beyond cancer: Taking action to improve outcomes is intended to inform the direction of survivorship work in England to 2015\u201d [Most of the research and clinical experience on the management of cancer survivors come from breast cancer and childhood leukemia. In recent years, however, interest in hematological malignancies has grown. For instance, an SCP was applied to lymphoma patients at the Cancer Free Clinic of Mayo Clinic-Rochester Hospital . From NoOne review described updated evidence on survivorship care models, identifying current gaps . The autWide heterogeneity emerged between the studies, considering the components of the survivorship care models, the type of neoplasm for which survivors had been treated, and the length of the follow-up.Data from survivorship care models are still lacking, particularly the advantages of different models, the impact on survivors\u2019 health outcomes, barriers to offering survivorship care, assessment of available programs, and the costs and benefits of this model . To helpInteresting experiences focused on lymphoma survivors included the nurse-led lymphoma survivorship clinic with a tailored SCP ,9, and tIn Italy, there is a growing number of out-patient cancer programs focused on lymphoma survivors. The first started in the 1990s at the Centro di Riferimento Oncologico in Aviano and the Humanitas Research Hospital in Milan. A recent survey mapping the current follow-up of the growing numbers of Italian lymphoma survivors showed broad heterogeneity and several multidisciplinary approaches .To collect the evidence to inform the development of an optimal model for Italian hematology centers, the Fondazione Italiana Linfomi (FIL) commissioned an analysis of the international follow-up approaches for long-term survivors after classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL). These two cohorts form the prevalent population of long-term lymphoma survivors.The specific aims of the proposed series of systematic reviews were to understand the best applicable model for the clinical management of long-term survivors after cHL or DLBCL, highlight the gaps in long-term monitoring and follow-up, and provide suggestions on further research in the field. The overall goal of this project is to help decision-makers and clinicians to plan follow-ups for lymphoma survivors in the near future.FIL launched its project in 2019. The first step involved setting up a multidisciplinary research team, representing all the different expertise relevant for the comprehensive management of long-term lymphoma survivors. The final research team comprised eight onco-hematologists, two cardiologists, two radiotherapists, a gynecologist, an endocrinologist, a psychologist, and a nutritional biologist. These researchers were part of one or more review teams and were supported by a methods team, comprising three experts in clinical research methodology and systematic reviews .The research group had a brainstorm meeting in March 2019 to define the clinical areas of interest and the research questions to be addressed by each review team. Six areas were identified: cardiological, endocrine-metabolic, neurological/cognitive and psychological disorders, secondary cancers, fertility preservation, lifestyles, and tailored survivorship care plans. The focus of the project was limited to cHL or DLBCL survivors treated as adults and in remission for more than five years from first- or second-line treatments, including autologous hematopoietic stem cell transplant.The meeting included the presentation of the methodological approach and a training session for the review teams. The proposal was to conduct a series of systematic reviews, one for each area, sharing a common structure but flexible enough to account for the specifics of the different clinical settings. First, evidence was collected on late effects after treatments in order to understand their incidence in relation to the previous therapeutic approaches. Second, the best approaches to monitoring any long -term sequalae related to toxicity of previous treatments were identified. The review teams were trained on the basic elements of a systematic review according to the Cochrane approach which inThe reviews were structured around three aspects: (i) the incidence of specific long-term toxicity; (ii) the comparison of old or standard therapies (for which more data are available) and more recent therapies (including modern radiation therapy); (iii) the best method for early detection and monitoring of long-term sequelae.This framework was applied with minimal adaptations by the teams on cardiological, endocrine-metabolic, neurological/cognitive disorders, and secondary cancers. The groups focusing on fertility preservation and lifestyles and tailored survivorship care plans took a different approach, as the objective of their analysis was slightly different.Each review team defined the relevant clinical questions and divided them into researchable questions through the population, intervention, comparison, outcome study design (PICOS) framework. This lays the basis for the definition of the inclusion and exclusion criteria of the reviews and for literature searches. Considering the aim of the project, the review team agreed on the inclusion of clinical trials, controlled observational studies (prospective and retrospective), and systematic reviews.With the support of the methods team, each review team conducted comprehensive literature searches on the following scientific databases: PubMed, Embase, Cochrane Library. Clinical study registries such as Clinicaltrial.gov, and hand-searched references of these studies were done to maximize the sensitivity of the searches. Titles and abstracts were screened by at least two independent reviewers, and the selected full-text publication was examined to confirm eligibility. Discrepancies were resolved by discussion with a third reviewer or a member of another review team. The screening process was reported using the PRISMA flow-chart .A study was considered eligible if information pertinent to one or more PICOS item was abstracted in a tabular format. The key elements can be summarized as: study design, duration, population, sample size, interventions, comparators, follow-up, outcome measures, main results and main conclusions, and reference. The evidence was summarized qualitatively as a meta-analysis was not considered adequate in this setting. Each review team assessed the risk of bias in randomized trials using the Cochrane risk of bias tool v1 , the quaTo our knowledge, this is the first comprehensive assembly of evidence on clinical management of long-term survivors after cHL or DLBCL. We hope our results will support guideline development and prioritization of research funding allocation, providing the evidence base on which recommendations may be developed, following a transparent and robust methodology. Specifically, it should inform the definition of optimal programs to support patients after complete remission of lymphoma and highlight the gaps where specific research programs are now important. The initiative started with bottom-up input from health professionals involved in the care of long-term lymphoma survivorship, who acknowledged a research priority and set up a project to respond to specific issues. The integration of different competences in a joint, coordinated effort is a major achievement in view of the multidisciplinary approach needed for long-term survivors. The project highlighted several gaps still not covered that could be taken into consideration in new research projects promoted by FIL or other funders (such as scientific societies).The following series reports the results of a wide project covering the main areas of late toxicity and conditions in the long-term survival of cHL and DLBCL patients and their follow-ups.While each article in the series will report detailed considerations, some main clinical and methodological conclusions can be drawn from an analysis of the evidence.From a clinical point of view, our series confirmed that the evidence on follow-up pathways focused mainly on solid tumors with scant information on hematological malignancies. cHL and DLBCL patients can be considered a separate population from those with other hematological diseases due to their good prognosis and life expectancy, the novel chemo-immunotherapy and PET/CT-guided approach during chemo-radiotherapy for patients with cHL, and the improved diagnosis of DLBCL .The improved survival of these patients calls for tailored follow-up specific to their characteristics based on treatments received and their disease history. This is in line with guidelines on solid tumors, such as the National Comprehensive Cancer Network (NCCN) for survivorship and the European Society for Medical Oncology (ESMO) guidelines for monitoring cardiac toxicity in survivorship ,19. FollA recent analysis reviewed cancer survivorship models, with a particular focus on those aimed at integrating primary care providers into the care of cancer survivors . AlthougLike other surveillance programs, the management of long-term lymphoma survivors must assess the potential overuse of diagnostic procedures or treatments. The international initiative Choosing Wisely reports a generic recommendation to start surveillance testing after cancer treatment only after providing the patient with a survivorship care plan to help in transitioning to long-term surveillance, avoiding unnecessary services, and seeking appropriate care and decision support . ChoosinThe overuse of diagnostic procedures or treatments may be associated with side effects, including the possible psychological distress caused by the status of being a \u201ccancer survivor\u201d. In the broader context of a patient-centered perspective on cancer, the development and implementation of survivorship plans should include a transparent approach to shared decision making, where patients\u2019 preferences are taken into consideration.From a methodological point of view, our series pointed out two main limitations. The first regards the indirectness of the results. Most of the evidence refers to mixed populations that include different hematological tumors and, in some cases, even solid tumors, so a good number of studies had to be excluded. The lack of stratification between solid and hematological malignancies and thorough evaluation of the differences precludes robust identification of the most adequate features in each setting. When trials and observational studies only assessed lymphoma survivors, they usually included groups of participants with different disease histories. In general, there is a lack of data on DLBCL patients and those who utilize second-line treatments such as transplants for both cHL and DLBCL. Other papers reported data on populations including children as well as adults, or mixed long-term survivors and patients still receiving treatment together without stratification. The study populations in almost all the studies varied as regards treatment received, age at diagnosis, and timing of the survivorship (intended as time after diagnosis).The second issue regards the overall quality of the evidence. Studies were seldom sufficiently powered to detect long-term sequalae as primary or secondary outcomes, and follow-up was generally too short to detect relevant medical issues in prospective observational and randomized controlled trials. Studies often had major methodological flaws and employed inadequate comparators.This project, promoted by FIL, summarized current evidence to find the best model for the clinical management of long-term survivors after cHL or DLBCL and offered suggestions on further research in the field. It also built up a new multidisciplinary research group, including hematologists with other relevant figures such as experts in radiotherapy, endocrinology, nutrition, and psychology, and research methodology. This group could support decision-makers in preparing sustainable evidence-based guidelines such as SCP, on an Italian national level, and help to fill research gaps through new projects covering unmet medical needs for lymphoma patients."} +{"text": "Difficult times ask for innovative and daring solutions to complex issues. In the interest of the health, safety, and well-being of all registered attendees and the general public, the Society for the Study of Neuroprotection and Neuroplasticity (SSNN) Board of Directors has decided to extend last year\u2019s decision regarding all upcoming events and hold the conferences in a virtual environment. We are committed to supporting public health authorities globally in their effort to slow and contain the spread of COVID-19. We must stay positive, healthy, and united more than ever to overcome this crisis.th European Teaching Course on Neurorehabilitation (ETCN) (17\u201318 September 2021) and the 16th International Summer School of Neurology (19\u201321 September 2020) will be offering outstanding opportunities for education, dissemination of scientific research, and the exchange of best practices, through a brand new online platform that has been tailored to promote lively interaction between participants.Our well-established conferences \u2013 the 11The current virtual events benefit from the active support of some of the longstanding partners like the European Federation of Neurorehabilitation Societies (EFNR), World Federation of Neurorehabilitation Societies (WFNR), the European Academy of Neurology (EAN), Iuliu Hatieganu University of Medicine and Pharmacy from Cluj-Napoca, Romania, the RoNeuro Institute for Neurological Research and Diagnostic, and the Journal of Medicine and Life.The ETCN is one of the most acclaimed events organized by the SSNN. This year\u2019s second online edition, out of eleven so far, promises to rise to participants\u2019 expectations and serve as a platform for disseminating and exchanging up-to-date scientific knowledge on neurorehabilitation and providing a space for teaching-oriented workshops. Each year, the event reaches a broader audience interested in this steadily expanding and exciting field .The event\u2019s focus is on rehabilitation and neurorecovery, along with identifying new avenues in science, education and delivery of service \u2013 the Scientific Program Committee, conducted by Volker H\u00f6mberg President-Elect of the World Federation Neurorehabilitation (WFNR) and Vice-President European Federation of Neurorehabilitation Societies (EFNRS), carefully curated the program developed on submissions from our top-grade international faculty.The event\u2019s objectives are (1) to further the development and improve quality of neurorehabilitation in Europe, (2) to enhance collaboration in neurorehabilitation between professionals, (3) to encourage and facilitate the exchange of knowledge and scientific research in rehabilitation professionals, and (4) to contribute to the development of cooperation and communication networks between national and international neurorehabilitation societies.th edition, coordinated by Natan M. Bornstein and Dafin F. Muresanu, the virtual event will address topics such as the COVID-19 impact, challenges of evidence-based medicine, stroke recovery monitoring, the right of patients for the suitable device aided therapies, and cost-effectiveness of interventions for neurorecovery after acute ischemic stroke.The International Summer School aims to facilitate the interaction between young neurologists-in-training and an internationally established faculty with extensive expertise in basic and clinical neuroscience. The pillars for this event were set in 2005 together with professors Natan Bornstein (Israel) and Ovidiu Bajenaru (Romania) to fulfill the need of young specialists and practitioners for connection with the latest developments in the field of neurosciences. This pursuit led to the development of a dynamic environment that promotes connection and learning. In the 16The 2020 SSNN virtual events will set the stage for five days of intensive talks and debates between over a thousand participants from 25 countries on a broad range of problems in neurosciences. An exciting achievement of this year is represented by the guideline on pharmacological support in early motor rehabilitation after acute ischaemic stroke. The guideline aims to support the clinical decision-making of healthcare professionals involved in the recovery of stroke patients. They were developed using the Grading of Recommendations, Assessment and Evaluation (GRADE) framework to identify early pharmacological interventions for stroke rehabilitation delivered alongside neurorehabilitation. This guideline provides clinicians with information regarding existent pharmacological support in post-acute stroke neurorecovery intervention, highlighting an exciting avenue for research and development.Despite the societal changes caused by the ongoing global pandemic, we are enthusiastic about finding innovative pathways of adapting to the current context. In our pursuit, we ought to work together to overcome these trying times and build a brighter future."} +{"text": "The Up-and-Coming-Scientist section of the current issue of the Journal of Membrane Biology features the invited essay by Dr. Mercedes Alfonso-Prieto, Assistant Professor at the Forschungszentrum J\u00fclich (FZJ), Germany, and the Heinrich-Heine University D\u00fcsseldorf, Vogt Institute for Brain Research.Dr. Alfonso-Prieto completed her doctoral degree in chemistry at the Barcelona Science Park, Spain, in 2009, pursued post-doctoral research in computational molecular sciences at Temple University, USA, and then, as a Marie Curie post-doctoral fellow at the University of Barcelona, worked on computations of enzyme reactions and modeling of photoswitchable ligands targeting neuronal receptors. In 2016, she joined the Institute for Advanced Science and the Institute for Computational Biomedicine at the FZJ, where she pursues research on modeling and simulation of chemical senses. The invited essay by Dr. Alfonso-Prieto discusses state-of-the-art modeling of molecular receptors involved in chemical sensing \u2013 the senses of taste and smell. These receptors, and computational methods to study them, are the focus of Dr. Alfonso-Prieto\u2019s research. Recently, Dr. Alfonso-Prieto and colleagues have presented a new methodology to predict ligand binding poses for GPCRs, and extensive computations that deciphered the ligand selectivity determinants of bitter taste receptors. These developments inform our current understanding of how taste occurs at the molecular level. In contrast with vision or hearing, the senses of taste and smell (or olfaction) involve the detection of chemicals present in the environment and thus are considered as \u201cchemical senses\u201d. They inform about the aroma and flavor of food and beverages and act as warning system for toxic substances. Hence, these two chemical senses strongly affect human well-being, food acceptance and intake are extremely chemically diverse . The GPCR superfamily is the largest in the human genome, with approx. 800 genes, of which half correspond to chemosensory receptors and is distributed among several databases (Marenco et al. The interplay of experimental and computational approaches has enabled a deeper molecular characterization of bitter taste and olfaction. However, the lack of experimental structures of bitter taste and olfactory receptors is still a hurdle that limits the accuracy of the computational structural models that can be generated. Moreover, a more extensive characterization of the physiological and pathological roles of extraoral TAS2Rs and extranasal ORs is required to exploit their potential as novel drug targets. In addition to computational molecular modeling and data science approaches, systems biology is expected to contribute to further understand the connection between ligand-receptor recognition and the subcellular response of the corresponding type II taste cell or olfactory sensory neuron."} +{"text": "Pyrazoles are also found in a variety of agrochemicals and are versatile compounds for synthetic manipulations. Their structural features , and diverse applications, have stimulated the work of several research groups towards the synthesis and functionalization of pyrazole-type compounds and study of their properties, and has inspired this Special Issue that aims to provide a broad survey of the most recent advances in pyrazole\u2019s chemistry.Pyrazoles and their reduced form, pyrazolines, are considered privileged scaffolds in medicinal chemistry, owing to their remarkable biological activities, physicochemical properties and occurrence in many low-molecular-weight compounds present in several marketed drugs . They discussed the most common size of the metallacycles\u2019 ring depending on the metal and analyzed the stability of different ring sizes dec-1-en-5-ium chloride pyrazoles pyrimidines were reviewed by Portilla et al., who have also highlighted the anticancer potential and enzyme inhibitory activity of these compounds, thus providing important insights for the rational and efficient design of new drugs bearing the pyrazolopyrimidine core [In this Special Issue, nine original research articles and seven reviews covering some of the most recent advances in the synthesis, transformation, properties and relevant applications of pyrazoles are reported. Two articles deal with the synthesis and computational study of metallacycles formed by pyrazolate ligands and the coinage metals M = Cu(I), Ag(I) and Au(I). Elguero and Alkorta reported a computational study of metallacycles formed by pyrazolate ligands and the coinage metals (pzM)ng sizes . By usinatalysts . Alam et luminol . Currentine core . Tu et aine core . Brullo ine core . Lee et ine core . In the ine core . Kokorekine core .In conclusion, pyrazoles\u2019 chemistry is undoubtedly a current and pertinent topic of investigation. Several research groups have contributed to the advancement of this topic by designing novel pyrazole-type compounds and developing synthetic strategies for the preparation and post-functionalization of pyrazoles, or by studying their structures, properties and potential applications. Herein, important advances in pyrazoles\u2019 chemistry have been disclosed. We thank all of the authors for their valuable contributions to this Special Issue, all the peer reviewers for their valuable comments, criticisms, and suggestions and the staff members of MDPI for the editorial support."} +{"text": "Background: The cranio-orbito-zygomatic (COZ) approach is a workhorse of skull base surgery, and each of its steps has a precise effect on target exposure and surgical freedom. The present study overviews the key techniques for execution and tailoring of the COZ approach, focusing on the quantitative effects resulting from removal of the orbitozygomatic (OZ) bar, orbital rim, and zygomatic arch. Methods: A PRISMA-based literature review was performed on the PubMed/Medline and Web of Science databases using the main keywords associated with the COZ approach. Articles in English without temporal restriction were included. Eligibility was limited to neurosurgical relevance. Results: A total of 78 articles were selected. The range of variants of the COZ approach involves a one-piece, two-piece, and three-piece technique, with a decreasing level of complexity and risk of complications. The two-piece technique includes an OZ and orbitopterional variant. Superolateral orbitotomy expands the subfrontal and transsylvian corridors, increasing surgical freedom to the basal forebrain, hypothalamic region, interpeduncular fossa, and basilar apex. Zygomatic osteotomy shortens the working distance of the pretemporal and subtemporal routes. Conclusion: Subtraction of the OZ bar causes a tremendous increase in angular exposure of the subfrontal, transsylvian, pretemporal, and subtemporal perspectives avoiding brain retraction, allowing for multiangled trajectories, and shortening the working distance. The COZ approach can be tailored based on the location of the lesion, thus optimizing the target exposure and surgical freedom and decreasing the risk of complications. The cranio-orbito-zygomatic (COZ) approach is an extension of the pterional approach, involving the adjunct of orbitozygomatic (OZ) osteotomy to allow wider exposure of the anterior and middle skull base and upper retroclival region. It provides advantages in giant aneurysms of the anterior communicating artery (ACoA) and distal basilar artery, tuberculum sellae, large anterior clinoidal, spheno-orbital meningiomas, large craniopharyngiomas, giant pituitary adenomas, cavernous hemangiomas of the hypothalamus, and crus cerebri of the midbrain. Over the years, a wide range of terms has been used to describe this approach, each of which refers to the key steps of the bony work of a specific variant. Similarly, many technical notes of the COZ approach have been reported to make its execution easier and decrease the risk of complications ,13,14,15The herein presented PRISMA-based literature review strives to exhaustively summarize the spectrum of possible technical variations of the COZ approach, particularly focusing on the different quantitative effects resulting from removal of the entire OZ bar, orbital rim, and zygomatic arch. The reported data constitute the key elements for rational tailoring of the COZ approach aimed at optimizing the volume of exposure of the target, augmenting surgical freedom, and decreasing the risk of complications.https://pubmed.ncbi.nlm.nih.gov access date 15 February 2022) and Web of Science (https://www.webofscience.com access date 17 February 2022) online databases. The keywords \u201ccranio-orbito-zygomatic\u201d, \u201corbitozygomatic\u201d, \u201corbitopterional\u201d, \u201czygomatic\u201d, \u201corbitozygomatic\u201d, \u201corbitocranial\u201d, and \u201corbitofrontomalar\u201d were combined with text words \u201capproach\u201d, \u201ccraniotomy\u201d, and \u201costeotomy\u201d. Articles in English or translated, without temporal restriction, were selected. Editorials, comments, case reports, and letters were excluded. Eligibility of the articles was limited to neurosurgical relevance, and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . Th. Th11]. 2.Orbitopterional Craniotomy (Al-Mefty Technique)The orbitopterional two-piece COZ approach includes two zygomatic cuts involving the anterior and posterior root of the zygoma, respectively. The zygomatic arch is mobilized inferiorly without detachment of the masseter muscle, thus avoiding the risk of postoperative masticatory imbalance. The other steps are those of the one-piece variant of the COZ approach, where all the cuts are carried out extracranially 3]..3].The three-piece COZ approach consists of a combination of both two-piece variants. It involves zygomatic osteotomy without detachment of the masseter, inferior mobilization of the zygomatic arch, pterional bone flap, and orbital osteotomy as separate piece entailing the superolateral orbital rim and the orbital roof .The dura is opened parallel to the posterior ramus of the Sylvian fissure, and two further curvilinear cuts are performed on the frontal and temporal side. This type of opening decreases the risk of damage to the Sylvian veins, especially in the case of swelling of the brain.The COZ approach allows for four different corridors: (1) subfrontal, (2) transsylvian, (3) pretemporal, and (4) subtemporal. The transsylvian and pretemporal corridors are related to four well-defined deep windows to the infratentorial region through the opening of the Liliequist membrane. The deep windows are as follows: (1) optic-carotid, (2) carotid-oculomotor, (3) supracarotid, and (4) oculomotor-tentorial.The galea-pericranium can be used as a double-layered autologous patch graft in the case of duraplasty or also if cranialization of the frontal air sinus is necessary. Preplating before proceeding to zygomatic osteotomy aids osteosynthesis and avoids the risk of postoperative facial asymmetry. Care should be taken in reconstruction of the orbital roof to limit the risk of enophthalmos. Low-profile titanium plates and 4 or 5 mm self-tapping screws are used for osteosynthesis of the bone flap. The temporalis muscle is reapproximated to the myofascial cuff at the level of the superior temporal line. An interrupted suture with 3/0 vicryl stitches is used for the superficial temporal fascia and galea. Subcutaneous drainage is left in place for 2 days to prevent blood collections. Skin suture can be optionally executed with 3/0 silk stitches or metallic agrafes.A large basilar apex aneurysm was incidentally found in a 54-year-old female patient. On digital subtraction angiography, the aneurysm was superior projecting and presented with a dome-to-neck ratio of 1.5. Both P1 segments of the posterior cerebral arteries arose from the partially calcified neck. Basilar bifurcation was low riding, lying 8 mm below the dorsum sellae. The patient underwent a two-piece COZ approach inclusive of orbitopterional craniotomy, zygomatic osteotomy, extradural anterior clinoidectomy, lateral mobilization of the internal carotid artery (ICA), and posterior clinoidectomy. Posterior clinoidectomy expanded the carotid-oculomotor window and allowed for control of the midbasilar trunk. Given the pattern of low-riding basilar bifurcation, the additional exposure resulting from the COZ approach and posterior clinoidectomy was paramount for temporary clipping. Anterior clinoidectomy and lateral mobilization of the ICA led to expanding the optic-carotid window, which was used to dissect the neck and the thalamoperforating arteries resulting from P1, and to definitively clip the aneurysm. The transsylvian, pretemporal, and subtemporal corridors were used in combination. The patient was discharged without deficits on the fifth post-op day .A 48-year-old female was diagnosed with an incidental large anterior communicating artery aneurysm. The left A1 segment of the anterior cerebral artery was hypoplastic, and both A2 segments originated from the ACoA. The aneurysm was anterior\u2013superior projecting, and the superolateral orbital rim hindered visualization of the left A2 segment. The patient underwent an orbitopterional approach, which allowed expanding the subfrontal corridor and the angular exposure of the aneurysm neck. Better visualization of the left Heubner artery and hypothalamic and subcallosal perforating arteries was also possible. The aneurysm was successfully clipped and the postoperative course was uneventful .The present review summarizes the key techniques for tailoring the amount of surgical exposure provided by the COZ approach, which is today considered a workhorse of skull base surgery. A gradual shift from the one-piece technique to the two-piece or three-piece technique occurred over the years .The reasons consist of easier execution of the latter two variants, as well as better functional and cosmetic outcome ,11,29,30In particular, for the basilar apex and posterior clinoid, the removal of the orbital rim and zygomatic arch as separate steps results in an increase of exposure of 28% and 22%, respectively 32]..32].Based on these data, the COZ approach can be tailored depending on the location and size of the lesion, as well as the specific corridor deemed more suitable for the target exposure ,46. ManyWhile subtraction of the orbital rim is useful for high-riding aneurysms of the basilar apex, the shallower operative field resulting from zygomatic osteotomy enhances the pretemporal, subtemporal transtentorial, and subtemporal transpetrosal (Kawase\u2019s) approaches in cases where the basilar tip aneurysm originates at the level of low-riding basilar bifurcation . An anatComplications of the COZ approach can be functional, aesthetic, or of both types. Some of the most frequent are injury of the frontotemporal branch of the facial nerve, atrophy of the temporalis muscle, masticatory imbalance, enophthalmos, diplopia, visual impairment, and cerebrospinal fluid leakage. The subfascial technique avoids deficit of the frontotemporal branch of the facial nerve, whereas compulsive subperiosteal blunt and \u201ccold\u201d (avoiding electrocauterization) dissection of the deep temporal fascia prevents postoperative atrophy of the temporalis muscle ,24,27,41In the one-piece COZ approach, zygomatic osteotomy is generally less generous, involving mainly the frontal process. Therefore, the one-piece COZ approach is theoretically more suitable for parasellar and orbital tumors where wider mobilization of the zygomatic arch does not add real advantages in target exposure. Conversely, the one-piece COZ approach is less indicated in ruptured aneurysms, hyperostotic spheno-orbital and sphenoid meningiomas, and large intraorbital tumors with raised intraocular pressure. In ruptured aneurysms, the coexistent brain edema increases the risk of parenchymal damages during extracranial osteotomy of the orbital roof. In tumors characterized by severe hyperostosis of the roof and lateral wall of the orbit, the fracture of the one-piece bone flap can accidentally give rise to force vectors involving the optic canal and sphenoid sinus with a consequent risk of damage to the optic nerve and cerebrospinal fluid leaks. In the case of intraocular hypertension, the greater manipulation of the eyeball, equired to cut the orbital roof from the extracranial intraorbital side, increases the risk of blindness, as well as dangerous bradyarrhythmia deriving from elicitation of the trigeminal oculocardiac reflex. The two-piece variant fits most other lesions for which the COZ approach is indicated thanks to its wide intrinsic versatility that characterizes both the Zabramski and Al-Mefty techniques. The Al-Mefty technique should be preferred for malignancies affecting the temporal and infratemporal fossa since this variant avoids detachment of the masseter muscle, thus eliminating an adjunctive risk for mastication. These tumors often involve the masticatory space apart from the middle fossa. Despite its greater facility of execution, the three-piece variant is considered disadvantageous in children where the physiologic growth of the facial skeleton can be compromised by the fixation devices. Furthermore, in pediatric and extremely thin patients, where the thickness of the facial soft tissues is reduced, the greater number of miniplates and burr hole covers required for reconstruction can be sources of poor aesthetic outcome. Apart from the aforementioned aspects, which should be considered as indicative rather than imperative, the preferences and the personal experience of the surgeon also have to be considered in the choice of a specific technique of execution.The present study has some limitations that can be summarized in its retrospective nature, the intrinsic bias of the different studies involved, and the type of morphometric and quantitative studies selected which were performed only on cadavers in most cases.The spectrum of variants of the COZ approach involves a one-, two-, and three-piece craniotomy, with a decreasing level of technical complexity and risk of complications.Superolateral orbitotomy expands the subfrontal and transsylvian corridor and raises surgical freedom to the basal forebrain, hypothalamic region, interpeduncular fossa, and basilar apex.Zygomatic osteotomy shortens the working distance to the main targets of the pretemporal and subtemporal route.Removal of the OZ bar eliminates the need for brain retraction and allows for multiangled trajectories.The COZ approach can be tailored based on the location and extension of the lesion, thus optimizing target exposure and decreasing the risk of complications."} +{"text": "The evolution of antibiotic resistance in Escherichia coli (E. coli) hampers the treatment of UTIs, mirroring the global public health concerns around antimicrobial resistance. Pivmecillinam, an oral prodrug of mecillinam (a \u03b2-lactam antibiotic), is used as first-line treatment for uUTIs in Denmark. Here, we examine the use of, and the prevalence of resistance to, mecillinam in Denmark in the primary care setting.www.danmap.org). Prevalence estimates of resistance reported by DANMAP 2019 were obtained from the Danish Microbiology Database (MiBA).Nationwide data on the use of and resistance to pivmecillinam was extracted and examined from the Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (DANMAP) 2019 report . In general, in spite of increasing use in Denmark, the development of resistance to pivmecillinam has remained low. In fact, a slight decline in pivmecillinam resistance was observed over the past decade.Despite the rising number of UTIs and the increasing use of pivmecillinam for uUTI in Denmark, over the past decade, the development of resistance to pivmecillinam remains low.Anne Santerre Henriksen, MS, Advanz (Consultant)Shionogi BV (Consultant)UTILITY Therapeutics (Consultant)"} +{"text": "In the context of fair trade and protection of consumer rights, the aim of this study was to combat adulteration, counterfeiting, and fraud in the tea market, and rebuild the image of high-quality Taiwan teas. Experts at the Tea Research and Extension Station, Taiwan (TRES), are engaged in promotion of the systems of origin identification (AOC) and grading for authentication of Taiwan\u2019s premium teas. From tea evaluation competitions , the flavor descriptions and consumers\u2019 perceptions were deconvoluted and characterized for the eight Taiwan specialty teas, namely, Bi-Luo-Chun, Wenshan Paochong, High-Mountain Oolong, Dongding Oolong, Tieh-Kuan-Yin, Red Oolong, Oriental Beauty, and Taiwan black tea. Then, according to the manufacturing processes, producing estates and flavor characters, the specialty teas were categorized into six sensory wheels. The flavor descriptors of the sensory wheels were also recognized in consumers\u2019 feedback. In recent years, the performance of international trade in tea also demonstrates that the policy guidelines for authentication of specialty teas are helpful to the production and marketing. Furthermore, the development of sensory wheels of Taiwan\u2019s specialty teas is the cornerstone to the establishment of the Taiwan-tea assortment and grading system (TAGs) for communication with the new generation consumers, enthusiasts, sellers, and producers. Camellia sinensis) is also one of the main agricultural commodities in international trade [Tea is the most popular beverage in the world after water, and the tea leaf . SpecialSince 1991, the import quantity of Taiwan\u2019s tea has rapidly surpassed the export quantity, as shown in Food authentication is the process of verifying compliance with a food label instruction. Whether from a business perspective or a legal perspective, food authentication has aroused significant interest. Labeling and ingredient regulations may vary by country or region for food safety issues or prevention of criminal activities . Many beNumerous technological approaches have also been utilized to profile the characteristic fingerprint of beverages with physical or chemical data ,13. HoweConsumers make purchasing decisions based on a variety of quality cues (brand reputation and price) controlled by marketing . The autIn tea purchases, consumers often need to try individual teas, and determining a favorite flavor is time-consuming. However, consumer preference for a tea flavor is difficult to state, and words used in professional evaluation are too artistic and metaphysical for others to understand. A recent study noted that the problem stems from the gap between the sensory perceptions of tea beverages by younger consumers and professional opinions in tea marketing . The appWith the aim of authenticating Taiwan tea to protect consumer rights and ensure trade fairness, numerous fast and accurate analytical techniques have been developed to combat tea counterfeiting, adulteration, and fraud . The aroThis aim of this study was to establish a systematic sensory lexicon to certify the flavor characteristics of specialty teas with high-quality, as flavor authentication. As the major official institute involved in the promotion of the tea industry in Taiwan, TRES must coordinate manufacturers, tea traders, and consumers to establish a functional medium with well-certified guidelines to reduce the gaps in traditional tea culture. Using an expert taster who evaluated the appearance, color, smell, taste, and mouthfeel, the overall impression of the quality of the tea infusion was obtained with a balance based on defect-free and sensory properties. Furthermore, the official sensory wheels of Taiwan specialty teas were developed for the tea industry to serve as communication and quality control tools to enhance the marketing of Taiwan tea for consumers, and to strengthen the core competitiveness of tea farmers. In this study, the characteristic flavors of Taiwan specialty teas were clearly identified based on consumers\u2019 perception using the flavor attributes of the sensory wheel.The main structure of this research consists of the eight specialty teas and six categories of sensory wheels, which have the flavor attributes of infusion color, taste, and aroma in the consumers\u2019 perception. Since the inception of TRES, the lexicon of flavor perceptions on teas has been dynamically reviewed by the professional staff. Our study uses the concept of identifying tea flavors to develop a sensory wheel with flavor terms in detail, and then verifies the accuracy of the flavor terms in each sensory wheel associated with the Taiwan specialty teas.Based on the sensory wheel, tea traceability establishes flavor clues in authentication, and can be used to express the flavor and quality perceptions of Taiwan specialty tea as a marketing tool. The official sensory wheels can be promoted to participating tea merchants, producers, and tea farmers to understand the basic quality requirements and flavor items in the evaluation. The protocols, including sensory evaluations and consumer surveys in this study, are certified as an exempted approval (document number: 1103408809) by the institutional review of TRES according to Article 5 of the Human Subjects Research Act (2 January 2019) of the Ministry of Health and Welfare, Taiwan. All identified data have been delinked for participants\u2019 anonymity and confidentiality before analysis.The flavor wheel working group and the sensory evaluation panel are composed of 25 professional researchers engaged in tea manufacturing and tea sensory evaluation at TRES, Taiwan. The panelists were recruited from certificated referees with qualifications obtained from training courses and practice assessments conducted by TRES for top-level tea sensory appraisers. The certification system of tea sensory appraisers in Taiwan is developed and classified in five levels, namely, elementary, junior, senior, advanced, and special appraisers. Certified appraisers must obtain the qualifications of appropriate training courses and assessments for tea sensory evaluation at different levels, consistent with the ISO 8586:2012 guidelines for sensory analysis [The development of the tea sensory wheel was used to standardize the flavor description and sensory evaluation of premium tea, so the high-quality tea samples were collected from tea evaluation competitions conducted from 2019 to 2020 in Taiwan. The flavor attributes of Taiwan green tea were assessed and graded using 40 samples of Bi-Luo-Chun green tea. The flavor attributes of the fragrant strip-type Paochong tea were assessed and graded using 50 samples of Wenshan-Paochong tea. The flavor attributes of the fragrant ball-type Oolong tea were assessed and graded using 73 samples of High-Mountain Oolong produced in locations including Nantou, Chiayi. The flavor attributes of the heavy roast ball-type Oolong tea were assessed and graded using a total of 210 samples of Dongding Oolong (169 in Nautou), Tieh-Kuan-Yin (19 in Muzha), and Red Oolong (22 in Taidong). The flavor attributes of Oriental Beauty tea were assessed and graded using 62 samples. The flavor attributes of Taiwan black tea were assessed and graded using a total of 60 samples of Sun-Moon-Lake black tea (20 in Nautou), Small-leaf black tea (20), and Honey-flavor black tea .The tea infusions were prepared as a liquor extraction with dry tea leaves, as described in the international standard ISO 3103:1980 . The teaResults of sensory evaluation in terms of color, flavor, taste, and aroma were conducted with hedonic scaling and a ranking test to determine a suitable grade based on the flavor attributes of the tea samples.To explore the feedback of consumers regarding the official sensory wheels of Taiwan specialty teas, participants were randomly invited to participate in a questionnaire survey at the Taiwan International Tea Expo on 11\u201316 November 2020 at the Taipei Nangang Exhibition Center. Participation was voluntary; participants had given verbal informed consent before the trial and could withdraw freely at any stage. A total of 90 valid questionnaire responses were obtained, including those of four foreigners with a questionnaire in English. Of the total number of respondents, 61% were male and the median age was 45 years old. Although the sensory wheel has different color attributes and the same taste attributes of tea infusions, it is difficult to analyze using questionnaires. Therefore, this questionnaire analyzed a total of 25 aroma attributes in six sensory wheels to profile the aroma characteristics of various Taiwan specialty teas. The design of the questionnaire used the Check-All-That-Apply method to verify the recognition coverage of consumer perception of the flavor attributes of Taiwan specialty teas.Based on the questionnaire data, the recognition percentage of an aroma attribute according to a consumer\u2019s perception was calculated and transformed into a 5-point scale, named the acceptance index of aroma attribute. For an aroma attribute with a recognition percentage of 45% or more, 5 points were given, 44.4\u201335% were given 4 points, 34.4\u201325% were given 3 points, 24.4\u201315% were given 2 points, and 14.4\u20131% were given 1.1 points. Those not recognized are not presented.Based on the production estates, the unique manufacturing process, and consumer impressions of the premium teas, the TRES focus group selected eight Taiwan specialty teas to characterize their flavor attributes. According to the tea manufacturing process, the color of tea infusion deepens with the degree of fermentation, as shown in Jacobiasca formosana), which feeds on leaves, stems, and buds without pesticide residues. The tea plant induces the secretion of the monoterpenediol and hotrienol, which gives the tea its unique flavor [Taiwan is the main producing area of partially fermented Oolong tea in the world , so the e flavor . Becausee flavor .Green tea is an unfermented tea made with relatively low processing, but differences in processing nonetheless have a significant impact on the flavor (mainly aroma) and appearance . Based osinensis var. assamica) with a high level of catecholamine are suitable for the flavor of black tea, and small-leaf cultivars (C. sinensis var. sinensis) with a low level of catecholamine are suitable for the flavors of green tea and partially fermented teas [According to the basic processes of tea manufacturing, as shown in ted teas . Due to ted teas , green tFrom the perspective of the producing estate, well-managed tea trees can be harvested for at least 30 to 40 years, and specific varieties are also suitable for planting and growing in the producing area of the specialty tea. Thus, the regeneration of tea planting varieties is very slow . HoweverTaiwan black tea is dominated by large-leaf cultivars. Characteristic Honey-flavor black tea is predominantly produced at the Hualien estate and made from Large-leaf Oolong, which is a tea tree of a small-leaf cultivar. Production of partially fermented teas, such as Paochong tea or Oolong tea, uses common small-leaf cultivars of Chin-Shin-Oolong and TTES No. 12 (Jhinhsuan). Because the catechin content of tea leaves in summer is too high and the flavor is too bitter for partially fermented teas , ten yeaFlavor affects the acceptance and choice of food intake, and helps people identify potentially harmful compounds. Based on the unique flavor attributes and consumer impressions, the sensory wheel working group further developed six sensory wheels of the flavor categories of specialty teas, which are Taiwan green tea (TGT), the fragrant strip-type Paochong tea (FSPCT), the fragrant ball-type Oolong tea (FBOT), the heavy roast ball-type Oolong tea (HRBOT), Oriental Beauty tea (OBT), and Taiwan black tea (TBT), as shown in The official sensory wheel has the function of setting standards and guidelines for each of Taiwan\u2019s specialty teas for the development of Taiwan tea industries, consumer behavior, and trade. The design framework of the sensory wheel has distinctive appearance, context, flavor lexicon, and sensory information, and includes the infusion color and an image representing the tea. Sun-Moon-Lake black tea, Small-leaf black tea, and Honey-flavor black tea are the three representative teas of TGT in Flavor studies ,36 utiliFlavor profiling identifies individual sensory attributes that contribute to the overall sensory impression of the tea infusion and evaluates its strength to establish a description of the flavor and aftertaste, such as in the case of mouthfeel, shown in The TRES is an official professional institution providing counseling for tea industry development and plays the role of guidance and supervision in the marketing of Taiwanese tea. However, flavor descriptions and standards of Taiwan teas are currently lacking a means of authentication compared to the international classification standards ,37 of ChThe official sensory wheel can be used not only as the flavor standard of the Taiwan specialty tea and an auxiliary tool for marketing, but also as teaching material for personnel training and the dissemination of tea-related knowledge on sensory evaluation. The six sensory wheels standardize the flavor lexicon for aroma and taste attributes, and provide a color atlas as a visual reference, as listed in From the comparison of the flavor components of the two extremes in In the future, the main challenge of psychological measurement will be to find a scale with proportional characteristics that is not affected by other factors used in the surrounding environment . Thus, aFlavor profiling includes formal procedures to describe and evaluate the taste, smell, mouthfeel, and flavor, in addition to an underlying complex of sensory impressions of a product in a reproducible manner. Taste is the sensation experienced by taste receptor cells located on the taste buds when stimulated by certain soluble substances. The sense of taste is combined with the olfactory and trigeminal system to produce an overall flavor . HoweverAccording to the results of the consumer questionnaire, the aroma descriptors in the sensory wheels were used to profile the characteristics of Taiwan specialty teas by fuzzy algorithm ,43, as sSensory evaluation techniques of QDA , consumeThe development of a variety of tea processed products has changed the culture of people drinking tea. In particular, the product concept of ready-to-drink tea has created a new tea culture . Tea is As shown in Nevertheless, this study is limited to specific areas and objects and cannot be accurately projected into the larger commercial tea or beverage markets. The quantitative data of flavor description are regarded as representing the objectivity and scientific statement of sensory evaluation . The medFor a long time, tea has been an important daily drink for East Asians. Drinking tea will make people feel happy because of its unique aroma, flavor, and taste. However, the sensory wheels are constructed with the criteria that were proposed by professionals for premium Taiwanese teas, and might not accurately project the consumer\u2019s perception of teas in general markets, such as the aroma attributes of root crop-nutty and bean-vegetal, which have lower acceptance in the consumer survey in From the perspective of the industrial development of beer, wine, coffee, and other popular beverages, professional knowledge education, product contests, media propagation, cultural links, and studies of health benefits can expand the penetration of tea beverages in society . The firIn summary, the development of premium teas has gradually dominated the international trade trend and supply chain structure of the entire tea industry in Taiwan. However, the expansion of the supply chains and the diversification of products have led to the prevalence of illegal business practices in the tea industry. Consumers\u2019 impression and perception have gradually faded for the high-quality Taiwan teas. Therefore, promoting the authentication of specialty teas is an urgent issue for the tea industry. Due to the generational differences of food culture and the rise of international industrial specialization, the flavor information of tea products must be dynamically updated and adjusted for the consumer groups whose lifestyle changes.The implementation of flavor authentication can be used to prevent the forgery of labeling in a traditional certification system of beverages, and the flavor lexicon can also expand consumers\u2019 interest in premium tea via assessor training for sensory evaluation. Further, the analytical techniques should be developed to establish an accurate and quantitative evaluation about the tea flavor. If the scientific clues of a flavor compound are identified, it can be applied to discriminate the quality, origin, and harmful residues of tea. The flavor profiling of the sensory wheels can be applied on the identification of specialty tea with Taiwanese label from general markets. The gap between industrial standards and consumer demand could be repaired with the development of sensory evaluation on tea flavors. Therefore, the use of quantitative descriptions of sensory evaluation, chemical analysis technology, and consumer testing to characterize the most important flavors of Taiwan specialty teas will help establish flavor standards, product traceability, and responsibility."} +{"text": "Regional framework for action on implementation of the End TB Strategy in the Western Pacific, 2016\u20132020 in countries and areas in the World Health Organization Western Pacific Region.To assess the implementation of the We used a mixed methods approach to assess the framework\u2019s measurable and perceived impact. We conducted an analysis of national tuberculosis strategic plans, a cross-sectional survey of senior staff of tuberculosis programmes, key informant interviews and some country case studies.Of the 37 countries and areas of the Western Pacific Region, 14 had a national tuberculosis strategic plan, including all countries and areas with a high incidence of tuberculosis. Most senior tuberculosis programme staff who responded to the survey (16/23) found the regional framework useful when developing their national targets and grant applications. Programmatic challenges identified included financing, human resources, public\u2013private mix, active case finding, and paediatric and drug-resistant tuberculosis. Most of the 17 key informants thought that the regional framework\u2019s categorization of actions was useful, but that the added value of the regional framework over other relevant documents was not obvious because of overlap in content.The regional framework influenced national level tuberculosis control planning and implementation in a positive way. A future regional framework should provide a longer-term strategic horizon and specifically address emerging trends and persistent problems faced by countries or areas of the region. The framework included 16 subtopics linked to proposed actions with defined regional targets and indicators. In view of the diversity of the region, a tiered approach was proposed with actions for all settings, specific settings and pre-elimination settings.We undertook a mixed methods evaluation to assess the implementation of the regional framework and progress towards its targets and indicators. We conducted the evaluation in collaboration with the End TB unit of the WHO Regional Office for the Western Pacific, WHO country offices, national tuberculosis programmes and other stakeholders. The main objectives of the evaluation were to: (i)\u00a0assess progress against the targets and indicators defined in the regional framework; (ii)\u00a0determine how the regional framework has been adopted at the country level; (iii)\u00a0ascertain the perceived value of the regional framework in achieving its objectives; and (iv)\u00a0describe country-level challenges and success stories, the influence of the regional framework and future challenges. For the first objective, our findings have been reported in a separate paper,We chose this comprehensive mixed methods approach to obtain multiple perspectives and critical real-life insights. We carried out the evaluation (including data collection/interviews) between July and December 2019.We developed several evaluation tools which included a data extraction guide for the policy review ,We did not require ethical approval for this quality improvement exercise. Countries and areas voluntarily provide their data to the WHO Global TB Programme, as part of standard reporting practices.Only 14 of 37 countries and areas of the region had a national tuberculosis strategic plan , includiThe four countries that had national tuberculosis strategic plans that were clearly informed by the regional framework were Kiribati, Lao People's Democratic Republic, Malaysia and Mongolia . The spehttp://www.who.int/bulletin/volumes/99/5/20-268060), provides a summary of the main objectives, indicators and targets in the national tuberculosis strategic plans of the seven priority countries of the region. The strategic plans of Cambodia, China, Papua New Guinea, Philippines and Viet Nam were mostly aligned with the WHO End TB Strategy,Implementing the End TB Strategy: the essentialsTowards tuberculosis elimination: an action framework for low-incidence countries.We received 23 of 37 completed surveys from senior staff members of national tuberculosis programmes and 19 respondents indicated that they had read the regional framework or part of it. Of these 19 respondents, 16 found the regional framework helpful in the development of their national tuberculosis strategic plan. Eleven of 22 respondents said that their national tuberculosis strategic plans were wholly or greatly guided by previous or current regional strategies. Other documents identified by respondents that guided the development of national tuberculosis strategic plans included: national development plans; national surveys and reports; the End TB Strategy; the MDGs; the SDGs; documents from the United States Centers for Disease Control and Prevention; the results of operational research; and other WHO documents including Respondents indicated that the distinction between guidance for all, specific and pre-elimination settings was useful and ensured that the regional framework could serve as a resource for all countries and areas. Programmatic hurdles that the respondents thought needed to be considered when planning technical assistance or developing future regional frameworks included financing, human resources capacity, public\u2013private partnership, active case finding, management of paediatric and drug-resistant tuberculosis and general health system challenges. Of 12 programmatic areas assessed, the senior tuberculosis staff thought that the regional framework provided the most relevant guidance on the treatment and care of adult tuberculosis patients, the development of adequate laboratory capacity to guide treatment of drug-resistant cases, and treatment and care of children with tuberculosis .We contacted 24 key informants for critical reflection on the value of the regional framework and we interviewed 17 of the informants contacted. Interviewees were with the main organizations and technical agencies working on tuberculosis control in the region and high-level national tuberculosis programme representatives in certain countries (list of organizations and agencies available in the data repository).Box\u00a01Successes: strong focus on active case finding; general laboratory improvement and expanded networks for drug-resistant tuberculosis diagnosis and treatment, including the use of Xpert Ultra\u00ae, line probe assay and whole genome sequencing; low number of multidrug-resistant tuberculosis cases among new casesRemaining challenges: maintenance of Xpert\u00ae MTB/RIF equipment and subsequent loss of skills in smear microscopy; scaling up of detection and treatment of paediatric tuberculosis; low case finding and treatment success for drug-resistant tuberculosis; inadequacy of efforts to find missing casesSuccesses: removal of the category two regimen; availability of child-friendly water-dispersible fixed-dose combination tablets; better patient support to reduce catastrophic costs; implementation of short-course regimens for management of MDR and rifampicin-resistant tuberculosis; access to bedaquiline and delamanid as requiredRemaining challenges: poor patient-centred care ; scaling up of detection and treatment of drug-resistant tuberculosis with high loss to follow-up; high cost of some medicines for multidrug-resistant tuberculosis which are not included in national drug lists and low treatment successSuccesses: better awareness of tuberculosis prevention and new WHO guidelines on infection prevention and control Remaining challenges: screening, prevention and treatment of latent tuberculosis infection; lack of commitment to provide preventive therapy to household contacts in high-incidence settings, even to vulnerable childrenSuccesses: on track to reach targets but much left to do; relatively low caseload of multidrug-resistant tuberculosis Remaining challenges: improvement in documentation to obtain funding; strengthening of surveillance and use of data for field-based research to provide scientific evidence for policy-makingSuccesses: more and better quality research undertaken, e.g. inventory studies, patient cost surveys, new diagnosticsRemaining challenges: strengthening of research capacity and securing fundingSuccesses: improved collaboration and better partnerships, and community engagement; improved private sector and donor engagement; more collaboration with other groups on tuberculosis care Remaining challenges: still insufficient engagement of the private and non-public sector; insufficient engagement of civil society in tackling tuberculosis; overwhelming of national programmes by international partnersSuccesses: increased funding from government; health system improvements, e.g. decentralized care; more attention on universal health coverageRemaining challenges: difficulty in using funding; regulatory barriers, e.g. excessive bureaucracy; strengthening of health-care delivery system; better trained human resources; large funding gaps for national tuberculosis plansSuccesses: improved commitment and top-level engagement after the UN high-level meeting on tuberculosis in 2018Remaining challenges: better cross-regional collaboration and harmonization between the WHO Western Pacific and South-East Asia regions; maintaining political advocacy at the top level following the UN high-level meetingMDR: multidrug-resistant; UN: United Nations; WHO: World Health Organization.Notes: Each success or challenge does not necessarily apply to all the countries and some refer to the region more broadly. Key informants were senior advisers from international donor and technical organizations, tuberculosis programme managers and senior tuberculosis consultants or programme staff in selected countries.Countries included in the case studies were Australia, Cambodia, China, Papua New Guinea, Philippines, Solomon Islands and Viet Nam. The focus of the cases studies was on key lessons learnt. Tuberculosis control in Papua New Guinea and the Philippines was facing significant challenges such as rising numbers of cases of multidrug-resistant tuberculosis and cases in children, while achievements such as productive research collaborations and a new social protection scheme were noted in Viet Nam. ,,,The framework aimed to assist the translation of the End TB Strategy to the national and regional context in the WHO Western Pacific Region. As such, the framework outlined ambitious tuberculosis targets for the region aligned with the End TB StrategyThe success of any global or regional tuberculosis strategy is based on its translation into national strategic plans and actual on-the-ground implementation.,Our analyses showed substantial gaps in case finding and access to treatment in all country case studies, especially for people with drug-resistant tuberculosis. The need for focused strategies to tackle tuberculosis in high-risk subpopulations was highlighted during key informant interviews. In 2018, WHO, the Stop TB Partnership and the Global Fund launched a joint initiative (FIND. TREAT. ALL. #ENDTB) to urgently scale up tuberculosis case finding.,,Responses from national tuberculosis programme managers and key informants highlighted several areas to consider in a future regional framework. Several technical and programmatic problems were highlighted including laboratory capacity, large-scale case finding for active tuberculosis, drug-resistant tuberculosis care, scaling up of preventive therapy and a lack of national research capacity to address key research questions specific to the country context. Health system challenges noted included the need for universal health coverage (UHC) and the integration of tuberculosis services into primary health care, especially for children, with adequate financing mechanisms in place.Of the seven priority countries of the Western Pacific Region, Papua New Guinea and the Philippines have the biggest challenge because of large numbers of undetected cases and health system inefficiencies.Our evaluation has some strengths and limitations. We used both quantitative and qualitative approaches and explored the perceptions of national tuberculosis programme managers and key informants. However, the scope of our evaluation was broad and captured mainly people\u2019s opinions: validation of findings was limited, except in some country case studies. Furthermore, we were unable to validate the specific effect of the regional framework on policies and activities. We also found some inconsistencies between the different components of the evaluation; for example, in the survey of national tuberculosis programme managers, most respondents said that their national tuberculosis strategic plan was influenced by the regional framework, but only four countries published new national tuberculosis strategic plans after the regional framework. Managers might have thought that the regional framework would have influenced their national tuberculosis strategic plans if it had been available at the time, or that it is influencing current plans in development. Determining the real effects of the regional frameworks and strategies is challenging given the large number of priorities, needs, strategies, documents, organizations and funders that influence disease control programming. Although the scope of our evaluation did not cover all aspects of policy development and implementation, preparation of the regional framework included comprehensive consultation with countries and areas, and the formation of a regional tuberculosis technical advisory group has provided a strong platform to develop, disseminate and monitor future regional frameworks.Thirteenth general programme of work, 2019\u20132023 of WHO, and the document: For the future: delivering better health in the Western Pacific Region.,For the future: towards the healthiest and safest region.Overall, the regional framework has had a positive influence on national tuberculosis programmes in the Western Pacific Region, where tuberculosis incidence and mortality are slowly declining. The findings of our evaluation will inform the development of a future regional framework. This framework will be aligned with the priorities of countries and areas, the"} +{"text": "Susac syndrome (SS) is a rare microangiopathy that involves arterioles of the brain, retina, and cochlea. Diagnosis is extremely difficult because of the rarity of the disease and because the signs and symptoms often occur at different times. Multidisciplinary approaches and multimodal images are mandatory for diagnosis and prompt therapy. In this report, we describe a case of SS and the application of multimodal retinal imaging to evaluate the ophthalmologic changes and to confirm diagnosis. Early diagnosis and therapy based on the associations of steroids and immunosuppressants are necessary to limit the sequelae of the disease. Susac syndrome (SS) is a rare autoimmune syndrome characterized by microvascular alterations involving the precapillary arterioles of the brain, retina, cochlea, and semicircular canals . This diIn this paper, we considered the application of the multimodal retinal imaging approach to describe a case of SS.A 33-year-old man was admitted to the emergency unit for headaches, a referred visual field loss, dizziness, and weakness of the limbs. The patient had a history of malignant external otitis , hearingAlthough the clinical trio including focal neurological deficits, hearing defeat, and retinal arterial occlusions is considered pathognomonic, the whole clinical manifestation occurs in only 13% of patients at onset ,3. The mIn conclusion, MRI and FA are the main diagnostic instruments and may lead clinical ophthalmologists to the correct diagnosis of SS; however, new diagnostic instruments such as OCTA and wide-field color retinal photography may provide an advantage in early diagnosis and follow-up of SS, offering an effective alternative to standard FA; in evaluating microvascular changes in all capillary plexuses; and in monitoring retinal vessel density alterations during prompt therapy without dye injection."} +{"text": "The purpose of this symposium is to highlight the mental health needs and factors associated with mental health among informal caregivers of older adults in Asia. The symposium consists of five papers. The first paper explores the perceived role, needs, and rewards of informal caregiving among caregivers of residents in independent long-term care facilities in South India. The second paper presents a systematic review and meta-analysis on the association between long-term care service use and informal caregiver burden, depression, and health status. The third paper examines the association between caregivers\u2019 characteristics and quality of life among informal caregivers of older adults with cognitive impairment in China. The fourth paper examines the association between coping strategies and caregiver burden and depression among Chinese caregivers of older adults with cognitive impairment. The last paper examines the association between cohort, meaning making, and depression among adult caregivers during the COVID-19 pandemic in Hong Kong. Taken together, these five papers underscore of the mental health needs and protective and risk factors of mental well-being among caregivers in Asia. Findings of those papers inform the development and adaptation of culturally sensitive interventions to improve mental health outcomes among informal caregivers in Asia. The disccuant will comment on the strengths and limitations of these papers in terms of their contributions to the theory, research, and practice on mental health among informal caregivers in Asia."} +{"text": "Meteorological disaster monitoring is an important research direction in remote sensing technology in the field of meteorology, which can serve many meteorological disaster management tasks. The key issues in the remote sensing monitoring of meteorological disasters are monitoring task arrangement and organization, meteorological disaster information extraction, and multi-temporal disaster information change detection. To accurately represent the monitoring tasks, it is necessary to determine the timescale, perform sensor planning, and construct a representation model to monitor information. On this basis, the meteorological disaster information is extracted by remote sensing data-processing approaches. Furthermore, the multi-temporal meteorological disaster information is compared to detect the evolution of meteorological disasters. Due to the highly dynamic nature of meteorological disasters, the process characteristics of meteorological disasters monitoring have attracted more attention. Although many remote sensing approaches were successfully used for meteorological disaster monitoring, there are still gaps in process monitoring. In future, research on sensor planning, information representation models, multi-source data fusion, etc., will provide an important basis and direction to promote meteorological disaster process monitoring. The process monitoring strategy will further promote the discovery of correlations and impact mechanisms in the evolution of meteorological disasters. As an important source of potential damage, natural disasters have long received universal attention in the field of disaster prevention and reduction. The mitigation of natural disasters is a key factor in ensuring people\u2019s livelihood. According to a sigma report published by the Swiss Re Institute, the total global economic losses from natural disasters reached 105 billion USD in 2021, again exceeding the average for the previous 10 years ,4. ThereIn recent years, along with the rapid development of sensor technology, aerospace platform technology, and data communication technology, the global observation capability of satellite, aircraft, and land integration has been greatly enhanced ,7,8. Rem(1)What are the objectives of meteorological disaster process monitoring?(2)How are remote sensing approaches being used for meteorological disaster process monitoring?(3)What are the current gaps in remote sensing-based meteorological disaster process monitoring?According to the fifth Climate Report of the United Nations Intergovernmental Panel on Climate Change (IPCC), climate warming will intensify in the future . At the The rest of the paper is organized as follows: Disaster is a general term for objects that have destructive effects on human beings and the environment on which human beings depend for their survival . As one For the remote sensing monitoring of meteorological disasters, the aim is to meet the disaster management needs of disaster prevention and mitigation, and to obtain various pieces of disaster information in different periods in time . FollowiAfter determining the arrangement for the remote sensing monitoring of meteorological disasters, it is possible to follow the relevant requirements to perform monitoring tasks and begin to extract various types of disaster information from remote sensing data. Disaster is the product of the comprehensive effect of three factors: pregnant environment, causing factor, and disaster-bearing body ,22. For Although different meteorological disasters present different patterns and ever-changing situations in disaster factors, the occurrence of meteorological disasters is always a gradual, evolutionary process ,26,27. IThe roadmap of meteorological disaster process monitoring based on remote sensing is shown in In the monitoring of meteorological disasters, it is first necessary to reasonably and comprehensively determine the monitoring tasks to clarify the monitoring timescale, carry out sensor planning and construct the conceptual model of monitoring information. The accurate representation of monitoring tasks is the basis and premise of accurately and effectively obtaining disaster information.As an important branch of geography, the meteorological disaster system has the dual attributes of \u201cnatural\u201d and \u201csocial\u201d, and it is also \u201cscale\u201d dependent on nature. On the one hand, the dependence is manifested in the significant timescale effect of disaster factors. With the introduction of the timescale, when conducting meteorological disaster monitoring, the time boundary to be monitored should first be determined according to the time extent, and the disaster monitoring is limited to a certain period . To undeThere are three main types of sensor planning solutions: single sensor, multi-sensor in single platform, and multi-sensor in multiple platforms. For the planning of a single sensor, due to the small number of sensors, the data processing steps are relatively simple, and the data specifications between the multi-period data are unified . For insHowever, most sensor planning is based on the technical conditions of the sensor itself, which lacks the planning based on the meteorological disaster process monitoring; thus, this kind of planning method would not obtain detailed and specific solutions . For exaIn disaster management, the use of multi-period, multi-area, multi-source, and multi-department meteorological disaster monitoring information has gradually become normal. If there is no uniform standard for meteorological disaster information, it will be difficult to share information in disaster management, which is disadvantageous to efficient monitoring and emergency warning . TherefoThe unified management of the distributed sensors and data resources by establishing metadata model specifications has become an important method for disaster information modeling. Considering the universality of the model, it is usually divided into the general metadata model and the dedicated metadata model. General metadata models include Common Alert Protocol (CAP), Emergency Data Exchange Language Distribution Element (EDXL-DE) and EDXL-rm . The dedThe knowledge representation method can provide semantic integration among people, heterogeneous systems, and people-to-systems. The following related techniques are gradually being introduced to disaster information modeling: 1) Ontology. Ontology is helpful in expressing the concept of disaster and eliminating semantic heterogeneity. After the foundation of standardized geographic ontology proposed by Kolas et al. , more spIn summary, the existing disaster information models rarely consider the spatio-temporal factor; most of them record spatio-temporal information as common attributes . A meteoThe pregnant environment is the natural and human environment that causes disasters. The monitoring of the pregnant environment, mostly before the disaster occurs, and the monitoring results can help to evaluate the disaster risk and predict the disaster. For meteorological disasters, monitoring the pregnant environment is mainly carried out by the extraction of surface environmental information from the lithosphere to the atmosphere. There is a lot of information regarding the pregnant environment, such as altitude, slope, river, road, formation lithology, fault zone, etc., which can be divided into two categories: surface parameters and land cover.The methods of extracting surface parameters using remote sensing methods mainly include the empirical model method and the physical model method. The empirical model method is mainly implemented by establishing an empirical regression model between remote sensing observation signals and surface parameters . To imprThe main strategies for retrieving surface parameters based on physical models are as follows: (1) on the basis of considering the influence of local terrain on the imaging geometry, the surface parameters are extracted using a physical model that is suitable for a flat surface ; (2) on To improve the accuracy of remote sensing extraction of land cover information, it is necessary to involve as much multi-source and multi-temporal remote sensing information and existing knowledge as possible, and also to develop scientific methods to effectively fuse heterogeneous information and eliminate redundancy ,71. A vaIn recent years, with the acceleration of global urbanization, a great deal of infrastructure construction has rapidly changed land cover in a few decades or less . The impThe cause of meteorological disasters is the weather phenomena that may cause disasters. The characteristic parameters of meteorological disasters can reflect the genetic characteristics, structural characteristics, and development process characteristics of disasters and are an important basis for the monitoring and evaluation of the causes. The monitoring of causes based on disaster-characteristic parameters focuses on the type of characteristic parameter on the one hand and on the method of extraction used for each characteristic parameter on the other hand. The extraction of information regarding the causes of different meteorological disasters is discussed in the following parts.In principle, remote sensing approaches to drought monitoring can be divided into two categories: 1) the change in soil moisture can cause changes of soil spectral characteristics; 2) the change in plant physiological processes caused by drought can change the spectral properties of leaves and significantly affect the spectral properties of plant canopy. Sensors for drought remote sensing include a visible light band, near-infrared band, thermal infrared band, microwave band, etc. The common approaches include the soil thermal inertia method, soil moisture inversion method, vegetation index method, surface temperature method, and composite index method .Precipitation is the comprehensive result of atmospheric dynamic and thermal actions, which determines the external shape of precipitating cloud. Precipitation monitoring is mostly used to calculate the precipitation indirectly by detecting the cloud temperature or cloud particle information. This is not the same as directly observed precipitation but is currently one of the most difficult to observe atmospheric variables. Sensors for remote sensing of precipitation include visible light band, infrared band, active/passive microwave bands, and a combination of multiple sensors. Due to the different remote sensing data and retrieval algorithms, the precision of precipitation retrieval is different. The research focus has gradually turned to the fusion of precipitation products retrieved by multiple sensors to obtain more accurate precipitation information .Snow cover, as the most common upper boundary condition during freezing and thawing, directly affects the distribution and migration of soil moisture, soil temperature, freezing rate, freezing depth, etc. Snow cover has the unique spectral characteristics of a high reflection of visible light and a low reflection of short-wave infrared. Additionally, the snow particle size and the content of optical impurity affect the snow spectrum reflection. Sensors for the remote sensing of snow include a visible-light band, near-infrared band, far infrared band, and microwave band. Using the spectral characteristics, remote sensing approaches for snow cover monitoring can be divided into two categories: (1) binary snow identification (judging whether there is snow or not); (2) sub-pixel snow cover mapping in the form of area percentage, also known as snow coverage .Haze is a mixture of particles with different diameters. The scattering and absorption of electromagnetic waves change the radiative transmission process and affect the quality of remote sensing data. Remote sensing approaches to haze monitoring include four categories: spectral-feature-based method, image-preferential-based method, aerosol optical-thickness-based method, and multi-source remote sensing stereo-monitoring method .As the temporal and spatial resolution of the weather satellite has improved, satellite imagery has become the primary means of monitoring typhoons . The satDust particles contain a lot of minerals and have strong backscattering to solar short-wave radiation. This changes the long-wave infrared radiation and seriously affects the visibility of the atmosphere. Thus, the spectral characteristics of dust are significantly different from those of clouds and the underlying surface . HyperspFor the disaster-bearing body, as the main body of human society that is directly affected and damaged by disasters, the core content of information extraction is used to analyze the damage to or recovery of personnel, social wealth, lifeline systems, etc. The target detection and scene classification approaches in remote sensing processing are mainly used to extract information on disaster-bearing bodies of different types.For the extraction of information on the disaster-bearing body, the target object is all kinds of ground objects that are affected by meteorological disasters. According to the morphological characteristics of the object features, typical objects are generally classified into linear objects, blob objects, and complex objects. A large number of target detection methods have been accumulated, including statistical-based detection methods , but changes in the internal features of the scene cannot directly lead to changes in the type of scene. It can be concluded that there is a \"spatio-temporal semantic gap\" between the low-level changes in objects and the high-level changes in scene semantics. An instance of this is provided in Presently, pixel-level change detection is mostly used to detect various kinds of land surface indexes, object-level change detection is used to detect the damage degree of buildings, and scene-level change detection is used for flood mapping .Monitoring of disaster occurrence area. The determination of the disaster occurrence area is based on the construction of a comprehensive disaster index, which considers the intensity of the causing factor, the damage degree of the disaster-bearing body, and the impact of the disaster. On the basis of multi-temporal comprehensive disaster index inversion using remote sensing images, on the one hand, the disaster occurrence area where the disaster index changes are obtained by comparing the pre-disaster and post-disaster images; on the other hand, by comparing the images of different times, the change process of the disaster occurrence area is simulated .Monitoring the degree of disaster. The disaster degree is mainly expressed by disaster grade, building damage degree, casualty, economic loss, etc. . Remote Disaster rescue progress monitoring. Restoration and reconstruction are based on a comprehensive assessment of disasters, and the transitional resettlement of the victims is carried out. According to the post-disaster recovery and reconstruction plan, housing construction, infrastructure construction, public service facilities construction, disaster prevention and mitigation, ecological restoration, and land-use recovery are carried out . A compaDifferent types of meteorological disasters have different causes and effects, but they will evolve with the changes in disaster-causing factors and disaster carriers. Effective monitoring of the evolutionary process of meteorological disasters can not only promptly obtain the real-time status of the current disasters but also provide an objective basis for the prediction and early warning of the next disaster. Based on the above analysis, most research focused on monitoring a specific phase or a certain disaster factor ,192. HowRegarding the methods for the remote sensing monitoring of meteorological disasters, most are multiple static spatiotemporal observations using multi-temporal remote sensing data. At present, machine-learning regression methods have advantages in terms of time dynamics, such as artificial neural networks with hidden layers, which can predict the temporal and spatial changes in geographic phenomena. As a typical geographical phenomenon, meteorological disasters can be used to compensate for the differences between disaster monitoring and disaster evolution at different timescales. Machine learning methods can be used to extract relevant information about the development process from the ever-increasing meteorological disaster monitoring data stream. This can not only simulate the evolution process of meteorological disasters, but also gain a further understanding of the scientific problems of the meteorological disaster system. Together, the theory and method research into meteorological disaster process-monitoring needs a further breakthrough.Based on the characteristics of meteorological disasters, the requirements of the monitoring cycle, monitoring type, and monitoring range for different types and periods of meteorological disasters are determined. On the one hand, the applicability of existing sensors to disaster monitoring is clarified. For example, space-based remote sensing, mainly consisting of polar-orbiting satellites and geostationary satellites, has a wide range of coverage, a strong capacity for repeated observations, and is suitable for all-weather monitoring and early warning of large-scale dynamic changes in the pregnant environment and causing factors; space-based remote sensing, which is mainly based on aircraft, unmanned aerial vehicles and aerostat, has strong mobility and high resolution and is suitable for the dynamic monitoring of sudden meteorological disasters and the rapid assessment of the physical quantity of losses in the disaster-bearing body in key areas. On the other hand, to evaluate the combined effect of different sensors to acquire data, sensor planning can be obtained quickly and accurately in the actual monitoring of meteorological disasters, and the effectiveness and feasibility of the planning scheme are also guaranteed.With the rapid development of big data technology, the availability of various types of data has been continuously broken, creating conditions for the comprehensive monitoring of meteorological disaster processes. Most of the recorded remote sensing data regard the natural environment of the earth\u2019s surface, but the perception of changes in the social environment is scarce, and there is a lack of semantic attribute information. The fusion of multi-source data is not limited to the remote sensing data, but needs to be combined with more types of information to make up for the shortcomings of remote sensing monitoring. Social media, such as Twitter, Facebook, and Weibo, has become an effective means for government departments to keep abreast of disaster developments, with its wide participation and multi-source communication channels . In the The purpose of meteorological disaster process-monitoring is to perform a semantic analysis of various types of disaster information in multi-temporal remote sensing data. The existing meteorological disaster monitoring, due to the decentralization of its tasks, makes it possible to obtain one-sided disaster information. It is necessary to construct a standardized meteorological disaster process-monitoring information model and organize all kinds of information obtained from meteorological disaster monitoring in a standardized and integrated way.The objects of meteorological disaster monitoring include the interaction law, spatial distribution and evolution process of various phenomena in the disaster system, with specific spatio-temporal characteristics. In the field of geographic information science, the geographic, spatio-temporal modeling methods mainly include the temporal snapshot model, event spatio-temporal model and process spatio-temporal model. (1) The temporal snapshot model represents geographic phenomena with continuous dynamic changes as a set of discrete objects with time stamps, displaying time as a property of space . As onlyThe process-oriented spatio-temporal modeling method can provide an important reference for the meteorological disaster process-monitoring information model. Moreover, the evolution mechanism of meteorological disasters is also reflected in the spatio-temporal process of disasters. Therefore, for information modeling in meteorological disaster process-monitoring, it is necessary to use time and space as the framework. This can formally describe the disaster content and mutual relationship among various disaster elements to provide an in-depth analysis, forecasting and early warning, disaster prevention, and relief.By abstracting the disaster state, which is complex and difficult to directly perceive, the information visualization methods can effectively express the change in the morphological characteristics and attribute information of the disaster elements. These methods also can directly and show live the influence degree and development trend of disasters, and help people acquire knowledge and discover patterns. In the present and future, it is important to realize the visual display of disaster monitoring information to assist in disaster simulation, analysis, and emergency rescue decision-making.Due to the diversity and persistence of meteorological disasters, the interrelation of all kinds of disaster information is complicated. The visualization of meteorological disaster monitoring information not only needs to deal with disaster data from different sources and complex disaster elements, but also needs to look at the key information of different users at various stages to develop visualization tasks. In the existing visualization research, no complete and universal method can accurately the characteristics of all meteorological disaster scenes and meet the needs of visualization information in different stages. In summary, visualizing the meteorological disaster monitoring information and displaying the evolutionary process of meteorological disasters is an urgent problem to be solved.The occurrence and decline of meteorological disasters occur in a cyclic evolution process, and the remote sensing monitoring of meteorological disasters is essential for disaster prevention, disaster control, disaster resistance, disaster relief, and other disaster management. As meteorological disaster monitoring has the characteristics of variable timescales, diverse monitoring objects, and complex monitoring content, it is extremely challenging to obtain information on meteorological disasters efficiently, accurately and comprehensively. Based on the analysis of the basic concepts and methodology of remote sensing monitoring in meteorological disasters, this paper reviews and studies the research status of remote-sensing monitoring for meteorological disasters from the perspective of different meteorological disaster remote sensing tasks. The reasonable and comprehensive determination of monitoring tasks is a prerequisite for accurate and effective access to disaster information. In compliance with the requirements of the monitoring task, based on the extraction of surface parameters, land-cover information extraction, target recognition and other remote sensing processing approaches, information on the pregnant environment, causes and disaster-bearing body is extracted. Furthermore, by detecting and analyzing the changes in multi-temporal meteorological disaster information, the comprehensive monitoring of meteorological disaster evolution processes, such as disaster occurrence scope, degree of disaster effects, and disaster relief progress is realized.Meteorological disaster monitoring is based on the time characteristics of the disaster process and analyzes the state changes in disaster content in each disaster element under a certain timescale. Although many remote sensing approaches were successfully used for meteorological disaster monitoring, there are still gaps in process monitoring. In the future, from the perspective of the process of meteorological disasters, the sensor-planning method and the information model of multi-temporal, remote sensing data should be studied. The improvement in various methods such as disaster information extraction abilities, the effective integration of multi-source data, and monitoring information visualization must be emphasized. More importantly, it is necessary to thoroughly study the objective internal laws of various disaster objects and disaster contents in meteorological disasters over different timescales, to reveal the relationship and influence mechanism of various pieces of disaster information in the evolution of meteorological disasters. This not only conforms to the logic and sequence of human understanding of meteorological disasters, but also provides support for the in-depth analysis of the evolution mechanism of meteorological disasters."} +{"text": "S. aureus adhesion on pristine PMMA, HA-5% lysozyme in The authors regret to inform that, the representative images of waterborne The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers."} +{"text": "Objectives: To investigate the epidemiological characteristics and infection routes of new cases in order to provide information for preventing COVID-19 resurgence in areas initially under control.Methods: The information of new symptomatic and asymptomatic patients in Chinese mainland was collected. The location distribution, epidemic course, infection routes and patients' characteristics of outbreaks were described and analyzed.Results: There were 43 new outbreaks with 3,795 symptomatic patients in Chinese mainland from March 21, 2020 to June 13, 2021. These outbreaks mainly occurred in central, border and coastal port cities. The main infection route of first generation indigenous patients was contact with imported cases and contaminated goods or environments. The infection routes of secondary generation patients mainly included family transmission, indoor social gathering infection, nosocomial infection and other infection routes. Family transmission was the most common infection route, and indoor social gathering was the most important reason for the large-scale outbreaks.Conclusions: Strengthen the management of imported patients and staff in high-risk posts was the key point to avoid the first generation indigenous patients. Adequate family isolation, prompt management policies for indoor public place and monitor of population at risk of infection were key strategies for preventing COVID-19 resurgence in areas initially under control. The coronavirus disease 2019 (COVID-19) pandemic, which began at the end of 2019, has been a worldwide epidemic of infectious disease . Over 17Therefore, to understand the epidemiological characteristics and main routes of the new outbreaks of COVID-19 in areas initially under control, we analyzed the epidemiological characteristics and infection routes of the outbreaks in different regions of Chinese mainland in recent 1 year, which will provide the basis for the corresponding preventive strategies.The daily new indigenous symptomatic and asymptomatic patients, start date, duration, patient number and clinical subtype were collected from the official documents released by the Health Commission of the People's Republic of China and the provinces \u201318. The The definitions of first and secondary generation indigenous patients were referred to guidelines for epidemiological investigation of COVID-19 release by the Chinese Center for Disease Control and Prevention .First generation indigenous patients were defined as the earliest symptomatic or asymptomatic patients in the epidemiological investigation of epidemics. According to the occupation of patients, the possible infection sources were investigated, including imported cases, imported goods or related environment contaminated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Second generation indigenous patients were defined as symptomatic or asymptomatic patients contacted with the first generation indigenous patients within 14 days without other potential sources of infection. After identifying the first generation patients, the infection routes of the second generation patients were determined by investigating the contacts with the first generation patients, and were classified into family transmission, indoor social gathering infection , nosocomial infection and other infection routes. The definitions of other secondary generation of patients were similar.The number of symptomatic and asymptomatic patients, start date, duration and clinical subtype of patients in different epidemics were summarized in the descriptive epidemiological analysis. The numbers of daily symptomatic patients were used to describe the epidemic curves of different outbreaks. Statistical map was used to describe the location distribution of outbreaks, in which the area of the circle was proportional to the number of patients. The infection routes of first and secondary generation patients were extracted and summarized from the epidemiological investigation to identify the key infection routes of patients.On March 21, 2020, the first indigenous patient cause by imported patient was reported in Guangzhou, who did not cause further transmission. However, in the past year, there have been some new outbreaks with a large number of indigenous confirmed cases in Harbin, Beijing, Urumqi, Dalian and other cities . In ApriIn May, four outbreaks also occurred in Yingkou, Lu'an, Guangzhou and Shenzhen. Among them, the outbreaks in Yingkou and Lu'an belonged to the same transmission chain, and the source might be cold chain food in Yingkou, resulting in 24 symptomatic and 23 asymptomatic patients in both cities. On May 21, a new indigenous patient was reported in Guangzhou, which leaded to rapid spread of COVID-19 through family transmission and indoor gathering, resulting in fifth generation of transmission and 139 symptomatic cases. On the same day, one indigenous asymptomatic patients was reported in Shenzhen, and four symptomatic and 12 asymptomatic patients were reported in the next few days, who were all employees of an international freighter operation company and their close contacts.By June 13, 2021, 43 new indigenous outbreaks have occurred in Chinese mainland, mainly distributed in central cities, border cities in the inland areas and coastal port cities . The citIn the new indigenous outbreaks, the infection routes of the first generation patients were mainly direct or indirect contact with imported patients, goods or environments contaminated by SARS-CoV-2. Therefore, the indigenous patient included staff or nearby residents contacted with imported cases in quarantine hotels, families infected by imported cases during home quarantine, and staff contacted with contaminated imported cold chain food or environment of inbound aircraft and freighter.The infection routes of secondary generation patients included family transmission, indoor social gathering infection , nosocomial infection and other infection routes . Family Prevention of COVID-19 pandemic is the top priority in the world. After the outbreaks have been controlled in some countries or areas, the normal work, life and foreign exchanges should be restored. Therefore, the focus of prevention in these countries was to prevent the resurgence of COVID-19 epidemic due to imported patients. In this study, we analyzed the epidemiological characteristics and infection routes of new indigenous outbreaks in Chinese mainland in recent 1 year after the pandemic in Wuhan was controlled. The results showed that the new indigenous outbreaks mainly occurred in central cities, border cities in the inland areas and coastal port cities. The main infection routes of first generation patients were direct or indirect contact with imported cases, imported goods or related environment contaminated by SARS-CoV-2. The infection routes of the secondary generation patients mainly included family transmission, indoor social gathering infection, nosocomial infection and other infection routes. Although these outbreaks have been controlled in a short time, there were still some gaps in community prevention and nosocomial infection control in new COVID-19 outbreaks.The first generation patients were the source of COVID-19 resurgence and the focus of preventive strategies. The first generation patients of 15 outbreaks were related with imported patients, suggesting the necessity of stricter isolation management of entry personnel \u201325. The The first generation patients of seven outbreaks were related with the contaminated imported goods or environments, including cold chain food, container, freighter, aircraft and so on \u201328. TherCompared with the first generation patients, the infection routes of secondary generation patients were more diversified, and there were a large number of asymptomatic patients, which increased the difficulty of prevention , 32. In Nucleic acid test was an important method for etiological diagnosis of COVID-19, especially for asymptomatic and atypical patients. However, false negative results were found in some imported patients, indigenous symptomatic and asymptomatic patients before diagnosis. In addition to the low viral load in some patients' nasopharynx, it may also be related with the process of collection and transportation of specimens , 38. TheIn summary, the prevention of new indigenous epidemic in areas initially under control was an important issue during the pandemic of COVID-19. We analyzed the new indigenous outbreaks in Chinese mainland, and found that these outbreaks mainly occurred in central, border and coastal port cities. The first generation patients were mainly infected by contacting imported patients, contaminated goods and environment, and secondary patients were mainly infected through family transmission, indoor social gathering and nosocomial infection. Strengthen the management of imported patients and staff at high-risk of SARS-CoV-2 infection was the key point to avoid the first generation indigenous patients. When the new indigenous epidemic occurred, prompt management of indoor public place and monitoring of population at risk of infection using big data can avoid large-scale epidemic.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.YL: investigation, visualization, and writing\u2014original draft preparation. KY: investigation, data curation, and writing\u2014reviewing and editing. SZ: investigation, methodology, and writing\u2014reviewing and editing. LW: investigation, writing\u2014reviewing and editing, and conceptualization. RC: conceptualization and writing\u2014reviewing and editing. All authors contributed to the article and approved the submitted version.This work was supported by the Emergency Research Project of COVID-19 of Zhejiang University (grant number: 2020XGZX024).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Despite the preventability of cervical cancer, the global burden remains high with 604,000 cases and 342,000 deaths estimated in 2020 . IncidenWith the political momentum in place to eliminate the disease over the next decades via national scale-up of the triple intervention strategy, we would like to highlight the current situation in the Newly Independent States (NIS) of the former Soviet Union.Opportunistic annual cytology screening of broad age groups \u2013 frequently using Romanowsky-Giemsa staining \u2013 remains a common practice in many NIS ; while nUsing the national and subnational cancer registry data from four NIS for the period 2008\u20132017, we examined the time trends in recorded age-standardised (world) incidence rates of invasive cervical cancer. Rates are uniformly high, and trends appear either stable or slightly increasing over the 10-year period . Given tAs a way forward towards cervical cancer elimination in the region, we advocate a radical shift in national policies in the NIS, away from opportunistic screening towards population-based, quality-assured HPV vaccination and HPV-based screening programmes. IARC partners with WHO Regional Office for Europe to improve screening policies and practices in the NIS, and to build capacity for quality assured screening and for population-based cancer registries, thus enabling the benchmarking of national progress in HPV-related cancer control in the forthcoming decades.Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.The authors report no declarations of interest."} +{"text": "This study used Latent Class Analysis to examine patterns of social participation among older adults in the US, the UK, and China, from the three nationally representative surveys conducted in 2018-2019: The Health and Retirement Study, the English Longitudinal Study of Ageing, and the China Health and Retirement Longitudinal Study. Although the profiles of social participation were distinctively different, several common patterns were found: Comprehensive Participants, Occasional Participants, and Deficient Participants. It was estimated that less than 10% of older adults from these countries were extensively engaged in social participation. Seventy-seven percent of Chinese older adults were shown being \u201cDeficient Participants\u201d, and the percentages were 29% and 20% in the US and the UK, respectively. The findings showed positive associations of levels of participation with socioeconomic status and health. The magnitudes of these associations varied across the nations. Actions are needed to promote levels of participation for Chinese older adults."} +{"text": "For 15 years, the Annual African Vaccinology Course (AAVC) hosted by the Vaccines for Africa Initiative, has been at the forefront of vaccinology training in Africa. The AAVC was developed in 2005 in response to the growing demand for vaccinology training in Africa. To date, 958 policy makers, immunization managers, public and private health practitioners, scientists, postgraduate and postdoctoral students have been trained. These participants are from 44 of the 54 African countries. The course content covers diverse topics such as considerations for new vaccine introduction, mathematical modelling, and emerging and re-emerging vaccine preventable diseases. As the landscape of vaccinology continues to evolve, the AAVC aims to expand the reach of vaccinology training using blended learning approaches which will incorporate online and face-to-face formats, while expanding access to this popular course. Ultimately, the AAVC endeavours to develop a big pool of vaccinology expertise in Africa and to strengthen regional ownership for immunization programmes. Immunization programmes in Africa have achieved remarkable progress since the introduction of the Expanded Programme on Immunization (EPI) in 1974 ,3. The sAims of the course: the aim of the AAVC is to: (i) broaden understanding of the challenges and opportunities in vaccinology at regional and global levels, (ii) equip participants with essential expertise to support national immunization programmes, (ii) build sustainable research capacity for vaccine development including the conduct of high quality phase I-IV vaccine trials in Africa, (iv) explore the roles and challenges of National Immunization Technical Advisory Groups (NITAGs) in strengthening immunization policies in Africa, and (v) foster collaboration and networking among African vaccinologists.Course content: since the inception of the AAVC in 2005, the course content has evolved in response to the rapidly growing field of vaccinology and the increasing demand for developing vaccinology expertise in Africa. Further information on the AAVC course content may be sourced from the VACFA website [ website . BrieflyFormat of the course: this is usually a five-day face-to-face course taking place in the last quarter of the year. While previous versions of the AAVC were held in several African countries [ountries , this waountries . The onlth AAVC in 2018, the NITAG workshop was held over 1.5 days. Attendees of the workshop included core members and secretariat of NITAGs from nine African countries, namely; Angola, Cameroon, Ghana, Nigeria, Rwanda, South Africa, Tanzania, Togo and Uganda. Discussions were facilitated by representatives from VACFA and the World Health Organization (WHO) [As part of VACFA\u00b4s initiative to strengthen the vaccine policy and decision-making landscape in Africa, the scope of the AAVC was extended in 2018 to include a workshop dedicated to exploring the roles of, and challenges faced by NITAGs. The workshop is a networking opportunity and explores possible technical and scientific support mechanisms for NITAGs in Africa. In its first offering during the 14on (WHO) . This waCourse participants: a report on the participants and faculty members of the AAVC held between 2005 and 2010 was previously published [ublished . BetweenCourse faculty members: about 116 faculty members have given talks in the AAVC between 2011 and 2019. On average, 33 faculty members regularly give talks at the AAVC each year. The AAVC faculty is well-represented by local, regional and international experts from relevant fields across the vaccinology cascade, including academia, global health agencies, non-governmental agencies and the pharmaceutical industry for vaccines and immunization, integration of health economics and mathematical modelling in EIDM, Covid-19 vaccine rollout, and vaccine safety monitoring. In addition, the AAVC may be adapted to meet specific training needs of NITAGs. As we move towards the Immunization Agenda 2030 , the AAV"} +{"text": "The Omnibus Budget Reconciliation Act (OBRA) of 1987 included provisions for the Preadmission Screening and Resident Review (PASRR) program, which requires states to create and maintain systems to assess persons with serious mental illness (SMI) seeking NH care. The prevalence of SMI in NHs is increasing, and little is known about the effectiveness of the PASRR program intervention. We conducted 20 interviews with state and national PASRR stakeholders, including assessors, hospital discharge planners, mental health advocates, geriatricians and geriatric psychiatrists. Interview data were triangulated with state provided materials on PASRR collection and implementation. Based on these interviews, we identified four themes: 1) variation in the implementation of federal PASRR legislation across states and jurisdictions, 2) the need for investment in professional development and workforce capacity, 3) lack of usefulness of PASRR in ongoing care planning, and 4) the need to consider the role of age, race/ethnicity, and stigma on quality of care for NH residents with SMI. Stakeholders agree that PASRR legislation was well intentioned, but also expressed concern regarding the completion of PASRR as an issue of compliance versus meaningful assessment. More work is needed to determine how best to develop and support the care needs of people with SMI, while being mindful of the original goals of deinstitutionalization that prompted OBRA passage. In order to assess the impact of the PASRR program on quality of care and mental health outcomes, further research should take an evaluative approach through meaningful use of PASRR data."} +{"text": "Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from different European regions. We identified and prioritized fifteen major challenges hindering the balanced provision of multiple FES and identified a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-oriented management through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey, most solutions were assessed as highly effective, transferable, monitorable, and with potential for being economically efficient. The implementation of the solutions could have synergistic effects when applying the notion of leverage points. Seven emerging pathways towards the sustainable supply of FES have been identified. These pathways build on each other and are organized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions between forest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparent knowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathways can contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES.The online version contains supplementary material available at 10.1007/s11625-022-01111-4. European forests are ecosystems that deliver manifold benefits to society via so-called Forest Ecosystem Services (FES) . On the first day, each thematic group prioritized and characterized the respective subsets of thematic challenges resulting from the exploratory survey. The prioritization included, for each challenge, a general assessment of the urgency , their impact , the types of FES affected, scale, and the inter-relations between each of these challenges and all the thematic areas. Accordingly, each thematic group reduced the list of challenges to the five most relevant. At the end of the first day, the number of challenges was reduced through a series of anonymous majority voting rounds in plenary to the three most pressing challenges for each thematic area. During the second day, the thematic groups reconvened to formulate and characterize strategic solutions for each of the three selected challenges. The characterization consisted of a description of the solution, the feasibility of implementation, a time frame, and the resources needed for application. A detailed account of the whole process, including the definition, framing and prioritization of the challenges (first day of the workshop); and the identification and characterization of the strategic solutions (second day of the workshop) can be found in S3.During the third phase, the identified solutions were evaluated in an online survey distributed to all participants in January 2021 (S2). The respondents rated each solution according to five different criteria of optimal solutions, adapted from the concept report on climate policy-mix optimality Gorlach see Box was usedThe participants in the solution scanning process were 24 experts from academia, policy, and practice working directly on FES in Europe. Most participants (90%) were related to the EU Horizon 2020 funded projects SINCERE and InnoForESt,\u00a0both dealing with the promotion of FES-related innovations. A team of three facilitators selected from both projects supported the implementation of the solution scanning exercise. About expert participants, particular attention was paid to balance backgrounds between academia and practice, disciplines, geographic foci, seniority level, and gender (S4).Most of the selected experts worked at research organizations at the interface between science, policy, and practice (41%). The covered areas of knowledge of the forestry sector were broad, including experts on forest ecosystem services governance and innovation, urban forestry and European forest policy. Partly because the coordination of both of the Horizon 2020 projects is based in Germany, most of the participants worked at German organizations (41%). However, seven other European countries were also represented in the exercise, namely Spain, Italy, Austria, Belgium, Switzerland, Finland, and Sweden. A balanced gender representation was achieved and consciously maintained along the process.This solution scanning exercise synthesizes the currently fragmented views on forest challenges and targets suitable solutions to foster the sustainable provision of FES. The organization of the exercise into three well-defined phases allows a clear and transparent communication among the coordinators and experts, facilitating a smooth iterative process. Due to COVID-19 restrictions, the participatory process was conducted entirely online. Two important aspects of this sequential participatory method have been the regular communication with the group to ensure a shared understanding of the process, the use of preparatory materials before and after each workshop through two surveys (S1 and S2), and the presentation of the state of the work at the beginning of each phase of the solution scanning session. However, we must emphasize that the results highly depend on the participant contributions and the specific timing of the survey and workshops, which is a limitation of our approach.After the prioritization process, 15 challenges were selected, three per thematic area, based on their urgency and impact . The suitability of each solution was subsequently assessed and ranked based on the following six criteria: social\u2013ecological effectiveness, economic efficiency, readiness, feasibility, and transferability potential (Box 1). Table Sustainability Area: Environment; Challenge 1\u2014Increasing frequency and intensity of extreme weather eventsClimate-smart forestry is a targeted approach to manage forests in response to climate change should be consistently supported by cross-scale European and national policies similar to those in place for timber and biomass production . These strategies are often coupled with a philosophy of embracing innovations towards improved forest management for the provision of FES bundles, especially for regulating and cultural FES, for the promotion of ecological and societal transformation, and for the sustainable use of public goods. Public forests would be used as niches of innovation Geels of, for Sustainability Area: Socio-culture; Challenge 13\u2014Homogenization of perceptions of forest values by societyUnderstanding forests as a mean to solve economic problems is a reductionist standpoint. In the pursuit of sustainable forest management, increased identification and inclusion of cultural bonds is crucial. To achieve a deeper understanding of the mutual constitution of the society\u2013forest relation, it is also necessary to recognize the multi-layered spectrum of forests\u2019 contributions . European studies of public perception for business model implementation to strengthen their adaptation to each specific context. For example, by refocusing on forest protection measures . These types of solutions would normally require long-term commitment, institutional changes, and socio- political will . Furthermore, they directly or indirectly interfere with long-established cultural elements or strong economic interests . These solutions can be considered as aiming for or being dependent on larger, perhaps even fundamental system changes which require the alteration of existing paradigms, institutions , and actors\u2019 behaviors.A closer look at the solutions\u2019 definitions and prioritization suggests a possible sequence of implementation. Inspired on the notion of leverage points, where solutions can induce shallow or deep changes connection between people and nature. Forestry education at all levels, forest management, and policies need to pursue a shift from the consideration of instrumental values, to increasingly considering intrinsic and especially relational value dimensions , or through user-financed PES in those areas where there is sufficient willingness to pay for a specific FES Supplementary file2 (XLSX 15 KB)Below is the link to the electronic supplementary material."} +{"text": "H\u00f4pital D\u2019instruction des Arm\u00e9es de Cotonou Centre Hospitalier et Universitaire]) laboratory in Benin launched a quality improvement programme in alignment with the World Health Organization Regional Office for Africa\u2019s Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA). Among the sub-Saharan African laboratories that have used SLIPTA, few have been francophone countries, and fewer have belonged to a military health system. The purpose of this article was to outline the strategy, implementation, outcomes and military-specific challenges of the HIA-CHU laboratory quality improvement programme from 2015 to 2018.In 2015, the Army Teaching Hospital\u2013University Teaching Hospital (HIA-CHU [The strategy for the quality improvement programme included: external baseline SLIPTA evaluation, creation of work plan based on SLIPTA results, execution of improvement projects guided by work plan, assurance of accountability via regular meetings, training of personnel to improve personnel competencies, development of external stakeholder relationships for sustainability and external follow-up post-SLIPTA evaluation.Over a period of 3 years, the HIA-CHU laboratory improved its SLIPTA score by 29% through a quality improvement process guided by work plan implementation, quality management system documentation, introduction of new proficiency testing and internal quality control programmes, and enhancement of personnel competencies in technical and quality management through training.The programme has yielded achievements, but consistent improvement efforts are necessary to address programme challenges and ensure continual increases in SLIPTA scores. Despite successes, military-specific challenges such as the high mobility of personnel have hindered programme progress. The authors recommend that further implementation research data be shared from programmes using SLIPTA in under-represented settings such as military health systems. H\u00f4pital D\u2019instruction des Arm\u00e9es de Cotonou Centre Hospitalier et Universitaire]) of the Benin Army Health Service in Cotonou is a reference health centre known for the quality of its services and training. The HIA-CHU laboratory plays a leading role in the public healthcare continuum by providing diagnosis, screening, and initial and follow-up treatment as well as preventative care.1 Therefore, the HIA-CHU laboratory prioritises quality, in that it promotes the accuracy, reliability and timeliness of results.The Benin Army Health Service provides healthcare to army personnel, their families and civilians across Benin. The Benin Army Health Service is involved in disaster response and supports the Beninese public health system, with approximately 75% \u2013 80% of its services provided to the civilian population. The Army Teaching Hospital\u2013University Teaching Hospital 15198:2012 standard, \u2018Medical Laboratories\u2013Particular requirements for quality and competence\u2019, serves as a standard for the laboratory quality management system (QMS) \u2013 a formalised system that outlines required structures and functions for medical laboratories. Progress made on the ISO 15189 standard can help a laboratory prepare for accreditation through a recognised agency; this allows the laboratory to demonstrate to clients, partners and staff that it has attained a high level of technical competence, thus instilling confidence in stakeholders on the accuracy and reliability of its results.In recent years, there has been an emphasis on improving medical laboratory services globally. Health priorities have been set forth by public declarations, such as the International Health Regulations and the Maputo Declaration (2008), in which signatories pledged to address and strengthen laboratory and health services.3 Though progress has been made, most clinical laboratories in sub-Saharan Africa remain under-equipped, under-funded and far from attaining international norms and standards. Few laboratories are accredited to international quality standards, and most of these internationally accredited laboratories are based in South Africa.4 Quality assurance, which comprises QMS including the existence of a quality manual, use of internal quality controls (IQC) and participation in external quality assessment (EQA), is poorly implemented and often unavailable in many laboratories in sub-Saharan Africa.7 In the absence of quality assurance, there is the risk of laboratory errors, which could adversely impact patient care.In sub-Saharan Africa, the clinical laboratory remains a weak link in the healthcare chain.8 The African Society of Laboratory Medicine serves as the secretariat of the World Health Organization Regional Office for Africa SLIPTA programme. The SLIPTA framework guides improvement of performance, measures and evaluates the progress of laboratories towards ISO 15189 international accreditation and awards a certificate of recognition from zero to five-star ratings.9To alleviate these challenges and support awareness of the importance of achieving quality standards in medical laboratories in sub-Saharan Africa, the World Health Organization Regional Office for Africa developed in 2009 a phased laboratory quality management evaluation system called the Stepwise Laboratory Quality Improvement Process Toward Accreditation (SLIPTA).The HIA-CHU in Cotonou, Benin, has a staff consisting of military and civilian personnel and includes a clinical pathologist, 12 medical laboratory scientists and support staff. The services provided include medical fitness evaluation, disease prevention, treatment and care, and teaching and research in medical, biological, pharmaceutical, paramedical, odontological and veterinary specialities. Laboratory services at HIA-CHU are versatile and the laboratory manages, on average, 20 000 patient files and 50 000 tests per year.In January 2015, the HIA-CHU laboratory service initiated, for the first time, a quality improvement (QI) programme in alignment with the SLIPTA framework. The QI programme goal was to improve laboratory services related to disease diagnosis and monitoring via the implementation of QMS using SLIPTA framework. The QI programme aimed to provide training for laboratory personnel on quality management concepts and practices, monitor laboratory quality and adherence to quality systems, conduct laboratory test method validation and provide proficiency testing panels for HIV, tuberculosis and other critical tests \u2013 successful implementation of the QI programme ensures that laboratory stakeholders and end-users have confidence in laboratory data which informs clinical decisions and optimises patient care.The HIA-CHU laboratory QI programme was launched through a collaboration with the US Department of Defense HIV/AIDS Prevention Program (DHAPP). As of 2015, the Benin Army Health Service already had a long-standing collaboration with DHAPP, which had been funding laboratory equipment and reagents, specifically to support HIV diagnosis and treatment monitoring. Over the years, both parties recognised that laboratory tests and equipment alone are not sufficient to demonstrate test result quality; tests and equipment must be accompanied by laboratory quality practices implemented by properly trained and motivated personnel. To address this recognised need, DHAPP began supporting the Benin Army Health Service in the execution of the HIA-CHU laboratory QI programme in 2015, with implementation assistance provided by the United States-based global health company Global Scientific Solutions for Health .The purpose of this article is to report on the implementation of the QI programme at the HIA-CHU laboratory from 2015 to 2018.The laboratory QI programme began in January 2015 with initial programme planning among stakeholders and the facilitation of a comprehensive baseline evaluation of the HIA-CHU laboratory by GSSHealth using the World Health Organization Regional Office for Africa SLIPTA checklist, version 2:2015. The baseline SLIPTA evaluation allowed the assessment of the 12 quality management sections: organisation and personnel, management reviews, process control and internal quality assessment and EQA, information management, corrective action, equipment, purchasing and inventory, documents and records, occurrence management and process improvement, internal audit, client management and customer service, and facilities and safety.Following the evaluation, leaders from HIA-CHU, DHAPP and GSSHealth convened for a collaborative session to review findings, identify priority QI areas and develop a tailored QI approach for each priority area.A tailored QI approach was developed to strengthen HIV testing processes \u2013 the focus of the funding agency DHAPP; it covered the identification of key quality indicators to track and improve upon over time and the development and execution of the QI work plan.The key indicators identified to measure laboratory improvement based on ease of collection and relevance to the work plan included:SLIPTA: Percentage improvement in total and by section.EQA: Percentage score in PT programme.IQC: Accuracy of quality control results.Personnel training: Percentage change in theoretical test scores for training workshops.Laboratory documentation: Number of documents created and adequately implemented to standardise laboratory practices and formalise the commitment to the QMS.The laboratory-set targets were: continual improvement in the SLIPTA score through the establishment and implementation of improvement projects tracked by work plans, participation in EQA and PT and improvement of performance where the score is less than 100%, participation in IQC activities and improvement of processes in case of discrepancies between expected and obtained results, strengthening of laboratory quality management processes guided by well defined documentation, and the advancement of laboratory personnel competencies through training and mentorship workshops.The HIA-CHU laboratory supervisor facilitated work plan development in collaboration with partners and laboratory staff. The work plan included high-level QI goals, specific objectives for each goal and details of specific, measurable, achievable, realistic, and timely, or \u2018SMART\u2019, tasks and deliverables to meet set targets within defined timeframes see .The work plan was progressively implemented and updated through improvement project execution, progress monitoring, ongoing data collection and review, and continual alignment with the funder\u2019s priorities. Staff were engaged in the work plan implementation through their appointments to specific QI projects with oversight by the laboratory supervisor, and through continuous engagement in recurring collaborative work plan update meetings to promote accountability. Quality improvement activities conducted in the context of the work plan included: nomination of new QMS personnel roles , targeted laboratory personnel training and mentorship, implementation of EQA and IQC, definition of essential QMS processes and development and use of associated documentation, and coordination of a follow-up SLIPTA evaluation to measure progress.From the baseline SLIPTA evaluation, the identified priority issues, which correspond to low-scoring SLIPTA sections, include the following: the lack of a quality manual or safety manual, the lack of standard operating procedures for all processes and technical procedures, the lack of PT and quality control for tests, the lack of equipment maintenance and repair logs, the lack of temperature monitoring processes, and the lack of mistakes or error logs.The initiation and implementation of a QI programme at the HIA-CHU laboratory yielded numerous positive changes as perceived by HIA-CHU hospital leadership, laboratory management and staff, and partners . Positive changes included the establishment of a laboratory quality management team, achievement of designated QI projects resulting in SLIPTA score improvements, the improvement of IQC and EQA test result accuracy, the development and implementation of over 50 standard operating procedures, and the strengthening of personnel competencies through targeted QMS training and mentorship. Throughout the years of the QI programme, support from funding partner DHAPP and implementing partner GSSHealth ensured continuous evaluation of processes via the internal and external evaluations and the update of work plans and associated QI projects.The engagement of laboratory staff was key to the establishment and implementation of the laboratory QI work plan at HIA-CHU. To encourage staff commitment to the QI approach and ensure staff in-depth orientation to quality management concepts and testing processes, the laboratory QI approach prioritised staff training and mentorship.Over 50 technicians participated in training workshops on QMS co-organised and co-facilitated by the Benin military health system and GSSHealth. All training sessions consisted of didactic and interactive sessions and tests were administered pre- and post-training to evaluate knowledge change among the trainees. The median change in test score from pre-training to post-training for all the trainees increased from 15% to 40% . ImproveIn the first year of the programme, two quality workshops were held for laboratory staff with GSSHealth facilitators. The objectives of the workshops were to improve the competency of laboratory staff in the areas of quality assurance, QMS and HIV and tuberculosis testing. These topic areas were priorities for the laboratory director and DHAPP \u2013 the funder, whose focus is the prevention and control of HIV and HIV comorbidities. The first workshop took place in April 2015 with a focus on quality management concepts for equipment management, document writing and EQA. Staff received guidance and mentorship on HIV rapid testing. A second workshop took place in September 2015, with a focus to increase staff competency on laboratory supply chain and stock management. At the end of the first year, a follow-up SLIPTA evaluation was conducted.In 2016, the QI programme continued with an updated work plan, and laboratory staff participated in a national biosafety and biosecurity workshop hosted by the Ministry of Defense and the Ministry of Health. The second year concluded with a poster presentation by the HIA-CHU laboratory supervisor on the quality programme at the African Society of Laboratory Medicine international conference in December 2016.In 2017, the laboratory quality team updated their quality work plan, worked with laboratory personnel on QI projects, implemented the use of quality controls for CD4 testing, and organised an internal SLIPTA evaluation. In April 2017, one laboratory staff member from HIA-CHU was sponsored to attend a multi-country, 5-day training workshop in Senegal. The workshop covered essential aspects of laboratory quality management, including document management and standard operating procedure writing; equipment management and maintenance; error occurrence management, prevention and corrective action, and quality indicators. Finally, a follow-up external SLIPTA evaluation was conducted in October 2017 to re-evaluate the laboratory system, measure progress since the previous external SLIPTA evaluation, and update the QI programme.As the QI programme moved into its third year in 2018, the laboratory again updated its work plan, based on the previous evaluation, and revised and updated key documentation including the laboratory quality manual and biosafety manual. In April 2018, a joint Ministry of Defense and Ministry of Health laboratory biosafety and quality management workshop was organised, to increase staff competency on principles and ISO standards for biosafety and biosecurity.Through its ongoing commitment to training personnel in both technical and quality management topics, the laboratory has observed significant improvements in staff competencies and performance. For example, the SLIPTA sections in which the laboratory achieved the most significant quality improvements correspond to the quality management topics covered during training workshops. Data from the QI programme showed that post-training, personnel knowledge was improved and retained . AdditioThe laboratory document management system has been developed gradually over time and has included the creation and implementation of a quality manual, a biosafety manual, a sample collection manual and more than 50 standard operating procedures, technical instructions, forms and logs . The laboratory supervisor and designated quality manager took the lead in developing documents, executing a document management process, and introducing new documents into circulation in the laboratory. Laboratory personnel were oriented to new documents and procedures during regular laboratory meetings, facilitating the understanding and proper use of new documents. The availability of procedures and other documents helped laboratory management ensure that personnel observed standardised processes across the pre-analytical, analytical and post-analytical phases, and simplified the training of new personnel. Furthermore, to ensure that only correct and updated documents were available in the laboratory, processes to control document revision, approval and version release were instituted by the laboratory supervisor and quality team.In September 2015, the HIA-CHU laboratory enrolled and participated in an annual PT programme for HIV serology with commercial EQA provider Thistle quality assurance, and later with the Benin Ministry of Health, to promote sustainability. During the four EQA events for HIV serology, nine technicians participated, and PT scores of 100% were obtained. No corrective action was needed to improve proficiency; laboratory personnel were nonetheless oriented on root-cause analysis, and corrective and preventive action in case of future instances of lower EQA scores.In 2018, the HIA-CHU laboratory participated in two commercial haematology EQA programmes with Human Quality Assessment Services. The laboratory results for the first haematology EQA test were in the acceptable range for all analytes except for monocytes or mid cells, due to a reporting error. As a corrective action, the laboratory established a system for the supervised recording of results, in which the laboratory section supervisor verifies the accuracy of test results entered manually by technicians, after which results are entered into a computer by a secretary and printed for final validation. This process has helped reduce transcription errors.The HIA-CHU also began an IQC programme in biochemistry for the first time, in which the laboratory used high, normal and low commercial controls on equipment daily. When control values are outside the acceptable range, the laboratory staff will conduct a root-cause investigation and analysis. Elements to be investigated include reagents , room temperature, quality of distilled water, quality of the control product, etc. If the issue persists after the above steps, the equipment is then recalibrated. All corrective actions and measures taken are documented and recorded.Overall improvement of the laboratory\u2019s quality system was demonstrated by a 29% increase in SLIPTA score, from 16% at baseline evaluation in 2015 to 45% at the follow-up evaluation in 2017 see .Since 2018, reliance on the Ministry of Health National HIV Reference Laboratory for the administration of an HIV serology PT programme has allowed the HIA-CHU laboratory and other military laboratories to ensure a more sustainable and affordable PT option.Several important factors can explain the successes achieved during the QI programme. The laboratory leadership and staff benefited from the strong support of the hospital management, thus underpinning laboratory staff motivation to sustain quality improvements. Also, the implementing partner provided support in the execution of work plans, drafting of procedures, funding of training visits and organisation of regular teleconferences to track progress. The implementing partner provided sound advice for the appropriation of the quality approach and the implementation of improvement steps.8 Military health systems face unique challenges that impact their laboratory QI efforts; the challenges and associated responses of HIA-CHU laboratory may be relevant to other military laboratory programmes or to non-military laboratories that have limited funds to invest in QI efforts. Regardless of improvements made, QI is a never-ending process and the sustainability of gains is not guaranteed.10 Despite the quality advancements made over the past several years, challenges remain, requiring corrective action to ensure the efficacy of the ongoing programme.13 The issue of the high mobility of military personnel has made it difficult to fully and consistently integrate staff into quality laboratory operations and maintain the laboratory QMS. As a result of high staff turnover \u2013 a key facet of the military system \u2013 all members of the starting laboratory quality team are no longer in service at the HIA-CHU laboratory in Cotonou. Continuous staff turnover in part explains the slowdown in progress observed between the 2016 and 2017 follow-up evaluations. Staff mobility has also negatively impacted the timelines for the execution of planned activities such as management reviews, internal evaluations and inventory processes, for all of which personnel must be properly trained and oriented to ensure their execution per SLIPTA and ISO 15189 requirements.Although SLIPTA is an adaptable structure and was used to guide the HIA-CHU laboratory\u2019s quality successes, its formal implementation in francophone African countries and military contexts has been limited.Although the laboratory QI programme has incorporated training workshops, the programme would benefit from the establishment of a structured framework for continous personnel training allowing the laboratory to maintain a pool of trained and dedicated personnel.Going forward, the ambition of HIA-CHU laboratory is to continue advancing in laboratory quality using the SLIPTA guideline, to ultimately achieve a five-star SLIPTA rating and become internationally accredited to the ISO 15189 standard. The HIA-CHU laboratory also has the support of the Benin military health system authorities to expand the QI programme to multiple laboratory sites, prioritise the accreditation of clinical laboratories, and to integrate accreditation programmes into health sector policy and development programmes. To date, the HIA-CHU laboratory has expanded the QI programme to military clinical laboratories in Ouidah, Porto-Novo and Parakou. Military laboratory leaders envision the further expansion of the QI programme to additional military sites using a network approach."} +{"text": "Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs. The Central Nervous System (CNS) produces and utilizes a series of neurochemical transmitters (or neurotransmitters), binding to different receptors to stimulate intracellular signaling pathways. These molecules are synthesized by a limited number of neurons pertaining to specific brain nuclei, and project their extensive ramifications to widespread CNS regions, regulating signals form external and internal stimuli . The catNE is synthesized in neurons, containing the dopamine-b-hydroxylase enzyme, catalyzing the conversion of DA to NE . The maiDespite dopaminergic control of eating and feeding-related reward remaining the most extensively studied issue in this field, a series of relevant studies have investigated the noradrenergic regulation of feeding behavior. In a classic study of Grossman , the injSuccessively, researchers have investigated the potential effect of variations in the noradrenergic activity on feeding behavior. Desmethylimipramine, a noradrenalin uptake antagonist, has been injected into the prefornical hypothalamus of satiated rats, thus promoting eating behavior . SibutraTogether, this evidence suggests the relevant role of the noradrenergic system in the regulation of feeding behavior, indicating the possible specific actions of endogenous and exogenous NE in influencing human nutrition.Besides its relevant direct, hypothalamus-based actions on feeding regulation, the noradrenergic system is indirectly implied in various endocrine networks controlling humane nutrition. Namely, ghrelin, neuropeptide Y (NPY), cholecystokinin (CCK), leptin, oxytocin, and insulin, six hormones involved in the regulation of feeding and satiety, may interact with noradrenergic peripheral networks . PeripheEating Disorders (EDs) are psychiatric disorders characterized by persistent disturbances of eating behaviors, resulting in the altered consumption or absorption of food and significantly impair physical health or psychosocial functioning . EDs areCurrent research suggests that multiple pathogenetic factors are involved in the development of EDs. Genetic and neurodevelopmental factors have been hypothesized to explain the significant comorbidities between EDs and a series of psychiatric disorders, such as Anxiety Disorders, Mood Disorders, and Autism Spectrum Disorder ,32. AddiThe role of the catecholaminergic systems in the pathogenesis of EDs has been addressed by a series of studies; in particular, a relevant systematic review by Kontis and Theochari assessed the involvement of dopamine in the development and management of Anorexia Nervosa (AN) . The autDespite the evidence on the links between catecholaminergic transmission and feeding behavior, no specific review has systematically addressed the relationship between the noradrenergic system and EDs.This systematic review aims to highlight the existing literature on the role of the noradrenergic system in the pathogenesis, transmission and treatment of EDs. The research questions addressed include: (1) Is there documented evidence of involvement of the noradrenergic system in the pathogenesis of EDs? (2) Is there a documented theorical background for the development and testing of treatments for EDs acting on the noradrenergic system?This systematic review was performed in August 2021 by browsing the following databases: Medline (PubMed), Cochrane Library, Clinicaltrials.gov. Research was enhanced by searching the most relevant websites of guidelines and clearinghouses and in the most important etextbooks sites.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) flowchart was usedInclusion criteria: Date: published between January 2000 and July 2021. Population: humans or non-human mammals; Language: English; Study Design: RCT, cohort studies, cross-sectional studies, retrospective studies, case reports; Outcomes: reported.Exclusion: Population: other than humans or non-human mammals; Language: other than English; Study design: descriptive studies, reviews, protocols; Outcomes: unreported.Search string: ((noradren* OR norepinephrine[MH]) AND (eating disord* OR bulimia nervosa OR binge-eating disorder OR anorexia nervosa OR avoidant/restrictive food intake disorder)).A total of 341 original articles were identified with the initial search and checked by two independent investigators (J.P. and D.M.C.), and disagreements among reviewers were resolved through a mediator (M.L.). Thirty-five studies were included in the final analysis after 306 studies were excluded on the basis of exclusion/inclusion criteria. The flow chart of the study is reported in A detailed description of the selected articles is reported in Along with preclinical and clinical research unveiling the link between noradrenergic regulation and feeding behavior, a series of studies have investigated the role of noradrenergic dysregulation in the pathogenesis of EDs.The effect of the serotonin and noradrenaline reuptake inhibitor (SNRI) sibutramine, an anti-obesity treatment, was studied in 10 rats by Tallet and colleagues . The autBello and colleagues measuredIn a further study, the same group tried toRomano and colleagues assessedRecently, Hicks and colleagues examinedGenetic studies have documented possible contributions of polymorphisms in NE transporters in the pathogenesis of ED.Urwin and colleagues hypothesThese results were further examined by a second study from the same group . The autRelevantly, Hu and colleagues tried toIn addition to these studies, a series of authors have investigated the presence and modifications of noradrenaline and its metabolites in the plasma and urine. The most relevant metabolite of noradrenaline in primates is 3-methoxy-4-hydroxyphenylglycol (MHPG), and MHPG in brain tissue, cerebrospinal fluid, plasma, and urine reflects the turnover of noradrenaline .In a large study on the prevalence of migraine and the tyrosine metabolism in patients with EDs, D\u2019Andrea and colleagues measuredPlasma levels of NE, together with a series of other neurotransmitters and measures of autonomic system activity, were assessed in a group of patients with AN and HC by Lechin and colleagues . VariablThe same group investigThe activity of NE and the autonomic nervous system was also studied by Yoshida and colleagues . Nine paBrambilla and colleagues assessedIn a relevant study by Bartak and colleagues , an in vIn another microdialysis study on adipose tissue NE concentration, Nedvikova and colleagues investigDostalova and colleagues investigVaz-Leal and colleagues analyzedZheng and Yang administRigaud and colleagues investigNo brain imaging study meeting the criteria of this review was identified investigating the noradrenergic system in patients with ED.Relevant research has provided a theoretical framework for treating these patients with NE-based drugs. The studies of Kaye and colleagues have dirAs for the studies included in this systematic review, a series of pharmacologic treatments influencing the NE system have been found to have an effect of disrupted food regulation and symptoms of EDs. Thus, studying the mechanism of action of these drugs may contribute to understanding the role of NE in the pathogenesis of EDs.Milano and colleagues studied Venlafaxine, a SNRI acting as a weak NE reuptake inhibitor at low doses (75 mg/day) indicateDuloxetine, a SNRI indicated in the treatment of depressive and anxiety disorders, as well as chronic pain, has been investigated by a series of articles in the field of EDs; Bernardi and Pallanti reportedLeombruni and colleagues assessedGuerdjikova and colleagues investigSimilar evidence has been documented for milnacipran, a dual-acting antidepressant that blocks both serotonin and noradrenaline reuptake., in the treatment of 16 outpatients with BN by El-Giamal and colleagues , showingFurther data are available on the effects of reboxetine, a selective norepinephrine reuptake inhibitor (NRI), in the treatment of ED. A case report published by Willeit and colleagues documentIn the same year, El-Giamal and colleagues documentSimilarly, Fassino and colleagues conducteThe effect of reboxetine has been studied by Silveira and collaborators on the tRelevant data may be found in studies assessing the effect of dasotraline, a novel serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI), in the treatment of EDs.Mattingly and colleagues investigAtomoxetine, a highly selective norepinephrine reuptake inhibitor associated with weight loss, was studied in a randomized, double-blind, placebo-controlled, flexible dose trial, assessing reduction in binge frequency in 40 patients with BED. Compared with placebo, atomoxetine was associated with a greater reduction in binge frequency, BMI, and psychopathology, showing efficacy in the treatment of BED .Relevantly, desipramine, an antidepressant medication inhibiting the reuptake of noradrenaline and, to a lesser extent, serotonin, appears to reduce binge eating and improve comorbidities in short-term treatments ,74. The This systematic review assessed the role of the noradrenergic system in the pathogenesis and treatment of EDs. A total of 35 studies were included, of whom 5 were preclinical trials on rats, and 29 were clinical studies on humans.The human nutrition encompasses a complex series of biological, genetic, and cultural factors ,76. EDs Preclinical studies have agreed in documenting a significant role of the noradrenergic system in the pathogenesis of EDs under experimental conditions. Relevantly, binge eating has been found to activate the mPFC in stressed rats, an effect that could be reduced by alpha-2A adrenergic agonist guanfacine , while dGenetic studies included in this review have reported conflicting evidence. The research by Urwin and colleagues documented the hypothesis that receiving specific NET and MAOA variants and may increase the genetic risk to develop ANR ,42. NoneClinical studies assessing variations of NE in bodily fluids and tissues have produced conflicting evidence. Plasma NE has been found to be reduced at baseline in AN and BN in a series of studies, both as absolute levels and whenNo brain imaging (magnetic resonance or positron emission tomography) study was found investigating the noradrenergic system in patients with EDs. Since a series of studies on this field exist on the roles of dopamine, as documented by a recent systematic review , future A number of pharmacological studies have documented the effect of drugs influencing the noradrenergic transmission in the CNS on the management of different EDs. SNRIs represent the most frequently studied molecules, with specific research targeting the effects of sibutramine, venlafaxine, duloxetine and milnacipran. SNRIs have been documented to have a positive effect in reducing binge frequency and psychopathology in BED ,56,57,58Taken together, these results indicate that psychopharmacologic therapies modulating the noradrenergic activity, namely SNRI, NRI, and SNDRI, may serve as effective treatments for binge and purge frequency, weight alterations, and psychopathology for BN and BED. No recent data concerning the use of these drugs in patients with AN was found. Research in this field is urgently needed, since scientific evidence exists supporting only a few molecules in the treatment of AN ,80,81.This study has some limitations. A major point to be considered when assessing the biochemical dysregulation in psychiatric disorders is the difficulty to clearly determine whether the documented modifications represent a causal factor or consequence of the disease. This can be particularly challenging when considering the field of EDs, since malnutrition and the metabolic imbalance determined by the underlying disorder may potentially alter endocrine and neuropsychological systems in the body . S\u00f6derstAs a second limitation, although we aimed at defining the evidence of involvement of the noradrenergic system in the pathogenesis of EDs, different studies did not concern all clinical entities of EDs. Namely, genetic studies were related to ANR only, as well as no clinical study assessing body concentrations of NE was found. Relevantly, no study was identified concerning preclinical or clinical aspects of the relationship between the noradrenergic system and the avoidant/restrictive food intake disorder. Thus, a further thorough systematic review in this field should include new research assessing both preclinical and clinical variables in these less studied conditions.The present systematic review identified a series of key data on the relationship between the noradrenergic system and EDs. EDs represent a group of complex conditions with a multifactorial pathogenesis, and no specific review has systematically addressed the relationship between the noradrenergic system and EDs so far. According to our results, preclinical studies in rats demonstrated the involvement of the noradrenergic brain system in binge-like behaviors, with a key mediating role played by the activation of stress circuits. Genetic studies documented conflicting evidence in the possibility of a noradrenergic-mediated, genetically transmitted increased risk to develop AN. Clinical studies on body fluid concentrations reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with AN and BN. Pharmacological studies documented an efficacy of SNRIs, NRIs, and SNDRIs in the treatment of BN and BED. Still, insufficient evidence is available concerning the noradrenergic-mediate heritability of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. Further in vivo experimental studies and psychopharmacological randomized controlled trials are urgently needed to provide solid scientific evidence in the treatment of these expanding and increasing psychiatric and metabolic disorders."} +{"text": "As a result, gene therapy treatments have been developed, and for some of the more prominent blood disorders these have reached the clinic and even market approval. Presently, the most advanced approaches are based on herapies ; 2021b, herapies . Permaneherapies . TherefoMutation-Specific Gene Editing for Blood Disorders covers an exceptional selection of contributions on mutation-specific gene editing in particular, and more generally on the development of associated concepts, protocols, technologies and corresponding regulatory and socio-economic conditions. The featured reviews and original articles offer expert perspectives on HSC-based therapies and particularly editing for hemoglobinopathies, on bone marrow failure syndromes and blood malignancies, on editing platforms, pathways and delivery methods, on targeted insertion of therapeutic transgenes and on the assessment of off-target activity of gene editing tools:To address these particular shortcomings of mutation-specific therapy and to enhance efficiency of treatments in general and thus to lower dosage requirements and risks to patients, therapy development for blood disorders needs novel strategies as much as it needs incremental improvements to existing protocols. In this respect, this Special Issue on Klaver-Flores et al. briefly cover HSC biology and gene editing platforms, before evaluating key areas of necessary improvement, the status quo of HSC engineering for therapy and the requirement for regulatory harmonization. In a different approach, Ferrari et al. comprehensively cover clinical development of homology-directed repair (HDR)-based editing for blood disorders, from editing platforms over HDR optimization, cyto-/genotoxicity and manufacturing protocols up to the post-treatment molecular follow-up. They also touch on the relationship of gene addition with conventional integrating vectors and the emerging gene editing therapies, and on the challenges of creating safe and efficient advanced therapies that are also financially sustainable. With further emphasis on clinical translation, Papanikolaou and Bosio review the current efforts and regulatory frameworks in the commercialization of advanced therapies, and provide an insightful perspective on the ongoing improvements to safety and efficacy, required for successful introduction of gene editing-based therapies.Several reviews give independent views on the state of the art and the path ahead for gene editing and therapies based on HSCs. In their perspective on the genetic engineering of HSCs, Zittersteijn et al. include mechanisms underlying globin expression, introductory to an up-to-date view on gene addition and on gene editing approaches and platforms for treatment of hemoglobinopathies. Insights into globin regulation are expanded by Mussolino and strouboulis, whose review places particular emphasis on regulatory complexes and therapeutic targets for epigenetic treatment of \u03b2-hemoglobinopathies. With focus on primary sequence editing for \u03b2-hemoglobinopathies, Barbarani et al. give an overview of editing strategies employed for treatment and point out the significance of reproducing naturally occurring therapeutic modifier mutations, of DNA double-strand break (DSB)-independent editing technologies, and of finding a suitable balance between efficiency and the level of precision required for editing. In this context, original research by Benitez et al. shows how modification of DNA repair factors and in particular their tethering to Cas9 can shift the balance between different DSB repair mechanisms, and thus editing outcomes, for the mutation causing sickle cell disease.Paradigmatic for application of editing to HSCs is the prolific and clinically most advanced field of gene editing for hemoglobinopathies. In their review covering both \u03b1- and \u03b2-hemoglobinopathies, Pavani and Amendola illustrate the extreme versatility of the TI approach, which is based on the insertion of promoterless transgenes behind endogenous promoters or on the insertion of promoter-driven transgenes in safe-harbor loci. TI enables a range of applications, including the deactivation of disease modifiers and the delivery of chimeric antigen receptors (CAR) in the production of CAR cells for adoptive immunotherapy.Controlling repair outcomes is critical for the safety and efficacy of localised sequence modifications, but also for the targeted insertion (TI) of therapeutic transgenes, which combines the safety of gene editing with key benefits of gene addition, including the ability to address multiple mutations with one and the same therapeutic tool. In their review, Antoniou et al.The alternative precision editing technologies of base and prime editors are then comprehensively assessed for their initial and latest developments, for their advantages and disadvantages and for their specific applications to blood disorders by Koyunlar and de Pater point out, these include inherited bone marrow failure syndromes caused by GATA2 mutations, of which 90% are found in the open reading frame and thus depend on precision edits, in the absence of a universal modifier as alternative target. Here, the consistent accumulation of additional oncogenic somatic mutations in other genes and the paucity of HSCs as the substrate for gene editing present particular challenges, representative of what holds true also for other blood disorders, such as Fanconi and Diamond Blackfan anemia. Importantly, many blood malignancies are based on and need to be addressed by changes in mesenchymal stromal cells (MSCs) instead of HSCs, as reviewed by Banjanin and Schneider, who in addition to the option of cross-correction of MSCs by modification of HSCs point out the specific challenges of in vivo and ex vivo editing and validation for MSCs.Taken together, research into shifting the balance of different DSB repair pathways towards precision edits and for TI, or into the employment of DSB-free precision editors has bearing on many diseases. As Simmons et al. demonstrates the utility of CRISPR/Cas9-based editing for the characterization of gene function and the development of Slc48a1-mutant mice as putative models for human SLC48A1-linked idiopathic iron disorders.For many of the rarest blood disorders, understanding of the underlying biology and availability of disease models are limiting. In this respect the original research article by ex vivo editing in HSCs by electroporation was in large part enabled by advances in synthetic CRISPR/Cas guide RNAs, as reviewed by Allen et al. Pointing out an editing technology alternative to protein and ribonucleoprotein-based editors, F\u00e9lix et al. address the concept and framework parameters of polypurine reverse Hoogsteen hairpin technology for editing, and its application to a selection of specific mutations causing different blood disorders. As an alternative to the delivery of naked editing molecules, virus-like nanoparticles conceptually enable ex vivo and in vivo application and make the exploration of editing, also using novel Cas9 flavors, accessible to any laboratory familiar with the production of viral vectors. Gutierrez-Guerrero et al. demonstrate in their primary research article efficient duplex-DSB-based excision and targeted insertion of an adeno-associated-virus\u2013encoded HDR donor into the Wiskott-Aldrich syndrome locus of T, B and CD34+ cells by delivery of CRISPR/Cas with virus-like Nanoblades.Vectors and delivery technologies are critical to the success of therapies based on gene editing, and the recent achievement of near-saturated Blattner et al., whose review comprehensively surveys biased and unbiased detection technology for off-target activities of different editing platforms, including the issue of translocation detection and remaining challenges, such as robust assays that can be applied in therapeutically relevant cells.For any editing application but even more so for the development of CAR and other technologies potentially drawing on multiple DSBs for editing, off-target activity of editing tools is of particular concern. This point is addressed by Driven by the rapid and ongoing development of gene editing tools, protocols and applications, editing technology is fast approaching such efficiency, accuracy and ubiquity, that clinically relevant mutation-specific applications for many diseases are within reach. We hope that the original research and authoritative reviews we had the privilege of putting together in this Special Issue will be a further step to making this exciting prospect a reality."} +{"text": "The emergence of COVID-19 and social distancing requirements have resulted in disruptions to daily life, reduced opportunities for social engagement, and diminished resource access for millions of older adults. Individuals with cognitive impairments (CI) are particularly vulnerable to risk for social isolation. This presentation will discuss the PRISM-CI pilot trial, which aims to examine the feasibility and potential efficacy of the PRISM-CI software system on enhancing connectivity and quality of life among a diverse sample of 50 older adults aged 65 and over with a CI. PRISM-CI, adapted from the PRISM system (developed by the Center for Research and Education on Aging and Technology Enhancement) for this population, is intended to support social engagement, memory, and access to resources and information. We will present data regarding the feasibility and perceived value of PRISM-CI and discuss the challenges, and strategies used, to adapt the PRISM-CI trial during the pandemic. We used a multi-modal approach to provide remote training and specialized tablet instruction that includes individualized training sessions tailored to individuals\u2019 learning needs, hobbies, and prior technology use. The adapted protocol also involves the use of remote access software for troubleshooting. We will also discuss how participant feedback guided the inclusion of additional features, such as Zoom videoconferencing and virtual library access, for the PRISM-CI application. Finally, we will demonstrate how the adaptation of the PRISM-CI protocol holds promise for the use of flexible, remote technology approaches to reach socially isolated older adults to foster psychosocial well-being."} +{"text": "Substandard and falsified (SF) medicines have important but neglected consequences including increased morbidity and mortality, economic losses, and diminished public confidence in health systems. SF antimicrobials, particularly those containing reduced quantities of active pharmaceutical ingredients (APIs), may also be key but overlooked drivers of antimicrobial resistance . SubstanAccording to a recent report from the World Health Organization (WHO), approximately 10% of medicines circulating in low- and middle-income countries (LMICs) are either substandard or falsified . The issThe Coronavirus Disease 2019 (COVID-19) pandemic has heightened the risk for SF medicines reaching patients by disrupting pharmaceutical production and supply chains, impeding regulatory inspection, and causing great economic hardship, making it difficult to afford genuine medicines. A surge of SF medical product cases has been reported, especially in settings with already vulnerable supply chains \u201310. In eMedicines Regulatory Authorities (MRAs) are the keystones for many of the interventions to prevent, detect, and respond to SF medicines. However, national MRA, international procurement agencies, and wholesaler/distributor medicine inspectors performing post-marketing surveillance (PMS) have to largely rely only on their own senses and knowledge to detect circulating SF medicines . SuspiciPLOS Neglected Tropical Diseases Collection, typically, inspection of medicines quality is conducted by medicine inspectors from the Bureau of Food and Drug Inspection (BFDI) within the Ministry of Health. Inspectors undertake routine inspection of pharmacies bi-annually, focusing on adherence to legislation and drug registration. Convenience sampling of certain medicines, especially antimalarials and antiretrovirals, is undertaken as part of specific vertical program projects supported by donors. In convenience sampling within a province, medicines are purchased from a selection of pharmacies in each district and brought back to a central location where they undergo initial screening using the Minilab of the implementation of the 6 devices tested in the field evaluation for PMS in Laos was conducted. The fifth article discusses the results presented in the series, highlights the evidence gaps, and provides recommendations on the key aspects to consider in the implementation of portable devices and their main advantages/limitations.The Collection is composed of 5 articles. This Editorial represents the first of these, introducing the background and rationale for the Collection. Twelve devices were first evaluated in a laboratory setting to provide information on their performances to identify SF medicines and to select the most field-suitable devices for further preliminary evaluation of their utility/usability by medicines inspectors with the devices in an office setting, allowing more scrutiny by the observers. The GPHF-Minilab was also tested by the chemists in the laboratory evaluation, and by FDQCC technicians, already trained in Minilab use, at their laboratory, in line with its current routine use in Laos.Using results of the above studies, the fourth article presents a CEA of implementing the 6 devices selected for the field phase experiments. Key criteria for each device such as cost per sample analysis, the sensitivity and specificity of each device, and experiment time were utilized to estimate the cost-effectiveness of using the devices under 2 scenarios of high and low prevalence of SF antimalarials in circulation. The results include a variety of device sampling strategies and multiway head-to-head comparisons.In the fifth article, these 4 components are synthesized and discussed, and recommendations are made. This is based on the discussion in a multi-stakeholders meeting held in April 2018 in Vientiane. The meeting included 53 participants from MRAs from 7 Asian and African countries and international health and funding organizations. Hands-on sessions with devices and group discussions about the promises and pitfalls of the devices were held during this 2-day meeting. The advantages/disadvantages, cost-effectiveness, and optimal use of medicine quality screening devices in the medicine supply chains were discussed. Based on the results from this multiphase study, we list policy recommendations for MRAs and other institutions who wish to implement screening technologies, as well as gaps of scientific knowledge to be filled.As far as we are aware, this multiphase study is the first collaborative independent investigation listing the advantages and disadvantages from diverse chemical, economical, and regulatory points of view. The overall study assesses and compares device accuracy, describes potential barriers, and evaluates the costs versus the benefits of the implementation of a wide diversity of portable medicine quality screening devices in a public health perspective. The series also highlights the difficulties and barriers to perform screening devices research and the important remaining gaps of scientific evidence."} +{"text": "Cardioembolism is one of the most frequent causes of ischemic stroke, accounting for at least 20% of all ischemic strokes. Moreover, cardioembolic stroke entails higher severity and poorer outcome compared to other etiologies. Atrial fibrillation is the most frequent underlying disease, although several other cardiac disorders such as ventricular akinesia, valvular heart disease, acute myocardial infarction, endocarditis, monogenic diseases with cardiac involvement, or complicated interventional cardiac procedures can also be involved in the development of cardioembolic stroke. Direct oral anticoagulants have revolutionized stroke prevention in patients suffering from atrial fibrillation, however, more knowledge is needed regarding the long-term outcomes in patients treated with these drugs.In recent years, much attention has been paid to the search for hidden cardioembolic sources for ischemic stroke, and the \u201cembolic stroke of unknown source\u201d (ESUS) concept was raised to improve the detection of occult embolic diseases, mainly paroxysmal atrial fibrillation. However, the failure of direct oral anticoagulants in recent clinical trials with patients diagnosed with ESUS has raised concerns regarding the appropriateness of a low-intensity diagnostic workup and points to the return of the diagnostic concept of cryptogenic stroke. This highlights the need to increase the search for potential hidden etiologies through advanced diagnostic procedures.This Research Topic issue provides an up-to-date collection of manuscripts focused on the challenge of diagnosis and management of cardioembolic strokes.Pagola et al. highlighting the potential application of Point of Care UltraSound (POCUS) as a helpful screening method at the Stroke Unit. Furthermore, Arnold et al. provide a comprehensive review on the most promising biomarkers for the diagnosis of cardioembolic stroke, including blood-based, genomic, transcriptomic, metabolic, electrocardiographical, echocardiographical, and advance cardiac imaging biomarkers. They discuss the existing evidence for possible clinical applications in risk stratification and in accelerating etiological classification as well as optimal management, from a perspective of the forthcoming implementation of personalized medicine in stroke management.The role of echocardiography is reviewed by Viedma-Guiard et al. provides an excellent and up-to-date overview of the role of aortic sources of embolism in ischemic stroke, focusing on the diagnostic challenges and the current evidence for the optimal treatment in stroke prevention.The importance of atherosclerotic plaques in the aortic arch as a potential cause of embolic stroke has been underestimated in the majority of the etiological classifications of stroke, being relegated in most of them to stroke of undetermined origin, mainly because of a clear recommendation for its systematic search in the stroke patients has not been established. The narrative review by Wan et al. also provides new data on this atherosclerotic-lookalike clinical profile in a prospectively collected series of 119 acute ischemic stroke patients. To deepen the current controversy surrounding the ESUS concept, Fuentes et al. list several arguments against the use of the ESUS concept in clinical practice, advising stroke physicians to be smart in the search for underlying causes of ischemic stroke, optimizing advanced diagnostic procedures according to the patient's and stroke's characteristics, attempting to find the correct diagnosis for stroke patients and reducing rates of cryptogenic stroke diagnosis.Recently the ESUS concept has been called into question. This concept was proposed in 2014 by the Cryptogenic Stroke/ESUS International Working Group under the rationale of the common underlying thromboembolism mechanism in the group of patients with non-lacunar ischemic strokes in which the basic diagnostic approach did not found any undoubtable cause for the stroke. This concept included minor-risk or covert cardiac sources , paradoxical embolism and non-occlusive atherosclerotic plaques in the aortic arch, cervical or intracranial arteries showing a low frequency of bleeding complications, with no significant differences between anticoagulant drugs at long-term follow-up (of up to 3 years from a stroke). Besides, they provide new insights on the main reasons for switching oral anticoagulant drugs in clinical practice, being the majority of them due to stroke recurrences and labile INR. The other manuscript on stroke prevention is the protocol for LASER a randomized clinical trial and an associated registry of early anticoagulation with edoxaban after ischemic stroke in patients with atrial fibrillation. It is aimed at recruiting 150 patients with ischemic stroke and atrial fibrillation who will be randomized within 5 days of stroke onset to early or delayed edoxaban initiation .In the field of stroke prevention in cardioembolic strokes, this Research Topic issue includes two interesting manuscripts. The prospective multicentre RESTAIC Registry by Sarti et al. highlighting the relevance of atrial appendage morphology on patients with atrial fibrillation and resistant stroke despite adequate anticoagulant therapy.Finally, this issue also includes a case report by We would like to thank all the contributing authors for their manuscripts in this challenging time in which the COVID-19 pandemic has severely impacted stroke care and research, limiting the number of the expected manuscripts for this Research Topic issue. We hope that the pandemic will soon disappear, and we can refocus all our efforts on fighting stroke, one of the leading causes of death and the first cause of disability worldwide.All authors contributed by drafting the work or revising it critically for important intellectual content and all of them provided approval for publication of the content.BF: Advisory Board (Bayer); Spearker's honoraria ; Travel grants to attend scientific meetings , Participation in clinical trials . GN: Speaker fees/Advisory Boards/Research support from Amgen; Bayer; BMS/Pfizer; Boehringer-Ingelheim; Elpen; European Union; Galenica; Sanofi; Winmedica. JP: Research funding: Helsinki and Uusimaa Hospital District, Academy of Finland, Business Finland, St Jude Medical, Pfizer. Research collaboration: Nokia Technologies, Bittium, BcB Medical, Vital Signum; Speaker's honorary: Boehringer-Ingelheim, BMS-Pfizer, Bayer, Abbot; Advisory Board: BMS-Pfizer, Boehringer-Ingelheim, Bayer, MSD, Portola. Other: ESO guideline working group: Post-stroke hyperglycemia, secondary prevention in patients with AF. Finnish Duodecim guideline working group: ischemic stroke and TIA; Terve Media: Visiting editor."} +{"text": "Amputation of the upper limb brings heavy burden to amputees, reduces their quality of life, and limits their performance in activities of daily life. The realization of natural control for prosthetic hands is crucial to improving the quality of life of amputees. Surface electromyography (sEMG) signal is one of the most widely used biological signals for the prediction of upper limb motor intention, which is an essential element of the control systems of prosthetic hands. The conversion of sEMG signals into effective control signals often requires a lot of computational power and complex process. Existing commercial prosthetic hands can only provide natural control for very few active degrees of freedom. Deep learning (DL) has performed surprisingly well in the development of intelligent systems in recent years. The significant improvement of hardware equipment and the continuous emergence of large data sets of sEMG have also boosted the DL research in sEMG signal processing. DL can effectively improve the accuracy of sEMG pattern recognition and reduce the influence of interference factors. This paper analyzes the applicability and efficiency of DL in sEMG-based gesture recognition and reviews the key techniques of DL-based sEMG pattern recognition for the prosthetic hand, including signal acquisition, signal preprocessing, feature extraction, classification of patterns, post-processing, and performance evaluation. Finally, the current challenges and future prospects in clinical application of these techniques are outlined and discussed. For human, the worth of hand is indisputable. The hand is the most diverse and dexterous part of the human body, which can execute various activities to interact with the environment by adopting a variety of different motion strategies and deep learning (DL). ML, which is the method based on feature engineering, could learn and perform tasks from the data input of automatic modeling. For conventional machine learning algorithms, there are limitations in processing raw data, because they could not effectively train on inconsistent, noisy, abstract, and high-dimensional data we comprehensively analyze the overall structure of DL in sEMG-based gesture recognition; (2) we comprehensively review the latest methods and technologies of sEMG based gesture recognition; (3) we raise the existing challenges and promising research prospects of sEMG based on motion intention recognition in prosthetic hand field.The approaches of gesture recognition model are very similar, but the method of each stage is different; in addition, not all studies use all stages of standard structure. Considering this, we propose a standard approach composed of six parts, which are data acquisition, data preprocessing, feature extraction, classification of patterns, post-processing, and performance evaluation. The sEMG signals are collected from sEMG sensors, which could adopt two different acquisition criteria, sparse multi-channel sEMG and high-density sEMG (HD-sEMG), in the density of the employed electrodes of view traditional manual feature extraction method is used to increase the data density of sparse multi-channel sEMG; (2) the raw sEMG signal is directly input into the network to realize end-to-end learning.For the traditional feature extraction methods, many researchers are devoted to propose new features based on professional knowledge , mean absolute values (MAV), integrated EMG (iEMG), histogram (HIST), root mean square (RMS), zero crossings (ZC), standard deviation (SD), slope sign change (SSC), Willison amplitude (WAMP), variance (VAR), V-order (V), simple square integral (SSI), and so on, which are often used in combination. The detailed information is shown in Frequency domain features: The FD features are calculated by Fourier transform of the autocorrelation function of sEMG signal and estimated by periodogram or parameter method. The common frequency domain characteristic of sEMG signal is frequency ratio (FR), total power (TP), mean power (MP), median frequency (MDF), mean frequency (MNF), power spectrum (PS), and so on. The detailed information is shown in Time-frequency domain features: The TFD features are expressed as locating the energy of sEMG signal both in time and frequency, which is usually an important approach in feature extraction. The typical representative of time-frequency analysis is wavelet transform is the mother wavelet, and \u03c4 is the translation parameter. ni is the length of the ith level decomposition coefficient ci ; \u03bc is the mean of ci , average power of the coefficient ci (APOCi), standard deviation of the coefficient ci (STDOCi), ratio between MOACi+1 and MOACi.where Parameter model: The basic principle of the parameter model is to regard it as a time series based on sequence information in the raw sEMG. Because sEMG signal is steady on short notice, the coefficients and intercept of the fourth-order autoregressive model are often selected as the characteristic values is the most extensive applications for DL architecture based on sEMG gesture recognition. Park and Lee proposedOne of the most important advantages of CNN is that it can automatically learn spatial features from input data or extract unlabeled features. However, the sEMG is the form of time series signal essentially, which is more suitable for recurrent neural network (RNN) that has dominant position in processing temporal or otherwise sequential information , whose goal is to recover the original data as lossless as possible from the abstract data; the other is probabilistic restricted Boltzmann machine (RBM) and its improved algorithm deep belief network (DBN), whose goal is to maximize the probability of the original data appearing when the RBM reaches a stable state. AE are data compression algorithm, which use efficient data encodings to map noisy input data into clean output Le, . VujakliApart from the above methods, there are many other DL methods applied to sEMG pattern recognition. Because of the simplicity of the structure, fully connected neural networks , skin conditions , what amputee can do after training (which is a reflection of behavior in life and working environment) (de Vet et al., This review paper briefly introduces the advances of DL-based sEMG pattern recognition techniques for the prosthetic hand in recent years. Through the literature survey of DL application in sEMG recognition, some of the core techniques are highlighted, some of the most common challenges to be solved are analyzed, and some of the most possible development prospects are discussed. It could be found that gesture recognition techniques based on DL has great potential in using sEMG signal to accurately interpret amputee's motion intention, which is of great significance to the development of intelligent prosthetic hand. However, their individual difference, real-time usability, and long-term stability are still being highly limited by many complex factors in these approaches. The high variability of sEMG, the lack of existing data, the limitation of hardware resources, and the lack of clinical evaluation conditions seriously affect the progress of pattern recognition techniques based on DL. In addition, the natural movements of the upper limbs are independent, continuous, and proportional activations of multiple DOFs, while the existing techniques can only use a limited number of patterns for discrete classification. These should be well-improved in the future real-time application of prosthetic hands.WL and PS wrote this paper. PS and HY suggested the methodology. PS supervised the entire project. All authors reviewed the manuscript, read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "For organic Cu speciation, an improved anodic stripping voltammetry (ASV) method, employed to eliminate the surface-active substances (SAS) interference on the voltammetric signal, was used in samples containing high organic matter concentration. Fulvic acid was used as a model of natural organic matter and the method was applied for Cu speciation in samples collected in the Arno River estuary . The binding of Cd(II), Pb(II), and Zn(II) by silica nanoparticles was studied using a combination of the electroanalytical techniques Scanned Stripping ChronoPotentiometry (SSCP) and Absence of Gradients and Nernstian Equilibrium Stripping (AGNES). The experimental system was chosen as a representative model for the role of natural and anthropogenic nanoparticles in the fate and behavior of trace metals in aqueous environmental systems .Several examples of speciation of metal cations in aquatic environment are reported in this Research Topic. The speciation of trace metals aquatic systems includes the determination of free ions, metal complexes, colloidal species, etc., as well as the total dissolved concentration. The integrated assessment of free ions and labile metal complexes can be obtained by Diffusive Gradients in Thin-films (DGT), a dynamic speciation technique. The determination of the organic pools of trace metals in freshwaters and the characterization of organic and inorganic complexes in sea waters were obtained by this procedure (Berto and Alladio). The investigation of the interaction of phytate ligand with biologically relevant cations, namely Mg2+, Zn2+, Fe2+, Cu+, and Cu2+ revealed that alkaline earth metals interact with different binding sites than the transition metals. Experiments with Cu+, and Cu2+ confirmed similar complexing behaviors, depending mainly on the ionic radius .Speciation studies on the interaction of metal cations with ligands having multiple binding sites, such as tannic acid, a natural polyphenolic compound, and phytate ligand, are very important for the fate of those metals. In the study regarding tannic acid, the approach used combines UV-vis and fluorescence spectroscopy with chemometrics, namely Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and Parallel Factor Analysis (PARAFAC) . The necessary degree of specificity in discriminating all the species of a given element in a sample can be attained by ultrahigh-resolution mass spectrometry based on the Fourier transformation, Orbitrap and Ion Cyclotron Resonance (ICR) cell. The case of the speciation analysis of the products of selenium metabolism by FT ICR MS was described . Metal speciation can be also performed by MALDI-MS and tandem mass spectrometry (MS-MS). The results obtained for Ca2+ interaction with biologically relevant ligands, as cysteine, D-penicillamine, reduced glutathione, and oxidized glutathione obtained by potentiometry and 1H-NMR spectroscopy were confirmed by MALDI-MS and MS-MS, elucidating also the mechanism of interaction .Metal speciation can be also performed by Electrospray Ionization Mass Spectrometry (ESI-MS). In this field, MS-MS approach guarantees exceptional sensitivity, as well as the use of high-resolution sectors, capable of well-resolving isotopic clusters. A further development is the merging of ESI-MS information with data obtained Migliore et al.).Speciation studies also include the search for novel drug delivery systems able to improve the performance of old-generation antibiotics. For example, the capability of two micellar polycationic calix[4]arene derivatives to recognize and host ofloxacin, chloramphenicol, or tetracycline in aqueous solution was investigated by nano-isothermal titration calorimetry, dynamic light scattering, and mono- and bi-dimensional NMR. Results evidenced that the formation of the chloramphenicol\u2013micelle adduct is enthalpy driven, whereas entropy drives the formation of the adducts with both ofloxacin and tetracycline. NMR spectra confirmed ITC data about the positioning of the antibiotics in the calixarene nanoaggregates . Different methodologies are employed for soil remediation. Among them, the use of chelating agents is one of the most promising method for removal of metal ions preserving the most meaningful properties of the original soils. One of these methodologies, the Nurchi's method, an extension of the Reilley procedure for EDTA titrations, is based on speciation studies, namely on the knowledge of the related protonation and complex formation constants. Its employment in biomedical and industrial applications is also discussed, namely in the evaluation of the role of different biomolecules such as bacterial metallophores, in metal uptake and homeostasis in living organism .Speciation studies are also very useful for the development of techniques for the decontamination of natural waters and soils containing toxic metals. In recent years, many efforts have been made to discover new technologies that are effective, robust, cost-effective and easy to handle for the decontamination of downstream water without endangering human health. Among nanomaterials and nanostructures proposed in the remediation field, graphene-based materials (G), are particularly suitable for the development of reliable water decontamination treatments, in particular for arsenic remediation . Ultra-trace urea in synthetic and real milk samples was determined by sensitive and selective methods using Fe/N-codoped carbon dots (CDFeN) and a probe with surface-enhanced Raman scattering (SERS), resonance Rayleigh scattering (RRS), and fluorescence (FL) signals . Novel methods for the monitoring of microcystins (MCs), one of the most common and harmful cyanotoxins, involve the use of aptasensors (aptamer-based biosensors) and immunosensors (antibody-based biosensors) for rapid, portable, easy-to-use, and on-site determinations . Early diagnosis of diabetes on entire blood samples was performed via near-infrared spectra (NIRS) combined with a support vector machine (SVM) and aquaphotomics .Determination of organic analytes such as urea or biotoxins in environmental and food samples using novel, advanced and combined analytical techniques was also performed. More in detail, the determination of saxitoxin in seawater samples was made by a novel flow injection microfluidic immunoassay system which allows Risoluti et al.).Quality of milk was assessed by an innovative MicroNIR and chemometric platform for the on-site and contactless monitoring of the samples (via indirect proxies) those specific chemical species in waters, soil solutions, biological fluids and food products, that provide the most relevant information in human health and environmental safety research. Altogether, these studies point to the wide possibilities underlying the combined use of active/passive sampling strategies, fractionation methods, orthogonal or hyphenated techniques and advanced multivariate analysis for the improvement of the accuracy and specificity of speciation data obtained in complex matrices.This Research Topic emphasizes the recent methodological improvements made in quantifying and identifying (either explicitly or All authors wrote the Editorial and reviewed it.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "DDD698, and American Association of State Highways Transport Officials (AASHTO). Slight modifications to the measurement procedures (such as the use of different surcharge loading and custom-made consolidation rings) reflecting special laboratory testing conditions and for the purposes of comparisons, are also reported.Most of the damaging geo-hazards recorded in modern history are caused by soil swelling or expansion. Therefore, proper evaluation of a soil's capacity to swell is very crucial for the achievement of a secure and safe ground for civil infrastructures and related land developments which are founded on the soil. In order to simulate as well as estimate the heave that can occur under field conditions, laboratory one-dimensional oedometer vertical swell-strain testing are most frequently used. Hence, in this brief, one-dimensional swelling tests adopted to measure soil swelling on laboratory-engineered and natural soils covering various regions on the globe are reported. The testing standards and procedures followed in the measurement of one-dimensional swelling are those enumerated in the American Standards for Testing of Materials (ASTM) DDD698, Turkish Standards (TS), American Association of State Highways Transport Officials (AASHTO)and a combination of both standard and modified efforts. A total of 395 data samples on soil swelling potential are reported. With regards to the corresponding soil properties, a total of 219 data records of soil specific gravity, 321 data records of initial moisture content, 163 data records of void ratio, 273 data records of dry unit weight, 347 data records of liquid limit, 347 data records of plastic limit, 395 data records of plasticity index, 209 data records of activity index, 339 data records of clay content, 174 data records of silt content, 246 data records of optimum moisture content, 228 data records of maximum dry density and 347 data records of Unified Soil Classification System (USCS) are presented. Finally, the dataset of one-dimensional soil swelling described herein are intended to aid geotechnical engineers and researchers who are involved in statistical correlation studies, data analytics, and machine learning predictions using soft computing methods mostly aimed at evaluating soil expansion especially during the preliminary phases of soil investigation and foundation design.Corresponding soil properties characterising the dataset includes moisture content, void ratio, specific gravity, unit weight, liquid limit, plastic limit, plasticity index, clay content, silt content, maximum dry unit weight, optimum moisture content, and soil activity index, all of which are known to bear either direct or indirect influences on soil. Determination of the state of compaction of the soils where applicable, are carried out based on the American Standards for Testing of Materials (ASTM) This dataset references studies spanning over 5 decades leading back to the period when important discourse on soil swelling-related disasters were first considered. The dataset consists of both naturally occurring (disturbed and undisturbed soils) and a mix of laboratory-engineered-soils. Based on the nature and format of reporting from the different sources, the soils are divided into groups with each having properties collated from the same experimental methods. The dataset for each group are saved in individual tabs within the .xlsx file with the tab names (notations) corresponding to the descriptions on 2Rigorous systematic literature studies were conducted to obtain the dataset. The literature search included data spanning across research articles and reports with experimental investigations conducted on various soil samples. The methodology of data collection involved thorough screening of articles\u2019 titles, keywords and abstracts that met the criteria of one-dimensional swelling for both compacted and non-compacted soils. Most of the collected data were derived from article tables and where data were only presented on graphs, WebPlotDigitizer Relevant data of soil properties not included in the original data such as the Plasticity Index (OrIn areas where soil Activity index, (To allow for an easy and extensive assessment and analysis of the degree of swelling of the different soils and their properties obtained from various sources, entries into each column of the dataset should be manually synchronised to account for missing data through the removal of such affected rows.The authors declare that the present work did not include experiments on human subjects and/or animals.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Eyo E. U: Conceptualization, Methodology, Software, Data curation, Writing \u2013 original draft. Uche Onyekpe: Visualization, Investigation, Writing \u2013 review & editing.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper."} +{"text": "Dear EditorThe new corona disease COVID-19) is very contagious and features a high risk of vast outbreak and infection. The World Health Organization (WHO) declared a global public health emergency condition on 30 January 2020 and a universal epidemic afterwards by given its rapid epidemic worldwide empowerment of economic, cultural, and political infrastructures as well as national and local policies, 2) entry of non-governmental and impartial organizations like Red Cross and Red Crescent into the exchange of healthcare and treatment equipment to the countries inflicted with sanctions, 3) decisive entry by the UN into the arena of the dismissal of all sanctions, 4) convergence of the neighboring and regional countries to respond the COVID-19 and overcome the sanctions, 5) concentration on healthcare and empowerment of domestic economy, 6) corroboration of the foreign policy to get prepared for post-COVID-19, 7) complete enforcement of the international agreements and conventions, including Joint Comprehensive Plan of Action (JCOPA), 8) arrangement of moderated political relations between Iran and the US by the UN, 9) the experiences transfer on the fight against sanctions by the allied countries, 10) the third intermediation and impartial countries to remove sanctions such as Switzerland, 11) the sanctions threats transformation to proper opportunities by politicians, 12) change in the power of pharmaceutical and healthcare-related productions by European and American countries, China, and India, 13) exercising realism on display of the sanctions effects and concentration on the local and national interventions in Iran, and 14) institutionalization of the national beliefs in the countries\u2019 self-reliance.National and international collaborations for preventing and controlling COVID-19 are very important by considering the daily increasing spread of the COVID-19 pandemic around the globe. Nevertheless, sanctions have exerted a considerable effect on COVID-19 control through weakening the economic resources and creating disruption in the process of drug and equipment transfer. However, national efforts play more considerable and vital role in COVID-19 management. Hence, healthcare policymakers and decision-makers in Iran and other countries afflicted with sanctions should elevate their national empowerment, make firm decisions, corroborate and concentrate on research and development as well as health-oriented and pharmaceutical industries, engage in acculturalization to take steps towards controlling and managing COVID-19, and become the new global players with the maximum influence in the area of COVID-19 management."} +{"text": "Powder bed fusion of thermoplastic polymers is a powder based additive manufacturing process that allows for manufacturing individualized components with high geometric freedom. Despite achieving higher mechanical properties compared to other additive manufacturing processes, statistical variations in part properties and the occurrence of defects cannot be avoided systematically. In this paper, a novel method for the inline assessment of part porosity is proposed in order to detect and to compensate for inherent limitations in the reproducibility of manufactured parts. The proposed approach is based on monitoring the parameter-specific decay of the optical melt pool radiance during the melting process, influenced by a time dependency of optical scattering within the melt pool. The underlying methodology compromises the regression of the time-dependent optical melt pool properties, assessed in visible light using conventional camera technology, and the resulting part properties by means of artificial neural networks. By applying deep residual neural networks for correlating time-resolved optical process properties and the corresponding part porosity, an inline assessment of the spatially resolved part porosity can be achieved. The authors demonstrate the suitability of the proposed approach for the inline porosity assessment of varying part geometries, processing parameters, and material aging states, using Polyamide 12. Consequently, the approach represents a methodological foundation for novel monitoring solutions, the enhanced understanding of parameter\u2013material interactions and the inline-development of novel material systems in powder bed fusion of polymers. Laser-based powder bed fusion of polymers (PBF-LB/P) is a powder-based additive manufacturing process of polymer components that is subject to a variety of process influences. These include exposure parameters , varyingLaser-based powder bed fusion of polymers is characterized by the iterative execution of the three consecutive process steps powder coating, laser-based exposure, and the subsequent consolidation of the molten polymer . ResultiIn order to enhance the understanding of underlying physical mechanisms and to enable the monitoring of the powder bed fusion process, several approaches have been proposed. Thermographic approaches for monitoring PBF have been demonstrated for use in metal-based PBF ,18,19 anSummarizing existing monitoring approaches, monitoring of PBF-LB/P predominantly focuses on the thermographic and optical investigation of the energy input. Although the consolidation step, characterized by the viscous flow of the material ,27, accoThe application of machine learning for modeling complex dependencies in powder bed fusion, specifically of polymers, has been adopted in various applications . ApplicaZhang et al. (2019) proposedThe use of artificial neural networks as a specific machine learning method has been proven especially useful for modeling complex dependencies when given sparse, high-dimensional datasets ,43. DeepTo date, the inline monitoring of the powder bed fusion of polymers is limited to the image-based detection and classification of defects. The presented approach aims to overcome the limitations of existing concepts by correlating optical data, derived by means of inline monitoring, and resulting part properties. The technological basis compromises the combination of time-resolved optical inline process monitoring and subsequent data processing using deep residual neural networks. The applied neural network is designed to model a regression of optical melt pool properties and the resulting, spatially resolved part porosity. The porosity of manufactured parts significantly influences the resulting part quality, as it directly affects resulting mechanical properties and is, Image post-processing of raw data, displayed in n, the contours of distinct cross-sections are detected using the Canny edge detector algorithm , In spite of the high variance of experimentally obtained porosity values in the validation step, the satisfactory modeling of structural defects can be demonstrated. Furthermore, morphologies that are described specifically for thin-walled samples can be mThe explanation of the underlying mechanisms of neural-network-based modeling is significant to assess the reliability of the underlying regression . Given tThe application of SHAP on exemplary datasets indicates the mutual dependence of the optical input values and the resulting contribution on the obtained porosity value. Displayed in Considering the applied process layout, increased energy density values are correlated with reduced part-specific layer times. Therefore, the divergent mechanisms determining the part-specific porosity values are expected to not exclusively rely on divergent processing parameters. However, depending on the applied process parameters, structural deviations in the contribution of distinct time steps on the resulting part property, derived by the neural network, are observed. The parameter-dependent contribution of distinct time steps on the resulting porosity value indicates the implicit distinction of divergent process states. The recognition of specific process states is considered essential for enabling the previously demonstrated ability of the network to model varying part-specific porosity values, influenced by variations of process parameters and material aging states. Consequently, underlying mechanisms for the in situ prediction of part-specific porosity values compromise the implicit recognition of superposed process influences.A novel approach for quantifying part porosity in the powder bed fusion of polymers based on optical data, assessed in situ, could be demonstrated within the present paper. The presented approach applies a deep residual neural network that allows for the process-integrated porosity analysis of PBF-LB/P based on the analysis of time series. Temporal changes in optical properties of exposed powder bed sections, representing the input data for the monitoring approach, are characterized by a quasi-monotonous, temporal decay of the radiance of the melt pool, correlated with a time dependency of the occurrence of scattering centers within the melt pool. Varying processing parameters lead to a variation of the time-resolved anisotropic radiance of the melt pool, representing the physical foundation of the subsequent regression, hence allowing for the determination of component properties both on component-specific and mesoscopic scales. The successful inline modeling of the part porosity could be demonstrated for the application of divergent processing parameters, part geometries, and the use of aged Polyamide 12 powder. By determining the influence of distinct optical input values on the corresponding porosity value, the predominant influence of the whole consolidation phase on the derived value was identified. Furthermore, the observed parameter-dependency of the numerical contribution of distinct time steps indicates the implicit distinction of process states, such as insufficient and excessive energy input into the melt. Future work will include enhancing the prediction accuracy and the robustness towards divergent geometries, materials, and processing parameters by enlarging the training dataset. Furthermore, the application of the demonstrated regression network in the real-time process monitoring and the automated, material-specific identification of optimized process parameters embeds relevance for future industrial applications. Considering the possibility of assessing the time-resolved evolution of part properties by determining the resulting part properties at distinct time steps, the proposed approach embeds a novel concept for enhancing the understanding of the consolidation step.Consequently, the presented deep learning-based approach represents the foundation for various applications, including the enhanced understanding of parameter interactions and the vastly accelerated development of novel materials in polymer-based powder bed fusion by means of in-process optimization of process parameters."} +{"text": "Despite decades of professional, academic, and policy interest in person-centered long-term care (LTC), the field continues to be challenged by the absence of a comprehensive depiction of the concept and a lack of consistency reflected across studies and measures. In response, a participatory action, research-focused, partnership between an institution of higher education and an LTC community (the University of Maine Center on Aging and The Cedars), with funding from The Mayer-Rothschild Foundation, is identifying and mapping the landscape of person-centered LTC in nursing homes and assisted living communities. A collaborative, ongoing, exploratory scoping literature review and evidence mapping has compiled a database of 663 academic and 115 grey literature articles through 65 systematic searches reviewing over 4,296 articles. An iterative process from both the resident and organizational perspectives revealed nine core domains and two substantive research gaps . For mapping purposes, domain content was analyzed categorically based on concept, information revealed about resident, family, and staff experience, and operations applicability. The identified person-centered LTC domains, categorical analysis, identified gaps, and visual representation via mapping will contribute to generating research ideas, supporting the development of effective operationalization for LTC settings, and contributing to an understanding of the theoretical scope and concrete elements of a person-centered care model that aims to improve the wellbeing and quality of life of older adults in long-term residential settings."} +{"text": "Western Journal of Emergency Medicine, co-sponsored by the Council of Emergency Medicine Residency Directors (CORD) and the Clerkship Directors in Emergency Medicine (CDEM), serves as a snapshot of the current state of emergency medicine (EM) education research and focuses on relevant topics published by a diverse group of education scholars. Our field has seen marked increases in scholarship, publication venues, funding, and training opportunities for EM education research over the past decade.This special issue of the"} +{"text": "The number of older adults who live in long-term care (LTC) is expected to increase worldwide. The COVID-19 pandemic has caused serious consequences in Canadian LTC homes, while homes in China and Japan reported minimal infection and death rates in residents. The differences in LTC policies may be one of the contributors. The purpose of this literature review was to identify elements of the LTC policies that might have impacted COVID-19 outcomes in LTC homes in Canada, China, and Japan. A scoping review was conducted following the framework proposed by Arksey and O\u2019Malley. Scholarly articles and grey literature published between January 2015 and June 2020 were identified in six databases, four in English , one in Chinese (CNKI), and one in Japanese (CiNii), using MeSH terms for LTC and health policy. Grey literature was identified using Google. Data were extracted, summarized and common themes identified through content analysis. A total of 52 articles and 26 grey sources were included in the review based on determined inclusion criteria. They were research articles, reviews, government or association reports, policy briefs, policy documents, and guides. Four common themes of challenges emerged: caregiver workforce, service provision, funding, and physical environments. Three sub-themes were identified for caregiver workforce and service provision. Differences in COVID-19 consequences in LTC homes in the three countries seem to be related mainly to the challenges with the caregiver workforce and the lack of funding. The result suggests Improvements of LTC policies are required, especially in Canada."} +{"text": "Despite the increasing burden of mental disorders, a lot of people worldwide suffer a gap in receiving necessary care in these countries. To close this gap, the WHO has developed mhGAP training modules aimed at scaling up mental health and substance use disorders services, especially in low- and middle-income countries. This article presents the experience of implementing the Mental Health Gap Action Programme (mhGAP) in Ukraine, Armenia, Georgia, and Kyrgyz Republic. Data were gathered from an electronic questionnaire administered to representatives from higher educational institutions where the Mental Health Gap Action Programme Intervention Guide (mhGAP-IG) was implemented in existing curricula for medical students, interns, and residents in family medicine and neurology, practicing physicians, and master\u2019s program in mental health students. More than 700 students went through the programs that provided the feedback. Evaluations of program effectiveness mainly involved standard discipline tests or pre- and post-tests proposed in the mhGAP trainer manual. This finding suggested that mhGAP-IG can be successfully adapted and implemented both on undergraduate and on postgraduate education levels and among medical and nonmedical specialists. Future evaluations need to more definitively assess the clinical effectiveness of mhGAP-IG implementation. Mental and behavioral disorders are highly prevalent across the globe. The World Health Organization (WHO) states that one in four people could have a mental health disorder during their lifetime . In 2016While mental and behavior disorders increase risk for noncommunicable diseases, and injuries ,7, indivUkraine, Armenia, Georgia, and Kyrgyz Republic are former Soviet republics, which have walked down different pathways after gaining independence in 1991.Ukraine is located in Eastern Europe and is the second largest country in the European region. It has a population of 42.0 million . After gGeorgia is a country in the Caucasus region located at the crossroads of Western Asia and Eastern Europe. The population of Georgia is 3.7 million . Since iArmenia is located in the Western Asia, South Caucasus region. The population of Armenia is 2.9 million . The iniThe Kyrgyz Republic is a lower-middle-income country of 6.5 million people in Central Asia. Since independence in 1991, the country has experienced instability, with political and social upheavals in 2005 and 2010 .Additional information on the countries can be found in Development of mental health systems in the Eastern Europe and the Asian region is characterized by gradual decentralization, with often disproportionately slow growth of community services . In manyThe estimated prevalence and burden of mental health and substance use disorders in Ukraine, Georgia, Armenia, and Kyrgyz Republic are shown in Mental health gaps remain high in the region ,4. The rIncorporation of mental health into specialized and primary care services could be a possible solution to existing challenges and could reduce the burden associated with mental disorders ,29,30,31In order to scale up mental health and substance use disorders services, WHO, in 2008, launched the Mental Health Gap Action Programme (mhGAP). To assist in implementation of mhGAP, WHO developed the Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), which provides evidence-based guidelines, tools, and clinical decision-making protocols for integrated management of priority conditions. The mhGAP-IG has been developed for use by healthcare providers working in nonspecialized healthcare settings, with adaptation to meet national and local needs ,34.According to a recent systematic review by Keynejad and colleagues, the mhGAP-IG was successfully used by clinicians, government ministries, trainers, educators, and academics in a range of LMICs . Forms aThere were several initiatives in Ukraine to implement the mhGAP program. In 2017, at the request of the Ministry of Health of Ukraine, WHO supported the launch of capacity-building activities for the mhGAP Humanitarian Intervention Guide in Eastern Ukraine. In 2019, it expanded the program and trained primary healthcare workers on Version 2.0 of the mhGAP Intervention Guide in the Donetsk region . HoweverAt the same time, ongoing and sustainable development of a mental health workforce should include strengthening of institutional capacity to implement training programs effectively . One of Ukraine, Armenia, Georgia, and Kyrgyz Republic work together towards strengthening mental health education within the framework of the Ukraine-Norway-Armenia (UNA) Partnership. The UNA Partnership initially included higher education institutions (HEIs) from Ukraine, Norway, and Armenia. Later, UNA Partnership activities were joined by Tbilisi State Medical University (Georgia) and Kyrgyz-Russian Slavic University (Kyrgyz Republic). Among other initiatives, the UNA Partnership focused on mhGAP-IG implementation in selected HEIs.The initiative of WHO mhGAP-IG implementation in pre-service training was discussed and developed during three consultative meetings in 2018, which took place concurrently with the 23rd World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions, the 18th WPA World Congress of Psychiatry, and the 2018 mhGAP Forum held at WHO\u2019s headquarters in Geneva, Switzerland.Later in 2018, in Kyiv, Ukraine, a three-day introductory mhGAP course brought together decision makers and clinical educators from postgraduate and undergraduate teaching institutions to discuss how mhGAP-IG can be used to strengthen pre-service training and to provide training on mhGAP-IG, with special emphasis on the module on child and adolescent mental and behavioral disorders. There were 20 faculty members from medical universities in Ukraine, Georgia, Armenia, and Kyrgyz Republic. Each University went through a preparation and adaptation phase, when specific modules and required number of hours were decided based on the existing curriculum and needs .This article provides a one-year follow-up on the implementation of mhGAP-IG in educational settings in Ukraine, Armenia, Georgia, and Kyrgyz Republic after initial assessment .The aim of this study was to collect one-year follow-up data on implementation of mhGAP-IG in education settings in Ukraine, Armenia, Georgia, and Kyrgyz Republic. The objectives were to collect information about curriculum changes of existing courses, development of new ones, teaching processes, and number of students one year after mhGAP-IG implementation; to collect information about evaluation methods used to assess effectiveness of mhGAP-IG implementation in education settings, and to gather recommendations from faculty members who have implemented the mhGAP-IG. We believe that information on the practical realities of implementing standardized training modules in different world regions is essential in optimally planning how to prepare the diverse global workforce of healthcare providers who have the potential to address a critically important healthcare need.A cross-sectional descriptive study was conducted from October 2019 to February 2020. Data were gathered from an electronic questionnaire.Participants were at HEIs in Ukraine , Armenia , Georgia , and Kyrgyz Republic .For the purpose of the study, a self-administered electronic questionnaire was developed. The questionnaire consisted of 20 questions, both open- and closed-ended, divided into four sections: (a) background ; (b) current use of mhGAP-IG in education settings ; (c) evaluation of effectiveness of mhGAP-IG implementation in education settings ; (d) recommendations .Descriptive data are presented as case examples and in tabulated form.Implicit consent was provided when respondents completed the questionnaire.Cumulative results are presented in Background: The official WHO Ukrainian translation of mhGAP-IG has been available since 2019. Kyiv Medical University implemented the mhGAP-IG-enhanced curriculum in September 2019. The existing training curriculum on Psychiatry and Narcology for 4th-year medical students was revised in several steps to implement mhGAP-IG. The mhGAP-IG was presented to the staff of the department of Neurology, Psychiatry and Physical Rehabilitation of Kyiv Medical University, and possible changes in the curriculum were discussed. Necessary changes have been introduced, and the updated curriculum on Psychiatry and Narcology was approved by the Scientific Council in June 2019 and signed by vice-rector of the Kyiv Medical University in August 2019. Additionally, in 2019, following the example of undergraduate curriculum, the curriculum for Neurology residents was updated using mhGAP-IG.The following modules were selected: dementia, epilepsy, substance use disorders, and child and adolescent mental and behavioral disorders. The introduction of the mhGAP-IG allowed reduction of didactic sessions while maintaining the same number of hours spent on interactive practical sessions and emphasizing self-study of mhGAP-IG online materials . The resThe mhGAP-IG has been received very well by the students, clinical instructors, and clinical administrators. Identified benefits include improved trainee knowledge about mental disorders.The program was evaluated based on students\u2019 and residents\u2019 performance , which showed improved knowledge, compared to in the standard curriculum, about mental disorders. Additionally, faculty members discussed their perceptions on the updated program at Scientific Council and expressed positive attitudes towards the mhGAP-IG.The students and residents were given the survey to assess their level of involvement and feedback about strengths and weaknesses of the modules of mhGAP-IG implemented in the program. In their feedback, both students and residents reported acquisition of better knowledge and skills to identify and manage mental disorders. On the other hand, teachers using different assessment measures found improvement of the students results on the topics after implementation of the mhGAP-IG modules concerning their ability to recognize the symptoms, to put the correct diagnosis, and to provide appropriate treatment of mental diseases.The implementation of mhGAP-IG was effective at both undergraduate and postgraduate levels of medical education. Well-structured information and visual materials have been identified as the main advantages of the mhGAP-IG training and implementation process. The program was evaluated based on students\u2019 and residents\u2019 performance and feedback surveys.The working group of the department initiated the translation of the textbook into Armenian. Staff members of Yerevan State Medical University, Department of Medical Psychology, developed and implemented programs for both undergraduate and postgraduate training levels. Adaptation of the mhGAP-IG-based curriculum took approximately 1 month.The pre-service curriculum for the second-year undergraduate students was updated with mhGAP and included eight academic hours for child and adolescent mental and behavioral disorders (with emphasis on attention deficit and hyperactivity disorder), depression, and suicide. Two modules of a continuing medical education (CME) for senior and mid-level medical professionals have also been developed as two-week, 60-h courses entitled \u201cMental Health of Children and Adolescents\u201d and \u201cMental Health of Primary Care for Children and Adolescents.\u201d The programs were attended by 11 pediatricians and 30 specialists from 11 orphanages and social services centers for the elderly and disabled. Additionally, a CME course on psychological aspects of palliative care was adapted using mhGAP-IG and attended by 27 oncologists. Additionally, it is planned to develop a CME course in conjunction with the Yerevan State Medical University Department of Family Medicine for doctors and nurses in the primary care setting. Three topics from mhGAP were also included in the curriculum of Psychology courses at American University of Armenia. Furthermore, several mhGAP topics were included as part of the training curriculum of military psychologists from the Ministry of Defense of the Republic of Armenia.The program was evaluated based on students\u2019 and trainees\u2019 performance (tests). Additionally, feedback questionnaires for 2-year students were used and showed that more than 85% of trainees found the course to be very useful .The program was evaluated based on students\u2019 and residents\u2019 performance and feedback surveys. Feedback from participants showed that mhGAP-IG pretraining can be successfully implemented in various conditions with different students (doctors and nurses) and can be adapted to meet the unique needs of each institution. It can be assumed that the introduction of mhGAP-IG techniques and approaches is possible and acceptable, with adequate preparation and under certain conditions.In 2018, Georgia joined the UNA (Ukraine\u2013Norway\u2013Armenia) partnership project. mhGAP-IG has been translated into the Georgian language and included into the pre-services curriculum and accredited CME courses for medical doctors of different specialties. The initial adaptation into the pre-service curriculum took around 1 week.The mhGAP-IG has been integrated into the medical student curriculum at Tbilisi State Medical University and into the Medical Academy curriculum for fourth- and fifth-year students. Accredited CME courses for primary healthcare professionals have been prepared. The mhGAP-IG has been integrated into the psychiatry clerkship and psychiatry internship syllabus. The chapters on psychoses, depression, dementia, self-harm/suicide, and child and adolescent mental and behavioral disorders were added to the curriculum of the mental health master\u2019s program at Ilia State University. In general, the learning process using the WHO mhGAP-IG was highly interactive. All students had the opportunity to actively participate in the discussion and role play process, which they liked very much.For knowledge assessment, the questionnaires from the mhGAP module for psychoses and child and adolescent mental health were used only as post-tests. The comparison of pre- and post-tests was not conducted. The average score on post-test was 82%. After each semester, the university usually assesses the satisfaction of students with the course. This year, the highest marks were received, even though only online classes were provided. Students stated that the WHO mhGAP-IG is a well-structured tool with practical mhGAP-IG supplementary materials that helped them to understand and realize the difficulties and consequences of mental health problems. The personal stories gave them clear messages regarding patients\u2019 and families\u2019 challenging experiences. The video instructions were very helpful in terms of learning interviewing skills, which the students could practice with the role-playing exercises. At the same time, students pointed out that they lacked sessions with real patients.mhGAP-IG was successfully incorporated on different levels of education, including in specialized mental health courses. Well-developed manuals and supporting materials make mhGAP-IG easy to implement. Support from the university leadership is necessary during the implementation process. The program was evaluated based on students\u2019 and residents\u2019 performance and feedback surveys.The mhGAP guideline was translated into the Kyrgyz language. A seminar on adaptation and implementation of mhGAP was conducted. Order No. 749 of the Ministry of Health of the Kyrgyz Republic of 7 July 2019 was signed, approving the usage of mhGAP in the training of medical personnel in universities of the country at the graduate and postgraduate levels. At the first stage, 20 trainers were trained to further teach the mhGAP program. Then, in the capital of the republic, a pilot mhGAP training was conducted, in which 15 general practitioners, 10 psychologists, and 15 nurses providing outpatient mental healthcare from 10 pilot regions participated. The training was evaluated and recommended for implementation in education settings. With support from the Ministry of Health, mhGAP was implemented in the educational sector at the graduate and postgraguate levels.Before the approval of the program by the Government of the Kyrgyz Republic for the protection of mental health of the population for 2018\u20132030 and the introduction of mhGAP in the country at the undergraduate and postgraduate levels, training in the subject of psychiatry only involved study of the following: the main criteria of the ICD-10; the main psychopathological symptoms such as disturbances in perception, thinking, emotions, motor function, and consciousness; psychopharmacology. After Government approval of and implementation of the mhGAP, the emphasis in teaching psychiatry shifted to practical management of the patient and provision of comprehensive care, including psychoeducation, stress management, and psychosocial care. In the final exam for medical students, questions related to mental health or to the study of behavioral sciences are almost not included. This absence creates a steady depreciation of psychiatric or psycho-educational skills among medical students. In Kyrgyzstan there is no system to reward general practitioners for identifying and treating patients with mental disorders. Recently, a program of monetary incentives for doctors has been developed; however, it is currently at the stage of pilot testing.Four topics were selected to implement the mhGAP guidelines in Kyrgyzstan: depression, suicide/self-harm, childhood and adolescent mental and behavioral disorders, and substance abuse. mhGAP topics have been included in the curriculum of medical institutes and universities . The Department of Family Medicine of the Kyrgyz State Medical Institute of retraining and advanced training provides postgraduate training for family doctors and nurses.The evaluation is based on post-training feedback questionnaires as well as pre- and post-tests from mhGAP. Evaluation of the training showed that 75% of general practitioners rated mhGAP guidelines as relevant and necessary for their practice. In addition, training was also evaluated based on medical records. Detection of depression and suicide among the population from regions where practitioners participated in the pilot training increased by 17%. Based on these results, it was recommended to include mhGAP-IG in the curriculum of medical HEIs.The mhGAP-IG was successfully implemented on under- and postgraduate levels. The program was evaluated based on students\u2019 and residents\u2019 performance and feedback surveys. Additionally, efficacy of practitioners training was evaluated based on medical records. Implementation of the mhGAP-IG contributed to increased awareness about mental health and recognition of mental health professionals.The mhGAP-IG has been successfully implemented in all four countries at both undergraduate and postgraduate levels. In all cases, the importance of support and recognition by the administration was pointed out. In one case (Kyrgyzstan), legislative changes and support were needed to permit the introduction of mhGAP-IG in educational programs at the country level.At the undergraduate level, the program was introduced into existing curricula for students of different years of study, including second year (Armenia), fourth year (Ukraine), and sub-internship year (Georgia). At the postgraduate level, existing programs were revised or new ones created based on mhGAP-IG. In two countries (Armenia and Kyrgyzstan), mhGAP-IG has been included in postgraduate programs for general practitioners. In Ukraine and Armenia, postgraduate programs for doctors of other specialties were developed based on or using mhGAP-IG. In one country (Armenia), a postgraduate educational program for nonmedical specialists was developed based on mhGAP-IG. Only in one country (Kyrgyzstan), educational programs including mhGAP-IG targeted for both family doctors and nurses. In one country (Georgia), mhGAP-IG modules were included in the educational program of psychiatry specialists .All countries implemented modules on depression, suicide, and child and adolescent mental and behavioral disorders. Three countries implemented the module on substance use disorders, and two countries implemented modules on dementia. Only Ukraine implemented the module on epilepsy. Only Georgia implemented the modules on psychosis and other significant mental health complaints.The scope and nature of evaluating the effectiveness of introducing mhGAP-IG into educational programs varied from country to country , but maiThe study is limited in its inclusion of only four countries, united by similarities in socioeconomic background and implementation of mhGAP-IG during a similar timeframe. It is envisioned that this description of the process of implementing mhGAP-IG in these countries can help other countries that may be interested in introducing what appears to be a helpful tool in advancing the population\u2019s access to mental healthcare. There is also the possibility of self-reporting bias, as the questionnaire were self-administered.This study shows that the mhGAP-IG can be successfully adapted and implemented on both undergraduate and postgraduate education levels for medical and allied specialties."} +{"text": "Surfactants, especially non-ionic surfactants, play an important role in the preparation of nanocarriers and can also promote the enzymatic hydrolysis of lignocellulose. A broad overview of the current status of surfactants on the immobilization of cellulase is provided in this review. In addition, the restricting factors in cellulase immobilization in the complex multiphase hydrolysis system are discussed, including the carrier structure characteristics, solid-solid contact obstacles, external diffusion resistance, limited recycling frequency, and nonproductive combination of enzyme active centers. Furthermore, promising prospects of cellulase-oriented immobilization are proposed, including the hydrophilic-hydrophobic interaction of surfactants and cellulase in the oil-water reaction system, the reversed micelle system of surfactants, and the possible oriented immobilization mechanism. Bioethanol, as a renewable, economically affordable, and environmentally safe energy material, will gradually become a substitute for fossil fuels. It has far-reaching research significance and application value for the development of a sustainable energy strategy . Due to In general, lignin-derived inhibition is the major physical obstacle restricting the enzymatic hydrolysis of cell wall polysaccharides . More imTo overcome these barriers, immobilization is usually used to improve enzyme stability and even activity or selectivity when properly designed, which can also facilitate the reuse of enzymes and effective cost of catalytic processes . The chaMoreover, the immobilization of cellulase has been achieved based on physical adsorption, covalent binding, or affinity interactions , includiThe surfactants have been widely used for the preparation of nanocarriers as shown in The basic physical and chemical properties of surfactants, such as micelle formation, dispersing, emulsifying, and solubilizing, have made them widely useful in the field of nanotechnology . SeveralSurfactants can also change the surface properties of nanocarriers, such as their morphology, magnetic properties, dispersion, and catalytic performances . This moThe structure and properties of carrier materials have great influence on the properties of immobilized cellulase, such as internal geometry , specific surface area, superficial activation degree, mechanical resistance, and pore diameter . MeanwhiThe physical effects of nanocarriers on immobilized cellulase are as follows: 1) The pore size and effective surface area of the nanocarriers. Not all porous carriers can be used for immobilization of cellulase due to the limitation of pore size, which should be larger than or equal to that of the cellulase to reduce steric hindrance. The effective surface area occupied by the enzyme determines the maximum load of the immobilized cellulase . When a 2). Moreover, the hydrophilic properties of the C-MNPs play an important role in the preparation of oriented-immobilized cellulase based on the SRM system. The conventional immobilization of cellulase molecules on a single magnetic nanocarrier is simple, the chitosan was usually first coated on the magnetic nanocarriers for further combination with cellulase , which are easier to co-precipitate with cellulase distributed at different ends. In the water-oil (W/O) system, the surfactants are dissolved in the nonpolar organic solvent when a trace of water is provided, and the reversed micelles are formed when the concentration exceeds the CMC (The SRM system has been widely used in the preparation of immobilized enzymes . The spe the CMC . In reve the CMC . Accordi the CMC .Multipoint covalent attachment is likely the most effective strategy for immobilization, but it is difficult to allow the immobilization of enzymes at a well-defined position since the proteins are usually attached to the solid surface by uncontrolled chemical bonds . The uncCellulase plays an important role in the production of fuel ethanol by the enzymatic hydrolysis of lignocellulose, and the immobilization of cellulase on the nanocarriers is an effective way to improve hydrolysis efficiency. However, the nanocarrier structure characteristics, solid-solid contact obstacles, external diffusion resistance, limited recycling frequency of nanocarriers, and nonproductive combination of enzyme active centers restricted the further improvement of hydrolysis efficiency in the complex multiphase system. Surfactants can promote the enzymatic hydrolysis of lignocellulose and play an important role in the preparation of nanocarriers. The special SRM system caused by the amphiphilicity in the oil-water reaction system can provide effective protection to obtain the immobilization of single-layer cellulase, which can effectively prevent the immobilization of cellulase and increase the effective attachment of immobilized cellulase and solid substrates."} +{"text": "Ferroptosis is a new form of programmed cell death due to iron-dependent excess accumulation of lipid peroxides and differs from other programmed cell deaths in morphological and biochemical characteristics. The process of ferroptosis is precisely regulated by iron metabolism, lipid metabolism, amino acid metabolism, and numerous signaling pathways, and plays a complex role in many pathophysiological processes. Recent studies have found that ferroptosis is closely associated with the development and progression of many lung diseases, including acute lung injury, pulmonary ischemia-reperfusion injury, lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Here, we present a review of the main regulatory mechanisms of ferroptosis and its research progress in the pathogenesis and treatment of lung diseases, with the aim of providing new ideas for basic and clinical research of lung-related diseases. Ferroptosis is a new type of iron-dependent programmed cell death caused by lipid peroxidation (LPO), which differs from other programmed cell deaths in morphology and biochemical characteristics. In terms of morphology, there is no chromatin agglutination and nuclear fragmentation as opposed to the process of cell apoptosis, nor the formation of autophagic vacuoles with two-layered membrane structures seen during autophagy, or swelling of organelles and rupture of the plasma membrane during necrosis. Its main morphological characteristics are mitochondrial shrinkage and increased mitochondrial membrane density, accompanied by the reduction or disappearance of mitochondrial cristae and outer membrane disintegration . The corLPO is the key link in triggering ferroptosis. Excessive accumulation of LPO will cause plasma membrane damage and eventually lead to cell ferroptosis. Polyunsaturated fatty acids (PUFAs) are more prone to oxidation to produce peroxy groups due to their labile double bonds, and are also one of the key mechanisms of ferroptosis. When PUFAs are present in large amounts, more lipid peroxides are produced, aggravating the degree of ferroptosis . With th2+ in cells, which is composed of transferrin receptor (TfR), divalent metal ion transporter-1 (DMT1), transferrin, ferroportin1 and ferritin (Ft), etc system. The IRP system can sense the concentration of free FeFt), etc . Fe3+ inol (LIP) . LIP can(LIP) is located in the cytoplasmic membrane and exerts an anti-ferroptosis effect through its N-terminal myristoylated motif. It is the redox of NADPH-dependent coenzyme Q (CoQ) oxidoreductase. FSP1 maintains the reduced form of CoQ at the plasma membrane, which antioxidant activity is not dependent on GSH. The reduced form of CoQ traps lipid peroxyl radicals and prevents the diffusion of LPO . In GPX4Nuclear transcription factor-2 (Nrf2) is a critical regulator of antioxidant response . Under nVarious types of cell death have been implicated in the regulation of inflammation. When ferroptosis occurs, it can mediate inflammation immunogenically, intervening in the immune system to dispose of dying cells. Intracellular components undergoing ferroptosis can release ATP, nucleotides, and pro-inflammatory cytokines from pro-inflammatory damage-associated molecular patterns (DAMPs) to promote the development of necroinflammation . In addiin vitro model of IR generates a large amount of ROS, which may recruit pro-inflammatory leukocytes and destroy the membrane integrity of plasma endothelial and epithelial cells is a disease with airflow obstruction as the main pathological change, which can cause irreversible lung injury. The etiology of COPD is not clear, and it is currently believed to be related to the abnormal inflammatory response of harmful gases and harmful particles. Cigarette smoke (CS) has an important effect on iron homeostasis in the lung. Exposure of mouse and human bronchial epithelial cells to CS increased the concentrations of iron, Ft, serum ferritin and non-heme iron in lung cells . EndoplaPulmonary fibrosis (PF) is an interstitial lung disease that develops from long-term inhalation of dust, the use of drugs such as amiodarone, bleomycin, or lung injury caused by radiation therapy. The formation of fibrotic foci is a prominent pathological feature of PF . Collage2+, ROS and mitochondrial superoxide, which inhibits ferroptosis by acting as a competitive endogenous RNA. It is also observed that overexpression of lncRNA LINC00336 limits ferroptosis induced by GPX4-inhibitor RSL3 in lung adenocarcinoma cells , macrophages to accumulate in the airways and release inflammatory factors leading to chronic airway inflammation. In a highly oxidized microenvironment, H2O2 can up-regulate Th2-driven airway inflammation by influencing the secretion of Th1 and Th2 cytokines and enhancing the airway\u2019s hyperreactivity, which makes the above symptoms prolonged and aggravated . Airway rticoids . In hypeMycobacterium tuberculosis (Mtb), the macrophages in the alveoli are the first to secrete large amounts of IL-1, IL-6, and TNF-\u03b1, allowing lymphocytes and monocytes to aggregate, forming combined granulomas to limit the spread of Mtb. Th1 cells play an immune protective role and promote the function of macrophages. The contest between Mtb and macrophages determines the direction of tuberculosis. Studies have found that Mtb-induced macrophage death was associated with decreased GSH and GPX4 levels and increased free iron, mitochondrial superoxide, and LPO. The destruction of macrophages by Mtb was reduced after Ferrostatin-1 treatment. Similar manifestations were also seen in necrosis of the lung, demonstrating that ferroptosis is the primary mechanism of necrosis in Mtb infection is an infectious inflammatory disease. In the early stage of infection, the symptoms are mostly fever, cough, muscle aches, and fatigue . Severe The pathological changes of COVID-19 mainly include hemoglobin damage, hypoxia, methemoglobinemia, and cellular iron overload . Iron isIron chelator has immunomodulatory and anti-inflammatory effects, and can bind to several receptors used by SARS-CoV-2 to prevent it from entering host cells. The therapeutic mechanism of iron chelators also includes down-regulation of hepcidin, binding of free iron, or depletion of iron from Ft, thus interfering with virus replication . After SReducing the concentration of intracellular iron and increasing the level of reducing agents is the most fundamental treatment to alleviate the redox and ROS damage of cells, especially in severe COVID-19 cases like ARDS. The correct selection of chelating agents and reducing agents to prevent the early formation of ROS is an important control measure.Ferroptosis is a new way of programmed cell death caused by the excessive accumulation of iron-dependent LPO, involving various metabolic pathways such as amino acid metabolism, lipid metabolism, and iron metabolism. With the progress of ferroptosis research, more and more influencing pathways and regulatory factors have emerged, forming a complex network of ferroptosis occurrence and development. A large number of experimental studies have revealed that ferroptosis is involved in the morphological changes and pathological processes of various diseases. In ALI, IR, COPD, and pulmonary infectious diseases where ferroptosis is clearly involved in the injury mechanism, intervention at a certain point in the ferroptosis network may play a role in the early prevention of the disease. This would lead to the improvement of clinical symptoms and control of the development of the disease course. In the future, we can also try to explore whether the combined use of ferroptosis inhibitors in various ways will achieve better therapeutic effects. Therefore, in the context of the many achievements in animal model experiments, it is essential to perform more in-depth studies on the mechanisms and targets of action of ferroptosis inhibitors. More efficient and specific modulation of cellular ferroptosis is key for future research."} +{"text": "Betula platyphylla Suk. is one of the most widely distributed temperate deciduous tree species in East Asia and has important economic and ecological value. Based on 231 species distribution data points of Betula platyphylla Suk. in China and 37 bioclimatic, soil, and topography variables (with correlation coefficients < 0.75), the potential geographical distribution pattern of Betula platyphylla Suk. under Representative Concentration Pathway (RCP) climate change scenarios at present and in the 2050s and 2070s was predicted using the MaxEnt model. We analyzed the main environmental variables affecting the distribution and change of suitable areas and compared the scope and change of suitable areas under different climate scenarios. This study found: (1) At present, the main suitable area for Betula platyphylla Suk. extends from northeastern to southwestern China, with the periphery area showing fragmented distribution. (2) Annual precipitation, precipitation of the warmest quarter, mean temperature of the warmest quarter, annual mean temperature, and precipitation of the driest month are the dominant environmental variables that affect the potential geographical distribution of Betula platyphylla Suk. (3) The suitable area for Betula platyphylla Suk. is expected to expand under global warming scenarios. In recent years, due to the impact of diseases and insect infestation, and environmental damage, the natural Betula platyphylla Suk. forest in China has gradually narrowed. This study accurately predicted the potential geographical distribution of Betula platyphylla Suk. under current and future climate change scenarios, which can provide the scientific basis for the cultivation, management, and sustainable utilization of Betula platyphylla Suk. resources.Climate is a dominant factor affecting the potential geographical distribution of species. Understanding the impact of climate change on the potential geographic distribution of species, which is of great significance to the exploitation, utilization, and protection of resources, as well as ecologically sustainable development. Climate plays a major role in species distributions on regional and global scales, influencing the biodiversity and the potential geographical distribution of species \u20133. GlobaBy studying the relationship between species distribution and environmental variables, we can explore the dominant environmental variables that affect the geographical distribution of species, determine the potential geographical distribution range of species, and analyze the impact of climate change on species distribution , 15. BasBetula platyphylla Suk. is one of the most important pioneers and associated tree species in the Larix forest community in East Asia . The boundary was obtained from Natural Earth . Based on the principle of national and territorial integrity, we have modified and adjusted the vector boundary.DEM was obtained from National Tibetan Plateau Data Center ((TIF)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file."} +{"text": "Dear Editor,A 60-year-old female patient with a history of chronic liver disease, portal hypertension, polycythemia vera, hypothyroidism, and type 2 diabetes mellitus, presented to the Emergency Section of a University Hospital reporting the appearance of painful purpuric lesions in the lower limbs three days before. She denied fever, chills, arthralgia, or trauma. She denied the use of new medications. She reported receiving the second dose of the COVID-19 vaccine (Oxford-AstraZeneca) approximately eleven days before. She denied a similar previous clinical picture. On physical examination, she had purpuric lesions and palpable papules, which did not disappear on digital pressure .Figure 1She reported daily use of propranolol, metformin and levothyroxine. She described stability of the polycythemia vera since December 2015. She was submitted to two lower-limb skin punch biopsies for histopathological analysis and immunofluorescence (IF). Prednisone (1\u202fmg/kg/day) was started once a day. The histopathological examination showed a mixed inflammatory infiltrate with predominantly perivascular fragmented neutrophils associated with extravasated red blood cells a\u2013c. IF sImmunization is a highly important resource in the fight against pandemics, especially the current one caused by COVID-19. However, possible side effects have not yet been fully described. As portrayed by Cohen et al. 2021) and Bostan et al. (2021), there are reports in the literature that point to leukocytoclastic vasculitis following the application of the COVID-19 messenger ribonucleic acid (mRNA) vaccine, such as the vaccine produced by Moderna and Pfizer.021 and BIt is unclear whether the COVID-19 vaccine can reactivate or trigger autoimmune diseases.None declared.Matheus Fritzen: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Gabriella Di Giunta Funchal: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Mariana Oliveira Luiz: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.Giovanna Steffenello Durigon: Statistical analysis; approval of the final version of the manuscript; design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.None declared."} +{"text": "We assess the differences in the effect of traumatic brain injury (TBI) on the decline in cognitive status and the risk of Alzheimer\u2019s disease and related dementia (AD/ADRD) between veteran and non-veteran respondents of the Health and Retirement Study (HRS) and measure the sensitivity of these differences to the incremental introduction of controls for associated risk factors. Three groups of AD/ADRD risk-related variables were used: i) demographic/socioeconomic factors, including gender, race, marital status, education, income, and the number of limitations in activities of daily living; ii) comorbidities, including co-existing depression/post-traumatic stress syndrome (PTSD), substance abuse, diabetes mellitus, stroke, and heart failure; and iii) genetic factors, including the presence of at least one pair of the APOE4 allele and a series of polygenic risk scores associated with AD hallmarks. The dynamics of changes in cognitive impairment in response to TBI, PTSD, and mild cognitive impairment were validated against respective measures estimated using the Department of Defense Alzheimer\u2019s Disease Neuroimaging Initiative (DoD-ADNI) data. The results of the analyses showed that TBI and PTSD were strongly associated with cognitive decline and the risks of AD/ADRD in both veteran and non-veteran subpopulations in HRS data and the difference between them was not statistically significant. Effect magnitude decreased with the addition of risk-related control variables but remained associated with the increased risks. Prevalence of mild cognitive impairment was associated with TBI at baseline in DoD-ADNI data, but no cognitive decline was observed during one year of follow-up."} +{"text": "IEEE Open Journal of Engineering in Medicine and Biology focuses on the major interrelated components of Rapid Acceleration of Diagnostics (RADxSM) Tech, a National Institutes of Health (NIH)-funded program launched on April 29, 2020 to accelerate development, validation, and commercialization of innovative point-of-care and home- based tests, as well as improvements to clinical laboratory tests, that can directly detect SARS-CoV-2, the virus that causes COVID-19. RADx Tech was implemented and coordinated by the Consortia for Improving Medicine with Innovation & Technology (CIMIT) in its role as the Coordinating Center for the Point-of-Care Technologies Research Network (POCTRN) in conjunction with the NIH and the four POCTRN Centers This Special Section of the Likened to a mini-Manhattan Project by Sen. Lamar Alexander et\u00a0al.), the expert review panels , the unique facilitation provided to the funded applicants , the POCTRN Cores that evaluated the technologies at the benchtop and in actual use , and the support for large-scale manufacturing and deployment of diagnostic tests . The final paper describes the impact of RADx Tech on future med-tech entrepreneurs and developers .This Special Section provides operational details for the key components and processes of RADx Tech that have proven to be vital to its success: software platforms that enabled the program's infrastructure and processes (Collins On behalf of POCTRN and as Co-Principal Investigators for the POCTRN Coordinating Center, we are grateful to NIH leadership for their invaluable support and guidance, especially National Institute of Biomedical Imaging and Bioengineering director Bruce Tromberg and NIH director Francis Collins, and are privileged to present this collection of outstanding papers from a group of dedicated colleagues committed to serving our nation, which we humbly suggest represents a new paradigm for medical technology development and a validated model for the United States to use and adapt when challenged by another national healthcare emergency.Steven C. Schachter, Guest EditorCo-PI of the Coordinating Center for POCTRNChief Academic Officer of CIMITBoston, MA 02114 USAsschacht@bidmc.harvard.eduJohn A. ParrishCo-PI of the Coordinating Center for POCTRNChief Executive Officer of CIMITBoston, MA 02114 USA"} +{"text": "Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease that can progress to liver fibrosis and cirrhosis, and requires timely diagnosis, optimal treatment, and risk stratification. Several guidelines for the management of PBC have been published, including the American Association for the Study of Liver Disease (AASLD) and European Association for the Study of the Liver (EASL) Clinical Practice Guidelines, which include goals for standards of PBC care. However, recent audits have identified deficiencies in real-world PBC care. In addition, the global coronavirus (COVID-19) pandemic has generally reduced access to care, diminished healthcare resources and accelerated the use of remote patient management. There is therefore a need for simple, actionable guidance that physicians can implement in order to maintain standards of care in PBC in the new environment.A working group of ten PBC specialists from Europe and Canada were convened by Intercept Pharmaceuticals in January 2020 with the aim of defining key criteria for the care of patients with PBC.Following the outbreak of the COVID-19 pandemic, based on these criteria, a smaller working group of six PBC specialists developed practical recommendations to assist physicians in maintaining standards of care and to guide remote management of patients.Figure 1).The working group defined five key criteria for care in PBC, encompassing PBC diagnosis, initiation of first line therapy with ursodeoxycholic acid (UDCA), risk stratification on UDCA, symptom management, and initiation of 2L therapy. The group developed 21 practical recommendations for the management of patients with PBC in the COVID-19 environment including modality, frequency and timing of investigations and monitoring. (The delivery of PBC care during the COVID-19 pandemic carries significant challenges. These consensus criteria and practical recommendations provide guidance for the management of PBC during the pandemic era and beyond.NoneIntercept Pharmaceutical"} +{"text": "Anal canal and peri-anal squamous cell carcinomas (ASCCs) are relatively rare cancers that affect approximately 8000 patients per year in the United States. The rate appears to be rising, which is potentially attributable to the increasing incidence of oncogenic Human Papilloma Virus (HPV) infection. Historically, patients were treated with abdominoperineal resection with resulting permanent colostomy dependence. Through landmark efforts and sequentially designed clinical trials, the majority of patients with localized disease are now effectively treated with radiotherapy and chemotherapy, or in select cases, sphincter-preserving surgery, with favorable outcomes. However, continued efforts are needed to gain a better understanding of ASCC disease biology and to continue improving cancer control while maximizing the quality of life for patients. The purpose of this Special Issue is to discuss the historical perspectives of surgery, radiotherapy, and systemic therapy; the evolution of therapy over time; and current areas of investigation to advance our understanding of the multi-disciplinary management of patients with ASCC.This Special Issue consists of six articles that provide an in-depth overview of contemporary practice and future areas of investigation. First, Dee et al. and PossIn conclusion, this Special Issue presents an in-depth discussion of the evolution of therapy for patients with ASCC, highlights the importance of multidisciplinary collaboration, and introduces numerous areas of active investigation to help improve outcomes for our patients."} +{"text": "The development of metal nanoparticle-based facile colorimetric assays for drugs and insecticides is an emerging area of current scientific research. In the present work, polypropylene glycol was used for stabilization of gold nanoparticles (AuNPs) in a simple one-pot two-phase process and subsequently employed it for the specific detection of cephradine (CPH). The characterization of the prepared PPG-AuNPs was conducted through various analytical techniques such as UV-visible spectrophotometry, Fourier transform infrared spectroscopy, atomic force microscopy (AFM), zeta potential and zetasizer techniques. As the major target of the study, the stabilized PPG-AuNPs were employed for colorimetric detection of CPH and other drugs. Typical wine-red colour of PPG-AuNPs disappeared immediately and surface plasmon resonance band quenched by addition of CPH in the presence of several other interferents and in real samples. PPG-AuNPs permitted efficient, selective, reliable and rapid determination in a concentration range of 0.01\u2013120 mM with a detection limit (LoD) of 11.0 mM. The developed sensor has the potential to be used for fast scanning of pharmaceutical formulations for quantification of CPH at production facilities. The coupling stoichiometry between PPG-AuNPs and CPH as obtained by Job plot is found to be 1 : 1, The efficiency of any developed method must be validated in the presence of other interfering drugs and salts in the context of real sample analysis. The developed sensor for CPH in this study was found to be robust in the presence of several other interfering drugs and salts. The presence of other drugs namely aspirin, ibuprofen, ampiciline acid, paracetamol, clindamycin, aminophylline, cephalexin, salbutamol, phenytoin, isoniazid, azithromycin, cefixime, cefuroxime, DL tryptophan, theophylline and salts namely potassium bromide, calcium carbonate, calcium bicarbonate and sodium chloride having concentration equal to CPH did not have any pronounced effect on the efficiency of the developed colorimetric CPH sensor, CPH analysis has been reported using many instrumental techniques such as HPLC, ELISA, voltammetry, NMR and GC-MS in different environmental and biological samples, All the above studies were carried out in DI water. Moreover, the authenticity of interference study and validity of PPG-AuNP-based proposed assay for CPH in context of real samples was evaluated by employing the optimized protocols for tap water, urine, serum and blood plasma samples. Immediate disappearance of wine-red colour of PPG-AuNPs and quenching of the typical UV-Vis peak confirms the applicability of the proposed CPH assay for all real samples in the presence of natural interferents, c. The amount of CPH as obtained by the calibration curve is fairly close to the manufacturer claim and analysis of the same sample by independent HPLC-UV and UV-Vis spectroscopy, As the next step, the developed CPH assay was used for quantification and quality control of commercial drugs containing CPH. An appropriate amount of the commercial drug as per claims of the manufacturer was added to the PPG-AuNPs. The immediate disappearance of the wine-red colour of the PPG-AuNPs gave the first indication of the presence of CPH. The next step is the evaluation of the quantitation capability of the proposed colorimetric sensor. The extent of quenching in the UV absorption band, evaluated by the absorbance after addition of the drug, is compared with the calibration curve, figure\u00a07The proposed colorimetric assay for CPH in this study is robust and applicable to samples containing different interfering species and for quick quality control in the production facilities. The advantages of the proposed colorimetric assay for CPH include fast, facile, on-spot analysis of drug contamination in environmental and biological samples without any involvement of high-tech instrumentation.. 4The uniquely developed colorimetric sensing based on PPG-AuNPs has proved to be a rapid and sophisticated one-pot quantitative assay for CPH. Characterization of PPG-AuNPs, CPH and PPG-AuNPs/CPH was done through zeta sizer, AFM, FT-IR and UV-visible spectroscopy. The synthesized PPG-AuNPs were found to be resistant to various external variables such as temperature, pH and the presence of electrolytes. Typical wine-red colour of AuNPs immediately disappears by the addition of CPH and SPR band of AuNPs quenched. The proposed method has a linear dynamic range from 0.025 to 120 mM with a limit of detection of 11.0 mM. The presence of other drugs and ions did not have any pronounced effect on the sensing ability of the PPG-AuNP-based assay for CPH. The proposed method can be used for environmental, biological and pharmaceutical samples. Reasonable selectivity, the simple procedure of preparation and application, a relevant dynamic range and limit of detection demonstrate the potential of PPG-AuNP-based CPH detection method for practical applications without any involvement of high-tech instrumentation. Furthermore, the proposed method can be employed for a quick screening of pharmaceutical formulations in the context of quantification of CPH on production facilities.Click here for additional data file."} +{"text": "Sambucus nigra L.) attracts attention due to its easy cultivation and high availability of bioactive compounds. Most of the available data concerning black elder\u2019s therapeutic action are focused on its effects such as activation of immune processes and anti-inflammatory processes and regulation of hormones and their receptors in cancer cells. The effects of elderberry on reproduction have been poorly investigated so far. Nevertheless, conducted studies so far demonstrate the stimulatory influence of black elder extract and its constituents, such as rutin, anthocyanins and agglutinins, on the viability and steroidogenesis of healthy ovarian cells as well as their ability to promote apoptosis and reduce the viability and proliferation of ovarian cancer cells. Furthermore, the action of black elder extract and its constituent biomolecules, such as anthocyanins and lectins, on embryogenesis and the embryonal estradiol-estradiol receptor system have also been reported. The available information, despite limitations, suggest the applicability of black elder constituents for improvement of reproductive processes in animal biotechnology, animal production and assisted reproduction, as well as for prevention and treatment of reproductive disorders (including cancer) in veterinary and human medicine.The present review summarizes the current knowledge concerning provenance, properties, physiological and therapeutic actions of elderberry and the bioactive molecules present in the plant, with emphasis on their action on female reproduction. Elderberry or black elder ( The search for new regulators of reproduction is important for the solution of various problems of modern society. Intensive animal production is associated with growing incidences of farm animal infertility . The occThe majority of reproductive dysfunctions have similar causes and mechanisms\u2014the ability of various adverse environmental factors to induce oxidative stress\u2014including the accumulation of reactive oxygen species, which are deleterious to DNA and proteins, ovarian folliculogenesis and embryogenesis. Oxidative stress can be prevented by antioxidants . The mosSambucus nigra L.). Due to its health-promoting and sensory properties, elderberry is used primarily in the food and pharmaceutical industries [One of the promising and widely accessible sources of antioxidants and other biologically active substances affecting reproductive and non-reproductive processes and health could be the black elderberry are rich sources of dietary phytochemicals, such as carbohydrates, lipids, terpenoids, flavonoids, phenolic acids, alkaloids, etc. ,20. The The characteristic aroma of elderberries is a result of (E)-\u03b2-damascenone, dihydroedulan, ethyl-9-decenoate, 2-phenyl ethanol, phenylacetaldehyde and nonanal. Alcohols, esters and aldehydes are frequently identified volatile groups in elderberries. Other major secondary metabolites comprise approximately 1% triterpenes and about 1% sterols . In addition, pectins, tannins and phenolic acids are found in the flowers ,36. EldeTherefore, various parts of the elderberry plant demonstrate the presence of high amounts of biologically active molecules with a wide spectrum of effects\u2014from antioxidative and phytoestrogenic polyphenols to toxic aldehydes and glycosides. The presence of these molecules could explain the physiological and therapeutic effects of this plant, as well as the variability in its action on different targets listed below.Elderberry is widely used in folk medicine through its pharmacological properties . CurrentElderflowers have been used in traditional medicines for the management of inflammation, skin disorders such as diuretic, colds, fevers and other respiratory disturbances ,64,65. FNo substantial adverse side effects of black elderberry have been reported so far . MoreoveIt is widely accepted that elderberries\u2019 curative capacity is due to the presence of high amounts of polyphenolic compounds, primarily flavonols, phenolic acids and anthocyanins. The presence of polyphenols, which assure the defense of plants against pathogenic microorganisms, can also explain the ability of black elderberry to suppress the activity of viruses ,53,54 anPlant polyphenols are known free radical scavengers and are able to protect the human body against oxidative stress and peroxidative processes ,76,77,78There is evidence that the positive action of elderberry on vascular health is due to the presence of anthocyanins, especially cyanidin-3-O-glucoside ,62. MoreIt may, however, be noted that search for an active compound of any plant, including elderberry, is difficult because the tested commercial and non-commercial dietary supplements usually contain multiple ingredients. In addition, substantial differences are often found between labelled and actual ingredients or their amounts . FurtherAs mentioned above, several curative effects of elderberry could be explained by high contents of antioxidants, which can either directly eliminate free oxygen species or promote antioxidative enzymes within the cells ,76,77,78kappa B (NF-\u03baB) and interleukin 8 (IL-8). Some similar signaling substances were changed during curative elderberry action on skin photoaging and inflammation. This effect was associated with a decrease in matrix metalloproteinase-1 (MMP-1) expression, secretion of inflammatory cytokines, mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1) and NF-\u03baB signaling pathways and skin inflammation. In addition, elderberry extract improved nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling to increase oxidative defense capacity, enhanced transforming growth factor beta (TGF-\u03b2) signaling activation to promote procollagen type I synthesis and blocked extracellular matrix degradation [Furthermore, the antioxidative and anticancer effects of elderberry anthocyanins are associated with the downregulation of promoters and markers of inflammation, such as monocyte chemoattractant protein-1 (MCP-1), transcription factor nuclear factor radation . The protective effect of elderberry flavonoids and pectins against the influenza virus is probably mediated by stimulating the immune system of the host through enhancing the production of inflammatory cytokines such as interleukins IL-6, IL-8 and tumor necrosis factor (TNF) ,68,83 anIn addition, black elderberry anthocyanins can improve vascular health by promoting the production of nitric oxide, which in turn promotes vascular permeability and vasodilation and reduces blood pressure . On the Finally, elderberry can influence some physiological processes via changes in steroid hormones and their receptors. Elderflower extracts promoted estradiol release, downregulated estrogen receptor alpha and upregulated progesterone receptor expression in cultured breast cancer cells, which are involved in the control of cell proliferation . The endTaken together, the available data suggest that the non-reproductive effects of black elderberry are mediated by changes in oxidative, inflammatory, and regenerative processes, as well as angiogenesis, steroid hormones and their receptors. The functional interrelationships between these processes are possible. At least, the influence of oxidative stress and antioxidants on inflammatory processes, which in turn trigger cancerogenesis/carcinogenesis, has been suggested . FurtherOur recent in vitro study demonstrated the promising stimulatory effect of elder-berry extracts on the viability of human ovarian granulosa cells . This inThe role of a particular elderberry molecule responsible for its effect could be detected by comparison of the effects of the whole elderberry extract and its particular constituents. The most known biologically active constituents of elderberry are rutin, anthocyanins and agglutinins. The most abundant polyphenol in elderflower and elderberry is the flavonoid rutin ,26. The In contrast to healthy ovarian cells, in the case of cultured cancer cells, native and hydrolyzed rutin exerted in vitro inhibitory activity against human ovarian adenocarcinomas by suppression of the viability and proliferation of OVCAR-3 ovarian carcinoma cells ,93. AddiThe present observations suggest the stimulatory influence of black elderberry substances on the viability of healthy ovarian cells and the ability of elderberry to promote apoptosis and reduce the viability of cultured ovarian cancer cells. These phenomena suggest that this plant can be principally useful for stimulation of healthy ovarian cells and suppression of cancer ovarian cell functions. The comparison of the action of elderberry and its constituents indicates that its action on ovarian cell viability and proliferation can be due to the presence of rutin, anthocyanins and/or agglutinins.Our recent study demonstrated the influence of both elderberry extracts from dark purple elderberry fruits, as well as from elderflowers on steroid hormone release by cultured human granulosa cells. The release of both progesterone and 17\u00df-estradiol by the cells was increased after supplementation by either elderflower extract or extract from the berries of the shrub. The results of this study demonstrated the benefits of elderberry extracts prepared from different parts of plant (flowers and fruits) in the upregulation of biosynthesis of ovarian steroid hormones in vitro . According to the above-mentioned hypothesis, the black elder constituents responsible for the elderberry\u2019s effects on ovarian steroidogenesis are to be suggested on the basis of the similarity of effects. Such similarity in elderberry and rutin has been reported. In vivo and in vitro studies on rats demonstrated the ability of rutin to promote the plasma luteinizing hormone (LH) level, expression of ovarian follicle-stimulating hormone (FSH) receptors, steroidogenic enzymes, ovarian folliculogenesis and fecundity ,91. In iThe current literature does not portray evidence concerning anthocyanins\u2019 action on ovarian steroidogenesis, although the phytoestrogenic effects of anthocyanins, especially of cyanidin and delphinidin, have been reported ,100. TheAgain, the current literature does not demonstrate the changes in ovarian steroidogenesis under influence of agglutinins. Therefore, there is no evidence so far that elderberry action on ovarian steroid hormones could be due to anthocyanins or agglutinins. On the other hand, the high similarity in stimulatory action of elderberry extract and rutin on healthy granulosa cell viability and steroidogenesis suggests that plant action on ovarian cells can be due to the presence of the most abundant plant flavonol rutin. Furthermore, the steroid-promoting effect of elderberry indicates the potential applicability of this plant and its constituent rutin for the promotion of steroid-dependent non-reproductive and reproductive events including ovarian folliculogenesis and fecundity.Xenopus laevis [Schr\u00f6der et al. did not s laevis or on ths laevis . TherefoOther black elder constituents, such as anthocyanins , and herIn contrast to elderberry anthocyanin, elderberry lectins blocked receptors of vascular endothelial growth factor (VEGF) in embryonal tissue, which is responsible for embryonal angiogenesis . These dSchr\u00f6der et al. also stuTherefore, the available publications indicate both stimulatory and inhibitory actions of elderberry extract and its constituents rutin, anthocyanins and lectins on regulators of embryogenesis, embryonal cancerogenesis and steroidogenesis. The ability of steroid hormones to promote both embryo development and maliAlthough numerous signaling pathways are involved in elderberry action on non-reproductive processes, research enabled the identification of only some pathways mediating the effect of black elderberry on reproduction, and less studies have been performed to detect mediators of this plant\u2019s action on female reproductive processes.The direct action of the elderberry extract on reproductive organs and the ability to affect cultured ovarian and embrThe ability of elderberry constituents rutin ,91 and aElderberry extract affected steroid hormones release by ovarian granulosa cells and embrThe current literature does not contain evidence concerning the intracellular mechanisms of the whole elderberry extract action on ovarian cells; however, there are some reports concerning the key elderberry constituents on cultured ovarian cells and cancer cells, which could help to understand the mediators of elderberry actions on either healthy or malignant cells. Treatment of mice with rutin boosted ovarian follicular health and ovarian cell proliferation, increased the number of active mitochondria and the intracellular level of the antioxidant glutathione, reduced ovarian cell ROS level and markers of apoptosis (PTEN/FOXO3a) pathway and mitigated the toxic effect of cisplatin on ovarian functions .The other elderberry constituents, namely anthocyanins includin(1)Black elderberry agglutinin activates the signaling pathways of AKT and ERK1/2, which promotes de-phosphorylation of dynamin-related protein-1 (Drp-1).(2)Upon its translocation to the mitochondrial fission loci, Drp-1 induces fragmentation of the mitochondrial membrane.(3)Mitochondrial outer membrane permeabilization results in the generation of ROS and cytochrome-c release into the cytosol\u2014the signs of mitochondrial apoptosis.(4)These changes may result in cell cycle arrest before the G2/M phase and programmed cell death.A similar mechanism of action on ovarian cancer cells was reported for black elderberry agglutinin. Chowdhury et al. demonstrResults of the study also demonstrated that black elderberry and its constituent rutin could promote healthy ovarian cell functions through the upregulation of gonadotropins, gonadotropin receptors, steroid hormones, antioxidants, reduction in oxidative stress and apoptosis, which in turn improves ovarian cell viability and fecundity. In contrast, in the case of ovarian cancer cells, elderberry and its constituents, rutin, anthocyanins and agglutinin, can suppress cell viability and functions via the downregulation of the similar mechanisms\u2014AKT- and ERK1/2-dependent intracellular signaling pathways\u2014promoters of cell proliferation and by induction of ROS-induced cytoplasmic/mitochondrial apoptosis. Understanding the causes of opposite action of elderberry and its molecules on healthy and cancer ovarian cells via similar intracellular mechanisms require further studies. Such studies could be helpful for possible application of elderberry for stimulation of healthy ovary and reproductive processes and suppression of ovarian cancer (see below). Available evidence concerning the possible regulators of female reproductive processes affected by black elderberry and its constituents are summarized in The reported effects of black elderberry and its constituents on female reproductive processes summarized here indicate that these plant preparations could be stimulators of healthy ovarian cells and embryogenesis. It is not to be excluded that these preparations can support ovarian folliculogenesis, oogenesis, fecundity, embryogenesis and gravidity, to relieve the age-related reproductive insufficiency and menopause-related problems. As promoters of release and reception of gonadotropins and steroid hormones, as well as phytoestrogens, they could be useful in veterinary and human medicine for the treatment of disorders induced by a deficit of these hormones\u2014age-related reproductive insufficiency, menopause-related problems, osteoporosis and polycystic ovarian syndrome. The ability of elderberry and its molecules to promote reproductive processes and fecundity could be useful in the induction of ovulation and superovulation in biotechnology in animal production and assisted reproduction. On the other hand, the ability of black elderberry substances to downregulate cell proliferation and viability of ovarian and trophoblast tumor cells indicates the potential ability of these substances for prevention, mitigation and treatment of ovarian and embryonal cancers. Efficiency of elderberry\u2019s polyphenols could be increased by search of its safe and effective dosage, and the improvement of its stability, bioavailability and delivery by using nano-emulsion and nanoliposome systems, which can enhance the biological and therapeutic activity of these plant molecules ,112. Analysis of the available literature performed here shows that black elderberry contains several biologically active substances with different, sometimes opposite, actions. Some elderberry constituents could be toxic see . Some otThe reproductive effects of black elderberry extract and its constituents have been investigated insufficiently. Nevertheless, the published reports demonstrate the stimulatory influence of black elderberry extract and its constituents\u2014rutin, anthocyanins and agglutinin\u2014on steroid hormones and their receptors in ovarian and embryonal cells. The stimulatory influence of anthocyanins on embryogenesis has also been reported. On the other hand, rutin, anthocyanins and agglutinins can suppress ovarian and embryonal cancer cell functions. The effects of black elderberry and its molecules could be mediated by intracellular signaling pathways regulating cell proliferation, oxidative processes, cytoplasmic/mitochondrial apoptosis and viability, as well as by estrogen and estrogen receptors and angiogenesis. The available evidence indicates the potential usefulness of black elderberry extract and its constituents rutin and anthocyanins as biostimulators of female reproductive processes, as well as the potential applicability of whole elderberry extract, with rutin, anthocyanins and agglutinins, for the treatment of ovarian cancer and other reproductive disorders in animal biotechnology, animal production, assisted reproduction and veterinary and human medicine.Nevertheless, the current state-of-art research invokes more queries concerning black elderberry action on female reproduction than answers. All biologically active constituents of black elderberry remain to be identified, and their biological activity remains to be investigated. The action of black elderberry extract has not been studied in in vivo experiments, whilst the reproductive effects of elderberry constituents were studied mainly in in vitro experiments and in a few animal studies. Adequate clinical studies have not been reported yet. Moreover, characteristics and mechanisms of action and biological activities of several elderberry constituents have not been compared in the same experiments yet. The conclusions concerning mechanisms of action of elderberry and its molecules are made mainly based on observations of changes in some signaling molecules after treatment, but the physiological role and functional interrelationships between particular signaling molecules remain rather hypothetical. Therefore, although the influence of black elderberry and its constituents on female reproductive processes has been demonstrated, its actions and potential applications require further studies."} +{"text": "In this article, we \u2013 the Bacterial Viruses Subcommittee and the Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) \u2013 summarise the results of our activities for the period March 2020 \u2013 March 2021. We report the division of the former Bacterial and Archaeal Viruses Subcommittee in two separate Subcommittees, welcome new members, a new Subcommittee Chair and Vice Chair, and give an overview of the new taxa that were proposed in 2020, approved by the Executive Committee and ratified by vote in 2021. In particular, a new realm, three orders, 15 families, 31 subfamilies, 734 genera and 1845 species were newly created or redefined (moved/promoted).The online version contains supplementary material available at 10.1007/s00705-021-05205-9. Given the revived interest in bacterial and archaeal viruses and recent enormous increase in the number of characterized isolates and need for creation of numerous taxa to classify them, the Executive Committee (EC) voted on the creation of two separate Subcommittees , formally starting their mandates after EC52 (October 2020). The new Bacterial Viruses Subcommittee is chaired by Evelien Adriaenssens, supported by Dann Turner as the Vice Chair, and the new Archaeal Viruses Subcommittee is chaired by Mart Krupovic. Both Chairs were elected for three-year terms ending in 2023. As a result, this taxonomy update summarises both bacterial and archaeal virus proposals for the last time, reflecting the fact that proposals were submitted prior to the formal reorganisation of the original Subcommittee.Bacteriophage and archaeal virus taxonomy has been formally under the auspices of the ICTV Bacterial and Archaeal Viruses Subcommittee, which, at its inception in 1966, was named the Viruses of Prokaryotes Subcommittee, led by David E. Bradley , regional representatives and general members. We would like to welcome new members Jesca Nakavuma (Uganda), Alejandro Reyes (Colombia), Cristina Moraru (Germany), Susan Lehman (USA), C\u00e9dric Lood (Belgium) and Andrey Shkoporov (Ireland) and would like to thank those who have left the Subcommittee for their service.Halopanivirales SG, chaired by Hanna M. Oksanen (Finland), oversees the taxonomy of evolutionarily related viruses of the order Halopanivirales, which includes two families of viruses infecting archaea (Sphaerolipoviridae and Simuloviridae) and one family of bacteriophages (Matsushitaviridae). Thus, the latter SG bridges the two Subcommittees. Additional SGs will be created in the near future, in particular, to develop the taxonomy of archaeal members of the class Caudoviricetes; only a handful of isolated representatives of this highly diverse and expansive group of archaeal viruses are currently classified.In the framework of the Bacterial and Archaeal Viruses Subcommittee, all taxonomic proposals dealing with archaeal viruses were handled by a single SG. The new Archaeal Viruses Subcommittee currently includes 11 SGs . Instead, below we provide a brief overview of the most notable changes.We had a record year of submissions of taxonomy proposals in 2020, with 188 proposals submitted, of which all but one were approved and ratified (Supplementary Table S1). The changes at each of the taxonomic ranks in use for bacterial and archaeal viruses are summarised in Table Adnaviria, was created for classification of archaeal filamentous viruses with dsDNA genomes that adopt the A-form conformation within their virions [Tristromaviridae, Rudiviridae and Lipothrixviridae, which are evolutionarily related to each other, but not to any other known group of viruses. The families Rudiviridae and Lipothrixviridae were already grouped together in the order Ligamenvirales [Primavirales, has now been created for the family Tristromaviridae. The two orders are unified in the class Tokiviricetes, kingdom Zilligvirae and realm Adnaviria.Recently, the taxonomic framework of the ICTV has been expanded from five to 15 ranks, with the highest-level rank, realm, being equivalent to the domain rank used for cellular organisms , 3. This virions , 5. The nvirales , and a sPodoviridae. The family Salasmaviridae, named in honour of Margarita Salas Falgueras, comprises the existing subfamily Picovirinae, which includes the classical bacillus phage \u03c629 and a range of related Bacillus-infecting phages with genomes between 18 and 27 kb in size. The family Rountreeviridae, named in honour of Phyllis Margaret Rountree, groups Enterococcus-infecting phages with genomes between 17 and 19 kb in size, whereas the family Guelinviridae, named after Antonina Guelin, groups Clostridium-infecting phages with genome sizes between 16 and 19 kb.We delineated three new families of short-tailed phages with small genomes that were formerly assigned to the family Schitoviridae, named after Giancarlo Schito, is the formalisation of the group of N4-like phages defined by the presence of a large virion-associated RNA polymerase, described in more detail in reference [The new family eference .Zobellviridae, named after Claude Zobell, groups a set of globally distributed podoviruses associated with marine ecosystems first proposed by Bischoff and colleagues [The new family lleagues .Leviviridae was elevated to the rank of class, named Leviviricetes (replacing the class Allassoviricetes), and expanded to include two orders and six new families: Fiersviridae , Atkinsviridae, Duinviridae, Solspiviridae, Blumeviridae and Steitzviridae. A detailed description of the new taxa will be published separately.Based on the investigation by Callanan and colleagues on the expansion of known ssRNA virus genomes , the famAutolykiviridae formalises the group of non-tailed dsDNA bacteriophages discovered and described by Kauffmann and colleagues [The new family lleagues , combiniSphaerolipoviridae, which includes icosahedral tailless viruses with internal membranes, consisted of three genera, Alphasphaerolipovirus, Betasphaerolipovirus and Gammasphaerolipovirus. The first two of these genera included viruses infecting halophilic archaea, whereas the last one included phages infecting thermophilic bacteria [Betasphaerolipovirus and Gammasphaerolipovirus have been renamed and moved from the Sphaerolipoviridae into new families, Simuloviridae and Matsushitaviridae (named after Isao Matsushita), respectively. The order Halopanivirales now contains a family of bacterial viruses, Matsushitaviridae, and two families of archaeal viruses, family Sphaerolipoviridae and Simuloviridae. As mentioned above, the order is under purview of a single Study Group, which is part of both the Archaeal Viruses SC and the Bacterial Viruses SC.Until recently, the family bacteria . Althougbacteria , they diPaulinoviridae addresses the challenge of defining family demarcation criteria for phages with small genomes, where members of the same family would share at least two orthologous proteins. Informed by prior work on a gene-content network of predicted filamentous prophage sequences [Bifilivirus and Thomixvirus from the family Inoviridae to the family Paulinoviridae.The new family equences , we movehttp://ictv.global/report, and summaries of the chapters on each virus family are published in the Journal of General Virology. In 2020, four new chapters on bacterial and archaeal viruses were produced by members of the Archaeal Viruses SC and Bacterial Viruses SC, namely, on the families Herelleviridae [Spiraviridae [Ovaliviridae [Finnlakeviridae [Virus Taxonomy: The Classification and Nomenclature of Viruses - The Online (10th) Report of the ICTV is freely accessible at eviridae , Spiraviaviridae , Ovaliviiviridae and Finneviridae .This past year has been extremely productive in terms of new bacterial and archaeal virus taxa described. It would not have been possible without an active pool of scientists, both within and outside the subcommittee and its study groups, who scour databases, perform analyses and submit proposals. We continue to encourage people to contact us to formalise new discoveries into the taxonomic framework and will keep reaching out to interested parties. Finally, we would like to acknowledge one person in particular, Prof Andrew Kropinski, the Subcommittee Chair from 2014-2020, who authored, co-authored and/or assisted with the majority of proposals that have been approved in the last decade.Supplementary file1 (PDF 175 KB)Below is the link to the electronic supplementary material."} +{"text": "In the future, AI technologies will likely be used for collecting, processing, and organizing patient-related datasets to provide patient-centered, individualized dental treatment.(1) Background: The rapid pace of digital development in everyday life is also reflected in dentistry, including the emergence of the first systems based on artificial intelligence (AI). This systematic review focused on the recent scientific literature and provides an overview of the application of AI in the dental discipline of prosthodontics. (2) Method: According to a modified PICO-strategy, an electronic and manual search up to 30 June 2021 was carried out for the literature published in the last five years reporting the use of AI in the field of prosthodontics. (3) Results: 560 titles were screened, of which 30 abstracts and 16 full texts were selected for further review. Seven studies met the inclusion criteria and were analyzed. Most of the identified studies reported the training and application of an AI system ( The principle is to simulate the transfer of information through a neuron: weighted nodes receive the inputs (representing the synapses), sum them to produce an activation (representing the axon), and pass this activation to a nonlinear function called activation or transfer function, in order to generate the output signal. Each neuron acts as an elementary processing unit. The output signal of one unit will feed the other units, organized in layers, and so on, forming an artificial neural network (ANN)\u201d . There aMachine learning (ML) is part of weak AI; by recognizing patterns, the computer system is able to learn and make predictions ,17. AfteAI technologies are well suited for repetitive work using large datasets. The greater the workload, the more precise the performance of AI becomes . Since dThe domain of AI in medicine is image data processing in radiological workflows, especially for detection of caries and periapical endodontic lesions , as wellTherefore, the aim of this systematic review was to analyze the recent scientific literature on the diagnostic performance and the clinical applications of AI in applied prosthodontics. The remainder of this systematic review was structured as follows: (a) introduction of the search strategy and related inclusion criteria for data extraction; (b) summary of the obtained findings of the identified and included studies; (c) critical discussion of the results; (d) conclusions.This systematic review was conducted in accordance with the guidelines of PRISMA .Based on the PICO criteria, a search strategy was developed and an electronic search was conducted. The PICO question was formulated as follows: What are the current clinical applications and diagnostic performance of AI in the field of prosthodontics?A systematic electronic search of PubMed MEDLINE, EMBASE, and CENTRAL was performed for English-language publications; in addition, Google Scholar was reviewed. Search syntax was categorized into population, intervention, comparison, and outcome (PICO). Each category was assembled from a combination of Medical Subject Headings (MeSH Terms) as well as free-text words in simple or multiple conjunctions: ((Prosthodontics [Mesh]) OR (prosthetic treatment) OR (reconstructive therapy)) AND OR ) .Additional manual searches of the bibliographies of all full-text articles and related reviews selected from the electronic search were also performed. Furthermore, manual searching was conducted in the following journals: Journal of Prosthodontic Research, Journal of Prosthetic Dentistry, Clinical Oral Implants Research, International Journal of Oral Maxillofacial Implants, Clinical Implant Dentistry and Related Research, Implant Dentistry, and Journal of Implantology.Studies at all levels of evidence, except expert opinion;Articles published in English;Articles published in the last 5 years (up to 30 June 2021).Inclusion criteria for the studies were defined as follows:Review articles, letter to editors and case reports involving less than 5 cases;Animal studies;Full-text not available/accessible.Exclusion criteria for the studies were defined as follows:Two reviewers (S.B. and T.J.) independently screened the titles and abstracts that were identified in the searches according to the defined inclusion and exclusion criteria. If sufficient information could not be extracted from titles and abstracts, the full text was consulted. The full texts of potentially relevant articles were obtained and reviewed in detail by both reviewers, from which the final list of articles was selected for further analysis. Disagreements were resolved by discussion.Author(s), year of publication, country, study design;Total number of patients/datasets;Training/validation datasets;Test datasets;Aim of the study;AI application; andOutcome.The following information was collected from selected articles:http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (Accessed on 7 September 2021)) to assess the quality of the studies ;Not a study in the field of AI application in prosthodontics (n = 3);Not a clinical study (n = 1);Full text not available (n = 1).Missing information on AI technology .n = 7). Although automated detection of caries has been investigated in AI dental imaging diagnostics a few years ago, the use of AI technology in prosthodontics is (still) rare. Prosthodontics itself is a diverse and complex area of dental medicine and one that may benefit from the routine application of AI technologies. Long-term success relies on good prognosis of abutment teeth (and/or implants) in all facets of periodontal, endodontic, operative and reconstructive principles, and include patient-specific factors, such as load situation, personal and medical issues, and supportive care [The overall number of eligible studies investigating AI applications in prosthodontics was relatively low dentists in choosing appropriate removable prosthetic options . Such suThe combination of AI technologies in the field of prosthodontics could lead to a wide variety of novel options, such as AI systems for generating occlusal surface design for crowns accounting for existing intraoral wear facets, as automatic set-up designers for complete dentures, for determining the emergence profile in implantology, or in automatic framework designs for removable partial dentures . FinallyIn principle, there are no limitations to using the power of AI in prosthodontics. In many cases, however, it is (unfortunately) financial factors that trigger the development and standard implementation of new AI technologies in the most economically profitable areas\u2014and tend to prevent interesting dental applications because a market appears too small for the dental industry. Nevertheless, future developments and research on AI can be eagerly awaited.Although this seems to be very promising, the obstacles of AI systems should not be ignored. Based on this systematic literature search, the identified trials must be seen as pilot studies and experimental, and the technologies used in these studies are not yet suitable for everyday clinical routine in the focus of prosthodontics. At the moment, AI is mainly used in undergraduate dental education and for academic research. Improvements in the technology and user interfaces is needed before the techniques can be implemented into routine dental practice. Some intermediate steps still need to be developed to make AI attractive and helpful for its routine implementation. Beyond the technical possibilities, the cost\u2013benefit ratio and ethical aspects of the use of patient-specific data also need to be critically examined in future research on AI technology in (reconstructive) dentistry .While the number of studies reporting the use of AI in prosthodontics identified in this systematic review was relatively low (inclusion of seven out of sixteen full-texts), these studies reflect an honest overview of the latest developments in AI focusing on diagnostics, predictive measures, classification, and identification tools. Prosthodontics is the dental discipline with the greatest variance in terms of diagnostics and, in particular, treatment options. Therefore, it does not seem surprising that the results of this systematic review are comparably diverse and heterogeneous.In addition, dentistry is (still) lagging behind medicine in terms of routine use of AI technology. Nevertheless, AI applications in prosthodontics have the potential to open up a wide range of opportunities for clinicians and patients, and could be used as a supplementary future basic tool for collecting, processing, and organizing patient-related datasets to provide patient-centered, individualized, and personalized treatment. Possible applications of AI algorithms are very diverse in prosthodontics and one can eagerly await further research foci and developments.The step-by-step implementation of digital applications (in dentistry) is linked to the necessary technical development and is dependent on the flexibility of the users in everyday life. The willingness to learn new treatment protocols and to trust computerized applications has been proven as a strong negative driver for dentists . In addiA critical topic and crucial factor for the successful rehabilitation of complex prosthetic cases is the correct clinical definition of vertical and horizontal maxillo-mandibular relationships. AI technology could be used for automatic registering of jaw relationships based on radiological landmarks in cone-beam computed tomography. In this context, the configuration of virtual dental articulators could be synchronized with the radiological situation to simulate individual patient movements for treatment simulation and final fabrication of prosthetic reconstructions.The use of AI technologies in prosthodontics is conceivable in many ways (and absolutely desirable) from the clinicians\u2019 point of view, but not least the demand and the economic efficiency will decide whether the MedTech industry will push AI in prosthodontics as fast and to what extent."} +{"text": "ABSTRACT IMPACT: Using network analysis and a systems science lens, UTMB\u2019s Institute for Translational Sciences is able to quantify the evolution of REACH (its Community-Campus Partnership) as measured by the creation of new partnerships among member entities, promoting the translation and sharing of ideas and resources, and formalization of relationships among members. OBJECTIVES/GOALS: o Present how network analysis and systems science can inform evaluation of community-campus partnerships o Describe results from our experience with evaluating the REACH coalition o Summarize lessons-learned and likely improvements we are considering for our methodology METHODS/STUDY POPULATION: In 2016, we administered a network survey to core members of the Research, Education, and Community Health (REACH) coalition. The survey captured attributes about each organization, including size, populations served, etc. The survey also captured data on the relationships among these organizations, including joint meeting attendance, joint event planning, shared tangible resources, shared information, and formal legal agreements between organizations. These data were analyzed using network analysis methods. The survey was again repeated in 2018, and comparisons were made to evaluate how the network structure had evolved from 2016 to 2018. RESULTS/ANTICIPATED RESULTS: Joint meeting attendance was high in both 2016 and 2018; however, there was evidence of increased sharing of information and tangible resources in 2018. We also observed an increase in joint event planning among partnering agencies. Most strikingly, we observed that the number of formalized agreements between agencies more than doubled between 2016 and 2018. By measuring the evolution of our network of partners, we are able to document the evolution of a community-campus partnership over time. DISCUSSION/SIGNIFICANCE OF FINDINGS: Over the course of 2 years, the coalition signaled an increase in deeper collaborations beyond simply meeting together. The use of network analysis demonstrated utility and provided another dimension for evaluating the development of teams, partnerships, and coalitions."} +{"text": "Teaching points: Gastroduodenal intussusception is an infrequent cause of abdominal pain in children, for which a lead-point is nearly ubiquitous, which imposes endoscopic reduction as the first line of treatment. Figure 1a), in the axial plane at the level of the stomach body , and the pancreatic head showed multiple enhancing gastric polyps (arrows), along with intussusception (arrowheads) of the stomach within the proximal portion of the duodenum. There was no compromise of the gastroduodenal wall enhancement. The CT findings were confirmed on subsequent gastroduodenal endoscopy carried out for air insufflation, resulting in successful reduction of the intussusception.A 16-year-old girl presented in the emergency department afebrile with hypogastric abdominal pain, nausea, and vomiting. The patient was known to have Peutz-Jeghers syndrome (PJS) with multiple hamartomatous gastrointestinal polyps since the histological analysis of a 50 cm small bowel resection, which occurred at the age of four in the course of acute ileo-ileal intussusception. A contrast-enhanced abdominal computed tomography (CT) on coronal curved reformation through the stomach and duodenal axes resulting in gastroduodenal and ileo-ileal intussusception, and mucocutaneous pigmentation predominantly on the lips and around the mouth. The diagnosis of PJS is based on histological analysis of the polyps, family history of PJS, or mucocutaneous lesions [Patients with PJS present with recurrent and variable degrees of abdominal pain due to intestinal occlusion, infarction, or gastrointestinal bleeding caused by the endoluminal polyps . Our patUltrasound is the first modality of choice when assessing abdominal pain in PJS . In our As 95% of intussusception occurs in the small bowel, gastroduodenal intussusception is an extremely rare occurrence, even in patients with PJS . An unde"} +{"text": "The overall aim of ICare was to establish a novel, comprehensive and effective model of mental health service delivery. ICare encompasses mental health promotion, risk detection, disease and relapse prevention of common mental health disorders (CMHD) and guided self-help for eating disorder (ED) patients as well as caregivers of people with an ED delivered through a common online platform.This supplement consists of two parts. The first part summarizes current research on Internet-based treatment and prevention for some of the most CMHD. The second part of the supplement is dedicated to the ICare Stakeholder Survey.Part I\u2014Evidence: As an introduction to the topic, Taylor et al. present an overview of existing systematic reviews and meta-analyses on Internet-based interventions for the treatment of depression, anxiety, EDs and substance abuse. The authors identified important research gaps including the need for more evidence on how to increase engagement, on more tailored interventions for various populations and on interventions delivered by mobile phones. The next article by Buntrock et al. summarizes the evidence on economic evaluations of Internet- and mobile-based interventions for substance use disorders. The results regarding cost-effectiveness of these interventions are promising. However, the authors emphasize that more economic evaluations are needed. The article of D\u00edaz-Garc\u00eda et al. presents a systematic review on the theoretical adequacy, methodological quality and efficacy of Internet-based interventions to promote well-being and resilience. They found a tendency for larger effects of programmes with a clear assessment theory, which underlines the need of strong theoretical foundation of Internet-based interventions. Finally, Zeiler et al. and Nacke et al. present systematic reviews evaluating reach, adoption, implementation and maintenance of Internet-based interventions to prevent EDs in adolescents and adults, respectively. Both reviews revealed a lack of reporting of external validity indicators. Overall, the results of the articles in the first part of this supplement show that Internet-based interventions are feasible and effective adjuncts to face-to-face interventions in order to deal with the increased need for mental health promotion and treatment. However, they identified also a range of research gaps, the need for better theoretical foundation and the need for higher reporting rates for external validity indicators in research studies.Part II\u2014ICare Stakeholder Survey: In their introductory paper on the stakeholder survey, Nitsch et al. describe in detail the development of the overall design of the ICare stakeholder survey which followed a mixed-methods approach to collect data from a range of different stakeholders in the healthcare, university and school settings. The next three papers deal with the results of the stakeholder survey in the healthcare, the university and the school setting, respectively. The first of three articles by Kuso et al. presents stakeholders\u2019 perspectives regarding Internet-based interventions to prevent mental health disorders in adults implemented into healthcare systems in Austria, Germany, Switzerland and Spain. Irish et al. describe the results of the stakeholder survey regarding Internet-based interventions to prevent mental health disorders in students implemented in universities in Austria, Germany, UK, Spain, Switzerland and The Netherlands. Zeiler et al. report on the perspectives of key stakeholders in Austria and Spain on Internet-based interventions to prevent mental health problems implemented in schools. The last two articles shift the focus to guided self-help interventions in the context of the treatment of EDs, targeted either to individuals who currently meet diagnostic criteria and are on a waitlist for treatment(to bridge waiting time), or to carers of patients currently in treatment. The results are presented country-specific. The perspectives of stakeholders\u2019 views on self-help programmes for EDs patients and caregivers implemented in the healthcare system in Germany are presented by Schmidt-Hantke et al. and for the UK by Yim et al.To the best of our knowledge, this was the first comprehensive stakeholder survey focusing on Internet-based mental illness prevention which was conducted concurrently in several countries and various settings. Overall, 36 focus groups with representatives from the target groups of ICare interventions and 75 interviews with ED patients and carers and policymakers across the three settings and participating countries were conducted. Furthermore, 423 potential facilitators/enablers filled in an online questionnaire. The findings are in accordance with the existing literature regarding barriers and facilitators for dissemination and implementation of Internet-based treatment in the healthcare system,Following the outbreak of the Covid-19 pandemic, a significant increase in the prevalence of mental health disorders is to be expected,This project has received funding from the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No. 634757.Conflicts of interest: None declared."} +{"text": "Rhizobium-legume symbiosis. It is characterized by inverted tip growth of the plant cell wall, resulting in a tunnel that allows invasion of host cells by bacteria during the formation of the nitrogen-fixing root nodule. Regulation of the plant-microbial interface is essential for infection thread growth. This involves targeted deposition of the cell wall and extracellular matrix and tight control of cell wall remodeling. This review describes the potential role of different actors such as transcription factors, receptors, and enzymes in the rearrangement of the plant-microbial interface and control of polar infection thread growth. It also focuses on the composition of the main polymers of the infection thread wall and matrix and the participation of reactive oxygen species (ROS) in the development of the infection thread. Mutant analysis has helped to gain insight into the development of host defense reactions. The available data raise many new questions about the structure, function, and development of infection threads.The intracellular infection thread initiated in a root hair cell is a unique structure associated with Frankia Pssym33 gad walls B in the sym33-3) . In somesym33-3) . There wP. sativum symbiotically-defective mutant RisFixV (Pssym42), callose deposition (Rhizobium infection as part of the defense response. Another striking feature of RisFixV (Pssym42) was the encapsulation of ineffective bacteroids with de-esterified HG, as detected by JIM5 immunolabelling. This mutant demonstrates unique defense reactions for symbiotic mutants [The deposition of callose in plant cell walls is an important aspect of many processes associated with developmental physiology, pathogenesis, or stress. In the position C,D was a mutants .The process of tissue and cellular infection is accompanied by the differentiation of plant cells originating from the apical meristem. The differentiation of host cells in the nodule cortex is associated with the release of bacteria into the plant cell as organelle-like structures termed symbiosomes, which are still bounded by a plant membrane that is structurally equivalent to the plasma membrane .The exact mechanism triggering the transition of rhizobia from the extracellular space (apoplast) to intracellular existence within organelle-like symbiosomes surrounded by a plant membrane is not yet known, but it is associated with further remodeling of the host cell wall and cell membrane. In indeterminate nodules of temperate legumes, the release of rhizobia occurs from infection droplets that lack a covering of cell wall material ,236,259.Phaseolus sp., bacterial release occurs at the tips of short intracellular infection threads [Lupinus angustifolius L. showed that rhizobia bud off from infection threads and are enclosed in membranes of plant origin [Sometimes, for example, in threads . A studyt origin . The relt origin .Presumably, the release of bacteria occurs due to the absence of a cell wall in the infection droplet and the possibility of close contact between the plasma membranes of the plant and rhizobia ,197,263.BacA controls the modification of the bacterial cell wall, including the development of Lipid -A derivatives with long-chain fatty acids [On the part of rhizobia, the gene ty acids . During ty acids ,268, whity acids . Evidencty acids .Senescence of nodule tissue is the final stage of symbiosis. There is autolysis of infected cells, and the nutrients stored in the nodules are recycled by the host plant . ProximaThe extent of nodulation and the efficiency of symbiotic nitrogen fixation can be influenced by environmental conditions, such as temperature, humidity, aeration, pH, salinity, soil structure, imbalance of nutrients in the soil . Other factors affecting nodulation include diseases and insects, as well as anthropogenic influences in the form of fertilization, soil and water pollution with pesticides, chemicals, and heavy metal ions ,276. EnvMost plants have two types of tip-growing cells: Pollen tubes and root hairs. Infection threads represent a third type of tip growth for the deposition of cell wall material. The infection thread is an inwardly growing tube in which polar growth is topologically inverted relative to the tip growth of root hairs or pollen tubes. The following model summarizRhizobium bacteria and altered transcriptional activity in the host cell nucleus. Among other things, this leads to the synthesis and deposition of new proteins in the microdomains of the plasma membrane of the infection thread. Vesicles derived from the ER and GA fuse with the plasma membrane at the tip of the infection thread, releasing their contents into the wall and extracellular matrix. This process is apparently controlled by a range of proteins, including: PI3K, GmVAMP721d, EXO7OH4, PvNod22. Targeted secretion from vesicles is the driving force behind the growth of the infection thread. Glycoproteins, proteins, and polysaccharide components of the infection thread matrix include the following: AGPEs, HRGPs, ENOD2/11, LOX, DAO and RG-II. In addition, H2O2 probably plays a role in cross-linking AGPEs and changing the biophysical properties of the infection thread matrix. Vesicles derived from the GA also contain cellulose synthases, xyloglucan and pectins . HG is synthesized in a highly esterified methyl form and may be transported along with PME/PMEI complexes (pectin methylesterase/pectin methylesterase inhibitor). All these components and other cell wall remodeling enzymes are released into the apoplast.The initiation and growth of the infection thread are the consequence of signal exchange with the infecting 2+ ions, thus increasing its rigidity. RG-I is present in the infection thread wall, and RG-II is also present in the form of dimers with the borate ion. The wall also contains extensins, AGPs, and expansins. Additionally, callose and phenolic compounds such as suberin can accumulate as part of defense reactions in response to an ineffective symbiosis.In the nascent wall of the infection thread, cellulose synthases are incorporated into the membrane and deposit the crystalline cellulose. At this stage, highly methyl-esterified HG is the major component of the infection thread wall. At its mature stage, the main polysaccharide components are: cellulose, xyloglucan, and HG with varying degrees of methyl-esterification. HG having a low level of methyl-esterification binds with CaMany enzymes are involved in the modification and degradation of the cell wall during the growth of an infection thread and the formation of an infection droplet. These include: MsPG3, LjNPL, MtPER, and endo-\u03b2-1,4-glucanases. Polar growth of the infection thread is mediated by the actin cytoskeleton, and the alignment of microtubules creates a constraining tunnel for infection thread growth. Within the lumen, bacterial polysaccharides play an important role: EPS, KPS, LPS, cyclic \u03b2-glucan, RosR, and Rhizobia-induced peroxidases (Rip1-10).Following the release of bacterial cells from the infection droplet, several plant proteins are associated with the symbiosomal membrane. These include: Lectin-like glycoprotein (PsNLEC1), synaptotagmin (MtSyt1/2/3), syntaxin (MtSYP132), inositol-containing phospholipid (JIM18 antigen), and AGP with a GPI anchor (JIM1 antigen). Within the symbiosome compartment, rhizobial cells differentiate into nitrogen-fixing bacteroids: They lose their exopolysaccharide capsule, and the structure Lipid-A and O-antigen groups of LPS becomes modified, partly as a result of the action of the protein BacA.From an evolutionary perspective, the nature of the legume-rhizobial symbiotic interface has become progressively more intimate and complex. On the one hand, it incorporates novel aspects of cellular morphogenesis, in particular the infection thread and the symbiosome compartments. On the other hand, there is a precise system for suppression of host defense responses. As with the other forms of tip-growth observed in root hair cells and pollen tubes, growth of the infection thread is due to the targeted deposition of cell wall and cell membrane material at the apex. However, there is an important distinction. Whereas the extension of root hairs and pollen tubes is driven by cell turgor, the driving force behind the growth of an infection thread is the synthesis and directed secretion of the extracellular matrix material into the lumen of the infection thread and the division of bacteria inside. Polar growth of the infection thread requires a high degree of coordination between many cellular and extracellular processes, including calcium dynamics, apoplastic reactive oxygen species, the cytoskeleton, and vesicular transport.The cell wall that surrounds the infection thread is a dynamic structure that performs both structural and defense functions. While the localization and distribution of the main pectins of the infection thread wall have been recently studied , the rolExperiments designed to investigate these questions will provide new insights into how an infection thread grows. Furthermore, these studies will help to elucidate the more general patterns of plant cell wall development during growth and differentiation. New probes targeting cell wall components will permit a more detailed analysis of the biochemistry and biomechanics of the cell wall of the infection thread. A major problem in studying the infection thread is that it is a dynamic and continually changing system. Its structure at an early stage in a root hair or root cortical cell may be very different from that in a host cell embedded deep in the tissue of a maturing nodule. These differences could affect the remodelling of the cell wall . The chaRhizobium is the relationship between intercellular and intracellular modes of infection. An interesting model has recently been developed based on interaction of L. japonicus with different strains capable of infecting the host plant either via intracellular or via intercellular modes [Rhizobium infection and endomycorrhizal symbiosis [One of the intriguing questions regarding the infection of legume tissues by ar modes . Furtherar modes and the ymbiosis ,283 clea"} +{"text": "The need for widely usable bioactive lipids and natural antioxidants continues to grow. Methods used for oil extraction may alter minor constituents that have functional properties and contribute to oil stability. In recent years, consumer demand for cold pressed oils as an alternative to conventional products has increased. This is probably due to the perception of these oils as natural, nutritional, and safe food products with better nutritive and healthy properties.Cold pressed oils are easy to obtain. The process does not involve heat treatment or solvent extraction. Therefore, the cold pressing technique results in a product that is free of organic solvents. Mechanical pressing does not require much energy and meets well the needs of small- and medium-sized companies. Cold pressed oils are promoted as specialty oils and are usually available on the market at a higher price. Cold pressed oil products are reported to contain pro- and anti-oxidative compounds.In recent years, consumption of cold pressed oils has been increasing. The international market already includes numerous cold pressed oils . However, due to high prices of cold pressed oils, they are exposed to adulteration with cheaper and lower-quality refined oils of vegetal origin. Several strategies have been applied to monitor and control the authenticity of cold pressed oils for reasons of both human health and demand, as well as concern for controlling product quality in industrial laboratories. Among these, new frontiers are open toward the use of rapid analytical methods and chemometrics.This Research Topic aims to report on recent advances in cold pressed oils as specialty oils, mainly focusing on their composition, physicochemical characteristics, organoleptic attributes, nutritional quality, oxidative stability, food applications, and functional and health-promoting traits.The main explored topics are as follows: (i) evaluation procedures and quality attributes , yield, quality parameter, and physicochemical properties, sensory and color attributes; (ii) compounds of nutritional and nutraceutical characters in cold pressed oils; (iii) oxidative stability; (iv) impact of cold technologies: extracting and processing parameters; (v) storage and shelf life evaluation; (vi) adulteration and authenticity; (vii) cold pressed cake as functional and value-added product; (viii) consumer perception; (ix) health benefits; (x) safety aspects and potential adverse reaction evaluations; (xi) conventional and innovative fields of applications; (xii) food composition database and dedicated databases; (xiii) regulatory challenges; and (xiv) current and future applications and research needs.Fratianni et al. described the fatty acid composition, antioxidant, and in vitro anti-inflammatory activity of five cold pressed Prunus seed oils and their anti-biofilm effect on pathogenic bacteria. Another example is given by Wang et al. who compared the antioxidant and antibacterial activities of camellia oil from Hainan with camellia oil from Guangxi, olive oil, and peanut oil. Gharby and Charrouf reviewed the chemical composition, extraction process, and quality control of argan oil.Tsao et al. on the application of OXITEST for the prediction of shelf-lives of selected cold pressed oils. Results first revealed that the UFA (Unsaturated Fatty Acid) portion was partially correlated with the shelf-lives of selected expeller-pressed seed oils as estimated by the OXITEST. Benincasa et al. reported the identification of phenolic compounds in spray-dried olive mill wastewater; the study showed that the use of dehumidified air as a drying medium, with the addition of maltodextrin, results an effective way to obtain a phenol-rich powder.It is worth mentioning the study of All the authors listed made a substantial, direct, and intellectual contribution to the article and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."} +{"text": "Pneumonia is the leading cause of under-five child deaths globally and in Bangladesh. Hypoxaemia or low (<90%) oxygen concentration in the arterial blood is one of the strongest predictors of child mortality from pneumonia and other acute respiratory infections. Since 2014, the World Health Organization recommends using pulse oximetry devices in Integrated Management of Childhood Illness (IMCI) services , but it was not routinely used in most health facilities in Bangladesh until 2018. This paper describes the stakeholder engagement process embedded in an implementation research study to influence national policy and programmes to introduce pulse oximetry in routine IMCI services in Bangladesh.Based on literature review and expert consultations, we developed a conceptual framework, which guided the planning and implementation of a 4-step stakeholder engagement process. Desk review, key informant interviews, consultative workshops and onsite demonstration were the key methods to involve and engage a wide range of stakeholders. In the first step, a comprehensive desk review and key informant interviews were conducted to identify stakeholder organisations and scored them based on their power and interest levels regarding IMCI implementation in Bangladesh. In the second step, two national level, two district level and five sub-district level sensitisation workshops were organised to orient all stakeholder organisations having high power or high interest regarding the importance of using pulse oximetry for pneumonia assessment and classification. In the third step, national and district level high power-high interest stakeholder organisations were involved in developing a joint action plan for introducing pulse oximetry in routine IMCI services. In the fourth step, led by a formal working group under the leadership of the Ministry of Health, we updated the national IMCI implementation package, including all guidelines, training manuals, services registers and referral forms in English and Bangla. Subsequently, we demonstrated its use in real-life settings involving various levels of stakeholders and worked alongside the government leaders towards carefully resuming activities despite the COVID-19 pandemic.Our engagement process contributed to the national decision to introduce pulse oximetry in routine child health services and update the national IMCI implementation package demonstrating country ownership, government leadership and multi-partner involvement, which are steppingstones towards scalability and sustainability. However, our experience clearly delineates that stakeholder engagement is a context-driven, time-consuming, resource-intensive, iterative, mercurial process that demands meticulous planning, prioritisation, inclusiveness, and adaptability. It is also influenced by the expertise, experience and positionality of the facilitating organization.Our experience has demonstrated the value and potential of the approach that we adopted for stakeholder engagement. However, the approach needs to be conceptualised coupled with the allocation of adequate resources and time commitment to implement it effectively. Pneumonia is the leading cause of childhood mortality, accounting for around 16% of 5.2 million under-five deaths globally . In addi2) [Hypoxaemia, defined by low (<90%) oxygen saturation in the arterial blood, is common among children with pneumonia and is one of the strongest predictors of mortality caused by pneumonia and other lower acute respiratory tract infections -12. Earl2) . In high2) . However2) -16.Bangladesh was one of the sites in the Multi-Country Evaluation of IMCI coordinated by WHO . Based oEngaging a wide range of stakeholders is a key step for ensuring the relevance of research studies and improving the utilisation of research findings in local health systems settings ,25. As aStep-1:Identification and prioritisation of stakeholders for subsequent sensitisation, involvement and engagement. Step-2:Sensitising the majority of stakeholders regarding the context, rationale, importance and process of the proposed research to build interest, confidence and trust. Step-3:Involving key stakeholders in planning, ensuring agreement regarding the implementation process and solidifying commitments for shared responsibilities. Step-4:Engaging the stakeholders at every stage of design, development, implementation and evaluation.Stakeholders are individuals, organisations, or communities that can influence or are affected by a project's process and outcomes, research or policy . StakehoIn Bangladesh, health services are provided by two directorates under the Ministry of Health and Family Welfare. They are the Directorate General of Health Services and Directorate General of Family Planning. Each directorate has a dedicated programme for child health, which manages the child health services, including IMCI services in Bangladesh. In addition, several other programmes are also related to child health services. Besides the government programmes, several development partners and professional societies support the Government of Bangladesh in managing and implementing child health services, including IMCI services. The National Newborn Health and IMCI Programme under the Directorate General of Health Services of the Ministry of Health and Family Welfare is responsible for coordinating with all partners and ensuring the delivery of IMCI services in Bangladesh.First, comprehensive desk review was conducted on IMCI related documents and eight key informant interviews to identify national and district level stakeholders related to IMCI implementation in Bangladesh , district level family planning manager , all (five) sub-district health managers and all sub-district level family planning managers . In addition, managers from the National Newborn Health and IMCI Programme attended the event. They presented the importance of identifying hypoxaemia in pneumonia assessment and classification and discussed the operational feasibility of introducing pulse oximetry in real-life settings.Subsequently, we organised five such sensitisation workshops in each sub-district, with 14 participants in each workshop, including IMCI service providers such as doctors, nurses and paramedics and their respective supervisors. For each sub-district level workshop, the respective sub-district health managers gave the keynote presentation.Lastly, 71 enlisted national and local level NGOs actively working in Kushtia district were identified, of which 21 had strong community acceptance and health-related activities. We organised another sensitisation workshop with representatives from these 21 organisations. The district health manager gave the keynote presentation, and all the sub-district managers contributed to the subsequent discussions. All participating NGO partners agreed to raise awareness regarding pneumonia and hypoxaemia and promote appropriate care-seeking practices in the local communities.Like the previous sensitisation phase, we organised workshops at the national, district, and sub-district levels to involve stakeholder organisations representing the high power and high-interest group, discuss a strategy, and develop a mutually agreed plan for introducing pulse oximetry in routine IMCI services of Bangladesh. At the national level, the Programme Manager of the National Newborn Health and IMCI Programme chaired the workshop. All the participants discussed and developed a national action plan to introduce pulse oximetry in routine IMCI services in Bangladesh. The roles of all key stakeholder organisations were clarified and defined in this comprehensive action plan. The National Newborn Health and IMCI Programme agreed to lead this process, and WHO, UNICEF, Save the Children and icddr,b committed to providing technical assistance and implementation support. The National Newborn Health and IMCI Programme also decided to update the National IMCI Implementation Package based on the updated WHO recommendations, including introducing pulse oximetry in pneumonia assessment and classification. This National IMCI Implementation Package consists of guidelines, registers, referral forms, reporting forms, job aids, monitoring checklist, list of essential equipment, medicine and logistics and training manuals. It was also decided that the development partners will be initially responsible for the procurement and supply of pulse oximetry devices in some demonstration facilities. The National Newborn Health and IMCI Programme declared to include pulse oximeters in the national procurement plan if the demonstration is successful.A small working group was formed with technical experts from each stakeholder organisation with high power-high interest to update the implementation package. The small working group recommended assessing the feasibility of implementing the updated implementation package (including pulse oximetry) through an implementation research study. icddr,b volunteered to lead this implementation research study in Kushtia district. The working group members identified the evidence gaps and finalised key research questions for the implementation research through a consultative process. Further, at this workshop, it was also decided that the experience gathered through this implementation research would assist the Government of Bangladesh in taking evidence-based decisions for a national scale-up.A planning workshop was organised in Kushtia district headquarter, which was chaired by the district health manager and attended by all sub-district health managers. At this workshop, the participating stakeholders decided that the implementation research would include all types of health facilities providing IMCI services. Hence, the Kushtia District Hospital, all five Upazila Health Complexes and one Union Health and Family Welfare Centre from each sub-district were selected as demonstration sites for the implementation research study. A district-level action plan was jointly developed outlining the roles of different district level stakeholders and the key activities, including training, distribution of pulse oximetry device, revised IMCI registers, referral forms and reporting forms, supportive supervision visits and assessments. Subsequently, a planning workshop was organised in each sub-district with the supervisors of IMCI service providers. The respective sub-district managers chaired this event and shared guidance on developing a sub-district level implementation plan for introducing pulse oximetry. A preparatory and planning meeting followed in each demonstration facility with IMCI service providers, respective supervisors, and facility managers, leading to the finalisation of a facility-specific implementation plan (with a timeline) to introduce pulse oximetry minimally impacting their routine services and existing practices.In this stage, National Newborn Health and IMCI Programme and icddr,b worked closely with the high power-high interest stakeholders on the following steps to update the IMCI implementation package and implement it in the demonstration facilities in real-life settings.Formation of a working group: The Line Director of Maternal, Newborn, Child and Adolescent Health Programme of the Ministry of Health and Family Welfare formed a small working group with 13 IMCI experts representing the five high power-high interest groups to review and update the National IMCI Implementation Package and shared their feedback.Afterwards, the updated training package was pre-tested among IMCI service providers, including doctors, nurses, and paramedics. The National Newborn Health and IMCI Programme organised the training, the national master trainers facilitated the sessions, and icddr,b conducted assessment and evaluations. A total of 40 doctors, 91 nurses and 67 paramedics received training in 10 batches. We collected feedback from the IMCI providers on the National IMCI Implementation Package, including the training manuals, registers, job aids and reporting forms. Finalisation of the National IMCI Implementation Package: Following the training workshops with master trainers and IMCI service providers, the working group updated the national implementation package based on their feedback. Then National Newborn Technical Working Committee for Newborn Health and the National IMCI Technical Working Committee, the highest-level technical committees regarding newborn and child health in Bangladesh, reviewed the updated package and shared feedback. The National IMCI Implementation Package was finalised after incorporating their feedback and inputs.Incorporation of the use of pulse oximetry and hypoxaemia in the national health service records: Over a series of six consultative workshops, the National Newborn Health and IMCI Programme convinced the Management Information System (MIS) department of the Directorate General of Health Services to update the national IMCI dataset based on the updated monthly reporting form (including updated pneumonia classification and hypoxaemia status). icddr,b provided technical assistant and secretarial support in organising these events.Involving national-level stakeholders in the implementation research: A co-design and co-creation approach was adopted to develop the implementation research protocol. icddr,b led the process and engaged the National Newborn Health and IMCI Programme and other stakeholder organisations representing the high-power and high-interest group to prioritise research questions and finalise the research design, data collection methods, and data collection instruments. Additionally, one of the Deputy Programme Managers of the National Newborn Health and IMCI Programme joined the research team as a Co-Investigator.Local-level involvement in the implementation research: A district advisory committee was formed to guide the implementation research study in Kushtia-district. The district health manager chaired the committee, and all the sub-district level health managers were included as members. First, the advisory committee was oriented regarding the research questions and study design. Later, the committee developed a macro plan to introduce pulse oximetry in the selected facilities and conduct quantitative and qualitative assessments as outlined in the research protocol. Subsequently, a planning meeting was organised in each facility with respective IMCI service providers and their supervisors to review the macro plan and develop a micro plan with a timeline. A dissemination meeting was organised with the district advisory committee after the baseline and each round of data collection. icddr,b provided technical assistance and secretarial support throughout the process.Resuming study activities during the COVID-19 pandemic: The Government of Bangladesh declared a nationwide lockdown in the last week of March 2020 to prevent the surge of COVID-19 infections and deaths. Unfortunately, all the implementation research-related activities were suspended due to the strict restrictions imposed during the lockdown period. In August 2020, the government started to reduce restrictions. The National Newborn Health and IMCI Programme issued an official order to resume the research activities with appropriate infection prevention and control measures. A series of meetings were organised in Kushtia-district with the district health manager and sub-district health managers to resume the suspended activities and revise the implementation plan (both macro plan and micro plan) accordingly.Desk Review: A total of 37 documents with approximately 2507 pages were reviewed to identify the stakeholders and update the National IMCI Implementation Package. It required around 120 person-days of effort by medical graduates with basic IMCI training.Resource person interview: A total of eight interviews and a group discussion was organised with IMCI experts to identify and prioritise the stakeholder organisations, requiring ten person-hours for interviewing and an additional 30 person-hours for transcribing and analysis.Document development, editing and formatting: The National IMCI Implementation Package containing 24 documents with 1685 pages were updated, which required approximately 140 person-days of reviewing, editing and formatting to prepare the final versions.Workshops: At the national level, 30 workshops were organised to sensitise (step 2), involve (step 3) and engage (step 4) the stakeholders, requiring approximately 416 person-days of involvement by IMCI experts and stakeholders. In addition, about 42 person-days of investment was needed from icddr,b for taking preparation and organising the events. Furthermore, around 30 person-days was required to prepare and approve the meeting notes for official documentation.At the district level, 45 meetings were organised, requiring approximately 183 person-days of involvement by IMCI service providers, 86 person-days by their clinical supervisors, and 101 person-days by district, sub-district and facility managers.Travel and transport: To sensitise (step 2), involve (step 3) and engage (step 4) stakeholders at the district level, extensive travel and transport were required. A total of 97 person-days of travel and transportation were needed from central-level staff and 312 person-days from local-level staff to organise and participate in the stakeholder engagement related eventsStep 1-Identify: This process began in October 2018 and continued till December 2018.Step 2- Sensitise: At the national level, the sensitisation process started in January 2019 and continued till the end of that year, while at the district level, the sensitisation activities went on from October 2019 till February 2020.Step-3-Involve: At the national level, the involvement process took place in June 2019 and at the district level, the process took place in March 2020.Step 4-Engage: The national-level engagement process started in June 2019 and ended in January 2021. The district-level engagement process began in December 2020 and ended in July 2021.2 assessment for improving pneumonia assessment, classification, and management. As a result, the Government of Bangladesh decided to introduce pulse oximetry in routine IMCI services in Bangladesh.The Government of Bangladesh and all the key stakeholders acknowledged the importance of identifying hypoxaemia through SpOThe National Newborn Health and IMCI Programme formed a national-level working committee with high power-high interest stakeholder organisations related to IMCI implementation in Bangladesh. This high-level working committee updated the National IMCI Implementation package including the chart booklet, register, referral form, reporting form, monitoring checklist and training manuals and incorporated specific recommendations to use pulse oximetry in relevant sections. Further, three hypoxaemia related indicators were included in the national IMCI data set in DHIS2. The Government of Bangladesh trained 4872 IMCI service providers from across the country based on the updated National IMCI Implementation Package.The Government of Bangladesh decided to scale up the use of pulse oximetry in routine IMCI services in a phased manner. As a result, the National Newborn Health and IMCI Programme revised its existing plan and decided to procure pulse oximetry devices for the IMCI corners in approximately 200 Upazila health complexes. In the next phase, the National Newborn Health and IMCI Programme is planning to procure pulse oximetry devices for the remaining of the IMCI corners in the Upazila Health Complexes (approximately 250) and other union-level facilities (approximately 5000). Additionally, UNICEF has committed to support the Government of Bangladesh\u2019s national scale-up endeavour by introducing pulse oximetry in eight districts. icddr,b has committed to support in two districts, and Save the Children in one district. Moreover, WHO has supported the government by printing the updated IMCI registers for all facilities..We present the key learnings from the stakeholder engagement activities based on the SWOT analysis approach ,37. The Context-driven: Our implementation research study primarily aimed to influence the national policy and programmes. Based on the context and prior experience, we adopted a framework with four steps for stakeholder engagement and prioritised only the high power-high interest stakeholder organisations. The framework guided the whole process and all related activities, and the prioritisation helped maximise the use of limited resources. Therefore, any implementation research study aiming to engage stakeholders need to adapt and modify the framework based on the objective and context.Country ownership, government leadership and multi-partner involvement: The Government of Bangladesh demonstrated leadership in forming and leading the national working group, chairing the workshops, developing the strategic plans, and bringing multiple partners together for building national consensus on introducing pulse oximetry in routine IMCI services in Bangladesh. All the major non-government organisations and development partners related to IMCI implementation in Bangladesh committed to using the updated National IMCI Implementation Package in their respective health system strengthening initiatives.Expertise, experience and relationships of the facilitating organisation: The technical expertise and experience of icddr,b in the introduction and scale-up of IMCI services in Bangladesh and pre-existing relationships with other high power-high interest stakeholder organisations substantially contributed to the identification, sensitisation, involvement, and engagement of other high power-high interest stakeholder organisations. Moreover, the communication, and organising skills of icddr,b contributed to facilitating the stakeholder engagement process efficiently. Therefore, the positionality of implementing organisations needs to be considered before adopting a particular approach for engaging stakeholders.Time-consuming: It took more than two and a half years to implement the stakeholder engagement related activities and achieve the objective of incorporating the use of pulse oximetry in national policy and programme. Numerous workshops were organised based on the availability of all high power-high interest stakeholders, which was difficult considering their busy schedules, especially during ongoing COVID-19 pandemic. Extensive deskwork and preparations were necessary before organising these workshops, which called for several days or weeks of preparation. Hence, engaging the stakeholders effectively is time-consuming and will require patience and commitment by the facilitating organisation.Resource-intensive: The initial stage involved reviewing a significant number of documents to identify stakeholders and update the National IMCI Implementation Package, which required a substantial amount of person-time involvement of project staff. In addition, organising workshops at national, district and sub-district levels required numerous person-days of involvement from IMCI experts, managers, service providers and project staff. It also required extensive travelling by the project staff. Since stakeholder engagement is a resource-intensive process, it is important to have a planning and specific budgetary allocation for stakeholder engagement at the outset of any project.Iterative: Reviewing, editing, and formatting several lengthy documents were essential for updating the National IMCI Implementation Package. Some of these documents required numerous rounds of editing and formatting to address and incorporate the feedback of all the stakeholders across the national, district and sub-district levels before finalisation. For example, IMCI chart booklet had 23 rounds of iteration and IMCI registers had 19 rounds of iteration before finalisation. Hence, the facilitating organisation need to have dedication and attention to details to effectively steer the stakeholder engagement process.Mercurial: The power-interest matrix of the stakeholders does not stay static and could change at any given time. For example, during the engagement process, one of the stakeholders with high power and low interest unexpectedly turned into a high power-high interest actor and started posing a risk to the process. Therefore, some part of the stakeholder engagement process was adapted based on the agenda of that particular stakeholder. In addition, during the stakeholder engagement process, there can be changes in leadership positions. For example, the National Newborn Health and IMCI Programme manager was changed twice, and the district health manager was changed three times during the engagement process, owing to administrative transfers. It required investing additional time and efforts to sensitise the new stakeholders and garnering their active buy-in to introduce pulse oximetry in routine IMCI services. Hence, stakeholder engagement is an adaptive process and will require flexibility in revising, updating and changing the plan based on the context and circumstances.COVID-19 pandemic- general awareness regarding hypoxaemia: The COVID-19 pandemic has raised awareness among the health care provider and care receiver for using pulse oximetry in measuring the oxygen saturation level and assessing the severity of pneumonia. This opportunity has facilitated the implementation process more easily.COVID-19 Pandemic- lockdown and restrictions: The stakeholder engagement related activities and plans required extensive modification and revision due to the COVID-19 pandemic. During the first lockdown period between March and August 2020, all project-related activities were suspended. The team advocated with the National Newborn Health and IMCI Programme to resume project activities after the COVID-19 related restrictions were eased.Other national and programme priorities: The engagement process and project-related activities were also interrupted by unanticipated events, such as implementing the national Measles-Rubella campaign, which kept the district and sub-district health managers and IMCI service providers occupied during February and March 2021. Therefore, the potential impact of an emerging threat on the overall outcome and timeline of the stakeholder engagement process must be acknowledged and should have the flexibility of modifying the plan to take course corrective measures.Our experience has demonstrated the value and potential of the approach that we adopted for stakeholder engagement. Our engagement process contributed to the national decision to introduce pulse oximetry in routine IMCI services and update the national implementation package, which are steppingstones towards scalability and sustainability. However, our experience also reveals that stakeholder engagement is a context-driven, time-consuming, resource-intensive, iterative, mercurial process that demands planning, prioritisation, inclusiveness and adaptability. It is also influenced by the expertise, experience and positionality of the facilitating organisation. However, the approach needs to be conceptualised coupled with the allocation of adequate resources and time commitment to replicate its impact and implement it effectively in other settings."} +{"text": "In 2010, the University of Utah Gerontology Interdisciplinary Program first offered GERON 5240/6240: Aging and the Arts. This course was developed to enrich program curricula by addressing a gap in content specific to the arts and humanities. The purpose of this presentation is to focus on identifying the opportunities and challenges experienced teaching this course over the past decade. Opportunities will highlight competency mapping, internal and external partnerships, the benefits of bridging disciplines, and innovation in teaching and problem-solving. Challenges experienced include addressing various needs , tuition differentials, and varying levels of enrollment. A stand-alone course is one method of increasing humanities, arts, and cultural gerontology within curricula. It has the potential of enhancing student interest in gerontology while also demonstrating how the arts and humanities can improve work across disciplines."} +{"text": "Ukraine has an extensive experience on creating and maintaining National Medical Networks.A variety of examples include:The National Register of the persons suffered from the Chernobyl disaster: Net of the Sanitary and Epidemiological Service of the Ministry of Health.The National Medical Network for monitoring oncology patients: this links Regional Oncology Dispensaries with Institute of Oncology.Ukraine has a membership to \"EuroTransplant\" and National Medical Network in this effort has linked Regional Centres with the National Informational Centre on Transplantation.Regional databases from Regional Venereologic Dispensaries, used for monitoring diseases, have been extended to include cases of AIDS.The Telemedical Cardiology Centre in Kharkiv, with trans-telephone ECG. All equipment, including portable ECG amplifiers and modems, is developed in the Ukraine.Teleconsulting Medical Centres, in Kiev, for the analysis of MRI images.The centre \"Patholog\", in which oncologists - cytologists carry out work.The Ukrainian Association of Computer Medicine (UACM) has created (http: //www.uacm.cit-a.net) WWW- server , which has become a nucleus of the Corporate medical network permitting to exchange the information to 78 institutional members and over 900 individual members. The UACM has created affiliate Web - EHTO-UKRAINE server on national language (http://www.ehto-ukr.cit-ua.net). Ukraine took part in the \"Telemedecine Medical Care Networks within the Baltic Region\" programme. Also, Ukraine started the Ukrainian- American project on the monitoring of birth defects.The National Telematics Medical Corporate Network 'UkrMedNet' is under construction on the basis of existing the HealthNet and some other autonomous medical networks, with the newest of telecommunication technologies, used in Internet. This project also envisages the integration of all existing separate medical nets, universities and R&D institutes into one 'UkrMedNet', as well as the creation of a common informational space and its integration into the European one.'UkrMedNet' has a three-level structure. The first level consists of the National and four Inter-Regional nodes, which have a similar structure and service 5 or 6 Districts. All Inter- Regional nodes are directly connected to: a) National node and b) one of Inter-Regional ones. Such connection layout ensures the \"doubling\" of the connections of the first level nodes. The second level is formed on the basis of the District Healthcare Departments. Nodes are connected to the nearest Inter- Regional node. They ensure connection to the net of medical organisations located in the district. The third level is Regional nodes and end users. They are connected to the District nodes.The goal of the \"UkrMed- Net' is to supply an infrastructure for all medical networks and Telemedicine Centres in Ukraine. It accelerates the integration of the country into the world informational space."} +{"text": "Occupational statements on death certificates of 2,457 males aged 25-64 who died from bladder cancer in selected coastal and estaurine regions of England and Wales during 1965-1980 were studied. Excess mortality was found for deck and engine room crew of ships, railway workers, electrical and electronic workers, shoemakers and repairers, and tobacco workers. An excess of cases also occurred among food workers, particularly those employed in the bread and flour confectionary industry or involved in the extraction of animal and vegetable oils and fats. Use of a job-exposure matrix revealed elevated risk for occupations in which most workers were exposed to paints and pigments, benzene and cutting oils."} +{"text": "During 1982\u20131992, the Maternal and Child Health Family Planning (MCH-FP) Extension Project of International Centre for Diarrhoeal Disease Research, Bangladesh , in partnership with the Ministry of Health and Family Welfare (MoHFW) of the Government of Bangladesh (GoB), implemented a series of interventions in Sirajganj Sadar sub-district of Sirajganj district. These interventions were aimed at improving the planning mechanisms and for reviewing the problem-solving processes to build an effective monitoring system of the interventions at the local level of the overall system of the MOHFW, GoB.The interventions included development and testing of innovative solutions in service-delivery, provision of door-step injectables, and strengthening of the management information system (MIS). The impact of an in-built monitoring system on the overall performance was assessed during the period from June 1995 to December 1996, after the withdrawal of the interventions in 1992.The results of the assessment showed that Family Welfare Assistants (FWAs) increased household-visits within the last two months, and there was a higher use of service-delivery points even after the withdrawal of the interventions. The results of the cluster surveys, conducted in 1996, showed that the selected indicators of health and family-planning services were higher than those reported by the Bangladesh Demographic and Health Survey (BDHS) 1996\u20131997. During June 1995-December, 1996, the contraceptive prevalence rate (CPR) increased by 13 percentage points (i.e. from 40% to 53%). Compared to the national CPR (49%), this increase was statistically significant (p < 0.05).The in-built monitoring systems, including effective MIS, accompanied by rapid assessments and review of performance by the programme managers, have potentials to improve family planning performance in low-performing areas. Inadequate basic management skill among health teams at the implementation level is one of the main constraints in providing primary healthcare (PHC) in developing countries . LiteratPathfinder International, a Rural Service Delivery Partnership (RSDP), was a part of the National Integrated Population and Health Programme (NIPHP) of the MoHFW, GoB. The RSDP collaborated with the University of North Carolina (UNC) at Chapel Hill, United States of America (USA), to introduce a local-level monitoring system through an action-plan intervention for strengthening team work and developing the competence of health and family-planning managers and frontline supervisors at the levels of sub-district and below. The RSDP complemented the government efforts to increase the accessibility and use of the MCH-FP programme by rural families in the context of the NIPHP . The actIn Bangladesh, the delivery of health and family planning services for 300 000 rural populations is coordinated from the sub-district (upazila), the lowest administrative structure with substantial responsibilities for planning and implementation of all development activities in rural areas . The DirThe MCH-FP Extension Project , in collaboration with the MoHFW introduced a local-level monitoring system during 1982\u20131992 in Sirajganj for improving the management capability where the programme managers had reviewed the progress of the performance of service providers on a few selected indicators from monthly service statistics using the MIS in various meetings. The FWA Register was designed as a longitudinal record keeping system for the FWA. Under the leadership of MIS Unit of the DFP, it provided a foundation for the monitoring of FWA activities through supervisory field-visits [The study was conducted to assess the impact of an in-built monitoring system on the sustainability of a few selected indicators of MCH-FP after the withdrawal of the interventions.A cross-sectional study design was followed. Both quantitative and qualitative methods were used for collecting data on selected indicators. A rapid survey methodology was developed to provide administrators with quick information on problems faced at the community level. The cluster sampling procedure has been used throughout the world in immunization surveys. The EPI (Expanded Programme on Immunization) 30-cluster rapid assessment survey was used as the quantitative method for collecting data on selected indicators. Multi-stage, simple random sampling was used \u2013 one in July 1995 and the other one in December 1996 \u2013 in order to minimize the sample size required. A list of villages of all unions (one sub-district consist 8\u201310 unions having average population of 25 000\u201330 000) was used as a sampling frame. Twenty villages were selected, covering all the unions of the sub-district. Selection of the number of villages from each union was proportional to the size of the union. A cluster of 30 MWRA from each village was selected that yielded a sample of 600 MWRA for interview. Female interviewers received seven days' intensive training on data collection using various research methods and techniques. They interviewed 600 MWRA under the supervision of a field research officer who had more than seven years' experience in field research work and had supervisory and monitoring skills. The interviewer asked the responsible person of the sample village to select a primary school or mosque/temple/church/pagoda (a place of worship). One household from one specific corner of the worship place or primary school was selected as an index household. The corner was specified beforehand and was constant for all the selected villages. Interviews of neighbouring permanent residence MWRA, following the one in the index household, continued until interviews of 30 such MWRA were completed. Female respondents were selected because they were the major recipients of reproductive healthcare services. The major indicators of health and family-planning were: (a) awareness about services available from FWAs; (b) frequency of contacts with FWAs; (c) number of desired children; (d) unmet contraceptive need; (e) accessibility to H&FWCs and SCs; and (f) use of contraceptive methods. Design effect was used for establishing that 210 children (i.e. 30 clusters with 7 children per cluster) are necessary for a survey. In this study, the required sample was doubled to avoid the design effect.The qualitative methods were used for assessing the routine activities of 66 FWAs. The routine activities observed included: (a) administration of injectables at the door-step and (b) record-keeping. Two research officers made three days' observations on the activities of each FWA in a year during their home- visits. A structured observation checklist was used. At the facility level, three categories of meetings were observed, namely:(i) fortnightly meetings of FWAs and their immediate supervisor and paramedics at H&FWC to review the performance of the previous month and current stock of contraceptives;(ii) monthly mid-level supervisory meetings and local managers to review the union-wise monthly performance, discuss the field problems, and made decision to solve those problems; and(iii) monthly salary-day meetings of field and union-level service providers, supervisors, and local managers to review the MCH-FP-related performance of field workers and paramedics. A structured observation checklist was used for collecting information on 34 meeting proceedings. Content analysis of meeting minutes was done, and reports from observers of meetings were analyzed manually.Univariate analysis was conducted using SPSS (version 10) to determine different indicators of health and family-planning use. Chi-square test was employed to observe any significant differences in proportions between the first cluster survey (referent) and the second cluster survey.In absence of division-wise selected indicators, we used the national survey data of BDHS 1996\u20131997 to compare the selected indicators of health and family planning service use with the cluster survey or rapid assessment survey.Data of 1995 and 1996 showed a consistent pattern of adherence to the recommended protocol for administration of injectables . Other than salary day meetings, formalities in terms of the recording of the agenda and post-discussion resolutions of issues after discussion were maintained in the majority of the meetings. The monthly performance of maternal child health and family planning indicators were reviewed in the majority (70%) of the meetings.Table The remarkable improvement in programme performance as reported in the present study is attributable to two major factors: first, a series of on-the-job-training activities were conducted on the record keeping system, screening checklists of family planning methods, administering injectable contraceptive, management of side-effects of contraceptive methods, supervision and monitoring, etc, that updated the existing knowledge and facilitated close interaction between the trainers and the trainees. Maintenance of the active learning process, use of feedback mechanisms, and job related hands-on training were instrumental. The FWAs almost universally maintained the recommended protocol for administering injectables even after the withdrawal of the interventions. The high coverage of routine activities of the FWAs, such as record-keeping and screening of contraceptive methods, was also sustained after the withdrawal of the interventions.Second, conducting regular performance review meetings was very powerful. The feedback system in those meetings was ensured to evolve close interaction between field workers and supervisors. The local manager had the opportunity to identify any problems and explore appropriate solutions. This led to efficient management of the programme and advance planning. In the meetings, high-performing workers were praised, and poor-performing workers were offered assistance. This process was found to be useful for monitoring individual performance and aggregated outputs at the union levels, which finally created positive attitude and improved motivation for the entire team. Thus, overall improvement of the programme performance took place. Another influential factor was the independent local survey, which was indicator-based and that ultimately motivated the programme managers to fix the target, organize field activities, and generally improve. The FWAs who provided services at the door step motivated their clients to avail of better-quality services at the fixed site centres. The higher use of SC and H&FWC services was an indicator of improved field activities.The in-built review system was crucial. The district and local managers reviewed the results of the rapid assessment survey. These reviews assisted the sub-district managers and front-line supervisors in identifying the weakness of the programme and develop field operational strategies. The local managers then instructed the front-line supervisors to strengthen their monitoring and supervision activities (to improve the work of field-level workers), which were reflected in the survey results. This was an effect of the managers' motivation and positive efforts towards the improvement of the programme.In a review paper on performance monitoring for family planning, experiences of different countries have been highlighted . IndonesThe present study succeeded in using a package of strong MIS systems, performance review meetings having feedback mechanism, in-service training, and ad-hoc rapid assessment surveys to improve the performance of the programme, particularly in the low-performing areas of Bangladesh."} +{"text": "Conflict and war have long been recognized as determinants of infectious disease risk. Re-emergence of epidemic sleeping sickness in sub-Saharan Africa since the 1970s has coincided with extensive civil conflict in affected regions. Sleeping sickness incidence has placed increasing pressure on the health resources of countries already burdened by malaria, HIV/AIDS, and tuberculosis. In areas of Sudan, the Democratic Republic of the Congo, and Angola, sleeping sickness occurs in epidemic proportions, and is the first or second greatest cause of mortality in some areas, ahead of HIV/AIDS. In Uganda, there is evidence of increasing spread and establishment of new foci in central districts. Conflict is an important determinant of sleeping sickness outbreaks, and has contributed to disease resurgence. This paper presents a review and characterization of the processes by which conflict has contributed to the occurrence of sleeping sickness in Africa. Conflict contributes to disease risk by affecting the transmission potential of sleeping sickness via economic impacts, degradation of health systems and services, internal displacement of populations, regional insecurity, and reduced access for humanitarian support. Particular focus is given to the case of sleeping sickness in south-eastern Uganda, where incidence increase is expected to continue. Disease intervention is constrained in regions with high insecurity; in these areas, political stabilization, localized deployment of health resources, increased administrative integration and national capacity are required to mitigate incidence. Conflict-related variables should be explicitly integrated into risk mapping and prioritization of targeted sleeping sickness research and mitigation initiatives. Sleeping sickness re-emerged in Uganda in the 1970s, and continues to pose a public health and economic burden . SimilarTrypanosoma spp.), a protozoan parasitic disease affecting humans, livestock, and a large number of sylvatic species in much of sub-Saharan Africa , trypanosomiasis represents an important public health and economic burden in sub-Saharan Africa is a public health problem in places where a research infrastructure can hardly exist\" p. 147].7.14,61] Prioritization of high-risk areas for sleeping sickness and trypanosomiasis control should explicitly integrate the occurrence of conflict and its impacts on transmission risk. The occurrence of conflict and presence of large number of internally displaced people can be integrated into current risk maps in addition to land cover, tsetse habitat, and livestock distributions. An understanding of areas where conflict may contribute to increased disease risk can guide prioritization of continent-wide as well as national mitigation programs.Conflict is an important determinant of sleeping sickness outbreaks in sub-Saharan Africa. In Uganda, the two sub-species of sleeping sickness can be expected to merge in the absence of immediate and targeted intervention in central districts; the presence of both diseases in one region will dramatically increase burden of disease as well as the complexity and difficultly of subsequent control initiatives. Control and prevention of sleeping sickness by national and international authorities should explicitly integrate consideration of conflict and its impacts into mapping and targeting of regions for priority intervention. Prevention and control campaigns should be assessed and evaluated against the ability of the initiative to address, mitigate, or alleviate the conflict-related drivers of disease risk. The occurrence of sleeping sickness in conflict-affected areas will severely constrain the success and cost-benefit evaluations of continent-wide tsetse eradication campaigns. Prevention of sleeping sickness risk in affected sub-Saharan African countries requires increased international focus on development of administrative policy, capacity, integration, and infrastructure to implement localized control strategies.HIV/AIDS Human Immuno-deficiency Virus/Acquired Immuno-deficiency VirusDRC Democratic Republic of the CongoWHO World Health OrganizationIDP Internally Displaced PersonsThe author(s) declare that they have no competing interests.LBF conceived, designed, researched, and prepared the manuscript."} +{"text": "Detailed data and statistics per each morphological site of various digestive neoplasms were obtained for the period 1976-87 from the Vaud Cancer Registry datafile, a population-based cancer registration scheme covering about 530,000 inhabitants from the French-speaking part of Switzerland. Tabulations presented include absolute number of cases , percent distributions, age-standardised rates, sex ratios and 5-year survival. The report has essentially a descriptive value, and should be viewed as a contribution towards quantification, in a well surveilled population of the West-central part of Europe, of the proportional distribution of digestive neoplasms by morphological type, and corresponding incidence and survival rates. Among the points deserving specific attention, there are the elevated frequency of upper digestive tract cancers, the very high male-to-female ratios for squamous cell carcinomas, adenocarcinomas of the oesophagus and hepatocellular carcinomas of the liver, the female excesses in infiltrating carcinoids of the colon, transitional and squamous cell carcinomas of the rectum and adenocarcinomas of the gallbladder, and the crossover in male-to-female ratio in squamous cell carcinoma along the digestive tract (i.e. from 6.0 at the level of the mouth/pharynx to 0.5 in the rectum). As concerns survival, rates were higher for lymphomas and sarcomas than for carcinomas in oral cavity and stomach, similar for carcinoids and carcinomas in the small bowel (about 35% at 5 years), as well as for colon (34%) and rectal (37%) cancers. Some of the findings, such as the higher survival of carcinomas arising from polyps in the colon and rectum, or the higher proportion of cholangiocellular and combined cholangio- and hepatocellular carcinomas in females than in males find plausible prognostic or aetiologic correlates, but others, such as the large proportions of squamous and transitional cell cancers of the rectum in females are more difficult to explain. These and several other indications emerging from careful examination of the data herein presented underline the interest of morphological analyses of digestive tract cancers."} +{"text": "EHP. Korach is director of the Environmental Diseases and Medicine Program, chief of the Laboratory of Reproductive and Developmental Toxicology, and chief of the Receptor Biology Section at the NIEHS. He received his PhD in endocrinology from the Medical College of Georgia in 1974. Korach\u2019s areas of research include the basic mechanisms of estrogen hormone action in reproductive tract and bone tissues, with an application toward understanding how hormonally active environmental estrogens influence physiological processes. He is the past editor-in-chief of Endocrinology, the flagship journal of the American Endocrine Society. Korach will guide EHP until a permanent editor-in-chief is selected.With this issue, Kenneth S. Korach becomes interim editor-in-chief of"} +{"text": "The behavioral and social sciences offer insights into the comprehensive understanding of human health, including disease etiology and treatment, and the promotion of health and well-being. To encourage the investigation of the impact of social and behavioral factors on health and disease, the participating institutes and centers invite qualified researchers to submit research grant applications on methodology and measurement in the behavioral and social sciences. Methodology and measurement encompass research design, data collection techniques, measurement, and data analysis techniques. The goal is to encourage research that will improve the quality and scientific power of data collected in the behavioral and social sciences, relevant to the missions of the NIH Institutes and Centers (ICs). Research that addresses methodology and measurement issues in diverse populations, issues in studying sensitive behaviors, issues of ethics in research, issues related to confidential data and the protection of research subjects, and issues in developing interdisciplinary, multimethod, and multilevel approaches to behavioral and social science research are particularly encouraged, as are approaches that integrate behavioral and social science research with biomedical, physical, or computational science research or engineering. Applicants are encouraged to contact the Program Contact for Scientific/Research issues (see \u201cAgency Contacts\u201d) of the IC that most closely matches their research focus to determine the IC\u2019s interest in the research topic.This Funding Opportunity Announcement (FOA) encourages applications addressing four general areas of methodology and measurement research in the social and behavioral sciences. These areas include research design, data collection techniques, measurement, and data analysis. Within the broad spectrum of research defined by these areas, applicants are encouraged (but are not required) to consider studies that address one or more of the following key issues: 1) methodology and measurement issues in developing innovative interdisciplinary, multimethod, and multilevel research designs for use in behavioral and social science research, with emphasis on developing new technologies and addressing the analytical complexities associated with the integration of behavioral, social, and biological data; 2) methodology and measurement issues in research relating to diverse populations, e.g., populations that are distinctive by virtue of age, gender, sexual orientation, ethnicity, culture, including culture-specific medical systems, socioeconomic status, literacy, language, or disability; 3) methodology and measurement issues in studying how dramatic changes in economic, social, environmental, physical, or political context affect human health and well-being, including developing new methods if older ones are no longer valid in the face of significant changes in populations and societies over the last several decades; 4) methodology and measurement issues in studying potentially sensitive behaviors, such as sexual behavior and abortion, and covert or illegal behaviors such as drug use, abuse, and violence; 5) methodology and measurement issues concerning ethics in research, with emphasis on the topics of informed consent, assessment of risk and benefit, and selection and retention of subjects, and ensuring subjects\u2019 confidentiality.Multidisciplinary and interdisciplinary approaches are strongly encouraged. Potential applicants are urged to explore the ideas and methods developed in social science and behavioral fields other than their own and to consider the development and integration of behavioral and social science measures with those of the biomedical, physical, or computational sciences or engineering. Consulting relevant literature and collaborating with colleagues from other disciplines may provide important opportunities for cross-fertilization in developing improved methodology and measurement.Research design determines how well a research plan can accomplish stated purposes and test hypotheses. Research design encompasses many decisions including the sampling plan; selection of appropriate study designs, methods, procedures and measures; and assuring confidence in the study\u2019s internal and external validity. An innovative sample design or sampling frame can be the centerpiece of a research design. Examples of topics within research design include the following: 1) conceptual design strategies appropriate for the study of culture in the context of health; culture may include ethnic group, professional affiliation , culturally specific medical system, or interaction of multiple subcultures within a health-related context; 2) designs to improve causal inference from nonexperimental and quasi-experimental research and natural experiments; 3) research to improve the efficacy of multilevel designs; 4) methods for improving the design and evaluation of community-based research and intervention trials ; 5) conceptual, methodological, and ethical issues in designing studies that use different sources of information; e.g., studies comparing self- and third-party reports ; 6) designs to improve and compare various approaches to economic analysis, including cost analysis, cost-effectiveness, cost\u2013benefit, and conjoint analysis for improving decision-making in health policy and health care systems; 7) designs to improve the inclusion of underrepresented groups in research, e.g., women; children; the elderly; ethnic and racial minorities; sexual minority groups; geographically isolated groups; mentally or physically impaired or disabled populations; immigrants and refugees; and language minority populations; 8) designs that allow for the meaningful integration of biological, behavioral, and social science data ; 9) ethical considerations in research design including issues of informed consent, assessment of risk and benefit, confidentiality, and selection and retention of subjects; 10) methods for archiving and disseminating complex data sets, especially longitudinal data sets, data sets including social network data or geographic identifiers so the identities of study participants are protected and so the data sets can be used by other investigators; 11) alternatives to randomized, controlled trials, including studies to investigate the feasibility, validity, and benefit of incorporating subject preference in intervention design and outcomes assessment; issues regarding blinding; and design of placebo and other control groups; 12) methods to improve the design of clinical research for enhancing quality of patient care ; 13) designs that allow assessment of the active components of multilevel interventions; 14) methodology to ensure the integrity and consistency of data obtained in multisite studies.Developing and validating research instruments and questions are vitally important for collecting reliable information, and have obvious impact on data validity and reliability. For example, health care practitioners must collect reliable reports of symptoms from their patients to accurately diagnose disease. In addition, data collection instruments and questions developed for a particular age, gender, or cultural group may not be valid for other groups. For example, a dietary history questionnaire developed for Americans of European descent may not contain the foods commonly eaten by Americans of African, Asian, or Hispanic descent. Specific consideration of the processes underlying potential bias in self-report data collection remains a measurement issue: perceptual, cognitive, cultural, demographic, motivational, and affective influences on self-report data. Finally, continued improvement and innovation in developing and validating data collection instruments are important for all types of research settings, ranging from the clinical interview and observational study to the survey. Examples of measurement issues include: 1) development and refinement of measures, instruments, or surveys used in behavioral and social science research that fill a gap in research needs, with an eye toward developing and validating core sets of items to reduce redundancy across research projects; 2) instrument design, calibration, and refinement; instrument design issues in studying age, gender, and culture, including methods of studying culture and self-identification of race/ethnicity, as well as the psychometric properties underlying data collection instruments; 3) measurement issues in using technology such as computer-assisted data collection, web-based technology and personal digital assistants; 4) direct and indirect measurement of attitudes, values, self-esteem, and other psychological variables; this includes examination of economic values, including willingness-to-pay, as a means of evaluating benefits; 5) development of instruments that assess degree of change, and rate and variable direction of change; 6) development of instruments or technologies that measure behavior objectively or reduce self-report burden; 7) development of objective measures of components of the built environment that ffect health and of measures for assessing interactions between people and the built environment; 8) methodology to objectively measure the cultural and social environment, including aspects of the community environment that influence health; 9) methodology for validating geographic information system (GIS) data obtained from different sources; 10) methodology to measure fidelity to behavioral interventions, including the development or adaptation of behavioral and interpersonal measures to better assess the fidelity of community-based and multisite behavioral interventions; 11) development of measures of self-management of chronic illness and disability and of family management of chronic illness and disability among children; 12) development of behavioral and social science measures that can be used for efficient data collection in clinical practice\u2013based research networks; 13) methodology to capture the behaviors of health care providers in clinical settings; 14) methods that incorporate relevant biological, physical, or computational measures into behavioral and social science research; 15) development of measures for evaluating quality of life near the end of life in a variety of populations, and refinement of existing measures through longitudinal studies and across various disease states.Data collection techniques are the tools and procedures scientists use for implementing research designs and obtaining measurements. Methods for collecting research data have an important impact on data validity and reliability. For example, studies have suggested that use of self-administered instruments can facilitate the reporting of sensitive or illegal behaviors. Innovative methodologies can also open the door to the collection of new or more complex types of data by behavioral scientists. For example, recent developments in computer-assisted interviewing have permitted more complex question sequences in survey research and the development of hand-held \u201cbeepers\u201d programmed for data entry have permitted the collection of time-specific data on activities such as cigarette smoking. In addition, implicit measures have allowed researchers to examine processes of which people themselves have been unaware. Continued improvement and innovation in data collection methods are important for all types of research settings, including clinical interviews, observational studies, participatory action research, and surveys. In addition, more research is needed to understand how various methods work in diverse populations, and how they can be modified to address the specific needs of populations. Potential topics within data collection techniques include, but are not limited to the following: 1) methods to improve data collection in surveys and epidemiologic self-report studies, ethnographic and other qualitative studies, participatory action research methods, and multimethod studies; this may include new approaches to instrument design and manipulation of method and mode of data collection, length, setting, and interpersonal factors in data collection exchanges; 2) methods to develop innovative gold standards to assess and improve the accuracy of self-reports, in the absence of health record checks ; 3) new methods for qualitative research; methods for validating narrative or text-based analyses; techniques for validating and replicating findings from qualitative research, including collection strategies, development of coding protocols, and techniques that facilitate the integration and validation of qualitative and quantitative measurement; 4) methods to reduce sampling, survey, and item nonresponse bias in research studies, including techniques to improve the coverage of relevant populations in household surveys, to increase the voluntary participation of eligible subjects, to reduce attrition in longitudinal studies and clinical trials, and to improve response rates on sensitive items; 5) techniques for collecting contextual data and for operationalizing the boundaries of particular social, economic, physical, and cultural contexts; 6) improved technologies for data collection, including automated collection and reporting technologies, such as computer-based data collection and computer adaptive methodology, and research on how the method/mode used to collect data affects the quality of the data in a variety of populations and substantive areas; 7) data collection techniques that address the needs of special populations and that address how these methods affect data quality and completeness across diverse populations; 8) issues surrounding the collection of self-report data from different settings , different collection methods , from different parties , and the use of implicit and explicit measures; 9) development of better data collection techniques for studies that involve populations which are small or difficult to access, such as the terminally ill.Analytic methods encompass the concepts and techniques used in analyzing data and interpreting and reporting results, to improve estimation, hypothesis testing, and causal modeling based on scientific data. Challenges include developing techniques that distinguish underlying regularities from the noise created by variability and imprecise measurement; developing causal inferences from nonexperimental data; improving both the internal validity and external validity of measures and studies; and developing appropriate analytic techniques for use with new kinds of data and new approaches to behavioral and social science research, and meaningful integration of behavioral and social science data with those obtained from the biological, physical, computational sciences, or engineering. Examples of topics within analytic methods include: 1) research to improve the analysis of longitudinal data, in particular, the analysis of correlated data, the modeling of different sources of error, and techniques for dealing with missing data at various levels of aggregation; 2) methods for improving the analysis of multicultural; community-based multilevel intervention trials ; 3) methodological research to improve the analysis of complex survey data, including the statistical modeling of nonresponse and other survey errors; 4) analytic issues in innovative techniques for improving causal inference from nonexperimental research; 5) analytic methods for integrating evidence from qualitative and quantitative research, such as research examining the complex relationships among multiple sources of information on a single construct ; 6) analytic methods that appropriately model social structures, social processes, and spatial relationships such as social networks, social influence, diffusion, and contextual effects; 7) statistical procedures for accurately estimating multilevel models; 8) development of novel mathematical and computational techniques for analyzing and modeling behavioral and social processes; 9) methods for improving the analysis of nonindependent data, such as data examining processes in interactions between couples, families, or other groups; 10) developing sophisticated analytic methods that take into account complex probability designs used in epidemiological research; 11) analytical methods to incorporate geographic and built environment measures into behavioral and social science research; 12) expanding current psychometric methodologies to handle the types of data collected in behavioral and social science research, e.g., multidimensional data, shorter scales, nonnormal score distributions, mixed response format, and complex survey structure; 13) methods for the detection and analysis of nonlinear or discontinuous changes in response to treatment.http://www.nichd.nih.gov/publications/pubs/diverse_voices.htm).Potential applicants specifically concerned with research regarding the inclusion of language minorities should see the 2001 report on the conference \u201cDiverse Voices\u2014The Inclusion of Language-Minority Populations in National Studies: Challenges and Opportunities,\u201d sponsored by National Institute on Aging, the National Institute of Child Health and Human Development, and the National Center on Minority Health and Health Disparities (see http://grants.nih.gov/grants/guide/pa-files/PA-05-029.html). However, the research agenda also included detailed recommendations relating to needed methodological research related to the social and cultural dimensions of health. Potential applicants are encouraged to consult this report (see http://obssr.od.nih.gov/Conf_Wkshp/higherlevel/conference.html).In June 2000 the Office of Behavioral and Social Sciences Research held a conference \u201cToward Higher Levels of Analysis: Progress and Promise in Research on Social and Cultural Dimensions of Health.\u201d After the conference, a panel of scientists developed an ambitious research agenda on the social and cultural dimensions of health. A program announcement based on the panel\u2019s recommendations for substantive research has been issued by OBSSR encouragement of research intended to develop methodological, evaluative, and analytic tools for studying stigma and its consequences with respect to health, and 2) development, evaluation, and optimization of interventions to prevent or mitigate the negative effects of stigma and discrimination on health. In both areas the social and cultural dimensions of stigma and its manifestations should be included. Applicants are encouraged to refer to the stigma conference website: In addition, the following reports may be useful as general references on behavioral and social sciences research as it relates to health:http://www.nap.edu/catalog/10002.html).New Horizons in Health: An Integrative Approach (2001) .Health and Behavior: The Interplay of Biological, Behavioral, and Societal Influences (2001) .From Neurons to Neighborhoods: The Science of Early Childhood Development (2000) .Bridging Disciplines in the Brain, Behavioral, and Clinical Sciences (2000) . Frank Kessel, Patricia Rosenfield and Norman Anderson, Editors. New York:Oxford University Press.http://www.nap.edu/books/030907259X/html/).Rebuilding the Unity of Health and the Environment (2001) (http://www.nap.edu/books/0309071992/html/).Cells and Surveys: Should Biological Measures be Included in Social Science Research? (2001) .Qualitative Methods in Health Research: Opportunities and Considerations in Application and Review (2001) .Applicants may also wish to consult the following report on the protection of human subjects in behavioral and social sciences research: Protecting Participants and Facilitating Social and Behavioral Sciences Research (2003) (http://grants.nih.gov/grants/funding/modular/modular.htm).This FOA will use the NIH Research Project Grant (R01) award mechanism. The applicant will be solely responsible for planning, directing, and executing the proposed project. This FOA uses \u201cJust-in-Time\u201d information concepts. It also uses the modular as well as the nonmodular budget formats , use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide .U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096 23 August 2006. Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms , although some of the \u201cAttachment\u201d files may be useable for more than one FOA.GrantsInfo@nih.gov.For further assistance, contact GrantsInfo: 301-435-0714, (telecommunications for the hearing impaired: TTY 301-451-0088), or by e-mail:http://grants.nih.gov/grants/funding/sub-missionschedule.htm. The complete version of this PA is available at http://grants.nih.gov/grants/guide/pa-files/PA-07-060.html.The application submission dates for this PA are available at http://grants.nih.gov/grants/guide/pa-files/PA-07-060.html.Contacts: The complete list of agency contacts is available at Reference: PA-07-060."} +{"text": "This paper investigates the wealth of medicinal plants used by the Apatani tribe of Arunachal Pradesh. Apatani have traditionally settled in seven villages in the Ziro valley of Lower Subansiri district of Arunachal Pradesh in the Eastern Himalayan region of India. The present study has resulted in the documentation of 158 medicinal plant species used by the Apatani group of villages. These medicinal plant species were distributed across 73 families and 124 genera. Asteraceae was the most dominant family of medicinal plants, followed by Zingiberaceae, Solanaceae, Lamiaceae and Araceae. For curing ailments, the use of aboveground plant parts was higher (80%) than the belowground plant parts in the Apatani group of villages. Of the aboveground plant parts, leaf was used in the majority of cases (56 species), followed by fruit. Different belowground plant forms such as root, tuber, rhizome, bulb and pseudo-bulb were used by Apatani as a medicine. About 52 types of ailments were cured by using these 158 medicinal plant species. The results of this study are further discussed in the changing socio-economic contexts. Tribal communities are mainly the forest dwellers who have accumulated a rich knowledge on the uses of various forests and forest products over the centuries. India possesses a total of 427 tribal communities, of these more than 130 major tribal communities live in North East India, which is comprised of the 8 states Meghalaya, Mizoram, Manipur, Tripura, Sikkim, Assam, Nagaland and Arunachal Pradesh. The major tribal communities of the North East India have been categorized into sub-tribes and if these sub-tribes are taken into account the total number of tribal groups reaches up to 300. In general, the tribes of North East India have been categorized into two broad ethnic communities, such as the Khasi and the Jaintia tribe of Meghalaya, who belong to 'Monkhemar' culture of Austoic dialect, and the rest of the tribal groups are basically Mongoloid, who belongs to Tibeto-Burman subfamily of Tibeto-Chinese group was used as medicine. These 158 medicinal plant species were used in curing about 52 types of ailments, of which the highest numbers of plant species (40 species) were used for the treatment of gastrointestinal disorders such as indigestion and constipation. About 19 medicinal plant species were used in curing cough and cold, and 15 medicinal plant species were used for healing cuts and wounds than the belowground plant parts. Of the aboveground plant parts, leaf was used in the majority of cases 56 species), followed by fruits. Different belowground plant forms such as root, tuber, rhizome, bulb and pseudo-bulb were also used by the Apatani as a source of curing ailments Table . The who6 speciesPrevious studies carried out in North East India have reported 41 medicinal plant species used by the Apatani of Arunachal Pradesh . However"} +{"text": "Electrodiagnostic medicine is a specific branch of medicine used by specialist physicians in the field of physical medicine and rehabilitation and/or neurology to diagnose, prognosticate and plan treatment options of peripheral nerve lesions. This meeting was hold to discuss multidisciplinary approaches to this common and important topic in the medical field.The Department of Physical Medicine, Rehabilitation and Electrodiagnosis of Shaheed Beheshti Medical University in collaboration with the Iranian Society of Physical Medicine and Rehabilitation (ISPMR) held the 1 Electrodiagnostic medicine is a specific branch of medicine used by specialist physicians in the field of physical medicine and rehabilitation and/or neurology to diagnose, prognosticate and plan treatment options of peripheral nerve lesions. This meeting was hold to discuss multidisciplinary approaches to this common and important topic in the medical field.The 1st Congress of Electrodiagnostic Medicine in Peripheral Nerve Lesions was held in Tehran,Iran organized by the Department of Physical Medicine, Rehabilitation and Electrodiagnosis of Shaheed Beheshti Medical University in collaboration with the Iranian Society of Physical Medicine and Rehabilitation and rehabilitation measures of peripheral nerve lesions. Twenty leaders in the field of peripheral nerve including: physiatrists, neurosurgeons, neurologists, orthopedists, hand surgeons, vascular surgeons, and plastic and reconstructive surgeons were invited as key lecturers to present the updates about peripheral nerves in upper and lower limbs. In addition to oral presentations, 2 panel discussions, \"Carpal Tunnel Syndrome\" and \"Thoracic Outlet Syndrome,\" were organized to discuss these challenging topics. About 160 participitants from diverse disciplines including physiatry, orthopedics, neurosurgery, hand surgery, neurology, physiotherapy, occupational therapy and also general practitioners participated in the congress. Seyed Mansoor Rayegani, M.D., associate professor of PM&R, was responsible as the secretary of the congress.The additional files contain the slides from the invited lectures and panel discussions [see additional file Slides from the invited lectures and panel discussions. Compressed PDFs of 15 presentations and 2 panel discussions during the conference.Click here for file"} +{"text": "Guide to Community Preventive Services. Initial foci for the Cancer Prevention and Control Research Network's research work groups include projects to increase screening for breast, cervical, and colorectal cancers; to promote informed decision making for prostate cancer screening; and to validate educational materials developed for low-literacy populations.The Cancer Prevention and Control Research Network is a national network recently established to focus on developing new interventions and disseminating and translating proven interventions into practice to reduce cancer burden and disparities, especially among minority and medically underserved populations. Jointly funded by the Centers for Disease Control and Prevention and the National Cancer Institute, the Cancer Prevention and Control Research Network consists of sites administered through Prevention Research Centers funded by the Centers for Disease Control and Prevention. The five sites are located in Kentucky, Massachusetts, South Carolina, Texas, Washington State, and West Virginia. The Cancer Prevention and Control Research Network's intervention areas include primary prevention of cancer through healthy eating, physical activity, sun avoidance, tobacco control, and early detection of cancer through screening. The Cancer Prevention and Control Research Network uses the methods of community-based participatory research and seeks to build on the cancer-relevant systematic reviews of the The Cancer Prevention and Control Research Network (CPCRN) is a federally funded, national network of academic, public health, and community partnerships that work together to reduce the burden of cancer, especially among those disproportionately affected. The CPCRN was initiated in October 2002, with funding from the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) as part of their effort to more effectively translate research into practice. The five CPCRN sites were selected through a competition among the CDC-funded Prevention Research Centers (PRCs). Three sites are operated by individual universities: the Universities of South Carolina, Texas-Houston, and Washington. Two sites are operated jointly by pairs of universities: Boston and Harvard Universities; and the University of Kentucky and West Virginia University. This paper introduces the CPCRN; outlines the context for its creation, along with its goals, structure, and operations; and summarizes progress to date.Guide to Community Preventive Services (Community Guide) , suggesty Guide) , with itThe creation of the CPCRN is, in part, a response to the growing magnitude of and persistent disparities in cancer burden. Cancer is the second leading cause of death in the United States as well as a leading cause of morbidity. Cancer accounts for one of every four deaths , and, inDisparities in cancer incidence and mortality persist. For example, the incidence of cervical cancer is four times as high among Vietnamese women as it is among other Asian American and Pacific Islander women . OverallThose disparities are the result of a complex array of economic, social, and cultural factors, and these factors are also reflected in disparities in preventive behaviors. For example, smoking prevalence is now highest among American Indian 38.6%) and Alaska Native (27.4%) men and women 8.6% and . ScreeniThe CPCRN embraces the principles of CBPR as core The need for the CPCRN is highlighted by recent reports of both progress against cancer and remaining challenges in disseminating and translating knowledge gained from efficacy and effectiveness research. During the late 1990s, death rates from the four leading cancers \u2014 lung, colorectal, breast, and prostate \u2014 declined nationally and in most states . Two impBoth the NCI and the CDC have given high priority to bridging the dissemination gap. The NCI's Translating Research into Improved Outcomes program has identified the dearth of dissemination research as a key impediment to the adoption of evidence-based cancer control intervention. The program has also identified the need to expand research/practice partnerships as critical to both the adoption and evaluation of evidence-based interventions in public health and clinical practice settings .Community Guide, developed under the aegis of an independent, nonfederal Task Force on Community Preventive Services and maintained at the CDC, has provided a partial summary of the state of the art of community-based cancer prevention and control. Based on a systematic review of the literature, the Community Guide currently recommends 14 interventions aimed at increasing physical activity, reducing exposure to and use of tobacco, and reducing exposure to ultraviolet light (The et light 10-13).-13.CommuThe CDC has a ready dissemination outlet for proven intervention strategies through its state-based cancer prevention and control programs: the National Breast and Cervical Cancer Early Detection Program and the Comprehensive Cancer Control Program.The prior investment of the CDC in its PRC program facilitated the creation of the CPCRN by providing a well-established administrative home for each of the five sites. In 1984, Congress created the PRC program at the CDC by authorizing the funding of academic health centers for innovative research and demonstration projects to prevent chronic disease. In 1986, the CDC established three PRCs for two years. Since then, the funding period has increased to five years, and the number of centers has grown to 28, which are located in 25 states.Three aspects of the PRC program strengthen the ability of the participating CPCRN sites to design, implement, and evaluate cancer prevention research with immediate application to public health practice. First, the PRC peer-review mechanism involves researchers experienced with CBPR. The peer review process provides assurance that applications are scientifically sound and that the research conducted is of practical use to communities. Second, the program's focus on CBPR enhances the likelihood that the PRCs will evaluate acceptable and sustainable community-based interventions. Partnerships and collaborations of PRCs with various entities increase the likelihood that PRCs will produce evaluations of interventions that are likely to be translated and sustained. Third, research conducted among the most disadvantaged and underserved populations in the nation provides the PRCs with the opportunity to evaluate the external validity of interventions among diverse populations, including the rural poor of Appalachia, African Americans in South Carolina, public housing residents in Boston, residents of the U.S.-Mexico border, and loggers and pulp-mill workers in Washington State.The overall goal for the CPCRN is to conduct community-based cancer prevention and control intervention and dissemination research that extends the knowledge base, addresses critical gaps, and leads to adoption, replication, implementation, and dissemination of successful programs in communities.Community Guide by conducting site-specific and multisite intervention and dissemination research. The four specific research areas include 1) research on the effectiveness of community-based interventions for which evidence is insufficient to justify a Community Guide recommendation; 2) research replicating Community Guide-recommended interventions in populations and settings where they have not been adequately evaluated; 3) research on how to disseminate and implement Community Guide-recommended interventions into communities by public health and community-based organizations; and 4) evaluation of community programs to determine their effectiveness.The CPCRN addresses gaps and builds on recommendations in the The initial funding of the CPCRN for a two-year period supported the development of both local network centers and the larger national network of the CPCRN sites. At both levels, expected outcomes are evidence of the networks' existence and viability, including mission and vision statements, short- and long-term objectives, and active working groups. Of special emphasis in the research arena are efforts to develop strong partnerships with communities bearing the greatest burden from cancer, where community-based participatory research projects are likely to contribute to the reduction and/or the elimination of disparities in cancer burden.The CPCRN is a national network of five sites, each of which is a local network of academic, community, and other organizations with an interest in cancer prevention and research. The work of the CPCRN is led by a Coordinating Center that organizes, among other things, cross-site work groups on research topics of mutual interest to the sites, the CDC, and the NCI. The six sections that follow describe the work of the Coordinating Center and of each of the five local sites.The University of Kentucky and West Virginia University share the coordinating center role for the CPCRN. The Coordinating Center guides discussions on developing research tools for community interventions in cancer prevention and control, organizes collaborative activities with CPCRN members and their partners, fosters relationships among CPCRN members and national/state/local partners to ensure that CPCRN objectives are being achieved, and provides leadership in developing and managing the CPCRN operational structure.Specific activities include 1) developing and implementing a plan and system for effective communication among CPCRN centers; 2) implementing a collaborative planning process resulting in a seven-year plan for CPCRN research, dissemination, and evaluation; 3) implementing processes and procedures for encouraging PRCs to develop collaborative cancer prevention and control research projects; and 4) ensuring that external evaluation is conducted and is focused on the Coordinating Center's performance.The site based at the University of Washington is the Alliance for Reducing Cancer, Northwest . The mission of the ARC NW is to increase primary-preventive and early-detection behaviors to prevent and control cancer in the Puget Sound region, Washington State, and the Pacific Northwest. ARC NW is a collaborative effort among the University of Washington PRC, the American Cancer Society Great West Division; Fred Hutchinson Cancer Research Center; Group Health Cooperative of Puget Sound, a health maintenance organization; Public Health Seattle and King County, a local health department; the Puget Sound Neighborhood Health Centers, an organization of several community health centers in the region; Qualis Health, the Medicare quality improvement organization for Alaska, Idaho, and Washington State; the Washington State Department of Health; and the Weyerhaeuser Company, a large timber products company.Data from the Washington State Behavioral Risk Factor Surveillance System reveal underuse of primary-preventive and early-detection behaviors. In 2002, 21% of Washingtonians aged 18 or older smoked, 15% were physically inactive during leisure time, 76% ate inadequate quantities of fruits and vegetables, and 60% were overweight or obese. Also in 2002, among appropriate age groups, 45% had never received a flexible sigmoidoscopy or colonoscopy, 40% had never received a fecal occult blood test, 26% had not received a mammogram within two years, and 13% had not received a Papanicolaou (Pap) test within three years . Employers of all sizes nationwide reported in the same survey the following health insurance offerings: 80% covered mammograms, 79% covered Pap smears, 68% covered colorectal cancer screening, and 10% covered smoking cessation treatment that included both prescription medications and counseling.The ARC NW focuses on employed populations and on underserved communities. Five current activities include 1) a pilot test, involving the Weyerhaeuser Company, of a policy intervention to promote primary prevention and early detection via the worksite and employment-based health insurance; 2) development of a work site-based, team-oriented intervention to promote primary prevention and early detection of cancer; 3) a pilot test of a tool to increase informed decision making regarding prostate cancer screening; 4) assistance to the Washington State Department of Health in designing and evaluating its colorectal and prostate cancer screening programs; and 5) a review of the literature regarding the quality of life after treatment of prostate cancer.The site based at the University of Kentucky and West Virginia University is the Appalachian Cancer Research Consortium (ACRC). The target population of the ACRC includes the poor, medically underserved, and primarily rural residents of West Virginia and the 51 counties in Appalachian Kentucky. The two universities have a long history of collaboration, with extensive experience in working with communities throughout Appalachia on critical health issues.The U.S. Department of Health and Human Services considers the rural residents of Appalachia a \"special population\" . These rAs a result, West Virginia and the Appalachian regions of Kentucky have higher total cancer mortality rates than the national average ,19. BothThe ACRC focuses its efforts primarily on four cancer sites \u2014 lung, cervix, colorectal, and breast \u2014 with high disease burden, high behavioral risks, and high importance to community members in the region. Current activities of the ACRC include 1) developing a standardized assessment tool to evaluate readability, format, illustrations, and content of cancer prevention and control materials; 2) developing a protocol for colorectal cancer intervention for men and women aged 50 and older; and 3) conducting work site focus groups to identify barriers to colorectal screening for public employees aged 50 and older.The site based at the University of Texas (UT) is Latinos in a Network for Cancer Control . The mission of the LINCC is to reduce cancer-related health disparities among Hispanics/Latinos through community-based intervention, replication, and dissemination research. LINCC is a collaboration among 1) academic researchers at the UT School of Public Health, the UT M.D. Anderson Cancer Center, and the Baylor College of Medicine; 2) cancer control organizations, including the American Cancer Society, Cancer Information Service, Sanchez Cancer Center, Texas Cancer Council, Texas Comprehensive Cancer Coalition, and the Texas Department of Health; and 3) community-based organizations, including the Center for Border Health Research, Hispanic Health Coalition, Migrant Health Promotion, the National Center for Farmworker Health, and the Racial and Ethnic Approaches to Community Health coalition.colonias, unincorporated areas where environmental pollution, inadequate wastewater systems, and inadequate access to public drinking water compound socioeconomic influences on health behavior.Hispanics/Latinos in Texas account for approximately 25% of the total U.S. Hispanic population and 32% of the total Texas population . Along tHispanics in the United States experience higher incidence rates of cervical cancer per 100,000 (16.3) compared with non-Hispanics (7.8) and higher rates of mortality per 100,000 (3.7 compared with 2.6) . Along tpromotora-) based interventions for increasing cancer screening; and 4) research on the effectiveness of small media interventions to increase cancer screening. Another major focus of LINNC is to identify important factors and effective strategies for replicating and disseminating effective cancer control interventions in Hispanic communities. To this end, LINCC is conducting research on the replication and dissemination of an evidence-based, effective breast and cervical cancer screening intervention for Hispanic women: Cultivando la Salud (Current LINCC activities include 1) new research on factors influencing colorectal cancer screening among Hispanics and the development of a community-based intervention to increase this screening; 2) research on informed decision making for prostate and colorectal cancer screening; 3) an evidence review and new research on lay health-worker- .The site based at Boston and Harvard Universities is the Massachusetts Cancer Prevention Community Research Network (MCPCRN). The MCPCRN's mission is to foster a network of partnerships among cancer prevention researchers and community collaborators to support CBPR and to reduce social disparities in cancer risk. The MCPCRN is a collaboration of the Dana-Farber/Harvard Cancer Center Risk Reduction Program, the Harvard Prevention Research Center (HPRC), and the Boston University Prevention Research Center, with participation from the American Cancer Society's New England Division and the Massachusetts Cancer Control Coalition.Massachusetts has 6.5 million residents, 82% of whom are non-Hispanic white . In BostTo reduce these risks, the MCPCRN is approaching four priority community sectors: 1) schools and youth, 2) work sites and labor unions, 3) health care providers, 4) and low-income housing. Among schools and youth, the HPRC faculty direct a range of school and community-based research to improve youth nutrition and physical activity. Work sites and union partners include the Massachusetts AFL-CIO , the Massachusetts Coalition on Occupational Safety and Health, and individual local unions. Approximately 50 community health centers, many with strong ties to MCPCRN partners, facilitate access to health care providers in Massachusetts. The cost of housing in Massachusetts ranks third nationally; MCPCRN collaborators have identified more than 100 housing developments in Boston, Cambridge, and Somerville as potential partners.The MCPCRN's current objectives are to strengthen ties with communities and to conduct pilot and developmental studies as a foundation for future research. An upcoming conference on CBPR will emphasize engaging community organizations in cancer prevention research opportunities. Collaborative community efforts support Health Ambassadors for African American and African immigrant women in Boston and train tobacco advocates in housing developments. Developmental research includes a work site protocol to increase informed decision making for prostate cancer screening; materials to promote timely follow-up for abnormal mammograms among low-income, ethnic minority women; and methods to improve decision making on colorectal cancer screening. Pilot studies include an intervention aimed at weight reduction and increased physical activity through the Young Men's Christian Association and data collection in low-income housing developments.The site based at the University of South Carolina is the South Carolina Cancer Prevention and Control Research Network (SCCRN). The SCCRN was created to address the large and growing cancer burden among African Americans living in South Carolina. Its aim is to serve the entire state, with a population of just more than 4 million people, comprising an area of 31,000 square miles, and ranging from a long, broad coastal plain to the Piedmont region of southern Appalachia. The SCCRN builds on a strong network of existing programs that have coalesced recently in the South Carolina Cancer Alliance (SCCA), which consists of more than 750 institutional and individual members. The constituent bodies of the SCCA include the South Carolina Department of Health and Environmental Control and numerous grassroots organizations in addition to all academic, clinical care, and nongovernmental organizations with cancer-related missions.South Carolina is a relatively rural state, with very high >40%) African American representation in rural areas. It is also a poor state, where the average personal income is about 81% of the national average . Cancer 0% AfricaResearch at the SCCRN focuses on investigating ways to implement programs that complement existing cancer prevention and control infrastructure and through which we can anticipate risk reduction based on changes in individual and organizational behavior. The SCCRN focuses on breast, cervix, colorectal, oropharyngeal, prostate, and thoracic cancers. Ongoing projects include 1) investigation of small media approaches to increase breast and cervical cancer screening in low-income, rural women at highest risk of aggressive forms of these cancers, 2) research on informed decision making for prostate cancer screening and treatment, and 3) identification of geographical determinants of prostate cancer. Formative work includes 1) exploration of a community-based, statewide program of research in oral cancer precancerous lesions, 2) development of a mammography registry to understand patterns of use in low-income, predominantly African American populations, and 3) a church-based participatory intervention of lay health advocate-delivered cancer education and referral.In its first year of operation, the CPCRN has focused on a strategic planning process. From the beginning, community partners from each of the five sites have played strong and active roles in these processes. The strategic planning process produced vision and mission statements; a set of operating structures, principles, and plans; and four research work groups (see below).Communities and researchers working together to reduce the burden of cancer, especially among those disproportionately affected.The mission of the CPCRN is to conduct cancer prevention and control research that extends the knowledge base, addresses critical gaps, and leads to adoption, replication, implementation, diffusion, and evaluation of successful programs in communities.The CPCRN has developed a governing structure with a steering committee, guiding principles, and a seven-year strategic plan. Further information on each of these documents is available from: URL: http://ukprc.uky.edu/CPCRN/home.htm.The strategic planning process also suggested the development of work groups to initiate and carry out CPCRN research. The CPCRN currently has work groups focusing on 1) screening for breast and cervical cancers; 2) screening for colorectal cancer; 3) informed decision making and quality-of-life issues for prostate cancer screening and treatment; and 4) validating low-literacy educational and media materials. The work groups involve cross-site collaboration among scientists from the network centers and have established research goals .Community Guide. Finally, the location of the CPCRN within the CDC's PRC program enables its research findings to be easily translated, both nationally and locally, through long-existing partnerships with other prevention organizations.The CPCRN represents a new and innovative approach for addressing the challenge of identifying effective interventions and promoting dissemination and adoption of these interventions into communities. The CPCRN sites are geographically distributed across the nation, enhancing opportunities to develop community partnerships and to conduct community-based assessments, evaluation, and research with populations that represent nearly all types of medically underserved racial and ethnic groups in the continental United States. A strong commitment to CBPR increases the likelihood that CPCRN research will benefit the underserved communities in greatest need. The CPCRN also provides an opportunity for the sites to collaborate in addressing research gaps, including dissemination research and research translation, and to build on recommendations provided in the Fostering the optimal results from the CPCRN will require that its members maintain a delicate balance between coordinated, centralized efforts and retaining and enhancing the critical, locally responsive nature of its individual members. Within the tension between centralization and decentralization lies the exciting opportunity to create new strategies for successfully reducing the burden of cancer, especially among those disproportionately affected."} +{"text": "This article is derived from a broad, twenty-year study of ethnobotany and folk medicine among pastoral nomads in the Middle East which took place from 1984 to 2004. The article presents examples of different treatments of diseases and disorders of the urinary tract carried out by healer herbalists. The preparation of remedies includes boiling infusions, extraction of dry or fresh leaves, flowers, seeds or whole plants. Some of these plants were used both as food and as medicine, by ingesting different parts of the plants, such as leaves, flowers, fruits, and so on, either while soft, cooked or dried. Data were collected by using unstructured interviews and by observation. These plants were identified by healers, patients, and university botanists. This paper identified eighty-five plant species, which belong to thirty-six families. The most representative families are: Asteraceae (8), Brassicaceae (6), Poaceae (6), Umbelliferae (6). Hadith) of the Prophet Muhammad on health and illness were systemized and became known as The Medicine of the Prophet [Bayt al-hikmah , where scholars worked to translate them into Arabic [People have been using traditional medicine including ethno-botany for several thousand years. Ancient Arabic medicine was influenced by the ancient medicinal practices of Mesopotamia, Greece, Rome, Persia and India. The Greco-Roman system of medicine was developed based primarily on the writings of Hippocrates 460-360 B.C.), Dioscorides (circa 54 to 68 AD) and Galen 130\u2013201 AD). A combination of political and religious factors caused many Greek and Syriac-speaking scholars to move eastward to Persia and to establish centers of learning there. The city of Gundishapur in southwest Iran also became a center of learning, with a well-known medical school, in the sixth century AD [30\u2013201 AD60 B.C., The Canon of Medicine , the epitome of Islamic medicine. This work is the culmination and masterpiece of the Arab systematization of medical science, and includes many descriptions of the uses of medicinal plants [The Comprehensive Book on Medicine . The material written by al-Hawi is arranged under headings of different diseases, with separate sections on pharmacological topics. Ibn Sina's and al-Razi's works were later translated into Latin, and continued to influence medical science well into the nineteenth century [Within a century, Muslim physicians and scientists were writing original contributions to medical and botanical knowledge. One of the greatest and most famous Islamic doctors was Ibn Sina Avicenna 980\u20131037), author of l plants . Other A80\u20131037, The Compendium of Simple Drugs and Food , in which he described more than 1400 medicinal drugs, 300 of which had not previously been described, recording them alphabetically and discussing them with great clarity and detail. The work specified the names of herbs and remedies in various languages, thus providing a first class tool for the comparative research of medicinal plants. Other well-known physicians who wrote on plant uses were: Ibn Juljul, al-Ghafiqi, Ibn Bajjah, Ibn Samajun, and Abu'l-Hassan al-Andalusi [In the western part of the Islamic empire, the Umayyads of Andalus (Islamic Spain) made their capital at Cordoba. Areas of Cordoba and Granada became centers of learning. The richness and diversity of the flora of Spain were major contributing factors to the development of medical botany. The majority of physicians were herbalists and vice versa. The physician Ibn al-Baytar 1197\u20131248), authored Andalusi ,7. Tradi\u20131248, aujinns, and the negative effects of sorcery and/or witchcraft. The pastoral nomadic tribes depend on their local healers and traditional medicine as recorded in Table 1 . The paper is based on interviews with healers and patients. All the material was recorded in field logs, and some was tape-recorded. Unstructured interviews and the observation of participants were carried out in the informants' homes (120 men and 120 women), as well as in the homes of traditional healers (15 men and 10 women). Most of the healers were in the age range of forty to eighty. All the informants were married and over thirty. There were five males from each desert, and four female healers from the Negev, three from Sinai and three from Jordan. The informants were divided into two groups of forty men and forty women from each desert. The collected information was used to construct a list of the indigenous ethnobotanic medicine. Samples from all the plants were collected and identified by healers, patients and university botanists.This paper describes the treatment of diseases and disorders of the urinary tract by traditional herbalists among the pastoral nomadic Bedouin tribes in the Middle East. In this study, we identified eighty-five plant species, which belong to thirty-six families.The use of traditional medicine by the pastoral nomads, and the appeal to traditional healers over the course of many centuries established a psychological-therapeutic dependence of the pastoral nomadic tribes upon these healers. The rich variety of approaches employed by pastoral nomadic healers to treat disorders and diseases of the urinary tract is indicative of the depth and breadth of indigenous medicine practiced among the pastoral nomads in the twentieth century. The analysis of my collected data, together with the information extracted from the literature on herbal and ethnobotanic medicine of countries in the Middle East ,15,21,18Table 1 presents information on which parts of the plants are used and in what manner. It should be noted that for some plants, the uses in different countries of the Middle East are similar ,16. HoweThe many medicinal substances which we were able to identify as used in traditional medicine included various plants species. The analysis of the findings shows that the three deserts where I conducted my research served as the geographic origin of the medicinal substances. These plants were available because they grew as wild and cultivated plants and were part of the natural flora of these deserts. The pastoral nomads used these plants as food and as medicine, by eating different parts of the plants including the following: leaves, flowers, barks, stems, stalks, roots, rhizomes, bulbs, pith, fruit, corms, inflorescenes, shells, berries, seeds, stones/pits (in fruit), soft seed pods, buds, and shoots.It should be noted that wild desert plants also contain a host of other biologically active compounds besides nutrients. The physiological effects of these other compounds in relation to plant nutrients are not well known, but could affect nutrient and medical utilization or other functions. These topics are of relevance for future research in terms of improving our understanding of human nutritional and medical requirements of the pastoral nomads in the Middle East.Table 1: Urinary Diseases and Ethnobotany among Pastoral Nomads in the middle EastClick here for file"} +{"text": "Perceptual decision-making tasks usually require subjects to recognize stimulus categories and select between different response alternatives. For example, in Go/No-go tasks, one has to respond to target stimuli and withhold responding to non-target stimuli. Accomplishing even just a single trial of such a task needs a complex sequence of functions (most of them executive) consisting, for example, in motor readiness, sustained attention, sensory processing, inhibitory control, conflict monitoring, stimulus-response mapping, context updating and, if any, error detection and awareness. In this context, the motor response reflects the behavioral outcome of the fast and proper interaction of the above-mentioned processes, and the response consistency (or variability) is often adopted as index of executive functioning.an inconsistent response is one of the most striking consequences of lesions to the cerebral cortex.\u201d More recently, consistent literature indicated response variability as an indirect index of top down control (Tamm et al., Nowadays, one challenge of the cognitive neuroscience is to understand how executive functions allow to make decisions. In fact, understanding decisional processes, and reasons of decision failure, would be helpful to clarify the executive dysfunctions of clinical conditions such as obsessive compulsive disorders, impulsivity, and addictions (typically intended as a failure of inhibition; Chamberlain et al., Even though it is evident the relationship between executive functioning and performance variability at group level (e.g., in the comparison between high- and low-level athletes in sport; Vestberg et al., Identification of neurophysiological correlates of executive functioning requires to investigate different cognitive abilities, which in part depend on the experimental paradigm: for example, in Stroop or sustained attention tasks (Demeter and Woldorff, When performing a decision-making task, the contribution of the PFC executive functions is manifested mainly through cognitive processes like top-down attentional control, maintenance of information in the short-term memory, ability to ignore distractors and focus on relevant features, and inhibition of the wrong schema and selection of the appropriate one. Since even one of these processes would be able to affect the inter- and intra-individual variability of the performance, they should be dissociated and investigated separately.Recent ERP studies described different pre-movement activities within the frontal cortex emerging both before and after the stimulus appearance in decisional tasks: as reviewed by Di Russo et al. , there iConcluding, there is a growing literature revealing the utility of the ERPs in the study of the executive functions of the prefrontal cortex. In fact, even if with a less spatial resolution of neuroimaging scans, recent ERP literature has proven to be able in overcoming some concerns such as the source localization and the presence of artifacts in the anterior sites, that in the past may have limited the EEG investigation of the frontal executive functioning. At the opposite, the background reviewed here on the functional roles and generators of prefrontal ERPs suggest the latter as a promising tool to foster a new-way approach in the neurocognitive study of the executive functions. In fact, the extensive review of Di Russo et al. revealedRP: conception and writing of the work; FD: contribution to writing and conception of the work, critical revision of the text; RP and FD: approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Xenopus, the progressive determination of the head is an extremely complex process involving the activation and localized antagonism of a number of interdependent intracellular signaling pathways including the Wingless/Int-1 (Wnt), bone morphogenetic protein (BMP), and nodal-related pathways. The sequence of events that specify the head are: dorsal-ventral polarization and head organizer specification in the blastula; gastrulation; neural induction; and patterning of the anterior-posterior and dorsal-ventral neuraxes. Wnt signaling is required for the specification of the dorsal side initially but is then inhibited within the organizer once it has formed. Similarly, Wnt signaling is required along the length of the neural tube, but must be suppressed at its rostral end for normal brain development. Nodal signaling is also necessary for induction of the mesendoderm, but is subsequently suppressed in its dorsal-anterior extreme to specify head organizer. BMP signaling is required for ventral mesoderm and non-neural ectoderm, and must also be suppressed in the head organizer region and for the differentiation of the ventral midline of the neural tube. Thus, development of the head, and indeed the body plan in general, requires precisely timed and spatially restricted activation and repression of these signaling pathways.The head represents the most dorsal and anterior extent of the body axis. In"} +{"text": "The degree to which comorbidities affect the diagnosis of prostate cancer is not clear. The purpose of this study was to determine how comorbidities affect the stage at which prostate cancer is diagnosed in elderly white and black men. We obtained data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute merged with Medicare claims data. For each patient, we estimated associations between stage of disease at diagnosis and each of the 27 comorbidities. The sample included 2,489 black and 2,587 white men with staged prostate cancer. Coronary artery disease, benign hypertension, and dyslipidemia reduced the odds of late-stage prostate cancer. A prior diagnosis of peripheral vascular disease, severe renal disease, or substance abuse increased the odds of being diagnosed with late-stage disease. The study shows some effect modification by race, particularly among white men with substance abuse, cardiac conduction disorders, and other neurologic conditions. The strongest predictors of late-stage prostate cancer diagnosis for both white and black men were age at diagnosis of at least 80 years and lack of PSA screening. Comorbidities do affect stage at diagnosis, although in different ways. Four hypotheses are discussed to explain these findings."} +{"text": "To increase the timeliness of detection of human cases of the new variant ofCreutzfeldt-Jakob disease (vCJD) and to reduce the risk of transmission, theBrazilian Ministry of Health has established and standardized rules and controlmeasures. These include the definition of criteria for suspect cases, reporting,monitoring, and control measures for illness prevention and transmission.Guidelines to be used by the team of health care staff were published anddistributed to health workers. A detailed proposal for a simplified system ofsurveillance for prion diseases was developed and mandatory reportingintroduced. Additional effort is necessary to increase vCJD case detection, thusmaking it necessary to establish a partnership with health care services forbest identification of suspected cases and dissemination of information to allinvolved in the service dealing with vCJD investigation. Materials derived from ruminants are used as components inthe production of medicines, cosmetics and other health related products.3In view of the recent emergence of the new variant of Creutzfeldt-Jakob Disease (vCJD) inhumans, along with its social and economic repercussions, the Brazilian Ministry ofHealth devised specific activities directed toward prevention of CJD in 2001, bycommissioning a Task Force with the following purposes: to produce a report on CJD, tostandardize the criteria for suspect cases, to standardize notification and monitoring,to suggest measures to reduce the risk of disease transmission within the countrythrough health related products and procedure adopted by health care services, and toprovide useful information for the institutions concerned, as well as for thecommunity.3Examples of health related products made from materials of animal origin include:heparin, glycerine, griseofulvin, insulin, magnesium stearate, stearin and polysorbate.For import of such products, ANVISA hasestablished several legal requirements based on the potential degree of infectivity ofanimal tissue being imported and the risk attributed to the country of origin, definedby the number of infected cases identified in the region.http://www.gov.br/vacalouca/index.htm.ANVISA has published two resolutions: RDC 3O5, of November 14, 2002 and RDC 68 datedMarch 28, 2003.4 The latter establishes conditions for importing, trading, and exposureto consumption of these products while the second measure clarifies rules and proceduresconcerning the proper processing of materials used in patients with clinical suspicionof CJD or vCJD; biosafety procedures for handling of patients, samples and othermaterials potentially contaminated with CJD or vCJD agent; procedures for the handlingof corpses; relative infectivity of the tissues and the body fluids of animals, as wellas definitions for those areas running a geographic risk of transmission. Information onthese measures is available at: In this same period, a few possible suspect CJD cases were reported to the HealthSurveillance Secretariat/Ministry of Health (SVS/MS). At this time however, there was nosurveillance protocol in place. Therefore, in December 2004, the Technical AdvisoryGroup for Prion Diseases (GTA \u2013 Prions) \u2013 was commissioned comprising members of the\u201cNational Health Regulatory Agency\u201d (ANVISA), and the Brazilian association ofneurologists (Academia Brasileira de Neurologia). GTA-Prions developed a detailedproposal for the establishment of the \u201cSimplified System for the Surveillance of PrionDiseases\u201d. The implementation of the system is currently directed towards the timelydiscovery of possible cases of Creutzfeldt-Jakob (CJD) Disease and its variant (vCJD);aiming to reduce under-reporting of prion diseases in Brazil; to better understand theepidemiological profile of this illness throughout the country; to enableepidemiological, clinical and laboratory investigation of reported cases; to adoptindividual and collective protective measures upon detection of new cases of suchdiseases; and to deploy possible prevention and control measures in the event of casesbeing identified within Brazilian territory.At the beginning of 2005, the Technical Advisory Group for Human Prion Diseases(GTA-Prions) put forward the following components of the surveillance system: anotification form with case definitions of the clinical categories of prion diseases; aprotocol for epidemiological, clinical and laboratory investigation of notified cases;the description of epidemiological, clinical and laboratorial information flows withinthe system; the definition of the reference clinics where the system will beimplemented, and the identification of laboratories that are equipped to carry out thetests proposed in the protocol.The National Seminar on Human Prion Diseases was held on June 8, 2005, with theparticipation of members of the Ministry of Agriculture, proposed surveillance actionsfor the Bovine Spongiform Encephalopathies, (BSE) and had the main objective ofsubmitting the surveillance system proposal to neurologists practicing at state leveland to the states\u2019 epidemiological surveillance units. In August the same year, ameeting was held by the GTA-Prion (TAG) to incorporate suggestions presented at theseminar.5 The inclusion of the disease onto thelists of diseases for which suspect cases must be notified to health surveillanceservices to allow further mandatory investigation, raised awareness of the disease tohealth authorities who then began reporting cases in many Brazilian states.On July 07, 2005, the Ministry of Health classified CJD as a disease requiring mandatorynotification through Regulation No. 33/2005, making the Simplified System ofEpidemiological Surveillance of Human Prion Diseases in Brazil official.From August 2005 through December 2006, 30 suspected cases of CJD were reported toSVS/MS, in 12 Brazilian states.5The complexity of some of the required procedures (including biosafety rules), andconsequently the difficulty in establishing a steady flow of samples can delaydefinitive diagnosis, and compromise the outcome of epidemiological investigations.The system still has some limitations, mainly concerning laboratory diagnosis and thevery nature of Human Prion Diseases.Despite the difficulties outlined, the state surveillance services have successfullyadapted their routines during investigations of suspected cases of prion disease andhave managed, with the assistance of reference laboratories and neurology servicesinvolved, to notify a number several of cases given the rareness of the disease andunprecedented nature of the proposal.With regard to laboratory surveillance, collaboration amongst research centers has beenpursued, to devise possible, often highly complex, methodologies. In this context,detection of the 14-3-3 protein achieved by the Laboratory of Hospital dasCl\u00ednicas/School of Medicine of S\u00e3o Paulo University (HCFMUSP), has greatlyaided diagnosis of the sporadic form of the disease, currently representing the soleparametric parameter included in the criteria for probable diagnosis of vCJD, andpresents greater than or equal sensitivity and specificity than typicalelectroencephalogram. In spite of current advances in diagnosing the disease, it isrecommended that other tests available for detection should be used in conjunction.Sc) with thedisease. Two PrPSc strains have also been reported, namely Types 1 and 2, along withthree possible genotypes at codon 129 (Methione homozygous (MM), valine homozygous (VV)and heterozygous], responsible for 6 sub-types of the disease. The majority ofsporadic CJD cases are MM1 or MV1.Molecular diagnosis is being carried out by the Ludwig Institute, through purification ofthe DNA obtained after leukocyte separation. Direct sequencing is performed using HighResolution Liquid Chromatography (DHPLC). Polymorphism studies and mutation research inthe human prion gene (PRNP) can be used as an aid to diagnose CJD, whereby researchershave associated the occurrence of polymorphisms at codon 129 and protease resistantchemical-physical properties of cerebral prion protein (PrPConcerning histopathological diagnoses, sending of material to Rio de Janeiro FederalUniversity laboratory is in place, where macroscopic studies of the brain, frontal lobefragments, basal ganglia, temporal lobe, occipital lobe, mesencephalon, bridge, bulb andcerebellum are being carried out. The diagnosis is considered positive for CJD when thefollowing 3 pathognomic characteristics of the disease are identified: Spongiosis,neuronal loss and gliosis. The microscopic aspect reveals spongiosis of the cortex dueto reactive astrocytic gliosis, in proportion to the degree of neuronal loss.Constant improvements in surveillance activities are aimed primarily at increasing thesensitivity of the system for early detection of vCJD cases, in view of the burden theseplace on the Brazilian health system. The decision to include other prion disease in thesystem stems from the syndromic features displayed by these pathologies, particularly intheir initial stages, which make the devising of a notification form exclusively forsuspected cases of the new variant unrealistic. Thus, all prion diseases are reported.At a later stage, cases not meeting the criteria for vCJD are excluded and may or maynot call for control responses, in addition to the natural interest for clinical andepidemiological research.The epidemiological notification form and flow of delivery of samples to the laboratoryare shown below."} +{"text": "Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm) and adverse proliferation (remodeling) of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK) and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke\u2014associated cardiovascular and lung diseases."} +{"text": "The pneumonia team at the Bill & Melinda Gates Foundation congratulates the Pneumonia Etiology Research for Child Health (PERCH) study on delivering on their grant to collect high-quality data from thousands of children with World Health Organization\u2013defined severe and very severe pneumonia and from controls in 9 diverse sites in 7 low- and middle-income countries. This supplement sets the foundation to understanding this complex study by providing an in-depth description of the study methodology, including discussion of key aspects such as antibiotic pretreatment, chest radiograph interpretation, utility of induced sputum in children, measurement of pathogen density, and use of C-reactive protein, and how these affect pneumonia etiology. Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugate vaccine (PCV) in the poorest countries, it remains the leading killer of children <5 years of age, with an estimated 900000 deaths per year in 2013 [The premise under which the Pneumonia Etiology Research for Child Health (PERCH) study was funded by the Bill & Melinda Gates Foundation deserves consideration . In 2008A large part of the funding premise was that obtaining a comprehensive set of specimens from cases and controls, applying state-of-the art laboratory tests, including use of a new, multiplex real-time polymerase chain reaction assay targeting an extensive array of >30 potential pathogens, and standardizing methodologies across a range of epidemiologic and geographic settings in low- and low- to middle-income countries, would update our understanding of pneumonia etiology and mortality , 4.Many of these tests, particularly the molecular technologies, were not available to a previous large study conducted 30 years ago . The US H. influenzae) post-PCV rollout remains to be determined. The use of a serotype-specific pneumococcal assay in children, like the one used to evaluate vaccine impact on pneumonia in adults [We have made enormous progress and are getting closer to determining the etiology of pneumonia, but there are still many unknowns. Future studies based on patterns of gene expression by these bacteria may be of interest, but unfortunately RNA was not collected as part of the study. The role in nonbacteremic pneumonia of non-vaccine-type pneumococci definition of standardized alveolar consolidation pneumonia , 12 alloA great strength of PERCH is the storage of specimens from cases and controls that may be useful for evaluation of newly discovered pathogens, and also the evaluation of biomarkers. The biobank repository that PERCH has created may yet hold more answers for future technologies to unravel further the etiology of childhood pneumonia.The detection of bacterial pneumonia remains crucial to understanding bacterial pneumonia burden and to improving treatment algorithms. Transcriptional profiling of host genes has been recently shown to be superior to the more established biomarker, procalcitonin, in adults , althougPreliminary data from the South African PCV efficacy trial suggest that, at least in an urban cohort of children, pneumonia mortality in infants is predicted by a low oxygen saturation in arterial blood together with indicators of undernutrition such as low weight for age and refusal of feeds. This Respiratory Index of Severity in Children (RISC) score has beenDespite the reduction in pneumonia\u2014related childhood deaths in infants <5 years of age, less impact has been seen on pneumonia- and sepsis-related mortality among neonates , 3. PERCIn view of the challenges, ascertaining the etiology of pneumonia, especially for commonly carried bacterial pathogens in children, is a daunting task. PERCH has approached this task with a thoughtful study design and state-of-the-art diagnostics. This study has achieved many important milestones including the standardization of methods in a complex multicountry study; the study paid careful attention to quality control; it delivered diagnostics through technology transfer to local laboratories; and it pulled together a unique collaboration of multiple investigators and collaborators. With the foundation set by the articles in this supplement, we look forward to the analysis of PERCH data in the future and its contribution to our understanding of both bacterial and viral etiologies of pneumonia."} +{"text": "The Ebola outbreak in West Africa underlined the urgent need for integration of public health systems, including the establishment of national laboratory networks, surveillance systems, and health research institutions at all levels of service delivery. The integration schema presented here would assist in driving the immediate steps needed for integration of public health systems, particularly laboratory networks, in support of the implementation of International Health Regulations and the Global Health Security Agenda in the African region. Increased funding, political willingness from countries, and coordination through enhanced technical assistance from international partners, are critical in achieving this objective. These concerns and challenges are not limited to the three countries that experienced the recent crisis. In general, challenges faced by public health systems in Africa, especially at the primary care level, include: (1) lack of laboratory facilities integrated across diseases and services; (2) poor funding and uptake of new rapid diagnostic technologies; (3) overemphasis on resourcing vertical disease-control programmes; (4) patient and health system delays; and (5) lack of fully-integrated electronic disease surveillance systems.The recent Ebola virus disease crisis in three West African countries \u2013 Guinea, Liberia and Sierra Leone \u2013 highlighted several concerns with respect to the functioning of public health systems in the resource-constrained settings of Africa.4 Donors and partners in several countries promote \u2018parallel\u2019, disease-specific laboratories, especially for the major diseases of poverty , as governments fail to address deficiencies. In a few countries, government-run centres-of-excellence were developed as public health research institutes with support from international partners.5 In some countries, environmental health protection and food safety services, as well as national drug testing laboratories, are also administered under public health services.Laboratories play a critical role in the prompt diagnosis of diseases and treatment monitoring. The specific administrative structures of public health laboratories within Ministries of Health differ among countries in Africa. In the majority of countries in the African region, laboratories fall under a directorate, department or unit for national laboratory services, which are housed within the Ministry of Health. Difficulties in coordination of laboratory services with disease control programmes have been observed in such conventional administrative structures. District and below district-level hospital laboratories act as the default \u2018integrated\u2019 laboratories, due to inadequate staff levels, skill sets and infrastructure. Intermediate-level laboratories are practically district-level laboratories and act as regional laboratories, but without the necessary functional dichotomy. Primary health centre laboratories are poorly equipped for rapid diagnosis or rapid response; and national-level laboratories are not fully networked with district-level laboratories for the functional management of laboratory networks.6 This has resulted in disparate and loosely-organised skill deployment, resource wastage and redundancies within the system. Laboratory workers with the cross-cutting skills to effect integrated services have been systematically under-utilised, as they are increasingly engaged in services for single-disease programmes.7The lack of adequate resources, both financial and technical, has contributed to undue prioritisation of key diseases, which has in turn resulted in vertical disease control programmes and laboratories . The absence of the integration of policy formulation, strategy and budgeting have been compounded by competing disease funding priorities and has created disjointed laboratory services in several developing countries.9 include: (1) under-resourced infrastructure, including equipment; (2) poor laboratory linkages to clinical services, resulting in low test demand and suboptimal utilisation of modern diagnostics for clinical decisions; (3) poor laboratory quality control and assurance systems; (4) a paucity of leadership to provide adequate policy intervention, technical guidance and supportive supervision; and (5) inadequate or absent national laboratory networks. These issues impact staff motivation and the overall credibility of laboratory services.Some of the key issues plaguing public health laboratoriesIn spite of the functional challenges in the delivery of services, there is an urgent need to integrate already-existing public health technical capacity within countries in the African region. Effective linkages between public health institutes and laboratories, in addition to optimisation of services, would facilitate early detection of emerging antibiotic resistance, cancers and other non-communicable diseases, as well as periodic epidemiological disease surveys, which would inform policy changes.10 works to facilitate the collaboration and strengthening of public health research institutes affiliated to the Network of African National Public Health Institutes in Africa.11 Present membership of the network comprises 16 institutions, including the Kenya Medical Research Institute, the Uganda Viral Research Institute, and the South African National Institute for Communicable Diseases. In addition, in some countries in Africa, private-sector clinical pathology laboratories, either corporate chains, or individual stand-alone laboratories, offer services to people who can afford quality care for a premium . Systematically engaging African national public health research institutions and centres of excellence, as well as private-sector laboratories, with national laboratory systems and integrated surveillances systems would enhance utilisation of available laboratory and research capacities, and management of resources.The Network of African National Public Health Institutes12 The Integrated Disease Surveillance and Response (IDSR) programme, a comprehensive regional framework for strengthening national public health surveillance and response systems in Africa, was initiated in 1998. In 2006, WHO Regional Office for Africa (WHO AFRO) Member States recommended that IHR 2005 be implemented using the IDSR framework. The IDSR strategy is aimed at integrating the collection, analysis, and reporting of data on 40 priority diseases and conditions at different levels of the health system, including relevant laboratory data. Over the past decade, the IDSR strategy has successfully reduced parallel disease-specific surveillance programmes, increased the capacity of central laboratories, and unified disease reporting matrices among implementing countries in the African region. It has enhanced adherence to IHR by encouraging and establishing early disease warning and real-time event management systems at the national level, including prompt reporting to the WHO through national IDSR focal point.In 2005, the IHR mandated countries to detect, assess and respond to all events that may constitute public health emergencies of international concern, and report the events to the WHO.14 In hindsight, such shortcomings may have contributed to the state of unpreparedness within the West African sub-region that increased vulnerability to the recent Ebola virus disease outbreaks.IHR core capacity target dates have been revised twice, first to 2014 and then to 2019 after the Ebola virus disease outbreak in West Africa. As of 2014, two-thirds of countries had not met their core capacity requirements and 48 countries had not responded to WHO queries with respect to their state of readiness.15 Provision of this level of coordination for active surveillance, timely analyses and response, especially for events of public health significance, are anticipated through the establishment of the Centres for Disease Control and Prevention in Africa.16Recent successes in efforts to strengthen African laboratory networks, laboratory infrastructure, rapid diagnostic technologies, and quality management systems need to be comprehensively integrated into the core functions of the IDSR through new regional structures or coordination mechanisms. Furthermore, enhanced research and development support through already-existing public health research institutes and centres of excellence would not only provide inter-disciplinary technical skills and capacity to staff for quality services and accurate diagnosis, but also assist in the systematic introduction of new and rapid diagnostic technologies and the provision of periodic epidemiological research surveys that will inform efficient planning for health services. Surveillance mechanisms need high-level coordination at the sub-regional and national levels, with frequent modification.17 To effect coordination, 11 action packages were designed and entrusted to contributing countries for enlisting political leadership and action. Action packages are bound by a Prevent\u2013Detect\u2013Respond framework. There is a need to develop in-country mechanisms and responsibilities to address the GHSA. Integration of health systems across diseases and structures would provide a path for this. It is envisaged that the capacity to respond to the objectives of the GHSA would depend on maximising detection and surveillance capabilities through integrated laboratory frameworks within target countries.The Global Health Security Agenda (GHSA), formed in 2014 in response to the Ebola virus disease crisis and supported by high-level international collaboration, is a multi-country concerted effort toward creating a world safe and secure from infectious disease threats.18Integration envisages a process whereby regional and country-level governmental services, including multi-dimensional functions such as health financing, human resources, strategic planning, and others, along with international developmental partners and donors, work closely to promptly reach and sustain the goal of health security for all. In the resource-limited settings of Africa, integrating and coordinating laboratory services and different service components of national health structures would lead to efficient use of resources and building of laboratory networks, as well as ensuring that laboratories contribute to national disease surveillance and control at all levels of health services .18In principle, integration of laboratory services should be achieved first at the country level, followed by the sub-regional level, as integration aims to best utilise the available resources in an unbiased fashion. The Ebola virus disease crisis has reinforced the need to act decisively on a new regional and global structure, as well as the necessity for integrating in-country and regional health systems under one unified, rapid service delivery mechanism, with early warning, detection and response capabilities. Political will and fiscal and administrative commitments are urgently required from governments to ensure that cross-cutting integration of health systems happens and that the IHR core requirements and the GHSA are met."} +{"text": "Cerebral palsy (CP) is the most common cause of chronic disability that restricts participation in areas of occupations for children. The main aim of rehabilitation is enhancement of their clients for participation in occupations. The aim of this study was to overview of the factors influencing the participations of children with CP in Iran. A systematic, evidence-based process (Duffy 2005) was used. For data gathering electronic databases including Google scholar and Iranian and foreigner famous journals in the fields of pediatrics, were used. The main key words for search were Activity of Daily Living (ADL), Instrumental Activity of Daily Living (IADL), play, leisure, work, rest/sleep, social participation, and education. All the papers of this study were about the factors influencing the participation of Iranian CP children during 2000-2016. Totally, 156 articles were found eligible as for Iranian CP children study, of which 100 articles were discarded. Because of repetitive and duplicability of some articles, 17 articles were removed as well.The most studies about Iranian CP children participations in life areas were in the ADL area of participation (N=12), and the lowest articles were in the area in the field of: Work (N=2), play (N=2), and sleep/rest (N=2). Most of the occupational therapists do not focus on the all life areas.In Iran, many researchers do not pay attention to the participation of CP children. Many articles just paid attention to the sensory, motor or cognitive components of their clients. Cerebral palsy (CP) is a general term used to describe motor function disorders, beginning early in life. This disability is the result of injury or dysfunction of the brain . This unCP causes or its risk factors are divided into several categories as pregnancy age under 20 years, birth weight below 2500 gr, the risk factors related to mother, factors related to pregnancy and fetal factors are common causes of CP disorder . According to the high prevalence of CP and disorders associated with that and eventually needs to follow disorders occur in people, knowing about their needs and try to decreasing their needs seems necessary. Knowing and understanding their demands, especially their expectation in the field of rehabilitation is very important . Among tActivity Daily of Living (ADL): Activities oriented toward taking care of one\u2019s own body. These activities are fundamental to living in a social world; they enable basic survival and well-being : Activities to support daily life within the home and community that often require more com\u00acplex interactions than those used in ADLs was used . For dat1. Electronic databases: Medlin, PubMed, Google scholar, CINAHL, OVID Medline, CINAHL, Cochrane, ProQuest, Up to Date, Web of Science, OT search, OT direct, Pedro, SID, Magiran, IRAN MEDEX, MEDLIB and Iran doc.2. Iranian and foreigner famous journals in the fields of pediatrics as follows: Iranian Journal of Pediatrics (IJP), Iranian Rehabilitation Journal (IRJ), Iranian Journal of Child Neurology (IJCN), Archive Physical Medicine and Rehabilitation, Developmental Medicine, Child Neurology, Physical and Occupational Therapy in Pediatrics, American Journal of Occupational Therapy. The key words used individually or in combination according to the MESH were as follows: Cerebral palsy (CP), participation, Iranian CP children, Activity of Daily Living(ADL), Instrumental Activity of Daily Living(IADL), play, leisure, work, rest/sleep, social participation, education, quality of life, occupational therapy, OT, physical therapy, rehabilitation, CP participation, OTPF, ICF, participation assessment, participation scale. The inclusion and exclusion criteria are categorized in According to the accessible databases, 156 articles were found in the scope of the study. Because of repetitive and duplicability of some articles, 17 articles were discarded. Thirty-nine articles were included . Some arThe aim of this study was to review the articles about Iranian CP children in different life areas. Participation promoting in different areas of occupations independently is the result and main outcome of rehabilitation services. Rehabilitation intervention in participating in life areas are more important that intervention in cognitive, motor, sensory, perceptual components (30). Furthermore, this systematic review helps to promote the rehabilitation interventions in the participations areas independently in contrast of rehabilitation interventions just on motor, sensory, or cognitive components. In this study, the most studies about Iranian CP children participations in life areas were in the ADL area of participation (N=12), and the lowest articles were in the area in the field of: Work (N=2), play (N=2), and sleep/rest (N=2). These findings can be inferred from the: 1) many of occupational therapist or other rehabilitation members, has not enough information about other life areas, many of them just know about ADL areas of participation; 2) maybe the parents of CP children do not know about the main aim of rehabilitation; 3) many of therapists do not know about occupation based practices; 4) the therapists do not know about the sufficient participation assessment tools. The most effective studies on the participation of Iranian CP children are as follows:1) Field of ADL: The Bobath technique, Conductive Education, and education to parents, high level of GMFCS of CP Children, Occupational Therapy Home Program in the form of workshops and educational pamphlets with telephone follow-up, self-steam and self-confidence education, psychological rehabilitation of children with cerebral palsy, high-level of upper extremity function, physical fitness, enhancement of parents knowledge about how to take care of a child with CP professionally, spasticity reduction, appropriate handling can be mentioned as the facilitators of the participation of Iranian CP children in ADL and factors consisting: poor internal physical modification at home, poor practical training to family members and lack of assistive device can be mentioned as barriers of participation of Iranian cerebral palsy children in ADL (n in ADL -23.2) Field of IADL: Minimizing barriers and providing more facilitators, appropriate handlings, right to access to housing, are the facilitators of the participation of Iranian cerebral palsy children in IADL. Participation diversity and intensity of CP children in the field of IADL are lower than their normal peers are (eers are -26.3) Field of Play: Participation diversity and intensity of CP children in the field of play are lower than their normal peers, and right to accesses to play and sport can promote their participation in the field of play Field of leisure: The participation enjoyments of CP children in leisure activities are lower than other children, and factors such as: lack of access and benefits of facilities to participate in leisure activities, individual , structural (Accessibility to the public facilities) and socio cultural , are the effective barriers to participation in leisure activities Field of rest/Sleep: the factors such as: enhancement of parent\u2019s knowledge about how to take care of a child with CP professionally and right to assess and benefits of facilities to participate in sleeping and rest activities of CP children had effective influence on participation of CP children in the field of rest/sleep Field of Education: The factors such as: poor handling at school because of inappropriate physical structure, poor attention to education and environmental barriers in two groups: 1) policies ; 2) physical and structural , leads to poor education of CP children and minimizing barriers and providing more facilitators to access to education and information improves the participation of education Field of Work: Minimizing barriers and providing more facilitators to access to job leads to work participation Field of social participation: The participation enjoyments of CP children in the field of social participation activities are lower than other children are. Factors such as: 1) lack of access and benefits of facilities, individual , structural (Accessibility to the public facilities) and socio cultural barriers; 2) poor handling at society consist of: psychological and religious abuse of CP children, inadequate government\u2019s supports and inadequate civil facilities for CP children; 3) poor attention of rehabilitation members team, and; 4) environmental barriers in two groups: 1) policies ; 2) physical and structural , leads to poor social participation of CP children the factors such as; 5) improvement in gross motor functions of CP children; 6) right to access to medical care and rehabilitation and right to access to places and transportation system; 7) psychological rehabilitation of children with cerebral palsy; 8) high level of upper extremity function; and 9) spasticity reduction leads to improvement of social participation activities of CP children that all of them are important in enhancement of quality of life of CP children. None of them is preferred over another. According to that for good intervention in participation of CP children, using good and properties assessment tools of participation is important. We achieved that in Iran many researchers did not pay attention to the participation of CP children and many articles just paid attention to the sensory, motor or cognitive components of their clients. Among the life areas of participation the most focuses is on the ADL and social participation areas and the other areas are least important. Therefore, the suggestion of this study is that the researchers pay attention to the other areas of occupations and life areas of Iranian CP children because none of these areas are preferred over another."} +{"text": "Nanoscience and Nanotechnology became the trend of the 21st century, influencing many areas such as electronics, biology, medicine, aerospace, agriculture, and the engineering of novel materials. Recently a new aspect of nanoscience and nanotechnology appeared and has been rising rapidly ever since: functional nanostructures, intelligent nanostructures for targeted applications. In the present Thematic Series a bright spectrum of such targeted functional nanostructures is presented demonstrating the unique possibilities of engineering at the nanometer scale. The self-organization of nanoparticles, nanowires or nanotubes and the introduction of those structures into various materials made it possible to solve long-standing problems. Examples presented in this Thematic Series are:the problem of treatment of multidrug-resistant tuberculosis, which can be resolved using the invented nano-encapsulated medicines penetrating through the cell membrane of the tuberculosis bacilli ,new applications of graphene-based nanostructures \u20134,smart nanoparticles with antitumor activity ,photonic crystals and flexible membranes \u20137 for viA lot of other unusual applications of functional nanostructures are presented in over 40 articles of this Thematic Series, giving the possibility to gain new knowledge about the rapidly developing area of nanoscience and nanotechnology.The idea to this Thematic Series appeared during the international conference \u201cNANO-2016: Ethical, Ecological and Social Problems of Nanoscience and Nanotechnologies\u201d, which took place in May 2016 in Chisinau, Moldova. It presented new technological approaches for assembling of functional nanostructures and nanomaterials with special properties. As the guest editor of this Thematic Series I would like to thank all colleagues and highly experienced experts who submitted their manuscripts with novel results, new ideas, and technological approaches. I believe that this Thematic Series will attract attention of scientists, technologists, engineers and will find many readers. The professional and friendly editorial support by the Production Team of the Beilstein-Institut is greatly acknowledged.Anatolie SidorenkoChisinau, January 2017"} +{"text": "In plants, the chloroplast is the organelle that conducts photosynthesis. It has been known that chloroplast is involved in virus infection of plants for approximate 70 years. Recently, the subject of chloroplast-virus interplay is getting more and more attention. In this article we discuss the different aspects of chloroplast-virus interaction into three sections: the effect of virus infection on the structure and function of chloroplast, the role of chloroplast in virus infection cycle, and the function of chloroplast in host defense against viruses. In particular, we focus on the characterization of chloroplast protein-viral protein interactions that underlie the interplay between chloroplast and virus. It can be summarized that chloroplast is a common target of plant viruses for viral pathogenesis or propagation; and conversely, chloroplast and its components also can play active roles in plant defense against viruses. Chloroplast photosynthesis-related genes/proteins (CPRGs/CPRPs) are suggested to play a central role during the complex chloroplast-virus interaction. Plant viruses, as obligate biotrophic pathogens, attack a broad range of plant species utilizing host plants' cellular apparatuses for protein synthesis, genome replication and intercellular and systemic movement in order to support their propagation and proliferation. Virus infection usually causes symptoms resulting in morphological and physiological alterations of the infected plant hosts, which always incurs inferior performance such as the decreased host biomass and crop yield loss.The most common viral symptom is leaf chlorosis, reflecting altered pigmentation and structural change of chloroplasts. Viral influence on chloroplast structures and functions usually leads to depleted photosynthetic activity. Since the first half of the twentieth century, an increasing number of reports on a broad range of plant-virus combinations have revealed that virus infection inhibits host photosynthesis, which is usually associated with viral symptoms fluctuation of chlorophyll fluorescence and reduced chlorophyll pigmentation , affect chloroplast ultrastructure and symptom development (see below).N. tabacum leaves have been demonstrated as determinants of symptom phenotypes for a much long period protein in tobacco plants results in a virus-like chlorosis symptom associated with the abnormal thylakoid stacks Figure , Table 2Studies on the effect of virus infection on expression of chloroplast proteins at the transcriptomic and proteomic levels provide insights into the molecular events during symptom expression. In the susceptible plant response to virus infection, the majority of significantly changed proteins are identified to be located in chloroplasts or associated with chloroplast membranes. Most of them are down-regulated and correlate with the severity of chlorosis Dardick, . During As the biosynthesis of CPRPs is a complicated process with a series of steps Seidler, , plant vflavum strain leads to a total depletion of PS II core complex and OEC, including chloroplast-encoded CPRP PsbA and nuclear-encoded CPRPs LhcB1, LhcB2 and PsbO. However, the PsbA mRNA accumulated to a higher level in the infected leaves gene transcripts and down-regulates its expression by RNA silencing with blocked chloroplast development and depletion of chloroplast-encoded proteins RNA which can disturb chloroplast function and induce disease symptoms pathway for targeting CPRGs transcripts. The tenuivirus RSV, causing a devastating disease in East Asia countries, hijacks CPRP during infection and perturbs photosynthesis to fulfill the transport via symplastic routes within plant hosts , a gene involved in the JA signaling pathway, accelerates the development of symptoms caused by co-infection of PVX and PVY, and accumulation of viral titers at early stages of infection in the chloroplast membranes , and the photosynthetic electron transport chain is responsible for ROS generation Asada, . Superoxs Asada, . The burs Asada, . Chlorops Asada, .N-mediated TMV resistance response. Further, a number of stromules surround nuclei during plant defense response, which is correlated with the accumulation of chloroplast-localized defense protein NRIP1 and H2O2 in the nucleus. In the absence of virus infection, suppression of chloroplast CHUP1 induces stromules and enhances programmed cell death constitutively protein of potyviruses is required for virus replication and cell-to-cell movement. CI protein from PPV and TVMV interacts with photosystem I PSI-K protein Table , the proL88 with high RNAi suppressor activity , a rhodanese sulfurtransferase which is destined to chloroplast under normal conditions, associates with both the tobacco N receptor and 126 K replicase during TMV infection; its relocation from chloroplast to cytoplasm and nucleus is required for N-mediated resistance to TMV , the National Basic Research Program of China (2014CB138400), the Special Fund for Agro-scientific Research in the Public Interest of China (201303028), and the China Postdoctoral Science Foundation (2014M550049), the Initial Funding of Zhejiang Academy of Agricultural Sciences, and the Cultural Funding for Youth Talent of Zhejiang Academy of Agricultural Sciences (2015R21R08E03).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the \u201ccontrol\u201d of the \u201cmaster biological clock\u201d reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders. At the same time circadian rhythms remain in a strong, reciprocal interaction with the hypothalamic-pituitary-adrenal (HPA) axis. Recent findings point to a role of circadian disturbances and excessive stress in the development of obesity and related food consumption and metabolism abnormalities, which constitute a major health problem worldwide. Appetite, food intake and energy balance are under the influence of several brain neuropeptides, including the orexigenic agouti-related peptide, neuropeptide Y, orexin, melanin-concentrating hormone and relaxin-3. Importantly, orexigenic neuropeptide neurons remain under the control of the circadian timing system and are highly sensitive to various stressors, therefore the potential neuronal mechanisms through which disturbances in the daily rhythmicity and stress-related mediator levels contribute to food intake abnormalities rely on reciprocal interactions between these elements. Circadian (~24 h) fluctuations of different components of the external environment, in particular light-dark conditions, shape animals' physiology and behavior for the optimal synchronization to the cyclical changes encountered. As a consequence of this influence, biological processes called circadian rhythms developed in most organisms , the anterior lobe of the pituitary gland, and the adrenal cortex. PVN neurons synthesize corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), which stimulates secretion of adrenocorticotrophic hormone (ACTH) from the anterior pituitary and ACTH controls the release of glucocorticoids (GCs) from the adrenal cortex of the hypothalamus is a key appetite regulatory center Banks, . It contAcute and chronic icv NPY administration result in hyperphagia, obesity and changes in metabolism neurons , by statutory funds of the Institute of Pharmacology, Polish Academy of Sciences (GH) and by National Health and Medical Research Council of Australia Project Grant 1067522 and Research Fellowship 1005985 (ALG).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "According to the World Health Organization, high-impact diseases (HID) including cardiovascular diseases, metabolic diseases, and a variety of types of cancer are the top challenge to the entire medical community globally . TherapeRecently, omics technologies including genomics, proteomics, transcriptome, and metabolomics have been developed and improved significantly. This is especially true for RNA sequencing together with the system-based pharmacology, which has overcome the barriers and greatly improved our understanding of the pharmacology of natural products for the prevention and treatments of HID.For example, Shuanglong Formula (SLF) and Qishen granules (QSG) are well-studied natural products for the treatment of cardiovascular diseases. Multiomics including metabolomics and comparative proteomics were performed to investigate the SLF's effects on the regulation of myocardial energy metabolism , 4. Y. WIn addition, new omics approaches are also developed to identify the active indigents and potential targets of natural products. A novel approach for relative and absolute quantitation was established to specifically and comprehensively identify the protein targets of andrographolide (Andro) , and BATRheum palmatum L., Gardenia jasminoides Ellis, and Artemisia annua L., had an improved therapeutic effect on hepatic injury syndrome through regulating dynamic patterns in metabolic biomarkers and target proteins and activating both intrinsic and extrinsic pathways [Due to the diverse components of natural products, systematically integrating the readouts of genomics, transcriptomics, proteomics, and metabolomics will dramatically facilitate our understanding of molecular mechanisms of natural product actions, as well as identifying biomarkers or targets for future research and clinical practice. Recently, an integrated proteomic and metabolomics research demonstrated that a combination of natural products comprising of pathways .Unsurprisingly, more omics studies are currently under way to reveal the molecular mechanisms of treatments using natural products. The current issue is a collection of selected works that use the approaches of genomics, metabolomics, RNA sequencing, and network pharmacology to comprehensively elucidate the natural product pharmacology in the treatments of HID including heart failure, diabetes and its complications, nonalcoholic fatty liver disease, and depression. It is a timely update to our knowledge on both the molecular mechanism and novel drug discovery for HID.Yong WangQin FengPeijian HeLixin ZhuGuoxun Chen"} +{"text": "Quantitative structure-activity relationship (qSAR) models are used to understand how the structure and activity of chemical compounds relate. In the present study, 37 carboquinone derivatives were evaluated and two different qSAR models were developed using members of the Molecular Descriptors Family (MDF) and the Molecular Descriptors Family on Vertices (MDFV). The usual parameters of regression models and the following estimators were defined and calculated in order to analyze the validity and to compare the models: Akaike?s information criteria (three parameters), Schwarz (or Bayesian) information criterion, Amemiya prediction criterion, Hannan-Quinn criterion, Kubinyi function, Steiger's Z test, and Akaike's weights. The MDF and MDFV models proved to have the same estimation ability of the goodness-of-fit according to Steiger's Z test. The MDFV model proved to be the best model for the considered carboquinone derivatives according to the defined information and prediction criteria, Kubinyi function, and Akaike's weights."} +{"text": "Endemism is an important concept in biogeography and biodiversity conservation. China is one of the richest countries in biodiversity, with very high levels of plant endemism. In this study, we analysed the distribution patterns of diversity, the degree of differentiation, and the endemicity of Chinese endemic seed plants using the floristic unit as a basic spatial analysis unit and 11 indices. The analysis was based on distribution data of 24,951 native seed plant species (excluding subspecies and varieties) and 12,980 Chinese endemic seed plant species, which were sourced from both specimen records and published references. The distribution patterns of Chinese endemic flora were generally consistent but disproportionate across China for diversity, degree of differentiation and endemicity. The South Hengduan Mountains Subregion had the highest values for all indices. At the regional level, both the Hengduan Mountains and the Central China regions were highest in diversity and degrees of differentiation. However, both the rate of local endemic to native species and the rate of local to Chinese endemic species were highest in the Taiwan Region and the South Taiwan Region. The Hengduan Mountains Region and the Central China Region are two key conservation priority areas for Chinese endemic seed plants. Thus, the regionalization of Chinese flora is also difficult and challenging. Wu was the first researcher to publish a comprehensive regionalization of Chinese flora based on pioneering works that had been published over decades. He classified Chinese flora into 2 kingdoms, 7 subkingdoms and 22 regionsAs described previously, many studies of biodiversity conservation have been conducted across China. However, they primarily used an administrative unit, particularly at the provincial level, as the spatial unit for analysis rather than a natural geographic or floristic unit. It is better to identify conservation priority areas on the basis of a natural geographic or floristic unit because such classifications substantially reduce the influence of and definition by human factors. Therefore, using the floristic unit as the basic unit of spatial analysis, we examined the distribution patterns, diversification and degrees of differentiation of Chinese endemic seed plants and identified conservation priority areas across the country for conservation planning and future effective conservation actions.Based on a previously published list of Chinese endemic seed plant speciesWe digitized the map of floristic regions of ChinaMeasurement of species diversity was based on species richness, i.e., the number of species in each spatial units)g)sf)The degrees of differentiation among endemic flora were represented by differentiation indices, which included a species differentiation index .where Proportions of endemism were calculated to compare the distribution patterns of endemic flora in China. These proportions included the rate of Chinese endemic to native species (RCENS), the rate of local endemic to native species (RLENS) and the rate of local to Chinese endemic species (RLCES).s), the number of genera (Ng), the number of families (Nf), the number of local endemic species (NLES), the degree of species differentiation (Ds), the degree of genus differentiation (Dg), the degree of species\u2013family differentiation (Dsf), weighted endemism (WE), the rate of Chinese endemic to native species (RCENS), the rate of local endemic to native species (RLENS) and the rate of local to Chinese endemic species (RLCES). These 11 indices were standardized by dividing their maxima and then summed to produce a total value. All floristic units were ranked according to their total value, and conservation priority areas for Chinese endemic seed plants were identified according to each unit\u2019s rank. The spatial floristic unit was used to prioritize conservation areas, and the units with the highest total values were the tip-ranked areas because higher values were determined by greater endemic species richness and the degree of differentiation and endemism. In this study, the top eight floristic units were designated conservation priority areas.To summarize, the 11 indices were as follow: the number of species and the Central Yunnan Plateau Subregion (IIIE13a) contained the most families . These tChinese endemic seed plant species were also unevenly distributed across the country. The South Hengduan Mountains Subregion (IIIE14b) was the richest, with 5177 species of Chinese endemic seed plants, which was followed by the Central Yunnan Plateau Subregion (IIIE13a), with 3688 species . The PamThe distribution patterns of Chinese endemic flora at family, genus and species levels across the country were generally consistent . The patThe degree of differentiation among endemic seed plant species was unevenly distributed across China . The higThe spatial distribution patterns of Chinese endemic plant species, local endemic species and weighted endemism were significantly correlated (P\u2009<\u20090.001) , and allThe endemic rates were also unevenly distributed across the country . The ratThe South Hengduan Mountains Subregion (IIIE14b), the Central Yunnan Plateau Subregion (IIIE13a), the Sanjiang Valley Subregion (IIIE14a) and the North Hengduan Mountains Subregion (IIIE14c) had the highest total values of all floristic units . These sThe degree of species differentiation among Chinese endemic seed plants was unevenly distributed across the country. Although the degree of differentiation was not high in many parts of China, it was particularly high in the Hengduan Mountains12The rate of Chinese endemic to native plant species was highest in the South Hengduan Mountains Subregion (IIIE14b), followed by the North Hengduan Mountains Subregion (IIIE14c). Based on this result, endemicity of flora in the Hengduan Mountains is very high across China. However, the South Hengduan Mountains Subregion and the North Hengduan Mountains Subregion differ in endemicity. The terrain of China from west to east forms a flight of three steps, commonly called the \u201cGeomorphological Three Steps\u201d. The First Step mainly encompasses the Qinghai-Tibet Plateau, north to the Kunlun, Aerhchin, and Qilian mountains and east to Min, Qionglai, Daxue and Hengduan mountains. The Second Step lies between the Hengduan Mountains to the west and the Daxing\u2019anling, Taihang, Funiu, and Xuefeng mountains to the east, primarily including the Inner Mongolian Plateau, Loess Plateau, Qinling Mountains, Sichuan Basin, and Yun-Gui Plateau. The Third Step covers the entire area east from the Second Step, and includes the Northeast China Plain, North China Plain, Middle-lower Yangtze Plain, Jiangnan hills, Nanling Mountains, Guangdong and Guangxi hills, Zhejiang and Fujian hills as well as Taiwan and HainanThe rate of local endemic to native plant species was highest in the Taiwan Region (IVG19) and the South Taiwan Region (IVG20), which indicates that the flora of Taiwan is distinctive. The rate of local to national endemic plant species was the highest in the Taiwan Region (IVG19), the South Taiwan Region (IVG20), the Altai Region (IA2) and the Pamir-Karakoram-Kunlun Subregion (III17c). This result shows that the island of Taiwan, the Altai Region (IA2) and the Pamir-Karakoram-Kunlun Subregion (III17c) have different flora that might be influenced by trans-boundary flora from neighbouring countries.The four top conservation priority areas were identified; the South Hengduan Mountains Subregion IIIE14b), the Central Yunnan Plateau Subregion IIIE13a), the Sanjiang Valley Subregion (IIIE14a) and the North Hengduan Mountains Subregion (IIIE14c). Most of these subregions are in the geographical terrain of the Hengduan Mountains. The Hengduan Mountains are rich in mountainous flora and are thus a key area for studies of the relationships among Laurasian, Gondwanian and Tethyan flora414b, the Ca, the SaThree other top conservation priority areas were identified; the Guizhou Plateau Subregion IIID10d), the Sichuan-Hubei-Hunan Border Subregion (IIID10c) and the Qinling-Bashan Subregion (IIID10a). These three subregions are in the Central China Region. The flora of this region comprises direct and nearly intact descendants of a Tertiary ancient flora0d, the S44112The diversity and degrees of differentiation among Chinese endemic seed plants are unevenly distributed across the country. Both the Hengduan Mountains and Central China regions are diversity centres that also have the highest degrees of differentiation. Moreover, the Hengduan Mountains Region and the Central China Region are two key conservation priority areas for Chinese endemic seed plants based on diversity, degrees of differentiation and endemicity. In addition, the Taiwan Region, the Altai Region and the Pamir-Karakoram-Kunlun Subregion have unique endemic flora, and greater attention should be paid to the flora of these regions or subregions in future conservation planning and actions.How to cite this article: Huang, J. et al. Diversity distribution patterns of Chinese endemic seed plant species and their implications for conservation planning. Sci. Rep. 6, 33913; doi: 10.1038/srep33913 (2016)."} +{"text": "Paralytic ileus is type of functional obstruction caused by the lack of intestinal peristalsis without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Paralytic ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced . The incIranian traditional medicine is one of the oldest traditional medicines. Avicenna (980\u20131037AD) was a great Iranian clinician and philosopher. He in his famous book, Qanun of Medicine thoroughly has reviewed all of the medical science of ancient Greek and Muslim scholars , 5.Based on Iranian traditional medicine, paralytic ileus, type of functional intestinal obstruction, has been described under title of Gholonj disease. This chapter deals with the physiopathology and management of the gastrointestinal obstructive disorders in Iranian traditional medicine , 7. GholGolonj is classified based on the etiology of obstruction to six categories . Non-mecExcluding type of mechanical obstruction, the strategy of treatment is based on medical because main pathology is no mechanical obstruction. For example, based on the definition of Gholonj-e-Reehi, Avicenna expresses that there is no any real obstruction agent; and accumulation of gas prevents from intestinal movement and defecation.Medical treatment strategies of Golonj disease are various and includes of procedures, medical herbs, and diet recommendations.Recent studies reveals pathophysiology of paralytic ileus is complex and multifactorial, consisting of neurologic and inflammatory agents. Activation of sympatic system or inflammatory response cells in muscle layers of bowel leads to generalized hypo motility of gastrointestinal tract . In explExcluding some of Avicenna\u2019s viewpoint and his etiology of intestinal obstruction based on humoral theories, most of his definition can be compared with medical current concepts. Increased insight into options mentioned in Qanun can be useful for new study, aiming to manage better of disturbances of gastrointestinal function. However, establishing of this concept requires further research and the generation of scientific evidence."} +{"text": "The results of numerous studies indicate that fish possess bacterial populations on or in their skin, gills, digestive tract, and light-emitting organs. In addition, the internal organs of healthy fish may contain bacteria, but there is debate about whether or not muscle is actually sterile. Using traditional culture-dependent techniques, the numbers and taxonomic composition of the bacterial populations generally reflect those of the surrounding water. More modern culture-independent approaches have permitted the recognition of previously uncultured bacteria. The role of the organisms includes the ability to degrade complex molecules , to produce vitamins and polymers, and to be responsible for the emission of light by the light-emitting organs of deep-sea fish. Taxa, including Pseudomonas, may contribute to spoilage by the production of histamines in fish tissue."} +{"text": "Advancements in next-generation sequencing and other -omics technologies are accelerating the detailed molecular characterization of individual patient tumors, and driving the evolution of precision medicine. Cancer is no longer considered a single disease, but rather, a diverse array of diseases wherein each patient has a unique collection of germline variants and somatic mutations. Molecular profiling of patient-derived samples has led to a data explosion that could help us understand the contributions of environment and germline to risk, therapeutic response, and outcome. To maximize the value of these data, an interdisciplinary approach is paramount. The National Cancer Institute (NCI) has initiated multiple projects to characterize tumor samples using multi-omic approaches. These projects harness the expertise of clinicians, biologists, computer scientists, and software engineers to investigate cancer biology and therapeutic response in multidisciplinary teams. Petabytes of cancer genomic, transcriptomic, epigenomic, proteomic, and imaging data have been generated by these projects. To address the data analysis challenges associated with these large datasets, the NCI has sponsored the development of the Genomic Data Commons (GDC) and three Cloud Resources. The GDC ensures data and metadata quality, ingests and harmonizes genomic data, and securely redistributes the data. During its pilot phase, the Cloud Resources tested multiple cloud-based approaches for enhancing data access, collaboration, computational scalability, resource democratization, and reproducibility. These NCI-led efforts are continuously being refined to better support open data practices and precision oncology, and to serve as building blocks of the NCI Cancer Research Data Commons. Precision medicine has evolved out of the seminal work of the Human Genome Project, advancements in DNA sequencing technology, developments in high throughput and large-scale molecular biology technologies, improvements in the speed and scale of computation, and innovations in biomedical informatics. This progress has resulted in the molecular characterization of individual patient tumors, the identification of actionable genetic alterations, and the development of evidence-based molecular cancer diagnostics and targeted therapies. Although, cancer types have been traditionally classified by organ or cell type, with the aid of genomics, cancer patients are increasingly being treated according to their cancer's unique molecular signature. Cancer is a diverse array of genetically-driven diseases. The identification and validation of actionable genetic alterations including amplifications, rearrangements, and gain-of-function mutations, has spurred the use of genomic data in oncology practices. Targeted gene sequencing panels, for example, offer insight into the genetic drivers of an individual's tumor and inform the diagnosis, prognosis, and targeted treatment of cancer patients. A number of targets for drug development have been outlined previously , Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) have generated large datasets amassing petabytes of data. These, along with other datasets and resources described in this paper are available to researchers both in the US and internationally Table .In December 2005, TCGA was announced as a new collaboration between the NCI and the National Human Genome Research Institute NIH, . Data tyTARGET was launched in 2006. TARGET's goal is to characterize the genome and transcriptome of hundreds of pediatric acute lymphoblastic leukemia, acute myeloid leukemia, Wilms tumor, clear cell sarcoma of the kidney, rhabdoid tumor, neuroblastoma, and osteosarcoma samples. Through genomic and transcriptomic analyses, researchers are studying the relationships among alterations at the DNA and RNA levels, cancer growth, cancer progression, and pediatric patient survival characterize the proteomes of tumor and normal tissues; (2) perform proteogenomic analyses of cancer biospecimens; (3) identify potential biomarker candidates through discovery proteomics and develop targeted assays against those candidates; and (4) perform verification tests on those targeted assays. Phase I of CPTAC consisted of technical quality assurance studies Network has emerged as a tri-agency collaboration to enable oncologists to use their patients' unique proteogenomic profiles to inform precision oncology treatments , a cloud-based infrastructure in support of data sharing, tool development, and compute capacity to democratize big data analysis and to increase collaboration among researchers. NCI has sponsored two recent initiatives that serve as the foundation for the Cancer Research Data Commons\u2014the Genomics Data Commons (GDC), and three Cloud Resources.The GDC, built and managed by the University of Chicago Center for Data Intensive Science, in collaboration with Ontario Institute for Cancer Research, all under an NCI contract with Leidos Biomedical Research, is a unified genomic data repository that hosts authoritative NCI reference datasets such as TCGA and TARGET Pilots. The purpose of the CGC Pilots was to explore multiple cloud-based approaches for enhancing secure data access, collaboration, computational scalability, resource democratization, and reproducibility. Through this program, the Broad Institute, the Institute for Systems Biology, and Seven Bridges have each developed what are now known as Cloud Resources. Each platform is deployed in a commercial cloud, and has applied a distinct approach to providing access to TCGA and TARGET genomic data in a cloud environment, and integrating proteomic data from CPTAC as well as radiology images and associated metadata from The Cancer Imaging Archive (TCIA). In addition to providing access to these datasets through rich Application Programming Interfaces (APIs) and graphical user interfaces, the Cloud Resources each provide a platform to enable the deployment of analysis, visualization, and other computational tools in the cloud, bypassing the need to bring data to a local infrastructure. The Cloud Resources support tool deployment through the use of Docker containers, which allow users to package their tools along with all associated dependencies. These \u201ccontainerized\u201d tools can be connected and executed as workflows in these cloud environments. End user documentation provides users with guidance on how to query data, install tools, as well as create and run workflows in each environment. All three platforms conform to strict federal information system security requirements and manage access to controlled data through Database of Genotype and Phenotype (dbGaP) authorization. In addition to their fundamental charter of providing secure cancer genomic data access co-localized with analysis pipelines and visualization tools, the Cloud Resources each offer unique capabilities suitable for a range of research needs.The Broad Institute's FireCloud, was built as the next generation of Broad Institute's Firehose data analysis infrastructure developed for the TCGA program Ulrich, . FireCloThe Institute for Systems Biology Cancer Genomics Cloud (ISB-CGC) runs on the Google Cloud Platform and offers an interactive web-based application and hosts Application Programming Interfaces (APIs) such as the Global Alliance for Global Health API. ISB-CGC takes advantage of Google Cloud Platform's built-in resources such as BigQuery, Compute Engine, App Engine, Cloud Datalab, and Google Genomics. Researchers can use BigQuery to explore clinical, biospecimen, level-3 open access TCGA, and CPTAC II data. ISB-CGC hosts numerous genomics tools and has recently added the Trans Proteomic Pipeline analysis suite. Researchers can now access complementary genomic and proteomic data, run multi-omic analyses, and perform BigQuery searches to investigate genetic alterations, copy number, transcript expression, protein expression, and molecular pathways that are involved in cancer biology. ISB-CGC has also made radiology and tissue images from TCIA and the GDC available through Google Cloud Storage. Additional datasets available at ISB-CGC include the Catalog of Somatic Mutations in CancerCurrently, over 1,600 researches from over 40 countries are using the Seven Bridges Cancer Genomics Cloud (SB-CGC) to analyze hosted genomic data, and/or their own dataThe initial versions of The NCI Cloud Resources, the CGC Pilots, were created to maximize the value of cancer -omics data through harnessing multi-disciplinary expertise. Synergizing technologies from the fields of medicine, molecular biology, informatics, and cloud computing, the CGC Pilots have begun to transform how cancer data analysis is conducted. Researchers, both in the US and internationally, have been able to advantage of these cloud-based resources. To ensure the success of this project and to identify areas for improvement, the CGC Pilot and NCI teams established mechanisms to support early adopters' use of these platforms and to collect their feedback.The CGC Pilots teams provided technical support to new users who sought to implement new tools, access data, or create collaborative workspaces. Through the three CGC Pilots, NCI provided cloud compute and storage \u201ccredits\u201d to offset the costs of evaluation of these platforms by cancer researchers. These funds directly impacted the work of researchers such as post-doctoral scholar Dr. Brittany Lasseigne, at the HudsonAlpha Institute for Biotechnology in Huntsville, AL. Dr. Lasseigne used the SB-CGC, to study dosage effects, context dependency, and tissue specificity of tumor suppressors across human cancers in TCGA. These Cloud credits supported the use of the large-scale genomic datasets co-located with computational resources and analysis tools, and increased research efficiency for many early stage researchers like Dr. Lasseigne .To evaluate the CGC Pilots and support on-going NCI-funded cancer research, NCI funded administrative supplements to the active grants of investigators performing genomics-based research. The Funding Opportunity Announcement, Supplements to Support Evaluation of the NCI Cancer Genomics Cloud Pilots (PA-15-305), funded projects to use one or more of the NCI CGC Pilots for ongoing research activities. Funds were awarded to investigators whose projects aimed to install and test the performance of new analysis tools on a CGC Pilot, upload locally-generated genomic data and perform analyses on a CGC Pilot, and/or perform analyses of hosted TCGA data. The researchers reported having a generally positive experience working on the CGC Pilots; however, as expected, some encountered technical hurdles. When those technical issues arose, the vast majority of the groups were able to resolve their problems by working directly with the CGC Pilot support teams. Each research group provided extensive feedback to the CGC Pilots and NCI teams on what elements of the CGC Pilots could be improved. The majority of the administrative supplement awardees reported that they plan to continue to use the CGC Pilots to accelerate their research and that the CGC Pilots have the potential to be a vital resource for the cancer research community. The activities and outcomes of projects funded through these supplements have helped inform NCI's decision to continue supporting this project beyond the pilot phase and to develop a more comprehensive computational infrastructure for -omics and other big data types.Cancer research in the era of big data presents major challenges: computing on large datasets, combining expertise from various disciplines, and developing the infrastructure needed to enhance research efficiency. Recognizing the importance and urgency of these needs, the Beau Biden Cancer Moonshot Blue Ribbon Panel has recommended that the cancer research community aim to, \u201ccollect, share, and interconnect a broad array of large datasets so that researchers, clinicians, and patients will be able to both contribute and analyze data, facilitating discovery that will ultimately improve patient care and outcomes BRP, .\u201d In linThe GDC and Cloud Resources currently support basic and translational research, primarily using genomic and clinical data. These activities serve as the building blocks of the cloud-based NCRDC Figure . The NCRThe era of big data in biomedical research and precision oncology calls for creative strategies borrowed from multiple scientific and technological disciplines. The GDC and Cloud Resources are important steps in supporting the next generation of data-driven cancer research. Looking ahead, the NCRDC represents an interdisciplinary solution to the challenges of big data in cancer research. NCI will continue to lead open science efforts toward the goals of improving prevention strategies, developing targeted diagnostics and therapeutics, and reducing the burden of cancer on patients, their families, and society.IH: Manuscript writing, figure design. TD, JK, AK, and WK: Manuscript and figure revision, approval of final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Hypertensive disorders of pregnancy (HDP), particularly pre-eclampsia and eclampsia, remain one of the leading causes of maternal mortality and are contributory in many foetal/newborn deaths. This editorial discusses a supplement of seven papers which provide the results of the first round of the CLIP (Community Level Interventions for Pre-eclampsia) Feasibility Studies. These studies report a number of enablers and barriers in each setting, which have informed the implementation of a cluster\u2013randomized trial (cRCT) aimed at reducing pre-eclampsia-related, and all-cause, maternal and perinatal mortality and major morbidity using community-based identification and treatment of pre-eclampsia in selected geographies of Nigeria, Mozambique, Pakistan and India. This supplement unpacks the diverse community perspectives on determinants of maternal health, variant health worker knowledge and routine management of HDP, and viability of task sharing for preeclampsia identification and management in select settings. These studies demonstrate the need for strategies to improve health worker knowledge and routine management of HDP and consideration of expanding the role of community health workers to reach the most remote women and families with health education and access to health services. A healthy mother and baby are the desired outcomes of all antenatal and intrapartum care. Hypertensive disorders of pregnancy (HDP), particularly pre-eclampsia and eclampsia, remain one of the leading causes of maternal mortality and are contributory in many foetal/newborn deaths. As a result, an estimated 76,000 maternal and 500,000 foetal/newborn deaths occur each year with more than 10 million pregnancy complications [Improving quality of care for mothers and babies during pregnancy and childbirth has the potential to prevent 2 million deaths each year \u20137. DespiSpecific to HDP, research is now underway through the CLIP (Community Level Interventions for Pre-eclampsia) trials in hopes of reducing the burden of adverse maternal and perinatal outcomes related to pregnancy hypertension through community engagement, mobile technology and task-sharing to community health-care providers . Using aThis editorial discusses a supplement of seven papers which provide the results of the first round of the CLIP Feasibility Studies \u201319. ThesUnderstanding the perspectives of women and their communities offers important insights into the enablers and barriers to accessing health care. More context-specific studies and opportunities for women themselves to be engaged in defining quality of maternal and newborn care are needed. One paper in this supplement specifically focuses on community perspectives on the determinants of maternal health in Mozambique, including women\u2019s perspectives, although literature from other settings is referenced in other papers . In MozaThese studies further elucidate the issues of health worker knowledge and routine pregnancy management related to HDP. For CHWs to effectively educate communities about HDP and serve their communities in identifying and managing cases, the CHWs themselves need to have the knowledge about the etiology, symptoms and treatment options available. Across the different settings of the CLIP Feasibility studies, the knowledge of CHWs regarding pre-eclampsia and eclampsia spanned a broad range: Lady Health Workers (LHWs) in Pakistan and Community Health Extension Workers (CHEWs) in Nigeria were correctly able to identify cases , 14; AccMagnesium sulfate \u2013 the World Health Organization (WHO) recommended medication for the treatment and prevention of seizures related to severe pre-eclampsia - is ineThese studies further examined the feasibility of task-sharing aspects of care for women with HDP , 18, in The two papers in this supplement on task sharing provide further important evidence on known strategies , 18 inclIn several of these countries, the CHWs are multi-purpose, delivering as many as 23 activities and services including nutrition, newborn care, health promotion and prevention and curative care for children . With thThe authors of the CLIP Feasibility Studies report a number of enablers and barriers in each setting, which have informed the implementation of the currently underway CLIP cRCT. This supplement adds to the knowledge base of HDP by revealing the diverse community perspectives on determinants of maternal health, variant health worker knowledge and routine management on HDP, and viability of task sharing for preeclampsia identification and management in select settings. These studies demonstrate the need for strategies to improve health worker knowledge and routine management of HDP and consideration of expanding the role of CHWs to reach the most remote women and families with health education and access to health services.We hope the readers of Reproductive Health find this supplement to be a rich resource for further understanding how best to improve the quality of maternal and perinatal health care in these settings and beyond."} +{"text": "In the studied units it isgenerated common waste (52-60%), infectious-sharps (31-42%) and recyclable(5-17%). The average rates of generation are: 0,09kg of total waste/outpatientassistance and 0,09kg of infectious-sharps waste/outpatient procedure. Thecompliance with regulations, initially 26-30%, then reached 30-38% a year later. the tool showed to be easy to use, bypassing the existence of a complex range ofexisting regulatory requirements, allowed to identify non-conformities, pointedout corrective measures and evaluated the performance of waste management. In thissense, it contributes to decision making and management practices relating towaste, tasks usually assigned to nurses. It is recommended that the tool beapplied in similar healthcare units for comparative studies, and implementation ofnecessary adaptations for other medical services. Services provided in healthcare facilities generate considerable amount of solid wastedenominated as a whole, Healthcare Waste (HW). Much of this waste (75-90%) is consideredsimilar to those generated in households (recyclable or not)-The management of HW involves planning, implementation and monitoring of actions thataim to prevent exposure, ensure the safety of users and professionals involved, preventthe occurrence of environmental impacts while minimizing the generation of waste-Although the management of HW is routinely practiced by healthcare facilities, studiesin developing countries* suffered progressive updates, involving the ministries of Health,Environment and Labor, ending with the establishment of the National Policy of SolidWaste in 2010. All these Brazilian regulations and directives, which are aligned andcomplementary, provide that any healthcare facility in the country, regardless of sizeand complexity of the service, is responsible for managing its waste, and must prepare,implement and monitor its Healthcare Waste Management Plan (HWMP).In Brazil, in the last two decades, the legal and regulatory framework geared toHW,-HWMP is the document that describes all internal and external steps for the managementof waste in healthcare services, in order to prevent occupational accidents, to avoidenvironmental impacts and to protect the public healthThe literature indicates that the simple formulation of the HWMP, involving multipleaspects such as sanitary, environmental, health, and safety of the workers, has been amajor challenge for healthcare institutions. Factors such as the lack of economicresources for the purchase of materials or equipment needed and the shortage of humanresources also hamper the subsequent stages of implementation and monitoring plan.In 2005, a study covering 21 hospitals and 48 outpatient public units of the State ofRio Grande do Sul, Brazil,The nursing sector has a key role in the management of waste, considering that isdirectly involved in the generation of HW and is often commissioned to theadministrative management of healthcare units because of the understanding of thecomplexity and the organization of these servicesIn practice, the presence of these qualified professionals has not happened, which isworrying. In the surgery department of an university hospital in Egypt, which provide basichealthcare services that do not require hospitalization are also called upon to properly manage their waste, according to the rulesin force in the country In December 2015, existed in Brazil 34,951 PHCs in activityIn this context, in order to support the work of healthcare facilities managers on theissue of management of HW, this paper aims to propose a facilitation tool, to supportthe diagnosis, formulation and evaluation of HWMP in PHCs, and present the results ofthe application of this tool in four units of the city of S\u00e3o Paulo. The merit of thisinstrument is the integration of the interdisciplinary among the subject areas involvedand the systematization of current legislation.This is a descriptive study, which used as a research method the multiple case study,applied in four PHCs (identified from PHC-A to PHC-D) in the city of S\u00e3o Paulo, Brazil,during the period from February 2011 to February 2012. The selection criteria of theunits considered all the PHCs that constituted, at the time, the West Project - apartnership for management between the Faculty of Medicine Foundation of the Universityof Sao Paulo (USP) and the Municipality of Sao Paulo Administration. The PHC-D wasanalyzed together with an Emergency Healthcare Unit because they sharedsome services and the outsourced cleaning service.This study consisted of three stages: i) design of a facilitation tool for diagnosis,formulation and evaluation of HWMP using as indicators: waste generation and performanceanalysis; ii) application of the tool in four PHCs, resulting in two consecutivediagnoses regarding the management of waste in 2011 and one year after; and iii)comparative evaluation of both diagnoses.The facilitation tool was formulated from the systematization of the existing legal andregulatory framework in the country, in the state and in the city of S\u00e3o Paulo, and theBrazilian technical standards, resulting in five forms identified from F-I to F-V.daily amount of totalgeneration and by group (kg/d and percentage) and two more appropriateindicators to represent the production of waste in services that provide care withouthospitalization: generation rate per outpatient assistance* andgeneration rate per outpatient procedure** performed in criticalareas***. To feed the indicators of generation, weighing was performed ineach PHC for five consecutive days (one working week of operation), recording thegeneration of each source sector , separately bywaste group: A (infectious), D (common: recyclable and non-recyclable) and E(sharps). Radioactive waste (group C) and chemical (group B) were not consideredbecause the former is not generated in the PHC, while the chemicals still presentincipient segregation. For infectious materials it was used the sum (A+E) becausethey are collected and treated jointly in this city. The values jotted down in theform (F-IV) are the average of values found in the five weighing procedures.Additionally, through administrative records in the studied PHCs, it was computed thedaily average of assistances and the daily average ofprocedures performed in critical areas (recorded in form F-I). Therate of total waste generation per assistance is obtained bydividing the daily average of total waste by the daily average of assistances. Therate of infectious and sharps waste generation (A+E) results fromthe ratio of the daily average of waste by the daily average of procedures performedin the sectors that produce such waste .1. Waste generation indicators: in the literature, these indicators are used toassess whether the generating institution adopts measures to reduce waste productionand performs the separation into different groups to give the appropriate destinationto each group. The indicators selected for this study: 2. Indicator of performance: represented by the scores that resulted from theevaluation of compliance with 142 regulatory requirements contained in Form V (F-V).For completing this form, various techniques were used: survey of secondary data,available documentation , interviews with leaders of different sectors, and on-site observationrecorded in a diary. During the application of the tool, the information collected bythe authors, fed the F-V, which resulted in two diagnoses of managerial andoperational situation of the HW of the four PHCs in 2011, and a year later, a perioddeemed as reasonable for the implementation of the HWMP. The evaluation of the HW management performance in each of the PHC under study,resulted from comparing the diagnoses in the two periods considered, before and afterthe implementation of the plan.Regarding the ethical aspects, the research project was approved by the Ethics andResearch Committees of the Public Health School/USP (OF. COEP 210/10), and of theMunicipal Health Department (CEP/SMS 361/10).facilitation tool. Thefive forms (F-I to F-V) that make up this instrument are described briefly in thefollowing.All requirements and applicable legal requirements - for health, environmental andlabor issues - were incorporated into the Information on the generator facility and responsible: itinvolves data on the location, physical and operational structure of theestablishment; registration data in the competent agencies; amount of human resourcesby function; monthly average of assistances and procedures, and liability relating toHW management and security.F-I. Characterization of the internal flow of waste by sourcesector: it involves the relationship of waste generated separately bygroups (A to E) and by source sector. Lends itself to mapping the property incritical and non-critical areas and the determination of the collection flow. Thesedata help in the distribution planning and calculation of the number and capacity ofthe needed containers, regarding the more efficient segregation and reduction ofwaste.F-II. Description of the external flow and measures to mitigategeneration: identifies the destination of waste indicating the collectioncompanies and receiving units of different waste streams. This information becomes important, as the generator islegally co-responsible for external stages of management. In addition, it assists inthe decision of minimizing the generation and optimization of costs.F-III. Records of indicators of generation and waste minimizationgoals: keeps the record of three indicators, fed with the resultsobtained by measurements and information gathered in the unit, regarding the numberof outpatients assistances and procedures performed during the period: i)rate of daily average waste generation by group (A to E) and therespective percentages; ii) rate of total waste generation perassistance (kg/assistance); and iii) rate of infectious andsharps waste generation (A+E) per procedure in critical areas(kg/procedure).F-IV. The use of these indicators enables the evaluation of the institution's performancein relation to minimizing waste both at whole as per sectors, and supports futuredecision-making. The goals outlined in this form may be checked during the period duefor their achievement or at the time of reapplication at a future date.Checklist of regulatory requirements: this form resulted in 142regulatory requirements, divided into 3 blocks: B1- documentation required; B2-preventive actions to avoid health and environmental risks and B3- steps of theinternal management . F-V. Answers to the checklist allow assessing whether relevant measures for the managementof HW are being adopted. Each requirement may take the following forms: S(Compliant), P , N (Not compliant), and NA (Not applicable). Theun-weighted sum of requirements met, generates a score that reflects the performanceof the unit analyzed. The challenge is to reach 100% of positive responses (S). Asthe documentation is provided, equipment is purchased and used, training programs aredeveloped and operational practices are corrected, the score increases, raising theperformance level and stimulating the search for better results. As an illustration,In 2011, all forms of the tool were filled with data at each PHC under study. Waste quantification indicateIn 2011, there were significant fluctuations in generation rates in the four PHCs.The PHC-C showed the highest values and PHC-D the smallest . Among tIn the second diagnosis, carried out in 2012, the quantification of waste and theconsequent application of the F-IV were affected, considering that management andoperating practices to provide the minimization of waste have not been adopted in anyof the four PHC. Then, the situation one year after, remained virtually the same asthe previous year.The application of F-V was feasible in 2011 and 2012. However, the results showedthat progress in performance management of HW in the PHC under study, was negligible,considering the 142 items to be met .The pro-,Inadequacies in the management of HW and consequent occupational and environmentalsituations of risk are often highlighted in studies conducted in hospitals in developingcountriesIn this study, specifically referring to waste on PHCs, management, operation andinfrastructure failures have been identified, comparable to those mentioned in theliterature. This situation indicates that the legal requirements are not being met,putting at risk the safety of health and cleaning workers as well as users, familycaregivers, workers of the external collection, informal waste pickers and even theenvironment.,In line with previous studies-It is noteworthy that, despite the recommendations set out in studies conducted indifferent countries-,--,-It is also apparent that the most widely used generation indicator in literature - dailyrate per hospital bed (kg of waste/bed.day)generation rate per assistanceand generation rate per procedure in critical areas. It isunderstood that this specificity brings greater reliability to the quantification ofwaste and is more appropriate for outpatient units. The rate of total waste generationper assistance in the four studied PHCs ranged from 0.05 to 0.17kg .This value appears to be higher than the value found in other PHC in Sao PauloIn this study, we proposed two more specific indicators to characterize the generationof waste in outpatient units: In the literature is also remarkable the lack of tools to assess the performance of theHW management. Generation and performance indicators as proposed in the present study,lend themselves both to assess progress in the same unit over time, as well as forcomparison and ranking of PHCs, at any given time.In the PHCs under study, the documented way of exposing the nonconformities served as awarning, however it was not enough to motivate their managers to invest in adapting themanagement of HW. Limiting aspects considered were: the delay in political decision ofthe PHC responsible for the management, and the lack of human and financial resources tomake the needed repairs and improvements.The proposed tool seeks to fill the identified gaps enabling the following procedures:Joint visualization of legal requirements dispersed in different regulatory areasinvolved ; Application by non-experts on the issue, afterbrief training; Identification of structural, operational and behavioral failures in thehealthcare facility; Easy identification of corrective measures to be implemented afteridentification of non-conformities; Setting goals and deadlines; Comparison of resultsin consecutive evaluations, in the same unit, and assessments between different units,evidencing the performance of the HW management; Minimizing the subjectivity of theevaluator; and Achievement of more consistent, reliable and measurable results, formaking decisions.This tool, which organizes all the requirements and legal requirements, may contributeto healthcare management practices, tasks usually attributed to nurses. When fullycompleted, the tool also has the role of documentary record of the healthcare facilitysituation at the completion dates.Because it is an easy-to-handle tool, generating consistent and comparable results, itis recommended to apply this tool in other similar outpatient units, public or privateservices that have size, type of service and of similar HW characteristics.It is also recommended that, for dental, veterinary and even hospitals this tool shouldbe adapted to meet the specific needs of these units. For facilities in othermunicipalities, excluding Sao Paulo should be considered the state and municipalregulations in force."} +{"text": "The conjunction of this narrow therapeutic index and the considerable inter-individual differences in distribution, metabolism and excretion of these cytotoxic agents in humans, results in increased risks of toxicity and sub-therapeutic dosing in the individual patient [Drug developers recruit and combine principles, procedures and strategies from chemistry, pharmacology, nanotechnology and biotechnology, focusing on the generation of functional vehicles as nano-carriers of drugs for improved stability and enhanced intracellular delivery. By exploring macromolecules such as lipids, polymers and proteins, both biocompatibility and cost-effective fabrication are favored, and a plethora of opportunities for architectonic and functional adaptation of vehicles to particular cargo drugs and therapeutic conditions enlighten the cancer treatment scenario. Molecular vehicles specifically developed as carriers for drugs are usually referred to as drug delivery systems (DDS). The application of nanoscale technologies has resulted in an already vast but still expanding catalogue of drugs and appropriate DDS, whose implementation in therapy is heavily represented in the different phases of drug development, from basic research to clinical trials . DDS, as patient .+ prostate cancer cells are representative examples [This landscape may soon change since many actively targeted nanoparticles for drug delivery are being evaluated in clinical assays . Among texamples . We expeexamples , and Breexamples . Current"} +{"text": "Editorial on the Research TopicMolecular Dynamics at the Immunological SynapseMartin-Cofreces et al.; is a specialized cell\u2013cell adhesion that mediates antigen acquisition, lymphocyte activation, and effector function. Seminal studies showed a structure composed of stable central and peripheral supramolecular activation clusters (cSMAC and pSMAC) organized at the interface of interacting helper T lymphocytes and B lymphocytes. The T cell receptor (TCR) and signaling molecules were found accumulated at the cSMAC, whereas the integrin LFA-1 and cytoskeleton components distributed at the pSMAC . Current et al.; , 4]. It et al.; , 6. The et al.; \u20139. Much Kapoor-Kaushik et al. provide a piece of original data to discuss how the spatial organization of Lck is regulated in activated T cells. Although the open conformation promotes clustering, signaling downstream the TCR further controls the spatial organization of Lck. Regarding the role of integrins in the triggering of the TCR and T cell activation, Hashimoto-Tane and Saito have recently demonstrated the existence at the IS of adhesion rings of integrins and focal adhesion molecules surrounding TCR-containing microclusters. This so-called microsynapse is proposed to support weak TCR activation via cell\u2013cell local adhesion signals.This research topic (RT) contains 10 articles that cover different aspects of the molecular dynamics at the IS. Data are contributed on the spatial regulation of the signaling molecule Lck, an important molecular requirement for TCR triggering. With the assistance of super-resolution microscopy, Comrie and Burkhardt is how mechanotransduction, the transformation of mechanical forces into biochemical modifications, contributes to the TCR triggering and the intracellular signaling. The authors focus on the role of mechanical forces directed by filamentous actin (F-actin). The review contributed by Hivroz and Saitakis focuses on other mechanical clues that regulate T cell activation, including the effect of membrane protrusions and oscillations, cell mobility and spreading, the TCR engagement itself, or the engagement of LFA-1 during the IS formation.One novel and timely aspect discussed by Ramirez-Munoz et al. propose that a local action of the cofilin activator Slingshot-1 at the IS might mediate an ultrasensitive/bistable response of the cofilin signaling module. This signaling module might then contribute to the specific and sensitive responses of na\u00efve T cells and the more efficient and faster activation of antigen-experienced T cells.Regarding the regulation of F-actin regulators, Benvenuti, who focuses her attention on the role of actin regulators, such as fascin and WASp, among others. The author also discusses about DC polarity and secretion induced by maturation stimuli. For example, the Cdc42-mediated polarization of the MTOC controls the delivery of IL-12 to the DC-T cell IS, a process mediated by VAMP7. Thus, it is envisaged that the activating signal three (inflammatory cytokines) is coupled at the IS to the activating signals one (TCR) and two (costimulation).The relevance of the cytoskeleton remodeling at the dendritic cell (DC) side is discussed by Onnis et al.. The authors revise the different Rab GTPases controlling the recycling routes targeting different receptors, such as the TCR and CXCR4, to the IS. They also highlight the recently noticed role of components of the intraflagellar transport system in controlling the traffic of the TCR to the IS downstream the centrosome polarization. This contribution poses the notion that IS and cilium constitute functional homologs. Important mechanisms of cell\u2013cell communication are also described, including the trogocytosis and the local delivery of exoxomes and microvesicles.The dynamics of the endosomal compartment is discussed in the review by Niedergang et al. remark this parallelism and discuss the organization, mechanism of assembly, and regulation of both structures. They pay attention to immune and phagocytic receptors, the interplay of the actin and tubulin cytoskeleton and the vesicular traffic. Discussion is provided about the role of soluble N-ethylmaleimide-sensitive factor attachment protein receptors and Rab GTPases in polarized vesicular traffic.Spatial organization of the IS also resembles the phagocytic cup, leading to the concept of the phagocytic synapse. Brzostek et al.. They describe the function of CD28 and CTLA4 in the immune response, the regulatory role in the cytoskeleton dynamics and signaling and the distribution to the IS in effector and regulatory T cell.The structure and function of costimulatory and coinhibitory receptors upon the engagement of B7 molecules expressed on APCs are discussed by Rocha-Perugini et al. discuss the role of tetraspanin-enriched microdomains in the local accumulation of receptors, adhesion molecules, and integrins at the IS. Associations are described between IS-located tetraspanins, several signaling molecules, and the actin cytoskeleton.In summary, this RT highlights the fine-tuned molecular dynamics at the IS that allows proper T cell activation and effector functions. Methodological and technical advances in microscopy techniques improving spatial and temporal resolution are helping us to understand how the dynamics of the cytoskeleton and the endosomal compartment reorganizes micro and nanodomains of signaling complexes that, in turn, mediate lymphocyte immune responses. In addition, complementary biophysical approaches as well as the comparison with biological systems mentioned in this collection may provide useful hints to unravel the complexity of ISs.PR-N wrote the first draft of the manuscript and updated the last version. AA and VB corrected and completed the initial draft.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "European Journal of Psychotraumatology focuses on traumatized refugees. It includes three review articles as well as four original articles on the mental health burden, screening instruments and interventions in different groups of refugees. The articles published in this special issue focus on important aspects of better understanding the needs of traumatized refugees, as well as on identifying and offering appropriate mental health care for this population. Future research recommendations are provided in the hope to contribute to improving mental health care strategies of this still underserved population.In the past few years the number of refugees worldwide has increased dramatically. Many of them were traumatized in their homelands due to violent conflict or persecution, as well as during their flight, and are confronted with ongoing stressors in the exile countries. In order to contribute to enhancing the clinical knowledge, this special issue of the International studies show that refugees suffer from increased rates of short-term and long-term mental health problems: approximately one in three refugees is suffering from PTSD or other trauma-related mental disorder (Bogic, Njoku, & Priebe, European Journal of Psychotraumatology has a strong tradition focusing on global mental health issues and populations forced to migrate (see special issues Hall & Olff, In a systematic review and meta-analysis, an overview of the effectiveness of psychosocial interventions for displaced war-traumatized minors is provided focusing on symptoms of PTSD, depression, anxiety, grief and general distress (Nocon, Eberle-Sejari, Unterhitzensberger, & Rosner, The third review article focuses on the special situation of Syrian refugees, their mental health conditions, and scalable evidence-based interventions. It outlines the newly launched STRENGTHS programme for adapting, scaling up and testing Problem Management interventions (Sijbrandij et al., Very little research has been done on the validity of instruments for refugee populations (Wind, van der Aa, de la Rie, & Knipscheer, This issue continues with the cultural adaptation and evaluation of a CBT programme for Farsi-speaking refugees, that was conducted with male refugees from Afghanistan and Iran (Kananian, Ayoughi, Farugie, Hinton, & Stangier, In the third research article, 76 adult patients at a treatment centre for torture victims and traumatized refugees were surveyed in the context of their regular multidisciplinary psychotherapeutic treatment (Stammel et al., Finally, a group-based multidisciplinary day patient treatment for refugees who experienced multiple traumatic losses was evaluated (de Heus et al., European Journal of Psychotraumatology looks forward to receiving more papers focusing on traumatized refugees, to improve the mental health care strategies of this underserved population.The articles published in this special issue focus on important aspects to better understand the needs of traumatized refugees, as well as on identifying and offering appropriate mental health care for this population. Cultural sensitive psychotraumatology remains a priority (Schnyder et al.,"} +{"text": "Studies emphasize the training of cognitive functions to decrease losses in the population. Memory training associated with neurotracker was performed by an 80-year-old man with memory complaints. A battery for measuring memory, quality of life and stress was initially applied and showed low scores. The patient underwent a program for stimulating memory and attention comprising 32 sessions (2 weekly sessions of 90 minutes each). The post-test follow-up showed improvements in the process of storage and retrieval of episodic and working memory, greater use of strategies, faster information processing speed, as well as reduction in complaints and positive impact on quality of life. The results suggest that the use of Neurotracker for training cognitive processes is valid for cognitive rehabilitation programs to promote improvements in quality of life in the elderly. In this scenario, cognitive rehabilitation programs for stimulating cognitive functions have become commonplace, proving effective in reducing cognitive deficits.The study by BalardinThe study of Barnes et al.,,In this context, many computerized techniques have proven useful resources for cognitive training.Thus, the present study reports the results of a memory training program incorporating the Neurotracker with pre and post-intervention cognitive assessments.We report the case of S.Z., an 80-year-old, right-handed male, married with four children, holder of a Doctorate in architecture and living with family members in S\u00e3o Paulo. There was no history of alcoholism, smoking or pathologies relevant to this report. The patient sought medical assistance in 2014 after presenting frequent memory complaints. Clinical and functional assessments conducted by a neurologist and neuropsychologists revealed no symptoms of cognitive impairment. This result was obtained based on clinical observations and on the Daily Activities Scale and Mini-Mental State Exam,The patient was undergoing medical and neurological treatment with the following medications: Galvus Met 850 mg, Betaserc 24 mg, Lipitor (Atorvastatin) 20 mg, Puran T4 50 mg, Rivotril (Clonazepam) 1 mg, Nexum 20 mg, Fluoxetine 20 mg, Benicar 20 mg, and Vitamin D, 8 gts.In August 2014, the subject was referred for assessment and brain performance training at the Neuropsychology Unit of the Institute of Psychiatry of the Clinicas Hospital of the University of S\u00e3o Paulo School of Medicine. The initial assessment included direct observation of the patient, determination of intelligence quotient, completion of a brief questionnaire on motivation, expectations and impairment prior to training, application of scales measuring self-conception and self-perceived memory, stress, anxiety, depression and quality of life. Tests of attention, memory, information processing speed and reaction time, simple and entailing selection, were also performed. All participants signed the free and informed consent form.The results of the pre and post-training cognitive assessments are given in both Pre-training and training. Intellectual performance was assessed using two sub-tests from the Wechsler Abbreviated Scale of Intelligence - WASI,The subject exhibited no depressive symptoms ,The Colored Trails TestPerformance on the Memo Checkup (randomized computerized test for assessing accuracy of episodic and working memory), showed medium episodic memory and significantly lower-than-expected working memory for age (Graph 1). NeurotrackerAfter the initial assessment battery, the intervention consisting of individual sessions of 90 minutes, twice per week, was run for a 12-month period. The computer was used for the cognitive training, both to access the Neurotracker software and run the Memory Training sessions. The sessions were devised according to the consciously learned mnemonic strategies which required effort to put into practice. The training employed verbal and visual mnemonic methods (image and rhyming cues), expanded repetition , errorless learning (technique for avoiding errors while learning new information), cue removal , PQRST , association , production (similar to association only sentences must be created for the register) and the categorization process (forming classes of the information to be memorized).At the post-training stage, improvements were evident in self-perceived attention, memory, quality of life and self-confidence on the M&M Scale. A similar result was found for perceived subjective memory on the MAC-Q scale.Greater use of the strategy trained was seen on the episodic memory task, suggesting that cognitive training acts as feedback, rendering visible the improvements and consequently, perceptions in terms of well-being and learning strategies, corroborating the results of other studies.,A reduction in stress symptoms was also observed, in line with studies suggesting that cognitive training serves to help improve stress symptoms.Training proved effective for sustained and alternating attention, with above-average cognitive flexibility on the Colored Trails testResults of the computerized memory test showed changes in score during and after training. The results, despite fluctuating at some points, showed a steadily rising curve for both Accuracy and Processing Speed on the test (Graph 1).Positive results were also obtained on the Neurotracker, the computerized stimuli employed, in the form of a rising curve for scores comparing accuracy, speed and difficulty provided by the software .1,2,8The results indicate that the use of the Neurotracker for training cognitive processes is valid as part of cognitive rehabilitation programs promoting improvements in the quality of life of the elderly, corroborating the results of previous studies.,Political issues regarding costs of pension, welfare and healthcare systems oblige societies to seek ways of improving assistance in the aging process. The psychological universe of older adults, besides the biological spectrum , also encompasses individual potentialities , in addition to influences from the environment and the sociocultural context.Given this scenario, such assistance should include computerized cognitive training programs in private and public institutions for elderly care to improve quality of life and delay the signs of senility during the aging process. Future studies focusing on the development of new techniques and furthering this area should also be encouraged."} +{"text": "Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain accompanied by symptoms like depression, anxiety, sleep disturbance and fatigue. In addition, affected patients frequently report cognitive disruption such as forgetfulness, concentration difficulties or mental slowness. Though cognitive deficits in FMS have been confirmed in various studies, not much is known about the mechanisms involved in their origin. This study aimed to investigate the contribution of affect-related variables to cognitive impairments in FMS. For this purpose, 67 female FMS patients and 32 healthy control subjects completed a battery of cognitive tests measuring processing speed, attention, visuospatial and verbal memory, cognitive flexibility and planning abilities. In addition, participants completed self-report questionnaires pertaining to positive and negative affect, alexithymia, pain catastrophizing and self-esteem. Clinical characteristics including pain severity, symptoms of depression and anxiety, insomnia and fatigue were also assessed. FMS patients showed markedly poorer performance than healthy controls in all of the cognitive domains assessed, in addition to greater levels of depression, anxiety, negative affect, alexithymia and pain catastrophizing, and lower self-esteem and positive affect. In exploratory correlation analysis in the FMS sample, lower cognitive performance was associated with higher pain severity, depression, anxiety, negative affect, alexithymia and pain catastrophizing, as well as lower self-esteem and positive affect. However, in regression analyses, pain, self-esteem, alexithymia, and pain catastrophizing explained the largest portion of the variance in performance. While interference effects of clinical pain in cognition have been previously described, the present findings suggest that affective factors also substantially contribute to the genesis of cognitive impairments. They support the notion that affective disturbances form a crucial aspect of FMS pathology, whereas strategies aiming to improve emotional regulation may be a beneficial element of psychological therapy in the management of FMS. Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain and accompanying symptoms like depression, anxiety, sleep disturbance and fatigue. Its prevalence is estimated at 2\u20134% in the general population, with women being predominantly affected . FMS is Complaints about cognitive disruption, such as forgetfulness, concentration difficulties or mental slowness are also frequent in FMS patients. These impairments, also referred to as \u201cfibro fog,\u201d may significantly affect patients\u2019 everyday life and therefore are perceived to be among the most serious symptoms of the disease . ProblemThough the occurrence of cognitive impairments in FMS has been well-established, not much is known about the mechanism involved in their origin. Interference effects of nociception and pain have been considered a relevant factor, as supported by studies showing positive correlations between the severity of clinical pain and the magnitude of cognitive decline . Pain isWhile most available FMS studies on the implications of affect-related variables in cognitive impairments refer to symptoms of depression and anxiety, mood states have not yet been specifically addressed. Positive and negative affect are regarded as virtually independent dimensions, where positive affect implies enthusiasm, activity and vitality-energy, while negative affect constitutes a general state of distress including aversive emotions like anger, fear and guilt . There iAffect-related coping styles may also be of interest in the present context. Alexithymia is conceptualized as a personality trait related to deficits in the cognitive processing of emotions that involves a lack of emotional awareness, difficulties in identifying and communicating feelings and an externally oriented thinking style , 2006. SFinally, self-esteem may be another relevant aspect. Self-esteem is a component of self-concept defined as an individual\u2019s set of thoughts and feelings about his or her own worth and importance, resulting in a global positive or negative attitude toward oneself . There iIn sum, affect-related factors, including affective dysbalance, alexithymia, pain catastrophizing and low self-esteem, may contribute to cognitive impairments in FMS, in addition to pain experience and symptoms of emotional disorders. However, knowledge concerning the actual magnitude of their impacts remains scarce. Therefore, the main objective of the present study was to evaluate the relationship between self-report measures of these factors and performance on a comprehensive battery of cognitive tests measuring processing speed, attention, visuospatial and verbal memory, and cognitive flexibility, as well as mental planning and organizational skills. Clinical characteristics including pain severity, symptoms of depression and anxiety, as well as sleep disturbance and fatigue were regarded as additional predictors. Moreover, in order to quantify the magnitude of the cognitive decline in the investigated FMS patients, their test performance was compared with a control group of healthy individuals matched for relevant sociodemographic variables.The following hypotheses were tested in the study: (1) Positive affect is positively, and negative affect is inversely, related with cognitive performance in FMS patients. (2) Higher levels of alexithymia and pain catastrophizing, and reduced self-esteem, predict lower performance. (3) Clinical pain severity, symptoms of depression and anxiety, as well as insomnia and fatigue demonstrate inverse associations with test performance. (4) In addition, FMS patients perform poorer than healthy individuals on the applied cognitive tasks.In total, 67 women with FMS, recruited from the Fibromyalgia Association of Ja\u00e9n (Spain), participated in the study. All of them were examined by a rheumatologist and met the 1990 American College of Rheumatology criteria for FMS . The conRey-Osterrieth Complex Figure Test (ROCF) (The t (ROCF) was usedVerbal Learning Test (TAVEC) (The (TAVEC) was usedZoo Map Task (ZMT) from the Behavioural Assessment of the Dysexecutive Syndrome was applied as a measure of strategic planning and self-regulation (The gulation . The tasTrail Making Test (TMT) was used to evaluate processing speed, attention and cognitive flexibility. The version of The The patients\u2019 clinical history and demographic data were obtained in a semi-structured interview. The Structured Clinical Interview for Axis I Disorders of the Diagnostic and Statistical Manual for Mental Disorders SCID, was applMcGill Pain Questionnaire (MPQ) (re (MPQ) . This 73re (MPQ) .State-Trait Anxiety Inventory (STAI) (y (STAI) . This iny (STAI) .Beck Depression Inventory (BDI) (ry (BDI) . This 21Fatigue Severity Scale (FSS) (le (FSS) . This scOviedo Quality of Sleep Questionnaire (COS) (re (COS) . The InsPositive and Negative Affect Scale (PANAS) ( (PANAS) . This quToronto Alexithymia Scale (TAS-20) ((TAS-20) . This inCoping Strategies Questionnaire (CSQ) (re (CSQ) . The 6-iRosenberg Self-esteem scale (SS) . On thisThe study was conducted in two sessions performed on the same day. During the first session, a clinical psychologist took the patients\u2019 clinical history, recorded sociodemographic data and medication use, and evaluated possible violations of the exclusionary criteria. After that, SCID interviews were conducted and the psychometric questionnaires presented. In the second session, the neuropsychological tests were administered in the following order: ROCF (copy), ZMT, R-SAT, ROCF (reproduction), TAVEC , TMT, and TAVEC . The tests were presented in this order to avoid an interference effect of different cognitive domains, especially between visual and verbal memory. Between each test, participants had a break of 5 min. The study protocol was approved by the Ethics Committee for Human Research of the University of Ja\u00e9n and all participants provided written informed consent.t-tests and \u03c72-tests. Group differences in cognitive performance were analyzed by means of multivariate analysis of variance (MANOVA). Age, years of education and body mass index were entered as covariates in this analysis. Effects of medication use and comorbid depression and anxiety disorders were evaluated by stratified analyses done for the FMS group (MANOVA) that compared patients using and not using each type of medication , and comparing patients suffering and not suffering from depression and anxiety disorders. Effect sizes are indicated by adjusted eta squared . Firstly, at an exploratory level, Pearson correlations were computed. Secondly, multiple regression analyses were performed. Two blocks of variables were used as predictors in the analyses: (1) to control for the effects of age, body mass index and years of education, these variables were entered simultaneously (enter method); (2) to determine psychological predictors of cognitive performance, questionnaire scales that showed significant correlations with neuropsychological parameters in the exploratory analysis were included (stepwise method). SPSS software (version 19.0) was employed for data analysis .Associations between questionnaire scores and neuropsychological test results were evaluated in two steps, both restricted to the FMS group FMS patients and 10 (45%) healthy participants exhibited TAS-20 values above the cut-off score.F = 3.11, p < 0.0001, Table 2 displays the means and standard deviations of the performance indices, together with the statistics of the univariate group comparisons. The results for most test parameters reflect lower task speed and accuracy in FMS patients than controls. Differences were significant for all speed and accuracy parameters of the ROCF (copy and reproduction conditions) and TAVEC . In the ZMT, group differences were seen in the total number of correct responses, execution time for both versions and mistakes in version 1. On the R-SAT, differences arose for the number of correct responses (short items). Among the parameters of the TMT, execution times for the number sequence, letter sequence, switching and motor speed tasks, as well as set loss and time out mistakes, differed between groups. The covariates of age, years of education and body mass index were non-significant. No differences were found between subgroups of patients taking and not taking antidepressants, anxiolytics, non-opioid analgesics, or opioids, or between patients suffering and not suffering from comorbid depression or anxiety disorders .The MANOVA for the neuropsychological test scores showed a multivariate group effect on the MPQ correlated negatively with the number of correct marks on both conditions of the ROCF and the correct responses in the recognition task of the TAVEC. This score correlated positively with execution time during the number sequence, letter sequence and motor speed tasks of the TMT, omission errors and false positive responses in the TAVEC recognition task, set loss and time out mistakes on the TMT, and execution time during version 2 of the ZMT. The sensorial and total pain scales correlated negatively with the number of correct responses on the ZMT, and positively with execution time during version 2 of this test. Emotional pain correlated negatively with correct responses on the TAVEC recognition task, and positively with omission errors and false positives. Trait anxiety (STAI) was positively associated with execution time during the copy condition of the ROCF, and with the visual scanning and motor speed tasks of the TMT. State anxiety was inversely associated with the number of correct responses (short items) on the R-SAT, and with the number of correct recognition responses, long-delay recall and the discrimination score of the TAVEC, and positively associated with long item mistakes on the R-SAT, omission errors in the TAVEC recognition task, and execution time during the TMT motor speed task. Depression (BDI) correlated positively with the number of long item mistakes on the R-SAT and set loss mistakes on the TMT, and negatively with correct responses on the R-SAT. Fatigue (FSS) correlated positively with execution time during the motor speed task of the TMS. No significant correlations arose for insomnia (COS).Table 4 includes the correlations of the questionnaire scores for positive and negative affect, alexithymia, pain catastrophizing and self-esteem with the indices of neuropsychological test performance in FMS patients. Positive affect (PANAS) was inversely associated with execution time during version 2 of the ZMT, omission errors and false positives on the TAVEC recognition task, execution time during the visual scanning, number sequence, letter sequence and switching tasks of the TMT, as well as set loss and time out mistakes on the latter instrument. Moreover, positive affect correlated positively with correct responses (short items) on the R-SAT, and recall (List B) and recognition performance on the TAVEC, as well as the discrimination score provided by this test. Negative affect (PANAS) correlated positively with face item mistakes on the R-SAT, false positives on the TAVEC recognition task, execution time during the visual scanning task of the TMT, and sequence and set loss mistakes. Negative affect correlated negatively with execution time during version 1 of the ZMT.Alexithymia (TAS-20) correlated negatively with the number of correct marks in the copy condition of the ROCF, and with correct recognition responses and the discrimination score of the TAVEC, and positively with execution time during the copy and reproduction conditions of the ROCF, the visual scanning, number sequence, latter sequence and switching tasks of the TMT, set loss and time out mistakes on the TMT, as well as omissions and false positives on the TAVEC recognition task.Pain catastrophizing (CSQ) correlated negatively with the number of correct recognition responses on the TAVEC, and positively with execution time during the reproduction condition of the ROCF, the number and letter sequence conditions of the TMT, long item and face item mistakes on the R-SAT, sequence and set loss mistakes on the TMT, as well as omissions errors and false positives in the TAVEC recognition task.Self-esteem (SS) was inversely associated with execution time during the copy and reproduction conditions of the ROCF, both versions of the ZMT, the visual scanning, number sequence, letter sequence, switching and motor speed conditions of the TMT, as well as set loss, sequence and time out mistakes on the TMT, and omissions and false positives in the TAVEC recognition task. Moreover, self-esteem correlated positively with the number of correct marks in the copy condition of the ROCF, correct responses (short items) on the R-SAT, and free recall performance (List B) and the discrimination score of the TAVEC.Table 5. Here, current pain intensity (VAS of MPQ) was inversely related to the number of correct marks in the copy and reproduction conditions of the ROCF and execution time during version 2 of the ZMT; and positively related to execution time during the number and letter sequence tasks of the TMT, and to set loss and time out mistakes on this test. The sensorial pain index was positively associated to mistakes in version 1 of the ZMT; emotional pain was inversely associated with correct responses, and positively with omission errors in the TAVEC recognition task. Depression (BDI) was positively associated with long item mistakes on the R-SAT. State anxiety (STAI) was positively associated with execution time during the motor speed task of the TMT and trait anxiety was positively associated with execution time during the copy condition of the ROCF.Significant results of the multiple regression analyses for the prediction of performance parameters, after controlling for the effects of age, years of education and BMI, are presented in Positive affect (PANAS) was inversely related to execution time during the switching task, and negative affect was positively related to execution time during the visual scanning task of the TMT. Alexithymia (TAS-20) was positively associated with execution time during the reproduction condition of the ROCF and the number sequence, letter sequence and switching tasks of the TMT, and with time out mistakes on this instrument. Pain catastrophizing (CSQ) was positively associated with face item mistakes in the R-SAT, false positive responses in the TAVEC recognition task, and sequence mistakes on the TMT. Self-esteem (SS) was inversely related to execution time during the copy condition of the ROCF, version 2 of the ZMT and the number sequence and motor speed tasks of the TMT. It furthermore was inversely related to false positive responses, omission errors in the TAVEC recognition task and set loss mistakes on the TMT. Self-esteem was positively associated with correct responses (short items) on the R-SAT, correct responses in the free recall (List B) and recognition tasks of the TAVEC, and the discrimination score of the test.This study revealed poorer performance in FMS patients vs. healthy individuals on neuropsychological tests of processing speed, attention, visuospatial and verbal memory, cognitive flexibility, as well as mental planning and organizational skills. According to an exploratory correlation analysis conducted in the patient group, test performance was associated with pain severity, symptoms of depression and anxiety, as well as affect-related variables including positive and negative affect, alexithymia, pain catastrophizing and self-esteem. In subsequent regression analyses, pain, self-esteem, alexithymia, and catastrophizing explained the overall largest portion of test score variance.The cognitive performance reduction in FMS patients confirms previous findings. The longer execution times during the number sequence, letter sequence and switching tasks, and the higher number of set loss and time out mistakes on the TMT, are in line with observations of deficits in attentional functions and processing speed . PatientIn the applied questionnaires FMS patients reported more severe symptoms of depression, anxiety, insomnia and fatigue than controls, which constitute typical bodily and mental symptoms accompanying FMS pain . ElevateAs its main aim, this study investigated the impact of FMS symptoms and affect-related variables on cognitive performance. Among clinical symptoms, pain severity was most closely related to neuropsychological test scores. In correlation analysis, high scores on the MPQ scales were associated with lower speed and accuracy on the attentional and planning tasks (TMT and ZMT), as well as fewer correct responses and more mistakes on both memory tests (ROCF and TAVEC). Similar associations also arose in regression analysis. The associations between MPQ scale scores and cognitive function are in line with previous FMS studies, where they were interpreted as indicative of an interference effect of pain with cognitive processing . DepressThe involvement of affect-related variables in cognitive impairment in FMS represents a novel aspect of this study. Positive affect demonstrated a close association with attentional and verbal memory performance. In correlation analysis, the corresponding PANAS scale score was predictive of faster performance and lower error rates in the visual scanning, number sequence, letter sequence and switching tasks of the TMT. This also applies to almost all TAVEC indices of verbal recall and recognition performance. A weaker association between positive affect and planning abilities is suggested by the negative correlation of the PANAS scale score with execution time during one of the two ZMT tasks, and by the positive correlation with correct responses on the R-SAT. Negative affect was related to more errors on the TMT, TAVEC and R-SAT and slower performance on one of the ZMT tasks. The associations of positive and negative affect with performance speed also arose in regression analysis. Beneficial effects of positive affect on cognition have repeatedly been reported in healthy individuals, for example in terms of facilitation of attentional processing, problem solving and decision making . AdverseAlexithymia also showed a close relationship with attentional and memory performance. The TAS-20 global score was positively related to execution time during the visual scanning, number sequence, letter sequence and switching tasks of the TMT, as well as to error rates in this test. It furthermore correlated negatively with speed and accuracy performance on the ROCF, and all parameters reflecting recognition ability on the TAVEC. The associations with the TMT parameters and reproduction performance on the ROCF were also seen in regression analysis. As a major source of emotional dysregulation, alexithymia has been implicated in somatosensory amplification, pain chronification and the pathogenesis of FMS . In addiSignificant associations with attention, memory and planning also arose for pain catastrophizing. The corresponding CSQ scale score correlated positively with mistakes on the TMT and R-SAT, and with execution time during the number and letter sequence conditions of the TMT and the reproduction condition of the ROCF. Furthermore, higher levels of catastrophizing were associated with fewer correct responses and more mistakes on the TAVEC. Less accurate performance in the TMT, TAVEC and R-SAT in patients with high catastrophizing scores was also reflected in the regression analysis. Pain catastrophizing is recognized as a crucial factor in the development of chronic pain, especially in FMS . CatastrFinally, low levels of self-esteem were related to poorer attentional, memory and planning performance. The SS score correlated negatively with execution time during the visual scanning, number sequence, letter sequence and switching tasks of the TMT, as well as with error rates on this test. Higher values were also associated with faster performance during all conditions of the ROCF and ZMT, and with improved free recall and recognition performance on the TAVEC. A large proportion of these relationships was also seen in regression analysis. The association between self-esteem and cognition may be mediated by motivational factors. Self-esteem is related to self-confidence and self-efficacy expectation . These vOne limitation of the study was the relatively small size of the control group, which may have limited the power of the statistical group comparison. Moreover, caution is required in the interpretation of the results of the exploratory correlation analysis considering the increased risk of alpha errors due to the high number of computed correlations. Regarding the selection of self-report scales, some relevant constructs may not have been taken into account. For example, emotional self-regulation, emotional competence or self-efficacy may be of interest in future studies. Finally, the conclusion of a causal contribution of affective factors to cognitive impairments in FMS cannot be drawn with certainty. By definition, the causal impact of cognitive deficits on affective variables, as well as mutual influences between cognition and emotion, also have to be considered.To conclude, this study confirmed marked deficits in the domains of attention, memory and executive functions in FMS and revealed new knowledge regarding the psychological factors involved in their mediation. Overall, affect-related variables, i.e., positive and negative affect, alexithymia, pain catastrophizing and self-esteem, were as closely associated with neuropsychological test scores as pain severity. Our findings underline the importance of these variables in the genesis of cognitive symptoms in FMS. As an important factor of FMS pathology, emotional aberrances may also be relevant with respect to optimizing psychological therapy of FMS. Techniques addressing affect-related variables may constitute a helpful component of cognitive therapy in the management of FMS . In addiAll authors contributed to the design of the study and to the analysis and interpretation of the data. CG-S conducted the experiment, acquired data, and drafted the first version of the manuscript. GRdP and SD critically revised and completed the manuscript and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MA and handling Editor declared their shared affiliation."} +{"text": "The world production of cement has greatly increased in the past 10 years. This trend is the most significant factor affecting technological development and the updating of manufacturing facilities in the cement industry. Existing technology for the production of cement clinker is ecologically damaging; it consumes much energy and natural resources and also emits pollutants. A new approach to the production of blended or high-volume mineral additive (HVMA) cement helps to improve its ecological compatibility. HVMA cement technology is based on the intergrinding of portland cement clinker, gypsum, mineral additives, and a special complex admixture. This new method increases the compressive strength of ordinary cement, improves durability of the cement-based materials, and - at the same time - uses inexpensive natural mineral additives or industrial by-products. This improvement leads to a reduction of energy consumption per unit of the cement produced. Higher strength, better durability, reduction of pollution at the clinker production stage, and decrease of landfill area occupied by industrial by-products, all provide ecological advantages for HVMA cement."} +{"text": "Aims: This review aims to evaluate the most recent evidence on the pathophysiology of impulse control disorders (ICDs) in Parkinson disease (PD).Methods: Computerised searches of Medline, Embase and PsycInfo, along with manual searches for grey literature, were conducted and resulted in a total of 16 studies suitable for review.Results: Evidence was divided into four categories: medication used in PD management, imaging studies, genetic analysis and subthalamic deep brain stimulation (STN-DBS). Analysis of the literature reveals that both intrinsic and extrinsic factors may play a role in the pathophysiology of ICDs in PD. Dysfunction of the mesocorticolimbic pathway and polymorphisms of the dopamine D3 and D4 receptors may increase an individual's susceptibility to the development of ICDs.Discussion: Dopaminergic medication, particularly dopamine agonists (DAs), increases the risk of developing impulsive behaviours in a PD patient. Further evidence, particularly in the form of prospective studies and randomised controlled trials is required to better establish the pathophysiology of ICDs in PD."} +{"text": "The Asia-Pacific region is a geographic source for emerging infectious diseases, including multidrug-resistant (MDR) organisms (MDROs) and pathogens with pandemic potential. Risks for emerging infectious diseases in this geographic region are complex and are presumed to include ecological, socioeconomic, and technological processes favorable to microbial transmission dynamics. In resource-limited settings, relative to resource-adequate settings, there continues to be a paucity of data in support of infection prevention and control, and patient safety interventions to ensure that regional, if not national, healthcare systems work effectively to improve infection prevention and control interventions. In addition, several viral pandemics and annual influenza strains have originated in the Asia-Pacific region, which, together, has global implications for population health.The prevention, control, and reporting of MDROs and healthcare-associated infections (HAIs) benefit from effective data dissemination plans and harmonized surveillance systems. HAIs compromise patient safety because they are preventable and serve as a reservoir for MDROs, which are associated with excess length of hospital stay, increased antimicrobial drug exposure, and excess costs . In the Clinical Infectious Diseases focuses on 3 key themes of infection prevention and control in healthcare settings across the Asia-Pacific regions: (1) epidemiology and evidence to support prevention and control interventions, (2) enhancements to infection prevention and control in healthcare settings, and (3) practices associated with the containment of emerging infectious diseases and outbreaks. The epidemiological data and evidence to support prevention and control interventions include 2 national survey studies for best practices and 4 epidemiology studies. A survey from Thailand and Japan relative to the United States compared evidence-based practices for prevention of HAIs and identified a modifiable gap associated with quality improvement for hospitals in these Asian-Pacific countries.This issue of Staphylococcus aureus (MRSA) and MDR Acinetobacter baumannii interventions in Thailand. Higher compliance (>75%) with bundled approaches was associated with reduction in MRSA, where containment of MDR A. baumannii necessitated bundle compliance along with additional infection control interventions. Four other publications describe the complex clinical factors, molecular epidemiology, and transmission dynamic associated with prevalent and emerging MDROs in Singapore and South Korea . Together, these studies provide information on the epidemiology of infection prevention and control and the transmission dynamic of MDROs in Asia-Pacific settings.A second national survey focused on policy, process, and outcomes associated with methicillin-resistant The second theme in this issue on infection prevention and control in the Asia-Pacific region is the innovative use of molecular diagnostics, electronically linked administrative data, and information technology to enhance infection prevention and control. Findings from 4 meta-analyses or network meta-analyses demonstrate the reduction in central catheter\u2013associated bloodstream infection with the use of minocycline-rifampin\u2013impregnated central venous catheters; the effects of antibiotic stewardship on outcomes including antibiotic consumptions, mortality rates, and the reduction in MDROs; infection control\u2013specific interventions associated with control of specific MDR gram-negative pathogens in intensive care units; and the potential role of the enteric microbiome in postoperative complications.Together, these studies also provide strong methodological approaches for the use of network meta-analyses, which permitted assessment of these exposure-response relationships inclusive of potential confounding factors. In addition, a report from Singapore describes the use of an electronic medical record\u2013linked administrative database that included language selectively of specific terms, using text parsing of chest radiographic reports to identify evidence of pneumonia. Use of this electronic medical record\u2013linked data source in a case validation of hospitalized adults with community-acquired pneumonia provides an enhanced method for conducting real-world evidence studies that can include enhanced case detection, diagnostic evaluations, and pathogen-specific treatment patterns in future studies. Finally, the real-life feasibility of using the Xpert MTB/RIF assay (Cepheid) in clinical practice in a tuberculosis-prevalent country was reported from Thailand. Results suggest the potential role of this molecular diagnostic method in the containment of MDR tuberculosis in the Asia-Pacific region.The third theme is practices associated with the containment of emerging infectious diseases and outbreaks in Asia-Pacific countries. Two publications describe successful containment for emerging infectious diseases, inclusive of lessons learned from the 15-year Hong Kong infectious diseases preparedness experience and the experience of zero secondary chain transmission of Middle East respiratory syndrome coronavirus in Thailand. Together, these 2 studies emphasize the key message that control of emerging infectious diseases is feasible and sustainable in these geographic regions.Streptococcus agalactiae infection in Singapore. Findings imply a potential role of regional collaboration to control S. agalactiae, because molecular epidemiological data were linked to the zoonotic spread from farmed freshwater fish. These fish share phylogenomic analysis of ST238, similar to human and fish isolates from Thailand and Hong Kong. A second report confirms a pseudo-outbreak of Bacillus spp. bacteremia linked to contaminated hospital linen, with emphasis on the benefit of good hygienic practice in central supply and sterilization services. These collective efforts complement existing evidence for the advancement of infection prevention science in the Asia-Pacific region.Finally, 2 interesting outbreaks are reported in this issue. The first is a large food-borne outbreak of Healthcare in the Asia-Pacific region has had notable milestones in infection and prevention control. The publications in this issue support future work focused on continued generation of evidence and dissemination of data, ongoing microbial surveillance, and implementation, if not adoption, of effective prevention strategies to contain the spread of MDROs and key emerging infectious diseases in the region. We thank the Infectious Diseases Association of Thailand for its partial sponsorship of this issue and share our hope that the collective experience from the study contributors reporting work in this issue will serve as a 2017 platform for improvement in the science and practice of infection prevention in the Asia-Pacific region and in other resource-limited settings."} +{"text": "Recent neuroimaging studies have shown altered brain connectivity in patients with schizophrenia, associated with disturbed myelination in different fiber tracts and disruptions of white matter (WM) integrity, including prefrontal WM. We aimed to perform a qualitative and morphometric study of the ultrastructure of oligodendrocytes, myelin-forming cells, in prefrontal WM in schizophrenia and normal controls.WM of the prefrontal cortex (Brodmann\u2019s area 10) was studied by transmission electron microscopy and morphometry. Size, volume density (Vv) and the number (N) of organelles in oligodendrocytes were estimated in 21 patients with schizophrenia and 20 normal matched controls. Pearson correlation analysis was performed to assess possible correlations between the parameters measured and age, post-mortem interval, neuroleptic treatment and duration of the disease. ANCOVA tests were used for group comparisons.Qualitative study showed swelling, vacuolation, paucity of ribosomes and mitochondria and accumulation of lipofuscin granules in oligodendrocytes in schizophrenia as compared to controls. Morphometry detected lowered Vv and N of mitochondria and higher Vv and N of lipofuscin granules and vacuoles in oligodendrocytes in the schizophrenic group as compared to the control group .Altered metabolism of oligodendrocytes, previously reported reduced number of oligodendrocytes, disrupted myelin/axon integrity, damage and progressive degeneration of myelin sheaths in prefrontal WM in schizophrenia may lead to disturbances in myelination, deficiency of nerve impulses propagation and contribute to network dysfunctions in schizophrenia. Oligodendrocyte and myelin abnormalities may be a target to prevent or restore WM abnormalities and dysfunction of neuronal connectivity in schizophrenia."} +{"text": "The Learning Health System Network clinical data research network includes academic medical centers, health-care systems, public health departments, and health plans, and is designed to facilitate outcomes research, pragmatic trials, comparative effectiveness research, and evaluation of population health interventions.The Learning Health System Network is 1 of 13 clinical data research networks assembled to create, in partnership with 20 patient-powered research networks, a National Patient-Centered Clinical Research Network.Herein, we describe the Learning Health System Network as an emerging resource for translational research, providing details on the governance and organizational structure of the network, the key milestones of the current funding period, and challenges and opportunities for collaborative science leveraging the network. The Patient-Centered Network of Learning Health Systems (LHSNet) Clinical Data Research Network (CDRN) is 1 of 13 CDRNs assembled to create, in partnership with 20 Patient-Powered Research Networks (PPRN) .http://www.lhsnet.org) Web site provides a map illustrating the geographic locations of the participating sites and describes each of the partnering organizations in the network [The LHSNet comprises 9 participating organizations and includes data on nearly 10 million patients. The LHSNet . As defiThe LHSNet leverages existing infrastructure, health information technologies, and data standards to connect its 9 sites and to build the foundation to facilitate patient-centered outcomes research; support large pragmatic clinical trials, and observational and interventional comparative effectiveness studies embedded within the health-care systems; and enable the dissemination, implementation, and evaluation of clinical and community efforts to improve population health. LHSNet is configured as a distributed data model wherein The 9 LHSNet partners represent an array of health-care delivery system stakeholders. Members of LHSNet have been collaborating for more than a decade and have strong relationships with patients and communities, academic medical centers, universities, health-care systems, and payers across the United States. Three Clinical and Translational Science Award recipients participate in the LHSNet ; all 3 institutions have a long-standing history of strong research collaboration and community engagement. The Clinical and Translational Science Awards at Mayo Clinic, Ohio State University, and the University of Michigan established processes to expedite Institutional Review Board (IRB) approval for multisite trials by creating IRB reciprocity agreements as part of the Midwest Area Research Consortium for Health, a consortium of upper-Midwest Clinical and Translational Science Awards. This experience formed the basis for the LHSNet-wide expansion of the IRB reliance model.http://midwestresearchnetwork.org/). The Midwest Research Network was founded in 2011 by a core group of research and clinical organizations in the Midwest to support collaborative grant proposals and resource sharing for population health research. The history of collaboration among these groups provides a foundation of trust and cross-institutional knowledge upon which the LHSNet is built.Five of the LHSNet sites such as Allina Health System, Essentia Health, Medica Research Institute, Mayo Clinic, and Olmsted County Public Health Services are also members of the Midwest Research Network (http://www.hcsrn.org/en/). This national collaborative of research departments and health-care systems includes nearly 2000 scientists and research staff with multidisciplinary content and methodological expertise. The extensive experience in multisite research efforts and data sharing of the Health Care Systems Research Network serves as a rich resource for the LHSNet.Essentia Health and Medica Research Institute are also members of the Health Care Systems Research Network , which is a learning network of delivery systems dedicated to data-driven improvement to deliver high-value care. The primary aims of the HVHC, to evaluate, disseminate, and facilitate the adoption of high-value care models in health-care settings, are closely aligned to the goals of LHSNet. Thus, the experience gained by our members in HVHC greatly informs the planning and execution of LHSNet efforts.The LHSNet is also benefited by the experience and expertise of members of the High Value Health Care Collaborative (HVHC). Intermountain Healthcare and Mayo Clinic are both founding members of the HVHC and with PPRNs to collaboratively conduct research.The governance structure of the LHSNet is comprised of 3 councils to oversee network processes and functions including the Governance Council, the Workgroup Council, and the Advisory Council . The GovRegulatory Workgroup oversees IRB requirements relevant to the multi-organizational research efforts, including streamlining IRB processes, enabling rapid start-up capabilities, and obtaining IRB approvals. The LHSNet Research Workgroup leads efforts to define clinical cohorts and integrate research into clinical practice. The Data Linkage and Data Governance Workgroup is responsible for enabling EHR and claims data linkages, informing data governance policies, and ensuring data completeness. The PCORnet (Informatics) Workgroup is tasked with the major technical aspects of developing the network including development of the following: the PCORnet CDM, the PCORnet Distributed Research Network Architecture, and basic PCORnet query capability. This workgroup is also responsible for data quality, informatics innovation, development of computable phenotypes, and enhancement of the PCORnet CDM. The Governance and Collaboration Workgroup leads the development of governing policies for research and collaboration. Finally, the Engagement Workgroup is leading efforts to understand existing patient engagement efforts across the network and to establish network-wide patient and stakeholder engagement strategies.Several workgroups have been assembled, including representatives from each participating site, to meet the required deliverables for the network . The RegAs one of the more recently funded CDRNs in PCORnet, the LHSNet is committed to meet an ambitious set of milestones within the 36-month period of performance. Key milestones, many of which have already been achieved, include the following: streamline IRB requirements across sites through development of a central IRB; increase data linkage for EHR and claims data from 1 million to 3 million lives; demonstrate full functionality of data mapping from each site to the PCORnet CDM; establish PopMedNet Node and demonstrate the ability to execute a basic query across sites; develop computable phenotypes for identifying condition-specific cohorts; validate cases for the 3 established disease cohorts ; and participate in a formally designated PCORnet study.Despite successful completion of milestones in the first 6 months of this project, we anticipate organizational, regulatory, and technical challenges as we ready the LHSNet for patient-centered comparative effectiveness research as part of the national PCORnet infrastructure . The LHSAs LHSNet works toward streamlining IRB infrastructure to support multisite research, ethical and regulatory challenges will need to be addressed. Systems will need to comply with the ethical and regulatory requirements of each site and support informed consent and enrollment of patients in an efficient manner across participating sites. Several members of LHSNet bring expertise in clinical research and clinical trials, including centralized IRBs and the identification of eligible patients using EHRs. This expertise will guide our efforts toward a centralized IRB and virtual patient consenting. Currently, members of LHSNet have signed master reliance agreements for Mayo Clinic to serve as the IRB of record. However, by January of 2017, LHSNet will adopt the Streamlined, Multisite, Accelerated Resources for Trials IRB Reliance Platform developed by the National Center for Advancing Translational Science. The National Center for Advancing Translational Science Streamlined, Multisite, Accelerated Resources for Trials IRB reliance model provides flexible resources to LHSNet investigators to harmonize and streamline IRB review through a set of agreements and standard operating procedures that enables each site to cede IRB approval to the institution leading the research effort.Technical challenges regarding observational research and longitudinal data capture, standardization and harmonization must be addressed by each participating site within LHSNet without disrupting the ways in which clinical data are routinely collected. Each site has successfully populated their DataMart as per the requirements of the CDM and is able to return data in response to data queries. However, individual research projects may require ongoing changes to the CDM. Furthermore, data capture must also be nimble enough to accommodate ongoing changes in clinical practice and related routine data collection. Technical challenges are also likely to be encountered in our planned data linkage efforts, as well as in the development and execution of computable phenotypes. Several members of LHSNet have robust expertise with methods and tools for longitudinal health-care data standardization, data linkage, data privacy, natural language processing, and computable phenotyping from EHRs and administrative claims. This expertise will guide our approach to addressing technical challenges as they emerge.The LHSNet is being developed as an LHS, including diverse members across a wide geographic region, to support clinical and translational research. As part of the PCORnet infrastructure, the LHSNet will enjoy the broader reach and potential for impact of the national research network. The PCORnet national data research network is being developed to support participation and data sharing with external investigators who are willing to participate in research studies in conjunction with the PCORI-funded CDRNs. Thus, opportunities for leveraging these networks for clinical and translational science will emerge as the networks mature.The LHSNet federated approach to an LHS has enormous potential to increase the efficiency with which clinical and biomedical knowledge is created, validated, and translated into practice . As a re"} +{"text": "Experiments in rodents have elucidated some of the molecular mechanisms underlying repetitive transcranial magnetic stimulation (rTMS). These studies may be useful in a translational perspective so that future TMS studies in rodents can closely match human TMS protocols designed for therapeutic purposes. In the present work we will review the effects of rTMS on glutamate neurotransmission which in turn induce persistent changes in synaptic activity. In particular, we will focus on the role of NMDA and non-NMDA transmission and on the permissive role of BDNF-TrKB interaction in the rTMS induced after-effects. Experiments in rodents are indeed valuable in providing information about the molecular mechanisms of action of repetitive transcranial magnetic stimulation (rTMS). From the hitherto published work on TMS/rTMS in rodents of almost two decades, it is possible to formulate a working hypothesis on the mechanism of action of rTMS so that future TMS studies in rodents can closely match human TMS protocols. The effects of rTMS in rodents are greatly dependent on: (1) the frequency and field intensity of the stimulation; (2) the acute and chronic mode of treatment; (3) the total number of pulses; (4) the shape and dimension of coils; and (5) the state, either anesthetized or awake, of the animals. Experimental evidences in rodents indicate that rTMS produces complex neurobiochemical effects such as induction of immediate early genes, changes in modulation of neurotransmitters release, effects on glutamate AMPA receptor/NMDA receptor expression , action on neuroendocrine systems, neuroprotective effects by reducing oxidative stress and inflammation, and a powerful activation of neurotrophic factors (Cirillo et al., ++ ions. Once sufficient numbers of AMPA receptors are activated, the membrane is depolarized from resting to active potential, the magnesium blockade is relieved, and the NMDA receptors are opened (Fleming and England, Having said that rTMS provides sustained effects, how does rTMS induce long lasting changes in cortical excitability? An important upstream regulator of synaptic plasticity is the BDNF-TrkB system. Indeed, we showed that 5-day rTMS enhances BDNF binding affinity for TrkB, BDNF-TrkB signaling, and NMDA receptor\u2013TrkB interaction in rat prefrontal cortex (Wang et al., in vitro model that rTMS may increase the steady state current in the presynaptic compartment independently from NMDA postsynaptic transmission. In this way, it is likely that longer duration rTMS protocol may enhance these presynaptic steady state currents thus prolonging the TMS induced after-effects (Banerjee et al., Despite the role of post-synaptic NMDA transmission on the long lasting effects of rTMS seems very clear, on the other hand there are evidences suggesting the involvement of presynaptic glutamatergic mechanisms (Banerjee et al., TS: study conception, drafting of the ms; MG, HW, and PB: critical revision; EM: critical revision, analysis of animal literature; DR: critical revision, clinical implications; AQ: study conception, drafting of the ms, crafting of the ms.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DP and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review."} +{"text": "Language disorders can be the first symptom of many neurodegenerative diseases, including Alzheimer's disease (AD) and primary progressive aphasia (PPA). The main variants of PPA are: the non-fluent/agrammatic variant, the semantic variant and the logopenic variant.Several additional variants of PPA, however, have been described and are considered as atypical presentations.We describe the case of a woman presenting a progressive isolated language disturbance, characterized by an early dysprosodia, phonological and semantic paraphasias, agrammatism, impairment in repetition, writing of non-words and sentence comprehension. This clinical picture pointed to an atypical presentation of the non-fluent variety. The frequent symptom overlap between the different variants of PPA, most likely reflecting differences in the topography of the pathological changes, needs to be considered in the definition of diagnostic criteria."} +{"text": "Neuroscience began with neuroanatomy and neurosurgery in Egypt more than 5000 years ago. Knowledge grew over time and specialized neurosurgery centers were established in north Africa in the eleventh century. However, it was not until the twentieth century that neuroscience research became established in sub-Saharan Africa. In most African countries, clinical research focused on understanding the rationale and improving treatment of epilepsy, infections, nutritional neuropathies, stroke and tumors. Significant advances were made. In the twenty-first century, African knowledge expanded to include all branches of neuroscience, contributing to genetic, biochemical and inflammatory determinants of brain disorders. A major focus of basic neuroscience research has been, and is, investigation of plant extracts, drugs and stress in animal models, providing insight and identifying potential novel therapies. A significant event in the history of African neuroscience was the founding of the Society of Neuroscientists of Africa (SONA) in 1993. The International Brain Research Organization (IBRO) supported SONA conferences, as well as workshops and neuroscience training schools in Africa. Thanks to their investment, as well as that of funding agencies, such as the National Institutes of Health (NIH), International Society for Neurochemistry (ISN), World Federation of Neurosurgical Societies (WFNS), World Federation of Neurology (WFN) and the International League Against Epilepsy (ILAE), neuroscience research is well-established in Africa today. However, in order to continue to develop, African neuroscience needs continued international support and African neuroscientists need to engage in policy and decision-making to persuade governments to fund studies that address the unique regional needs in Africa. The earliest evidence of neuroscience research dates back more than 5000 years. Egyptian embalmers were the first to obtain knowledge of human anatomy through the mummification process. However, they had very little regard for the brain and did not try to preserve it , nutritional neuropathies, stroke, tumors, motor disorders and the adverse effects of snake venom Lambo, . SignifiIt is impossible to do adequate justice to all of the neuroscience research that has been carried out in Africa. This mini-review will therefore trace a few of the major trends based on a PubMed search of neuro-related publications by African neuroscientists in the eight African countries listed as having an H index of 20 or greater, in the SCImago Journal & Country Rank Report 2016)61).In the twentieth and twenty-first centuries, neuroscience research in Tunisia and Algeria involved mostly clinical studies on neurogenetics and movement disorders an addictive psychostimulant grown in abundance in Kenya and impairment of executive function in children with malaria, to name a few 2016; IdrOver the years, science-based non-profit organizations such as the International Brain Research Organization (IBRO) have supported African neuroscientists and helped to build scientific capacity for sustainable education and research by sponsoring training courses and workshops across Africa. Training programmes in Neurosurgery, Neurology and basic Neuroscience, supported by, the World Federation of Neurosurgical Societies (WFNS), the World Federation of Neurology (WFN), the Society of French Speaking Neurosurgeons (SNCLF) the International League Against Epilepsy (ILAE), the National Institutes of Health (NIH), IBRO and the International Society of Neurochemistry (ISN), amongst others, have led to the production of many generations of neuroscientists in Africa. IBRO and ISN, in particular, have engaged in basic neuroscience with a strong translational approach to brain disorders in Africa. IBRO African Centres for Advanced Training in Neuroscience have been established in Morocco and South Africa. WFNS-recognized Centres of Excellence for training neurosurgeons have been established in Nigeria, Ivory Coast, Senegal, Kenya, Zimbabwe and South Africa by James Kimani in 1993. IBRO generously supported SONA conferences, as well as several workshops and neuroscience training schools in more than 14 African countries. Thanks to their investment, as well as that of the other funding agencies, neuroscience research is well-established in Africa. However, in order to continue to develop, African neuroscience needs continued international support and African neuroscientists need to engage in policy and decision-making to persuade governments to fund studies of unique regional needs in Africa (Bentivoglio et al., VAR wrote the mini-review.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Based on a great number of literatures, we established the database about the Chinese endemic seed plants and analyzed the compositions, growth form, distribution and angiosperm original families of them within three big natural areas and seven natural regions. The results indicate that the above characters of Chinese endemic plants take on relative rule at the different geographical scales. Among the three big natural areas, Eastern Monsoon area has the highest endemic plants richness, whereas Northwest Dryness area is the lowest. For life forms, herbs dominate. In contrast, the proportion of herbs of Eastern Monsoon area is remarkable under other two areas. Correspondingly the proportions of trees and shrubs are substantially higher than other two. For angiosperm original families, the number is the highest in Eastern Monsoon area, and lowest in Northwest Dryness area. On the other hand, among the seven natural regions, the humid and subtropical zone in Central and Southern China has the highest endemic plants richness, whereas the humid, hemi-humid region and temperate zone in Northeast China has the lowest. For life forms, the proportion of herbs tends to decrease from humid, hemi-humid region and temperate zone in Northeast China to humid and tropical zone in Southern China. Comparably, trees, shrubs and vines or lianas increase with the same directions. This fully represents these characters of Chinese endemic plants vary with latitudinal gradients. Furthermore, as to the number of endemic plants belonging to angiosperm original families, the number is the most in humid and subtropical zone in Center and Southern China, and tropical zone in Southern China in the next place. In contrast, the endemic plant of these two regions relatively is richer than that of The Qinghai-Tibet alpine and cold region. All above results sufficiently reflect that the Chinese endemic plants mainly distribute in Eastern Monsoon area, especially humid and subtropical zone in Center and Southern China and tropical zone in Southern China. Furthermore, the flora of Eastern Monsoon area, in particular humid and subtropical zone in Center and Southern China and tropical zone in Southern China, is more ancient and original than that of Northwest Dryness area and Qinghai-Tibet alpine and cold area. Almost mountain . This clmountain , and makmountain ,6, but amountain ,7.Formation and changes of land and sea, climate change, large-scale mountain or plateau uplift as well as regional ecological complications play different and important roles in speciation and diversification of flora. They all directly or indirectly affect speciation, differentiation, migration, extinction and preservation of flora. The early Paleozoic Caledonian movement makes land lift and Chinese continent disperse. Main mountains in northeast and northwest China and Qinling Mountains formed in later Paleozoic Hercynian tectonic period. In this period, Chinese continent was connected to the Siberian continental platform, and Tianshan Mountain was interlinked with mountains and plateau of central Asia. Tanggula mount, Karakoram and Hengduan mountains were formed during Yanshanian Tectonic Period between Mesozoic Jurassic and before Cenozoic . In the In recently years, China has been developing in the field of biodiversity research including Species Catalogue, biodiversity monitoring, phylodiversity, biodiversity informatics and biodiversity conservation \u201315. EndeMany studies on biodiversity conservation and endemism of Chinese flora have carried out across China \u201327. ChinFlora of China [Flora Reipublicae Popularis Sinicae [According to checklist of Chinese endemic seed plant species , we compof China and Flor Sinicae , b) locaAccording to map of geographical regions of China , we digiWe analyzed the compositions of both the Chinese endemic plants and local endemic plants , and counted quantitative characteristics of each main group in terms of different growth forms. To detect the distribution pattern of Chinese endemic seed plant species in the entire country, we calculated Chinese endemic plants richness and local endemic plants richness separately. In addition, we compared and analyzed compositional characteristics of original taxa for each geographical region according to checklist of orders and families for original taxa . All calChinese endemic seed plants are very unevenly distributed in natural geographical units. In three geographical areas, the Eastern Monsoon area is highest in number of endemic plants, while the Northwest Dryness area is lowest in that . Ratio oChinese endemic plants are mostly limited to relatively narrow areas . Only 7.Chinese endemic seed plants were divided into four kinds of growth forms: tree, shrub, herb, and liana or vine. Herb is dominant in any geographical region Tables , Fig 3. Halerpestes tricuspis var. heterophylla and Berberis farreri, are present commonly in both the Northwest Dryness area and the Qinghai-Tibet alpine and cold area, but are absent in the Eastern Monsoon area. One thousand three hundred and twenty Chinese endemic plants (accounting for 62.3%) from 18 original families are distributed restrictively within the Eastern Monsoon area. Only 56 Chinese endemic plants (accounting for less than 2.6%) form original families are limited in the Northwest Dryness area. There are 310 Chinese endemic plants (accounting for 14.6%) distributed limitedly within the Qinghai-Tibet alpine and cold area. These endemic plants mainly belong to Ranunculaceae, Papaveraceae, Berberidaceae and Lauraceae.There are 2120 Chinese endemic plants belonging to 19 original families in ChinaRanunculus furcatifidus and Clematis akebioides, which both belong to Ranunculaceae family, are common endemic plants in seven geographical regions. Four Chinese endemic plants, which all belong to Ranunculaceae family, are common in six geographical regions. Thirty Chinese endemic plants, which are dominant in Ranuculaceae, are common in five geographical regions. Eighty six Chinese endemic plants are common in four geographical regions. These endemic plants belong to Ranunculaceae, Papaveraceae, Berberidaceae. There are 1409 endemic plants (accounting for 66.5%) from original families present in the humid and subtropical zone in Center and Southern China (Geo3). Among of them, 653 plants (accounting for 30.8%) are restricted in this geographical region. There are 744 endemic plants (accounting for 35.1%) from original families present in the humid and tropical zone in Southern China (Geo4). Among of them, 255 plants (accounting for 12.0%) are restricted in this geographical region.Only Chinese endemic seed plant species are very unevenly distributed in three geographical areas and seven geographical regions. The Northwest Dryness area is arid because Qinghai-Tibet Plateau, Qinling Mountains, Taihang Mountain, and Yanshan and Da Hinggan Ling Mountain prevent The proportions of tree, shrub, and liana or vine in the Eastern Monsoon area are higher than that of in the Northwest Dryness area and in the Qinghai-Tibet alpine and cold area. On the contrary, the proportion of herb in the Eastern Monsoon area is less than that of in the Northwest Dryness area and in the Qinghai-Tibet alpine and cold area. Herb is considered to be more evolutionary group than tree . On thisBoth Chinese endemic plants richness and local endemic plants richness are higher in the humid and subtropical zone in Center and Southern China than that in the Qinghai-Tibet alpine and cold area. This might implicate that endemic flora in the humid and subtropical zone in Center and Southern China is older than that in the Qinghai-Tibet alpine and cold area . ConsideChinese endemic plants take on relative rule at the different geographical scales. The Chinese endemic plants mainly distribute in Eastern Monsoon area, especially humid and subtropical zone in Center and Southern China and tropical zone in Southern China. The flora of Eastern Monsoon area, in particular humid and subtropical zone in Center and Southern China and tropical zone in Southern China, is more ancient and original than that of Northwest Dryness area and Qinghai-Tibet alpine and cold area.S1 Table(DOC)Click here for additional data file.S1 Appendix(XLSX)Click here for additional data file.S2 Appendix(DOC)Click here for additional data file."} +{"text": "Antimicrobial use in food-producing animals selects for antimicrobial resistance that can be transmitted to humans via food or other transmission routes. The World Health Organization (WHO) in 2005 ranked the medical importance of antimicrobials used in humans. In late 2017, to preserve the effectiveness of medically important antimicrobials for humans, WHO released guidelines on use of antimicrobials in food-producing animals that incorporated the latest WHO rankings.WHO commissioned systematic reviews and literature reviews, and convened a Guideline Development Group (GDG) of external experts free of unacceptable conflicts-of-interest. The GDG assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and formulated recommendations using a structured evidence-to-decision approach that considered the balance of benefits and harms, feasibility, resource implications, and impact on equity. The resulting guidelines were peer-reviewed by an independent External Review Group and approved by the WHO Guidelines Review Committee.These guidelines recommend reductions in the overall use of medically important antimicrobials in food-producing animals, including complete restriction of use of antimicrobials for growth promotion and for disease prevention . These guidelines also recommend that antimicrobials identified as critically important for humans not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option.To preserve the effectiveness of medically important antimicrobials, veterinarians, farmers, regulatory agencies, and all other stakeholders are urged to adopt these recommendations and work towards implementation of these guidelines. The increasing prevalence of antimicrobial resistance is a worldwide problem , 2. AntiTo address the growing public health problem of antimicrobial resistance, the 68th World Health Assembly adopted the World Health Organization\u2019s (WHO) Global Action Plan on Antimicrobial Resistance (GAP) in May 2015 . The WHOAntimicrobials are widely used in food-producing animals for therapeutic use , prophylactic use , and growth promotion use (to improve rate of gain or feed efficiency) . Such usWith the ever growing public health threat of antimicrobial resistance and the recognized need to preserve the effectiveness of medically important antimicrobials, particularly those antimicrobials judged to be critically important to human medicine on the WHO CIA List, WHO elected to develop formal, evidence-based, guidelines on use of antimicrobials in food producing animals.WHO Handbook for Guideline Development, three groups were organized [In accordance with the rganized . A WHO SA Guideline Development Group (GDG), comprised of thirteen external experts from five WHO regions with expertise in clinical human medicine, infection prevention and control, evidence-based medicine, tropical medicine, epidemiology, veterinary medicine, microbiology, infectious diseases, public health, antimicrobial resistance, economics and veterinary ethics. The GDG assessed the available evidence and formulated recommendations. One member of the GDG was a Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodologist. GDG members were selected in a way that sought geographic representation and gender balance, and avoided conflicts of interest. An External Review Group (ERG), composed of eleven technical experts and stakeholders with interest in use of antimicrobials in food-producing animals including veterinarians, microbiologists, animal scientists, public health practitioners, food safety experts, public health policy officials, and physicians. The ERG reviewed the final draft of the guidelines to identify errors of fact and commented on the clarity of the language, contextual issues and implications for implementation.http://apps.who.int/iris/bitstream/10665/258970/1/9789241550130-eng.pdf). Following a public solicitation for applications, the WHO Steering Group selected the applications from teams at Bond University and University of Calgary (Canada). The systematic review teams interacted regularly with the WHO Steering Group but worked independently of each other.WHO commissioned systematic reviews of the published evidence that restrictions in use of antimicrobials in food-producing animals reduced the prevalence of antimicrobial resistance in bacteria isolated from food-producing animals and humans and March 2017 . The GDG formulated recommendations based upon the summarized evidence and judgments of the overall quality of the evidence. Using the GRADE approach, the GDG also judged the strength of each recommendation by considering the importance of the problem, the quality of evidence, the balance between benefits and harms, the values and preferences of affected populations, resource implications, the impact on equity, human rights, gender and social determinants of health, acceptability, and feasibility [As per WHO regulations, all external experts and contributors disclosed their secondary interests prior to participating in the WHO guideline development process. When a conflict of interest was identified, WHO followed standard procedures to determine whether or not the expert was permitted to participate in the guideline development process. A biographical sketch of each nominated GDG member was posted online for public comments. The WHO Steering Group reviewed all information gathered before approving final GDG membership.Governments of Japan and The Netherlands provided funding for the guidelines but were not involved with guidelines development. WHO facilitated the development of the WHO Guidelines, in accordance with the WHO guideline development process, and provided additional funding for the guidelines.http://apps.who.int/iris/bitstream/10665/259241/1/WHO-NMH-FOS-FZD-17.2-eng.pdf.The systematic reviews yielded a large number of studies that demonstrated a consistent decrease in the prevalence of antimicrobial resistance in bacteria isolated from food-producing animals or humans following restrictions on use of medically important antimicrobials in food-producing animals. The Bond University systematic review team provided a narrative report of the quality of, and summary of findings from, 93 studies and concluded that limiting the antimicrobial use in food animals is likely to reduce the presence of antimicrobial resistance in food \u2013producing animals and humans. The University of Calgary systematic review team provided a quantitative report from 177 studies that included an assessment of the quality of the primary studies and provided a meta-analysis of the risk differences for reductions in the prevalence in antimicrobial resistance reported with various restrictions on antimicrobial use in food producing animals . The Unihttp://apps.who.int/iris/bitstream/10665/259241/1/WHO-NMH-FOS-FZD-17.2-eng.pdf .Of the three commissioned content specific literature reviews, one review provided evidence from illustrative examples of probable transfer of resistant determinants for streptothricins, glycopeptides and colistin from food-producing animals to humans . The sechttp://apps.who.int/iris/bitstream/10665/259242/1/WHO-NMH-FOS-FZD-17.3-eng.pdf .The evidence presented to the GDG was predominately from observational and ecologic studies. Additionally, the systematic reviews found few studies from middle-income and low-income countries, and few studies included small-scale food-producing animal operations. Despite these limitations, the GDG determined that there was sufficient evidence that use of medically important antimicrobials in food-producing animals selects for antimicrobial resistance in bacteria, and that such antimicrobial resistant bacteria can be transmitted to humans, including in middle-income and low-income countries, and small-scale operations. Summaries of the information used by the GDG to develop best practice statements and recommendations related to the use of medically important antimicrobials in food-producing animals, including evidence profiles, summary of findings tables, and evidence-to-recommendations tables, are available at Any new class of antimicrobials or new antimicrobial combination developed for use in humans will be considered critically important for human medicine unless categorized otherwise by WHO.Medically important antimicrobials which are not currently used in food production should not be used in the future in food production, including in food-producing animals or plants.The GDG developed two best practice statements for classes of antimicrobials not currently used in food-producing animals.The GDG judged that these best practice statements were needed to provide a basis for taking actions to preserve the effectiveness of critically important antimicrobials for humans that are not currently used in food-producing animals. Furthermore, given the critical need for new classes of antimicrobials for the treatment of some serious and life-threatening infections in humans, the development and eventual marketing of new classes of antimicrobials will likely be antimicrobials required for infections in humans with no or limited treatment options.Since these antimicrobials are not yet used in food-producing animals, direct evidence is not available. Instead, the best practice statements are supported by considerable indirect evidence, including a large body of evidence from the systematic reviews and from mechanistic studies of antimicrobial resistance , 19.An overall reduction of use of all classes of medically important antimicrobials in food-producing animals is recommended. .Complete restriction of use of all classes of medically important antimicrobials in food-producing animals for growth promotion is recommended. .Complete restriction of use of all classes of medically important antimicrobials in food-producing animals for prevention of infectious diseases that have not yet been clinically diagnosed is recommended. .It is suggested that antimicrobials classified as highest-priority critically important for human medicine should not be used for treatment of food-producing animals with clinically diagnosed infectious disease. It is also suggested that antimicrobials classified as critically important for human medicine should not be used for control of the dissemination of a clinically diagnosed infectious disease identified within a group of food-producing animals. .The GDG developed four recommendations, supported by both direct and indirect evidence, concerning the use of medically important antimicrobials in food-producing animals.The GDG determined that the first three recommendations should be strong despite the low-quality evidence due to the large human health benefits of lowered prevalence of antimicrobial resistance in bacteria isolated from humans and the limited evidence of undesirable consequences of restrictions on antimicrobial use of medically important antimicrobials in food producing animals. Specifically, there was a large amount of consistent evidence from the systematic reviews and the literature reviews that resistant bacteria can spread among food-producing animals, into their environment, and to humans, and that restrictions on use of antimicrobials in food-producing animals reduces the prevalence of antimicrobial resistance in bacteria isolated from food-producing animals that are, and can be, transmitted to humans. The GDG also concluded that for the fourth recommendation, although evidence from the systematic reviews and additional studies indicates it will achieve the human health benefit of lowered antimicrobial resistance in bacteria, this recommendation should be conditional due to the very low quality of available evidence. In order to protect animal health and welfare, the GDG concluded that exceptions to recommendations 4a and 4b can be made when, in the judgement of qualified veterinary professionals, susceptibility results demonstrate that the selected drug is the only treatment option.The GDG also concluded that in order for people in all countries to realize the benefits of continued effectiveness of medically important antimicrobials, the recommendations in these guidelines should be applied in all animal production settings and in all countries.With the recognition of the need to reduce the use of medically important antimicrobials in food-producing animals, the GDG identified the following research areas which can be addressed to help facilitate reduced antimicrobial use: identifiThe use of antimicrobials in food-producing animals has been a public health concern for decades . In 1997In accordance with the WHO guideline development process , the GRAThe GRADE approach follows a rigorous and transparent process, and is the most widely used approach for evidence appraisal for guideline development. The GRADE approach was initially developed for decision-making in clinical settings, where randomized clinical trials are commonly available. It rates evidence derived from randomized controlled trials as high quality, while evidence from epidemiological studies, surveillance programmes and other sources of observational data, in which confounding cannot be adequately controlled, is rated as \u201clow quality\u201d. In common with many important public health issues, due to ethical and technical complexity, there are no randomized controlled studies that have assessed associations between use of antibiotics in food-producing animals and risks of human exposure to infection by drug-resistant zoonotic pathogens. Most of the supporting scientific evidence, representing the best available evidence, was collected from epidemiological studies, surveillance programmes and observational studies. In addition to the quality of the evidence and the balance of benefits and harms of an intervention, a number of other factors are considered when GDGs formulate recommendations. These factors include the relative value placed on the potential beneficial and harmful outcomes of an intervention, the acceptability and feasibility of the intervention, resource considerations, and effects on equity across subpopulations. A \u201cstrong recommendation\u201d means that after taking all relevant considerations into account, the GDG is reasonably certain that the desirable consequences (benefits) of an intervention outweigh the undesirable consequences (risks or harms), such that the intervention should be implemented in most settings.The GRADE approach has been used successfully in public health settings where only observational studies are available. There are challenges, however, in using the GRADE approach in all settings, especially in the formulation of recommendations on complex interventions in public health settings . AlthougUsing the rigorous and transparent WHO guideline development process, the GDG determined that three of the four recommendations on use of medically important antimicrobials in food-producing animals should be strong recommendations given (1) the large body of evidence from the commissioned systematic reviews using a rigorous and evidence based approach of the strength and consistency of the association between restrictions of antimicrobial use in food-producing animals and antimicrobial resistance in animals and humans, (2) the suggestion of a dose-response relationship with this association, (3) the large potential health benefits, and (4) the evidence of limited unintended consequences. The GDG also recommended implementation of the WHO guidelines worldwide. As with all WHO guidelines related to food safety, implementation relies on the impetus of Member States and other stakeholders, including the FAO/WHO Codex Alimentarius Commission, to translate the recommendations into national and international standards or guidance. In order to reach the overall goal of reducing antimicrobials in food-producing animals, there is a particular need to identify management alternatives for use of antimicrobials for disease prevention. The GDG acknowledged that implementation in lower-income or middle-income countries may require special considerations such as assistance in improvement of hygienic and agricultural practices including improved housing and husbandry. Furthermore, many countries may need technical and laboratory capacity building assistance for conducting the recommended bacterial culture and antimicrobial susceptibility testing. It is important for countries to conduct surveillance and monitoring of antimicrobial usage in food-producing animals to evaluate the effectiveness of any interventions.In conclusion, the WHO guidelines recommend overall reduced use of medically important antimicrobials in food-producing animals, including complete restriction of uses of medically important antimicrobials for growth promotion and for disease prevention. Exceptions for disease prevention can be accepted when based upon the judgement of a veterinary professional and if such judgement is based on recent culture and sensitivity testing results. The WHO Guidelines also suggested that antimicrobials identified as critically important for human medicine not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option. To preserve the effectiveness of medically important antimicrobials, all stakeholders should implement the recommendations in the WHO guidelines. Such implementation will support the WHO GAP to control antimicrobial resistance by reducing unnecessary use of antimicrobials in food-producing animals."} +{"text": "Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources . Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is inspired by the quadruple helix concept and by the replication of innovative good practices; creating new Reference Sites for the benefit of Citizens. Europe faces the global challenge of population aging with strong impact in the quality of life of individuals and families, society cohesion, health, and economic resources of citizens and member states. The percentage of people aged 65 or over in the population is expected to grow from 18.4% in 2013 to 28.4% in 2060 for the average of European countries of 143.9 in 2015 compared to 27 in 1960.Within Portugal, the population living in the Centre Region is particularly old due to the increase in life expectancy, migration of young adults and decrease in birth rate. Within the Centre Region, some areas are already facing the demographic scenarios expected for the European landscape in 2060, e.g., municipalities with Ageing Index above 700.Taking together, the demographic landscape of Europe, with a particularly and striking case in Portugal, urges the need of defining new strategies and implementing actions to deliver innovative and disruptive solutions. These solutions are expected to have impact at the individual, family, labor, societal, and economic dimensions to support individual health and well-being, at all ages, and deliver solutions to support health and social care sustainability. As we will elaborate bellow, the EIP on AHA movement, and the particular case of Ageing@Coimbra (as a Community Case Study), may be inspiring for the required change management processes, delivering solutions for the challenges of aging and opening new opportunities for economic growth.The EIP on AHAThe EIP on AHA grew from recognition that the quality of life of older people is strongly affected by life style habits across the life cycle in all ages. Many older people suffer from multiple chronic conditions that demand continuous support by medical and social care providers and limit functional independence. Ultimately, poor health in later life strongly impacts on health and economic resources, human suffering, human dignity of individuals, and families .The EIP on AHA fosters collaborative work of European partners to support three main strategic pillars of AHA: (1) prevention, screening, and early diagnosis; (2) care and cure; (3) independent living and active aging. EIP on AHA partners are organized in six action groups: A1, adherence to prescription and medical plans; A2, personalized health management and prevention of falls; A3, lifespan health promotion and prevention of age-related frailty and disease; B3, replicating and tutoring integrated care for chronic diseases; C2, development of interoperable independent living solutions; D4, innovation for age-friendly buildings, cities and environments.The main goal is to achieve a triple win for Europe: (1) Health and quality of life of European citizens; (2) Sustainable and efficient care systems; and (3) Growth and expansion of EU industry.EIP on AHA is a wide interdisciplinary and transdisciplinary network that seeks innovative collaborative models, removing silos and developing citizen-centered processes. EIP on AHA partners joint academia, health, and social care providers, citizens and patient associations and several other stakeholder groups with innovators, entrepreneurs, and business partners. The aim is to deliver knowledge and user-based competence into innovative good practices, products, and services. Only disruptive innovation and knowledge-based added value will deliver efficient meaningful large-scale interventions to face the societal challenges, opening, at the same time, new opportunities for entrepreneurs, business activity, and job creation , 4.Reference Sites have been defined by the EIP on AHA as \u201cinspirational ecosystems, delivering creative and workable solutions that improve the lives and health of older people.\u201dReference Sites include regions, cities, integrated hospitals, or care organizations that focus on innovative and holistic approaches to support AHA. Reference Sites show diverse levels of impact and maturity toward the goal standard of regional ecosystems aligning actors across the quadruple helix: academia, authorities, business, and civil society. The impact of the activities of Reference Sites provides evidence of innovative components, and indicators are measurable in line with the Monitoring and Assessment Framework of the EIP on AHA (MAFEIP), under the dimensions \u201cQuality of life,\u201d \u201cSustainability of health-care systems,\u201d and \u201cEconomic growth and jobs.\u201dThe first call for Reference Sites by the European Commission resulted in the award of 32 Reference Sites in 2013. The second call led to a total of 74 Reference Sites in 2016. Recently , the Reference Sites launched a non-profit association based in Brussels to promote synergies and collaborative work \u2014the Reference Site Collaborative Network .The Ageing@Coimbra ConsortiumAgeing@Coimbra is an informal network of 5 founder and 65 associated partners that build a \u201cquadruple helix\u201d, aligning: (1) public institutions , (2) academia , (3) industry partners , and (4) civil society organizations . The consortium was founded under a leadership initiative of the University of Coimbra, the Municipality of Coimbra, the Regional Health Authority, the University of Coimbra Hospital, and the Pedro Nunes Institute . The Administrative Authority of the Centre Region of Portugal has been a major supporter and driver for the success of Ageing@Coimbra, actively engaging in the implementation of activities, international visibility and ownership of responsibility to include AHA in the key priorities of the Smart Specialization Strategy (RIS3) of the Center Region of Portugal. In 2017, CCDRC launched a regional competition to award three cases of good practices in three clusters: Knowledge, Health, and Life.Ageing@Coimbra was the first EIP on AHA Reference Site in Portugal. The innovative formula and lean governance structure created an inclusive partnership with agility, rapid implementation, and growth potential. Concordantly, other regions in Portugal and regions in other European countries embraced Ageing@Coimbra example to replicate the model and launched new reference sites in 2016, or they will do so in a future call expected for 2019. The same example has replication potential in other countries in Europe and globally .As an active member of EIP on AHA Action Groups, Ageing@Coimbra participates in the collaborative activities and delivers success cases of projects and good practices.Multimorbidity and the related prescription of multiple drugs are becoming common problems among older people, frequently associated with poor health outcomes, being inadequate and/or poor adherence to medical plans one of the relevant factors that compromise the success of treatments . TherefoThe collaborative work of Ageing@Coimbra in the A1 Action Group resulted in the successful development of the third Health Program Project SIMPATHY (Stimulating Innovative Management of Polypharmacy and Adherence in the Elderly), a project coordinated by the Scottish Government (Grant Agreement 663082)falls are a major indicator of increasing frailty and loss of independence and mobility in older people.\u201d The main objective of the A2 Action Group has been to deliver EU wide evidence-based, validated and operational programs for the prevention, early identification, and minimization of risk and management of falls in order to reduce falls and the personal, system, and societal consequences of fall-related injuries. In order to reach relevant joint achievements and goals four different areas of collaborative work are being developed: (1) implementation of an integrated and person-centered service pathway for fall prevention and management; (2) data collection for evidence-based interventions on falls; (3) awareness, information, and education, to support the training of the workforce; (4) Governance: innovation, sustainability, and scaling-up, including models for exploitation, business analysis, and strategies for falls prevention technologies take up.The relevance of the topic addressed in the A2 Action Group is supported by the Joint Declaration of the European Stakeholders Alliance for Active Ageing through Falls PreventionThe collaborative work of Ageing@Coimbra in the A2 group resulted in joint activities and collaborative work in the Prevention of Falls Network for Dissemination (ProFouND), an EC funded initiative dedicated to the dissemination and implementation of best practices in falls prevention across Europe.Also, within the scope of the A2 action group, the Project \u201cGood practices to develop physical activity programs at work\u2014FitWork\u201d was developed within the framework of the ERASMUS\u2009+\u2009SPORT program aimed at developing good practices to implement physical activity programs at work attending to specific risks of workplaces . The project is coordinated by Instituto de Biomec\u00e1nica de Valencia and more information can be found at.Reflecting a growing awareness of the need for better care and sustainable and effective health services, the A3 Action Group aims to contribute to AHA with a life-course approach, implementing the shift from reactive disease management to anticipatory care of functional decline through community-based prevention, early diagnosis, and screening programs, and integrated care management systems. This patient-centered approach involving social and health-care systems is based on innovative solutions that support interactions in the areas of nutrition, frailty and functional decline, cognitive decline and physical activity. It also fosters the development of networks strengthening education and training of the health workforce, citizens empowerment through health and ICT literacy, and advancing knowledge on the determinants of frailty and chronic diseases to support early detection and sustainable interventions. The joint effort of A3 partners is the improvement and alignment of services delivered to the needs of older populations and enabling caregivers\u2019 education and empowerment.Frailty Management Optimization through EIPAHA Commitments and Utilization of Stakeholders\u2019 Input) was launched to monitor and control the symptoms of allergic rhinitis , 10 Fig.The objective of the C2 Action Group is to develop interoperable independent living solutions, including guidelines for business models. This should boost the deployment of open and personalized solutions for active and independent living that are supported by global standards and new evidence on the return of investment. The C2 Action Group provides essential input to the creation of a new market for cost-effective products and services that help older people live a more active and independent life. This reinforces ongoing research and innovation activities in Europe (and elsewhere), supported through public\u2013private partnerships.Within the scope of the C2 Action Group, in 2017, the AAL Forum, the biggest European event in the field of Technologies for AHA was organized in Coimbra, by the Pedro Nunes Institute, in partnership with the Portuguese Foundation for Science and Technology and some of the Ageing@Coimbra core partners. The theme of the Forum was \u201cBridging the gaps between technology solutions and aging well. What can YOU do?\u201d Interoperable solutions were discussed as crucial to assure the value of the digital solutions, for example contributing for the integration between social and health care.An inspirational fresh addition to this year\u2019s AAL Forum exhibition hall was the attendance of over 120 end-users above the age of 65, all eager to give their honest opinion on what they saw. Exhibitors had approximately 7\u2009min to present and sell their AAL solution to the guests, which turned out to be more of a challenge than the majority of exhibitors expected Figure . After vFor the first time in the AAL Forum, the jury responsible for awarding the Exhibition Prize was constituted only by end-users above the age of 65. This activity was supported by Ageing@Coimbra and the Administrative Authority of the Centre Region of Portugal.Another example of the collaborative work of Ageing@Coimbra members within the scope of C2 Action Group is well represented by the project GrowMeUp, funded under the H2020 call PHC-19-2014 \u201cAdvancing active and healthy aging with ICT: service robotics within assisted living environments\u201d; coordinated by the University of Coimbra and including the active partnership with Caritas Coimbra as an end-user organization (Grant Agreement 643647).The D4 Action Group has its main roots on the concept of Age-Friendly Environments, as envisaged by the World Health OrganizationCaritas Coimbra is also a founder member and Vice-President of the European Covenant on Demographic Change, an organization that aims to gather local, regional, and national authorities as well as other stakeholders in order to cooperate and implement evidence-based solutions to support AHA.The collaborative work of Ageing@Coimbra in D4 group includes the leadership of the University of Coimbra in the H2020 project Euro-Healthy with a key goal to deliver a Population Health Index and a Web Geographic Information System (Web-GIS) addressing health inequity across the EU (Grant Agreement 643398) .15The area of biomarkers for neurodegenerative diseases, particularly concerning Alzheimer\u2019s disease, profits from the solid basis of neuroscience research provided by CNC.IBILI. Fundamental research is transferred from bench to bedside by means of knowledge-based genetics, biochemical, imaging, and neuropsychology biomarkers of cognitive dysfunction.Genetics and biochemical biomarkers currently used to identify risk factors and biomarkers of Alzheimer\u2019s disease include APP, tau, amyloid beta 1-42, genotyping for PSEN1, PSEN2, APP, ApoE .The Faculty of Psychology of the University of Coimbra provides neuropsychology tests to screen for functional and memory competence of older adults including Adults and Older Adults Functional Assessment Inventory (IAIFA), World Health Organization Quality of Life-OLD module, Geriatric Depression Scale (GDS-15), cognitive performance .The early diagnosis pipeline is complemented with robust brain imaging tools to ensure high quality diagnosis of putative neurodegenerative conditions. The Applied Nuclear Sciences Institute (ICNAS) pipeline launches innovative cyclotron-based synthesis methods of radiotracers including PET/FDG, PET/PiB, PET/PK11195, and other radiotracers upgrading the diagnosis tools.This integrated approach, aligning technologies and professionals/resources for a better public service results in relevant assets for Ageing@Coimbra stakeholders, creating the most valuable and reliable integrated health service in Alzheimer\u2019s diseases in Portugal; with recognized impact in the Health Cluster Portugal, the Joint Program in Neurodegenerative Diseases, and the EIT Health Knowledge Innovation Community (KIC).The diagnostics pipeline for early detection of Alzheimer\u2019s disease contributes to better health-care management and also to liaise with patient associations for better social care and support to patients and care providers.The territory of the Center Region of Portugal offers peculiar conditions as a regional living laboratory. In the region, about 23% of residents are aged 65 or over living in diverse environments, urban versus rural, highly dense versus low-density territories. In inland areas, especially in the mountain area, low-density territories also create geographic barriers to mobility especially of frail people contributing to social isolation. On the other hand, social isolation is also a burden of older persons living alone in urban areas of the Centre Region of Portugal.These particular conditions create a local need to develop integrated care and personalized solutions to support older people living in socially challenging conditions.The majority of municipalities in the Region have been equipped with health mobile units to deliver primary care and social care support to frail older people living in rural isolated areas. The added value of these services is well recognized by users and professionals, showing increase demand in terms of individual requests by the citizens and attracted interest by other municipalities.Portugal launched in 2016 a new coordination structure of the National Network for Integrated Care Units. This network provided complementary health and social care support to populations, being socially isolated frail older people the main beneficiaries. The regional network includes 3 main units for palliative care, 9 units for convalescence care, and more than 62 integrated home care teams. Ageing@Coimbra links with integrated home care teams in close collaboration with the regional health authority, the national insurance office, and municipalities.The social support to isolated frail older people in the region is a key priority for local players, including municipalities. Several important actions support intergeneration activities to tackle social isolation, ICT literacy, polypharmacy, and adherence to therapy strategies, assisted living programs, innovative strategies to engage older citizens with meaningful activities, and an humanitarian approach in health care\u2014both in rural and urban areas.The regional health authority launched a program (\u201cp\u00e3o.come\u201d) to reduce the content of salt in the daily food of Portuguese citizens, in particular the amount of salt in bakery. Traditionally, Portuguese citizens use excess salt in food, specially in bakery. This fact has been associated with high-prevalence of cerebrovascular diseases . InteresA schematic representation of the innovation clusters of Ageing@Coimbra is depicted in Figure Research on the mechanisms of aging-related diseases is a solid and established research area at the University of Coimbra and at the Center for Neuroscience and Cell Biology of Coimbra. Research in this area delivers high-impact and highly cited publications, international collaborations, advanced training of Ph.D., and postdoctoral students as well as entrepreneurship training and new spin off companies. Highlighting the priority of aging research, in 2016, a new ERA Chair group was appointed by the Faculty of Medicine of the University of Coimbra to develop a research program, advanced teaching and translational research in cardiovascular aging .16In 2015, three founder members of Ageing@Coimbra, the University of Coimbra, University of Coimbra Hospital and Pedro Nunes Institute, were accepted, as Associated Partners, in the new KIC in Active Living and Healthy Ageing from EIT Health. Together with the pharmaceutical company BIAL, they formed a cluster of Innostars, a legal entity member of EIT Health.EIT Health is a powerful consortium of more than 140 members from academia and industry partners that develop collaborative market-driven projects to tackle societal challenges: (1) promote healthy living; (2) support active aging; (3) improve health care. Projects deliver better training of students, executives, and citizens (Campus); transform innovative ideas into products and services (Innovation Projects); and create and catapult business creation (Accelerator).The University of Coimbra Hospital offers a well-established multidisciplinary geriatric assessment service. The knowledge gathered by the clinical team supported the creation of a new clinical service entirely dedicated to AHA, including daily clinical care, a hospital residence, outpatient consultations and community health-care services. The key pillars of the new unit enclose clinical care of geriatric patients, training of new health-care professionals and research on aging and geriatrics.The clinical unit on AHA establishes strong links with other hospital specialty services for prevalent and multimorbid conditions, including Neurodegenerative and Psychiatric Diseases, Pneumology and Respiratory Diseases, Immunology, Cardiovascular Diseases, Diabetes, Cancer, Musculoskeletal Diseases, among others.Geriatric Medicine profits from the institutional collaboration of the University of Coimbra Hospital and the Rehabilitation Hospital Rovisco Pais and other local Hospital units in the region. Dedicated patient-centered rehabilitation services profiting from holistic approaches and multidisciplinary care are key success factors to prevent and treat geriatric frailty, particularly ortogeriatric frailty. Long-term care and palliative care multidisciplinary services in the region offer support to patients and families affected by long-term functional dependence and end-of life care for older patients and their families, including a hospital palliative care team offering support across clinical services at the University of Coimbra Hospital and two inpatient palliative care units, at the Portuguese Cancer Institute\u2014Coimbra and Cantanhede Hospital . Reinforcing this strategic area, the Calouste Gulbenkian Foundation supports a \u201cProfessorship in Palliative Care\u201d at the Faculty of Medicine of the University of Coimbra to strengthen research and education in Palliative Care in the Centre Region.The training of formal caregivers (working in institutions for older people), or informal caregivers (providing non-remunerated care for older people) is extremely important, especially when taking into account the growing older population that depends on care for chronic and degenerative diseases.The University of Coimbra, together with Ageing@Coimbra, knowing the demand for specialized caregivers\u2019 training and the need to reach an audience with time limitations and geographically dispersed, concluded that a distance learning modality (e-learning course) was among the most appropriate responses. The Distance Learning Course, \u201cActive and Healthy Ageing,\u201d which is a method of active learning providing training in the basic care areas of older people, was created by a team of lecturers of the Faculty of Medicine.Health literacy in aging is also a priority topic in postgraduate training. The Faculty of Medicine offers a masters degree in geriatrics and gerontology, where medical doctors can learn and upgrade their knowledge in age and age-related chronic diseases. Geriatrics in Coimbra is supported by advanced teaching, clinical health care and professional training. Advanced teaching at the Faculty of Medicine of the University of Coimbra includes the Ph.D. program in health sciences, the Ph.D. program in aging and chronic diseases, the masters in geriatrics and undergraduate training in geriatrics under the scope of the masters course in medicine. Postgraduate training of health-care professionals also includes the annual course on Ageing and Geriatrics .Nursing School of Coimbra promotes the implementation of the comprehensive geriatric assessment at a national level. The activities include cultural adaptation and validation of tools for use in the field of geriatrics and participation in the development of national and international web platforms to support National and European strategy to intervene on older adults\u2019 frailty and to involve stakeholders in this process. The measurable impact of work of Nursing School of Coimbra is also observable in prevention of cognitive decline in advanced age by promoting the implementation of cognitive stimulation-based practice in different health-care contexts and by enabling multidisciplinary teams to implement autonomously this practice in different regions of Portugal. In addition, Nursing School of Coimbra is also training health professionals at a national level by enabling them to achieve critical reasoning, questioning of the ongoing practices and seeking and evaluating information to support Evidence-Based Practice. Nursing School of Coimbra is also offering postgraduate programs in Geriatric Health and Ageing, Health, and Citizenship.Ageing@Coimbra profits from the engagement of several institutional partners that promote the social inclusion and participation of seniors in meaningful social activities and long-life learning. These institutions include Third Age Universities, Citizenship Associations, Science Centers, Museums, among others. Together, these institutions mobilize thousands of older citizens and their families in a number of activities involving the society: including heart and cardiovascular diseases awareness; Diabetes; Brain Awareness Week; International Day of the Older Person; European Scientists Night; among others.In 2017, the Regional Authority of Centre Region, in a partnership with Ageing@Coimbra, launched a call to award good practices supporting AHA and age-friendly territories in the 100 Municipalities of the Region. This initiative contributes to (1) identify innovative good practices; (2) publicly recognize individual and institutional stakeholders; (3) disseminate knowledge to support adoption and scaling-up in other territories. The call awarded, in 2017, three categories: (1) Life+ (\u201cVida+\u201d), to support healthy life styles; (2) Health+ (\u201cSa\u00fade+\u201d), supporting innovative health care for older people; and (3) knowledge+ (Conhecimento+), to support research and technology applied to AHA.We received 128 valid applications from diverse thematic and geographic origins, including 74 applications for the category \u201cLife,\u201d 38 for \u201cHealth,\u201d and 16 applications for \u201cKnowledge,\u201d from a total of 118 institutions. These institutions included 34 municipalities, 12 social care providers, and several citizenship associations and universities, from a total of 49 municipalities Figure .\u201cLife\u201d projects include programs for physical activity, with or without assessment of health parameters, multidimensional evaluation , intergenerational dialog, therapy by arts, creation, and development of informatics platforms. The winner \u201cNovas Primaveras,\u201d submitted by the Arts and Music Association of Pousos village, describes a program focused on therapy for older people through arts. This good practice was launched in 2004 and involves (currently) 12,711 direct and 84 indirect users from 30 Institutions, engaging users in music, dancing, theater, poetry, and other artistic expressions.\u201cHealth\u201d projects enclosed areas related with new mobile health units to support home care, implementation of new methodologies of health care , prevention of frailty in older people, screening and diagnosis of disease, physical and cognitive stimulation and rehabilitation, monitoring of chronic diseases using ICT\u2019s, support of patients in hospital and care residence settings , health literacy, and health promotion. The winner good practice described specialized care for dementia patients submitted by the network of care providers \u201cUni\u00e3o das Miseric\u00f3rdias Portuguesas\u2014Unidade de Cuidados Continuados Bento XVI (F\u00e1tima)\u201d. This dementia care residence is a pilot unit established in 2013, including environmental, professional, therapeutics competences, recognized as a reference model for the care of patients with cognitive impairment and dementia. It includes 20 beds for mid-term care and rehabilitation (up to 90\u2009days) and 30 beds for long-term care and maintenance (up to 180\u2009days).\u201cKnowledge\u201d projects include: research and application of programs and new models; application of ICT solutions; collaborative models using telehealth and teleassistance; intergenerational approaches; infrastructures; equipment and access to knowledge; multimorbidity research and care; AHA and longevity, databases and population profiling. The winner was a project submitted by the Faculty of Medicine of the University of Coimbra and the Center for Neuroscience and Cell Biology: \u201cNoMicro Technologies.\u201d This project describes the development of a technology to support healing of chronic wounds and prevention of infection by pathogens. NoMicro Technologies is currently in a phase of preclinical proof of concept.In conclusion, the number and quality of the applications received in the call exceeded the best expectations of the organizing committee, reflecting the growing involvement and awareness of stakeholders of the Centre Region to support AHA of citizens.Standing on the big societal challenges created by the impact of population aging in individual\u2019s health, but also for efficiency and sustainability of the health and social care systems, the movement created by EIP on AHA addresses the individual\u2019s and societal hurdles, under a positive perspective of stimulating the economic growth and job creation.The collaborative work developed by EIP on AHA partners, under the scope of the six active action groups or under the scope of the quadruple helix-based Reference Sites, has delivered an impressive number of ground-transforming good practices, innovation schemes, and change management process, with big societal impact and economic potential.EIP on AHA Reference Sites like Ageing@Coimbra have shown to be instrumental bodies for helping the European Commission in the implementation of policies, including the \u201cBlueprint for Digital Transformation on Health and Care in an Ageing Society\u201dThe impact of Reference Sites in the European landscape is also revealed by the collaborative work under the twinning collaborative scheme, involving delivery of good practices by innovator regions/actor and adoption by twin Reference Sites. The example of the twinning project lead by MACVIA and adopted/replicated by Ageing@Coimbra, and many other Reference Sites is a good example of a successful twinning project with impact in the society (see text footnote 20).The challenges imposed to societies by population aging and demographic changes are of paramount complexity. Innovative formulas to deliver practices and services and organization models, like those embedded in EIP on AHA Reference Sites and Ageing@Coimbra, might prove to be key elements of the change management schemes needed to deliver quality of life to citizens and sustainability of health and care systems, starting from pilot twinning schemes to large scale-up replication across Europe and Globally.In conclusion, the innovative and successful example of Ageing@Coimbra as a Reference Site of EIP on AHA supports the adoption of bottom-up, inclusive, and holistic approaches to create regional networks and partnerships with the aim of supporting the creation and replication of good practices for Active and Healthy Ageing. This methodology has proven to be successful in Coimbra/Centro de Portugal and other regions of Portugal, as well as in other European countries. Other examples of innovative regions embracing this model may follow and reinforce the change management objectives pursued by the EIP on AHA and the European Commission. However, important hurdles related with poor commitment of partners, oversimplification of processes in lean management structures are also difficulties that need to be constantly monitored and overcome.Ageing@Coimbra is a growing consortium, consolidating its unique position as an aging network in the Centre Region of Portugal, with strong collaborations with other Reference Sites and international networks. Ageing@Coimbra will support the replication of good practices emerging from its stakeholder members and will twin with other European partners to foster the adoption of innovative practices and technologies for the benefit of Centre Region and European citizens.JM: concept design, writing the text, editing figures, and manuscript correction. AA: concept design, manuscript correction. AR: concept design, writing the text, editing figures, and manuscript correction. AM-P: writing the text and manuscript correction. AFC: concept design; writing the text; and manuscript correction. AT: concept design; writing the text; and manuscript correction. AT-B: editing figures and manuscript correction. AD: concept design and manuscript correction. AFA: manuscript correction. ALC: concept design; writing the text; and manuscript correction. CD: concept design; writing the text; editing figures; and manuscript correction. BG: writing the text and manuscript correction. CA: concept design; writing the text; and manuscript correction. IS: manuscript correction. JB: editing figures and manuscript correction. JA: concept design; writing the text; and manuscript correction. LS: concept design; writing the text; and manuscript correction. LA: concept design and manuscript correction. MI: writing the text; manuscript correction. RV: manuscript correction. VR: concept design and manuscript correction. MV: concept design; writing the text; editing figures; and manuscript correction.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD . However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD.We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn\u2019t experience onset of CVD) and Cox proportional regression analysis, with offspring\u2019s age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD.Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD and for paternal age of onset of CVD . A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders.Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of identification of high-risk patients in clinical settings. Cardiovascular disease (CVD), defined as coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, and heart failure, is the leading global cause of death, accounting for over 30 percent of all deaths worldwide\u2013 17.3 million deaths per year. In the United States, someone dies from cardiovascular diseases every 39 seconds , yet 72%Associations have long been established between CVD and a wide variety of risk factors, including non-modifiable variables such as age, sex, and family history, and modifiable atherosclerotic risk factors, such as cigarette smoking, alcohol intake, increased BMI, systolic blood pressure (SBP), diabetes mellitus, high-density lipoprotein (HDL) level, and hypercholesterolemia \u201310. HighDespite this evidence that recognizes that both parental history and genetic factors are modifiers of MI risk, neither element is routinely used in the clinical determination of CVD risk. Currently, few analyses delineate the association between parental history of CVD and manifestations of CVD other than MI . Furthermore, measuring parental history as a binary variable (\u201cyes\u201d or \u201cno\u201d) is an oversimplification that fails to recognize the effects of several variables within the parental history, including the relatives\u2019 age of onset of disease, patient\u2019s relation to relative, and quantity of relatives affected with cardiovascular disease, all of which have been shown to impact CVD risk \u201317.The Framingham Heart Study has published multivariate models for estimation of the 10-year absolute risk of developing CVD ,19, and While the effect of parental history of premature cardiac events and the effects of advanced age on CVD risk is well-studied ,27, no rn = 3261) and the FHSO Exam 1 . There was a total of 2622 linked parent-offspring pairs. The age of onset of CVD is the age at which either parent or offspring was diagnosed with CVD, including coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, and heart failure, by a medically trained professional. This \u2018time-to-event\u2019 data was collected based on follow up data of both the original and offspring cohorts. Baseline values of the covariates of interest, collected at first clinical visit, were used in data analysis. Participants were included if they had not yet developed overt symptoms of cardiovascular disease or suffered a heart attack or stroke, and subjects were excluded if they had missing data.The study was approved by University of Texas Health Science Center in Houston Institutional Review Board and Biologic Specimen and Data Repository Information (BioLINCC). For this study we used The Framingham Heart Study (FHS) database. The data comes from a well-known, longitudinal prospective cohort study that is a premier database for study of cardiovascular diseases and other terminal disease. The FHS Original Cohort was launched at Exam 1 in 1948 and has continued with biennial examinations to the present. The FHS Original Cohort consists of 5,209 respondents aged 28\u201362 years residing in Framingham, Massachusetts, between 1948 and 1951. Nearly all subjects were Caucasians. The Offspring Cohort (FHSO) was launched at Exam 1 in 1971 and has on average been examined every 3 to 4 years since enrollment. The FHSO dataset consists of a sample of 3514 biological descendants of the Original Cohort, 1576 of their spouses and 34 adopted offspring for a total sample of 5124 subjects . This analysis used values collected during the FHS Original Cohort Exam 12 was used for statistical analysis. The proportional hazard regression calibration approach employed in this paper for analyzing the time to event outcome and censored predictor is similar to the proportional hazards regression model for survival data with measurement error ,30. ThisUnlike binary thresholding approaches that have shown increased risk of CVD if a first-degree blood relative has had coronary heart disease or a stroke before the age of 55 years or 65 years , we can compute a hazard ratio for each unit increase or decrease of parent age of onset. The conditional imputation approach employed in this paper combined the non-modifiable risk factors, age of onset of CVD in mother or father and parental history, by defining parental onset of CVD as the instantaneous risk of cardiovascular event, given that the event has not previously occurred. This leads to a relatively stable estimate and avoids bias estimates as the thresholding approach shown by Rigobon & Stocker and AustThe age of onset of CVD is defined as the age at which either parent or offspring was diagnosed with CVD by a medically trained professional. The dependent variable, age of onset of CVD in offspring, is potentially right-censored. That is, offspring that truly had CVD but were not diagnosed with CVD by a medical professional during this study are considered censored. Similarly, for the primary predictor variable, age of onset of CVD in parents, those that truly had CVD but were not diagnosed with CVD are considered censored. In order to consider`censored parents in the Cox model for age of onset of CVD in offspring, we employed the conditional mean imputation technique ,38.Our primary variable of interest is parental age of onset of CVD, which is potentially right-censored. We controlled for the following confounders: offspring smoking status, offspring diabetes status, offspring BMI, offspring SBP, offspring HDL, and offspring LDL Tables and 4. TSeparate analyses were performed for each parent, and the data was separated into two groups. There were 2622 linked parent-offspring pairs in total, with 1401 mother-offspring pairs and 1221 father-offspring pairs. The median age of onset of CVD was 68 years and 64 years for mothers and fathers, respectively . The oveThe baseline characteristics for the separate analysis with the primary predictors, maternal age of onset of CVD and paternal age of onset of CVD, are shown in The Cox proportional hazard (Cox PH) models were used to analyze the relationship between offspring age of onset of CVD and parental age of onset of CVD. We presented a separate analysis for the association between offspring age of onset of CVD and maternal age of onset of CVD and offspring age of onset of CVD and paternal age of onset of CVD Tables and 4. TWe fit a Cox model for the association of age of onset of CVD in parents and offspring. The Schoenfeld residuals against age of onset CVD in offspring with a smooth line (cubic spline) are fit to the points . These sMaternal age of onset of CVD is statistically significantly related to age of onset of CVD in offspring with a hazard ratio of 0.959, while paternal age of onset has a hazard ratio of 0.973. Our analysis describes hazard ratios based on unit increase or decrease of maternal and paternal age of onset of cardiovascular events. Although several papers have evaluated the link between CVD in parents and CVD risk in offspring, they have categorized parental history of CVD as a dichotomous variable using a thresholding approach ,39 or inThis is the first study to link parental age of onset to offspring age of onset of CVD using continuous variables in survival data. Currently, multivariate models for estimation of the 10-year absolute risk of developing CVD, including the Framingham calculator and the European SCORE calculator, can underestimate subclinical atherosclerosis ,24. NeitSeveral studies have suggested that a maternal transmission of CVD is more important for the development of CVD than paternal transmission \u201344. SomeThe Framingham data comes from a well-known prospective cohort study. Advantages of using the Framingham Heart Study data include access to near-complete data on the development of selected cardiovascular diseases due to their careful longitudinal follow-up of subjects. The Framingham Study was the first large scale cohort study of its kind that compare one generation to the next using a wide variety of data parameters. However, practitioner error may lead to a CVD sensitivity and specificity of less than 100%. That is, some subjects with CVD may be diagnosed an indefinite period of time after time of actual CVD onset or not at all, introducing information bias into the study. As technologies for detection of CVD have improved dramatically, CVD can be detected more definitively at an earlier time in the disease course and subsequent cohorts (offspring) may have experienced different sensitivity and specificity of diagnosis. Furthermore, nearly all subjects enlisted in the study in 1948 were White. The homogeneity of the cohorts may limit generalizability to a more diverse population, and future studies should include subjects from a variety of ethnic backgrounds to improve the ability to apply findings to the general population.Lastly, the statistical interpretation of this study can be confusing; both independent and dependent variables are potentially right-censored so they may not have clean interpretations. However, based on the sign of the coefficient (negative) it can be determined that the increasing parental age of onset of CVD is protective of early CVD in offspring.rd and 4th generation of this cohort study. More comprehensive understanding of cardiovascular risk factors will allow practitioners to more accurately identify patients at high risk for CVD who would not otherwise be identified by traditional risk calculators.Further research on the role of family history of CVD, including age of onset, number of family members affected, and differential effect of sex of family members affected, and its implications for CVD risk should be explored. The Framingham data is an excellent body of data for use in analyses of this nature, and future research should focus on risk factor studies in the 3"} +{"text": "Scientific Reports5: Article number: 10198; 10.1038/srep10198 published online: 05142015; updated: 05312017.The Acknowledgements section in this Article is incomplete.\u201cWe would like to express our gratitude to all the participants of the study, management of both King Fahad Medical Research Center (KFMRC) and Arabian centers, and all the students who volunteered to help us in recruiting the subjects. We thank all the support staff of department of Pharmacology, King Abdulaziz University Hospital, Al-Salaam mall and Mall of Arabia. We are particularly grateful to both Iuliana Denetiu and Mohammed Ali Majrashi for their help in collection, input and validation of data. We express our appreciation towards Hussain Ahmad for his help towards database development. We acknowledge the Stratified Medicine Graduate Training Programme in Systems Medicine and Spectroscopic Profiling (STRATiGRAD) for funding of Torben Kimhofer. The authors declare that there are no conflicts of interest.\u201dshould read:\u201cThis project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under grant no. 2-141-35-HiCi. The authors, therefore, acknowledge with thanks DSR for technical and financial support. We would like to express our gratitude to all the participants of the study, management of both King Fahad Medical Research Center (KFMRC) and Arabian centers, and all the students who volunteered to help us in recruiting the subjects. We thank all the support staff of department of Pharmacology, King Abdulaziz University Hospital, Al-Salaam mall and Mall of Arabia. We are particularly grateful to both Iuliana Denetiu and Mohammed Ali Majrashi for their help in collection, input and validation of data. We express our appreciation towards Hussain Ahmad for his help towards database development. We acknowledge the Stratified Medicine Graduate Training Programme in Systems Medicine and Spectroscopic Profiling (STRATiGRAD) for funding of Torben Kimhofer. The authors declare that there are no conflicts of interest.\u201d"} +{"text": "Nowadays, most of the research in the field of gerontology is focused on the effects of the grape polyphenols. In particular, resveratrol has been shown to increase life expectancy of various living organisms, including mammals. Resveratrol also plays an important role in cancer prevention and decreases the risk of developing cardiovascular disease. In our research, we proposed the development of the therapeutic product from Cabernet Sauvignon grapes that would exhibit the beneficial properties of polyphenols. Standard operating procedures were developed in our laboratories to collect alcohol free concentrate of polyphenols from the Kazakhstan Cabernet Sauvignon collection of grapes. The purpose of the study was to investigate the composition, biological safety, and potential therapeutic effects of the polyphenol concentrate.The total polyphenol amount was determined using the Enology Analyzer Y15 . HPLC analysis of the polyphenol composition was performed using Agilent 1290 chromatograph. The polyphenol concentrate was analyzed for the microbiological purity and the presence of the toxic elements. The cytoprotective effect of the polyphenol concentrate was studied in experimental models of diabetes, toxic hepatitis, doxorubicin cardiomyopathy, and acute radiation sickness.The total polyphenol amount in one sample was 12,819 mg/l. Polyphenol composition analysis showed presence of the following polyphenols: catechin, epicatechin, gallic acid, quercetin, miricetin, 3-glucosylkaempferol, epicatechin gallate, 3--2-propenoic acid, catechin gallate, pitseid, kaempferol, n-hydroxy-cinnamic acid, resveratrol and chlorogenic acid. The concentrate was proven to be biologically safe and acceptable for use as a dietary supplement. The polyphenol concentrate demonstrated high antioxidant activity against ABTS and DPPH radicals in vitro. It also showed the following impacts on the various experimental models in vivo: reduction of sugar levels in diabetes; regeneration of the structure and function of the heart tissue in cardiomyopathy; regeneration of the nephron structure and function in nephropathy; regeneration of liver in toxic hepatitis; recovery of the antioxidant status in oxidative stress; and recovery of the hematopoiesis in acute radiation sickness.The polyphenol concentrate from Kazakhstan Cabernet Sauvignon collection of grapes was proved to be biologically safe and acceptable for use as a dietary supplement. The concentrate showed high antioxidant, antiradiation activity, and regenerative effect in diabetes, cardiomyopathy, nephropathy, and hepatitis in the corresponding organs."} +{"text": "A number of major, minor, and trace elements function as important nutrients in foodstuffs of crop and animal origin. These elements occur in a broad range of concentrations in an exceedingly vast array of foods available commercially and home-prepared. In disciplines such as regulatory compliance, product development, quality and safety, and research, reasonably reliable analytical information is mandatory for conclusions and decisions of impact. Although analytical scientists recognize the need for valid data, solid analytical information is at times elusive not only in the area of determination of chemical elements at low (trace) levels \u20135 but alOf the many analytical techniques available for determination of inorganic nutrient constituents in biological matrices, those based on atomic spectrometry (AAS) are convenient and widely applied. The thrust of current research is to define impacts of a number of parameters on the performance of flame AAS (FAAS)-based methods of analysis of soil and biological materials to lead to reference methods for the measurement of major, minor and trace levels of elements of nutritional and toxicological pertinence. Some of these parameters as well as the excellent performance possible with well-applied versions of FAAS procedures are discussed.In spite of wide acceptance of the technique and the proliferation of published articles on its application, very few AAS-based methods have reached official method or reference method status , Require3/HClO4 with further separate treatment of insoluble siliceous residues with HF for measurement of total concentrations of Na, K, Mg, Ca, Mn, Fe, Cu and Zn. Flame atomic absorption measurements were performed under optimized standard operating conditions. Measurement techniques were based on either bracketting of sample with appropriate standard solutions or second order calibration curves incorporating appropriate standard and procedural reagent blanks. Two types of working standard solutions were prepared with one set (regular standard) containing the eight analytes at concentrations required for analysis. The second set (matrix-matched) contained the analytes at approximate concentrations occurring in the plant materials being analyzed and, in addition, contained three other major constituents, Al, S and P present in the samples to match the analytes and matrices of the analytical samples, The scheme of analysis is depicted in Experiments were conducted with four plant Standard Reference Materials as test materials, SRM 1570 Spinach, SRM 1571 Orchard Leaves, SRM 1573 Tomato Leaves, and SRM 1572 Citrus Leaves, from the National Bureau of Standards with the last product uncertified at the time of the study. Samples were dissolved with HNODevelopment and application of a high reliability version of an analytical procedure requires familiarity with all factors having a possible bearing on the precision and systematic errors of the overall procedure. The effect of calibration expressed as differences in elemental concentrations measured using regular and matrix-matched standard solutions is a function of element and sample type. Differences in concentrations ranged from 0.2% to 10.2% depending on element and matrix, indicating that for measurements of the highest reliability, systematic error arising from calibration can be reduced by using reasonable close matrix-matched standard solutions , EffectsThat meticulous attention to detail can lead to a high precision and high accuracy procedure is demonstrated by information in"} +{"text": "Dear Editor-in-ChiefMyxoid tumors of the oral cavity encompass a broad spectrum of lesions, primarily neoplastic . SignifiThis classification is based on the predominance of the areas of myxoid degeneration in histopathology of the tumors of oral cavity. This classification includes adipose, neural, fibroblastic, chondroblastic, muscle, odontogenic and miscellaneous tumors. This classification wouldprovide a better insight into the histopathology of myxoid tumors of oral cavity and wouldbe useful for oral pathologists and cytopathologists."} +{"text": "The implementation in China is warranted, since the leading Chinese research institutes as well as the most important local stakeholders, e.g. water suppliers, are involved.The Taihu (Tai lake) region is one of the most economically prospering areas of China. Due to its location within this district of high anthropogenic activities, Taihu represents a drastic example of water pollution with nutrients , organic contaminants and heavy metals. High nutrient levels combined with very shallow water create large eutrophication problems, threatening the drinking water supply of the surrounding cities. Within the international research project SIGN (SinoGerman Water Supply Network, Water is essential for all forms of life. However, in many parts of the world, water quality is threatened by multiple pollution sources. In the last few decades, China has undergone rapid industrial and economic growth. Especially in densely populated areas, the need for clean water is constantly increasing . At the 2 ).Responsible: IGB Leibniz-Institute of Freshwater Ecology and Inland Fisheries, TZW Water Technology Center.Chinese partners: Chinese Research Academy of Environmental Sciences (CRAES), Nanjing Institute of Geography & Limnology, Chinese Academy of Sciences (NIGLAS), Tongji University.Biodegradation of organic pollutants and nitrogen-containing compounds as beneficial ecosystem services is investigated by using modern PCR-techniques , 20 as wOnset and duration of cyanobacteria blooms are controlled by the nutrient content as well Responsible: bbe Moldaenke GmbH, FZJ Forschungszentrum J\u00fclich GmbH, inge GmbH.Chinese partners: Suzhou Water Group Co. Ltd., Tongji University, Hua Yan Water Group.Algae are measured within the lake itself in order to monitor their growth under different environmental conditions. Online analyses at the inlet of the drinking water treatment reveal changes in raw water quality. Further measurements at the different steps of drinking water treatment allow the assessment of the removal efficiencies for the algae themselves, their toxins as well as algae-released drinking-water-relevant taste & odour (T and O) compounds/precursors. New measuring tools are developed in order to assess the integrity status of algae cells and thus the risk of toxin release.Due to the impaired raw water quality, efficient solutions for drinking water treatment of algae contaminated water are needed. Ultrafiltration membranes are employed to efficiently remove algal cells and/or algal compounds. This reduces the formation of disinfection by-products and/or T and O compounds/precursors in subsequent oxidation steps within the drinking water treatment plant. The membrane itself is improved regarding material and geometry. Additionally, the operating modes are optimized with respect to energy-efficiency and maximum performance, supported by the data obtained from an algae-online analyser.Precursors of T and O compounds are identified by in-depth analysis of raw water and water from different treatment steps. Formation of T and O compounds is investigated by mechanistic laboratory studies in order to optimize advanced oxidation processes. Improved elimination of drinking-water-relevant substances by technological process optimization using the above-mentioned ultrafiltration and advanced oxidation techniques is evaluated for practical application within drinking water treatment plants in China.Responsible: F.A.S.T. GmbH, TZW Water Technology Center.Chinese partners: Suzhou Water Group Co. Ltd., Tongji University, Hua Yan Water Group.Drinking water leaving the waterworks in Suzhou has good and stable quality. However, water discoloration and problems with T and O compounds reoccur during transport through the drinking water pipes. In order to remove deposits and thus increase drinking water quality at the consumer\u2019s tap, an innovative optimized flushing strategy is adapted and tested in a model region of the distribution network in Suzhou. Based on the deposit accumulation velocity, the needed flushing intervals are defined in order to allow deposit-free maintenance of the distribution network in the future.Tools for the automatic acoustic detection of leakages within the drinking water pipes are adapted and tested for a model region of the distribution network in Suzhou. The measuring data of the noise loggers are collected via wireless transmission, accessible via internet and evaluated with a specialized software tool. The gained knowledge about the occurring water losses helps the water suppliers to reduce the water losses from their water distribution networks to a minimum being obligatory for technical, hygienic as well as economic reasons.Responsible: UFZ Helmholtz-Zentrum f\u00fcr Umweltforschung GmbH.Chinese partners: Chinese Research Academy of Environmental Sciences (CRAES), Tongji University.Achieving a sustainable urban environmental water cycle is not only a technical challenge. Feasibility, adequacy and performance of technical concepts are highly dependent on the socio-economic and institutional settings. Thus, recommendations for sustainable water policy and administration that consider the particular framework conditions in China are deduced. Further initiatives for effective participatory processes and awareness-raising campaigns are suggested.Responsible: TZW Water Technology Center.www.water-sign.de, with publications and with presentations at local and international conferences.All results obtained are actively shared with the scientific community as well as with the concerned Chinese stakeholders e.g. via the website German best practice examples of pollution elimination and improvement of water resource quality are analysed in view of appropriateness for the Taihu region. Based on the existing Chinese standards and guidelines as well as on the raw water situation of Taihu, the most important parameters for drinking water quality are selected in order to facilitate future monitoring and control."} +{"text": "Non-mainstream scholarly journals are struggling to maintain a healthy flow of the best submissions, influence science growth locally and internationally, and become indexed in prestigious bibliographic databases. There are financial and non-financial factors confounding editing and publishing practices across low-resource countries. Publishers in these countries often face difficulties with involving experienced reviewers and editors in the processing of submissions to their journal. As a result, non-mainstream scholarly journals are at risk of publishing unchecked, poorly edited, erroneous, and unethical papers. They face challenges of inappropriate authorship, non-disclosure of conflicts of interests, plagiarism, and other forms of scientific misconduct. Journals\u2019 applications to global indexing abstract and citation databases are often declined due to the lack of transparent and ethical editorial strategies, inappropriate scope of interest, low level of evidence, and low citation rates. A hhandful of the indexed regional journals are aggressively targeted by unethical authors and brokering editing agencies, exploiting the deficiencies in the editorial strategies and thus further damaging the reputation of the journals. To curb the problems with editing and publishing, journal editors from non-mainstream science countries are encouraged to upgrade their strategies of ethical editing and research reporting in accordance with the updated recommendations of editorial associations, such as the International Committee of Medical Journal Editors (ICMJE), the Committee on Publication Ethics (COPE), and the Council of Science Editors (CSE). Academic institutions and professional societies from these countries are called to provide guidance for researchers and science editors and allocate resources for improving editing and publishing practices.Croatian Medical Journal and other MEDLINE-indexed journals. As the main problems with editing regional journals were highlighted, the decision was made to draft this Declaration. Journal editors from non-mainstream science countries are called to upgrade and enforce their instructions for authors in accordance with the listed points on integrity and visibility.How to address the problems with journal publishing in non-mainstream science countries was discussed at the First Mediterranean Seminar on Science Writing, Editing and Publishing, which was organized by the Academy of Medical Sciences of Bosnia and Herzegovina in Sarajevo, December 2-3, 2016. The idea of organizing such a meeting and drafting an instructive document for editors and publishers struggling with poor quality and visibility of their journals was proposed by numerous regional experts. They voiced their concerns and suggested to act jointly. The Seminar attracted more than 100 researchers, experienced journal editors, and publishers from Balkan and Mediterranean countries, who shared their experience with writing, reviewing, editing, and publishing. Updates to the recommendations of the most influential editorial associations, such as the ICMJE, COPE, and CSE, were presented to incorporate in the regional journal instructions. Participants had a unique opportunity to receive hands-on training on editing from the flagship regional journals, such as the The Sarajevo Declaration is aimed at upgrading standards of editing and publishing scholarly journals across Balkan and Mediterranean countries. Journal editors from regional and other non-mainstream science countries are encouraged to familiarize themselves with the statements and amend their instructions accordingly.The endorsement and enforcement of the Sarajevo Declaration may help avoid \u2018wasteful\u2019 or unethical publishing practices and improve visibility, scientific prestige, and indexability of the adherent scholarly publications.Transparency of in-house editorial procedures and external editing supportSupport of professional editorial teamsFocus on regional and local scientific research problems defined in the journal aims and scopePromotion of ethical research and reviewsScholarly publications are essential for research productivity, academic promotion, sharing professional information, and networking among scientists worldwide. Authors, reviewers, and editors are required to ensure the trustworthiness and ethical soundness of what they write, edit, and publish. To maintain the quality and ensure the impact of their publications, all stakeholders in science communication should make effort to ensure the integrity and promote innovative and evidence-based sources of information.1. Scholarly papers are final products of collective efforts of all stakeholders in science communication. It is increasingly important to promote these papers post-publication by indexing and archiving on relevant global digital platforms. Responsible editors and publishers alike are in the position to contribute to the post-publication communication. To improve visibility of their publications, authors can rely on reliable social media, sharing platforms, and individual and institutional repositories.2. Authors, reviewers, and editorial board members can increase visibility of their scholarly activities by registering with the Open Researcher and Contributor ID (ORCID) and providing information on their own authoring, reviewing, and publishing activities via their permanent accounts. Publishers of scholarly journals can maintain the integrity of pre- and post-publication communication by joining the ORCID global initiative.3. Erroneous publications are common, and take place because of the authors\u2019, editors\u2019, and publishers\u2019 oversights. Authors, reviewers, editors, and readers have the responsibility to notify publishers about any instances of known research misconduct and erroneous publications, necessitating corrections or retractions.4. Effective functioning of scholarly journals is dependent on skilled individuals involved in the processing of manuscripts. Publishers encountering problems with erroneous and poorly written publications should expand their editorial teams by inviting experienced editors responsible for statistics, publication ethics, language, and design.5. Continuing professional development (CPD) should be complemented by publications in scholarly journals that serve as platforms for distributing professional information of interest to both novice and seasoned authors. To achieve this goal, publishers may create journal sections for students, researchers, and specialists seeking CPD credits. Efforts should be made by publishers to acknowledge their contributors and obtain CPD credits for publishing and reviewing activities.6. Professional societies can take the lead and contribute to the promotion of scholarly journals by taking responsibility for healthy flow of journal submissions from their memberships, quality checks, and publishing established and start-up periodicals and awarding the contributors with academic credits.7. Science editors should adhere to the most recent recommendations of global editorial associations and incorporate relevant sections in their journal\u2019s instructions to improve the quality of pre- and post-publication communication.8. Websites and editorial management platforms of scholarly journals should contain transparent information on the editorial management, peer review, open access or subscription models, and acceptable editing practices. Commercial editing services, which are offered by publishers and other organizations, may help improve the quality of journal submissions. However, all these services require transparency and acknowledgment in accordance with the recommendations of global editorial associations.9. Traditional and alternative impact indicators are instrumental for assessing the scholarly journals in terms of distributing information, attracting readership, and facilitating science growth. Combined quantitative and qualitative approach to citations, downloads, and distributions of individual papers through social networking channels can reveal interest of readers toward certain topics and types of publication, but not necessarily the quality of scholarly journals. Editors and publishers can increase the impact of their journals by improving the functionality of their journal websites and online content, ensuring the completeness of meta-data in the published papers.10."} +{"text": "They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP), four subtypes of the PGE receptor , the PGF receptor (FP), PGI receptor (IP), and TXA receptor (TP). Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.Prostanoids, consisting of the prostaglandins (PGs) and the thromboxanes (TXs), are a group of lipid mediators formed in response to various stimuli. They include PGD"} +{"text": "This study aimed to investigate the effectiveness of cognitive-behavioral therapy on relieving migraine headaches in migraine sufferers.In this quasi-experimental study with pre-test and post-test method, the samples were outpatients of public hospitals in Ilam City, southwestern Iran since May-Jul 2010. They were selected based on inclusion and exclusion criteria, and divided into experimental and control groups. The data were analyzed using SPSS ver. 16 and via multivariate covariance method.P<0.05). Cognitive-behavioral therapy affected on reducing the duration of symptoms of migraine in sufferers (Cognitive behavioral therapy effects on reducing the time duration of symptoms of migraine headaches. Thistherapeutic method increases the level of individual, familial, social and occupational activities by reducing the time duration of symptoms and this method helps the individuals to resume their activities and regain their previous control instead of founding themselves incapable and helpless due to the pain they suffer from. Prevalence of migraine is different in various cultures, but it affects approximately 12% of general population and it is more effective on women. In various populations, the prevalence of migraine is about 6% in men and 18%of women aged between 15-45 yr old. Lifetime prevalence of migraine, is 8%-13% in women and 25%-33% in men in IlamCity, southwestern Iran were examined since 2010. Out of 635 patients who were willing to cooperate, 30 migraine sufferers were selected regarding several factors: no pregnancy, lack of heart disease, minimum literacy and older than 15 yr old. These participants were divided into two experimental and control groups. The participants of experimental group received both drug and cognitive-behavioral therapy, and the participants of control group only received drug. The pre-test was conducted for both groups. The number of migraine attacks, duration of attacks, severity and the number of taking pain relief pills were controlled by phone within 4 wk. Eleven cognitive-behavioral therapy sessions were held for experimental group.The study was approved by Ethics Committee of the university and informed consent was taken the patients.The key issues trained in form of therapy sessions by the researcher included: Cognitive Restructuring (learning how to recognize the cognitive errors and replacing the positive and efficient thinking with negative and inefficient thinking), training the relaxation methods , doing tasks and activities progressively regarding the time duration based on the resting/activity periods (without doing excessive activities ), assigning the home works in order to reduce the activities and resuming an active and effective life style.Two participants of control group and one participant of experimental group discontinued the research processes. After the implementation of the independent variable, headache indicators were measured within 8 wk. The results were analyzed using SPSS software and multivariate analysis of covariance.Various descriptive indicators such as mean, standard deviation, and the Kolmogorov-Smirnov normality test results showed that the distribution of various scores tends to a normal distribution To examine the effectiveness of cognitive-behavioral therapy on reducing the number of attacks, severity and duration of migraine headaches and the degree of taking drugs in migraine sufferers, Wilkes Lambda test was used, but at first, the precondition for the equality of variances using Lyon test was investigated in P<0.05). According to Eta squared (0.401), the difference wasin moderate. Totally, Eta squared value (0.401) showed that there was an approximately strong relationship between cognitive-behavioral therapy and reducing the symptoms of migraine headaches and F value (3.013) and degree of freedom of 18 & 4, there weresignificant difference between the mean of post-test scores in 4 variables in both control and experimental groups (eadaches .P<0.05). In respect of duration of headache symptoms, Eta squared value (0.174) showed an approximate weak relationship between cognitive-behavioral therapy and the duration of migraine headache symptoms showed that there wasno significant difference between the mean of post-test scores of control and experimental groups. However, there wasa significant difference between the mean of post-test scores of duration of headache symptoms in control and experimental groups (symptoms . In respect of the results of this research, cognitive-behavioral therapy effects on reducing the duration of headache symptoms in migraine sufferers. The results of this study are in consistent with another study. AnotherTherefore, long duration of migraine attacks have detrimental effects on the quality of individual and family life and career of the migraine sufferers as well.It affects on the ability and competence of people to perform social tasks because migraine sufferers have to rest somewhere dark and quiet to relieve headache pain . MoreoveThere were some limitations in this study such as refusing the patients to get involved in different stages of screening and researcher\u2019s follow-up, age control, gender, and education level of patients and making limitations for generalizing the results and not increasing the number of samples due to the high cost of visiting neurologists. In Conclusion, all centers for counseling and psychotherapy, welfare, medical science, physicians, psychologists, consultants, psychotherapists, and neurologists should access to the results of the present study in order to provide better services, and reduce side effects in patients with migraine and tension headaches, and also prepare a therapist and patient handbook and deliver to the rated centers."} +{"text": "It is with my deepest sorrow that I announce the untimely death of the passing of Dr Dimitri Tassiopoulos.Dr Dimitri Tassiopoulos was a Chief Research Manager with Social Aspects of HIV/AIDS Research Alliance (SAHARA) within the HIV/AIDS, STIs and TB (HAST) research programme of the HSRC. He held a BA (Hons.) degree in Political Science from the University of Stellenbosch, and obtained an MBA and PhD in Management and Administration from the University of Stellenbosch Business School in South Africa.Before joining the HSRC in May 2011, he was an Associate Director at the School of Tourism and Hospitality at the Walter Sisulu University (WSU) in East London, South Africa. He spent the majority of his academic career as a head of a School or as a Departmental Chairperson. After 1993, he was involved in various national and international tourism research projects, of a multidisciplinary and multi-institutional nature, concerning agritourism, event, cultural and wine tourism, amongst others. In 2004 he was appointed as a member of the South African Qualifications Authority\u2019s Standards Generating Body (SGB) for Travel, Tourism and Events, and was appointed as its chairperson. He was the vice president of the Tourism and Hospitality Education Providers of South Africa (THEPSA). This Federation represents further (FET) and higher education (HET) institutions offering the spectrum of qualifications related with the management of the tourism industry. He was also the chairperson of the Tourism and Events Educators Chamber of South Africa (TEECSA), an association representing higher education travel, tourism and events related programme providers.Dr Tassiopoulos successfully supervised post-graduate mini-theses/theses/dissertations and served as an external examiner for post-graduate theses at various universities in South Africa. Dr Tassiopoulos was a board member of a number international peer-reviewed research journals. The evidence of Dr Tassiopoulos\u2019s work is reflected in his publication record that spans the authoring and co-authoring of more than 16 presentations, at local, regional and international conferences, and, nine scientific publications in peer-reviewed journals. He was awarded six grants for research, published six books, published 33 chapters in books, has been involved in seven commissioned research projects. He has been rated a C3 researcher by the National Research Foundation. He served as a book reviewer for a number of publishers and as a proposal reviewer for the National Research Foundation.Tourism Today: published annually by the College of Tourism and Hotel Management, Nicosia, Cyprus (ISSN 1450-0906) (http://www.cothm.ac.cy/research.htm), and European Journal of Tourism Research: an academic refereed journal published bi-annually by International University College, Bulgaria (ISSN: 1994-76580) (http://ejtr.vumk.eu/). He was a regular reviewer of articles submitted to the prestigious Tourism Management Journal for publication.Dr Tassiopoulos was involved as an International Reviewer for the European Council on Hotel, Restaurant and Institutional Education (EuroCHRIE), Dubai 2008 Conference. He was involved as a session chair for the 2008 International Council for Small Business (ICSB) Conference, Halifax, NS, Canada; and, the 7th International Conference for Consumer Behaviour and Retailing Research (CIRCLE), Estoril Higher Institute for Tourism and Hotel Studies (ESHTE), Estoril, Portugal. He served on the following journal editorial boards as a board member of a number international peer-reviewed research journals. In particular, SAHARA-J: Journal of Social Aspects of HIV/AIDS (SAHARAJ). He successfully, while working closely together with Prof. Phaswana-Mafuya, managed to bring the journal under the Taylor & Francis Online stable with Routledge Press. SAHARAJ\u2019s impact factor has risen during his leadership. Dr Tassiopoulos also managed the SAHARA Conference.Among some of his achievements since joining HSRC Dr Tassiopoulos served as Managing Editor of Dr Tassiopoulos was involved in collaborating in cross-disciplinary research projects. He was involved in researching the effects of HIV and AIDS within higher education and the management of this syndrome that is afflicting the higher education population. More recently, he was involved in co-editing and publishing a book entitled non-communicable diseases in developing countries. Most recently, he led both international and South African research in the field of HIV and the World of Work Initiatives.Dr Dimitri Tassiopoulos made a significant contribution to South Africa\u2019s social science capital and his bright mind, dedication and passion will be missed. I take this opportunity again to convey my condolences to all of you who have known and worked with Dr Dimitri Tassiopoulos."} +{"text": "Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease. In Japan, the legal definition of a RD is one that affects fewer than 50\u2009000 patients in Japan, or ~1 in 2500 people.3 However, while individually these diseases may be considered rare, collectively they are not. It is estimated that 8% of people have one of the 6000\u20138000 RDs, and ~36 million Europeans are affected by one or will be. Eighty per cent of RDs are genetic in origin and often result from a dysfunction of a particular pathway (such as a defective gene or protein). Thus, understanding the impact of a single defect can yield insights into more complex pathways and, as result, RDs can serve as models for more common conditions, in particular in the context of precision medicine.A rare disease (RD) is defined as such by the fact that it affects a small percentage of the population. However, there is no internationally recognized definition of a RD. In the European Union (EU), a disease is defined as rare when it is life-threatening or chronically debilitating and when no more than 1 in 2000 people has it.4 setting out an overall Community strategy to support Member States in diagnosing, treating and caring for EU citizens with RDs. Three main areas were identified: improving recognition and visibility of RDs, supporting national plans for RDs in the EU Member States, and strengthening co-operation and co-ordination for RDs research at the European level. Indeed, RDs are a challenge too big for any one country or world region to tackle alone due to their low prevalence. Research on RDs is not only limited, but also scattered across laboratories and clinics throughout the world. This scarcity of expertize and practice translates into delayed diagnosis, few medicinal products and difficult access to care. That is why the field of RD research is a prime example of a research area that substantially benefits from co-ordination on a European and international scale, as co-operation can bring forth the development of new diagnostics and treatments. By increasing the number of patients available for each study and bringing together the scattered specialists with complementary expertize, the development of new diagnostics and treatments can be notably accelerated. This paper focuses on the efforts in the RDs field in Europe with some additional insights into international activities through the perspective of the International Rare Diseases Research Consortium (IRDiRC).In 2008, the European Commission (EC) adopted a communication5 The EU continues to offer funding opportunities for RD pre-clinical and clinical research and to strengthen international collaboration, in particular, in view of supporting the development of new therapies for RD and the diagnostic characterization of RD thus to develop better and faster means of high quality and clinical utility for the correct diagnosis of undiagnosed RD.The EU has been funding cross-border research on RD for more than two decades through its Framework Programmes for Research and Technological Development (FP) with complementary projects and actions. Since 1998, more than \u20ac1 billion has been invested in over 270 projects on RD , bringin6 European Reference Networks (ERNs) are virtual networks bringing together medical specialists across Europe to tackle rare or complex diseases and conditions that require highly specialized healthcare and a concentration of knowledge and resources. For the first time, a formal structure of voluntary collaboration between healthcare providers across the EU has been created for the direct benefit of the patient. The first 24 thematic networks include over 900 highly specialized healthcare units located in more than 300 hospitals of 25 EU countries plus Norway, and cover a wide range of disease groups including bone disorders, hematological diseases, pediatric cancers and immunodeficiencies; these ERNs will become operational over the course of 2017.7Set-up under the 2011 Directive on Patient Rights in Cross-Border Healthcare,Healthcare providers who are members of ERNs will be connected through a dedicated IT platform and, using a variety of telemedicine tools, offer access to expertize and knowledge of multidisciplinary teams, enabling patients suffering from such conditions to receive the best advice for treatment and diagnosis. A fundamental principle of the ERNs is the stipulation that knowledge should travel rather than patients (with the exception of few cases where patients may be referred for treatment in another country).Research will be a key element of the ERNs providing a structured framework for joining research efforts across countries, thereby creating a knowledge hub, facilitating translational research and the development of good practice guidelines for diagnosis and care, and supporting cross-border registries. By gathering and analyzing a large pool of patient cases, ERNs should contribute to observational studies and clinical trials, leading to new insights into RD and new drug therapies with potentially far-reaching benefits for patients.n=468), in FP7 (n=704) and\u2014until January 2017 (n=322)\u2014in Horizon 2020. The EC, together with European Member States, have been working on ways to support international collaboration in RD research. Statistics of Framework Programme 6 (FP6), Framework Programme 7 (FP7) and Horizon 2020 provide insight into how various aspects of the international collaboration were supported by EU-level public funding. First, the diversity of types of organizations supported by the EU throughout the Framework Programmes: Second, a landscape of the countries that were most frequently participating in FP7 and active in RD research emphasizes how important it is to promote international collaboration . ThroughIn Finally, funded projects foster a variety of medical domains and therapeutic areas. Within FP6, the 59 projects addressing RD covered essentially the following research themes: cardiovascular diseases, diabetes, diagnostics, diseases of the nervous system and cancer. Within FP7, 118 projects addressed neurodegenerative and neuromuscular disorders, pediatric and adult cancers, immunological disorders and immune deficiencies, respiratory disorders and metabolic disorders. In Horizon 2020, the therapeutic areas cover certain infectious diseases in addition to the ones covered in FP7.n=7), number of new patent applications (n=43) and number of publications (n=1989). Of interest, a vast majority of finished projects (76%) prepared peer-reviewed publications, with many publications in high quality journals such as Nature, Nature Genetics, Nature Immunology, Nature Medicine, Cell, New England Journal of Medicine, EMBO Molecular Medicine and Journal of the American Medical Association.The impact of EU funding and how international collaboration has been fruitful is highlighted by the preliminary outcomes of FP7 based on the first 66 projects completed: there are clear benefits in terms of number of spin-off companies included 15 countries and annual calls for proposals. During this time, the focus was on deepening the co-operation and co-ordination among the E-Rare partners by enabling the systematic exchange of information on national programs and by implementing strategic activities aimed at sustainable development and extension of the network of RD research funders.8 Through its easy-to-access transnational calls, E-Rare has provided a successful platform for entities interested in collaborative transnational research funding. The participation of national funding agencies in E-Rare Joint Transnational Calls (JTCs) is an effective tool to increase interoperability of funding practices and programs. Continuous co-operation of funding organizations, particularly for the implementation of JTCs, influences the alignment of processes, funding procedures and timelines of JTCs in addition to the gained common knowledge. The high number of proposals received in response to the JTCs of E-Rare highlights the great potential and diversity of the European RD research community and the need for funding of collaborative projects. Special consideration is given to avoid duplication with Horizon 2020 calls in the area of RD.Currently, E-Rare-3 is composed of 26 public bodies, ministries and research funding organizations from 18 countries: Member States , three Associated Countries and two Third Countries (Canada and Japan).In addition to the annual transnational calls, the collaborative approaches now extend to the relevant European Research Infrastructures with the aim to customize their services to the demand of RD researchers. The long-established collaboration with EURORDIS-Rare Diseases Europe has been further strengthened by the development of new funding models and the involvement of patient organizations in research. In 2012, E-Rare also became a member of the International Rare Diseases Research Consortium (IRDiRC) and strongly contributes to its ambitious objectives (see below).Since 2006, E-Rare has launched eight JTCs for projects, investing over \u20ac92 million in research on RD. Exceptionally, in 2015, the EC contributed to funding of research projects. The competitive nature of the JTCs has resulted in the funding of high quality projects. A large proportion of submitting researchers have outstanding track records with publications in high impact journals. 498 scientific teams compose 106 funded consortia. The multinational projects involve a range of three (mandatory) to ten research groups. Interestingly, the collaborations follow geographical, historical and linguistic proximity . In ordeThe transnational collaboration within projects is reflected at different levels. One of the most important aspects is the training and exchange of personnel. The analysis of 37 projects completed since 2007 showed that, in total, 83 MSc students and 108 PhD were trained. In addition, at least half of the projects reported an exchange of students, PhD and post-docs, in either short- or long-stays . A surveThe topics of E-Rare calls are broad and cover the whole range of medical domains. In all calls, the projects have to involve a group of RDs or a single RD following the European definition, that is, a disease affecting not more than five in 10\u2009000 persons in the European Community, EU-associated states and Canada. In all calls (except for the JTC 2016), interventional clinical trials were excluded due to budget limitations of national funding agencies. Furthermore, research concerning rare infectious diseases, rare cancers and rare adverse drug events in treatments of common diseases were also excluded in the past joint calls. When necessary, and based on the consultation of RD research community, the so-called \u2018focused\u2019 calls are implemented. As a result, in 2012, E-Rare launched a call dedicated specifically to young investigators. In 2014, the call focused on new therapeutic approaches and, in 2016, the goal was to finance clinical trials using repurposed molecules to treat RD.All medical domains are represented in projects submitted and financed . The bigOne of the most important goals of E-Rare funding schemes is to allow transnational collaborations that foster pooling of scarce resources, access to patients and knowledge. The ex-post analysis of 37 projects financed between 2007 and 2011 showed that all of them were able to achieve critical mass of resources necessary to complete their goals. In addition, 26 of the consortia demonstrated intensive exchange of samples as well as creation of databases (17 projects), biobanks (14 projects) or registries and Patient Organizations (POs) are part of this strategy.9 These infrastructures refer to major equipment, resources or e-infrastructures . This consolidation of knowledge and resources lying in different countries would enable the progression of high-caliber science and technology and facilitate knowledge sharing and innovation.The European Strategy Forum on Research Infrastructures was established and mandated by the EU Council in 2002 with the aim of supporting a strategic approach to the development of pan-European RIs to meet the long-term needs of the research communities across all scientific areas.10 Out of them, 11 are particularly relevant for biological and medical sciences and seven were chosen by E-Rare as most pertinent for RD research: (i) Biobanking and BioMolecular Resources Research Infrastructure (BBMRI), (ii) European Advanced Translational Research Infrastructure in Medicine, (iii) European Clinical Research Infrastructure Network (ECRIN), (iv) Distributed Infrastructure for Life-science Information (ELIXIR), (v) European Infrastructure of Open Screening Platforms for Chemical Biology (EU-OPENSCREEN), (vi) Integrated Structural Biology Infrastructure (INSTRUCT) and (vii) European Research Infrastructure for the Generation, Phenotyping, Archiving and Distribution of Mouse Disease Models (INFRAFRONTIER).At present, 14 European RIs dedicated to health & food domains are operational.The analysis of collaborative research projects submitted and financed by E-Rare revealed that 98% of them use services/infrastructures like biobanks, data repositories, imaging, high throughput sequencing or screening and animal model facilities. This was also confirmed by the outcomes of funded projects where creation or use of existing data and registries together with extensive exchange of samples and animal models were reported regularly. However, only a few projects indicated use of the European RIs, putting in question the origin of applied standards as well as sustainability of generated results. Based on these inputs and corresponding feedback from the E-Rare funding bodies, it was agreed that close collaboration with the European RIs should both mitigate the problem of discrepancies in practiced standards, and ensure the dissemination and sustainability of outcomes especially biobanks, registries, databases or models.http://erare.eu/infrastructures). Moreover, since 2015, E-Rare encourages the use of European RIs within its calls for transnational projects. In 2016, an explicit pilot action was implemented in collaboration with ECRIN where applicants using ECRIN services could benefit from so-called \u2018ECRIN on board\u2019: free-of-charge assistance in the preparation of their proposal to the E-Rare call. Among 30 projects submitted, 11 included collaboration with ECRIN, eight passed the pre-selection stage and four of them were eventually granted (out of eight recommended for funding) ensuring 36.4% success rate (in comparison with 22% success rate of projects not using ECRIN). In this specific case, the added value of using the European Research Infrastructure reflected, as expected, the quality and knowledge of the management of transnational clinical trials that is particularly complex. Thus, the alliance of dedicated institutions from different countries gathered into one infrastructure can directly target the issues and bring added value to the transnational consortium of researchers.In order to facilitate the access of RD research community to those initiatives, a comprehensive list and dedicated thematic pages were created on the E-Rare website expressed their interest in participating actively in E-Rare and a strong willingness to collaborate with researchers, including providing logistical and financial support. Since some of the E-Rare funding organizations already had experience co-funding research with POs, it was agreed that, with the support of EURORDIS-Rare Diseases Europe, a new model of collaboration between funders and POs would be established. The goal was to engage patients, in a transparent manner, at all levels of research funding: from definition of topics, through evaluation of projects, to budgetary investment . In addi15 It is co-financed by Member States and the EU. It comprises 40 countries in which Orphanet experts collect, annotate and classify (according to the Orphanet nomenclature) information on RD. This includes data on expert centers, patient organizations, diagnostic laboratories, research projects, clinical trials, registries, databases and infrastructures for research.Orphanet is the most comprehensive source of information, in terms of geographical and domain coverage, specific for RD worldwide.The classification of research projects is performed according to their main objectives, and those qualifiers can be grouped in the following categories: basic research, pre-clinical research and observational/epidemiological/natural history studies. In addition, information on the origin of the projects , related source of funding (funding bodies), as well as starting and end dates are collected.Data on 3052 research projects started or ongoing from 2010 on was collected. Importantly, 14% of them are international collaborations funded mainly funded by the EU and/or through the E-Rare mechanism. This confirms that, at present, EU and E-Rare schemes ensure major support of RD transnational research projects in Europe although 86% of RDs research funding remains national. Interestingly, the comparison of national and international projects revealed that the latter focus on pre-clinical research while national projects cover mostly basic research approaches (67%).Gene therapy development represents a substantial part (22\u201324%) of pre-clinical research studies, and this proportion does not differ between national and transnational studies. The three main medical domains in which these projects focus on are neurology, immunology and metabolic diseases. Transnational pre-clinical gene therapy projects are devoted to rare immune diseases (24%) followed by neurological diseases (20%) and inborn errors of metabolism (12%), whereas rare neurological diseases predominate in national gene therapy projects (36%) followed by metabolic diseases (16%) and immune diseases (7%).17) involving 42 participants from 14 countries. Its role was to foster interaction between all stakeholders\u2014regulators, pre-clinical and clinical investigators, scientists, companies and patient representatives\u2014in order to streamline integration of multidisciplinary expertize and generate new knowledge; to establish the quality, safety, efficacy and ethically acceptable standards for clinical gene transfer products; and to identify and accelerate the \u2018critical path\u2019 from pre-clinical to clinical phase. One particular feature of this network, organized into seven technology platforms, was the possibility to fund its own internal collaborative and exchange program that could target specific bottlenecks such as establishment of improved producer cells, development of validated production and purification protocols for viral and non-viral vectors, address the ethical, legal and regulatory component and facilitation of clinical trials for rare or common diseases . The main results of CliniGene were: integration of EU-wide research and facilities in the field of gene therapy; overcoming of most scientific bottlenecks identified and targeted by the seven technology platforms; publication of more than 745 papers; financial support to over 90 projects targeting novelty and international collaborations between 45 laboratories and companies; creation of new improved producer cells; development of highly efficient production and purification for most important viral and non-viral vectors; implementation of a reliable and validated vector biosafety platform addressing safety and efficiency in vitro and in vivo; contribution to the ethical, legal and regulatory components of these new therapies to the European Medicines Agency and facilitation of clinical trials performance; training as well as technology transfer to industry.The EU had supported during FP6 a \u20ac12 million European network of excellence for the advancement of clinical gene transfer and therapy (CliniGene18 (10 partners from five countries) aims to restore dystrophin production in a subset of Duchenne muscular dystrophy boys by administration of a drug, which \u2018skips\u2019 the mutations causing Duchenne muscular dystrophy. The presence of the US-based Sarepta Therapeutics in the consortium led to the expansion of the initial clinical trial and provided expertize in bringing an oligonucleotide to the market.19 The project is a follow-up to previous EU projects on neuromuscular dystrophies. In addition, the partners also co-ordinate the worldwide endeavors of several laboratories developing standardized methods of dystrophin quantification, which could be used as an outcome measure in clinical trials involving Duchenne muscular dystrophy patients.During the FP7, several clinical trials for RD were supported by the European funds. As example, the Skip-NMD project20 (12 partners from six EU countries) deals with multi-center lentiviral-based gene therapy trials for severe combined immunodeficiency diseases: adenosine deaminase severe combined immunodeficiency, Artemis and SCID-X1, and also derives from previous successful collaborative EU grants. Importantly, for adenosine deaminase severe combined immunodeficiency, the planned clinical trial should lead to marketing authorization of the gene therapy product as a licensed medicine.Amongst the ongoing Horizon 2020 projects, the SCIDNET consortiumhttp://www.erare.eu/all-funded-projects).. In the project CAV-4-MPS, intracranial administration of helper dependent canine adenovirus type 2 vector coding for the missing enzyme in mucopolysaccharidosis VII resulted in short and long-term expression of the therapeutic enzyme in an mucopolysaccharidosis VII mouse and an MPSVII dog model, resulting in global biochemical correction in the brain. In the project Theralymph, several therapeutic approaches for treatment of hereditary lymphedema are investigated: pharmacological and tissue engineering next to gene therapeutic approaches.The IRDiRC was created in 2011 to facilitate co-operation and collaboration on a global scale among the many stakeholders active in RD research, to maximize the output of RD research efforts around the world.21 As such, membership of IRDiRC was expanded to include those constituents.IRDiRC was originally conceived in 2009 by the Directorate General of Research and Innovation for the EC and the Director of the US National Institutes of Health (NIH), who envisioned speeding progress in RD research by coordinating their RD research funding. Over the course of the first preparatory workshop in Reykjav\u00edk, Iceland in 2010, it became clear that the success of the initiative would be dependent on the integration of the activities of not just funding agencies, but also academic researchers, companies, regulatory agencies and patient advocacy organizations.IRDiRC aims to facilitate the achievement of two overarching objectives by the year 2020: to contribute to the development of 200 new therapies and the means to diagnose most RDs. The crucial outcome of this work will be improved health through better diagnostic capabilities and novel therapies for people living with RDs throughout the world.Organizationally, IRDiRC is comprised of a Consortium Assembly, an Operating Committee, three Constituent Committees , three Scientific Committees , Task Forces and the Scientific Secretariat . Represe22IRDiRC focuses on strengthening international co-operation to bring about rapid progress in the field of RD research. Co-ordination of efforts that address common roadblocks is key to maximizing the collective impact of global investments in RD research and accelerating progress. To guide its work, IRDiRC developed a set of Policies and Guidelines, which are the principles that IRDiRC members agree to follow, focused on the following areas: data sharing and standards, ontologies, diagnostics, biomarkers, patient registries, biobanks, natural history, therapeutics, models, publication and intellectual property, and communications about the Consortium.23 The International Consortium of Human Phenotype Task Force developed standards for interoperability among databases which has enabled the linkage of a variety of RD phenotype and genotype databases. The Patient\u2014Centered Outcome Measures Task Force and Small Population Clinical Trials Task Force investigated aspects of RD clinical studies and produced recommendations to, respectively, (1) enable the development of clear outcome measures that benefit patients,24 and (2) advance discussions on optimizing efficient and innovative trial designs relevant to small populations.25 Similarly, the Data Mining and Repurposing Task Force made recommendations on strategies for optimizing the capture, sharing and integration of research and patient data to further research and development investments and realize the full potential of data mining and drug repurposing approaches (draft in review). Another joint IRDiRC-GA4GH effort was the Automatable Discovery and Access (ADA) Task Force that developed an ADA matrix which provides a standardized way to represent consent and other conditions of clinical data use, making the information computer-readable and available for automated search and sharing activities .26 The Privacy-Preserving Record Linkage Task Force, also a joint effort with GA4GH, is developing guidelines on the ethical, legal and technical requirements of participant identifiers in RD research. In addition, they are investigating a technical solution for a system to de-duplicate and link data sets for use by researchers without knowledge of participants\u2019 identity, and to enable the potential re-identification of participants for clinical purposes. Among the additional Task Forces due to commence shortly are those addressing approaches for investigating diagnostic cases unsolved via current technologies, addressing bottlenecks in data sharing including making policy recommendations around clinical data sharing, and developing best practices for patient engagement in RD research.The members of IRDiRC support research projects that contribute to the Consortium objectives and goals. A number of Task Forces have been created by the Scientific and Constituent Committees to identify limitations to efficiency and effectiveness in global RD research, suggest and/or create solutions including standards and tools, and publish recommendations. One of the earliest Task Forces initiated was a collaboration with the Global Alliance for Genomics and Health (GA4GH) and others to create Matchmaker Exchange, which enables RD gene discovery through a federated network of genotype and rare phenotype databases.27 To receive this designation, resources must undergo a peer-review process by IRDiRC Scientific Committee members and external experts in the field. To date, the label has been given to 13 resources: three guidelines, four platforms, two reference databases, two standards, and an advisory committee highlight to funders the most pressing areas that necessitate support and (2) emphasize the importance of issues like data sharing and harmonization to researchers. The involvement of patients as main actors and crucial stakeholders completes this picture.All these efforts led to the creation of a favorable ecosystem promoting the development of both new and more sustainable collaborations, connecting researchers from internationally dispersed laboratories. The outcomes of these collaborations are tangible: faster diagnosis of RD patients through enhanced discovery of causative genes and production of relevant clinical practice guidelines; better understanding of natural history of diseases through creation of common registries and databases; accelerated creation of animal and cellular models laying the basis for research on disease mechanisms and treatment options and boosting of innovative therapeutic approaches and clinical trials for new and more suitable treatment options.28 Thus, more efforts focused on shortening the translational pipeline and closing the gap between research and care are needed. In February 2017, at the 3rd IRDiRC Conference in Paris, France, stakeholders of RD research from around the globe gathered to discuss global progress to date, transformative new approaches to RD research, and challenging goals to be set for the next decade. What is clear after the 2-day conference: the international RD research community is eager to share knowledge and experience, work collaboratively across borders and address common roadblocks to maximize the impact of investments in order to bring diagnoses and therapies to RD patients. It is time to build new bridges and raise the bar for RD research worldwide.Notwithstanding, these encouraging results also illuminate new challenges that have yet to be overcome as too many RD patients continue to remain without adequate diagnosis and treatment. It is clear that many challenges still remain: (i) better understanding of RD mechanisms and faster translation of this knowledge into new diagnostics and treatments; (ii) development of novel approaches to clinical trial methodologies in small populations to facilitate the demonstration of the safety and efficacy of orphan drug candidates; (iii) improvement of health technology assessment methodologies that can be applied to the RD field and support best practices; (iv) investment in RD research databases and patient registries that are less fragmented and encourage data sharing and re-use via linking to other international platforms. In the EU Member States, ensuring and improving the equitable provision of health care on RD is also very challenging."} +{"text": "Editorial on the Research TopicCancer Metabolism: Molecular Targeting and Implications for Therapysensu stricto, refers to rewiring of metabolic circuitry, which in turn involves alteration of multiple energy producing pathways , metastasizing cancer cells (peroxide-driven ATP production), tumor cells under stromal influence , and late-stage cancers (hypoxia).\u201d Finally, the review emphasizes on the prospects of therapeutic targeting of cancer metabolism and the necessity to consider a combinatorial approach to overcome any potential challenges.Eidelman et al.) present a detailed overview of the metabolic characteristics of prostate cancer. In addition to the distinguishing feature of citric acid metabolism between the benign and malignant prostate tumors, the review focuses on other energy-producing pathways as well. Noteworthy, the diagnostic potential and implications of versatile techniques involving metabolomics have also been discussed. In the words of Siddiqui and colleagues, \u201cthere is still a great deal of research to be done, as many of the mechanisms of cellular cancer metabolisms are not well understood,\u201d and the review provides a summary of current knowledge on the cancer metabolism of prostate cancer.Although metabolic alteration is common and frequent among cancers, variations do exist in the type of metabolic change between benign and malignant neoplasms. By using prostate cancer as a prototype, Siddiqui and colleagues have delineated the functional link between metabolic reprogramming and its epigenetic regulation in cancer. With a focus on the chromatin remodeling enzyme, Brg1, the review describes in detail the molecular intricacies involved in metabolic reprogramming, especially the lipid metabolism. The biochemical and functional significance of Brg1-dependent transcriptional regulation of key lipogenic enzymes in breast cancer has been discussed in detail with reference to reprogramming of cancer-related fatty acid metabolism. Notably, the review also emphasizes on one of the emerging areas of research, the \u201cmetaboloepigenetics.\u201dIt is well known that oncogenic events regulate cancer metabolism either directly or indirectly, through signaling mechanisms. In the review, Nickerson and colleagues exquisitely present the functional association between TME and cancer metabolism. Besides cancer cells, the review also discusses the mechanistic insights on the role of TME and its components on cancer-associated immune cells, adipocytes, endothelial cells, and fibroblasts. Dwarakanath and colleagues appropriately state that advances in the complete understanding of metabolic reprogramming and TME may provide an opportunity to develop effective anticancer therapies.Multiple lines of evidence demonstrate that the immediate vicinity of tumor, commonly referred as the tumor microenvironment (TME) impacts the metabolic phenotype of cancer. In an extensive review, Dwarakanath and colleagues (Ganapathy-Kanniappan) discusses the contributions of tumor glycolysis in escaping immune surveillance and the therapeutic opportunities of its deregulation. Recent data demonstrate that cellular and/or metabolic stress augments the sensitivity of cancer cells to natural killer (NK) cell-mediated cytotoxicity discuss the molecular and biochemical correlations of aldo-keto reductases in breast cancer and prostate cancer. More importantly, the review deliberates on the catalytic function-dependent and function-independent roles of one of the isoforms of aldo-keto reductase as well. The review focuses on the opportunities and therapeutic potential of targeting aldo-keto reductases with small molecule inhibitors and emphasizes on the need for further research.Among several metabolic enzymes, aldo-keto reductases have been known to play an indispensable role in intermediary metabolism, macromolecular biosynthesis, and the detoxification of free radicals. Recent research has shed light on the association between aldo-keto reductases and cancer growth and therapeutic resistance. In the comprehensive review, Yang and colleagues discusses the effect of disruption of arachidonic acid metabolism by COX inhibition in prostate cancer. By using the example of NSAID, aspirin, the authors discuss the mechanism underlying its anticancer effects in prostate cancer. Although aspirin-dependent antimetastatic effects have been reported, controversies exist in the mechanism that is implicated for such anticancer effects. With the availability of substantial epidemiological data, the authors underscore al beit with caution the need for further investigation of aspirin-dependent biochemical or metabolic alterations in prostate cancer to verify any beneficial outcomes of aspirin in prostate cancer.Arachidonic acid metabolism has only recently been implicated in prostate cancer, and the review by Abou-Kheir and colleagues , and the natural product compounds, i.e., AG36 and Curcumin . These articles advance our understanding of the antiproliferative effects of miR-150, AG36, and Curcumin in leukemia (miR-150) and breast cancer .The next three research articles are related to the anticancer effect of microRNA, i.e., miR-150 (Overall, the collections of reviews and research articles presented under the research topic will enable us to advance our knowledge on cancer metabolism and stimulate critical evaluation of therapeutic targeting of metabolism in cancer.The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The purpose of this study was to estimate the degree of seasonality and prevalence of winter- and summer-type seasonal affective disorder (SAD) in African immigrant college students in comparison with African American peers. A convenience sample of 246 African immigrants and 599 African Americans studying in Washington, D.C. completed the Seasonal Pattern Assessment Questionnaire (SPAQ), which was used to calculate a global seasonality score (GSS) and to estimate the prevalence of winter- and summer-type SAD. Degree of seasonality was related to a complex interaction between having general awareness of SAD, ethnicity, and gender. A greater percentage of African students reported experiencing a problem with seasonal changes relative to African American students, and had summer SAD, but the groups did not differ on GSS and winter SAD. African students reported more difficulties with seasonal changes than their African American peers, which could represent a manifestation of incomplete acclimatization to a higher latitude and temperate climate. As Africans also had a greater rate of summer SAD, this argues against acclimatization to heat."} +{"text": "Recommendations on antenatal care for a positive pregnancy experience,As governments are developing schemes for universal health coverage (UHC) and progressing towards the sustainable development goals (SDGs), they need relevant and context-sensitive evidence to support different policies and interventions. Decision-makers are increasingly using qualitative evidence to understand various socioeconomic contexts, health systems and communities. This type of evidence is useful to assess the needs, values, perceptions and experiences of stakeholders, including policymakers, providers, communities and patients, and is thus crucial for complex health decision-making. For instance, during the development of the World Health Organization (WHO) Qualitative evidence syntheses, which combine and analyse evidence from individual qualitative studies, have emerged as a key approach to inform guideline development and address implementation considerations in diverse country settings and complex health systems.Beyond global guidance, qualitative evidence is invaluable for national and local decision-makers and practitioners to understand factors influencing the implementation and scale-up of health policies and programmes. For instance, policy-makers require evidence on factors that influence vaccination coverage, satisfaction and retention of health-care workers or quality of care in health facilities. Qualitative data have proven essential in planning, developing and implementing health policies and interventions, including in low- and middle-income countries, for example to prevent and treat malaria during pregnancy,Yet, despite the relevance of findings from qualitative evidence syntheses, there is limited guidance on how to assess and use this evidence in policy and practice. To address this need, the Alliance for Health Policy and Systems Research and the WHO Department of Reproductive Health and Research have supported the development of a new approach called GRADE-CERQual . The GRADE-CERQual approach is used to describe how much confidence decision-makers and other users can place in findings from qualitative evidence syntheses by transparently assessing methodological limitations, coherence, adequacy and relevance.New guidance on how to apply the GRADE-CERQual approach is now available as a special series of articles to support stakeholders conducting reviews of qualitative research and using their findings to inform decision-making.,The GRADE-CERQual approach was developed as a global public good to advance research methods and promote the uptake of qualitative findings in decision-making within and beyond the health sector. This guidance is also aligned with a global movement towards the generation and use of a wide array of evidence in policy-making."} +{"text": "Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI."} +{"text": "The objective of the Balearic Islands Palliative Care (PC) Program is to improve the quality of PC through a shared model consisting of primary health care professionals, home-based PC teams, and PC units in hospitals. According to the World Health Organization (WHO), patients with advanced cancer and other terminal diseases benefit from early identification and proactive PC. We will evaluate the effectiveness of an intervention in which a PC leader is established in the primary health care center, and assess the effect of this intervention on the early identification of patients in need of PC, the efficient use of health care services, and direct health care costs.Design: A two-arm cluster randomized clinical trial of 30 Primary Health Care Centers (PHCC) in Mallorca (Spain), in which each center was randomized to an intervention arm or a usual care arm. We expect that the number of patients identified as suitable for PC is at least 5% greater in the intervention arm.Sample size: A total of 4640 deceased patients. Outcomes will be assessed by a blinded external review of the electronic records.Interventions: General practitioners (GPs) and nurse leaders in PC for each PHCC will be appointed. These leaders will help promote PC training of colleagues, improve symptom management and psychological support of patients, and evaluate the complexity of individual cases so that these cases receive assistance from PC home-based teams.Measurements: Early identification (>90\u00a0days before death), evaluation of case complexity, level of case complexity , use and cost of hospital and primary care services, and quality of life during the last month of life .PC leaders in primary care teams will improve the early identification of patients eligible for PC. This initiative could improve the quality of end-of-life care and utilization of hospital resources.ISRCTN92479122. Retrospectively registered on 28 February 2017.ISRCTN Registry identifier: The populations of European countries are getting older, and this is leading to major increases in the number of patients needing palliative care (PC) because of chronic incurable diseases or advanced stages of terminal diseases . The 201PC was initially proposed for cancer patients , but wasearly identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual\u201d , an, an22],"} +{"text": "To alleviate and repair this damage, plants have developed a complex antioxidant system to maintain homeostasis through non-enzymatic and enzymatic antioxidants . To this end, the exogenous application of Si has been found to induce stress tolerance by regulating the generation of ROS, reducing electrolytic leakage, and malondialdehyde (MDA) contents, and immobilizing and reducing the uptake of toxic ions like Na, under stressful conditions. However, the interaction of Si and plant antioxidant enzyme system remains poorly understood, and further in-depth analyses at the transcriptomic level are needed to understand the mechanisms responsible for the Si-mediated regulation of stress responses.Silicon (Si) is the second most abundant element in soil, where its availability to plants can exhilarate to 10% of total dry weight of the plant. Si accumulation/transport occurs in the upward direction, and has been identified in several crop plants. Si application has been known to ameliorate plant growth and development during normal and stressful conditions over past two-decades. During abiotic stress, one of the immediate responses by plant is the generation of reactive oxygen species (ROS), such as singlet oxygen ( Following this several Si transport genes have been characterized in other corps such as barley and maize has a strong affinity with oxygen; therefore, it usually exists as silica , superoxide (2O2), or hydroxyl radicals (OH) in cells , such as singlet oxygen , and lipophilic metabolites or indirectly through the regeneration of the two major redox molecules (ascorbate and glutathione) in the cells Figure . AccumulAnethum graveolens plants. Same pattern of SOD, GPX, APX, GR, and CAT activities was observed by Al-aghabary et al. , and found that the activities of SOD, APX and GPX were increased and contrarily that of CAT was decreased stress may also disturb the balance between ROS and antioxidants activity. Soundararajan et al. treated ed Table . Liu et ed Table observeded Table . Almost Normally, natural wounding stress is caused by herbivory or lodging and these events could increase hydrogen peroxide level inside plant tissues and decreasing MDA activity.During abiotic stress conditions, the Si application shows varying response to ROS scavenging by activating the defense system plants. In doing so, the activity of antioxidant arsenals may also oscillate depending upon the intensity of stress and plant type. Si supplemented plants showed resistance to abiotic stress through, lowering ROS production by (i) enhancing CAT and APX activities as both are involved in conversion of HYK wrote the manuscript; MW and AK contributed in drafting and revising manuscript; IL draw the figure and revised the manuscript.This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agriculture, Food and Rural Affairs Research Center Support Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (716001-7)The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The discovery of prostate-specific antigen (PSA) as a biomarker represented a major discovery in the early diagnosis and monitoring of prostate cancer. However, the use of PSA is limited by the lack of specificity and an inability to differentiate indolent from life-threatening disease reliably at the time of diagnosis. A multitude of studies have aimed to improve the performance of PSA as well as identify additional biomarkers. The purpose of this study is to review available data on prostate cancer biomarkers for prostate cancer screening and prognostication, including prostatic acid phosphatase, PSA, PSA derivatives , PCA3, GSTP1, AMACR, and other newly emerging molecular and genetic markers."} +{"text": "The lack of proper water and sanitation infrastructures and poor hygiene practices in health-care facilities reduces facilities\u2019 preparedness and response to disease outbreaks and decreases the communities\u2019 trust in the health services provided.To improve water and sanitation infrastructures and hygiene practices, the Liberian health ministry held multistakeholder meetings to develop a national water, sanitation and hygiene and environmental health package. A national train-the-trainer course was held for county environmental health technicians, which included infection prevention and control focal persons; the focal persons acted as change agents.In Liberia, only 45% of 701 surveyed health-care facilities had an improved water source in 2015, and only 27% of these health-care facilities had proper disposal for infectious waste.Local ownership, through engagement of local health workers, was introduced to ensure development and refinement of the package. In-county collaborations between health-care facilities, along with multisectoral collaboration, informed national level direction, which led to increased focus on water and sanitation infrastructures and uptake of hygiene practices to improve the overall quality of service delivery.National level leadership was important to identify a vision and create an enabling environment for changing the perception of water, sanitation and hygiene in health-care provision. The involvement of health workers was central to address basic infrastructure and hygiene practices in health-care facilities and they also worked as stimulators for sustainable change. Further, developing a long-term implementation plan for national level initiatives is important to ensure sustainability. Water, sanitation and hygiene in health-care facilities are preconditions for providing health care of good quality. Despite this knowledge, a 2015 report revealed that 38% of the 66\u2009101 health-care facilities assessed in low- and middle-income countries had no source of water.In Liberia, a low-income country in western Africa, only 45% of 701 surveyed health-care facilities had an improved water source in 2015, and only 27% of health-care facilities had proper disposal for infectious waste . The 2013\u20132016 Ebola virus disease outbreak in the country emphasized the importance of cleanliness, sanitation and regular hand washing. During the outbreak, the majority of patients were fearful of seeking care within health-care facilities due to risk of contracting the virus. The poor compliance with infection prevention and control measures and poor water and sanitation infrastructures and hygiene practices within the facilities further contributed to the fear. Between August and December 2014, outpatient visits were 61% lower and antenatal care visits 40% lower than the same timeframe in 2013.Here we describe the efforts made to improve the quality of health services in Liberia, focusing on the development and implementation of a package to improve water and sanitation infrastructures and hygiene practices during and after the epidemic.A survey of 701 of the 727 health-care facilities in Liberia showed that the majority of them are public (62%), followed by private for-profit (31%) and private not-for-profit facilities (7%). Most of the facilities are clinics (88%), while health centres account for 7% and hospitals 5% .During the epidemic, the Liberian health ministry introduced an infection prevention and control focal person into each of the 15 county\u2019s health management team. In some resource-constrained counties, the focal person also serves as the environmental health officer working on water, sanitation and hygiene. The focal person oversees the delivery of routine infection prevention and control measures and water, sanitation and hygiene health-care interventions at health-care facilities, in collaboration with the facility-based infection prevention and control focal person. The focal person is also responsible for county outbreak preparedness and response efforts related to water, sanitation and hygiene and infection prevention and control.To inform the development of a package of interventions to improve and monitor water, sanitation and hygiene, the health ministry, with support from the World Health Organization (WHO), first conducted a situational assessment in 63 health-care facilities. The assessment revealed challenges in water treatment, testing of water quality and health-care waste management, including segregation, handling, treatment and final disposal of waste, a lack of ash and placenta pits and lack of protective fencing in waste management areas. In addition, environmental management was shown to be poor.In 2015, the health ministry, with support from WHO and the United Nations Children\u2019s Fund launched the package, using a systematic and multisectoral approach, involving health and water, sanitation and hygiene sectors. The overall aim of the implementation was to have complete country coverage on components for water, sanitation and hygiene as well as measures of infection prevention and control. The implementation involved county health teams, since these teams are critical as a first line of defence against potential future outbreaks and overall health systems strengthening.A national train-the-trainer course was held for focal persons, medical directors, community health department directors, community health social administrators, coordinators for water, sanitation and hygiene, coordinators for infection prevention and control, and environmental health technicians. The objective of the course was to teach the trainer to train health workers in their county and to support the roll-out of the package. The course involved four sessions each lasting four or five days, and a total of 94 people were trained between November 2015 and February 2016. The training curriculum was both theoretical and practical, including techniques, such as hand washing. The trainees visited a facility to conduct an assessment and used the results to identify areas for improvement and suggested actions. The course was conducted in close collaboration with infection prevention and control efforts, which provided focal persons with sufficient technical knowledge to improve and monitor water and sanitation infrastructures and hygiene practices, including safe management and treatment of health-care waste. Participants received a certificate upon completion of the course. To ensure trainers\u2019 involvement in future district and health-care facility level training, a database of certified county trainers was created and made available to all water, sanitation and hygiene partners. To catalyse institutional change, the health ministry launched in-county collaborations between health-care facilities, so-called twinning exchange, which included workshops and facility visits.The development of the package was informed by a global risk-based management toolFurther, the national minimum standards for infection prevention and control include water, sanitation and hygiene components. To ensure compliance with the minimum standards, the health ministry, along with WHO and relevant partners, conduct monthly facility assessments using the Liberia Health System Minimum Standards Tool.Key changes introduced in the health system included placing a strong emphasis on training of health workers at the facility level to deliver health services of good quality and to be prepared for future outbreaks. Local ownership, through engagement of local health workers, ensured development and refinement of the package. To improve effectiveness, accountability and efficiency of health programmes, multisectoral collaboration between environmental health; water, sanitation and hygiene; and health colleagues was put in place when developing the package. This exchange informed national level direction, which led to increased uptake of water sanitation and hygiene and infection prevention and control practices. Finally, the monthly facility assessments, which focused attention on functional infrastructures for water, sanitation and hygiene, were an important support for change. Also, the focus on accountability led to facility-based quality improvement processes to facilitate further improvements.The changes have led to high engagement on improving water and sanitation infrastructures and hygiene practices from all health workers involved, including the package\u2019s inclusion in programmes for infection prevention and control training. The engagement has also contributed to broader efforts to improve drinking-water quality and its management through development of national guidelines and a national quality strategy. Similarly, to address identified problems on infection prevention and control and water, sanitation and hygiene standards, the health ministry, in collaboration with partners, launched training for health workers known as Keep Safe \u2013 Keep ServingIt is important to highlight that during this time of the outbreak, very little was being measured due to increased attention on containing and stopping the outbreak in Liberia.After the epidemic, the government wanted to ensure that improvements made during the outbreak were sustained; the government has identified health-service delivery of high quality as a key investment area,Challenges encountered during the implementation of the package included poor water and sanitation infrastructures and poor infection prevention and control measures, specifically hand hygiene practices, at health-care facilities. The lack of a long-term roll-out plan, despite national training-of-trainers undertaken, has resulted in incomplete national implementation of the package. Nonetheless, package components are being implemented in a wider effort to improve the quality of health services. The findings from further implementation of the package, combined with service delivery tools\u2019 implementation, will inform future national direction for quality planning, control and improvement of health services.The main lessons learnt are summarized in Box\u00a01National leadership was important to identify a vision and to create an enabling environment for changing the perception of water, sanitation and hygiene in health-care provision.The involvement of health workers was central to address basic infrastructure and hygiene practices in health-care facilities.Improvements in water and sanitation infrastructures, hygiene and infection prevention and control practices helped re-establish trust between health-care providers and communities and increased the use of health-care services.This paper provides some insights on how water, sanitation and hygiene can be embedded into health service provision. The efforts made during the epidemic to improve water, sanitation and hygiene were used as a catalyst by the government for improvement of the quality of health service provision. The progress includes improving infection prevention and control practices; increasing staff performance; improving outbreak preparedness; and enhancing community engagement. The strategies presented here could be adopted and adapted for low-resourced health settings facing similar challenges."} +{"text": "The epidermis of amniotes forms a protective barrier against the environment and the differentiation program of keratinocytes, the main cell type in the epidermis, has undergone specific alterations in the course of adaptation of amniotes to a broad variety of environments and lifestyles. The epidermal differentiation complex (EDC) is a cluster of genes expressed at late stages of keratinocyte differentiation in both sauropsids and mammals. In the present study, we identified and analyzed the crocodilian equivalent of the EDC. The gene complement of the EDC of both the American alligator and the saltwater crocodile were determined by comparative genomics, de novo gene prediction and identification of EDC transcripts in published transcriptome data. We found that crocodilians have an organization of the EDC similar to that of their closest living relatives, the birds, with which they form the clade Archosauria. Notable differences include the specific expansion of a subfamily of EDC genes in crocodilians and the loss of distinct ancestral EDC genes in birds. Identification and comparative analysis of crocodilian orthologs of avian feather proteins suggest that the latter evolved by cooption and sequence modification of ancestral EDC genes, and that the amplification of an internal highly cysteine-enriched amino acid sequence motif gave rise to the feather component epidermal differentiation cysteine-rich protein in the avian lineage. Thus, sequence diversification of EDC genes contributed to the evolutionary divergence of the crocodilian and avian integuments. The phylogenetically closest extant relatives of crocodilians are the birds. These two groups constitute the clade Archosauria and their last common ancestor lived 219\u2013255 Ma in mammals is shared, with clade-specific modifications, among all amniotes investigated so far. The organization of the EDC has been previously defined for birds, lizards, snakes, and turtles , 2017. ELOR) in lizard scales (SCFN) in avian claws and feathers (EDCRP) in feathers (EDMTFH) in feathers and the saltwater crocodile (Crocodylus porosus). Accession numbers of genome sequence scaffolds corresponding to the EDC can be found in Gallus gallus) and turtle (Chrysemys picta bellii), already identified in previous studies (S100A12 and S100A11) bordering the EDC in the investigated species. Genes coding for functional proteins were included in comparative studies whereas pseudogenes belonging to EDC gene families with functional members in the same species were not investigated further. In case of EDC regions with seemingly low gene density, the nucleotide sequence of the region in question was translated in silico and additional open reading frames of candidate EDC genes were identified by our already published protocol information about exon coverage by RNA-seq reads was consulted to check for transcribed regions in the EDC of A. mississippiensis. Nucleotide sequences of transcribed regions were translated in all reading frames and the possible translation products were compared with known EDC proteins of other amniotes. To test for expression of predicted crocodilian EDC genes, we performed tBLASTn searches in the transcriptome of A. mississippiensis was kept at the Vienna Zoo, Vienna, Austria as part of an international breeding program. Skin tissue was sampled through a biopsy at the flank of a 3-year-old female Morelet\u2019s crocodile in agreement with the national laws regulating animal welfare and the guidelines of Good Veterinary Practice. For histological investigation, the sample was fixed with 7.5% formaldehyde, embedded in paraffin, thin-sectioned and stained with hematoxylin and eosin according to a published protocol and the saltwater crocodile (Crocodylus porosus), sequences of EDC-encoded proteins of chicken and turtle (Chrysemys picta bellii) were used as queries in tBLASTn searches of the crocodilian genomes , we found that some EDC genes were correctly annotated, whereas others were missed by the automatic algorithms and some gene annotations included splice sites and reading frames that were not plausible A. AppareCRNN and SCFN) are present close to one end of the EDC, and SEDC genes form the main part of the EDC in crocodilians. Comparative analysis suggests that a cluster of crocodilian CBP (beta-keratin) genes is syntenic with CBPs in the EDC of other sauropsids and also with that of the EDC in turtles . Only 2 uropsids . Two EDCodilians , suggest mammals , 2017 , EDPE, and EDQA , serine (S), proline (P), lysine (K), cysteine (C), and glutamine (Q) . In manyMany EDC proteins of crocodilians exhibit sequence repeats rich in the above-mentioned amino acids online. C. moreletii) (C. porosus) and 21 (A. mississippiensis) having an intact and complete open reading frame , which have a unique organization with an amino-terminal domain rich in cysteine and histidine residues and a carboxy-terminal domain rich in cysteine and proline residues A, were preletii) online. ng frame online wng frame B, it appEDPQ genes were found in the EDCs of the saltwater crocodile and the American alligator, respectively. In a previous study, two EDPQ genes were also identified in the turtle C. picta , EDMTFH EDAA clusters of turtles and crocodilians indicategeticus) , and disgeticus) which wageticus) . As the geticus) , furthervice versa. However, there are also important differences which have likely contributed to the divergent evolution of skin phenotypes in crocodilians and birds. In fact, the epidermal stratum corneum of crocodilians evolved into a particularly mechano-resistant and water-proof component of the skin, and the beak and particularly the feathers of birds represent unique evolutionary innovations that depended on modifications of the epidermal differentiation process.Comparison of alligator and crocodile versus chicken shows that there is a high degree of conservation of EDC genes in archosaurs. Only few SEDC genes of crocodilians lack an ortholog in birds and Our data suggest that the EDC underwent only few changes in gene composition and arrangement in the crocodilian lineage after its split from the avian lineage. These changes were inferred from our comparison of the EDCs of crocodilians with the EDC of birds and turtles. Both the saltwater crocodile and the American alligator have at least 4 times as many EDCH genes as birds, suggesting that the EDCH gene cluster expanded in the stem lineage of crocodilians . Other aEDCRP, we identified orthologs in crocodilians , and a precursor of EDCRP. The cooption of epidermal structural proteins may be a common theme in the evolution of feathers and hair . It remaodilians , whereasodilians . The chaodilians . The croodilians , 2015. Todilians , a layerodilians . This leIn conclusion, the results of the present comparative genomic analysis of the EDC in archosaurs provide a basis for studying the specific roles of genes involved in epidermal differentiation in crocodilians and allow to further delineate the evolutionary divergence between the crocodilian and avian skin.Genome Biology and Evolution online.The authors declare no competing financial interests.Supplementary Figures and TablesClick here for additional data file."} +{"text": "The Community Assessment of Psychic Experiences (CAPE) is a self-report questionnaire that has been developed to measure the dimensions of psychosis in the general population. The cross-national equivalence of a questionnaire allows the comparability of a scale across different populations in different countries, i.e., using different versions of the scale according to the considered language. In this study, our aim was to investigate the equivalence of the CAPE across different countries.Data were drawn from the European Union Gene-Environment Interaction (EU-GEI) study. Participants were recruited across in six countries: United Kingdom, the Netherlands, Italy, Spain, Brazil and France. To analyse the cross-national equivalence of the dichotomised version of the CAPE, we used the multigroup categorical confirmatory factory analysis (MCCFA). The cross-national equivalence can be stated after the establishment of three invariances characterised by increased constraints: the configural invariance, the metric invariance and the scalar invariance across the multiples groups.The configural invariance model fits well, providing evidence for identical factor structure across countries. The assumption that factor loadings are identical across countries is granted based on the negligible change in the fit indices in the metric invariance model. Moreover, the fit indices suggest that the CAPE shows scalar invariance across countries.These findings suggest that comparisons across countries of factor and observed means of the CAPE are possible. Thus, differences observed in scores between samples from different countries can be considered as different levels of psychosis."} +{"text": "Prior to the Ebola virus disease outbreak in Liberia, the laboratory system was duplicative, fragmented and minimally coordinated. The National Reference Laboratory was conceptualised to address the existing challenges by promoting the implementation of effective and sustainable laboratory services in Liberia. However, in a resource-limited environment such as Liberia, progress regarding the rebuilding of the health system can be relatively slow, while efforts to sustain the transient gains remain a key challenge for the Ministry of Health. In this paper, we describe the pre-Ebola virus disease laboratory system in Liberia and its prevailing efforts to address future emerging infectious diseases, as well as current Infectious diseases, all of which are exacerbated by poverty. We conclude that laboratory and diagnostic services in Liberia have encountered numerous challenges regarding its efforts to strengthen the healthcare delivery system. These challenges include limited trained human resource capacity, inadequate infrastructure, and a lack of coordination. As with most countries in sub-Saharan Africa, when comparing urban and rural settings, diagnostic and clinical services are generally skewed toward urban health facilities and private, faith-based health facilities. We recommend that structured policy be directed at these challenges for national institutions to develop guidelines to improve, strengthen and sustain diagnostic and curative laboratory services to effectively address current infectious diseases and prepare for future emerging and re-emerging infectious diseases. Kennedy Memorial Hospital, a tertiary referral hospital in Monrovia. With prevailing viral infectious diseases as its initial core, its primary laboratory diagnostic capacity was limited to measles, rubella and yellow fever. At the time, samples for Lassa fever were collected, packaged and transported for diagnosis at the Lassa Fever Laboratory in Kenema, Sierra Leone. With support from international partners, basic equipment and human resource development aimed at expanding the capacity of the NRL were secured, and the laboratory was subsequently relocated in 2009 to the compound of the Liberia Institute for Biomedical Research in Charlesville, Lower Margibi County. Afterward, a programme known as the National Diagnostic Unit (NDU) was established.The primary focus regarding the implementation of effective and sustainable laboratory services in Liberia was accentuated with the conceptualisation of the National Reference Laboratory (NRL) in 2008.2 and subsequently culminated with a drastic brain drain as the result of the migration of trained Liberians to politically-stable countries. In a resource-limited environment such as Liberia, progress regarding the rebuilding of the health system has been relatively slow and sustaining the gains from transient spikes in improved health indicators remain a major challenge.Liberia has gradually been rebuilding its healthcare delivery system after 16 years of devastating civil conflicts which erupted in December 1989, destroyed the country\u2019s health infrastructure3 of the Ministry of Health that established the minimum threshold for trained human resources development, laboratory infrastructure, disease surveillance and laboratory diagnostic capacities at each level of the healthcare delivery system in the country.Accordingly, laboratory-based service delivery in Liberia has been basically defined in several key policy documents3 The National level comprises the NRL and NDU; the County level involves the referral hospitals in the political subdivisions of the country; and the Peripheral level accounts for the district and community health facilities. With the development of the Country\u2019s National Decentralization Policy4 for the regionalisation of services within the country, geared toward the improvement of services in the disenfranchised rural areas, a fourth level of the laboratory system was incorporated; thereby, allowing for (1) National; (2) Regional; (3) County; and (4) Peripheral levels. Accordingly, the NRL and NDU are strategically situated within the National level. The regional tier consists of five regional laboratories based on the decentralisation of the country, namely: (1) Southeast A; (2) Southeast B; (3) North central; (4) South central; and (5) Western. The county and peripheral tiered systems are basically the same levels as in the prior three-tiered approach.Liberia\u2019s laboratory system was initially classified into a three-tiered health system structure consisting of the: (1) National; (2) County ; and (3) Peripheral levels.In general, there are two main categories of laboratory services in Liberia. The first is the clinical laboratory services designated for clinical specimen testing for diagnostic purposes and the second is public health laboratory services directed at disease surveillance.According to its mandate, the NRL has a four-fold responsibility: (1) perform diagnostic testing services on specimens for diseases with epidemic potential that are under surveillance, especially those that are immediately notifiable to the World Health Organization, now inclusive of Ebola virus disease (EVD), as required by the International Health Regulations; (2) oversee the network of public laboratory structures within the country and the provision of services through quality assurance, training, monitoring and supportive supervision; (3) assess new and available technologies; and (4) provide technical advice to the Ministry of Health.Similar to the NRL, the NDU conducts quality assurance, monitoring and evaluation, and training. Furthermore, it coordinates procurement processes for the distribution of laboratory commodities for special programmes supported by the Global Funds, such as HIV, AIDS, malaria and tuberculosis programmes. When constructed, the regional laboratories will support the NRL in its surveillance testing , as well as the county-level coordination of the activities of the laboratory system. In addition, they will lend diagnostic support to the laboratories at the county hospitals.These structures are responsible solely for clinical specimen testing for diagnostic purposes. Test categories include, among others, chemistry, haematology and parasitology. Apart from the traditional structures indicated for service delivery, certain programs of the Ministry of Health are also involved in cross-cutting testing activities . These programmes include: (1) the National AIDS Control Program; (2) the National Malaria Control Program; (3) the National Tuberculosis & Leprosy Control Program; and (4) the National Blood Safety Program.Laboratory equipment, reagents and supplies for the operations of the various laboratory structures are either procured by the Ministry of Health or donated by international partners. The operation of the procurement activities is performed by two organisations: (1) the National Drug Service; and (2) the Global Fund, which supports the HIV, tuberculosis and malaria programmes. Both of these key operational processes (procurement and donations) for the effective functionality of the laboratory system in Liberia exist without defined \u2018Maintenance and/or Service Contracts\u2019.There are two accredited faith-based and one publicly-owned laboratory training institutions in Liberia. These are: (1) the Mother Patern College of Health Sciences in Monrovia, Montserrado County; (2) the Phebe School of Nursing in Suacoco, Bong County; and (3) the Tubman National Institute of Medical Arts in Monrovia. The qualifications offered by these training institutions, based on a duration of training that ranges from 2\u20134 years, includes Diploma in Laboratory Science ; Associate of Science and Bachelor of Science in Laboratory Technology by the Mother Patern College of Health Sciences.6 Poor health infrastructure, lack of logistics during the beginning of the outbreak, and an inadequate number of trained staff in public health disease surveillance and laboratory diagnostic response in emergency situations, were key factors leading to the delay in response to the outbreak. These pre-EVD laboratory challenges, among others, included:The status of the existing laboratory structure and service delivery system in Liberia is characterised by numerous challenges, which were uncovered during the EVD outbreak in Liberia that became a major public health problem in the country and the sub-region.Lack of integration between public health surveillance and laboratory diagnostic services, resulting in fragmented service delivery.Lack of a well-defined organisational structure with clearly-defined objectives, including existing duplications of roles and responsibilities within the tiered laboratory systems to support an effective leadership and management system.Lack of adequate financial resources for infrastructure support and operational costs.Inadequately trained laboratory workforce, including inadequate deployment across the country.Unavailability of maintenance and service contracts for procured and/or donated laboratory equipment and supplies to sustain the effective operation of the laboratory infrastructure.Lack of adequate biomedical equipment technicians to maintain and repair laboratory equipment.Unstable electric power supply and inadequate water supply for laboratory service utilisation.Lack of effective Laboratory Information Management System for coordination, operations, and the efficient functionality of the various tiered systems.7 It was aimed at addressing the challenges associated with limited diagnostic services, which subject patients to inappropriate treatment, chronic illnesses, high out-of-pocket expenditures on healthcare, loss of income and, ultimately, loss of confidence in health services. To mitigate the challenges, the proposed policies targeted the following areas:Despite these challenges, efforts were directed at the development of a National Laboratory Policy to prioritise the delivery of laboratory services within the health system.Organisation: Strengthen the legal and regulatory framework, as well as the technical and administrative organisational structures, for the delivery of laboratory services nationwide.Test selection and referral linkage: Ensure that appropriate tests are performed at the appropriate facility level in a decentralised network and the provision of oversight to establish appropriate communication structure and processes in order to create a referral linkage or network between facilities.Human resources: Ensure the presence of certified laboratory personnel in all public and private laboratories, regulate through periodic certification and develop curriculum standards to support training institutions.Quality assurance: Ensure that laboratories are certified according to defined standards with established systems for independent certification.Infrastructure: Provide safe and adequate infrastructure standards for all public and private laboratories at each level of care and ensure, through certification, that laboratories have standard operating procedures and required infrastructure for laboratory safety and operation.Equipment: Ensure that all laboratories have properly working equipment with both preventative and curative maintenance, and enforce standardisation such that all equipment and supplies meet national specifications and are maintained according to manufacture guidance.Supply chain management: Support an uninterrupted distribution of reagents and supplies to all laboratories, and ensure that an effective system is in place to select, quantify, procure, transport, store, distribute and keep records of all equipment, reagents, and supplies.National blood safety: Ensure a safe supply of blood for transfusions and promote voluntary blood donations.Biosafety: Provide a safe environment and ensure laboratory personnel adhere to safety protocols and quality assurance standards, including laboratory safety for protection of professional staff, public and the environment.Financial resources: Allocate resources to sustain quality laboratory services.Research and development: Identify major laboratory research priorities and promote the culture for operational research, and evaluate and introduce new innovative technologies into the laboratory system.Collaboration: Improve laboratory services through public and private partnerships, as well as support for national and international collaborations.Ethics: Ensure a professional code of conduct and client confidentiality.Information system: Design a laboratory information system that is fully integrated for information flow between laboratories within a referral network.Policy implementation: Monitor and evaluate the efficiency and effectiveness of the laboratory system, as well as its sustainability.Policy regulation: Ensure that laboratory guidelines are updated regularly and in compliance with internationally-accepted standards.We recommend that a joint public\u2013private partnership team be established to conduct a comprehensive technical assessment of the laboratory system within the country and provide appropriate recommendations to combat emerging infectious diseases. Enhancing the laboratories\u2019 capacity for research requires: the availability of essential equipment and appliances; development of relevant and sustained human capacity through continuing education, on-the-job training and mentorship; formulation and adherence to guidelines and standard operating procedures, and compliance with Good Laboratory Practice and other international standards, such as ISO 15189.The EVD outbreak in Liberia has necessitated improved laboratory capacity to respond to an epidemic of emerging infectious pathogens as well as support for the development of a suitable research platform during such public health emergencies. Accordingly, we propose a framework to strengthen the laboratory system of the country based on a preparedness strategy to mitigate future outbreaks of emerging and re-emerging infectious diseases See .Laboratory and diagnostic services in Liberia have encountered numerous challenges regarding their contributions toward the strengthening of the healthcare delivery system in Liberia. These challenges are a consequence of limited trained human resource capacity, inadequate infrastructure, and lack of coordination among the four tiers. Diagnostic services are skewed in urban health facilities as compared to those in rural communities, and also skewed in favour of private and faith-based health facilities when compared to public health facilities. These disparities are markedly observed throughout the country and significantly impact patient care and emergency situations. The lack of in-country diagnostic laboratories for the diagnosis of viral haemorrhagic fevers, such as Lassa fever and EVD, prior to the EVD outbreak, confirmed the limitations and challenges the country faced with regard to diagnostics services. Prior to the EVD outbreak, suspected Lassa fever specimens were transported to Sierra Leone for diagnostic confirmation, which significantly increased the duration of the reporting and turnaround time for case confirmation, especially in a Lassa fever-endemic country, such as Liberia. Limited training of laboratory personnel in molecular diagnostic techniques, and laboratory response in a health emergency, were also a major challenge.Disease surveillance on the national level has been limited to a paper-based system. Protracted turnaround time and delay in reporting has been a key diagnostic and service delivery challenge in most areas, predominantly in rural settings. Surveillance of diseases has been limited to those in humans and not in animals. In the recent EVD outbreak, active case findings were primarily based on the assumptions of humans as the portals for sporadic outbreaks or re-emerging infections. EVD being a zoonotic disease, its surveillance in animals such as bats, monkeys and other primates should also receive adequate attention from the laboratory diagnostic and public health surveillance systems. Furthermore, hunting communities should also be considered as sources of information gathering and active case findings.8 Religious practices such as bathing the dead, wake-keeping for the deceased, gathering in groups and rituals for worship, and secret societies for men and women regarding cultural initiation, also predispose communities by creating favourable portals and suitable enabling environments for the transmission of emerging infectious diseases. For these reasons, the development and availability of diagnostic platforms remain paramount for rapid detection and control of emerging and re-emerging diseases.As with our West African neighbours and other countries in sub-Saharan Africa, Liberians have close cultural ties and extended families across the porous borders. Cultural practices, such as eating bush meat , are common cultural norms which could expose communities to zoonotic-associated diseases, such as EVD."} +{"text": "The Polio Eradication and Endgame Strategic Plan (PEESP) established a target that at least 50% of the time of personnel receiving funding from the Global Polio Eradication Initiative (GPEI) for polio eradication activities should be dedicated to the strengthening of immunization systems. This article describes the self-reported profile of how GPEI-funded personnel allocate their time toward immunization goals and activities beyond those associated with polio, the training they have received to conduct tasks to strengthen routine immunization systems, and the type of tasks they have conducted.A survey of approximately 1000 field managers of frontline GPEI-funded personnel was conducted by Boston Consulting Group in the 10 focus countries of the PEESP during 2 phases, in 2013 and 2014, to determine time allocation among frontline staff. Country-specific reports on the training of GPEI-funded personnel were reviewed, and an analysis of the types of tasks that were reported was conducted.A total of 467 managers responded to the survey. Forty-seven percent of the time of GPEI-funded personnel was dedicated to tasks related to strengthening immunization programs, other than polio eradication. Less time was spent on polio-associated activities in countries that had already interrupted wild poliovirus (WPV) transmission, compared with findings for WPV-endemic countries. All countries conducted periodic trainings of the GPEI-funded personnel. The types of non\u2013polio-related tasks performed by GPEI-funded personnel varied among countries and included surveillance, microplanning, newborn registration and defaulter tracing, monitoring of routine immunization activities, and support of district immunization task teams, as well as promotion of health behaviors, such as clean-water use and good hygiene and sanitation practices.In all countries, GPEI-funded personnel perform critical tasks in the strengthening of routine immunization programs and the control of measles and rubella. In certain countries with very weak immunization systems, GPEI-funded personnel provide critical support for the immunization programs, and sudden discontinuation of their employment would potentially disrupt the immunization programs in their countries and create a setback in capacity and effectiveness that would put children at higher risk for vaccine-preventable diseases. The Polio Eradication and Endgame Strategic Plan (PEESP) defined its second objective around the strengthening of immunization systems and established a target that at least 50% of the time of field personnel funded by international partners of the Global Polio Eradication Initiative should be dedicated to the strengthening of immunization systems; additional components of the second objective involve increasing coverage with the third-dose of diphtheria, tetanus, and pertussis containing vaccine DTP3) in districts where the risk of polio is high, introducing inactivated poliovirus vaccine, and withdrawing oral polio vaccines following certification of eradication of the wild type virus . This is in distrBecause wild poliovirus has been endemic until recently in many countries with very weak health systems, significant investments have been made by GPEI to increase human-resources capacity at national levels and in high-risk polio districts to achieve the eradication goal. In 2012, close to 28 000 GPEI-funded personnel were active in the 10 focus countries of the PEESP These peIn their assessment of the impact of polio eradication activities on RI programs, Closser et al , 5 concl6\u2013Until recently, there had not been a formal assessment on the amount of time that GPEI-funded personnel spent on broader immunization and mother-and-child-health goals. This article describes the self-reported profile of how GPEI-funded personnel allocate their time toward immunization goals and activities beyond those associated with polio eradication, the training they have received to conduct tasks to strengthen RI systems, and the type of tasks they have conducted. A survey was conducted among about 1000 managers of GPEI-funded personnel involved in frontline polio eradication activities, to develop a quantitative view of the proportion of time frontline staff spend on polio eradication, RI, and other health and development priorities. The survey collected information on broader issues, such as the criticality of polio eradication programs to other health priorities, the impact of these programs on broader immunization goals, and the capabilities that could be at risk if polio funding and support for personnel was reduced .Haemophilus influenza type B, and hepatitis B), pneumococcal conjugate vaccine, and rotavirus vaccine; the second dose of measles vaccine; development of proposals for new-vaccine introduction; and support provide to governments with respect to readiness assessment and planning, development of operational guidelines, postintroduction evaluations, and surveillance. The fifth targeted activities related to creating awareness around issues of child health, including advocacy with political, administrative, religious, and community leaders; assistance with health education; provision of basic health services to children; and implementation of child health days. The sixth category included activities related to improving sanitation and hygiene, such as social mobilization to sensitize communities on importance of sanitation and hygiene, supporting water quality assessment and data gathering, assistance with education on waste disposal and infection control, and supporting installation of toilets in schools. The seventh focused on activities to counsel and educate pregnant women and their families, including communication on exclusive breast feeding and importance of institutional delivery; assistance with policy development, program evaluation, and high-level advocacy; supporting distribution of vitamins; and monitoring of nutritional support for malnourished children. The eighth targeted activities related to improving overall healthcare systems and infrastructure, such as provision of data to governments to improve services; assistance with development of government strategy and long-term planning; supporting the overall supply chain; strengthening partnerships among donors, nongovernmental organizations, and governments; and surveillance for other diseases. The ninth comprised activities related to the response to disease outbreaks and other crises and disasters, such as floods, landslides, earthquakes, and humanitarian crises. The tenth was composed of other diseases or program areas that were not included in the first 9 categories.Respondents were asked to approximate the amount of time spent activities across 10 categories . The first category (polio eradication activities) addressed support for the following polio eradication efforts: policy and strategy development, planning, management and oversight, implementation and service delivery, communications and community engagement, disease surveillance and data analysis, and partnership and coordination. The second (RI) targeted activities related to strengthening local RI systems, such as Expanded Program on Immunization (EPI) capacity building, monitoring and supervision of immunization sessions, data management and analysis, and design and implementation of communication strategies for RI. The third (measles and rubella) focused on activities related to targeted measles and rubella prevention and elimination, including vaccination campaign support and case surveillance. The fourth category (new vaccine introduction) consisted of activities related to facilitating the introduction of new and underutilized vaccines, such as pentavalent vaccine , the United Nations Children\u2019s Fund (UNICEF), the Centers for Disease Control and Prevention, and Rotary International were tasked with distributing the survey link via email to their respective country program leaders across the 10 countries, who then identified the managers of frontline staff. The managers completed the survey on behalf of their teams. The number of surveys to managers of frontline workers distributed is presented in Alongside the survey, Boston Consulting Group conducted interviews with country-level leadership not only to validate insight from the survey, but to better understand reasons for success or failure in supporting other health priorities, particularly with regard to meeting or exceeding targets for RI support. The interviews were free-flowing discussions and played an important part in contextualizing the situation and options for moving forward in each country.From the 10 priority countries, responses from 467 GPEI-funded personnel were included in the analysis . GPEI-fuThe time spent on RI activities, by country, ranged from 15% to 32% . WHO and UNICEF personnel allocated a similar proportion of time to RI . The program area with the next-highest time allocation was measles and rubella control , with values of 3% in Afghanistan, 5% in Pakistan, 7% in Nigeria, 7% in Chad, 11% in Somalia, 11% in India, 13% in Angola, 14% in the DRC, 14% in South Sudan, and 21% in Ethiopia.There was variation in time allocation across countries. Countries in the WHO Eastern Mediterranean Region (EMR) countries\u2014particularly the polio-endemic countries of Afghanistan and Pakistan\u2014spend substantially more time on polio eradication activities and comparatively less time supporting other health priorities . CountriGPEI-funded staff were asked to rank their views of the most important influences of the polio eradication program on non\u2013polio-related health and development programs and goals. The top 5 program activities selected (in rank order) were communication and social mobilization, capacity building, monitoring and supervision, strengthening RI, and support for control of other diseases, such as measles and rubella .P < .025). The same relationship holds true for RI-related activities , compared with the number of frontline workers (close to 29 000), making it logistically feasible under the challenging circumstances of conducting this field survey to achieve a response rate that is high and representative of the universe of frontline workers. Second, some frontline staff may not be able to reliably access an online survey or may not read English (the only language the survey was coded in), which could therefore reduce the response rate and data confidence.The exact number of surveys distributed was reported for 6 of 10 countries. In the 4 remaining countries, the survey was distributed to about 200 managers.Some country and agency data are more robust than others. In particular, the number of responses and yield associated with UNICEF personnel managers for South Sudan and Pakistan are quite low, despite reminders sent to the managers. In these 2 instances in particular, we caution drawing broad implications from the survey results, given the sample size and yield.GPEI-funded personnel spent substantial time on broader immunization and mother and child health program activities. While the amount of time varied by country, GPEI-funded personnel were being used to improve RI program activities and strengthen systems, control measles and rubella, conduct surveillance activities, and support broader maternal, newborn, and child health programs. This is particularly true in countries where wild poliovirus circulation had been interrupted and the number of campaigns was reduced. This finding is in line with findings reported by Closser et al .Analysis of the type of activities conducted in RI reveals that, across regions, GPEI-funded personnel were most frequently engaged in advocacy, communications, and community engagement, followed by research, which included activities related to learning and refining RI approaches in the field, and special studies. Notably, training and capacity building was a top activity in India and less so in the other regions. Personnel terms of reference included RI as per survey data, demonstrating the increasing formal role of GPEI-funded staff in RI activities. However, RI training rates are quite variable\u2014in Chad, all GPEI-funded personnel (100%) have been trained in RI. In contrast, only 56% of surveyed personnel in the EMR countries have received RI training. In Chad, the revitalization of the RI programs depend largely on GPEI-funded staff both at national level and decentralized levels.GPEI-funded assets have helped raise awareness of the importance of RI for polio and other vaccine-preventable diseases, yield data and surveillance information that allow countries to develop evidence informed RI planning and implementation, facilitate systematic RI microplanning, provide RI services to deprived communities, such as nomads, migrants, rural remote populations . Sudden While self-reported data by GPEI frontline managers may introduce some bias, it is clear that the polio eradication program has been successful in increasing capacity at the local level in countries and places where systems are weakest\u2014districts where the risk of polio is high. Decentralizing support to RI microplanning, and conducting district taskforce meetings to analyze data for action are promising approaches to improve the program, as shown in India. In Nigeria and India, GPEI has shifted its social mobilization efforts from being externally driven to local agents, often women, who promote immunization, child health, and birth registration in their own communities, with tangible results and impacts.Although a direct causal relationship between national RI improvements and GPEI-funded personnel\u2019s\u2019 time spent on non\u2013polio eradication activities is challenging to establish, in 6 of 10 focus countries , DTP3 coverage improved between 2013 and 2015; in 2 , no progress was reported; and in 2 (Angola and South Sudan), coverage regressed between 2013 and 2015, based on WHO and UNICEF estimates for immunization coverage ["} +{"text": "A 69-year-old man, native of metlaoui in Tunisia, presented to the Department of Rheumatology at our institution with 10 years of non-inflammatory rachialgia with polyarthralgia. On examination, the patient had no fever or joint swelling, his teeth had brown strains and rough, there was diffuse tenderness at the cervical and lumbar spine and neurological examination was normal. Standard radiographs revealed diffuse bone condensation involving all vertebrae of the cervical, dorsal (A) and lumbar (B) spine, the skull (C), the pelvis (D) and the limbs. The origin of the patient, the brownish color of the teeth and the radiological appearance led to suspicion of fluoride poisoning, which was confirmed by the very high blood fluoride and urine dosage. Skeletal fluorosis is a rare toxic osteopathy characterized by massive bone fixation of fluoride. Its origin is dominated in the countries of North Africa by hydro-telluric poisoning. Its severity lies in the development of skeletal deformities and neurological complications. Management of fluorosis generally focuses on symptom treatment."} +{"text": "Amine oxidases (AOs) are ubiquitous enzymes involved in the metabolism of biogenic amines. Copper AOs (Cu-AOs) catalyze the oxidative deamination of primary amine groups of several biogenic amines, such as putrescine, cadaverine, and histamine. In the present review, the effects of a plant amine oxidase purified from pea seedlings in the modulation of IgE-mediated allergic reactions, and in the prevention of cardiac and splachnic postischemic reperfusion damage are reported."} +{"text": "In the Author Contributions section, Omri Tal (OT) should also be listed under Wrote the paper, Wrote the Appendix and performed and analyzed the simulations, and Revision of manuscript.The legend of"} +{"text": "A global initiative on sharing avian flu data\u2019 (GISAID) [Ten years ago, a correspondence ,2, signe(GISAID) , leading(GISAID) . Its conIn 2006, the reluctance of data sharing, in particular of avian H5N1 influenza viruses, created an emergency bringing into focus certain limitations and inequities, such that the World Health Organization (WHO)\u2019s Global Influenza Surveillance Network . This daA unique collaboration ensued, involving, in addition to members of WHO\u2019s GISRS and OIE/FAO reference laboratories, the wider influenza research community along with officials in governmental institutions and non-governmental organisations. Facilitated by a well-connected broadcast executive with background in licensing of intellectual property, an agreement was drawn up on the sharing of genetic data to meet emergency situations, without infringing intellectual property rights - the GISAID Database Access Agreement (DAA). The DAA governs each individual\u2019s access to and their use of data in GISAID\u2019s EpiFlu database . It was The essential features of the DAA encourage sharing of data by securing the provider\u2019s ownership of the data, requiring acknowledgement of those providing the samples and producing the data, while placing no restriction on the use of the data by registered users adhering to the DAA. It essentially defines a code of conduct between providers and users of data, cementing mutual respect for their respective complementary contributions, and upholding the collaborative ethos of WHO\u2019s GISRS, initially established 65 years ago this year [Launched in 2008, the EpiFlu database was of key importance in the response to the 2009 influenza A(H1N1) pandemic, allowing countries to readily follow the evolution of the new virus as it spread globally . AcceptaGISAID provides the data-sharing platform particularly used by GISRS, through which sequence data considered by the WHO CCs in selecting viruses recommended for inclusion in seasonal and pre-pandemic vaccines are shared openly and on which research scientists, public and animal health officials and the pharmaceutical industry depend. Such openness of the most up-to-date data assists in an understanding of and enhances the credibility of the WHO recommendations for the composition of these seasonal and potential-pandemic vaccines.Furthermore, in promoting the prompt sharing of data from potential pandemic zoonotic virus infections, as well as from seasonal influenza viruses, GISAID ensures a key tenet of the WHO Pandemic Influenza Preparedness (PIP) Framework , highligTraditional public-domain archives such as GenBank, where sharing and use of data takes place anonymously, fulfil a need for an archive of largely published data; however, that conventional method of data exchange notably has not been successful in encouraging rapid sharing of important data in epidemic or pandemic situations, such as those caused by Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola viruses. While the GISAID EpiFlu database is hosted and its sustainability ensured through the commitment of the Federal Republic of Germany , the estThat GISAID has become accepted as a pragmatic means of meeting the needs of the influenza community in part reflects the particular characteristics of influenza and the continual need for year-round monitoring of the viruses circulating worldwide, essential for the biannual vaccine recommendations and assessment of the risk posed by frequent zoonotic infections by animal influenza viruses . In the Given the crucial importance of genetic data in improving our understanding of the progress of an emergent, potentially devastating epidemic, the effectiveness of GISAID in influenza pandemic preparedness is self-evident and provides important lessons for future pandemic threats. While the genetic makeup and the necessary associated data of the different viruses are distinct requiring separate databases/compartments for unambiguous analysis, the modi operandi for sharing genetic data are generic and the GISAID mechanism could be applied to other emerging pathogens. Indeed, the wider implementation of such a data sharing mechanism should be key in concerted efforts to contain spread of disease in animals and threats to human health, in realising the concept of One Health."} +{"text": "Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested and deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. We review the neurocircuitry and up-to-date clinical concepts which are behind the use of DBS in posttraumatic stress disorder (PTSD). The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. DBS for PTSD is in its preliminary phases and likely to provide hope for patients with medical refractory PTSD following the results of randomized controlled studies. In the Diagnostic and Statistical Manual of Mental Disorder\u2013V (DSM-V) post-traumatic stress disorder (PTSD) is described not only as a feeling of fear and helplessness, as it was classified in the DSM-III, but also as a disorder including negative cognitions, negative emotional states, and reactivity symptoms . VictimsThe anatomical structures involved in the neurocircuitry of fear conditioning are amygdala, prefrontal cortex, and hippocampus. Basolateral complex (BLA) of amygdala, consisting of the lateral nucleus (LA), the basal nucleus (BA), and the accessory basal nucleus, is the main receiver of the sensory afferences coming from two sources: the thalamus sensory nuclei and the primary sensory areas of the cerebral cortex. For many types of emotions, and especially for fear, the amygdala is of great importance, and valuable information retransmitted through this path reaches the amygdala more rapidly than sensory information retransmitted by the cortex. For example, lesions of the basolateral complex abolish classic fear conditioning . Other nPharmacotherapy, based on paroxetine, sertraline, fluoxetine, risperidone, topiramate, and venlafaxine, associated with psychotherapy can be effective in PTSD ; howeverLangevin et al. demonstrated a therapeutic response and a decrease of amygdala hyperactivity after DBS stimulation of the BLA complex in PTSD model rats using 4 h/die stimulation with 160 Hz, 120 \u03bcs and 2.5 Volts in monopolar configuration ,26. DeveThe effects of ventral striatum (VS) DBS have been tested in a rodent PTSD model. DBS of the VS (the VC/VS homolog in rats) during extinction training allowed reduction of fear expression and strength of extinction memory; stimulation of dorso-medial VS, just above the anterior commissure, allowed facilitation of extinction while stimulation of more ventro-lateral sites in VS impaired extinction .Disruptions of fear extinction-related potentiation of synaptic efficacy in the connection between the hippocampus (HPC) and the medial prefrontal cortex (mPFC) have been shown to impair the recall of memory extinction in rats. Moreover, low-frequency hippocampal stimulation delivered after extinction impaired the extinction learning and the development of hippocampal-PFC plasticity . Medial Treatment-resistant PTSD is an important mental health issue in terms of the number of people affected and morbidity and functional impairment associated with the disorder.Neuroimaging studies in humans support the hypothesis of the involvement of limbic regions in the pathophysiology of the disorder. The application of DBS for PTSD is still strictly investigational and animal models suggest that stimulation of the amygdala, ventral striatum, hippocampus, and prefrontal cortex may be effective in fear extinction and anxiety-like behavior. The limited data from humans support the potential safety and effectiveness of high frequency DBS of the basolateral amygdala (BLA) in treating PTSD.Optimal targets and stimulation parameters, greater knowledge of the action mechanisms, and established criteria of inclusion/exclusion need to be characterized prior to the launch of multidisciplinary larger scale studies, always keeping in mind the risks associated with the surgical procedure and long-term neurostimulation."} +{"text": "A 35-year-old man of Tunisian origin complained of inflammatory arthralgia and he had noticed a progressive enlargement of his hands and feet as well as facial furrowing. On examination, he had thickening of the skin of the head and distal extremities and deep folds and furrows of the skin of the forehead (A), digital clubbing of fingers (B) and toes (C), spadelike enlargement of the hands and feet, hyperhidrosis of the hands and feet and seborrhea. Inflammation tests were disturbed. Radiographs showed periostosis of the long bones (D) and sacro-iliac osteosclerosis. After excluding secondary causes, primary hypertrophic osteoarthropathy also called pachydermoperiostosis (PDP) was established. This disease is characterised by thickening of the skin of the head and distal extremities, deep folds and furrows of the skin of the forehead, cheeks, and scalp, seborrhea; hyperhidrosis; periostosis of the long bones and digital clubbing. The treatment consisted in our case of analgesics and NSAIDs."} +{"text": "A 45-year-old man presented with low back pain evolving since 8 years associated sometimes with a radicular radiation. The clinical examination found a patient in good general condition, a loss of the lumbar lordosis, an exaggeration of the dorsal kyphosis with stiffness of the lumbar spine. The cutaneous-mucosal examination showed a brownish appearance of the ears, conjunctiva, and lower eyelids. In biology there was neither inflammatory syndrome nor perturbation of the phosphocalcic balance. The standard radiographs of the lumbar spine (A) and dorsal spine (B) revealed multiple disc calcifications associated with large staggered disc clumps and discal empty images. Due to mucocutaneous signs, normality of biology and the radiological aspect, the diagnosis of ochronosis was suspected and confirmed by the test of blackening of the urine to the ambient air, the results of the cutaneous biopsy showed pigmented deposits yellow ocher and brownish in the dermis and the dosage of alkaptonuria. Symptomatic treatment resulted in moderate improvement. The family survey did not reveal any similar cases. Ochronosis or alkaptonuria is a rare autosomal recessive disorder of tyrosine metabolism. Deficiency of homogentisate 1,2 dioxygenase results in accumulation of oxidized homogentisic acid in the connective tissues of the skin, eyes and ears, musculoskeletal system, and cardiac valves, and in urolithiasis. Ochronosis is of late onset, responsible for the rachis of extended disc calcifications with maximum spinal fusion. It is the cause of degenerative arthropathy. Early diagnosis and screening of this disease are then of great interest, especially for genetic counseling."} +{"text": "Based oDiagnostic laboratories in Senegal operate within a three-tiered laboratory system: (1) district and peripheral health centre level laboratories; (2) regional level laboratories; and (3) central and hospital level laboratories . The orgThe Laboratory of Bacteriology and Virology (LBV) at Cheikh Anta Diop University (CADU), which is located at Le Dantec Hospital in the capital city, has been recognised by health authorities as the HIV National Reference laboratory since 1986. In partnership with the Ministry of Health and the National AIDS programme, LBV/CADU is responsible for evaluating and validating diagnostic testing technologies, and technologies for CD4 count, viral load and EID. Additionally, LBV/CADU ensures the supervision of other laboratories through a national external quality assessment (EQA) programme, through distribution of regular proficiency testing panels, collection of data for analysis, and follow-up and corrective actions in partnership with the Ministry of Health, the National Committee for the Control of AIDS and the Division for the Control of AIDS and Sexually Transmitted Diseases.At the central and reference laboratory level, the HIV viral load, EID, CD4-count monitoring and HIV-diagnosis capabilities of LBV/CADU are described in 7 and proficiency testing is one of the major components of a quality assurance programme. In Senegal, laboratory infrastructure is relatively well developed at the national and regional levels. However, issues such as inadequate infrastructure, shortage of qualified staff, lack of equipment, limited quality assurance and control procedures are frequently seen among district and peripheral health centre laboratories.Quality assurance is the backbone of quality laboratory performance9 LBV/CADU has been working recently with the US Centers for Disease Control and Prevention to strengthen laboratory systems in Africa and Senegal though the implementation of quality management systems. The LBV/CADU-hosted AFRIQUALAB has been created for that purpose. AFRIQUALAB aims to improve laboratory quality in Africa through regular organisation and distribution of proficiency testing panels across the African continent, including in francophone countries. AFRIQUALAB works in partnership with the US Centers for Disease Control and Prevention, Westat and One World Accuracy, a private Canadian-based organisation specialising in EQA. During 2015, there were 174 participating laboratories from 28 countries, of which eight laboratories were from Senegal. The proficiency testing organized by AFRIQUALAB is mostly free and focused on HIV-related proficiency testing panels, including HIV serology and flow cytometry. Through technology transfer from the US Centers for Disease Control and Prevention, the programme is also offering free EQA for EID using dried-blood specimens and for HIV viral load using dried-tube specimens. Currently, more than 60 laboratories are participating in this EQA sub-programme for EID using dried-blood specimens and for HIV viral load using dried-tube specimens in Africa, including eight laboratories in Senegal.The maintenance of a quality management system, including quality assurance, is crucial for having and providing good and reliable laboratory services.Additionally, AFRIQUALAB is also involved in an EQA programme focusing only on CD4 count technologies within Senegal, with the support of the National AIDS programme and the Public Health Agency of Canada, an international programme for quality assessment and standardisation for immunological measures relevant to HIV. AFRIQUALAB also offers other panels, such as haematology, biochemistry, hepatitis B and C and mycobacteria, to participating labs using a fee-based service structure. LBV/CADU has made major improvements to its own quality management system and has recently achieved International Organization for Standardization 15189 accreditation of its medical laboratories.Additionally, within Senegal and at the national level, the Ministry of Health has recently released a national strategic plan that will guide the quality management system across the medical laboratory services and system in the country.Laboratories participating in the EQA programme for HIV rapid testing and CD4 (including POC) received feedback and, based on their results, have implemented corrective actions, as needed, to improve the quality of services, and were encouraged to participate in a laboratory network for continuous improvement. These outcomes are positive steps toward the implementation of quality management systems.The feedback received from the EQA programme has been used as an opportunity for participating laboratories to be more vigilant in many aspects of their work; for example, with respect to the expiration date for reagents, implementation of corrective actions, and on-site training for staff. The quality assurance programme and the external quality control activities must be followed up by systems-strengthening activities, such as staff training at all levels. We found that there is a need for more communication between the National Reference Laboratories and the Bureau of Laboratories, located at the Ministry of Health, regarding the type of corrective actions and support to be provided from the central/national level to regional and peripheral laboratories. There is also a need to provide incentives such as certificates of participation or achievement to successfully performing labs.Currently, all 24 sites in-country with POC diagnostic technologies, including POC for CD4, are participating in an EQA programme organised by LBV. Since 2004, LBV, with the support of the national AIDS programme, has provided voluntary, free-of-charge EQA of HIV rapid testing to assess the performance of laboratories conducting HIV diagnostics in Dakar and other regions. Currently, the EQA programme for HIV rapid testing uses dried-tube specimens. The proficiency testing panels consist of four specimens distributed at ambient temperature to participants. The results from the participants are sent to the national reference laboratory via email or cell-phone text messaging.With regard to the 90-90-90 goals, the affordability of viral load testing and CD4 count measures is a key factor in plans to expand HIV laboratory services and scaling antiretroviral therapy across Senegal. The country will need to put in place an affordable and sustainable strategy to reinforce the capacity of the public laboratories as well as to advocate for a strong political commitment from the Ministry of Health and sponsors. In partnership with the National AIDS programme, LBV/CADU is planning to estimate the costing and to undertake a cost-effectiveness study of implementing a nationwide HIV POC testing system, for CD4 count and viral load testing. The costing for, and cost-effectiveness of, a related quality assurance programme will be also taken into account. A model of costing for HIV POC testing, including quality assurance activities is currently under review with the International Diagnostics Centre of the London School of Hygiene and Tropical Medicine."} +{"text": "Xishan Hao, CAE academician from NCRCC and Prof. Raju Kucherlapati, member of the National Academy of Science of the United States (US) from Harvard Medical School. As the conference chair, Prof. Hao, together with co-chair Prof. Kucherlapati, delivered a warm welcome speech. More than 300 people from all over the world attended this conference and 23 talks were presented at this meeting, focused on precision medicine in China. Then Prof. Ping Wang, President of Tianjin Medical University Cancer Institute and Hospital, and Zhaofeng Zhang, Director, Division of Biotechnology and Medicine, Department of Science and Technology for Social Development, Ministry of Science and Technology of China, also gave their brief remarks for welcome. The conference was preceded by a next-generation sequencing (NGS) and bioinformatics analysis workshop on Sept 22, covering topics from DNA/RNA extraction to sequencing data analysis. In this report, we provided a short introduction on the talks and briefly recapitulated each one of them referring to related publications whenever possible. At the end, we summarize this report with a few comments on the success of IConCPM.Cancer, as a global health issue, has been attracting increasing attention from scientists, medical professionals, as well as the general population. During the past several decades, many therapeutic approaches, including surgery, chemotherapy, radiotherapy and immunotherapy, have come into play for cancer treatment. Nonetheless, many of these treatments are not personalized according to the specific situation or genetic context of a particular patient. Nowadays, precision medicine, defined by President Obama as \u201cdelivering the right treatments at the right time\u2014every time\u2014to the right person\u201d, opens a new era of cancer research with the hope to provide personalized treatment for different patients. To foster the knowledge share and promote potential collaboration on cancer precision medicine domestically and internationally, the first International Conference on Cancer Precision Medicine (IConCPM) took place on September 22\u201324, 2016 in Tianjin, China. The conference was hosted by the National Clinical Research Center for Cancer (NCRCC), Chinese Anti-Cancer Association (CACA), China Medicinal Biotechnology Association (CMBA), Medical and Health Engineering Division of Chinese Academy of Engineering (CAE), Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, as well as the National Foundation of Cancer Research (NFCR). IConCPM was initiated by Prof. Hao overviewed the current status of cancer care and precision medicine projects in China, touching global burden of cancer, status of cancer prevention and control, precision medicine and clinical applications in cancer precision medicine. NCRCC, under his leadership, has been committed to establishing precision medicine research platform which includes cancer tissue bank, clinical trial unit, cancer molecular diagnosis, and bioinformatics core. This platform will offer risk prediction, early diagnosis, target therapy, prognosis evaluation, and drug development to help realize the power of precision medicine. Next, Prof. Webster Cavenee from the Ludwig Institute for Cancer Research emphasized in his talk the necessity of international cooperation in cancer clinical trials for precision medicine. One single traditional clinical trial would need hundreds to thousands of patients, but it may turn out impossible to recruit enough patients for certain diseases. Take the US as an example, there are simply not enough patients, say for glioblastoma (GBM), in the entire country to do more than an extremely small number of clinical trials, not even to mention stratification on the basis of ethnicity or other factors. In this context, GBM-AGILE was born to address these issues, which has to accrue needed numbers of patients for combination trials. The goals of GBM-AGILE are rapid and efficient testing of therapeutic agents and their combinations, as well as developing databases of clinical trials, biomarkers, and molecular data. This global platform will bring frontline trials to a consortium of countries, providing sufficient patients to stratify and test drug combinations. Afterward, Prof. Yixin Zeng from the Beijing Hospital focused his talk on molecular classification and personalized medicine. How does molecular classification lead to precision medicine? The answer is to find the right patients, give the right drug at the right timing. Prof. Zeng took the example of nasal pharyngeal cancer (NPC) to illustrate the importance of personalized prevention strategy and molecular classification, which mainly refers to immune markers including immune cell sub-typing, cytokines, major histocompatibility complex (MHC) I and II molecules, B7 family and immune-related inhibitors. He concluded that precision medicine, on the basis of molecular classification, will lead to future development of clinical practice and make modern medicine more cost-effective. In the following talk, Prof. Qimin Zhan from the Peking University Health Science Center introduced his research on genomic alterations of esophageal squamous cell carcinoma (ESCC) Zhan and his group identified 8 significantly-mutated genes in ESCC and mutations in the gene encoding family with sequence similarity 135 member B (FAM135B) are correlated with clinical characteristics. They also found miR-548k, a microRNA (miRNA) that was amplified and overexpressed in ESCC, possesses oncogenic characteristics in vivo and in vitro. In addition, genetic alterations are also revealed in genes encoding components of multiple pathways including Wnt pathway, Notch pathway, RTK-Ras, and Akt pathways. Their findings support the notion that cancer is now considered fundamentally as a disease of genomic alteration. After the four presentations, there was a panel discussion \u2013 Roles of technology, data and analytics in precision medicine. Dr. Lynda Chin from Institute for Health Transformation, University of Texas System and Dr. Peter Bahrs from IBM Watson Health Implementations Team co-chaired this section and discussed the roles of technology, cognitive analytics, and public\u2013private partnerships in precision medicine.In the morning session on Sept 23, three academicians from CAE or Chinese Academy of Sciences (CAS), China, and one member of the National Academy of Science, US, presented their work on precision medicine. Prof. Kucherlapati summarized the Precision Medicine Initiative of the US, featured by disease prevention, detection, and treatment through the precise manner. He also introduced the Moon Shots Program with the ultimate goal to end the threats of cancer. This program was launched by M. D. Anderson Cancer Center in 2012. On January 12, 2016, President Obama announced a Cancer Moonshot\u00a0initiative to accelerate cancer research, which aimed to make more therapies available to more patients and improve our ability to prevent cancer and detect it at an early stage. Next Qing Li, Director, Science and Development Centre, the National Health and Family Planning Commission of China, introduced the reform of science and technology program management system and the foundation of the several national-level projects. And in the end, he shared his view on the China Precision Medicine Initiative. Then Prof. Daniel Sulivan from the Moffitt Cancer Center presented their practice of the precision medicine in the Oncology Research Information Exchange Network (ORIEN), which is a network of several major cancer centers in the US, with ultimate goals to provide evidence for decision-making and clinical care. Following these talks was the immunotherapy and chimeric antigen receptor T-cell (CAR-T) session. First, Prof. Steven Burakoff from Mount Sinai School of Medicine presented their work of identifying hematopoietic progenitor kinase 1 (HPK1) as a novel immunotherapy target Renier J. Brentjens from the Memorial Sloan Kettering Cancer Center, who leads one of the first teams conducting CAR-T therapy in the world, introduced their latest clinical trials on several cancers with diverse modifications of the therapeutic cells Cheng Qian from the Third Military Medical University shared their clinical practice with modified dendritic cells (DCs) and CAR-T on several cancer types. Then Prof. Chunrong Tong from the Lu Daopei Hematology Oncology Center introduced their experience on utilization of anti-CD19 CAR-T cells for refractory/relapsed b acute lymphoblastic leukemia. Next as a collaborator of Prof. Tong, Prof. Hongsheng Zhang from the Tongji University School of Medicine presented their translational research and clinical application of CAR-T therapy. Prof. Weidong Han from the Chinese PLA General Hospital then summarized their clinical practice of CAR-T cell therapy on both hematologic cancer and solid tumor Zhong Li from the Second Military Medical University talked about his perspective on cancer immunotherapy. At last, Prof. Xiubao Ren from the Tianjin Medical University Cancer Institute and Hospital summarized the overall clinical progress of CAR-T cells in cancer treatment.In the afternoon session on the first day (Sept 23), 11 speakers were invited to share their insightful opinions or brilliant work. Prof. Ying Wang, Secretary General of CACA, and Dr. Michael Wang from NFCR both introduced the contribution of academic societies in precision medicine. In her presentation, Dr. Wang introduced CACA, the role of CACA in cancer prevention and control, as well as the role of CACA in cancer precision medicine. Then Prof. Bruce Johnson from the Harvard Medical School and Dana Farber Cancer Institute gave his presentation about the impact of genomic changes on precision medicine for lung cancer BRAF, are the most common genomic changes in lung cancer. The Lung Cancer Mutation Consortium (LCMC) is planning analyses on these genomic changes and will establish a virtual database that may help doctors and researchers determine the frequency of certain mutations and explore opportunities for clinical trial enrollment. Prof. Toshifumi Wakai from Niigata University next introduced the genomic sequencing for optimal cancer treatment in gastrointestinal cancer. He and his group demonstrated concordance of CancerPlex with whole-exome sequencing from the TCGA in identifying hypermutated samples and microsatellite instability in multiple cancer types, such as colorectal and gastric cancers. They also highlighted the clinical utility of CancerPlex in guiding treatment strategies with targeted therapy in solid tumors, thus demonstrating how to harness the power of NGS in actualizing precision medicine. Prof. Mu-Sheng Zeng from Sun Yat-sen University presented his work on advances of basic and translational study of NPC. They found that expression of B lymphoma Moloney murine leukemia virus insertion region 1 homolog (Bmi-1) or human telomerase reverse transcriptase (hTERT), and knockdown of p16 enabled immortalization of nasopharyngeal epithelial cells (NPECs). Sphere-like culture of Bmi-1 immortalized cells supported high efficiency of cell-free infection of Epstein\u2013Barr virus (EBV), an oncovirus for NPC. They also demonstrated that RNA binding motif protein 24 (RBM24) played a role in NPC by modulating the stability of miRNAs and long non-coding RNAs. In the next talk, Prof. Andreas Keller from Saarland University focused on miRNAs and cancer. They found that blood-borne miRNAs were stable and powerful biomarkers for early diagnosis and companion diagnostics in cancer that are currently pushed from research to clinics. He also cautioned the biases present when measuring microRNA expression from different sources or using different platforms. These issues should be well appreciated and taken into account for translation into clinical practice. After the talk, there was a panel discussion co-chaired by Prof. Qiang Li from Tianjin Medical University Cancer Institute and Hospital and Prof. Xiaoming Zou from EOC Pharma, discussing the target therapies and drug development in the era of precision medicine.In the morning of Sept 24, Dr. Tuan Ha-Ngoc from KEW and Tom Miller from Greybird Ventures, respectively. In the following session chaired by Prof. Keller and myself, Zhimin Yang from Center for Drug Evaluation, China Food and Drug Administration, talked about issues that should be considered for development and evaluation of oncology products in the perspective of precision medicine. She illustrated her viewpoint on the model evolution of oncology product development, precision medicine, development of clinical innovation products, as well as the considerations for development and evaluation under the new model for precision medicine. Prof. Yi Zhao from Institute of Precision Medicine, CAS reported his work on big data platform construction under the China Precision Medicine Initiative, aimed to build the most complete genetic library of the Chinese population. The conference ended with a panel discussion co-chaired by Prof. Hao and Prof. Kucherlapati. Featuring the future of precision medicine in China, participants provided their comments to questions including (1) what technologies are for precision medicine; (2) how these technologies can impact the patient treatment today; (3) how to identify the right patients for new trials; (4) who are going to pay; and (5) what China can benefit from the lessons learnt in precision medicine projects in the US.In the afternoon session on the second day (Sept 24), the meeting started with two panel discussions about genetic testing for cancer and investments in precision medicine in China which were chaired by The conference ended successfully and has received numerous positive feedbacks from the participants. The conference provided a perfect chance for overseas and domestic scientists and physicians to communicate and share their understanding and practice of the Precision Medicine. Meanwhile the conference provided a productive platform for elite from the related fields to collaborate from decision making to drug development and investment. Other than the informative talks and insightful discussion, the conference organizers also made kind arrangements in having slides in both English and Chinese simultaneously with the live interpretation, making sure smooth communication.Given the emerging need of precision medicine in China, the conference introduced overseas system and practice of precision medicine into China as examples. Involvement of people with diverse roles in precision medicine from doctors, researchers, policy makers, industrialists to investors altogether would help to find answers or address specific concerns for China as raised during the conference, and hopefully result in a wider and deeper collaboration among different parties along the whole process of precision medicine for cancer clinical care."} +{"text": "There are two key features in nanoparticle-based probes which are seldom found in traditional imaging probes: multimodality and multifunctionality. The use of, at least, two complementary imaging techniques like PET/MRI or MRI/Fluorescence and the possibility of incorporating several vectors on the surface and/or drugs expand the use of these probes. Furthermore, the properties of some nanoparticles can be used to create new imaging techniques, for example, the superparamagnetism of iron oxide nanoparticles for magnetic particle imaging.The combination of the size-dependent properties of nanomaterials with the noninvasive characterisation in molecular imaging is a powerful combination that is being successfully applied across disciplines. In the past ten years, we have witnessed the development of, literally, hundreds of nanoparticle-based probes for molecular imaging. All major imaging techniques have been enhanced by the use of nanoparticles, particularly magnetic resonance imaging (MRI), positron emission tomography (PET), and optical imaging. The use of iron oxide nanoparticles for TIn this issue, we have aimed to provide a platform for high-quality contributions on nanoparticles application to molecular imaging. Original papers and review articles focusing on the latest application of nanoparticle-based imaging probes were submitted. The topics treated include the application of iron oxides for MRI, for PET/MRI, and for drug delivery; new synthesis approaches to obtain magnetic nanoparticles-based contrast agents; polymeric nanoparticles for ultrasound imaging; new computed tomography (CT) contrast agents; and quantum dots for multiplex optical imaging. We received a total of 16 submissions, and after two rounds of rigorous review, 9 papers were accepted for publications in this special issue."} +{"text": "This mini-review covers the newly developed biosensoristic and chemosensoristic devices described in recent literature for detection of contaminants in both environmental and food real matrices. Current needs in environmental and food surveillance of contaminants require new simplified, sensitive systems, which are portable and allow for rapid and on-site monitoring and diagnostics. Here, we focus on optical and electrochemical bio/chemosensoristic devices as promising tools with interesting analytical features that can be potentially exploited for innovative on-site and real-time applications for diagnostics and monitoring of environmental and food matrices . In near future, suitably developed and implemented bio/chemosensoristic devices will be a new and modern technological solution for the identification of new quality and safety marker indexes as well as for a more proper and complete characterization of abovementioned environmental and food matrices. Integrated bio/chemosensoristic devices can also allow an \u201cholistic approach\u201d that may prove to be more suitable for diagnostics of environmental and food real matrices, where the copresence of more bioactive substances is frequent. Therefore, this approach can be focused on the determination of net effect (mixture effect) of bioactive substances present in real matrices. Over the last few years, the abiotic contaminants levels in the environmental compartments and food increased to the point where they can cause potential human health effects due to exposure to chemical toxic substances. In particular, the interactions between environment and food supply chain that mainly occur at primary production level can cause serious both short- and long-term detrimental effects on human health.Environmental and food safety remains a major global challenge, in particular in developing countries, where socioeconomic status predisposes a large share of the population to a direct environmental-origin contamination and/or consumption of contaminated food products.To minimize the negative and dramatic impacts of chemical toxic substances of anthropic origin on environmental and human health, several focused actions are needed. For instance, promoting a sustainable use of chemicals and agrochemicals ; the development of toxicovigilance practices and systems and moreAgainst this background, such critical issues have produced a great demand for simplified, sensitive, and rapid screening methods , 3, withOn-site, cost-effective sensoristic devices capable of routine, sensitive, and selective detection of a range of targeted contaminants present in the environment and foods can be employed, for instance, to overcome time limitations and to reduce costs of sample collection and transport to laboratories, thus providing benefits for a rapid diagnostics and early corrective actions.For on-site diagnostics and environmental/food monitoring purposes, the application of standard and traditional analytical techniques is in contrast with the current need of rapid, cheap, easy-to-use, and portable devices .For these purposes, chemosensoristic and biosensoristic devices (herein collectively referred to as bio/chemosensoristic devices) are promising tools with interesting analytical features, which can be potentially exploited for on-site real-time applications, diagnostics, and screening for both environmental and food matrices. Such devices could be employed, e.g., to overcome existing limitations in measurements currently used in environmental and agro-food fields. While those measurements are mainly focused on the independent analyses of various parameters and analytes, complexity of environmental and food matrices requires a new holistic-like approach .For instance, regarding nutritional and toxicology characterization of foods, a broader modern vision based on the concept of \u201cwhole food\u201d is taking off , 5. Enviwww.alert2015.it), aims at developing the BEST prototype for industrial-scale production. Another new interesting approach for innovative monitoring and diagnostics of the environment and the agro-food supply chain is provided by a recent patented physicochemical sensing device called SNOOP \u201cas a whole,\u201d integrated analyses of physical, chemical, and biological parameters through sensoristic devices could be more suitable. The multichannel platform BEST is a HACed SNOOP . SNOOP ian integrated receptor\u2013transducer device, which is capable of providing selective quantitative or semiquantitative analytical information using a biological recognition element) . In particular, biosensors or biosensoristic devices (element) hold proaminants , 11.A recent review on key research interests in the development of biosensors in South Africa has highlight a particular interest on the development of electrochemical biosensor due to low fabrication and analytical equipment costs, in particular, for pesticides and heavy metals detection. Other research areas include nanotechnology, identification and validation of biomarkers, and development of biorecognition agents (antibodies and aptamers) and new biosensor design approaches .In recent literature, enzymes \u201315 and wRegarding electrochemical devices, they possess unique features to address the challenges of field and on-site analytical chemistry: possibility of miniaturization and portability, sensitivity, selectivity, a wide linear range of detection, minimal power requirement, and cost-effective instrumentation. Voltammetry is one of the most widely used electroanalytical techniques for electrochemical detection in bio/chemosensoric devices . In fact, various voltammetric techniques possess intrinsic analytical advantages and features and included excellent sensitivity, rapid analysis times, and possibility of simultaneous determination of different analytes. In voltammetric pulse techniques, through different modulation of the applied potential, a higher speed of measurement and sensitivity (useful for determination of species at trace levels) can be achieved. In particular, differential pulse voltammetry and square-wave voltammetry have been extensively described in the recent literature for detection of various chemical contaminants in environmental samples , 30\u201335. The recent interest in optical biosensoristic devices for food analysis, with fluorescent, bioluminescent or chemiluminescent labels for detection, as well as the direct (label-free) detection , 55, is Actually, biosensoristic devices based on SPR are ideal platforms for the label-free detection of molecular monolayers as they allow for qualitative and quantitative multiplexing measurements of biomolecular interactions in real-time without requiring a labeling procedure in the framework of food safety , 58.Indeed, by using SPR-based immunosensors, one can obtain robust and quantitative results with narrow- or broad-spectrum specificity in relatively short time. In the case of milk, SPR circumvents the issues related to turbidity and protein fouling by measuring the refractive index modulation on the reverse side of the metal film where the biological selective element is immobilized , 59.Since late 90s, SPR biosensoristic devices have become the main tool for the study of biomolecular interactions in life science, with successful applications in the field of food safety .Although there are great advantages of the SPR technology, some disadvantages are evident: high cost of the readout instrumentation and a still high cost of the consumables (sensing chip and reagents) and large instrumentation footprint.In recent years, nanoplasmonics has shown a great potential in overcoming the technological/commercial limits of SPR and for The development of advanced photonic biosensoristic devices has to be brought beyond the state of the art of the point-of-care-diagnostic systems by the synergetic integration of the different technological building blocks with consequent improvement of the single-component outputs. Moreover, the introduction of outperforming light-excitation/detection scheme allows for unraveling the potentiality of the sensor in terms for disposability, reliability, miniaturization, and multiplexing while providing laboratory quality analysis .Within the current point-of-care diagnostic market, there is a limited number of systems that operate without the requirement for a dedicated desktop reader, and there are no quantitative, portable diagnostic platforms with multiple detection methods. The components from existing laboratory equipment are too bulky, fragile, and expensive and require too much mechanical integration to be consolidated into a point-of-care device .Miniaturization (from microelectrodes/nanosensors to microfluidic platforms) is an increasing trend as a response to these needs to develop new miniature and portable analytical devices for environmental and food monitoring and diagnostics.In this scenario, LOC devices have shown themselves to be highly effective for laboratory-based research, where their superior analytical performance has established them as efficient tools for complex tasks and a promising tools for a number of environmental monitoring applications, i.e., continuous surveillance of selected parameters and contaminant concentrations and for However, to date, they have not been well suited to point-of-care or in-the-field applications: although the chips themselves are cheap and small, they must generally be used in conjunction with bulky optical detectors, which are needed to identify or quantify the analytes or reagents present. Furthermore, most existing detectors are limited to analysis of a single analyte at a predetermined location on the chip. The lack of an integrated, multiplexing, and fast detection scheme is a major obstacle to the deployment of diagnostic devices in the field. This issue has prevented the development of more complex tests where rapid, kinetic, or multipoint analysis is required.Development of improved electrochemical and optical bio/chemosensoristic devices represents a technological challenge to broaden boundaries of field diagnostics and monitoring environmental and food samples. In particular, specific improved features of integration, portability , cheapness, simplification of experimental protocols (less time- and labor-demanding protocols), and development of efficient high-throughput approaches are required. Concerning LOC devices, fast detection scheme and the ability to monitor at multiple locations on the chip could ensure a high selectivity and sensitivity for the analyte of interest. All these devices could be employed for the identification of new quality and safety marker indexes in real matrices as well as for the determination of mixture effects of bioactive substances.All authors have made equal contributions in the writing and revising of this mini-review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The blood-brain barrier (BBB) is a complex network of microvasculature, comprised primarily of brain microvascular endothelial cells (BMECs), astrocytes, and pericytes, which regulates cellular, macromolecule, and metabolite passage between the peripheral circulation and the central nervous system (CNS). Damage to the BBB has been linked to neurocognitive deficits sustained in multiple diseases, including stroke, Alzheimer's Disease, and numerous infections, including human immunodeficiency virus type 1 (HIV-1) have not yet been reported in detail.Numerous in vitro and in vivo -7-(t-butyl)-pyrazolopyrimidine (PP2) in rats subjected to ischemic insult resulted in the rescue of ischemic BBB leakage exposed to vascular endothelial growth factor , and a C-terminus bearing the inhibiting tyrosine site (Y529) and thus generates nitric oxide (NO). This leads to an induction of the S-nitrosylation of c-Src, which then promotes the auto-phosphorylation of c-Src at the activating tyrosine (Y416), which further phosphorylates the NR2A subunit of NMDAR alter the repair of the BBB and whether the regulation of c-Src is at the center of this question is an open area of significant research to understanding the mechanisms that underlie HIV-1 neuropathogenesis and HAND , the National Institute of Drug Abuse , National Institute of Mental Health , Comprehensive NeuroAIDS Center (CNAC) , and under the Ruth L. Kirschstein National Research Service Award T32 MH079785 . The contents of the paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. MN was also supported by faculty development funds provided by the Department of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This study targets the lesser-known ingredients of smokeless tobacco products, i.e., the toxic metals, in Indian brands. The metals selected in the study included lead (Pb), cadmium (Cd), arsenic (As), copper (Cu), mercury (Hg), and selenium (Se). The differential pulse anodic stripping voltammetry (DPASV) technique was used for estimating the metals Pb, Cd, and Cu; square wave voltammetry for As; and the cold vapor atomic absorption technique for Hg. The resulting levels of the metals were compared to the daily consumption of the smokeless tobacco products. It was observed that almost 30% of gutkha brand samples exceeded the permissible levels of metals Pb and Cu, when compared to the provisional tolerable intake limits determined by the FAO/WHO. The reliability of data was assured by analyzing standard reference materials."} +{"text": "Intrinsically Disordered Proteins (IDPs) lack a stable, three-dimensional structure under physiological conditions, yet they exhibitnumerous biological activities. Protean segments (ProSs) are the functional regions of intrinsically disordered proteins that undergodisorder-to-order transitions upon binding to their partners. Example ProSs collected from the intrinsically disordered proteins withextensive annotations and literature (IDEAL) database. The interface of protean segments (ProSs) is classified into core, rim, and support,and analyzed their secondary structure elements (SSEs) based on the relative accessible surface area (rASA). The amino acid compositionsand the relative solvent accessible surface areas (rASAs) of ProS secondary structural elements (SSEs) at the interface, core and rim werecompared to those of heterodimers. The average number of contacts of alpha helices and irregular residues was calculated for each ProSand heterodimer. Furthermore, the ProSs were classified into high and low efficient based on their average number of contacts at theinterface. The results indicate that the irregular structures of ProSs and heterodimers are significantly different. The rASA of irregularstructures in the monomeric state (rASAm) is large, leads to the formation of larger \u0394rASA and many contacts in ProSs. An intrinsically disordered protein (IDP) is a protein that isdisordered (as a whole or in part) in the unbound state andundergoes a disorder-to-order transition upon binding to theirpartners ,2,3. TheProtean segments (ProSs) are the functional regions of intrinsicallydisordered proteins that undergo disorder-to-order transitionsupon binding to their partners ,11,12. The goal of this work is to investigate the properties of secondarystructure elements (SSEs) at the interface of ProSs relative to thoseof heterodimers. The interfaces of ProSs and heterodimers were classified into the core, rim, and support based on their relativesolvent accessible surface area (rASA) . The aveAll ProSs (210) in 70 protein sequences were collected from theIDEAL database (as of August 2013) ,12. If mA non-redundant dataset of 276 heterodimers was selected from theProtein Data Bank (PDB) , using tThe program DSSP was usedThe propensities of amino acids are represented as the Chou\u2013Fasman parameters , CF were discarded from this classification. Several propertieswere analyzed for each high and low efficient ProSs (See Resultsand Discussion). The datasets contain 11 and 14 ProSs for high andlow efficient, respectively . The radWilcoxon rank-sum test was performed by RStudio to calcuThe secondary structure assignments for each of the ProS andheterodimer interface were determined by the DSSP program .This anThe amino acid propensities of the different secondary structureelements (SSEs) for ProSs vs.heterodimers were examined. The Chou\u2013Fasman parameters for alphThe core residues at the interface are the hydrophobic residues,generally in the central region of the interface, and play animportant role in the interaction. The rim residues are the polarresidues, located on the outer edges of the interface. The supportresidues represent the intersection between the interior and theinterface .Previous studies have been indicated that the ProS interface can bein contact with a larger number of residues of the interactionpartners compared with the heterodimer interface ,29. ToeOur previous study showed that the average \u0394rASA correlates wellwith the average number of contacts in ProSs . \u0394rASA oBased on the average number of contacts at the interface, the ProSswere classified into high and low efficient ProSs (See Methods). Toexamine the properties of high efficient ProSs, several factors, suchas average rASAm, average rASAc, average \u0394rASA, rate of theinterface, rate of the core, rate of the rim, radius of gyration (Rg), and length of the ProSs for each high and low efficient ProS wereanalyzed. Boxplots of the distributions of high and low efficientProSs are shown in The radius of gyration is used to describe the compactness of aprotein, as well as the folding process from the denatured state tothe native state ,31. The The properties of secondary structure elements (SSEs) at theinterface, core, and rim of ProSs were analyzed relative to those ofheterodimers. The results demonstrate that irregular structures ofProSs and heterodimers are significantly different. Irregularstructures have a larger rASA in the monomeric state (rASAm) thatleads to the formation of many contacts in ProSs."} +{"text": "As tick-borne diseases are on the rise, an international effort resulted in the sequence and assembly of the first genome of a tick vector. This result promotes research on comparative, functional and evolutionary genomics and the study of tick-host-pathogen interactions to improve human, animal and ecosystem health on a global scale. Ticks are obligate blood-feeding arthropod ectoparasites that are distributed worldwide and one of the most important vectors of pathogens affecting humans and animals and funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Annotation for this assembly was produced in a joint effort between JCVI and VectorBase (https://www.vectorbase.org/) with support from The Broad Institute (Gulia-Nuss et al., More recently, a global consortium of 93 scientists described the 2.1 Gbp nuclear genome of the black-legged tick, I. scapularis project proved challenging due to the large size and high repeat content of the genome. However, the results show the assembly and description of features associated with ~57% of the genome. As the only assembly available for a tick, the I. scapularis genome constitutes an invaluable reference for comparative genomic analyses, including resolution of phylogenetic relationships within the diverse phylum Arthropoda. Analysis of the I. scapularis genome revealed new features that may be unique to this organism and with important implications for future research. Highlights include the identification of two new repeat elements, a large-scale gene duplication event that likely occurred ~40 MYA coinciding with tick radiation, gene exon-intron structures more closely resembling that of an ancient protostome/deuterostome ancestor than of extant arthropods examined to date, an expansion of Kunitz domain proteins and other proteins implicated in tick blood feeding, possible remnants of a heme synthesis pathway contrasting with an expansion of heme carrier and storage proteins. Also identified were orthologs for at least 39 invertebrate neuropeptides and neuropeptide receptor genes that are believed or known to regulate tick diuresis, ecdysis, cuticle synthesis, blood feeding and reproduction. The genome contains one of the largest expansions of cytochrome P450 genes known for sequenced arthropods, suggesting potential for rapid development of acaricide resistance in ticks, and it will be important to explore the families of candidate acaricide targets uncovered by genome analyses, the de-orphanisation of which is underway.The I. scapularis genome sequence and annotation also contributed to the characterization of the transcriptome in related tick species such as I. ricinus (Genomic Resources Development Consortium et al., I. scapularis and other tick species, and extend genome analyses were described based on the publication of the I. scapularis genome sequence (e.g., Cabezas-Cruz et al., I. scapularis genome also provides a key reference for comparative genomics with other Parasitiformes like the western orchard predatory mite (Hoy et al., The first genome-wide population genomics study suggested genetic variation between ticks from Lyme prevalent northern and mid-western states compared with southern states in the U.S., paving the way for identification of genes tied to vector competence (Gulia-Nuss et al., I. scapularis genome sequence and assembly on these studies (Figure Anaplasma phagocytophilum, the causative agent of HGA (Ayll\u00f3n et al., A. phagocytophilum and the encephalitis-causing Langat virus (Grabowski et al., Recent results on the characterization of tick-host and tick-pathogen interactions highlighted the impact of s Figure . TranscrI. scapularis genome provide insights into parasitic processes unique to ticks, including host \u201cquesting,\u201d prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of hemoglobin digestion, heme detoxification, vitellogenesis, reproduction, oviposition, prolonged off-host survival and host-tick-pathogen interactions. The I. scapularis gene models will advance research on comparative and functional genomics, while the assembly and physical map will underpin much needed studies of tick genetics. Recent efforts addressed the need for additional tick genomic resources by focusing on tick species relevant for human and animal health (Guerrero et al., The features discovered in the All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.I. scapularis genome.The National Institutes of Health, the National Institute of Allergy and Infectious Diseases and the U.S. Department of Health and Human Services provided principle funding for the sequence and assembly of the The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The interdisciplinary studies between neuroscience and computer science have greatly promoted the development of these two fields. The achievements of these studies can help humans understand the essence of biological systems; provide computational platforms and intelligent methods for biological experiments; and improve the intelligence and performance of the algorithms in computer science.We present 10 papers in this research topic, which are mainly focused on neural mechanisms underlying the perception of vision, motor and pain; computational modeling of visual processing; bio-inspired visual models; and novel machine learning algorithms to reliably predict pain.As our dominant sense, the ultimate purpose of visual processing is to support us in perception, cognition, learning, and activities.Perry et al.) gives a brief review of alterations in visual processing near hand, which supports the hypothesis that there exist parallel, and separate, effector-based attentional systems. Whereas the oculomotor system enhances visual responses through gain modulation, and near-hand attention system sharpens features (such as orientation) relevant to reaching and grasping. This article provides a potential structure for visual-motor interaction modeling in bio-inspired imitation learning.One article on visual processing near hand. The authors analyzed the functions of neurons in VisNet model through a biologically plausible process of unsupervised competitive learning and self-organization both with realistic and natural images. The experiments showed that individual output cells of the network could develop single, localized, hand-centered receptive fields which are invariant to retinal location. Eguchi et al. modified VisNet to model the neural representation of object shape in the primate ventral visual system. By unsupervised visually-guided learning, the individual neurons show similar firing properties with V4 and TEO. The neurons in the higher layer of the network could learn to respond to localized boundary contour elements and show translation invariance across different retinal locations through the use of a trace learning rule.The work of Both of these two computational modeling methods simulate the principles and mechanisms of the visual pathway, and may inspire the future work in bio-inspired visual modeling for image processing applications.Li et al. proposed an enhanced HMAX model for image categorization. By mimicking the attention modulation, memory processing and feature encoding mechanisms of visual cognition, a bottom-up saliency map, an unsupervised iterative clustering method and multi-feature fusion method are introduced to the HMAX model. The enhanced bio-inspired model with small memory size showed better accuracy than other unsupervised feature learning methods in Caltech101 dataset. Fu et al. proposed an CNN model for feature construction in text analysis. By modifying the CNN model to adapt to the text inputs, introducing similarity of asker-answer information as attention modulation, and bringing in reputation information to imitate memory, the improved CNN model showed better performance in answer recommendation task.Galeazzi et al.; Eguchi et al.), these two bio-inspired visual models had excellent performance in public datasets focusing on computer science application, which shows that biological research can promote the development of computer science.Different from the computational modeling of visual processing . In addition, Li et al. investigated the effects of placebo analgesia on spontaneous brain oscillations during tonic muscle pain. They observed that placebo-induced decreases in the subjective pain perception significantly correlated with the increases of the amplitude of alpha oscillations, which suggested that alpha oscillations in frontal-central region could serve as the cortical indicator of placebo effect on tonic muscle pain . Finally, Peng and Tang provided a comprehensive summary of the functional properties of pain-induced modulations of ongoing cortical oscillations. In addition to the traditional methods, they proposed that novel approaches should be adopted to comprehensively explore the dynamics of oscillatory activities associated with pain perception and behavior. Based on these understandings, Peng and Tang pointed out the potential clinical applications of neurostimuation techniques and transcranial alternating current stimulation (tACS)) based on the modulation of pain-related cortical oscillations, which could help promote the establishment of rational therapeutic strategy in the framework of intelligent systems.Three articles provide recent advances to better understand the neural mechanism related to the central processing of pain perception. Bai et al. observed that pain-evoked EEG responses were significantly correlated with spontaneous EEG activities at interindividual level, and proposed a normalization approach to reduce the interindividual variability of pain-evoked EEG responses based on the spontaneous EEG activities for each subject. In addition, Bai et al. found that the relationship between pain-evoked EEG responses and pain perception was nonlinear, which inspired them to develop a novel two-stage pain prediction strategy, a binary classification of low-pain and high-pain trials followed by a continuous prediction of high-pain trials to significantly improve the prediction accuracy . From a different aspect, Tu et al. provided evidences showing that the joint use of both pre-stimulus ongoing and post-stimulus evoked EEG/fMRI activities could significantly improve the performance of pain prediction compared to using just post-stimulus evoked brain responses. Both studies shed new lights on the development of novel algorithms that could improve the prediction accuracy based on functional neuroimaging signals.Two articles in this Research Topic developed novel techniques to improve the performance of pain prediction based on non-invasive functional neuroimaging signals. Taken together, this research topic provides a series of work in the interdisciplinary studies of vision, motor and pain. The biological findings and models of the topic could inspired the future studies both in biology and computer science.HQ and LH are the organizers of the research topic \u201cEditorial: Modeling of Visual Cognition, Body Sense, Motor Control and Their Integrations.\u201d For this editorial, we discussed and built the outline together. HQ was in charge of Section 1, 2 and 3 and the figure. LH was in charge of Section 4, 5. Both of the authors commented on the manuscript.HQ was supported by the National Natural Science Foundation of China , the Beijing Municipal Science and Technology Commission , and the Strategic Priority Research Program of the CAS (No. XDB02080003). LH was supported by the National Natural Science Foundation of China and the Scientific Foundation project of Institute of Psychology, Chinese Academy of Sciences (No. Y6CX021008). The funders had no role in study design, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The environmental sources and behaviors of chlorinated 2- to 5-ring polycyclic aromatic hydrocarbons (ClPAHs). ClPAHs are ubiquitous contaminants found in urban air, vehicle exhaust gas, snow, tap water, and sediments. The concentrations of ClPAHs in each of these environments are generally higher than those of dioxins but markedly lower than the concentrations of the parent compounds, PAHs. Environmental data and emission sources analysis for ClPAHs reveal that the dominant process of generation is by reaction of PAHs with chlorine in pyrosynthesis. This secondary reaction process also occurs in aquatic environments. Certain ClPAHs show greater toxicity, such as mutagenicity and aryl hydrocarbon receptor activity, than their corresponding parent PAHs. Investigation of the sources and environmental behavior of ClPAHs is of great importance in the assessment of human health risks."} +{"text": "Overall Abstract: Alastair Campbell, talking from personal and family experience, and based on years of campaigning and study, urges a rethink of how we view mental health and mental illness."} +{"text": "In recent years, the incidence of severe infectious diseases has increased, and the number of emerging infectious diseases continues to increase. The Chinese government and military forces have paid a great deal of attention to infectious disease prevention and control, and using military-civilian cooperation, they have successfully prevented numerous severe epidemic situations, such as severe acute respiratory syndrome (SARS), influenza A (H1N1), avian influenza H5N1 and H7N9, and Ebola hemorrhagic fever, while actively maintained public health, economic development, and national construction. This paper focuses on the mechanisms of the military-cooperative emergency response to infectious diseases--the joint working mechanism, the information-sharing mechanism, the research collaboration mechanism, and the joint disposal mechanism--and presents a sorted summary of the practices and experiences of cooperative emergency responses to infectious diseases. In the future, the Chinese military and the civilian sector will further strengthen the cooperative joint command system and emergency rescue force and will reinforce their collaborative information-sharing platform and technical equipment system to further improve military-civilian collaborative emergency infectious diseases disposal, advance the level of infectious disease prevention and control, and maintain public health. In recent years, the prevalence of severe infectious disease has increased, and the number of emerging infectious diseases continues to increase . The ChiThe military-civilian collaborative emergency response to infectious diseases refers to the integration of military and government strengths and resources during a certain time period and range, according to the principles of unified command, resource sharing, and close cooperation, in order to solve and jointly respond to epidemic outbreaks of infectious diseases, minimize harm to human health, and maintain social stability .In 2004, the Chinese government disseminated \u201cthe Law of the PRC on the Prevention and Treatment of Infectious Diseases,\u201d which clearly defined many aspects of infectious diseases, such as epidemic reports, epidemic situation control, medical rescue, supervision and management, guarantee measures, and legal liability, among others; this law provides a legal basis for effectively preventing and eliminating infectious disease occurrence and prevalence and guarantees the health and hygienic safety of the public. The general principle of this law clearly stipulates that military prevention and control of infectious diseases should be consistent with the law and relevant national provisions . MoreoveUnder the unified leadership and overall deployment of the nation and the military, the collaborative emergency response mechanism of military-civilian integration and efficient linkage has been established, and it develops a pattern of complementary advantages and efficient collaboration as well as rapidly improves national and military infectious disease prevention and control \u201316. For The nation has established a joint working mechanism among different departments, and this mechanism indicates that each department is responsibility for itself, coordinates with the other departments, and jointly implements the prevention measures under central unified leadership. The military joint prevention and control came into effect by the unified leading, joint supervision, persevering management, and workforce formation of medical treatment, health, publicity, and rear service among multiple departments. The military and the civilian sector cooperated often and closely, establishing the joint working mechanism; for example, military experts were appointed to participate in leading expert groups for joint prevention and controlled response to emergency events and in the formulation of relevant policies, regulations, and professional documents. Meanwhile, the military\u2019s working progress was reflected over time, and the military-civilian coordination and communication mechanism was constructed.An epidemic information report and sharing mechanism has been established. Multiple tasks, such as information report development, joint notification and report release, and joint research on case diagnoses and epidemic announcements, are undertaken daily. The epidemic data from local disease control and prevention institutions are shared nationwide in a timely manner using similar procedures and the epidemic report channel, which establishes the collaborative surveillance and forewarning mechanism that discovers early epidemic outbreaks and provides strong technical support so that prompt and effective military-civilian control measures can be taken.Once an epidemic situation has occurred, the military immediately initiates the emergency research mechanism, sets up rapid research channels, and deploys emergency research tasks to scientific research institutions. In the meantime, the national and military disease control and prevention systems immediately integrate scientific research, organize scientific problem-solving measures, collaboratively establish research and development engineering projects, and jointly develop detection reagents and drug-resistant vaccines in response to outbreaks and the prevalence of infectious diseases. These actions can prevent and control epidemic situations.According to the national statement on epidemic information and the national strategy for prevention and control, epidemic prevention and control are jointly deployed at all military-civilian levels, the infection source and close contacts are traced over time, medical quarantine is carefully carried out, and personnel screening and medical observation are put into practice. Military experts and military disease control and prevention institutions at all levels, who are obligated to execute these plans due to national requirements, should actively participate, following the laboratory test index, outbreak investigation program, and clinical treatment standards. In addition, the military is also required to participate in the emergent disposal of local epidemic outbreaks; successful past experiences that resulted in preferable public effects can be attributed to the army.The government and the military have always attached great importance to infectious disease prevention and control. After the SARS epidemic, the country rapidly intensified construction of its public health system, effectively controlled the spread of several severe epidemic situations, and showed the strong capability of the military-civilian collaborative emergency response, relying heavily on the national military system. This was especially evident when the Ebola epidemic outbreaks occurred in West Africa in 2014; China was the first to lend a helping hand, sending approximately 1,200 military-civilian medical and health personnel to carry out laboratory tests, make diagnoses, provide treatment and public health training, and build a biological safety laboratory for the affected countries. This is the largest healthcare foreign-aid action of a military-civilian collaborative emergency response since the founding of new China . The maiThe primary principles of the military-civilian collaborative emergency response are unified command, graded responsibilities, and resident management. By establishing a unified national and military command organization, the comprehensive coordinative command of the military, police, and people was implemented; scientific and effective emergency decisions were made; institutional and functional orientations at all levels were defined; emergency power from all fields was motivated and coordinated for joint participation; unblocked government decree was ensured; and an advantageous configuration of resource integration was achieved.To effectively address severe epidemics, the government and military formulated several laws, regulations, policies, strategic development plans, joint action programs, emergency safety measures, and various types of operable emergency predetermined plans; clearly defined the division of duties and transactions; established an assessment mechanism for military-civilian joint epidemic situations and a docking mechanism for military-civilian relevant departments; and jointly improved the ability to respond to infectious disease emergencies.By using network and communication technologies, an information-sharing mechanism was established and characterized by directional coverage and frequent communication, and a military-civilian collaborative management platform for emergency rescue that can acquire real-time epidemic information, quick responses, and integrated linkage of emergency epidemic situations was built. After the Wenchuan earthquake in 2008, an epidemic reporting system was established based on the mobile network, which greatly improved the capability of the military-civilian collaborative emergency response.Military emergency prevention and control provides important support for not only the military itself but also national missions, such as emergency disposal during public health emergency events, major activity security, and major domestic and overseas disaster rescue. Since 2009, the Military Emergency Medical Rescue Team, the Emergency Epidemic Prevention Team, the anti-Nuclear, Chemical, and Biological (anti-NBC) Medical Field Rescue Team; and the Veterinary Health, Prevention and Control Team have all been included in the national emergency system, which can greatly enhance the capacities of military-civilian collaborative emergency rescue, prevention, and control.In recent years, the national health department has taken the lead and constructed multi-department cooperation, including a health emergency work mode for joint prevention and control that involves the military and coordinates the linkage and efficient decision-making across departments and regions . A serieAlthough the Chinese military-civilian emergency collaboration has accomplished certain achievements regarding prevention and control of infectious diseases, there are still many problems with the collaborative organization and command, professional power construction, equipment performance level, and emergency theory research, which can be solved by establishing a deep civil-military integration mechanism . ChineseThis paper focuses on the mechanisms of the military-cooperative emergency response to infectious diseases--the joint working mechanism, the information-sharing mechanism, the research collaboration mechanism, and the joint disposal mechanism--and presents a sorted summary of the practice and experience of the cooperative emergency response to infectious diseases. The Chinese military and the civilian sector will further strengthen the military-civilian collaborative joint command system and emergency rescue, reinforce the military-civilian collaborative information-sharing platform and technical equipment system, develop theoretical research on the military-civilian collaborative emergency response, enhance the training and modular exercises of the emergency teams, and strengthen the measures for epidemic information sharing, technical cooperation, disposal linkage, and integral prevention and control, which may further improve military-civilian collaborative emergency disposal, promote infectious disease prevention and control, and maintain public health."} +{"text": "This paper reviews the current research on the speciation and determination of mercury by various analytical techniques, including the atomic absorption spectrometry (AAS), voltammetry, inductively coupled plasma optical emission spectrometry (ICP-OES), ICP-mass spectrometry (MS), atomic fluorescence spectrometry (AFS), spectrophotometry, spectrofluorometry, and high performance liquid chromatography (HPLC). Approximately 96 research papers on the speciation and determination of mercury by various analytical instruments published in international journals since 2015 were reviewed. All analytical parameters, including the limits of detection, linearity range, quality assurance and control, applicability, and interfering ions, evaluated in the reviewed articles were tabulated. In this review, we found a lack of information in speciation studies of mercury in recent years. Another important conclusion from this review was that there were few studies regarding the concentration of mercury in the atmosphere. Mercury is the only metal that exists in a liquid state among the elements in our modern periodic table. Determination and speciation studies of mercury attract researchers because of the toxicity of mercury to humans, as well as to other animals in the food web. The difference between the toxicity of mercury and that of other metals is that mercury easily accumulates in organisms. A few studies have reported bioaccumulation of mercury in various aquatic animals, such as fishes, pelagic seabirds, and earthworms \u20139.This section describes the sources and fate of mercury in the environment and its toxicity.Mercury can enter the environment from natural and/or anthropogenic sources. Natural sources of mercury include volcanoes, forest fires, cinnabar (ore), and fossil fuels, such as coal and petroleum. Anthropogenic sources are numerous; a large number of human activities are responsible for mercury deposition in the environment. Anthropogenic sources of mercury are landfills, dental preparations, and combustion processes, such as coal-fired power generation, medicinal waste incinerators, and municipal waste combustion. Manufacture of metals, alkali, and cement also releases mercury into the environment . AnthropXu et al. revealedResearchers determine the concentration of mercury in environmental segments because of its toxic nature. Numerous journal articles have been published regarding the toxicity of mercury and its different forms. Yoshida et al. reportedPlants are exposed to mercury compounds through the administration of antifungal agents. The toxicity of mercury affects seed germination, growth, and development in higher plants. It also causes the breakdown of photosynthesis by affecting chlorophyll and magnesium molecules . MercuryIn this present study, we reviewed speciation and determination studies of mercury in different environmental samples using various analytical techniques, including the atomic absorption spectrometry (AAS), voltammetry, inductively coupled plasma optical emission spectrometry (ICP-OES), ICP-mass spectrometry (MS), atomic fluorescence spectrometry (AFS), spectrophotometry, spectrofluorometry, and high performance liquid chromatography (HPLC). Over 96 research papers published since 2015 in reputable international journals were reviewed. This review clearly summarizes the current research on speciation and determination studies of mercury from locations worldwide.The toxic nature of mercury and its different species encourage researchers to determine their concentrations in different environmental samples. Recently, a number of reviews were published concerning the determination of mercury, which described various factors regarding the concentrations of mercury in the environment. This section summarizes recent reviews of the determination of mercury.Hanna et al. reviewedColorimetric and visual assay determination of Hg(II) based on gold nanoparticles, fluorescent gold nanoparticles, gold nanorods, gold nanoflowers, and gold nanostars was reviewed by Chansuvarn et al. . They reJagtap and Maher reviewedIn recent years, a large number of research articles were published regarding the determination and speciation of mercury using various analytical techniques. We have divided this section into four parts based on the analytical techniques used in the determination of type and levels of mercury. They are (i) spectrometric techniques , (ii) electrochemical techniques (voltammetry and potentiometry), and (iii) miscellaneous techniques.The determination and speciation of mercury using spectrometric techniques, such as AAS, AFS, ICP-OES, ICP-MS, spectrophotometry, and spectrofluorometry are presented in Regarding the usage of analytical techniques in the determination studies of mercury, as presented in The analytical variables of merit, such as limits of detection and linearity, quality control and assurance studies, applicability to natural samples, and interference, are indicative of the validity of the method. Detection limit indicates the lowest level of analyte that can be detected using the method. A few studies \u201351 reporTwo very important analytical parameters, in the determination of mercury, are quality assurance (QA) and quality control (QC). The validity and reliability of the data produced by the researchers depend on the quantification of these variables. Quality assurance studies can be performed by testing the accuracy of the data obtained against standard reference materials (SRMs) provided by the National Institute of Standards and Technology or certified reference materials (CRMs) provided by various reputable institutes or organizations. Quality control can be determined by measuring the precision of the data (repeatability and sensitivity) obtained by each method. The precision of the data can be obtained in many ways, such as the analysis of replicates, interlab comparison of data, and relative standard deviation (RSD) of blank or standard material analysis . RegardiThe validity of analytical methods can be enhanced by applicability to natural samples. Regarding the analysis of natural samples, most of the reviewed papers analyzed water samples, such as those from rivers, lakes, seas, groundwater, and spiked water and wastewater. Following water samples, the most frequently analyzed material for mercury was seafood samples, such as fish, shrimp, and seaweed. A few studies reported the determination of mercury in various environmental samples, such as petroleum hydrocarbons , human hAnother important aspect of analytical parameters of the methods is interference. Interference of other ions in the determination of mercury levels is very important, particularly when those methods are applied to the analysis of natural samples. Natural samples are typically a complex of different ions; the selectivity of the method is very important in the determination of mercury in environmental samples. In this respect, electrochemical methods had a higher degree of selectivity and did not suffer from interference from other ions. Determination of the level of interference was not performed by a large number of authors , 102\u2013106Toxicity of mercury depends upon its chemical form. For example, methylmercury is more toxic than inorganic mercury. Speciation studies revealed the exact toxicity of mercury in environmental samples. However, very few authors , 92, 107The present study reviewed research articles published in recent years (2015-2016) involving determination and speciation of mercury using various analytical instruments. Approximately 100 research papers were reviewed and all the analytical parameters established in their studies were tabulated. Our study concluded that most of researchers used spectrometric instruments for the determination of mercury in different environmental samples. We addressed the quality of the data based on reported QA and QC data by the authors. Another important finding from this review was that most researchers measured inorganic mercury or total mercury, whereas only a few reported speciation of mercury. Speciation studies are very important in the accurate prediction of the toxicity of the mercury in the environment because mercury toxicity depends on its chemical form. Because of the difficulty in sampling and analysis, most researchers did not report the concentrations of mercury in the atmosphere. We conclude by stating that speciation studies and the determination of mercury in the atmosphere should receive greater attention in the future."} +{"text": "Crocus sativus L.) is a crop species cultivated for its flowers and, more specifically, for its red stigmas. The flower of crocus is bisexual and sterile, since crocus is a triploid species. Its perianth consists of six petaloid tepals: three tepals in whorl 1 and three tepals in whorl 2 . The androecium consists of three distinct stamens and the gynoecium consists of a single compound pistil with three carpels, a single three-branched style, and an inferior ovary. The dry form of the stigmas constitutes the commercial saffron used as a food additive, in the coloring industry, and in medicine. In order to uncover and understand the molecular mechanisms controlling flower development in cultivated crocus and its relative wild progenitor species, and characterize a number of crocus flower mutants, we have cloned and characterized different, full-length, cDNA sequences encoding MADS-box transcription factor proteins involved in flower formation.Crocus and its modification named familyRCA-RACE (famRCA-RACE). Furthermore, the characteristics of the protein structure and their common and specific domains for each type of MADS-box transcription factors in this lower nongrass monocot belonging to the Iridaceae family are described. Finally, a phylogenetic tree of all the MADS-box sequences available in our lab is presented and discussed in relation to other data from studies of species of the Iridaceae group and closely related families from an evolutionary perspective. The structural and phylogenetic analyses are based on both published and unpublished data."} +{"text": "Disturbances in cognitive function, particularly memory, are a common complaint of patients with epilepsy. Factors contributing to cognitive dysfunction are the type of epilepsy, type and frequency of seizures, anti-epileptic drugs and the location of underlying brain lesions. Whilst a great deal of attention has been paid to permanent cognitive impairment, the nature and underlying mechanisms of ictal and peri-ictal cognitive changes are poorly understood. In-depth investigation of seizure related cognitive dysfunction is of great clinical relevance, as these changes are potentially reversible and treatable, thus reducing the cumulative effect of frequent seizures Greater knowledge of peri-ictal and ictal cognitive dysfunction would improve seizure prediction, localization of seizure focus and assessment of treatment effectiveness, greatly reducing distress and disability. This paper will review current understanding of peri-ictal and ictal cognitive dysfunction and discuss future directions for research."} +{"text": "In the elderly, fear of falling (FoF) can lead to activity restriction and affect quality of life (QoL). Our aim was to identify the characteristics of FoF in Parkinson's disease and assess its impact on QoL. We assessed FoF in 130 patients with Parkinson\u2019s disease (PD) on scales measuring perceived self-efficacy in performing a range of activities (FES), perceived consequences of falling (CoF), and activity avoidance (SAFFE). A significant difference was found in FoF between PD patients who had previously fallen and those who had not and between frequent and infrequent fallers. Patient-rated disability significantly influenced FoF. Difficulty in rising from a chair, difficulty turning, start hesitation, festination, loss of balance, and shuffling were the specific mobility problems which were associated with greater FoF in PD. Disability was the main predictor of FoF, additionally depression predicted perceived consequences of falling, while anxiety predicted activity avoidance. The FoF measures explained 65% of the variance of QoL in PD, highlighting the clinical importance of FoF. These results have implications for the clinical management of FoF in PD."} +{"text": "Editorial on the Research TopicSecond Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological and Molecular Aspects of Novel Promising DrugsLazzari et al.; Sullivan and Planchard; Tran and Klempner; K\u00f6hler). In addition, the introduction of immunotherapy, with anti PD-1 Pembrolizumab, in first-line treatment of NSCLC represents the best choice for EGFR, ALK, and ROS1 wild-type patients expressing PD-L1 on \u226550% of neoplastic cells . Despite the survival improvement achieved with these new therapeutic options in first-line treatment, about 30% of patients do not obtain a tumor response . Moreover, those patients, initially sensitive to these treatments, acquire resistance and develop tumor progression. Approximately 60% of the patients progressing from first-line therapy receiving further systemic treatment in the second-line setting Also in second line, the armamentarium for the treatment of patients with NSCLC, includes a pletora of new drugs, such as immune checkpoint inhibitors , third generation tyrosine kinase inhibitors (Osimertinib) , and anti-angiogenic agents (Nintedanib and Ramucirumab) .The advent of precision medicine and predictive molecular pathology led to a revolution in clinical management of patients with non-small cell lung cancer. The discovery of oncogene addiction allowed the development of targeted therapies that represent newer therapeutic options reserved to those patients harboring specific gene alterations, such as EGFR mutations, ALK, and ROS1 translocations . Probably the right way is to give all the available opportunities to patients, but challenges and pitfalls should be carefully debated.This exciting therapeutic scenario for NSCLC patients still has unsolved questions and challenging issues, in particular regarding the optimal selection of the patient population through the individualization of the correct methodology and biological source of material (tissues vs liquid biopsy) for clinical relevant biomarkers assessment (Taken together, the papers published in Research Topic \u201cSecond Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological and Molecular Aspects of Novel Promising Drugs\u201d represent a critical discussion focused on the older therapies and the historical development of second line, putting into perspective the new agents available in clinical practice, defining their importance from a clinical point of view, but also to consider and exploit the complex molecular mechanisms responsible of their efficacy or of the subsequently observed resistance phenomena, to support the oncologist to design the best therapeutic strategies for NSCLC patients.UM and PP contributed equally to this paper.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies."} +{"text": "Ubiquitin (UB) is a small inactive peptide which dramatically changes the fate of ubiquitinated proteins when enzymatically activated and covalently attached to proteins in the process known as ubiquitination has been defined as a multifaceted network of cellular pathways that are activated after DNA damage . The group of Simone Sabbioneda discussed how UB and SUMO control DNA damage tolerance, the last line of defense that allows completion of DNA replication in the presence of an unrepaired template. They focused on post-replication repair, the mechanism cells use to bypass highly distorted templates caused by damaged bases . Jacqueline Jacobs (Netherlands Cancer Institute) and her group demonstrated that UB and SUMO play an essential role in both telomere maintenance and protection, but are also key contributors for the cellular response to dysfunctional telomeres . Besides the physiological role of the UB and SUMO pathways in DNA replication and telomere function, this issue also covers the majority of DNA repair pathways. Thus, Coleman and Huang (New York University School of Medicine) nicely summarized how SUMOylation plays a major role in fine-tuning of the Fanconi-Anemia Pathway, the main pathway for repairing DNA interstrand crosslinks. The group of Hanspeter Naegeli (University of Zurich) highlighted the essential importance of ubiquitination, SUMOylation but also Neddylation in the regulation of nucleotide excision repair, the main mechanism that protects us from UV-light . Smeenk and Mailand (University of Copenhagen) gave us comprehensive overview of UB and SUMO in the repair of DNA double strand break (DSB) repair, the most cytotoxic DNA lesion. Their work clearly demonstrates how ubiquitination and SUMOylation are highly sophisticated and complex PTMs in the DDR. Harding and Greenberg (University of Pennsylvania) presented an additional perspective on DSB repair, with a special focus on nuclear architecture, chromatin dynamics and chromatin organization in DSB repair and how UB and SUMO control and connect these processes. Himmels and Sartori (University of Zurich) went even deeper in the understanding of DSB repair and described how UB and SUMO regulate DNA-end resection, the initial step in DSB repair. Interestingly, they concluded that the UB pathway in DNA-end resection is mostly linked to protein degradation processes, where SUMO acts as an intermolecular \u201cglue\u201d in modulating protein-protein or protein-DNA interactions required for homologous recombination rather than specifically affecting the activity of individual proteins. Dantuma and Pfeiffer discussed how the E3-UB and E3-SUMO ligases are recruited to sites of DNA damage and the importance of the spatiotemporal relationship among different DNA repair proteins and PTMs. Pellegrino and Altmeyer (University of Zurich) nicely explained how the crosstalk between ubiqutination, SUMOylation and PARylation, another PTM that also forms a chain signal (PAR), regulate genome stability. Pinto-Fernandez and Kessler (University of Oxford) demonstrated the importance of inactivation of the ubiquitin signal in the DDR in their summary of how deubiquitinating enzymes counteract DDR-related ubiquitination. Beside the essential role of UB, SUMO and PAR in the spatiotemporal recruitment of different DNA replication and repair proteins at sites of DNA damage, the group of Thorsten Hoppe (University of Cologne) discussed how protein disassembly is equally as important as protein recruitment for genome stability . The disassembly of proteins from chromatin is mostly orchestrated by the ubiquitin-dependent AAA+ATPase p97/Cdc48, also known as VCP in humans, that serves as the unfoldase and segregase to remove ubiquitinated proteins described the involvement of the DDR in the G2/M-checkpoint and mitosis and how these two processes are regulated by PTMs. In addition to molecular mechanisms of UB and SUMO in DDR and genome stability, this issue also contains one technical article, which helps us to better understand how to quantitatively investigate UB and SUMO pathways in DDR. Heidelberger et al. described mass spectrometry-based approaches for quantitative analyses of site-specific protein ubiqutination in the context of the DDR.Helle Ulrich (Institute of Molecular Biology - Mainz) and her group highlighted that ubiquitination and SUMOylation control all aspects of DNA replication, from its initiation, elongation and termination, and not only translesion DNA synthesis as was initially proposed (By reading these outstanding articles one can easily conclude that all authors strongly emphasize the promising therapeutic potential that targeting two PTMs- ubiquitination and SUMOylation- as well as other components of the DDR, has for cancer therapy (Hoeller and Dikic, All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer PB declared a past co-authorship with one of the authors ID to the handling Editor."} +{"text": "Regarding American Psychiatric Association, Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in early childhood. The symptoms of ADHD include inattention, impulsivity, and hyperactivity. Such disorders lead to disruption in the educational, social and individual relationships areas and in other life aspects. Studies have highlighted the side effects of medications in the rehabilitation of individuals with ADHD and supported that many of children with ADHD despite pharmacological treatments experience cognitive dysfunctions ,2. In reThe goals of mHealth apps as one of the main subsets of e-health, are behavior change, education and diagnostic evaluations, collecting and reporting data, direct recording of health status, providing electronic decision supports, facilitating communication, planning and scheduling, alleviating the economic burden of diseases, enhancing the quality of health research and generally improving the effectiveness of healthcare services and health outcomes . mHealthThe interactive nature of mHealth apps along with their capability to be adapted and customized based on individuals\u2019 needs, leads in improving care, promoting rehabilitation and enhancing the quality of life."} +{"text": "Substance-using women who exchange sex for money, drugs or shelter as a means of basic subsistence have remained largely at the periphery of HIV and harm reduction policies and services across Canadian cities. This is notwithstanding global evidence of the multiple harms faced by this population, including high rates of violence and poverty, and enhanced vulnerabilities to HIV transmission among women who smoke or inject drugs. In response, a participatory-action research project was developed in partnership with a local sex work agency to examine the HIV-related vulnerabilities, barriers to accessing care, and impact of current prevention and harm reduction strategies among women in survival sex work. This paper provides a brief background of the health and drug-related harms among substance-using women in survival sex work, and outlines the development and methodology of a community-based HIV prevention research project partnership. In doing so, we discuss some of the strengths and challenges of community-based HIV prevention research, as well as some key ethical considerations, in the context of street-level sex work in an urban setting. Substance-using women working in open street-level sex work markets face a myriad of health risks, including pervasive violence and assault, high rates of poverty and homelessness, drug-related harms, stigma, and social isolation -3. MortaOf particular concern, women who exchange sex for money, drugs, shelter, or other commodities as a means of basic subsistence have been shown to face an elevated risk of HIV transmission , increasIn Vancouver, Canada, a city drug policy response, known as the Four Pillars strategy, and several innovative harm reduction efforts have been shown to be highly successful in reducing the harms of drug users, including primary and secondary prevention, extensive fixed and mobile syringe exchange programs, a heroin maintenance trial and two supervised injection facilities ,25. Yet In an effort to respond to existing gaps in prevention and policy, a community-based HIV prevention research project was developed to investigate the health-related harms, service barriers, and impact of current harm reduction and prevention strategies among women working in survival sex work in Vancouver, Canada. This paper outlines the development and methodology of the Maka Project Partnership, and discusses some of the strengths and challenges of community-based HIV prevention research, as well as ethical considerations, in the context of survival sex work in an urban setting.An initial gap in service access, HIV prevention and harm reduction for survival sex workers was identified as a key issue through informal conversations between health providers, staff, and sex workers at an inner city drop-in centre. In operation since 1987, Women's Information Safe Haven (WISH) Drop-In Centre Society connects with an estimated 200 women engaged in survival sex work per night. While the mandate is not exclusive to Aboriginal women, over half of the women that come through its doors are of First Nations, Metis and Inuit ancestry. The project works closely with WISH's well-established Aboriginal Health and Safety Project for Women in the Sex Trade (AHIP), as well as other key Aboriginal and sex work collaborators.In 2004, researchers were approached to collaborate on an initial needs assessment of women attending the drop-in. The results led to the conception and design of both a research and a service arm . The serA key component of the project is capacity-building among a team of women in survival sex work, supported by an open Community Advisory Board (CAB), that inform all stages of the project. Initial CAB tasks were to identify the working role of the CAB and develop a hiring process for peer team of women. The hiring process aimed to ensure a transparent process, including extensive and flexible options for informing and inviting women to contact the project and the creation of a community-peer hiring panel (CAB members). Through this process, a team of women with a lived experience of survival sex work were hired, trained and support to play an active role in guiding, developing and conducting the research. These positions are low-threshold employment positions that work from a harm reduction perspective, similar to models of other sex work and drug-user groups. There is considerable focus on capacity building and training, as well as ongoing support and referral for addictions counselling, drug treatment, supportive housing, and child care. Extensive training modules were conducted in collaboration with local community agencies and sex work groups, including sex work specific training created and conducted by PACE Society on lateral oppression, vicarious trauma, debriefing and conflict resolution; participatory-action research principles, methodologies, ethics, and informed consent; and health, HIV/HCV prevention, and harm reduction conducted by community health providers, sex work groups, and Aboriginal agencies.In keeping with community-based research principles, this project adopts multiple research methodologies, including ongoing qualitative focus group discussions, social mapping, and a prospective cohort (6 monthly interview questionnaires and HIV screening) over a three-year period. All focus group discussions are facilitated or co-facilitated by a member of the peer team and inform the 'lived experiences' of survival sex work and barriers to and facilitators for prevention and harm reduction efforts. Individual informed consent is obtained prior to the discussion group and verbal rather than written consent is provided at the time of the interview, due to participant concerns of confidentiality. Discussion groups last approximately two hours and all participants receive Can$25 compensation for their expertise and time.A particularly novel component of the project is the social mapping, a participatory-action research tool that facilitates community access to hidden populations and highlights local expertise. Initial piloting of the maps with over 60 women facilitated by the Maka peer team has informed subsequent recruitment and outreach efforts for both research and service arms of this project. In particular, women are provided with a map of Vancouver's Downtown Eastside and surrounding communities and asked to mark 1) strolls where they work and live; 2) current working conditions ; 3) high and low risk areas for violence and bad dates; 4) working areas impacted by police presence and harassment; 5) areas of health and syringe availability and disposal.Given the difficulty in accessing a representative sample of sex workers due to the illegal and clandestine nature of sex work and unknown boundaries of this population , mappingThrough time-space sampling, a total of 205 women were initially invited and agreed to participate in a baseline visit over a six month period in 2006 (response rate of 93%), with ongoing 6 monthly follow-up visits scheduled to continue through 2008. Baseline and follow-up include detailed interview questionnaires administered by the peer interviewers and HIV screening by the project nurse, supported by extensive pre and post-test counselling. Women 14 years of age and older who have used illicit substances (not including marijuana) within the last month and are actively engaged in street-level sex work are eligible to participate. Semi-structured interview questionnaires elicit responses related to current and past experiences of sex work, violence and trauma, health and addition service access, working conditions, and sexual and drug-related harms. HIV screening is completed by the project nurse using the INSTI rapid HIV test , and new reactive tests are confirmed by western blot. A pre-test counseling questionnaire is completed by the project nurse on detailed questions relating to overall health, experiences with HIV and Hepatitic C testing, and current and past abuse experiences in order to facilitate counselling and referral to support services. Participants receive Can$25 compensation at baseline and each follow-up visit.Sex work researchers have described some of the key ethical issues and challenges in conducting non-exploitative research in this population both in Canada and internationally ,35,38-40The concern of ensuring privacy and confidentiality of participants requires particular consideration in the sex work context, in addition to raising some key ethical issues related to HIV prevention research. Given the historically oppressive nature of research of sex work, significant concern from the onset by both the community partner and sex work activists was that the research did not further stigmatize a highly marginalized population of women, or falsely precipitate sex workers as \"vectors of disease\". A concern similarly voiced in other settings across the globe ,41. As sTwo key ethical issues emerged of important relevance in HIV related research with sex work populations. First, while HIV is a reportable illness using the standard ELISA test, the new rapid point of care test provides women with the opportunity to receive anonymous HIV screening. Women are advised during extensive pre-test counselling that the INSTI test is not a diagnostic test, and a reactive test needs to be confirmed by a western blot, as per standard of care. Women have the choice of being referred to a physician for follow-up testing, or completing the follow-up testing at the Maka Project office. Early findings suggest increased acceptability and utilization of point of care testing among a highly marginalised population of women, with 96% of women agreeing to HIV screening at first visit. Within this context, the role of HIV reportability and disclosure in survival sex work needs to be explored , particuSecondly, reporting of violence experienced by youth less than 18 years of age is a major limitation to research with legal minors , and hasConsistent with recent literature on public health partnerships , the CBRHowever, a particular challenge to the CBR process in this community has been the balancing of interests of academic and community partners, as well as survival sex workers themselves. Three sets of partners are represented in the research: a service agency for sex workers, survival sex workers, and the researchers. Emerging discussions in community-based HIV prevention research have focused on the challenges of defining a \"community\" in the CBR process . In healIn addition to the many strengths of ensuring active involvement of those currently involved in survival sex work for both sex workers and researchers ,39,49, tHigh rates of health and drug-related harms, including violence and victimization, persist among women in open street-level sex worker markets in cities across Canada, and globally ,28,50,51KS conceptualized the manuscript, wrote the original draft, and incorporated suggestions from authors into the final version of the manuscript. VB, SA, DA, KG and MWT were involved in conception of the methodology and provided critical feedback on content and revisions to the original draft. All authors read and approved the final version of the manuscript."} +{"text": "Work-hour limitations have been implemented by the Accreditation Council for Graduate Medical Education (ACGME) in July 2003 in order to minimize fatigue related medical adverse events. The effects of this regulation are still under intense debate. In this literature review, data of effects of limited work-hours on the quality of life, surgical education, and patient care was summarized, focusing on surgical subspecialities.Studies that assessed the effects of the work-hour regulation published following the implementation of ACGME guidelines (2003) were searched using PubMed database. The following search modules were selected: work-hours, 80-hour work week, quality of life, work satisfaction, surgical education, residency training, patient care, continuity of care. Publications were included if they were completed in the United States and covered the subject of our review. Manuscrips were analysed to identify authors, year of publication, type of study, number of participants, and the main outcomes.Twenty-one articles met the inclusion criteria. Studies demonstrate that the residents quality of life has improved. The effects on surgical education are still unclear due to inconsistency in studies. Furthermore, according to several objective studies there were no changes in mortality and morbidity following the implementation.Further studies are necessary addressing the effects of surgical education and studying the objective methods to assess the technical skill and procedural competence of surgeons. In addition, patient surveys analysing their satisfaction and concerns can contribute to recent discussion, as well. Resident work-hour restrictions have been implemented nationwide under the guidelines established by the Accreditation Council for Graduate Medical Education (ACGME) in July 2003 . The maiwork-hours, 80-hour work week, quality of life, work satisfaction, surgical education, residency training, patient care, continuity of care. Synonyms were used to find further relevant literature. In addition, we reviewed the references from the resulting publications to identify further potential articles to be included in our study.To identify the relevant publications, a Medline database search of articles published following the implementation of ACGME guidelines through PubMed was performed. Relevant studies were retrieved using the following sequences of key words: Studies were included that assessed the effects of work-hour limitations on residents quality of life, surgical education, and the quality and continuity of patient care, respectively. Publications were selected if they covered at least one subject of our review and were completed in United States. Review articles, textbook chapters, poster presentations, and abstracts were exluded from this study. Studies were eligible if they were prospective, retrospective, or descriptive.A total of twenty-one articles satisfied the inclusion and exclusion criteria for this analysis. We reviewed and summarized the findings published in the studies. Variables of interest included authors, year of publication, type of study, number of participants, and the main outcomes.Resident work hour regulations have been implemented in the State of New York during the 1980s . It was One publication reports emotional exhaustion and depersonalisation among most residents before and after introduction of work-hour reduction, whereas, important clinical activities such time spent in the operating room, clinic, and making rounds did not changes as well .In summary, almost all investigations have reported improved quality of life and work-related satisfaction in surgical residents. However, most authors agree that the working conditions cannot be improved by reducing work-hours only. It is concluded that due to limited work time, the work load should be distributed to colleagues or auxiliary staff (physician extenders).Surgery is a procedure \u2013 based specialty requiring the acquisition of technical skills and procedural competence. This experience depends on the variety of cases and case load during the residency. Several surveys have demonstrated improvements in theoretical surgical education with a significant increase of American Board of Surgery In-Training Examination (ABSITE) scores as a consequence of additional time for reading, more time for self preparation, and for conferences ,14,19,20Many clinicians argue that such work hour limitations adversely affect the training experience and report reduced quantity of operations, reduced consultations seen, and reduced conference attendance ,27,28. TIn summary, it is still controversial whether the restricted work hours negatively influence the surgical education and training. The new regulation reduces the duration of stay in the hospital and may lead to fewer opportunities to participate in operative cases. Thus, less experience may ensue for the surgeon in training. Further observations and objective evaluations of the surgical education can indicate whether the ACGME work-hour policy has adversely affected the clinical experience. Certainly, the estimation of ABSITE scores is an objective method to analyze the theoretical education of surgical residents. Unfortunately, the degree of surgical experience, procedural competence, and technical skills are difficult to assess. Therefore, it has been tried to use analyses of surgical adverse events, mortality, and morbidity to assess operative skills ,31-33.The ACGME work-hour regulation caused the development of shift models with multiple residents being responsible for a given patient . Thus, iAccording to several surveys, surgical residents are concerned about the negative impacts on patient continuity and quality of care. Otherwise, objective studies have demonstrated that the quality of care of surgical patients rather did not change following the implementation of the ACGME work-hour reform. Certainly, particularly the patient-resident relationship and previous patient focused attitude in treatment may suffer under the new regulation. Whether these changes also have an impact on patient satisfaction has yet to be determined. Surveys among patients are missing to date.To comply with the guidelines of the work-hour regulation, residency programs have to reduce or distribute the work-load that would have been completed by residents. Several benefits were reported after the incorporation of physician extenders (nurse practitioners or physician assistants) into the surgical service -45. StudOur review appears to support the following main findings: The new work-hour regulation improves the quality of life and work-related satisfaction especially in junior residents. In contrast, senior residents were less satisfied with the new reform. The effects on surgical education remain unclear due to inconsistency in studies, problems in assessment of the quality of the education and the quality of the surgeon's performance. Also, there appears to be no evidence whether the reduction of work-hours and the expected decrease of fatigue increased patient safety. Moreover, objective studies demonstrate no changes in mortality and morbidity following the implementation, although, residents perceptions regarding the quality of patient care were mostly negative. Finally, we observed a lack of patient surveys analysing patient satisfaction, quality and changes of care. This data could contribute to the recents debate. Moreover, further studies are necessary to analyse the effects on scientific research in teaching hospitals, to evaluate the changes of medical error and complication, and to assess the development of costs.The authors declare that they have no competing interests.All authors were involved in the research project and preparation of the manuscript. PHC: He made a substantial contribution to conception and design, and gave a critical and final approval. PR: He has collected the data and made an analysis and interpretation of these data. He also made a draft of the manuscript and revisions. All authors read and approved the final version of the manuscript."} +{"text": "Previous cross-sectional data suggest a positive association between serum cholesterol and brain neoplasms, but the results of cohort studies are inconclusive. There is evidence that in women the growth of meningiomas and astrocytomas depends on the hormonal status. The present investigation comprised data on serum cholesterol and beta-lipoprotein concentration among 229 participants in a health survey with subsequently diagnosed central nervous system (CNS) tumours. Data analyses included comparison of mean serum cholesterol and beta-lipoprotein level between cases and randomly selected controls--five for each case, matched for sex, age at screening and time of examination. The results showed a positive relation between the beta-lipoprotein level and the development of a CNS tumour in women under 50 years of age, and a negative association in those of older age with development of malignant tumours, which implies a possible influence of the menopausal status. Repeating the computations after excluding cases diagnosed within 5 years from screening revealed significant associations also between the serum cholesterol concentration and the development of a malignant CNS tumour, with a pattern similar to that of beta-lipoprotein. In conclusion, in women, irregular variation in the beta-lipoprotein level, which is involved in the synthesis of progesterone in the CNS, may enhance oncogenic transformation of astrocytes and meningeal cells; however, transformation of the latter is restricted to younger women."} +{"text": "Microarray data are often used for patient classification and gene selection. An appropriate tool for end users and biomedical researchers should combine user friendliness with statistical rigor, including carefully avoiding selection biases and allowing analysis of multiple solutions, together with access to additional functional information of selected genes. Methodologically, such a tool would be of greater use if it incorporates state-of-the-art computational approaches and makes source code available.. All source code is available from Bioinformatics.org or The Launchpad. The R package is also available from CRAN.We have developed GeneSrF, a web-based tool, and varSelRF, an R package, that implement, in the context of patient classification, a validated method for selecting very small sets of genes while preserving classification accuracy. Computation is parallelized, allowing to take advantage of multicore CPUs and clusters of workstations. Output includes bootstrapped estimates of prediction error rate, and assessments of the stability of the solutions. Clickable tables link to additional information for each gene , and output can be sent to PaLS for examination of PubMed references, GO terms, KEGG and and Reactome pathways characteristic of sets of genes selected for class prediction. The full source code is available, allowing to extend the software. The web-based application is available from varSelRF and GeneSrF implement a validated method for gene selection including bootstrap estimates of classification error rate. They are valuable tools for applied biomedical researchers, specially for exploratory work with microarray data. Because of the underlying technology used they are also of methodological interest to bioinformaticians and biostatisticians. Patient classification and gene selection related to classification are common uses of microarray data , but stFrom a users' perspective, an ideal tool should also be user friendly and provide additional resources to ease the interpretation of results . Web-basFinally, a tool that fulfills the above requirements is of much greater relevance if it makes its source code available under an open-source license. Source code availability allows the research community to experiment with, and improve upon, the method and fix bugs, encourages reproducible research, allows to verify claims by method developers, makes the international research community the owner of the tools needed to carry out its work and, thus, creates the conditions for swift progress upon previous work, concerns of particular importance in bioinformatics ,16.We have developed GeneSrF and varSelRF , that satisfy the above requirements. The only available web-based tools with similar scope are M@CBETH and PropThe core statistical functionality is provided by the varSelRF package for R . This paThe input for the web-based application are either plain text files, or files that come from other tools of the Asterias suite . GeneSrFThe parallelization has been implemented over bootstrap resamples. The speedups achieved by parallelizing are shown in Figure The scaling of user wall time of the R code (varSelRFBoot) with number of arrays and number of genes is shown in Figure The run time for the web-based application for a wide range of data sets is shown Figure Scripts for timing experiments are included with the source code (directory \"Benchmarks\").Our procedure is explicitly targeted to select very small sets of genes, and has been shown to have To avoid underestimating the error rate of the classification procedure, we use the bootstrap (the 0.632+ approach of ). As in Since we obtain 200 resamples in the process of bootstrapping (see above) there is little added computational cost to providing analysis of stability and multiplicity of solutions. We report the number of genes selected and the identity of the individual genes selected in the original sample and the 200 bootstrap runs, including frequencies of every gene selected in the solutions. Moreover, the biological interpretation of the results is enhanced by the access to additional information. If the input file contains gene identifiers for either human, mouse, or rat genomes , for each gene in the results, the web-based application provides a link to IDClight , which aFinally, GeneSrF is one of the very few tools for the analysis of gene expression data that uses parallelization and, as far as we know, the only web-based tool to use parallelization for gene selection and classification. This is an important methodological novelty, as we can no longer expect that increases in single-CPU speed will allow us to analyze larger data sets in shorter time: the rate of increase in CPU speed has slowed down considerably in the last five years but, in contrast, increasing numbers of CPU cores are becoming much more affordable ,14. ThusFuture work focuses on extending the software to use random forest-related techniques applicable to heterogeneous types of variables such as addition of categorical data and othevarSelRF and GeneSrF implement a validated method for gene selection and provide bootstrap estimates of classification error rate, take advantage of computing clusters and multicore processors, and encourage careful examination of the multiplicity of solutions problems. Thus, these are both useful tools for applied biomedical researchers using microarray and gene expression data, and represent unique methodological developments in the area of web-based gene expression analysis tools.For GeneSrF:Project name: GeneSrFProject home page: Operating system: Platform independent (web-based application)Programming language: R, PythonOther requirements: A web browser.License: None for usage. Web-based code: Affero GPL (open source).Any restrictions to use by non-academics: None.For varSelRF:Project name: varSelRFProject home page: Operating system: Linux, UnixProgramming language: R, PythonOther requirements: LAM/MPILicense: GNU GPLAny restrictions to use by non-academics: NoneCGI, Common Gateway Interface; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; LAM, Local Area Multicomputer; MPI, Message Passing Interface."} +{"text": "The experimental data providing evidence for the above roles of tryptase are summarized in the present review, as well as the effects of tryptase inhibition in animal asthma models. The potential strategies for the development of anti-asthmatic agents based on the inhibition of tryptase are discussed.Recent physiological and pharmacological studies have indicated the potential importance of tryptase, the major protein component in mast cells, in inflammatory diseases . Being released at inflammatory sites after the activation of mast cells, tryptase is capable of causing bronchohyperresponsiveness and infiltration of eosinophils, neutrophils, etc. in animal airways. The mechanisms by which tryptase causes bronchoconstriction involve probably the potentiation of other chemical mediators such as histamine, production of bradykinin via the hydrolysis of kininogen, and cleavage of the bronchodilating peptides VIP and PHM (peptide histidine-methionine). Tryptase has also been found to be a potent mitogen"} +{"text": "Manjeet Singh, the immediate Past President and Executive Member of the Indian Pharmacological Society passed away on 30th April 1946, Dr. Singh obtained BPharm, MSc (Pharmacology) and PhD from Punjab University, Chandigarh. He started his career in 1973 in the Department of Pharmaceutical Sciences at the University. He established a cardiovascular sciences laboratory in the department and was known for original basic research in ischemia reperfusion injury and oxidative stress. Dr. Singh joined Punjab University, Patiala in 1994, as Professor and Dean and established the Department of Pharmaceutical Sciences and Drug Research. During his stay, Dr Singh and his team of PhD students described the concept of resident mast cell in heart and its role in ischemia reperfusion injury. They also identified several other molecular targets for new drug development for cardio-protection. This research was very well recognized and a large number of awards were conferred on him such as: Fellow of International Academy of Cardiovascular Science, KG Nair Oration, Dr. OD Gulati Award, Achari Oration, PP Surya Kumari Award, Univas Prize, Achari Prize, NS Dhalla Oration and many more.Born in a small town of Punjab on 18Prof Singh's latest achievement was the establishment of a model private college of pharmacy (Indo-Soviet Friendship College of Pharmacy) at Moga, Punjab. This college has a unique establishment with \u201cstate-of-the-art\u201d research facilities not only in pharmacology but also other disciplines of pharmacy. Although this institute is in a small remote town in Punjab, it attracted a large number of experts as devoted faculty. In November 2008, a high profile scientific conference was also organized under his leadership.Our Society has lost a dynamic and enthusiastic member; the pharmacy community has lost an affectionate and popular teacher, the pharmacology especially cardiovascular fraternity has lost a proud researcher and prolific writer, who made significant and original contributions in the field of basic cardiovascular physiology and pharmacology."} +{"text": "Tumour-associated prostaglandin-like material, assessed by bioassay, has been examined in 37 patients with primary and metastatic squamous carcinomas of the head and neck, previously treated by radiotherapy and chemotherapy followed by radical surgery. High amounts of prostaglandin-like material were extracted from tumours excised within 3 months of radiotherapy and chemotherapy. These amounts correlated with necrosis, inflammation and fibrosis, but not with tumour site, size or degree of differentiation. Most of the prostaglandins formed by these treated tumours thus seem to be associated with host stromal and inflammatory cells, rather than the neoplastic cells. The possible roles of prostaglandins in facilitating the spread of squamous carcinomas are discussed."} +{"text": "The diagnosis of bronchus cardiacus accessorius dexter (BCAD) has occurred in 25 casesduring the bronchoscopic investigations of 30,000 adult patients of the authors. In most of thecases, this bronchial anomaly has been revealed as an accessory phenomenon, nevertheless, inone of the patients, it was the source of a considerable hemorrhage. In another case reportedhere in detail, it occurred together with multiple developmental anomalies, such astracheobronchomegaly, mitral valve prolapse, pectus excavatum, hypoplasy of sinus frontalison the right side, inguinal hernia on the left side and hyperlipidemia type IV. Familyanalysis did not confirm the presence of any chromosomal disorders or accumulation ofsimilar developmental anomalies. The forms and frequency of associations of the anomaliesare surveyed on the basis of literary data. The recognition of BCAD is of diagnosticimportance, since it may explain the persistence of some bronchopulmonary symptoms;furthermore, the exploration of the associated abnormal vascular branches may be very usefulin case of an eventual thoracic surgical intervention."} +{"text": "Africa is confronted by a heavy burden of communicable and non-communicable diseases. Cost-effective interventions that can prevent the disease burden exist but coverage is too low due to health systems weaknesses. This editorial reviews the challenges related to leadership and governance; health workforce; medical products, vaccines and technologies; information; financing; and services delivery. It also provides an overview of the orientations provided by the WHO Regional Committee for Africa for overcoming those challenges. It cautions that it might not be possible to adequately implement those orientations without a concerted fight against corruption, sustained domestic and external investment in social sectors, and enabling macroeconomic and political environment. Out of 58.03 million people who died globally in 2005, 10.9 million (18.8%) were from the WHO African Region [Firstly, there are serious leadership and governance challenges that include weak public health leadership and management ; inadequSecondly, extreme shortages of health workers exist in 57 countries of which 36 are in Africa . The criThirdly, there is rampant corruption in medical products and technologies procurement systems, unreliable supply systems, unaffordable prices, irrational use, wide variance in quality and safety . This haFourthly, there is a dearth of information and communications technology (ICT) and mass Internet connectivity, compounded by a paucity of ICT-related knowledge and skills limiting capacities of national health management information systems (HMIS) to generate, analyze and disseminate information for use in decision-making .Fifthly, health financing in the Region is characterized by low investment in health, lack of comprehensive health financing policies and strategic plans, extensive out-of-pocket payments, lack of social safety nets to protect the poor, weak financial management, inefficient resource use, and weak mechanisms for coordinating partner support .Finally, in terms of service delivery, the lack of effective organisation and management of health services combined with the above indicated challenges have in tandem led to the current situation where 47% of the population have no access to quality health services, 59% of pregnant women deliver babies without the assistance of skilled health personnel. In relation to water and sanitation which contribute to reducing burden of communicable diseases, 64% of the population lack sustainable access to improved sanitation facilities, and 42% lack sustainable access to an improved water source [Cognizant of the abovementioned challenges, the 46 Ministers of Health from the African Region adopted and signed the Ouagadougou Declaration that proSubsequently, the fifty-eighth WHO Regional Committee for Africa endorsed a framework for implementing the Ouagadougou Declaration . The fraFirstly, regarding leadership and governance, it proposes updating of national health policy and strategic plan; updating and enforcing public health laws; and strengthening mechanisms for transparency and accountability and intersectoral collaboration .Secondly, concerning HRH, it recommends generation and use of evidence in HRH policy development, planning and management; reinforcing health training institutions capacity; strengthening HRH leadership and management capacities; implementing HRH retention strategies; and increasing fiscal space for HRH development .Thirdly, with regard to medical products and technologies, it proposes development of formulae for determining the requirements and forecasting for medicines, commodities, essential technologies and infrastructure; and creation of a transparent and accountable procurement system .Fourthly, relating to health information and research, the Declaration on Primary Health Care and Health Systems suggests development and implementation of a comprehensive HMIS policy and strategic plan; and establishment of a functional national HMIS by leveraging ICT . In addiFifthly, pertaining to health financing, it recommends development of a comprehensive health financing policy and a strategic plan; institutionalization of national health accounts and efficiency monitoring; strengthening of financial management skills at all levels; allocation of at least 15% of the national budget to health development; implementation of the Paris Declaration on aid effectiveness; and develop social protection mechanisms .Finally, as regards service delivery, the Declaration proposes building on the elements of essential health services, mode of delivery and costs; development of norms, standards and procedures for service provision and health infrastructure construction and maintenance; formulation of integrated service delivery model at all levels including the referral system; development of mechanisms to involve all private health providers in provision of essential health services; development and implementation of multi-sectoral health promotion policies and strategies to optimize community involvement in health development .Effective public health interventions are available to curb the heavy disease burden in Africa. Unfortunately, health systems are too weak to efficiently and equitably deliver those interventions to people who need them, when and where needed. Fortunately, the health policy-makers know what actions ought to be implemented to strengthen health systems. However, it might not be possible to adequately implement those actions without a concerted and coordinated fight against corruption, sustained domestic and external investment in social sectors , and enabling macroeconomic and political environment.HMIS: Health management information systems; HRH: Human resources for health; ICT: Information and communications technology; PHC: Primary health care; WHO: World Health OrganizationThe authors declare that they have no competing interests.JMK and SPB contributed equally in drafting the editorial. All authors read and approved the final manuscript."} +{"text": "Diarrhoea was estimated to account for 18% of the estimated 10.6 million deaths of children aged less than five years annually in 2003. Two\u2014Africa and South-East Asia\u2014of the six regions of the World Health Organization accounted for approximately 40% and 31% of these deaths respectively, or almost three-quarters of the global annual deaths of children aged less than five years attributable to diarrhoea. Much of the effort to roll out low-osmolarity oral rehydration solution (ORS) and supplementation of zinc for the management of diarrhoea accordingly is being devoted to sub-Saharan Africa and to South and South-East Asia. A number of significant differences exist in diarrhoea-treatment behaviours and challenges of the public-health systems between Africa and Asia. The differences in rates of ORS use are the most common indicator of treatment of diarrhoea and vary dramatically by and within region and may significantly influence the roll-out strategy for zinc and low-osmolarity ORS. The prevalence of HIV/AIDS and the endemi-city of malaria also differ greatly between regions; both the diseases consume the attention and financial commitment of public-health programmes in regions where rates are high. This paper examined how these differences could affect the context for the introduction of zinc and low-osmolarity ORS at various levels, including the process of policy dialogue with local decision-makers, questions to be addressed in formative research, implementation approaches, and strategies for behaviour-change communication and training of health workers. Over a quarter-century has passed since the introduction of oral rehydration therapy (ORT) for diarrhoea in 1978 , while rIn May 2004, the WHO and United Nations Children's Fund (UNICEF) issued new recommendations for the management of all episodes of childhood diarrhoea, including new low-osmolarity oral rehydration salts (ORS) and supplementation of zinc for 10\u201314 days . When prZinc is an effective treatment for diarrhoea and resembles a modern pharmaceutical (tablets or syrup); therefore, zinc has the potential to reduce inappropriate use of antimicrobials for childhood diarrhoea through a replacement effect. Results of a community-based trial in Bangladesh showed that, in areas where zinc was introduced into the management of diarrhoea, inappropriate use of antibio-tics was significantly less than in control areas without zinc treatment . PrelimiThere are now calls for a sustained effort to roll-out zinc and the new formulation of ORS and to ensure that it is in the hands of low-income and marginalized populations who most need it ,15. SuchRates of ORS use for the management of diarrhoea vary greatly throughout sub-Saharan Africa and South Asia, reflecting regional variations in promotion and acceptance of ORS. High rates of incidence of HIV and malaria represent an added burden to already struggling health systems. This paper focuses on how these three factors\u2014(a) current childhood diarrhoea-management practices, (b) prevalence of HIV, and (c) endemicity of malaria\u2014affect the context of introduction of low-osmolarity ORS and supplementation of zinc at various levels: national policy, health programmes, health facilities, and households. We demonstrate that current rates of ORS use, HIV/AIDS, and malaria might affect the process of policy dialogue with local decision-makers, dictate questions to be addressed through formative research, and influence strategies for behaviour-change communication and training of health workers.For the purpose of this paper, countries in these two regions have been classified by rates of ORS use and rates of prevalence of HIV/AIDS and malaria Table . These cCountries in this first category are primarily francophone, in the Sahel region of West Africa, and have among the highest levels of under-five mortality in the entire world , low rates of ORS use (10\u201320%), high levels of malaria-related morbidity and morta-lity, relatively low but increasing prevalence of HIV, and relatively poor access to government health facilities. The 2003 Lancet child-survival series describes five profiles or patterns of under-five mortality in countries with high rates or contributing large numbers of under-five deaths . These cThis setting includes countries of southern Africa characterized by high ORS use, lower but still considerable under-five mortality , overall high prevalence of HIV (over 20%), and highly seasonal and focal transmission of malaria, resulting in a relatively low burden of malaria-related disease. These countries were assigned to Profile 5 in the 2003 Lancet series .Countries in this setting include nations of eastern and southern Africa, falling in Profile 4 of the 2003 Lancet series , with meThis category includes countries of South Asia corresponding to Profile 1 in the Lancet series , with meThe final setting is represented by parts of South Asia with lower but still considerable under-five mortality , high ORS use (over 60%), and a relatively small burden of disease attributable to HIV/AIDS and malaria ,17.ORS and ORT have been recommended for the treatment and prevention of dehydration since the late 1970s , while the highest levels were observed in Bangladesh, Viet Nam, The Philippines, and the smaller Indian States, such as Kerala, Manipur, and Goa. Factors contributing to lower levels of ORS-use in parts of South Asia include low levels of knowledge and awareness of ORS among some groups and poorWhere rates of ORS use are high, ORS sachets are generally widely available, affordable, or free of charge and theiThe availability of and access to ORS sachets vary greatly between regions and can have a significant impact on use-rates. In many Asian countries, ORS sachets are available through various channels, such as health facilities, general stores, and medicine shops , and popAcross southern Africa, ORS sachets tend to be readily available through both public and private channels, whereas in West Africa, ORS sachets are frequently available only at health facilities and pharmacies. These are few in number, making it difficult for people to access ORS, particularly in the rainy season. With the introduction of zinc and new ORS, strong advocacy should be carried out for policies which promote the increased access and availability of these products through private and community distribution channels. African countries also tend to not have as many local manufacturers of ORS as Asian countries do, therefore may only have one public-sector supplier and no private-sector ORS market. The adoption of the new formulation of ORS may be dependent upon the rate at which exporters of ORS adapt to the new formulation. In some cases, suppliers of ORS are producing both original and low-osmolarity ORS, but are only providing the new formulation when requested, thus leaving the choice of which formulation up to the procuring body.The epidemiology of malaria and HIV/AIDS differs greatly across the five settings, with rates of childhood malaria highest in Setting 1 and 3 and HIV/AIDS taking the greatest toll in Setting 2 and 3. The presence of these diseases can affect the receptiveness of a given setting to introduction of zinc and low-osmolarity ORS and the feasibility of attaining an adequate coverage with these interventions control programmes. Categorical programmes can weaken health systems by hiring already scarce personnel away from existing services into new categorical programmes, or offering specific courses, meetings, and other activities that take away from general patient care , althougComplex clinical presentations of diarrhoea among HIV-positive young children require greater skills to manage appropriately. Acute diarrhoea occurs more often in HIV-infected children, and episodes tend to be more severe and persistent ,36 and aAlthough there is little scientific evidence supporting biological interaction of malaria and diarrhoea -40, the Household structure: Thus far, pilot interventions introducing supplementation of zinc and low-osmolarity ORS have relied upon community education on management of diarrhoea to increase treatment-seeking from public and private sources and, hence, improve management of diarrhoea. In countries where prevalence rates of HIV are high, severe illness and death among young adults have led to an enormous increase in the number of households headed by parents incapacitated by illness, elderly caregivers, or older children the policy environment and policy-makers, (b) the supply chain for medications and other health-related commodities, (c) the availability of human resources in the health sector, (d) the quality of case management by health workers, and (e) home management of diarrhoea by parents Table .Considering only rates of ORS use, endemicity of malaria, and rates of prevalence of HIV, the most favourable context for the accelerated introduction of zinc and low-osmolarity ORS will be where current rates of ORS use are high, and the burden of disease attributable to HIV/AIDS and malaria is low. This situation is represented by Setting 5 in Table Setting 1 and 4, where rates of ORS use are the lowest, may present the greatest challenges to introduction of these new treatments. If the lowest rates are due to ORS being unavailable, efforts may be needed to both promote local manufacturing of zinc and ORS and ensure that these products are available through multiple public and private distribution channels. Although the burden of disease attributable to HIV is currently lower compared to other countries, these regions have difficulties in achieving high coverage with other critical public-health interventions. Thus, achieving coverage of zinc and low-osmolarity ORS may require additional technical assistance to overcome challenges. The francophone countries in Setting 1 are characterized by high levels of under-five mortality, weak health services, poor transport, and limited ability of governments to implement policies and provide services . Under tIn Setting 2 and 3, considerable progress has been made in strengthening health systems, and this is reflected in the high rates of ORS use and lower levels of under-five mortality compared to many other parts of Africa. HIV/AIDS threatens to reverse many of these gains and is a constant concern in the minds of policy-makers, health workers, and communities. In Setting 3, the challenge of HIV/AIDS is overlaid on the persistent high malaria-related burden of disease. In Setting 2 and 3, strong advocacy before policy-makers for investments to improve case management of diarrhoea is required. At the household and community levels, promotion of appropriate management of diarrhoea should be complemented by adequate care and support for orphans and other vulnerable children. As with Setting 1 and 4, we need to seek new ways of integrating ongoing efforts of new diarrhoea-management guidelines directed at HIV/AIDS and malaria through better training and supervision of health workers and other measures to improve quality of care.It is widely appreciated that national strategies to introduce zinc for the management of diarrhoea and new low-osmolarity formulation of ORS must be adapted through formative research to take into account local understandings of diarrhoea and home-management practices. What is less well-appreciated is the enormous impact the other public-health problems, such as malaria and HIV/AIDS, can have on the environment for the introduction of these new treatments, as summarized in Table This paper was written with support from the Zinc Task Force with funding from the Bill and Melinda Gates Foundation and support from the Office of Health, Infectious Diseases and Nutrition, Global Health Bureau, United States Agency for International Development (Award No. HRN-A-00-96-90006-00)."} +{"text": "Blood-transfusion services are vital to maternal health because haemorrhage and anaemia are major causes of maternal death in South Asia. Unfortunately, due to continued governmental negligence, blood-transfusion services in India are a highly-fragmented mix of competing independent and hospital-based blood-banks, serving the needs of urban populations. This paper aims to understand the existing systems of blood-transfusion services in India focusing on Maharashtra and Gujarat states. A mix of methodologies, including literature review (including government documents), analysis of management information system data, and interviews with key officials was used. Results of analysis showed that there are many managerial challenges in blood-transfusion services, which calls for strengthening the planning and monitoring of these services. Maharashtra provides a good model for improvement. Unless this is done, access to blood in rural areas may remain poor. Blood is a vital healthcare resource used in a broad range of hospital procedures, viz. accidents, emergency obstetric services, and other surgeries. It is also a potential vector for harmful, and sometimes fatal, infectious diseases, such as HIV, hepatitis B and C. Every year, millions of people are exposed to avoidable, life-threatening risks through the transfusion of unsafe blood. As per a global database, 6 million of 81 million units of blood collected annually in 178 countries are not screened for transfusion-transmissible infections ,4. AccesResults of a study of the circumstances for maternal deaths in Indonesia indicate that the lack of blood supplies and inability of some healthcare professionals to administer a transfusion contributed to deaths due to haemorrhage . SimilarIn India alone, according to a review of the Sample Registration Survey 1997-2003), postpartum haemorrhage accounts for nearly 38% of all maternal deaths 97-2003, , they arThis global scenario is evidenced from a statement by Director General of the World Health Organization made on the World Health Day 2000. He said, \u201cDespite all the technological marvels that humani-ty is experiencing, a reliable and safe blood supply is still out of the reach for untold millions of people around the world\u201d.To achieve Millennium Development Goal 5, access to effective EmOC, along with provision of professional care at birth, has been identified as vital for reduction in maternal mortality . In IndiThe primary responsibility for blood supply for blood-storage centres at the FRUs lies with the government/national health authority. Regional Blood Transfusion Centres (RBTCs), identified based on the amount of blood collected , carries out this responsibility. Licensing and monitoring of the blood-banks in India is the responsibility of the Drug Controller of India. The National Blood Transfusion Council (NBTC), established in accordance with the agreed national blood policy and within a legislative framework, has the major advisory role in the formulation of policy on safe blood-transfusion services in India. The National AIDS Control Society is responsible for collection of safe blood while providing financial assistance and State AIDS Control Societies (SACSs) in Maharashtra and Gujarat. The policy guidelines of the National AIDS Control Organization (NACO) have also been reviewed to understand the role of NACO vis-\u00e0-vis NBTC. We have compared blood-banking management in India with the framework proposed by the World Health Organization (WHO) . StatistThe Blood Safety Programme in India began to take shape in 1987 with the establishment of the NACO, a government organization to oversee. In 1992, the Drug Controller General, India, was vested with the power of Central License Approving Authority to approve licensing of notified drugs, viz. blood and blood products. During the same year, under the National AIDS Control Programme I , the NACO launched a scheme to modernize blood-banks by providing assistance to states to upgrade and provide minimum facilities to blood-banks in the public sector and those run by charitable organizations, such as Indian Red Cross Society. Under the NACP I, the NACO modernized 815 blood-banks (282 major blood-banks and 533 district-level blood-banks) and also set up 40 blood component separation facilities to promote the rational use of blood. . Nearly 90% of the blood-banks modernized through this scheme were in the government sector. Meanwhile, in 1996, as a result of a case\u2014Common Cause vs Union of India and others\u2014the Supreme Court of India passed an order directing the Government to improve blood-transfusion services. Consequently, the NBTC and SBTCs were created to develop policies and programmes for improving blood-transfusion services in India.The Blood Safety Programme initiated in the NACP I was considerably strengthened in the NACP II (1999-2004) with modernizing more blood-banks, establishing model blood-banks, and setting up blood-storage centres in rural areas. The Government of India adopted the National Blood Policy in 2002 which aimed at ensuring easy accessibility to and adequate supply of safe and quality blood and blood components collected from voluntary and non-remunerated blood donors. In India, different organizations play different roles in licensing, controlling, and regulating blood-banks. While the Drug Controller General is the licensing authority, the NACO and SACSs aim at preventing the transmission of HIV and ensure 100% screening of all collected blood units, providing training and financial assistance to blood-banks for technical modernization for ensuring the quality of blood-banks. The NBTC and SBTCs aim at ensuring safe and quality blood for transfusion services, promote voluntary and non-remunerated blood donors, follow up quality-control assurance programmes in blood-banks, and conduct training programmes. The Council collects funds by 100% tax-free donations.Despite a directive of the Supreme Court regarding formation and functioning of SBTCs, all SBTCs are functioning under the SACSs. Since the SACSs have many other responsibilities relating to AIDS control , blood sOver the years, a fragmented mix of competing independent and hospital-based blood-banks of different levels of sophistication, serving different types of hospitals and patients, have emerged. Besides the government blood-banks, there are blood-banks run by charitable trusts, independent commercially-oriented private organizations, and specific non-government health organizations, such as the Indian Red Cross Societies (IRCSs). The piecemeal evolution of blood-banking is linked to the burgeoning population and the expanding and poorly-regulated private healthcare market. Most blood-banks in public hospitals often operate with minimal infrastructure, lack of leadership, and resources; this has resulted in an inadequate/irregular supply of blood in the public system. .Blood-bank activities include recruitment and retention of donors; collection, testing, processing, and storage of blood; and clinical use of blood and blood components and training . Review Following the Supreme Court intervention, the State Government of Maharashtra established its Blood Transfusion Council in 1996 as an independent entity separate from the Maharashtra SACS. The SBTC has a full-time professional of the rank of Assistant Director, supported by a research officer, statistical assistant, and MIS (management information system) staff. It has an objective to coordinate the fragmented blood-supply system while providing adequate, safe, and affordable blood units and components. Given its autonomous status and administrative staff, the SBTC maintains good coordination with other blood-safety units in Maharashtra, such as SACS and international development agencies. It involves the entire health infrastructure, primary hospitals to tertiary hospitals, in blood-donation campaigns as each health facility is given an annual target for blood-donation camps.The organizational structure of the Maharashtra SBTC extends to the regional and district levels. Maharashtra has eight regional blood-transfusion officers and 34 district blood-transfusion officers. The Council has also established the following committees to improve various aspects of blood transfusion in the state: (a) Technical Committee, (b) Voluntary Blood-donation Committee, (c) Thalassaemia Committee, (d) Post-graduation Committee, and (e) Project Formulation Committee.Many other state governments, including Gujarat, established its SBTC as a part of SACS and appointed the Additional Director of SACS as head of SBTC. Thus, the SBTC is not an independent unit and works under the head of SACS. In Gujarat, the SBTC does not have any full-time professional and administrative staff. The Council is mainly composed of honourary members and is headed by the health secretary. As the members and chairperson have many other responsibilities, the meetings of the Council are not held regularly. Compared to Maharashtra, Gujarat lacks systematic organization of the blood-transfusion council.In India, there are 2,063 licensed blood-banks. A significant portion of blood-banking activity is carried out by voluntary (n=257) and private blood-banks (n=980). The total recorded blood collection in India is four million units, which meet only 40% of need against a least requirement of 10 million units . TherefGiven the overall negligence to blood-banking in India, it is not surprising that its quality control has not been seen as an essential part. A lack of quality-assurance measures, including manuals of standard operating procedures, appropriate training and competency certification programmes, and continuous assessment systems, often hinders the implementation of good laboratory and manufacturing practices. For example, in Gujarat, some stakeholders reported that different blood-banks use different testing procedures and testing standards which hinders the exchange of blood between blood-banks. This may lead to more wastage of blood.Under the Blood Bank Modernization scheme of NACO, till November 2006, the Government of India has provided support to modernize 883 district-level blood-banks and 255 major blood-banks and established 82 blood-component separation units in the country. Ten state-of-the-art blood-banks were also established . The MahMaharashtra conducts regular training programmes on various issues to strengthen the capacities of professionals engaged in blood-banking services. The training programmes cover the following:\u2022Modular training for all blood-bank personnel\u2022Training on hepatitis C, ELISA Reader maintenance and repair, biosafety measures for all zonal BTC Blood Transfusion Officers and Technicians\u2022Component preparation for Blood Transfusion Officers and Technicians\u2022Blood group serology for Blood Transfusion Officers and Technician at the Indian Council of Medical Research\u2022Genetic blood disorder detection for Blood Transfusion Officers and Technicians\u2022Training for Drug Inspectors\u2022Quality-management training\u2014Blood Transfusion Officers\u2022Transfusion and transplantation science\u2022Key Blood Transfusion Officers from medical colleges trained as key trainers to undertake training for technicians of the FRU.In Gujarat, training programmes for blood-bank personnel are offered for updating their skills and knowledge. The training programmes, usually offered once in three months in various regions of the State, usually address topics on necessity of safe blood, the rational use of blood, and clinical procedures.Recently, the Medical Council of India has approved a postgraduate course in blood-banking and immunology haematology/immunology haematology and blood transfusion. Presently, five medical colleges offer this postgraduate course in the states of Gujarat, Jammu and Kashmir, Maharashtra, Tamil Nadu, and Uttar Pradesh .th of every month, and feedback is given to the regional health officers by the 15th of every month. At the start of each year, monthly analysis of blood collection of the previous year is done to formulate strategies to compensate for the deficit in blood collection in a particular month. Maharashtra has also developed an excellent system of web-based monitoring of storage and availability of blood units and components of each blood group in every blood-bank in the state. This allows hospitals and blood-banks to request blood from neighbouring blood-banks where the needed group may be available. This ensures the most efficient use of available blood and minimizes wastage.Maharashtra maintains a reasonably good computerized management information system (MIS). Reports are compiled at the state level by the 5Gujarat, unfortunately, does not have a similar system. Hence, in the case of need, either blood-bank managers have to call the other blood-banks to check the availability or the relatives of the patient have to visit more than one blood-bank to procure required type of blood. For monitoring the blood-banks, the state maintains a regular database for all the reporting blood-banks. However, feedback is only occasionally provided to blood-banks by the GSACS.Blood is urgently required for saving women's lives in the case of massive postpartum or antepartum haemorrhage or severe anaemia. As the majority of blood-banks are located in urban areas, the availability of blood in rural areas is difficult. To address this lack of availability of blood in rural areas, the policy was changed in 2001, allowing the establishment of blood-storage units in rural regions. However, nothing much happened on this front as it was given low priority in the states. In 2005, the National Rural Health Mission dedicated a part of its funds for the establishment of blood-storage units at the FRUs. These blood-storage units will be attached to large regional blood-banks in urban areas for blood supply.In Maharashtra, 44 blood-storage centres are currently functional in the FRUs. By the end of March 2009, the target is to open 171 blood-storage units. By 2012, 400 blood-storage units will be functional in rural hospitals. Under a recent amendment (2006) of the Nursing Home Registration Act of Maharashtra, all nursing homes, clinics, and private hospitals should be affiliated with a licensed blood-bank for procurement of blood for patients admitted to their hospitals. Along with this, the state also requires blood-bank or storage facility within five km of any registered private abortion facility to ensure the availability of safe blood for transfusion services, if required . All regAll blood-banks and blood-storage centres have to maintain a record on blood collection and distribution in Maharashtra. All regional blood-banks supplying blood units to blood-storage centres record the information on the number of blood units supplied, blood group of the supplied blood units, and dates of issue and expiry. The storage centres and private hospitals/clinics also maintain information on similar indicators to avoid wastage of blood units, as unused blood units can be returned to the regional blood-bank before the date of expiry. However, it has been observed that the government centres discard units after the expiry as there is not much accountability relating to this. The institutions also maintain the records of distribution of blood units, with the name of the patient and hospital, blood group of the patient, and units of blood given. However, this information is not analyzed for management purpose in Maharashtra.The below poverty-line (BPL) population is entitled to receive blood and blood products free of charge from any government blood-bank or storage centre in Maharashtra. Individuals affected by thalassaemia, haemophilia, and sickle-cell anaemia also receive blood free of charge on their identity card. Approximately 40,000 units of blood are given to thalassaemia patients every year in Maharashtra. All voluntary donors of blood are also entitled to one free unit of blood on production of the voluntary blood donor card.The Gujarat State AIDS Control Society arranged a meeting to discuss the \u201cReorganization of blood-transfusion services and developing blood-storage centres at the FRUs\u201d at the end of 2005 to make safe blood available. Recent data on blood-storage units by the Government of Gujarat showed that 26 of the 39 functional blood-storage units in Gujarat are attached to the FRUs required in the state. The blood-storage units are located in the FRUs attached to charitable hospitals, community health centres, and district hospitals. All blood-storage centres are linked to the RBTCs for blood supply. The Government of Gujarat is also planning to recognize more blood-banks as RBTCs to strengthen blood supply in rural areas. Recently, the Gujarat State AIDS Control Society has initiated a free blood scheme for thalassaemia, haemophilia, and sickle-cell patients.By law, there is no charge for blood but blood-processing and testing cost is generally allowed. The charge for blood-transfusion service in the government blood-banks is only Rs 425 to any patient (approximately US$ 9.4). The cost in private blood-banks varies from centre to centre and is generally higher.While the Indian health sector has made some noteworthy achievements over the last 50 years, it has not responded satisfactorily enough to meet the national goals on blood-transfusion services as is witnessed by the substantial negligence to blood-banking services in the country. In India, blood transfusion relies on very fragmented blood-supply systems, where control is exercised by different layers of the Government, making it difficult to assure the quality of blood and blood products. Two parallel systems are in place to monitor the blood-safety programme in India\u2014NBTC/SBTC and NACO/SACS.Given the fact that there are a large number of Charitable Trusts and independent commercial and private blood-banks, the control of quality and coordination of all blood-banks to ensure easy access to blood and minimize wastage are a challenging task. This requires much more managerial capacity, skills, and resources within the State Blood Transfusion Councils. The promotion of postgraduate courses in blood-transfusion services will help in getting the trained and skilled human resource in the field of blood-banking. Given the lack of government resources in blood-transfusion services, there has been poor quality of service and periodic shortages of blood. Many blood-banks depend on philanthropic funding for their basic operations. The Government needs to increase its commitment towards improvement of blood-banking services and ensure that all needy patients get blood on time and free of charge for the BPL population.The existing MIS for blood-banking seems weak although it has been improved in Maharashtra. There is a lack of proper records on the use of blood in India. Due to this, it is not possible to estimate the need, supply, and unmet need for blood in obstetric emergency. Besides, the monitoring of the clinical use of blood and blood products is weak. No systematic analysis is done to measure adverse reactions following blood transfusion. Blood-banks also lack registering or monitoring of the total demand for blood and blood products (requests received) for each blood group that could not be met due to the non-availability of blood or blood products. They only record blood collected and used. They also do not report systematically the proportion of stored blood that expired due to non-use. Thus, substantial improvement in the MIS is needed.We find that, although the overall availability of blood is almost the same in both the states, the organization of blood-transfusion services is much better in Maharashtra as the Maharashtra Blood Transfusion Council is an independent unit with full-time staff under active leadership. Learning from this experience of Maharashtra, we recommend all the states to have independent and well-staffed blood councils. In Gujarat, the NGOs and the Indian Red Cross Societies are actively promoting voluntary donation of blood and, hence, per-capita collection in Gujarat is slightly better than in Maharashtra. Learning from Gujarat indicates the possibility of the dynamic role being played by the NGOs and IRCS in blood-banking.Ensuring a safe supply of blood and blood products and the appropriate and rational clinical use of blood are important public-health responsibilities of every national and state government, especially for saving lives of mothers who need comprehensive EmOC services because of pregnancy-related haemorrhage, severe anaemia, or abortions. The mechanism of availability of blood in rural areas is quite frail. There is a need for networking between urban blood-banks and rural blood-storage units. And as there is no special provision for timely blood supply for maternal emergencies in rural areas, it may not be possible to reduce maternal mortality due to haemorrhage, anaemia, and abortions. The use of blood components, at least in urban areas where facilities exist for storage of components, will also enhance supply of whole blood for rural areas.The authors acknowledge the International Centre for Diarrhoeal Disease Research, Bangladesh, Department of International Development (DFID), United Kingdom, and GSACS for partial funding for the study. They are also thankful to the Maharashtra State Blood Transfusion Council and the Gujarat State AIDS Control Society for their valuable contributions and whole-hearted cooperation in carrying out this study.Its content are solely the responsibility of the authors and do not necessarily represent the official views of the DFID."} +{"text": "Adjustable rate mortgages and the downturn in the California housing market caused a 300% increase in notices of delinquency in Bakersfield, Kern County. This led to large numbers of neglected swimming pools, which were associated with a 276% increase in the number of human West Nile virus cases during the summer of 2007. Flaviviridae, genus Flavivirus) has remained epidemic in California since its arrival in 2003 because of decreased rainfall, snow pack, and water allotments to agriculture. The Kern River, which flows through Bakersfield, remained mostly dry during spring and summer; key bird species decreased in abundance because of the drought and the previous negative effect of WNV infection; and surviving birds in key species had high herd immunity to WNV acquired during previous seasons.An outbreak with 140 laboratory-confirmed human cases of WNV was centered in the Bakersfield area of Kern County, California, during 2007 . This case cluster formed the WNV epicenter for California during 2007, was the largest mosquito-borne encephalitis virus outbreak in Kern County since the 1952 epidemic of western equine encephalitis virus and an aerial survey of Bakersfield showed an extensive number of green or neglected pools, most of which were producing mosquitoes. The likely reasons for neglected pools are the adjustable rate mortgage and associated housing crises in Kern County and throughout California, which have led to increased house sales, notices of delinquency of payment, declarations of bankruptcy and home abandonment. Kern County was especially affected , with a Cx. p. quinquefasciatus were now occupied by Cx. tarsalis, a more competent vector of WNV than Cx. p. quinquefasciatus occurred during June 2007.Number of swimming pools treated by mosquito control personnel per month in Bakersfield, California, 2005-2007. KMVCD, Kern Mosquito and Vector Control District."} +{"text": "We conducted a preliminary survey on 3064 patients who underwent upper gastrointestinal endoscopy at the Al-Thawra Hospital in Sana'a, Republic of Yemen, between January and December 1991. The age/sex distribution, demographic features and social habits with respect to cigarette and water-pipe smoking and Qat chewing were compared for patients with oesophageal and gastric cancers (n = 183). A preponderance of women with carcinoma of the mid-oesophageal was noted, previously only recorded in areas of high prevalence. Unlike Western populations, smoking and alcohol consumption were not significant risk factors. A high frequency of Qat chewing and water-pipe smoking was found for both men and women and for a group with tumours of the gastro-oesophageal junction or cardia . Numbers were insufficient to identify independent effects of each factor individually. Dietary habits alone were insufficient to account for the excess of affected females. A case-control study is now underway to investigate further the role of dietary factors, social habits, demographic features and Helicobacter pylori infection on the development of upper gastrointestinal cancer in the Yemen."} +{"text": "This paper describes an integrated flow injection (FI) system for the determination of ammonia, sulphate and Fe(II)/Fe(III) which can work unattended for long periods. The system was designed for the determination of individual analytes in long series of samples. Each batch of samples requires manual selection of parameters and units, such as wavelength for monitoring, preconcentration column, loops and switching of three valves to select the carrier, reagents and eluent. The system then works automatically."} +{"text": "Fear of falling and avoidance of activity are common in old age and are suggested to be (public) health problems of equal importance to falls. Earlier studies of correlates of fear of falling and avoidance of activity did hardly differentiate between severe and mild levels of fear of falling and avoidance of activity which may be relevant from clinical point of view. Furthermore, most studies focused only on socio-demographics and/or health-related variables and hardly incorporated an extensive range of potential correlates of fear of falling including psychosocial variables. This study analyzes the univariate and multivariate associations between five socio-demographic, seven health-related and six psychosocial variables and levels of fear of falling and avoidance of activity in older persons who avoid activity due to fear of falling.Cross-sectional study in 540 community-living older people aged \u2265 70 years with at least mild fear of falling and avoidance of activity. Chi-squares, t-tests and logistics regression analyses were performed to study the associations between the selected correlates and both outcomes.Old age, female sex, limitations in activity of daily living, impaired vision, poor perceived health, chronic morbidity, falls, low general self-efficacy, low mastery, loneliness, feelings of anxiety and symptoms of depression were identified as univariate correlates of severe fear of falling and avoidance of activity. Female sex, limitations in activity of daily living and one or more falls in the previous six months correlated independently with severe fear of falling. Higher age and limitations in activity of daily living correlated independently with severe avoidance of activity.Psychosocial variables did not contribute independently to the difference between mild and severe fear of falling and to the difference between mild and severe avoidance of activity due to fear of falling. Although knowledge about the unique associations of specific variables with levels of severe fear of falling and avoidance of activity is of interest for theoretical reasons, knowledge of univariate association may also help to specify the concepts for developing interventions and programmes to reduce fear of falling and avoidance of activity in old age, particularly in their early stages of development. Fear of falling and avoidance of activity due to fear of falling are common in older people. Prevalence rates for fear of falling in community-living older persons range from 20 to above 60% -8 and foPrevious research has shown that fear of falling and/or avoidance of activity were associated with sociodemographic factors , health-related variables and psychosocial variables -8,13-18.severe and mild levels of fear of falling and avoidance of activity which might be relevant from clinical point of view. Knowledge of these factors may facilitate identification of those older persons who are suffering from severe levels of fear of falling and avoidance of activity, and thereby offer routes to effective intervention.Zijlstra and colleagues , in reviThe present cross-sectional study was performed in a sample of community-living older people in the Netherlands who reported at least some fear of falling and associated avoidance of activity. The objective was to examine the relationship between severe levels of fear of falling and avoidance of activity on the one hand, and an extensive range of potential correlates on the other, including socio-demographic, health-related and psychosocial variables.The study was of cross-sectional design and used the baseline data of a trial evaluating the effects of a cognitive behavioral group intervention to reduce fear of falling and fear-related activity avoidance among community-living older persons .Between November 2002 and July 2003, local municipal registry offices of two cities in the south of the Netherlands selected a random sample of 7,431 community-living people aged 70 years and over. They received a short screening questionnaire , which 4Fear of falling was assessed by asking \"Are you afraid of falling?\", and avoidance of activity due to fear of falling was measured by asking \"Do you avoid certain activities due to fear of falling?\" Possible answers to these questions were: \"never\", \"almost never\", \"sometimes\", \"often\", or \"very often\". For the mentioned trial we included only participants who reported either \"sometimes\", \"often\" or \"very often\" on both questions. The answer option \"sometimes\" was denoted as mild fear of falling and avoidance of activity due to this fear. The answer options \"often\" and \"very often\" was denoted as severe fear of falling and avoidance of activity due to this fear.Three groups of correlates were assessed: 1) socio-demographic, 2) health-related and 3) psychosocial correlates.First, we assessed the following socio-demographic variables: age, sex, educational level and living arrangements. Educational level was based on all schooling and professional courses completed in the course of life (lower versus middle/high) and living arrangement was assessed as living alone or living with one or more others.Second, the health-related variables we assessed were limitations in activities of daily living, impaired vision and hearing, perceived general health, number of chronic conditions, cognitive functioning and falls history. Limitations in activities of daily living were assessed with the 11-item subscale of the Groningen Activity Restriction Scale . ImpaireLastly, the psychosocial variables assessed were general self-efficacy, mastery, social support interactions, feelings of loneliness, and feelings of anxiety and symptoms of depression. General self-efficacy was assessed with a 16-item general self-efficacy questionnaire (score range 16\u201380) . MasteryChronic medical conditions, TICS, GARS and impaired vision and hearing were assessed by telephone interviews. All other data were collected by means of self-administered questionnaires. The study was approved by the medical ethics committee of Maastricht University/Academic Hospital in Maastricht, the Netherlands.First, descriptive analyses were performed for all selected variables. Second, we performed chi squares and independent t-tests to study univariate associations between the socio-demographic, health-related and psychosocial variables on the one hand and the two levels of fear of falling (mild and severe) on the other. We then repeated the same analyses for avoidance of activity. Finally, we conducted logistic regression analyses for each of the two dependent variables: fear of falling and avoidance of activity. Only the socio-demographic, health-related or psychosocial variables that showed a univariate association of p < .05 were included simultaneously in these analyses. We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Analyses were conducted using SPSS for Windows version 14.0 . A significance level of less than .05 was considered statistically significant.Table Table The outcomes of the logistic regression analyses are presented in Table Our objective was to study the impact of an extensive range of socio-demographic, health-related and psychosocial variables on levels of fear of falling and avoidance of activity in older persons who avoid activity due to fear of falling. The results clearly show that due to the interrelationship between socio-demographic, health-related and psychosocial variables in older people, only a few of them correlated independently with either severe fear of falling and avoidance of activity due to this fear. Although we identified four socio-demographic, five health-related and five psychosocial factors significant univariate correlates of fear of falling, the independent correlation of only female sex, limitations in activity of daily living and falls history remained when covariates were taken into account. With respect to avoidance of activity due to fear of falling, we identified two socio-demographic, five health-related and five psychosocial significant univariate correlates; this pattern is consistent with fear of falling except for low education and living alone status being non-significant. When all significant univariate correlates were taken into account, only higher age and limitations in activity of daily living correlated independently with severe avoidance of activity. The correspondence between correlates for fear of falling and avoidance of activity may partly be explained by the interrelation of both outcomes. In effect, we were trying to determine what influences avoidance of activity in addition to fear of falling.severe fear of falling. However, in our final multivariate model where we took all significant univariate associations into account, only the impact of age, limitations in activity of daily living and falls history remained significant in the model. This latter finding indicates that none of the psychosocial factors we studied can differentiate between severe and mild levels of fear of falling.In a recent review Scheffer and colleagues identificlinical point of view particularly older people with sever fear of falling and avoidance of activity due to fear of falling are relevant for interventions. Therefore it is important to identify the factors associated with severe levels of fear of falling and related avoidance behavior. Such knowledge may help to specify the contents, approach and length of interventions for these persons. So from clinical point of view it is relevant and important to distinguish between mild and severe levels of fear of falling.Our study has several limitations. First, all measures were self-reported and performance-based measures were not included in the current study. Future studies should include objective measures of balance, gait, muscle strength, vision, etc. to establish a further understanding of the complex construct of fear of falling. Second, our study was cross-sectional so we may not take causal inferences from our data . Future research may identify which correlates can be considered as predictors and which as consequences of severe fear of falling and related avoidance of activity. Third, we included community-living older persons which can be considered as a heterogeneous sample. Future studies could focus on whether different patterns of correlates exist between more frail and less frail older persons. Finally, we included only persons who reported at least mild fear of falling and avoidance of activity. Also having people without fear of falling in our study would have enabled us to say whether, for example, women are more likely to develop any level of fear of falling or only severe fear of falling. However, our interest was not in the development of fear of falling, but rather in those factors that differentiate between mild and severe levels of fear and related avoidance behavior. From severe levels of fear of falling and avoidance of activity. We identified old age, female sex, limitations in activity of daily living, impaired vision, poor perceived health, chronic morbidity, falls, low general self-efficacy, low mastery, loneliness, feelings of anxiety and symptoms of depression as significant correlates of severe fear of falling and avoidance of activity. Although the knowledge about the unique associations of specific variables with levels of fear of falling is of interest for theoretical and scientific reasons, the awareness of the above univariate associations may help to specify the concepts for developing interventions and programmes to reduce severe levels fear of falling in old age, particularly in their early stages of development. A further strength of our study was the attempt to separate fear of falling and the resultant avoidance of activity as outcomes; particularly the latter is under researched in previous studies. This is important, as while fear of falling in itself may be an unwelcome anxiety for an older person, it is the related avoidance of activity that is arguably more significant in terms of its effect on social engagement, functional decline, quality of life, and further falls, particularly when this avoidance is severe. Our work suggests that avoidance of activity in older people with severe levels of fear of falling may be particularly high in those of advanced age and with limitations in activities of daily living, people for whom continued independence may be especially fragile and who will need rapid intervention to maintain that independence.The strength of our study is that in contrast to previous studies we focused on secondary prevention) but also to specify the concepts for developing interventions and programmes to reduce fear of falling and avoidance of activity in old age, particularly in their early stages of development (tertiary prevention).We conclude that female sex, limitations in activity of daily living and one or more falls in the previous six months correlate independently with severe fear of falling. Higher age and limitations in activity of daily living correlate independently with severe avoidance of activity. Psychosocial variables did not contribute independently to the difference between mild and severe fear of falling and to the difference between mild and severe avoidance of activity due to fear of falling. However, old age, female sex, limitations in activity of daily living, impaired vision, poor perceived health, chronic morbidity, falls, low general self-efficacy, low mastery, loneliness, feelings of anxiety and symptoms of depression were identified as univariate correlates of severe fear of falling and avoidance of activity. Although the knowledge about the unique associations of specific variables with levels of severe fear of falling and avoidance of activity is of interest for theoretical reasons, the knowledge of univariate association may also help to identify older people at risk for severe levels of fear of falling and avoidance of activity (The authors declare that they have no competing interests.GIJMK designed the study as a part of a randomized controlled trial. GARZ and JCMvH collected the data. GIJMK analyzed the data and drafted the manuscript with contributions of KJM, KD, JCMvH and GARZ. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:"} +{"text": "Liza haematocheila (syn. Mugil soiuy), native to the Western North Pacific, provides opportunities to examine the changes of its parasite fauna after its translocation to the Sea of Azov and subsequent establishment in the Black Sea. However, the information on macroparasites of this host in both ranges of its current distribution comes from isolated studies published in difficult-to-access literature sources.The mugilid fish Data from 53 publications, predominantly in Chinese, Russian and Ukrainian, were compiled from an extensive search of the literature and the Host-Parasite Database maintained up to 2005 at the Natural History Museum, London.L. haematocheila throughout its distributional range comprises summarised information for 69 nominal species of helminth and ectoparasitic crustacean parasites, from 45 genera and 27 families and includes the name of the parasite species, the area/locality of the host capture, and the author and date of the published record. The taxonomy is updated and the validity of the records and synonymies are critically evaluated. A comparison of the parasite faunas based on the records in the native and introduced/invasive range of L. haematocheila suggests that a large number of parasite species was 'lost' in the new distributional range whereas an even greater number was 'gained'.The complete checklist of the metazoan parasites of L. haematocheila in its natural and introduced/invasive ranges cannot be dealt with the current data because of unreliability associated with the large number of non-documented and questionable records. This stresses the importance of data quality analysis in using host-parasite database and checklist data.Although the present checklist provides information that will facilitate future studies, the interesting question of macroparasite faunal diversity in Liza haematocheila , nativeisheries ; its expKazanski predicteet al. parasitise fish-eating birds as adults. Unfortunately, the above picture is associated with a large number of non-documented records in the introduced/invasive range of Gusev may depart from the real situation in the region and should be treated with caution .The systematics of the species of . Shigin ; Niewiad. Shigin ). Furtheercariae -53. Any ercariae . TherefoL. haematocheila in its native and introduced/invasive range based on the records in the present checklist [L. haematocheila (1978 through 1984) attempted in the Azov Sea basin involved both fry and fish of different ages caught in the Amur and Ussuriisk bays of the Sea of Japan [i.e. Gyrodactylus mugili, G. zhukovi, Ligophorus kaohsiangsieni, L. llewellyni and L. pilengas) transferred to the new distributional areas of the host [A comparison of the parasite faunas of hecklist ,47,54-77the host ,22,35,42L. haematocheila in the Western North Pacific probably do not exist in the new areas (e.g. the absence of the mollusc intermediate host). Further support to the 'supply-side' ecology of parasite transmission provides the 'gain' of the large suite of larval parasite stages (16 species utilising fish as second intermediate and fish-eating birds as definitive hosts). Although this may reflect both high bird and mullet abundance in the areas studied , all Ramsar wetlands of international importance supporting hundred thousands migrating and overwintering birds, I consider these records questionable since none is documented .The replacement of the adult forms (notably the haploporid and haplosplanchnid digeneans) by 'alternative' species of the same families can be considered a change related to the feeding habits of the host. This process appears to reflect biogeographical differences in the 'supply' since opportunities for transmission of the digenean species infecting L. haematocheila in its natural and introduced/invasive ranges cannot be dealt with the current data because of unreliability associated with the large number of non-documented and questionable records. This stresses the importance of data quality analysis in using host-parasite database and checklist data.Although the present checklist provides information that will facilitate future studies, the interesting question of macroparasite faunal diversity in The author declares that they have no competing interests.Liza haematocheila. Checklist of helminth and crustacean parasites of Liza haematocheila with documented (*) and questionable (?) records marked. Abbreviations: MS, Mugil soiuy; LH, L. haematocheila.Checklist of macroparasites of Click here for file"} +{"text": "Rickettsial diseases, important causes of illness and death worldwide, exist primarily in endemic and enzootic foci that occasionally give rise to sporadic or seasonal outbreaks. Rickettsial pathogens are highly specialized for obligate intracellular survival in both the vertebrate host and the invertebrate vector. While studies often focus primarily on the vertebrate host, the arthropod vector is often more important in the natural maintenance of the pathogen. Consequently, coevolution of rickettsiae with arthropods is responsible for many features of the host-pathogen relationship that are unique among arthropod-borne diseases, including efficient pathogen replication, long-term maintenance of infection, and transstadial and transovarial transmission. This article examines the common features of the host-pathogen relationship and of the arthropod vectors of the typhus and spotted fever group rickettsiae."} +{"text": "Meta-regression models were fitted considering linear and non-linear effects of alcohol intake. The effects of characteristics of the studies, of selected covariates (tobacco) and of the gender of individuals included in the studies, were also investigated as putative sources of heterogeneity of the estimates. A total of 235 studies including over 117\u2008000 cases were considered. Strong trends in risk were observed for cancers of the oral cavity and pharynx, oesophagus and larynx. Less strong direct relations were observed for cancers of the stomach, colon and rectum, liver, breast and ovary. For all these diseases, significant increased risks were found also for ethanol intake of 25\u2008g per day. No significant nor consistent relation was observed for cancers of the pancreas, lung, prostate or bladder. Allowance for tobacco appreciably modified the relations with laryngeal, lung and bladder cancers, but not those with oral, oesophageal or colorectal cancers. This meta-analysis showed no evidence of a threshold effect for most alcohol-related neoplasms. The inference is limited by absence of distinction between lifelong abstainers and former drinkers in several studies, and the possible selective inclusion of relevant sites only in cohort studies. \u00a9 2001 Cancer Research Campaign"} +{"text": "The Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex. RAGE is highly expressed only in the lung at readily measurable levels but increases quickly at sites of inflammation, largely on inflammatory and epithelial cells. It is found either as a membrane-bound or soluble protein that is markedly upregulated by stress in epithelial cells, thereby regulating their metabolism and enhancing their central barrier functionality. Activation and upregulation of RAGE by its ligands leads to enhanced survival. Perpetual signaling through RAGE-induced survival pathways in the setting of limited nutrients or oxygenation results in enhanced autophagy, diminished apoptosis, and (with ATP depletion) necrosis. This results in chronic inflammation and in many instances is the setting in which epithelial malignancies arise. RAGE and its isoforms sit in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress. Understanding the molecular structure and function of it and its ligands in the setting of inflammation is critically important in understanding the role of this receptor in tumor biology. The Receptor for Advanced Glycation Endproducts [RAGE] is a member of the immunoglobulin superfamily, encoded in the Class III region of the major histocompatability complex -4. This RAGE is expressed as both full-length, membrane-bound forms and various soluble forms lacking the transmembrane domain. Soluble RAGE is produced by both proteolytic cleavage of fl-RAGE and alternative mRNA splicing. The soluble isoforms include the extracellular domains but lack the transmembrane and cytoplasmic domains -15. Soluin vivo is are fl-RAGE, sRAGE, and esRAGE , Matthew Albert , W. Herve Fridman and Catherine Sautes , and David Chou served as mentors in this program.LJS, DT, RK, HJZ, AAA, and MTL are part of a coalition of laboratories known as the DAMP Lab. It was formed in 2006 at University of Pittsburgh to focus on the role of Damage Associated Molecular Pattern Molecules [DAMPs] released or secreted by damaged or injured cells or the inflammatory cells responding to the \"danger\". Along with Dr. Michael E. de Vera and Dr. Xiaoyan Liang, they focus on the critical role of DAMPs in the initiation of chronic inflammation and the disease that often eventuates as a consequence, cancer."} +{"text": "This is a report of a meeting sponsored by MundiPharma International to identify ways to exploit the cerebrospinal fluid system pharmacologically, for more effective management and prevention of primary and metastatic CNS tumors. The Science of Prevention: New Insights into the Importance of Intra-CSF Prophylaxis', was organized around several provocative theses to stimulate discussion of novel ways to treat, and even prevent, brain and meningeal tumors.Thirty investigators from numerous cancer research centers in the United States and Europe were convened by conference organizer, Michael Glantz (University of Utah School of Medicine \u2013 Huntsman Cancer Institute), to brainstorm the understanding of novel mechanisms, and the development of new paradigms involving the cerebrospinal fluid (CSF) system, for thwarting the spread and improving the treatment of nervous system cancers. This retreat brought oncologists and clinical neuroscientists to St. Thomas, Virgin Islands on February 22\u201324, 2007. The conference, entitled 'Pathophysiogically and pharmacologically, the CSF is an important circulatory system in the brain and spinal cord that, on the one hand disseminates malignant cells, but on the other hand might be harnessed to distribute corrective chemotherapeutic drugs. As knowledge of the CSF system increases, so do the opportunities for managing brain cancer. Successful CSF prophylaxis for medulloblastoma and acute leukemia could well serve as a paradigm for more effective treatment of lymphomas. Conference introductory keynotes by Ching-Hon Pui and Eckhard Thiel (Charite University Medicine Berlin) provided historical perspective and state-of-the-art reviews on acute leukemia and non-Hodgkin's lymphoma. Michael Glantz then addressed the feasibility of a randomized, controlled trial of CSF prophylaxis in patients with high-risk non-Hodgkin's lymphoma. The treatment-refractory glioblastoma multiforme, in dire need of a new therapeutic model, was addressed by Lawrence Recht who analyzed gliomagenesis in the context of growth factor effects on cancer stem cells in the subventricular zone. Utilizing new basic science information, Glantz then proposed a phase II trial incorporating intra-CSF chemotherapy into the initial treatment of patients with newly diagnosed glioblastoma multiforme.Three decades of experience with neoplastic meningitis (NM) has afforded many clinical insights on treatment, but cures remain exceedingly rare, and controversy persists regarding the most basic tenets. Marc Chamberlain (Fred Hutchinson Cancer Center) reviewed prognostic variables within subgroups of patients with solid tumor neoplastic meningitis, and urged tumor-specific strategies for CSF-directed therapy. However, the whole concept of intrathecal chemotherapy as a treatment for solid tumor NM was questioned by Willem Boogerd (Netherlands Cancer Institute) who emphasized the urgent need for a randomized clinical trial to address this issue, and presented such a proposal on behalf of the European Organisation for Research and Treatment of Cancer (EORTC). The rationale and techniques for treating malignant cells in CSF were discussed by William Shapiro , while the expectations for significantly improving survival in solid-tumor patients were outlined by Stuart Grossman . Conrad Johanson introduced the potential role of pharmacologically modifying choroid plexus function to treat or prevent cancer spread along the ventriculo-subarachnoid CSF system. Recognizing the limitations of CSF cytology and magnetic resonance scanning, Glantz outlined the need for more sensitive techniques to diagnose CSF malignancies and evaluate treatment outcomes. The importance of novel markers for diagnosing and monitoring responses in NM and lymphomatous meningitis was extensively treated by Morris Groves (M.D. Anderson Cancer Center) and Wyndham Wilson .The final session of the conference was both practical and visionary. Clinical trials, both newly completed and projected, were discussed. New insights for protecting against brain metastases (including lung and breast cancer) were delineated by Wallace Akerley (University of Utah School of Medicine \u2013 Huntsman Cancer Institute), Frankie Holmes (Baylor College of Medicine) and Ricardo Soffietti (University of Turin). Gudrun Fleischhack introduced opportunities for pediatric primary brain tumor initiatives, while Ulrich Herrlinger (University of Bonn) discussed primary central nervous system lymphoma. Randy Jensen (University of Utah School of Medicine \u2013 Huntsman Cancer Institute) reviewed the evidence in favor of post-neurosurgical prophylaxis. Finally, Jennifer Smith (Geron Corp) treated statistical issues in designing critical trials, including identifying predictive and prognostic markers. She also offered advice on clinical trial proposals developed during the conference.Science of Prevention conference was the first of its kind to focus on the CSF as a medium around which to marshall research and clinical strategies for preventing and treating brain cancer. Brain tumor development or spread, from both the pathologic and the pharmacologic point of view, is critically dependent upon functional relationships between CSF dynamics and brain metabolism. Considerably more information is needed about CSF-bordering cells in order to more effectively thwart dissemination of cancer cells throughout the CSF and interstitial fluid compartments. Also, analysis of primary brain tumor development in the subventricular zone deserves more attention as a site for modulating (by growth factors and antagonists) stem cell oncogenicity. The efficacy of intrathecal versus combined intrathecal and systemic administration of chemotherapeutic drugs also merits more attention. Clearly new CSF markers and diagnostic techniques are essential for improving disease identification and monitoring response to therapy in a class of diseases which continues to challenge oncologists, neurologists, neurosurgeons, basic scientists, and, most especially, patients. As a result of this conference, the rationale for expanding the intra-CSF prophylaxis approach to brain and meningeal tumors has now been more sharply defined.This The author(s) declare that they have no competing interests.Both authors contributed equally to this report and have read and approved the final version of the manuscript."} +{"text": "In this manuscript, the information available on the molecular epidemiology of HBV in India has been reviewed and the results of studies among the eastern Indian population have been summarised.Hepatitis B virus (HBV) is one of the major global public health problems. In India, HBsAg prevalence among general population ranges from 2% to 8%, placing India in intermediate HBV endemicity zone and the number of HBV carriers is estimated to be 50 million, forming the second largest global pool of chronic HBV infections. India is a vast country, comprised of multiracial communities with wide variations in ethnicity and cultural patterns, which is attributable to its geographical location, gene influx due to invasion and/or anthropological migrations in the past. Moreover, recent increase in trade, trafficking and use of illicit drugs has also considerably influenced the epidemiology of HBV, specifically in the eastern and north eastern parts of India. However, data on the molecular epidemiology of HBV in India is scanty. HBV genotypes A and D have been well documented from different parts of mainland India. Interestingly, in addition to genotypes A and D, genotype C having high nucleotide similarity with south East Asian subgenotype Cs/C1 strain, have been detected exclusively from eastern Indian HBV carriers, suggesting a recent introduction. Thus, compared to other parts of India, the molecular epidemiology of HBV is naturally distinct in eastern India. Very recently, taking the advantage of circulation of three distinct HBV genotypes within the population of eastern India, different aspects of HBV molecular epidemiology was studied that revealed very interesting results. In this study, the clinical significance of HBV genotypes, core promoter and precore mutations, possible routes of introduction of HBV genotype C in eastern India, the clinical implications of About 30 percent of the world's population has serological evidence of current or past infection with HBV. Of these, an estimated 350 million are chronically infected with HBV and approximately 1 million persons die annually from HBV-related chronic liver diseases, including severe complications such as liver cirrhosis (LC) and HCC .In conclusion, the results of this thesis sheds light on many important aspects of HBV molecular epidemiology that are very much important for identifying the population at risk of acquiring HBV and developing severe disease, and also pose a risk of transmission through different modes. This information are essential for determining the risk factors associated with HBV infections, to formulate necessary preventive measures to lessen the burden of new infections and spread of newly introduced genotype to other parts, from eastern India. Moreover, considering the higher pathogenic potentials associated with certain HBV genotypes, the results of the thesis work will be helpful in prognosis and better management of HBV infected subjects.Emergence of new genotypes/subgenotypes, clinically important mutations have immense importance in determining the clinical outcome, efficacy of vaccination and therefore strict surveillance of these variants are extremely important. Hope that the present study will advance the understanding of changing molecular epidemiology of HBV, and will also help in formulation of effective preventive measures. Last but most important, the results of this thesis work, demonstrating compartment specific high prevalence of HBV DNA associated with vaccine/immune escape mutation in the PBL of HBsAg negative subjects have extremely important implications in the field of transfusion medicine, organ transplantation, and in vaccination strategies, and thus need further investigations. Finally, together with contributing unique data on molecular epidemiology of HBV in India, this thesis work also open new avenues for further studying the molecular virology of HBV.The author declares that they have no competing interests.The author studied Zoology at the Bachelor and Master Degree level and later joined the Indian Council of Medical Research Virus Unit, for doctoral research. He specializes in the fields of molecular diagnostics, epidemiology, evolution and genomics of viruses.Molecular Epidemiology of Hepatitis B virus in Eastern India: Role of Genotypes, X gene Variability and Disease Outcome\", which has been approved by the doctoral committee of Jadavpur University, for the award of PhD degree.The author compiled the above information for writing the background section of his doctoral thesis entitled \""} +{"text": "Integrated vector management (IVM) is defined as \"a rational decision-making process for the optimal use of resources for vector control\" and includes five key elements: 1) evidence-based decision-making, 2) integrated approaches 3), collaboration within the health sector and with other sectors, 4) advocacy, social mobilization, and legislation, and 5) capacity-building. In 2004, the WHO adopted IVM globally for the control of all vector-borne diseases. Important recent progress has been made in developing and promoting IVM for national malaria control programmes in Africa at a time when successful malaria control programmes are scaling-up with insecticide-treated nets (ITN) and/or indoor residual spraying (IRS) coverage. While interventions using only ITNs and/or IRS successfully reduce transmission intensity and the burden of malaria in many situations, it is not clear if these interventions alone will achieve those critical low levels that result in malaria elimination. Despite the successful employment of comprehensive integrated malaria control programmes, further strengthening of vector control components through IVM is relevant, especially during the \"end-game\" where control is successful and further efforts are required to go from low transmission situations to sustained local and country-wide malaria elimination. To meet this need and to ensure sustainability of control efforts, malaria control programmes should strengthen their capacity to use data for decision-making with respect to evaluation of current vector control programmes, employment of additional vector control tools in conjunction with ITN/IRS tactics, case-detection and treatment strategies, and determine how much and what types of vector control and interdisciplinary input are required to achieve malaria elimination. Similarly, on a global scale, there is a need for continued research to identify and evaluate new tools for vector control that can be integrated with existing biomedical strategies within national malaria control programmes. This review provides an overview of how IVM programmes are being implemented, and provides recommendations for further development of IVM to meet the goals of national malaria control programmes in Africa. Malaria and other vector-borne diseases contribute substantially to the global burden of diseases and disproportionately affect poor and under-served populations living in tropical and sub-tropical regions [The control of vector-borne diseases represents one of the greatest global public health challenges of the 21 regions . In the Integrated vector management (IVM) is not a new concept and the basic principles of IVM have been used over the past century in the U.S.A. and elsewhere for mosquito control. An example includes the vast network of Mosquito Abatement Districts throughout the U.S.A. -9. TheseAll the tactics of standard vector control are included in the IVM approach. IVM goes beyond the integration of traditional control measures to emphasize strategies to make vector control programmes compatible with national health systems. IVM also incorporates decision-making based on human and institutional resources, and engages communities to promote sustainability. IVM encourages integrative, multi-disease approaches and promotes the systematic application of different interventions in combination and in synergy with each other. The framework for implementation strategies extends beyond the health sector and involves multiple stake-holders. To promote success, IVM requires continual monitoring, evaluation and legislation, linked with a strong commitment and concerted action by governments and international organizations .In 2004, the global strategic framework for IVM was prepared establishing new, broad principles and approaches to vector control that are applicable to all vector-borne diseases . IVM wasmost programme managers are unaware of this possibility that an integrated approach can, in principle, be introduced without additional resources\"; 2) over-sophistication of integrated control: \"in short, for many mosquito species enough is already known ....to base the introduction of integrated control\"; 3) insufficient conviction of the advantages of integrated control; 4) misconceptions about the use of pesticides in integrated control: \"project managers need to be assured that integrated control does not, nor cannot, mean exclusion of pesticides, but their more rational and correct use.\"; and 5) insufficient consciousness of comparative costs, effectiveness, benefits and risks: \"application of pesticides, especially via indoor residual spraying (IRS), frequently becomes a routine practice, regardless of the need or the results obtained\" [Historically, the implementation of integrated approaches to vector control has been a slow and complicated process. In the 1970's, WHO listed five reasons for the slow uptake of integrated vector control: 1) over-estimation of the requirements of integrated control: \"btained\" . Additioeffective IVM requires the establishment of principles, decision-making criteria and procedures, together with time-frames and targets\" [Like traditional approaches to vector control, IVM relies on an understanding of how environmental factors affect the distribution and densities of different species of vectors, and how effectively control measures reduce vector-human contact, vector survival and the overall intensity of pathogen transmission. IVM expands on traditional approaches to vector control in that collaboration with local communities, other stakeholders , and public health regulatory and legislative frameworks support the evolution of vector control. Programmes seeking to implement IVM must appreciate that \"targets\" ,16. ThesFigure Advocacy, social mobilization and legislation. Promotion and embedding of IVM principles in the development policies of all relevant agencies, organizations and civil society; establishment or strengthening of regulatory and legislative controls for public health and pesticide management; empowerment of communities.\u2022 Collaboration within the health sector and with other sectors. Consideration of all options for collaboration within and between public and private sectors; strengthening channels of communication among policymakers, vector-borne disease control programme managers and other IVM partners.\u2022 Integrated approach. Ensure rational use of available resources through a multi-disease control approach, integration of non-chemical and chemical vector control methods, and integration with other disease control measures, such as active and passive case detection and treatment.\u2022 Evidence-based decision-making. Adaptation of strategies and interventions to local vector ecology, epidemiology and resources, guided by operational research and subject to routine monitoring and evaluation.\u2022 Capacity-building. Development of essential physical infrastructure, financial resources and adequate human resources at local and national levels to manage IVM programmes based on needs assessments.\u2022 Are malaria vector control approaches involving ITNs and IRS sufficient? Where and when are they effective? What else is needed to eliminate the remaining low-levels of transmission? There is also a strong case for implementing larval control to target immature stages of anopheline mosquitoes to reduce malaria transmission [Plasmodium falciparum and Plasmodium vivax malaria will take at least another 50 years [Throughout Africa, National Malaria Control Programmes have recently embarked on emphasizing vector control as an essential component ,17. Mostsmission -27, but smission . Even wi50 years .In developing countries, Ministries of Health are normally charged with mosquito control as part of their overall public health programme, although lines of responsibility and organizational networks vary according to different countries. National guidelines are often developed with input from international organizations, such as the WHO and the CDC; these guidelines influence the strategies and tools employed for control programmes that are carried out by decentralized units of the government. However, there are many reasons why vector-borne diseases remain a major public health problem: 1) entomologists and vector-control specialists often fail to convince decision-makers of the importance of sound vector control; 2) intersectoral collaboration has been recommended as a method to improve mosquito control, but in practice, this type of collaboration has proved difficult; 3) modeling and adaptive management have not been used effectively to quantify the effect of disease and vector control interventions on the economic and social development of communities and nations; 4) failed management of insecticides has created a conflict of \"to spray or not to spray\"; 5) there has been a failure to connect the true disease burden with other societal burdens to establish the public health importance of vector-borne diseases in low-transmission settings; 6) the interaction between proper utilization of law enforcement and health education has not been explored in sufficient detail; 7) economics plays a central role in mosquito-borne disease control but has not been fully integrated in the evaluation of disease control programmes; 8) entomologists and public health specialists have failed to convince decision-makers that they have an ethical duty to control mosquitoes and the pathogens they transmit; and 9) biomedical strategies, such as active and passive case-detection and treatment, are often used instead of preventative vector control measures, as a result of international donor requirements.A comparative evaluation of vector-control programmes in five countries suggestsProgress in implementing IVM continues to be slow. In an Institute of Medicine review of Vector Borne Diseases, David Morens cites five fundamental deficiencies that inhibit our ability to find realistic solutions for vector-borne disease problems: deterioration of public health infrastructure, lack of adequate funding, lack of adequate training and training models, over-specialization in the biomedical sciences, driven by emerging technology and emphasis on the basic sciences, and bureaucratization . If IVM A recent report by Chanda et al. describeWhile much remains unknown about the impact of fully developed IVM programmes on malaria transmission -36, the Castro and colleagues describeOne of the largest integrated disease control schemes developed in the 1980's was the Blue Nile Health Project . The 10-Sri Lanka has long linked vector control with agricultural development. In the 1970s and 1980s, the Mahaweli River hydroelectric and irrigation development project caused new foci of malaria transmission to emerge around Kandi. The hydrological changes and the relocation of people between malaria endemic and non-endemic areas as a result of resettlement due to the dam reservoirs, contributed to an upsurge in malaria and JapaEritrea uses national-level ITN distribution strategies, larval habitat management in malarious areas, and indoor residual spraying in areas with the appropriate eco-epidemiological characteristics. Although Eritrea has seen a marked drop in malaria parasite prevalence and disease, no rigorous evaluation of the IVM activities linked to health outcomes has been done. Among the reasons why impact evaluation exercises have not been done are cost and time. In many instances, not enough resources are allocated for the proper evaluation of an intervention programme, forcing the use of a less rigorous study designs for establishing causal inference.IVM should be seen as a framework and a strategy rather than a circumscribed, tactical intervention. As such there are a large number of African national malaria control programmes that incorporate some, but possibly not at the present time, all of the IVM elements. \"Community-based\" IVM programmes incorporating larval source management have recently been implemented in two different settings: in Rusinga Island, Western Kenya , and in The implementation of IVM requires a needs assessment of vector control capability through:Policy needs: reform and adjustment of the policy framework which provides the enabling environment for vector control;\u2022 Institution building needs: the strengthening of existing institutions and the arrangements between them that aim at facilitating vector control;\u2022 Managerial development needs: the establishment of clear criteria and decision-making procedures to manage the vector control programme;\u2022 Technical strengthening: development of the technical facilities to support vector control programmes;\u2022 Human-resource development needs: the formation and in-service training of personnel in the relevant disciplines and skills.\u2022 Community participation; this will ensure the sustainability of control approaches.\u2022 Needs assessments of vector control capability must identify approaches that will assure that the elements from Table IVM in the Africa region was launched at a regional workshop of policy makers and vector control specialists in Harare in February 2001. From that workshop a strategic plan was further developed to initiate the implementation of IVM in Africa.Subsequently, a series of regional IVM training workshops were organized in Nairobi, Kenya in 2002 and 2004, and in Accra, Ghana in 2003. A total of 31 participants from 23 countries, including entomologists and vector control specialists working with Ministry of Health disease control programmes and Ministries of the Environment, attended the workshops .National plans of action were prepared and implementation of IVM was started in 16 countries. Vector-control needs assessments and the organization of national consensus workshops on IVM have been conducted in nine countries. In order to support all these efforts, the \"Partnership for IVM in Africa\", called \"IVM Africa,\" was founded in Harare with six organizations initially: WHO, UNEP, ICIPE, the USAID Environmental Health Project (EHP), The Hashimoto Initiative, and the Panel of Experts on Environmental Management (PEEM) .There is a rapidly increasing number of programmes incorporating ITNs with IRS . For exaThe Global Malaria Business Plan and a recent technical review of Global Malaria Control and Elimination recognizThere is a need to show that IVM approaches are being implemented and that they are making an impact. In addition to the basic requirements for implementing IVM at the national level for malaria control, further coordinated national and international efforts and financial support are needed to achieve the following:\u2022 Strengthen capacity-building for IVM at national level, improve the scope and quality of regional IVM training initiatives, and support post-graduate education.\u2022 Further promote interdisciplinary integration and inter-sectoral cooperation by engaging appropriate stake-holders at the national level, including community groups and NGOs, and engaging experts from outside traditional entomological and public health frameworks for vector-borne disease control.\u2022 Promote the incorporation of emerging technologies in database management, information systems, and communication into the IVM strategy for better national and regional level operations.\u2022 Develop novel training models that also have interaction components among entomologists in the field, health-care workers in the clinics and decision-makers in national and local government offices.\u2022 Support research that further elaborates approaches and tactics needed to combat malaria, especially for low-transmission settings where national programmes have successfully reduced levels of transmission and are now pursuing or moving toward country-wide elimination.\u2022 Support research in options for improving strategic management and decision-making to more comprehensively integrate IVM strategies into national malaria control programmes.\u2022 Support international research to develop new tools for malaria vector control, including new generation insecticides, new biological control strategies, new trapping methods, and innovative methods that target mosquitoes at different points in their life history cycles .\u2022 Identify and support activities that establish long-term partnerships between national malaria control programmes and international experts and institutions to strengthen capacity building and operational research components of IVM programmes.\u2022 Establish and fund IVM demonstration projects across different malaria-endemic environments to illustrate the importance of integrated IVM approaches for vector-borne disease control.\u2022 Increase research on the financial and economic costs of IVM including projected estimates of IVM, real-world cost-effectiveness calculations of IVM programmes from demonstration projects, and financial and economic models related to scaling-up IVM in Africa.IVM: Integrated Vector Management; ITNs: Insecticide-treated bednets; IRS: Indoor Residual spraying; WHO: World Health Organization; CDC: Centers for Disease Control; FAO: Food and Agriculture Organization; NGOs: Non-governmental organizations; UNEP: United Nations Environment Programme; ICIPE: International Centre of Insect Physiology and Ecology; USAID: United States Agency for International Development; LLINs: Long-lasting insecticide-treated bednets; NMCPs: National Malaria Control Programmes.The authors declare that they have no competing interests.JCB conceived the review concept, organized the draft sections, co-wrote sections of the draft and edited the overall manuscript. JK participated in the conception, helped organize the draft sections, co-wrote sections of the draft and helped in editing the overall manuscript. JIG participated in the conception and helped in editing the overall manuscript. MBM participated in the conception, co-wrote sections of the draft, and helped in editing the overall manuscript. DEI co-wrote and edited sections of the manuscript and formatted the draft for submission. RJN participated in the conception, provided specific IVM information, co-wrote sections of the manuscript and helped in editing the overall manuscript."} +{"text": "An automated apparatus to assist in the development of analyticalcontinuous flow methods is described. The system is capable ofcontrolling and monitoring a variety of pumps, valves, anddetectors through an IBM PC-AT compatible computer. Systemcomponents consist of two types of peristaltic pumps (including amultiple pump unit), syringe pumps, electrically and pneumaticallyactuated valves, and an assortment of spectrophotometric andelectrochemical detectors. Details of the interface circuitry are givenwhere appropriate. To demonstrate the utility of the system, anautomatically generated response surface is presented for the flowinjection determination of iron(II) by its reaction with1,10-phenanthroline."} +{"text": "Transposable elements are the most abundant components of all characterized genomes of higher eukaryotes. It has been documented that these elements not only contribute to the shaping and reshaping of their host genomes, but also play significant roles in regulating gene expression, altering gene function, and creating new genes. Thus, complete identification of transposable elements in sequenced genomes and construction of comprehensive transposable element databases are essential for accurate annotation of genes and other genomic components, for investigation of potential functional interaction between transposable elements and genes, and for study of genome evolution. The recent availability of the soybean genome sequence has provided an unprecedented opportunity for discovery, and structural and functional characterization of transposable elements in this economically important legume crop.Using a combination of structure-based and homology-based approaches, a total of 32,552 retrotransposons (Class I) and 6,029 DNA transposons (Class II) with clear boundaries and insertion sites were structurally annotated and clearly categorized, and a soybean transposable element database, SoyTEdb, was established. These transposable elements have been anchored in and integrated with the soybean physical map and genetic map, and are browsable and visualizable at any scale along the 20 soybean chromosomes, along with predicted genes and other sequence annotations. BLAST search and other infrastracture tools were implemented to facilitate annotation of transposable elements or fragments from soybean and other related legume species. The majority (> 95%) of these elements (particularly a few hundred low-copy-number families) are first described in this study.SoyTEdb provides resources and information related to transposable elements in the soybean genome, representing the most comprehensive and the largest manually curated transposable element database for any individual plant genome completely sequenced to date. Transposable elements previously identified in legumes, the third largest family of flowering plants, are relatively scarce. Thus this database will facilitate structural, evolutionary, functional, and epigenetic analyses of transposable elements in soybean and other legume species. Transposable elements (TEs) are the most abundant genomic components in flowering plants. For example, approximately 40% of the rice genome and 80% Pack-MULEs in rice . In addition, genes captured by TEs and TEs that carry gene fragments in soybean and these relatives will be identified, classified and integrated into the database in the context of the comparative genome maps of multiple species.Future SoyTEdb development includes the integration of TE data from http://www.soytedb.org, which is publicly accessible. These data are freely available without any restrictions to use by non-academics.All TEs or subsets of TEs can be downloaded from the SoyTEdb website LINE: Long interspersed repetitive element; LTR: Long terminal repeat; SoyTEdb: Soybean Transposable Element Database; TE: Transposable element; TSD: Target site duplication; WGS: whole genome shotgun sequencing.JD, ZT and LZ identified transposable elements. DG and RTN constructed the web-based database and helped to draft the manuscript. RCS and JM conceived of the study, participated in its design and corordination, and drafted the manuscript, and served as principle investigators of the project. All authors read and approved the final manuscript."} +{"text": "TGF-beta is the prototype of a large family of multifunctional regulatory proteins. The principal sources of the peptide, platelets and bone, suggest that it plays a role in healing and remodeling processes. In vitro, TGF-beta is chemotactic for monocytes and fibroblasts and can greatly enhance accumulation of extracellular matrix components by fibroblasts. Its ability to stimulate the formation of granulation tissue locally and the demonstration of specific time- and tissue-dependent expression in embryogenesis suggest that similar mechanisms are operative in vivo. By analogy to its effects in wound healing and embryogenesis, it is proposed that TGF-beta, secreted by tumour cells, can augment tumour growth indirectly by effects on the stromal elements. These effects include suppression of the immune response, and enhancement of both angiogenesis and formation of connective tissue. Many tumour cells have escaped from direct growth inhibitory effects of TGF-beta by a variety of mechanisms including inability to activate the latent form of the peptide, loss of cellular receptors for TGF-beta, and loss of functional intracellular signal transduction pathways."} +{"text": "Central and northern Europe are now at risk from bluetongue virus. Keywords: Bluetongue, BTV-8, epidemiology, cattle, sheep, Europe, disease perspectives, vectorial capacity, vector competence, vaccination, perspective Bluetongue (BT) is a reportable disease of considerable socioeconomic concern and of major importance in the international trade of animals and animal products. Before 1998, BT was considered an exotic disease in Europe. From 1998 through 2005, at least 6 BT virus strains belonging to 5 serotypes were continuously present in the Mediterranean Basin. Since August 2006, BTV-8 has caused a severe epizootic of BT in northern Europe. The widespread recrudescence and extension of BTV-8 infections in northern Europe during 2007 suggest that requirements for BTV establishment may now be fulfilled in this area. In addition, the radial extension of BTV-8 across Europe increases the risk for an encounter between this serotype and others, particularly those that occur in the Mediterranean Basin, where vector activity continues for more of the year. This condition increases the risk for reassortment of individual BTV gene segments. Bluetongue virus (BTV). The virus belongs to the family Reoviridae, genus Orbivirus; there are 24 serotypes (Bluetongue (BT) is an infectious but noncontagious viral disease caused by BT is a World Organization for Animal Health reportable disease and is of considerable socioeconomic concern and of major importance in the international trade of animals and animal products since BTV\u2019s introduction in 1998. To this effect, we provide a short overview of the epidemiologic situation in Europe, followed by a brief description of the susceptible species, a discussion of the vectorial capacity and competence of the Culicoides imicola (Kieffer), which is an Afro-Asiatic species of biting midge have been continuously present in parts of the Mediterranean Basin, including several member states of the EU (C. obsoletus (Meigen) and C. scoticus (Downes and Kettle), collected in central Italy (C. pulicaris (Linnaeus) in Sicily (C. dewulfi (Goetghebuer) in the Netherlands were positive by PCR for BTV were also PCR positive for BTV (19). In for BTV . AlthougCulicoides spp. were captured in animal housing during the winter period .Culicoides biting midge and a few deer species conditions. Vector capacity can be defined as the number of infective bites that an infected vector causes during its lifetime or inanimate means; through the active flight of infected vector Culicoides spp. ; and through passive flight of infected vector Culicoides spp. on the wind (responsible for long-distance dissemination).Introduction of BTV from 1 area into another can occur in 4 ways: through animal movement (domestic and wild ruminants) or animal product transport ; by infected vector Culicoides spp. becoming infected by feeding upon local viremic hosts, surviving long enough to ensure completion of the intrinsic incubation period , and transmitting the virus by bite to new hosts . In addition, the radial extension of BTV-8 across Europe (including the jump across the English Channel) (39) incChannel) .C. imicola, the Afro-Asiatic vector of BTV, occurs in addition to the C. obsoletus complex. As the population abundance of C. imicola peaks later in the year than the Obsoletus complex, this means that virus may be transmitted for a much greater portion of the year.Furthermore, in the southern epidemiologic system, With regard to prophylaxis, possibly the best strategic option for control of clinical BT outbreaks in the European endemic areas is vaccination of susceptible animals with inactivated vaccines to protect against disease and to exclude the possibility of reversion to virulence of the vaccine viruses and reassortment between vaccine and field strains of the virus ("} +{"text": "Risks of being thin and stunted were higher if girls had general morbidity in the last fortnight and foul-smelling vaginal discharge than their peers. Consumptions of non-staple good-quality food items in the last week were less frequent and correlated well positively with the household asset quintile. Girls of the highest asset quintile ate fish/meat 2.1 (55%) days more and egg/milk two (91%) days more than the girls in the lowest asset quintile. The overall dietary knowledge was low. More than half could not name the main food sources of energy and protein, and 36% were not aware of the importance of taking extra nutrients during adolescence for growth spurt. The use of iron supplement was 21% in nutrition-intervention areas compared to 8% in non-intervention areas. Factors associated with the increased use of iron supplements were related to awareness of the girls about extra nutrients and their access to mass media and education. Community-based adolescent-friendly health and nutrition education and services and economic development may improve the overall health and nutritional knowledge and status of adolescents.This study estimated the levels and differentials in nutritional status and dietary intake and relevant knowledge of adolescent girls in rural Bangladesh using data from the Baseline Survey 2004 of the National Nutrition Programme. A stratified two-stage random cluster-sampling was used for selecting 4,993 unmarried adolescent girls aged 13\u201318 years in 708 rural clusters. Female interviewers visited girls at home to record their education, occupation, dietary knowledge, seven-day food-frequency, intake of iron and folic acid, morbidity, weight, and height. They inquired mothers about age of their daughters and possessions of durable assets to divide households into asset quintiles. Results revealed that 26% of the girls were thin, with body mass index (BMI)-for-age <15 Childhood undernutrition, highly prevalent in South Asia , continuAdolescence is a unique intervention point in the life-cycle for a number of reasons . Early aIn developing countries, factors associated with undernutrition of adolescents are: poor household economic condition, periodic food-shortage, child-labour (marker of household income-poverty), burden of disease, poor knowledge about long-term consequences of undernutrition of adolescents, quantity and quality of food, and access to health and nutrition services . In BangDietary knowledge and access to resources are critical to improve health and nutrition in a sustainable way. Adolescence is the time to learn and adopt healthy habits to avoid many health and nutritional problems later in life . AdolescTo combat the high prevalence of micronutrient deficiencies, the Government of Bangladesh recommends supplementation of micronutrients , 13. TheNutrition promoters need information on levels and differentials in undernutrition of adolescents, burden of disease, dietary knowledge, and intake and coverage of iron supplement to meet the needs of those who need them most. The objectives of this study were to provide them with such information that would assist in planning for remedial actions to address health and nutrition needs of adolescent girls in Bangladesh.This study used data from the Baseline Survey 2004 of the National Nutrition Programme (NNP) conducted in rural areas of Bangladesh. The NNP is the successor to the Bangladesh Integrated Nutrition Project (BINP), which was launched in 1994. The BINP expanded its activities in phases and continued up to 2003. The community-based nutrition centres run by female community nutrition promoters (CNPs) were the focus of the BINP activities. The CNPs imparted health and nutrition education to mothers of children aged less than two years (under-two children), adolescent girls, and pregnant women; monitored growth of under-two children; and provided food supplements to severely-underweight and growth-faltered under-two children and to undernourished pregnant women (BINP implementation plan 1994). They organized never-married adolescent (out-of-school and schoolgoing) girls of the community to form Adolescent Girls Forum and to hold its meeting monthly to discuss their health, nutrition and social safety issues and distributed iron and folic acid tablets to the participants of the meeting.A stratified two-stage random cluster-sampling was used for selecting 5,028 never-married adolescent girls aged 13\u201318 years from 708 clusters in 113 upazilas (subdistricts) spread in all six administrative divisions (strata) of Bangladesh. The first stage was the random selection of clusters from cluster lists in programme and non-programme upazilas where each cluster contains about 300 households. The second stage was the random selection of nine unmarried adolescent girls from each cluster of the NNP and comparison upazilas and six unmarried adolescent girls from each cluster of the BINP upazilas for interview. Upazilas were grouped into BINP upazilas, NNP upazilas (where NNP activities were yet to start), and comparison upazilas (selected to assess the effects of NNP interventions later). Analysis included 4,993 never-married adolescent girls aged 13\u201318 years (excluded were 35 girls with flagged BMI-for-age or height-for-age z-score).Female interviewers, trained by social scientists and nutritionists, visited adolescent girls at their homes with a structured questionnaire to obtain consent of parents and to collect data on health and nutrition status of the adolescent girls. Field supervisors checked work of the field interviewers daily to ensure the quality of data collected in the field. Interviewers inquired girls about their education, occupation, and access to electronic and print media. Education was measured with grade passed and categorized as: up to primary (passed grade 5 or less) and secondary or above (passed grade 6 or more). Access to media was considered high if she had listened to radio or watched television at least weekly or read a newspaper or magazine (no matter how frequent it was); otherwise, it was considered low.To assess their dietary knowledge, a checklist of food items was used. Girls were asked to name the check-listed foods that provide mainly energy, protein, vitamin, and minerals. They were asked if they were aware of the importance of taking extra nutrients during adolescence and use of iron supplements to assess their dietary knowledge and intake. Despite the possibility of recall bias, the girls were asked about the seven-day food-frequency questions to assess eating patterns of energy, protein, fat, and vitamin- and mineral-rich food items. A checklist was used for recording general morbidity symptoms they had experienced in the preceding two weeks. The checklist included fever, cough/cold, diarrhoea/dysentery, stomachache, respiratory problems, ear and eye problems, skin problems, and others. The girls were asked privately about menstrual irregularities, avoidance of any food during last menstruation, and passage of white discharge with foul smell. Self-reported morbidity symptoms were taken at face value.th percentile value of the WHO growth reference for girls refers to severely thin and BMI-for-age in between the 5th and the 15th percentile value refers to moderately thin. BMI-for-age below the 15th percentile value and height-for-age z-score <-2SD were used in measuring the prevalence of thinness and stunting respectively.Weight, height, and mid-upper arm circumference (MUAC) of the girls were measured by Uniscales, locally-made height scales and TALC (Teaching Aid at Low Cost) tape respectively. Weight and height were used for computing BMI and height-for-age z-score using the WHO growth reference for school-age children and girls , 15. BMIMothers were inquired about age or date of birth of their daughters and household possessions of durable items. A local calendar was used for determining age or date of birth accurately. Misreporting, particularly under-reporting of age, is likely and so are the underestimation of the prevalence of stunting and thinness. Household durables included bed-stand, chair, table, cupboard, radio, television, bike (including motor bike), land owned, wall material of the main dwelling unit , and type of toilet used. The principal components analysis of household durable assets retained one factor and assigned factor score to each household . The higBivariate and logistic regression techniques were used for estimating the differentials in nutrition status, dietary consumption, and knowledge and intake of iron supplement. The differentials included age, education, morbidity, access to mass media, household asset quintile, and type of upazila (proxy for exposure to the community-based nutrition education project). Bivariate differentials are shown in terms of prevalence (in %) and mean of seven-day food intake. Logistic regression was used in estimating the differentials, controlling simultaneously for others and expressed as odds ratios.The sampled girls were mostly young because some older ones got married and did not fit the inclusion criteria . A very The burden of disease measured with self-reported morbidity was quit high; 33% of the girls had one or more morbidity symptoms in the last two weeks . Morbidith percentile value of BMI-for-age for girls), 16% moderately thin , and 0.3% obese . The ageStunting (measured with height-for-age z-score <2SD) was prevalent among 32% of the girls, and its prevalence increased with increase in age. Girls with symptomatic RTI and lower education were more likely to be stunted than their counterparts. Knowledge of girls about the need for extra nutrients in adolescence, exposure to mass media, and household asset quintile were not associated with the prevalence of stunting.dal (lentils), fruits, and leafy vegetables, were not frequent in rural areas in the last seven days was universal with no difference between the asset quintiles (data not shown). Consumptions of non-staple food items, such as meat, eggs, al areas . Half ofTo estimate the economic differentials in consumptions of protein- and fat-rich foods, we grouped together fish and meat and egg and milk . The mean frequencies of eating fish/meat and egg/milk were 4.7 and 3.3 days respectively . The houdal (lentils) (21%), meat (32%), and fish (43%). Knowledge on vitamin- and mineral-rich foods was common; 75% mentioned vegetables, and 51% mentioned fruits as vitamin- and mineral-rich foods.Knowledge of adolescents on common food sources of energy and protein was limited. When asked to name main food sources of energy, 31% mentioned rice and 12% mentioned wheat, and these are correct responses (data not shown). Less than half correctly named high-protein foods: Two-thirds (64%) of the girls were aware of the need to take extra nutrients during adolescence to attain growth spurt . FactorsThe results of the study revealed that, in rural Bangladesh, the prevalence of thinness and stunting among the adolescent girls aged 13\u201318 years was widespread and persistent. Severe thinness was 9%\u2014lower than 16% found in schoolgirls aged 10\u201316 years in Dhaka city in 1995 , the preAlthough education was not associated with the risk of being thin, girls with higher education were less likely to be stunted than girls with lower education . Household economic condition (measured by the asset quintile) was not associated with the risk of being thin or stunted. This could happen for a number of reasons. The seven-day food-frequency data showed no difference in the intake of rice/wheat (staple diet) among economic groups. Selectivity can be another possible reason; healthier girls looked mature and belonged to wealthier households and got married at a higher rate at earlier age than girls of poor households. Some like to look slim to improve body image and may have lowered the economic differential in thinness and stunting. Last but not the least is the frailty; girls of the poor households died off at a higher rate leaving behind the healthy ones and underestimating the economic differentials in the cross-sectional survey. Only a longitudinal study can resolve the frailty issue.We explored the dietary patterns among rural girls in relation to household economic condition (measured with asset quintile). Food items, such as fish, meat, eggs, and milk, are the major sources of animal-protein, calcium, and vitamin A. Half of them could not have meat, eggs, or milk in a week. Girls of the households in the highest asset quintile did consume fish/meat 2.1 (55%) days more, and eggs/milk two (91%) days more than the girls of the households in the lowest asset quintile. The difference in intake of quality food between income-groups was reported for schoolgirls in Dhaka city . The larIron deficiency is common among adolescent girls in Bangladesh , 6, as lWidespread undernutrition, micronutrient deficiency, low dietary knowledge, and low coverage of iron supplement among adolescents are concerns for public-health nutrition in Bangladesh. Adolescents are not the sole decision-makers. Parents, particularly mothers, often make decisions on their behalf, and they need to be sensitized about diet and nutritional needs in adolescence and adverse effects of undernutrition of adolescents to change their mindset. The CNPs, with appropriate communication materials, can do the job effectively. Dietary education in schools, communities, and health facilities in a coherent manner can bring larger effects than stand-alone interventions. Schools can incorporate dietary education and nutritional needs at this age into family-life education or health education.The school education programme cannot reach out-of-school girls who account for 34% or more in Bangladesh . An effeThe study used the data from the Baseline Survey 2004 of the National Nutrition Programme (NNP) implemented by a collaborative effort of ICDDR,B, Institute of Public Health Nutrition, and National Institute of Population Research and Training. The NNP, World Bank, and Canadian International Development Agency provided guidance and financial assistance to the baseline survey. The study was funded by ICDDR,B and its donors which provide unrestricted support to the Centre for its operation and research. Current donors providing unrestricted support include: Australian Agency for International Development (AusAID), Government of the People's Republic of Bangladesh, Canadian International Development Agency (CIDA), Embassy of the Kingdom of the Netherlands (EKN), Swedish International Development Cooperative Agency (Sida), Swiss Agency for Development and Cooperation (SDC), and Department for International Development (DFID), UK. The authors gratefully acknowledge these donors for their support and commitment to the Centre's research efforts."} +{"text": "Lyme disease is the most commonly transmitted vector-borne disease in the United States, with many regions of the country at risk. Like other spirochete-borne infections, Lyme disease progresses in stages, making diagnosis in the early stages of the illness and prompt treatment important for cure. An early diagnosis is made difficult by the less-than-ideal serologic tests and the varied clinical presentations of the disease. Although Lyme disease has been reported in pregnancy, the transmission rate to the fetus and potential harmful effects are largely unknown. This review discusses the diagnosis, clinical course, and treatment of Lyme disease with an emphasis on the pregnant patient."} +{"text": "The full set of symposium articles, including recommendations for future research, appear in Archives of Physical Medicine and Rehabilitation.The Rehabilitation Research and Training Center on Measuring Rehabilitation Outcomes and Effectiveness along with academic, professional, provider, accreditor and other organizations, sponsored a 2-day State-of-the-Science of Post-Acute Rehabilitation Symposium in February 2007. The aim of this symposium was to serve as a catalyst for expanded research on postacute care (PAC) rehabilitation so that health policy is founded on a solid evidence base. The goals were to: (1) describe the state of our knowledge regarding utilization, organization and outcomes of postacute rehabilitation settings, (2) identify methodologic and measurement challenges to conducting research, (3) foster the exchange of ideas among researchers, policymakers, industry representatives, funding agency staff, consumers and advocacy groups, and (4) identify critical questions related to setting, delivery, payment and effectiveness of rehabilitation services. Plenary presentation and state-of-the-science summaries were organized around four themes: (1) the need for improved The growing population of older adults who sustain strokes, hip fractures, joint replacements, and other conditions, Centers for Medicare & Medicaid Services' (CMS) inpatient prospective payment system (PPS), and technical advances in medical and surgical care have led to increasing demand for medical rehabilitation services. Medical rehabilitation provides crucial services that help people with chronic illness and disability learn to live as independently as possible. In inpatient rehabilitation facilities, physician coordinated, multidisciplinary teams focus on reducing impairments, enhancing independence in daily activities and quality of life, and minimizing caregiver burden. As documented in a recent Medicare Payment Advisory Commission (MedPAC) report , the heaOver the past 20 years the cost of postacute services, including postacute rehabilitation services, have grown much faster than overall inflation, reflecting an increased demand for services and growth in number of providers. The U.S. Congress passed a series of laws intended to reduce Medicare's PAC expenditures by establishing and refining PPSs for rehabilitation hospitals, nursing homes, long-term care hospitals (LTCHs), and home health (HHAs).Changes in payment mechanisms alters providers' incentives and indirectly the organization and availability of PAC. The consequences of payment changes on Medicare beneficiaries' access to high-quality rehabilitation services, independence, and quality of life are unknown. Research on access to, organization of, and the effectiveness of rehabilitation services is needed in order to understand the consequences of new payment mechanisms.Rehabilitation-focused health services research has concentrated on patients' natural recovery in single types of rehabilitation settings \u2013 rehabilitation hospitals and units, SNFs, LTCHs, and HHAs. It is often too expensive and unfeasible to evaluate costs and benefits of rehabilitation across sites of care, let alone specific paths of care, such as from hospitals to nursing homes to home. We know that most patients' functional independence improves during rehabilitation, but we know little about the \"active ingredients\" of rehabilitation and which types of patients are best suited for which setting so that optimal outcomes are achieved at a reasonable cost.Comparing outcomes across postacute settings has been hampered by the lack of a common outcome assessment instrument across settings, or a cross-walk between the instruments used by rehabilitation hospitals, SNFs, LTCHs, and home health agencies (HHAs). Imagine if Maryland's weights and measures differed from California's and Illinois's and Texas's \u2013 and we had no way to convert their measures. With only a bit of hyperbole, this is the situation Medicare finds itself in when trying to evaluate the relative effectiveness and cost effectiveness of rehabilitation hospitals, nursing homes, LTCHs, and HHAs.In the absence of scientific evidence and a way to compare outcomes across settings, Medicare has promulgated rules that limit access to IRFs. The so-called \"75% rule\" and Medicare fiscal intermediaries' \"local coverage determinations\" are based on expert opinion and on a dearth of scientific evidence. In developing these regulations, Medicare was dependent on anecdotal information. While the 75% rule was written to distinguish rehabilitation hospitals and units from acute care hospitals, Medicare revised inpatient rehabilitation facility (IRF) regulations to require explicit documentation of medical necessity and adopted the 75% rule to limit the types of patients admitted. Beneficiaries' access to rehabilitation services could suffer if the truism that \"the absence of evidence of effectiveness does not imply evidence of absence of effectiveness\" is not recognized.The need for expanded rehabilitation-focused health services research was addressed during a workshop in 2005 that was sponsored by the National Center for Medical Rehabilitation and Research (NCMRR) within the National Institute of Child Health and Human Development (NICHD) and the CMS [The Rehabilitation Research and Training Center on Measuring Rehabilitation Outcomes and Effectiveness, funded by the National Institute on Disability and Rehabilitation Research (NIDRR), was asked to lead the planning for what became the Symposium on Post-Acute Rehabilitation. The symposium was guided by a planning committee (see Acknowledgments) with representatives from the American Academy of Physical Medicine and Rehabilitation, the American Congress of Rehabilitation Medicine, the Association of Academic Physiatrists, the Foundation for Physical Medicine and Rehabilitation, the American Hospital Association, and the Federation for American Hospitals. The same organizations provided financial support. Major financial and staff support was provided by the American Medical Rehabilitation Providers Association (AMRPA). Additional sponsors included the American Physiatric Education Council, CARF International (formerly the Commission on Accreditation of Rehabilitation Facilities), Casa Colina Centers for Rehabilitation, eRehabData, Fowler Healthcare Associates, HealthSouth Corporation, IT Health Track, Johns Hopkins University Department of Physical Medicine and Rehabilitation, Kessler Institute for Rehabilitation, Moss Rehabilitation Hospital, MetroHealth Rehabilitation Institute of Ohio, the Rehabilitation Institute of Chicago, and UDSMR.The goal for the symposium was to serve as a catalyst for expanded research efforts on PAC rehabilitation so that relevant research can be used as the basis for policy and funding decisions. The planning committee sought to develop an agenda for research that supports an evidence base for PAC rehabilitation, including issues related to measurement and research design, access to PAC rehabilitation services, organization of rehabilitation services, and outcomes attained for beneficiaries of Medicare and other insurers. The objectives were to: (1) describe the current state of our knowledge regarding utilization, organization and outcomes of postacute rehabilitation settings; (2) identify methodologic and measurement challenges to conducting research in this area; (3) foster the exchange of ideas among researchers, policy-makers, industry representatives, funding agency staff, consumers, and members of advocacy groups; and (4) identify critical questions related to setting, delivery, payment, and effectiveness of rehabilitation services that are of the highest priority for investigation.The activities of the symposium were designed to help formulate a research and policy agenda and to stimulate policy discussions, to engage stakeholders who are involved in policy decisions, and to provide emphasis for the need for an evidence base for rational policymaking. Symposium organizers sought balance in perspectives of key stakeholders, including Congress, the CMS and private insurers, providers of rehabilitation services, patients and their advocates, and health service researchers.The planning committee invited research and policy leaders to present plenary and track-specific state-of-the-science summary speakers, and rehabilitation researchers to provide reports on contemporary work funded by AMRPA, the Rehabilitation Research and Training Center and other agencies. The planning committee invited 3 keynote speakers, former Senator Robert Dole; Laurence Wilson, director, Chronic Care Policy Group, CMS; and Steven Tingus, director, NIDRR. Four plenary speakers were invited to address each of the track themes. Articles by Pamela Duncan and Craig Velozo and discussion leaders summarized the recommendations which appear as the final report in the series. The remainder of this summary encapsulates key points from the plenary and state-of-the-science presentations followed by the track-specific research recommendations.Patient assessment data are collected in 3 of the 4 PAC settings. SNFs use an instrument called the Minimum Data Set 2.0, HHAs use the Outcome and Assessment Information Set, and IRFs use the Inpatient Rehabilitation Facility Patient Assessment Instrument, which includes the FIM instrument. LTCHs do not have a mandate to use an assessment instrument. Although these instruments include similar items, the item definitions and assessment periods are different. Further, for the functional assessment domain, all 3 instruments were designed with a fixed set of items, regardless of relevance. In their plenary session, Duncan and Velozo called fResearch priorities suggested by the measurement and methodology track participants included: develop validated measures of rehabilitation treatments; develop stronger cognitive and psychosocial outcome measures; develop long-term outcomes measures; develop robust severity and selection adjusters across the PAC rehabilitation patient population; assess the role of environmental factors on patient outcomes; and continue development of evidence-based treatment guidelines.Buntin identifiResearch priorities related to access include projecting the PAC needs of the population and determining the range and geographic distribution of existing PAC entities. Research should be directed to understand better how access is influenced by attitudes about family dynamics, social support, and cultural differences, as well as assumptions about the value of improvement for a patient who will not achieve complete independence.Kaplan describeChan describeParticipants in the processes of care track suggested that future research include randomized trials that test individual components of PAC care to determine optimal intensity, duration, and frequency of interventions. To overcome the current barriers of conducting research across provider types, the experiences of other health care systems such as the Veteran's Administration and Kaiser Permanente should be examined.Kane discusseParticipants in the effectiveness group suggested that future research should focus on what kind of treatment, or combination of services, is most effective in achieving specific outcomes for whom across the continuum of care. In addition, better measures of PAC rehabilitation treatments are needed so that key contents or treatments are identified and can be studied systematically and compared across the continuum of PAC. Participants expressed a strong need for a strategic research plan that is shared by payers, providers, research funders, and researchers; a common measurement time period; and collaboration between CMS, National Institutes of Health, the NIDRR, and the research community to provide flexibility within rigorously designed research protocols, because the PPS itself is a primary obstacle to treatment innovation.uSPEQ: Giving Quality a Voice, CARF International's customer feedback service. Keith began his affiliation with Casa Colina in the 1950s. He began volunteering as a clinical psychologist and soon developed a special interest in rehabilitation services, which eventually led him to develop Casa Colina's Research Department. He became a pioneer in the study of rehabilitation outcomes, published extensively, and helped contribute to the development of the industry standard method of assessing functional status. Our accomplishments are a reflection of their dedication and inspiration.Two colleagues who made major contributions to research and policy discussions on rehabilitation outcomes were very much with symposium participants in spirit, though their recent passing leaves us with a major loss. Deborah Wilkerson and Robert Allen Keith made enormous contributions to rehabilitation research. Wilkerson was a researcher, administrator, and national leader on outcomes measurement, rehabilitation services quality, postacute payment policy, and independent living issues. She led the outcomes measurement and performance indicator programs at CARF and spearheaded the research and development for Postacute rehabilitation care is a key component of the health care delivery system, yet we know little about the active ingredients of the rehabilitation process that produce the best outcomes. Well-designed research is needed to develop better measures for case-mix adjustment and outcomes of care. To advance rehabilitation effectiveness research and support the development of evidence-based policies, we must invest in developing new and improve existing measures of patient characteristics, treatment contents, and long-term outcomes. Critical research needs include (1) developing validated measures of rehabilitation interventions and case mix; (2) standardizing PAC measures and timing of routine measurement for payment and quality assurance purposes across sites of care; (3) examining differences in content and processes of care both within facilities of the same type and across types of facilities; (4) identifying patient characteristics that vary by region such as rural and urban mix, cultural characteristics, and provider referral patterns; and (4) implementing a \"strategic plan for effectiveness research\" that is characterized by collaboration between CMS, federal research funders, researchers, and care sites.The organizers and sponsors of this symposium trust that our goal of catalyzing expanded research on PAC rehabilitation is furthered by the publication of this set of articles. Our nation's health policy requires a solid base founded on compelling evidence. We look forward to the benefits of greater research attention to improved measurement and research design, access to PAC rehabilitation services, organization of rehabilitation services, and outcomes attained for patients, taxpayers, and Medicare and other insurers.Archives of Physical Medicine and Rehabilitation .Supported by the National Institute on Disability and Rehabilitation Research through a Rehabilitation Research and Training Center on Measuring Rehabilitation Outcomes and Effectiveness (grant no. H133B040032).No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author or upon any organization with which the author is associated."} +{"text": "The establishment and characterisation of six cell lines from primary human colorectal adenocarcinomas is described. These lines were established from surgical specimens, from 49 unselected patients, without the use of 'feeder' cells, 'conditioned' medium or passage of cells in nude mice. The six cell lines exhibit considerable variation in morphology, CEA secretion and tumourigenicity in nude mice. At least two of the lines retain some of the differentiated characteristics of colorectal epithelium."} +{"text": "The HomB encoded outer membrane protein was shown to contribute to the proinflammatory properties of H. pylori and also to be involved in bacterial adherence.The homB and homA genes in 455 H. pylori strains from East Asian and Western countries, and carried out sequence comparison and phylogenetic analyses.This study investigated the distribution of homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains.Both homB and homA sequences revealed diversity regarding the number of copies and their genomic localization, with East Asian and Western strains presenting different genotypes. Moreover, homB and homA sequence analysis suggests regulation by phase variation. It also indicates possible recombination events, leading to gene duplication or homB/homA conversion which may as well be implicated in the regulation of these genes. Phylogenetic reconstruction of homB and homA revealed clustering according to the geographic origin of strains. Allelic diversity in the middle region of the genes was observed for both homB and homA, although there was no correlation between any allele and disease. For each gene, a dominant worldwide allele was detected, suggesting that homB/homA allelic variants were independent of the geographical origin of the strain. Moreover, all alleles were demonstrated to be expressed in vivo.Analysis of homB and homA genes are good candidates to be part of the pool of H. pylori OMPs implicated in host-bacteria interface and also contributing to the generation of antigenic variability, and thus involved in H. pylori persistence.Overall, these results suggest that H. pylori infection is implicated in the development of several gastroduodenal diseases, ranging from chronic active gastritis and dyspepsia to peptic ulcer disease (PUD), and associated with an increased risk for gastric cancer .The sequences used in this study are under the GenBank accession numbers [GenBanK: (PUD): Peptic ulcer disease; (NUD): non-ulcer dyspepsia; (OMP): outer membrane protein; (ORF): open reading frame; (Ks): synonymous substitutions; (Ka): non-synonymous substitutions.MO carried out experimental design of the study, phylogenetic analysis and co-drafted the manuscript; RC carried out bacterial cultures, PCR and phylogenetic analysis; AM co-drafted the manuscript; YY and DQ carried out bacterial cultures and PCR; FM and LM supervised the study. All authors have read and approved the final version of the manuscript."} +{"text": "The epidemiology of foodborne disease is changing. New pathogens have emerged, and some have spread worldwide. Many, including Salmonella, Escherichia coli O157:H7, Campylobacter, and Yersinia enterocolitica, have reservoirs in healthy food animals, from which they spread to an increasing variety of foods. These pathogens cause millions of cases of sporadic illness and chronic complications, as well as large and challenging outbreaks over many states and nations. Improved surveillance that combines rapid subtyping methods, cluster identification, and collaborative epidemiologic investigation can identify and halt large, dispersed outbreaks. Outbreak investigations and case-control studies of sporadic cases can identify sources of infection and guide the development of specific prevention strategies. Better understanding of how pathogens persist in animal reservoirs is also critical to successful long-term prevention. In the past, the central challenge of foodborne disease lay in preventing the contamination of human food with sewage or animal manure. In the future, prevention of foodborne disease will increasingly depend on controlling contamination of feed and water consumed by the animals themselves."} +{"text": "The relationship between food intake and cancer of the large bowel was assessed by calculating the average intakes of foods, nutrients and dietary fibre in the different regions of Great Britain and relating these to the regional pattern of death from colon and rectal cancers between 1969 and 1973. No significant associations were found with the consumption of fat, animal protein or beer, nor with current estimates of total dietary fibre intake. Average intakes of the pentose fraction of total dietary fibres, and of vegetables other than potatoes, were negatively correlated with the truncated age- and sex-standardized death rates from colon cancer (r = -0.960 and -0.940). Specific components of dietary fibre may therefore inhibit colon carcinogenesis."} +{"text": "Tourism has been an instrument of social, cultural, religious, and economic phenomena throughout the globe since ancient time. Progress in opportunities of travel, stay, and information and communication technology has further facilitated people moving from one place to another for leisure, business, education, or medical purpose. A booming economy has far-reaching consequences on all sectors of human development including health. This is true for countries in transition especially India.International tourist arrival throughout the globe was 922 million and India\u2019s share of foreign tourist arrivals (FTAs) stood at 5.4 million during 2008 whereas it was 2.38 million in 2002. Though tThe International Passenger Survey (2003) estimates that about 2.2% of the foreign travelers and 10% of the non-resident Indians (NRIs) visited India with the objective of health care and treatment. India trMedical tourism (MT) involves traveling to an advanced facility in another country for receiving requisite medical/surgical treatment at a much lower cost that is often linked with using the savings to opt for and enjoy a holiday during recovery. However, this is largely true for ambulatory/elective interventions. Some of the favored destinations for MT across the globe include Cuba, Costa Rica, Hungary, Israel, Jordon, Lithuania, Belgium, South Africa, Singapore, Thailand, Philippines, Malaysia, India, and South Korea. MT is noDue to aggressive promotion from stakeholders, Indian private hospitals are increasingly finding a mention in the travel itineraries of foreigners. MT is witnessing an upward trend because India has large number of world heritage monuments, archeological and religious sites, and diverse cultural festivals at one end to state-of-the-art infrastructure and skilled medical manpower that is using innovative technology; quality care of service with high success rate/outcome; compassionate nursing care, English-speaking staff, no waiting time for surgeries; and the most critical element of service delivery at a very affordable cost in comparison to well-developed nations. The indicative cost is shown in On the similar front, outsourcing of diagnostics, promotion of research and development (R&D), rapid growth of research institutes, well-established pharmaceutical industries, initiation of large number of clinical trials, development of newer concepts like surrogate mothers, preservation of cord blood/stem cells, milk banks, and successful use of telemedicine at various settings are some of the catalyzing factors ensuring high visibility and prominence of the Indian health sector in the global news. The rise of Sports Medicine as a subspecialty and successful culmination of Commonwealth Games in New Delhi during the latter half of 2010 will further propagate the phenomenon of MT by leaps and bounds. In addition to above, other value-added service offered in India includes a bouquet of preventive check-ups, wellness therapies, yoga, meditation/spiritual enlightenment, hydrotherapy, mud-therapy, and ayurvedic healing, thus enlarging the scope from \u201cmedical\u201d to \u201chealth\u201d tourism.Tourism is overwhelmingly an industry of private sector although public sector has a significant role to play at different levels including the promotion of public private partnership (PPP). Government of India (GoI) has recognized the economic potential of MT and is promoting this underexplored arena through its market development assistance (MDA) scheme especially for accredited institutions to strengthen the Indian health care brand overseas. Under this, hospital groups will be provided financial assistance for publicity through printed materials, travel and stay expenses for sales-cum-study tours, and participation fees for trade fairs and exhibitions. Calendars of international health events are being planned and the events are being held annually. Efforts are being made for introducing uniform pricing band through various consultative processes by stimulating stakeholders for the formation of common platform/consortium. GoI has introduced medical visa for patients desirous of undergoing treatment in India.On the regulation of human resource for health, Planning Commission (GoI) is encouraging all State Councils to shift to a system of periodical renewal of registration of medical personnel. In the field of paramedical education including physiotherapy and occupational therapy, priority is being given to the establishment of National Paramedical Council as an apex body to determine standards of education/training and to ensure uniform enforcement on the lines of Medical Council of India (MCI) for MBBS/higher courses. In the rTo enhance visibility and scalability and attract more clients, health institutions in India will require intensive efforts on the establishment and compliance of rigorous quality standards, implementation of international best practices, and communication thereof. Health services are increasingly coming under independent evaluation by accreditation agencies in many countries. Accreditation is a voluntary process by which an authorized agency/organization evaluates and accredits health service according to a set of standards describing the structure and processes that contribute to desirable patient outcomes. The patients get services by credential medical staff. Rights of patients are respected/protected and regularly evaluated through patient satisfaction and simultaneously there is an element for professional growth/enrichment.Accredited institutions are potential winners in attracting and retaining foreign clients. Some private health institutions in India have taken up accreditation from JCI and stilIn spite of very optimistic, supportive, and economically driven environment being garnered for MT, some of the issues and concerns could be incentives, concessions and taxation, follow-up services, limited presence of global health insurers, exodus of specialists from public health system to private sector, malpractices by patients/attendants, litigation, legal stay, and import of exogenous infection(s). However, taking a clue from the current scenario, it would be apt to conclude that MT has a huge potential in times to come as more and more foreign travelers will be visiting India for their health needs and keeping an eye on future will lead to quantitative and qualitative gains for both international and national clients."} +{"text": "The characteristics of sites of intramural cancer spread were examined by comparing theintraductal ultrasonography (IDUS) and wall thickening findings at sites of intramural cancerspread and non-spread, in patients with malignant bile duct stenosis who had undergonepercutaneous transhepatic biliary drainage (PTBD).The subjects were ten patients with extrahepatic bile duct cancer, two with pancreaticcancer, one with cancer of the gallbladder, and one with cancer of the papilla of Vater whounderwent preoperative IDUS. From these patients, 50 IDUS slices were examined with acongruent relationship with the histologic section of resected tissue. The maximumthickening, minimum thickening, maximum/minimum thickening ratio, and form factor of themedial and lateral margins of the medial hypoechoic layer were determined using diagnosticimaging, and the results were compared at sites of cancer spread and non-spread.Twelve slices were obtained from the site of stenosis, 14 from sites of cancer spread, and 24from non-spread sites. The maximum thickening, minimum thickening, and maximum/minimumthickening ratio differed significantly between the sites of spread and the non-spread.The absolute values for wall thickening are useful for diagnosing the presence of intramuralspread in patients with malignant biliary duct stenosis."} +{"text": "N-deacetylated derivative chitosan, have been identified as versatile biopolymers for a broad range of applications in medicine, agriculture and the food industry. Two of the main reasons for this are firstly the unique chemical, physicochemical and biological properties of chitin and chitosan, and secondly the unlimited supply of raw materials for their production. These polymers exhibit widely differing physicochemical properties depending on the chitin source and the conditions of chitosan production. The presence of reactive functional groups as well as the polysaccharide nature of these biopolymers enables them to undergo diverse chemical modifications. A complete chemical and physicochemical characterization of chitin, chitosan and their derivatives is not possible without using spectroscopic techniques. This review focuses on the application of spectroscopic methods for the structural analysis of these compounds.Chitin, the second most important natural polymer in the world, and its For HPLC separation a different type of column is used, and the mobile phase often consists of acetonitrile or water with added formic acid + and [M + H]+, respectively . This haversus right-handed polarized light that arise due to structural asymmetry [et al. [N-acetylation of low-molecular-weight chitosan (LMWC) prepared from pectolytic hydrolysates of chitosan. Circular dichroism spectra showed a decrease in the segment of N-acetylated glucosamine units in LMWC.CD spectroscopy measures differences in the absorption of left-handed polarized light symmetry . A CD sp [et al. used CD In general spectroscopic techniques are very useful and important in the structural analysis of chitin, chitosan and their derivatives, although we need to mention that there are many other non-spectroscopic analytical methods that are routinely used in such studies: viscosity measurements, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), cyclic voltamperometry, high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC).N-acetylation, pattern of N-acetylation, degree of polymerization, molecular weight, crystallinity, the sequence or degree of substitution, as well as in monitoring reactions, controlling the purity of these compounds and in characterizing their intra- and intermolecular interactions, is discussed. It should also be mentioned that the structural analysis of chitin/chitosan and their derivatives is based on the application of at least a few different types of spectroscopic methods during the same study. The main reason for this is the possibility of obtaining different but compatible and complete information about the structure and physicochemical properties of these compounds, which is impossible using only one spectroscopic technique. Continuous improvements in sampling techniques, analysis software and instrumentation hardware, mean that spectroscopic methods have revolutionized the chemical and physicochemical characterization of chitin/chitosan samples, and are now routinely used by scientists working in the chitin/chitosan field.Chitin and chitosan are natural aminopolysaccharides with unique structures and interesting properties such as biocompatibility and biodegradability; they are non-toxic, have a wide range of applications, and the raw material sources for their production are unlimited. Chemical modification of these polymers results in improved solubility in water or organic solvents, which enhances their biological activities and favors the continuous development of their applications as new functional biomaterials with excellent potential in various fields. In order to acquire a deeper understanding of the mechanism of these properties, it is necessary for chitin/chitosan and their derivatives to be structurally and physicochemically well characterized. Knowledge of the microstructure of these compounds is essential for an understanding of structure\u2013property\u2013activity relationships. Although spectroscopic methods are of great use to scientists working in the chitin/chitosan field, many researchers lack specialist knowledge of these techniques. This paper focuses on the practical aspects of using the five spectroscopic methods most often applied \u2013 X-ray spectroscopy, infrared (IR) and UV-Vis-spectroscopy, mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR-spectroscopy) \u2013 in the structural investigation and physicochemical characterization of chitin, chitosan and their derivatives. The application of other spectroscopic methods is also discussed. This paper provides hands-on information about these valuable research tools, emphasizing practical aspects such as sample preparation or typical measurement conditions, their limitations and advantages, and interpretation of results. The usefulness of these methods in establishing and confirming molecular structures, determining physicochemical parameters such as the degree of"} +{"text": "In contrast to most other forms of cancer, data from some developing and developed countries show surprisingly similar survival rates for ovarian cancer. We aimed to compare ovarian cancer survival in Philippine residents, Filipino-Americans and Caucasians living in the US, using a high resolution approach, taking potential differences in prognostic factors into account.Using databases from the SEER 13 and from the Manila and Rizal Cancer Registries, age-adjusted five-year absolute and relative survival estimates were computed using the period analysis method and compared between Filipino-American ovarian cancer patients with cancer patients from the Philippines and Caucasians in the US. Cox proportional hazards modelling was used to determine factors affecting survival differences.Despite more favorable distribution of age and cancer morphology and similar stage distribution, 5-year absolute and relative survival were lower in Philippine residents than in Filipino-Americans . After adjustment for these and additional covariates, strong excess risk of death for Philippine residents was found . In contrast, no significant differences were found between Filipino-Americans and Caucasians living in the US.Multivariate analyses disclosed strong survival disadvantages of Philippine residents compared to Filipino-American patients, for which differences in access to health care might have played an important role. Survival is no worse among Filipino-Americans than among Caucasians living in the US. Ovarian cancer is the second most common gynaecological cancer worldwide and the sixth most common cancer in women overall ,2. The mComparisons in ovarian cancer survival between developed and developing nations, as well as between ethnic groups within countries, are few -7, but aIn this paper, we take a \"high resolution\" approach -10 to elUsing the Surveillance, Epidemiology and End Results (SEER) 13 database , ovarianPatient information for residents of the National Capital Region (NCR) of the Philippines was abstracted from the Philippine Cancer Society-Manila Cancer Registry (PCS-MCR) and the Department of Health-Rizal Cancer Registry (DOH-RCR). The registries are regarded as among the high-quality registries from developing countries and have consistently been included in the \"Cancer Incidence in Five Continents\" series -15. TheyUsing the same inclusion and exclusion criteria as for the SEER databases, a list of 2,898 ovarian cancer cases diagnosed between 1998 and 2002 was generated, from which sub samples of 200 cases diagnosed in each calendar year of interest were randomly drawn using the .sample command in STATA version 6 . PatientThe project proposal was approved by the Ethics Review Board of the National Institutes of Health of the University of the Philippines Manila. The information obtained strictly conformed to the code of conduct stipulated by the Guidelines on Confidentiality for Population-based Cancer Registries .To derive survival estimates, cohort-based analyses such as the conventional life-table method or the Kaplan-Meier method ,19 have As commonly practiced in population-based cancer survival analysis, both absolute and relative survival rates were calculated. The relative survival probabilities are estimated as ratios of the observed survival of cancer patients and the expected survival of a group of people with the same age and sex distribution from the general population, and reflect the survival experience of cancer patients in the absence of competing causes of death ,27. UsinTo enable comparison of ovarian cancer survival estimates between different cancer populations, age adjustment was done. Age-specific period survival estimates (absolute and relative), using age groups 15-39, 40-49, 50-59, 60-69 and 70 and above, were first obtained from the Philippine resident, the Filipino-American and the Caucasian populations. The age-specific estimates were then weighted and summed for each population group, using weights from the World Standard Cancer Patient Population (WSCPP) .The differences between survival estimates for the three cancer patient populations were tested for statistical significance using a novel modelling approach for period analysis . First, To explain possible survival differences and identify factors affecting survival, both within and between the three cancer patient populations, the Cox Proportional Hazards model was used. For each population group, bivariate associations of age, stage at diagnosis, histology, and receipt of surgery and of radiotherapy with survival were determined using individual Cox models. A multivariate model was then built jointly for all three groups to compare survival probabilities between populations. Relative hazards were calculated using Filipino-Americans as the reference group, while controlling for the effects of age, stage, histology, surgery and radiotherapy, first individually and then simultaneously. Those with missing information were excluded in the multivariate analysis. The assumption of proportional hazards for Cox models was checked by plotting the log of the negative log of the survival density functions vs the log of survival time. The plotted lines were roughly parallel over time and no violations of the proportional hazards assumption were found.Age at diagnosis was categorized into the age adjustment groupings mentioned earlier. Stage categories were based on the Federation of Gynecology and Obstetrics (FIGO) stages I, II III and IV . HistoloAll analyses were done with the SAS Statistical Analysis Software. Special macros were used for standard and modelled period survival analysis as previously described ,34.A total of 463 Filipino-American and 22,290 Caucasian ovarian cancer patients were included in the analysis, after exclusion of around 1% of cases who are coded in situ and those who were identified by death certificates only (DCO). From the 2,000 randomly sampled patients from the Philippine databases, 1,475 ovarian cancer patients (73.8%) were included after 220 (11%) and 305 (15.2%) patients were removed due to invalid data, such as incorrect age, sex and primary site, and due to the absence of any survival time information, respectively. Of the included patients not known to be dead, complete 5-year follow-up information was obtained for 33.8%, while at least some follow-up could be ascertained for another 41.3%.The distribution of cases by age groups, stage at diagnosis, histology, surgery and radiotherapy are shown for each population in Table Age adjusted and age-specific estimates of absolute and relative 5-year survival are shown in table As shown in table In bivariate comparative survival analysis between population groups table , substanIn this \"high resolution\" study comparing ovarian cancer survival in the Philippine resident and Filipino-American patients, sharing the same ethnicity, and in Filipino-American and Caucasian patients in the US, sharing the same health care system, overall survival differences were found to be relatively small. However, Philippine resident patients showed a more favorable distribution with respect to major prognostic factors, such as age, stage and morphology, and major excess mortality in this patient group was disclosed after control for these factors in age specific and multivariate analysis. By contrast, an apparent survival disadvantage of Caucasian patients compared to Filipino-American patients essentially disappeared after controlling for these factors. Taken together, these results point to the relevance of health care related factors for explaining survival differences.Disadvantages in absolute and relative survival of Philippine residents compared to Filipino-Americans were particularly large for age groups 50-59 and 60-69, which can be explained to some extent by more unfavorable stage distributions. The proportions of patients presenting with advanced stages in age groups 50-59 and 60-69 were much lower in Filipino-Americans than among Philippine residents .In the absence of effective screening methods, only a small proportion of ovarian cancer cases are diagnosed in early stages, where surgery alone will be effective ,35,36. MIn developed countries, survival rates have improved in the recent decades -40, mainIn the NCR, Philippines, adjuvant chemotherapy has been shown to improve survival . HoweverCompounding the problem among Philippine residents is the persistent disbelief in chances to be cured from cancer . In spitWhile much of the differences are likely to be explained by health care access, dissimilar distributions by age, stage and histology suggest a possible role of biological factors. The differences in tumor biology between populations might be reflective of the heterogeneous nature of ovarian cancer, and should be investigated in more detail, given that previous studies have shown significant variation of survival by histologic subtypes ,47-49.Between Filipino-Americans and Caucasians, slightly higher absolute and relative survival rates were observed for the former group. The distributions by age and stage at diagnosis vary between the groups, with Filipino-Americans having more favorable characteristics. The Cox model showed that the higher proportion of Caucasian women with older age and advanced disease explains most of the apparent survival difference. After adjustment for these variables, as well as morphology and treatment, the residual excess risk was small (15%) and not significant. Sensitivity analyses regarding difference in survival estimates between Caucasian population with and without Hispanics did not show a significant difference.Our study is limited to variables that were available and comparable in the databases, and not all possible factors that could affect survival were considered. Information on chemotherapy is not included in the SEER public use database whereas some tumor characteristics such as grade, size and heterogeneity were not available from the Philippine database. In addition, socio-economic status, family history of ovarian cancer and lifestyle factors, like contraceptive use and hormone intake, were also not studied. Similarly, more detailed information on health care access, particularly on access to and availability of various treatment regimens, as well as application of treatment guidelines, protocols used, specialization and expertise of treating physicians, were not obtainable.Patients with invalid data and those who do not have follow-up time were excluded from the study, but it is unlikely that they have higher survival than those who were included. Most such patients have incomplete records and were not traced to other hospitals in the NCR, indicating that they might not have consulted physicians after the initial diagnosis, or have had limited consultations afterwards. They most probably have not received any form of treatment as the availability of cancer treatment is limited outside the NCR. The survival rates presented might therefore overestimate true survival of Philippine residents to some extent.In conclusion, the results of the multivariate analyses disclosed strong survival disadvantages of Philippine residents compared to Filipino-American patients, despite similar overall survival rates observed in the presence of more favorable distributions of major prognostic factors. The survival disadvantage of Philippine resident patients most likely reflects differences in access to and affordability of effective health care and treatment, such as chemotherapy. Emphasis should therefore be given on improving access to and affordability of effective treatment regimens. Prognosis is no worse among Filipino-Americans than among Caucasians living in the US.cancer registry-based study on survival and care of cancer patients; FIGO: Federation of Gynecology and Obstetrics; RR: Relative risk; IACR: International Association of Cancer Registries; IARC: International Agency for Research on Cancer; ICD-O: International Classification of Diseases for Oncology; NCR: National Capital Region; PCS-MCR: Philippine Cancer Society-Manila Cancer Registry; RS: Relative survival; SE: Standard error; SEER: Surveillance, Epidemiology and End Results; WSCPP: World Standard Cancer Patient Population; US: United StatesAPI: Asian and Pacific Islanders; AS: Absolute survival; DCO: Death certificates only; DOH-RCR: Department of Health-Rizal Cancer Registry; EUROCARE: European The authors declare that they have no competing interests.The contributions of the authors are as follows: MTR contributed in the planning of the study, supervised data collection, performed the analysis and wrote the manuscript; AL, MRL, GU, JT and DB planned and supervised data collection, reviewed and edited registry abstracts, and performed data management; AG assisted in the analysis; HB contributed in the planning of the study and supervised data analysis and writing of the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/340/prepub"} +{"text": "The carcinogenic effects of dimethylnitrosamine (DMN) and nitrosomethylurea (NMU) injected subcutaneously at 3 different dose levels in European hamsters were studied. DMN induced malignant haemangioendotheliomata of the liver and kidney, hepatocellular carcinomata and, in one animal, a cholangiocellular carcinoma. The effect of NMU was localized at the site of administration and resulted in subcutaneous fibrosarcomata, carcinosarcomata or epidermal carcinomata."} +{"text": "There is no national joint replacement registry in the country of Asia and reports of national outcomes of joint replacement in Asia as yet. Therefore, this study was then to report a national data of the number of hip replacements, incidence rate, demographic characteristics of hip replacement patients, and short-time survival rate after hip replacement of Han Chinese in Taiwan.We analyzed 105,688 cases of hip replacements from National Health Insurance research database between 1996 and 2004. The survival rate of primary hip replacement was estimated for each disease by the Kaplan-Meier method.Average annual number of primary partial hip replacement and primary total hip replacement were 4,257 and 6,206 cases, respectively. The most two common diagnosis of primary partial hip replacement were femoral neck fractures and avascular necrosis . In primary total hip replacements, the most two common diagnosis were avascular necrosis and osteoarthrosis . Both the number of primary partial hip replacements and primary total hip replacements increased steadily between 1996 and 2004. The cumulative survival of primary partial hip replacements and primary total hip replacements in all patients were 93.97% and 79.47% in 9 years follow-up, respectively.Avascular necrosis is the main disease in total hip replacement in Taiwan. The epidemiology of hip diseases was different between Han Chinese (in Taiwan) and Caucasian and the number of hip replacements increased substantially in Taiwan between 1996 and 2004. National joint replacement registry is a good solution to record and publish the information for the orthopaedic community on the outcome of joint replacement surgery. Norway in 1987) [987 [1] aSince the implementation of the National Health Insurance (NHI) in Taiwan in 1995, we have accumulated a huge database of clinical cases greater than 96% of the total population in Taiwan. People have received medical health care coverage from this universal national health care system. There were greater than 95% of all the hospitals contained in the NHI databases in Taiwan . InformaThe purpose of this study was then to report a data of the number of hip replacements, incidence rate, demographic characteristics of hip replacement patients, and short-time survival rate after primary hip replacement in Taiwan.The National Health Insurance program has implemented since March 1995, and the development of the Taiwan's health economy has really taken off. It provides several measures to protect the unemployed, the poor, and the victims of natural and manmade disasters. Moreover, by safeguarding the right of the weak to have access to medical care, the program maintains social order and provides security during this time of economic recession. Until June 2006, there were 22.3 million individuals enrolled in the NHI with a coverage rate of 99% populations (22.7 million) and 18,289 healthcare providers contracted with NHI, representing 91.45% of all providers in Taiwan.In order to survey the results of hip replacement surgery, we analyzed 105,688 cases of registry for contracted medical facilities and inpatient expenditures by admissions from NHI research database between 1996 and 2004, on the basis of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code for THR (81.51), partial hip replacement (PHR) (81.52) and revision of hip replacement (including PHR and THR) (81.53) listed as the major operation. These cases included 38,349 cases of primary THR, 55,884 cases of primary PHR and 11,455 cases of revision of hip replacement. We excluded 51 cases (26 cases of primary THR and 25 cases of primary PHR) which aged less than 16 years old. The insurance data was registered by physicians before operation. The data of inpatient expenditures contained six categories including personal information, date of inpatient, diagnosis, operation, expenditures, and hospital information. The items including patient identity, date of operation, birthday, gender, diagnosis, and treatment were used in this study. We compared the patient identity between primary operation (PHR and THR) and revision of hip replacement, and found there were 1,201 and 1,905 cases of revision from the failure of primary PHR and THR originally enrolled in the database, respectively. Survival of primary hip replacement was estimated for each disease by the Kaplan-Meier method .The reports of primary THR in Taiwan, Norwegian ,13 and SIt is worth to be taken notice of the difference that the mean age of OA patients in Taiwan (60 years) were younger than Norwegian and Swedish (70 years) as shown in Table This study reported statistical data of primary PHR and THR in Taiwan and showed the difference in epidemiology of hip diseases between Han Chinese and Caucasian. AVN is the main disease in primary THR in Taiwan and it is very different form Caucasian in age and gender. Moreover, mechanical complication of hip prosthesis is the main reason for revision. We should be careful with the generalizing results from western countries to other ethnic groups.The authors declare that they have no competing interests.YS wrote the initial manuscript drafts. HW ensured the accuracy of analysis and revised the initial manuscript drafts. YS and HW participated in the design of the study and performed the statistical analysis. YS and CK conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript."} +{"text": "In a series of patients drawn from the Birmingham Regional Cancer Registry (England) with tumours of the salivary glands, a significant excess of second primary tumours was observed. For females, the excess was found mainly in breast and bronchus and, for males, in prostate and skin. In a parallel series of female breast-cancer patients, the observed number of second primary tumours in salivary glands significantly exceeded expectation. These results support the reported association between salivary gland and breast cancer, and suggest that other hormone-dependent sites are also at risk."} +{"text": "East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities.Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building.Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-the-job training and short courses were the preferred modes of training.There is inadequate capacity for managing medicines and related commodities in East Africa. There is an urgent need for training in aspects of pharmaceutical management to different categories of health workers. Skills building activities that do not take healthcare workers from their places of work are preferred. Over the past few years, East African countries have experienced a tremendous increase in the volume of antiretroviral drugs. This is a direct result of the commendable global initiatives towards improving access to effective treatment of HIV/AIDS ,2. Lack To build in-country and regional capacity in pharmaceutical management, Uganda's Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established the Regional Technical Resource Collaboration (RTRC), a network of academic institutions to build capacity for pharmaceutical management. The initiative , which iA cross-sectional survey of fifty governmental and non-governmental institutions accredited to provide ART services in the four countries was conducted in the months of February and March 2005. One researcher from Makerere University and one in-country collaborator carried out the assessment. The assessment used a qualitative research methodology that included interviewing key informants, in-depth interviews of health care workers, and a survey of health facilities and programs.The survey covered both urban and rural areas and looked at different facets of healthcare provision including, public, private-for-profit, and private not-for-profit sectors. By convenience sampling, a minimum of 10 facilities were targeted in each country and at least three healthcare workers from each facility were interviewed.The assessment was standardized across the participating countries through a planning workshop, which brought together collaborators from Makerere University, Harvard Centre for International health, Management Sciences for Health, and two representatives of the AIDS Control Program from each of the four countries. The workshop reviewed the data collection tools, discussed the assessment logistics and process and agreed on time lines. Data collection tools were piloted at three health facilities and two programs in Uganda and their validity and reliability ascertained. These were later excluded from the main study. Permission to carry out the survey was obtained from the national HIV/AIDS control programs of the respective countries. Appointments with heads of the facilities and respondents were made by personnel from the national AIDS control program in each country.The heads of the National AIDS Control Programs, Ministry of Health Pharmacy Services, and HIV treatment programs were identified as key informants. Using the data collection tool information on; the general features of the country's ARV supply system , qualification and training of health care workers involved in supply management of ARVs and related commodities, and the training needs for the supply management of pharmaceuticals was sought in a face to face interview.The heads of the facilities providing ART services in the four countries were the key informants at the program level. The survey looked at the types of HIV/AIDS services provided, the existence of guidelines for management of ARVs and related commodities, the qualification of healthcare workers managing the supply of pharmaceuticals, existence of any ongoing skills building activities, and areas covered in ongoing training programs.Structured in-depth interviews of healthcare providers were held with physicians, pharmacists, pharmacy assistants, nurses and clinical officers. Information was sought on training background, knowledge of ARV supply management systems and the quality of the service provided.At the end of each survey, questionnaires were checked for completeness, accuracy and consistency. At the end of each assessment, analysis of the data involved discussion with various in-country stakeholders for more in-depth interpretation of perceptions and opinion on possible interventions to address identified problems. Quantitative data were analyzed using EPI INFO Version 3.3, while qualitative data were coded and manually analyzed. No statistical comparisons were made as this was a situational analysis survey without sufficient power for such analysis.National AIDS Control Programs were responsible for the development and implementation of HIV/AIDS treatment policies in all four countries. Public, private-not-for profit and private-for-profit institutions were involved in HIV/AIDS treatment and care in all the four countries. In the public institutions HIV/AIDS treatment was limited to district level facilities or higher at the time of the assessment.A total of 54 facilities involved in ART services were surveyed in the four countries, comprising of 27 public, 18 private not-for-profit, 5 private-for-profit, and 4 academic institutions were delivering a series of training courses on managing procurement and logistics of HIV/AIDS drugs and related supplies . The tarEven though retail pharmacy outlets dispensed ARVs in Kenya, Uganda and Tanzania, clinical training programs on ART seldom included them. Future training initiative should include private pharmacies. In Kenya, policy makers believe that professional bodies such as the Kenya Pharmaceutical Society could contribute significantly to the training of community pharmacists providing ART services.Capacity for ARVs supply management in Uganda, Kenya, Tanzania, and Rwanda were found to be limited due many problems. These problems included poor human resource with inadequate skills and capacity to select, quantify and distribute the drugs, with irrational prescribing and dispensing. This calls for There is thus need to provide training in drug supply management in all four countries. Training processes that include local institutions are more sustainable and likely to cover wider geographical areas. The preferred modes of training are on-the-job training and short courses that do not draw participants away from their workplaces.The authors declare that they have no competing interests.PJW: Participated in designing the study, planning, data collection, data analysis and manuscript writing. ROA: Participated in designing the study, planning, data collection, data analysis and manuscript writing. CO: Participated in designing the study, planning, data collection, and manuscript writing. EO: Participated in designing the study, planning and data collection. WT: Participated in designing the study, planning and data collection. JO: Participated in designing the study, planning and data collection. WWA: Participated in designing the study, planning and data collection. LM: Participated in organizing funding, data analysis and manuscript writing. OA: Participated in applying for funding, designing the study, data collection, data analysis and manuscript writing."} +{"text": "To the Editor: The global increase of antimicrobial-drug resistance, including resistance to the new and most potent antimicrobial agents, is a major public health concern. In low-resource countries, where bacterial infections are still among the major causes of death, especially for children, it is of particular concern (www.unifi.it/infdis/antres/default.htm). In 2002, the baseline ANTRES study showed a high rate of fecal carriage of Escherichia coli with acquired resistance to several antimicrobial drugs, especially older drugs , in preschool children from 4 urban settings in Bolivia and Peru is a research project on antimicrobial-drug use and resistance in low-resource countries of Latin America and 2 in Peru . The study design, sampling and inclusion criteria, methods, and ethical issues were the same as those of the baseline study . StatistE. coli population in both surveys. The most relevant finding of the 2005 survey was the remarkable increase since 2002 in the resistance rates to fluoroquinolones and expanded-spectrum cephalosporins . The increased prevalence of resistant E. coli strains in preschool children most likely reflects increased exposure within a contaminated household setting, in the food chain, or both (,,Increasing resistance to fluoroquinolones and expanded-spectrum cephalosporins among E. coli, to evaluate the effects of these important reservoirs of resistance genes distributed in the community, to investigate the epidemiologic relationship with clinical isolates, and to define the role of the food supply. Investigation into whether carriage of resistant strains in adults correlates with data on antimicrobial-drug use in hospitals and in the community would also be of interest.Our findings support the need to continue monitoring the evolution of resistance in commensal"} +{"text": "Symposium: A Practical Approach to Evidence-Based OrthopaedicsThe process of scientific discovery is, in effect, a continual flight from wonder.Albert EinsteinJournal of Bone and Joint Surgery adopted EBM and levels of evidence grading for all clinical papers. Since then, all major North American orthopedic meetings and journals have adopted evidence-based orthopedic teachings in some format or another.Evidence-based medicine (EBM) was recently noted as one of the top 15 medical discoveries over the past 160 years. The term EBM has become so commonplace in the practice of medicine that it seems hard to believe that the term, itself, was only coined in 1990 at McMaster University (Canada). The popularity of EBM has only recently expanded to evidence-based orthopedics. In 2003, the Evidence-based orthopedics requires an understanding of a new language and principle in the evaluation of clinical research and its impact on patient decision-making. While the concepts may not be entirely intuitive, they are an absolute prerequisite to any surgeon who wishes to practice in the era of EBM. Educational efforts have largely focused on medicine with little focus on the unique educational needs of surgeons. The unique features of surgical research and the associated challenges have often been minimized by researchers and practitioners promoting double randomized controlled drug trials as the gold standard.The current symposium has been developed to cover practical concepts of evidence-based orthopedics including its history, definitions, quality of the literature, checklists for surgeons to evaluate orthopedic literature and communication with patients.The core articles were developed by researchers at McMaster University in collaboration with experts from Boston (Massachussetts), Toronto (Ontario), Greenville (South Carolina), Zurich (Switzerland), Kiel (Germany), New Delhi (India) and Pune (India)."} +{"text": "Concerns about the impact of the oceans on human health can be traced to ancient times. Jewish law prohibited the consumption of shellfish, probably reflecting the fact that filter-feeding bivalves can accumulate pathogens and toxins. The Portuguese explorer Pedro Fernandes de Queir\u00f3s described symptoms associated with ciguatera fish poisoning after eating Caribbean sea bream in 1606, and several of British explorer James Cook's crew experienced similar symptoms after eating fish off the coast of Vanuatu in 1774 [ impacts . A tsuna impacts . LookingDespite concerns about biological, physical and chemical risks, and the possible long-term effects of global warming, the oceans remain a resource of immense value to mankind. Many marine fish and shellfish, for example, are excellent sources of protein, selenium, and omega-3 polyunsaturated fatty acids. Around the globe, the coastal ocean is a recreational destination for a substantial percentage of the human population as well as a venue of intensive commercial activity. In 1999, the National Research Council (NRC) published From Monsoons to Microbes: Understanding the Oceans Role in Human Health , a seminRecognizing the growing need for interdisciplinary basic and applied research addressing the linkages between human health and the oceans, in 2004 the National Science Foundation (NSF) and the National Institute of Environmental Health Science (NIEHS) jointly funded grants establishing four Centers for Oceans and Human Health (COHH). These centers are: (i) the Oceans and Human Health Center at the University of Miami, (ii) the Pacific Research Center for Marine Biomedicine at the University of Hawaii, (iii) the Pacific Northwest Center for Human Health and Ocean Studies at the University of Washington, and (iv) the Woods Hole Center for Oceans and Human Health at the Woods Hole Oceanographic Institution, the Marine Biological Laboratory, and Massachusetts Institute of Technology. Through an internal competitive process, the National Oceanic and Atmospheric Administration (NOAA) in the same year designated three NOAA centers of excellence in oceans and human health under their Oceans and Human Health Initiative (OHHI): (i) the West Coast Center for Oceans and Human Health at the Northwest Fisheries Science Center in Seattle, Washington, (ii) the NOAA Center of Excellence in Oceans and Human Health at the Hollings Marine Laboratory in Charleston, South Carolina, and (iii) the NOAA Center of Excellence for Great Lakes and Human Health at the Great Lakes Environmental Research Laboratory in Ann Arbor, Michigan. The NOAA initiative also includes external competitive grant, distinguished scholar, and traineeship programs.V. vulnificus wound infections have a death rate of some 50% [Vibrio bacteria and Noroviruses) as a result of the consumption of raw and even cooked molluscan shellfish remain a concern [In the United States, one of the motivations for OHH research arises from the fact that some 62 million Americans swim in the coastal waters of the United States and spend 800 million person-days at beaches annually . Wound, some 50% . Public concern ,15. The concern .Oceans and Human Health is a growing integration of several disciplines, from physical oceanography to molecular biology to epidemiology, emerging largely from the recognition that ocean processes have important implications for public health, and human activities can influence these processes. Details on approaches to this new area of concern may be found in the Interagency Oceans and Human Health Research Implementation Plan . The fivThe primary concern regarding microbial pathogens is human exposure associated with the recreational and commercial use of coastal waters containing either indigenous or introduced pathogens. The primary route of transmission is the consumption of seafood, but can occur also by contact with seawater or exposure to marine aerosols and zoonoses. Almost all major bacterial lineages that contain human pathogens have also been detected in samples from ocean environments or organisms. Yet forStaphyllococcus aureus, Naegleri fowleri and Legionella pneumophila). Recent epidemiological studies conducted at recreational beaches impacted by non-point source pollution have revealed no statistically significant correlation between FIB concentrations and morbidity [For years, the standard strategy for monitoring introduced pathogens has been measuring the concentration of so-called fecal indicator bacteria (FIB). There are acknowledged and serious problems associated with the use of FIB for this purpose . These iorbidity . These iorbidity ,19; and orbidity .Vibrio cholerae at natural concentrations in New England estuarine water, suggesting that microarrays may be applicable to broad environmental monitoring of co-occurring pathogens [Polymerase chain reaction methods for example, are being used to rapidly and specifically target microbes of public health concern, including those not examined previously because of an inability to culture them. New molecular assays have been introduced for detection of FIB, bacterial pathogens, viral pathogens, and protistan (protozoan) parasites. And recent methodological improvements are allowing simultaneous detection of multiple targets in a single assay. Scientists from MIT in the Woods Hole Center, in collaboration with colleagues from Northwestern University, have recently developed a protocol involving DNA microarrays that enables accurate identification of specific bacterial sequences in natural samples. Applied to environmental samples, the microarrays are able to detect athogens . OHH resathogens .The acronym \"HAB\" is somewhat misleading since some HAB-designated problems , though caused by algae, are not associated with blooms in any conventional sense of the word, and others are caused by cyanobacteria, which are prokaryotic and, strictly speaking, not algae. Regardless, there are a variety of human health problems associated with HABs. The most common is acute intoxication resulting from the consumption of shellfish or finfish that contain neurotoxins produced by HABs . Other pKarenia brevis blooms off the west coast of Florida by scientists at the University of Miami COHH in collaboration with NOAA OHH researchers [Alexandrium fundyense blooms in the Gulf of Maine by the Woods Hole COHH [In some cases remote sensing has been very successful in detecting HABs (and warning the public). A good example is detection of earchers . Scientiearchers . In Pugeearchers . As withole COHH ,21,23.Pseudo-nitzschia [Vibrio cholerae, for example acquires the cholera toxin gene via phage transduction [A concern with modeling and forecasting is the growing awareness that the abundance and, in particular, the toxicity of HAB species may not be explainable solely in terms of the physics and chemistry of the environment. Interactions with bacteria and/or viruses, for example, may play an important role in toxin production. Interactions with bacteria appear to play a role in the production of the neurotoxin, domoic acid, by the diatom, itzschia . The impsduction ,Another emerging issue has been the discovery by scientists at the Hawaii COHH and others that the neurotoxin, \u03b2-N-methylamino-L-alanine (BMAA), is produced by all known groups of cyanobacteria . BMAA ha2 emissions, fertilization of large areas of the ocean with iron, could also stimulate HABs. Field studies of the impact of iron fertilization by researchers at the Hawaii OHH Center have indicated that pennate diatoms are the primary beneficiaries of iron fertilization; Pseudo-nitzschia, the genus containing a number of species associated with the production of the neurotoxin domoic acid and amnesiac shellfish poisoning, is particularly responsive [In terms of human health effects worldwide, a very important yet poorly understood issue emerging in OHH is the potential impact of climate change on the ecology of pathogens and harmful algal species. Among the eukaryotic microalgae, dinoflagellates are expected to benefit from a warmer climate and more thermally stratified water column . Most HAsponsive .Various agencies, in part through the Centers, are helping to train a new generation of scientists in the interdisciplinary aspects of OHH through the participation of students and post-docs in OHH research projects and related activities, including the NSF-funded OHH research experience for undergraduates (REU) program and a new NOAA-funded OHH Traineeship Program.. Synergistic and collaborative contributions to the ongoing work of the Interagency Working Group on Harmful Algal Blooms, Hypoxia and Human Health have played an important role in the success of the Working Group in producing the first comprehensive assessment of the status of OHH research and opportunities for advancement in this new field [Collaborations among the various OHH centers and other OHH researchers have: (i) produced a noteworthy multi-center and interdisciplinary microbiological study of New Orleans and Lake Pontchartrain following Hurricane Katrina ; (ii) prew field . HopefulThe authors declare that they have no competing interests."} +{"text": "The objective of this paper was to analyze the data supporting the possible role of melatonin on bone metabolism and its repercussion in the etiology and treatment of bone pathologies such as the osteoporosis and the adolescent idiopathic scoliosis (AIS). Melatonin may prevent bone degradation and promote bone formation through mechanisms involving both melatonin receptor-mediated and receptor-independent actions. The three principal mechanisms of melatonin effects on bone function could be: (a) the promotion of the osteoblast differentiation and activity; (b) an increase in the osteoprotegerin expression by osteoblasts, thereby preventing the differentiation of osteoclasts; (c) scavenging of free radicals generated by osteoclast activity and responsible for bone resorption. A variety of in vitro and in vivo experimental studies, although with some controversial results, point toward a possible role of melatonin deficits in the etiology of osteoporosis and AIS and open a new field related to the possible therapeutic use of melatonin in these bone diseases. Bones are structures under a continuous process of remodelating by the coupled activity of cells with resorptive functions (osteoclasts) and cells responsible for the formation of new bone (osteoblasts). The balance between the activities of both cell types is under the control of systemic hormones including parathyroid hormone (PTH), estradiol E2), and growth hormone as well as of cytokines and growth factors produced in the bone marrow . A major, and groMelatonin is an indoleamine secreted primarily by the pineal gland but also synthesized in other organs such as retina, gastrointestinal tract, and bone marrow. Melatonin plays a regulatory role in many physiological processes including bone physiology \u201310. NoctThe objectives of the current paper are (a) to review the data supporting the possible role of the age-dependent decrease of melatonin in the development of osteoporosis and the therapeutic value of melatonin as a treatment for this disease, and (b) to analyze the evidence related to the role of melatonin in the etiology and treatment of the AIS. Before doing so, we will describe the effects of melatonin on bone physiology, as the basis to understand the participation of this indoleamine in bone pathology.\u03b2-adrenoceptor blockers, serum concentrations of calcium dropped [The effects of melatonin on bone physiology were reviewed in an excellent article by Cardinali et al. . The pos dropped an effec3) were also described. These results led the authors to conclude that lighting conditions influence bone metabolism in rats, and that melatonin likely plays an important role in these photoperiodic effects. Secondary changes in daily IGF-I and T3 oscillations, caused by short- and long-day conditions, also result in altered rhythmicity of daily bone resorption [More recently, Ostrowska et al. re-examisorption . This exsorption . de novo [One interesting finding potentially related to melatonin and bone health is the demonstration of high concentrations of melatonin in bone marrow cells from mice and humans , 33, witde novo . The prede novo , 35. A variety of in vitro studies support the hypothesis of stimulatory effects of melatonin on both osteoblast differentiation and activity. Preosteoblasts cultured in the presence of melatonin underwent early cell differentiation and a major expression of bone marker proteins compared to control cells incubated without melatonin . These e\u03bcM range), (a) stimulates the proliferation and alkaline phosphatase activity of these cells; (b) promotes the expression of type I collagen, osteopontin, bone sialoprotein, and osteocalcin; (c) stimulates the formation of mineralized matrix. The signaling mechanisms mediating the melatonin actions on osteoblasts are still unknown although the role of the MAPK pathway seems relevant [In cultures of human osteoblasts , 40, melrelevant .\u03baB (RANK) on the surface of the osteoclast activating bone resorption [The activity of osteoclasts is under the control of paracrine factors produced by the osteoblasts. PTH and 1,25-dihydroxycholecalcipherol stimulate the expression of an osteoclast differentiating factor (ODF) by the marrow stromal cells and osteoblasts. ODF binds to the receptor activator of nuclear factor-sorption , 41. In sorption . Via thiOne important component of the osteoclasts activity is the generation of free radicals which contribute to the process of bone degradation and resorption . MelatonThere are, however, data contrary to the hypothesis of the effect of melatonin on bone-forming osteoblasts. Ostrowska et al. found, i\u03b1 in MCF-7 cells by mechanisms involving calmodulin [An interesting question is the interaction of melatonin with estrogens at the level of the osteoblast. Estrogens have a positive impact on bone growth. Melatonin, according to the studies summarized above, has similar effects. Under many other circumstances, however, estrogens and melatonin usually have opposing effects. Thus, it is well known that estradiol modulates the function of the melatonin receptors in rat ovary and Chinlmodulin \u201353. A stlmodulin ; howeverlmodulin . The natOsteoporosis is a prolonged structural deterioration of the skeletal system, usually associated with age, and with a major prevalence in women. Antiosteoporosis therapies include the use bisphosphonates, estrogen, and calcitonin to inhibit bone-resorbing osteoclasts preventing further bone breakdown. However, these therapies are insufficient in cases of individuals suffering from severe osteoporosis. Drugs that stimulate bone-forming osteoblasts are expensive and with important associated side effects . These fAt present, no clinical trials have focused on the possible therapeutic value of melatonin in the treatment of osteoporosis. Some epidemiologic studies re-enforce the possible etiologic role of melatonin in osteoporosis. This is the case from a recent study of Feskanich et al. . This grExperimental studies carried out mostly in ovariectomized rats (as a model of menopause) suggest, in general, a protective role of melatonin in preventing bone degradation and promoting bone formation most probably through an action that involves melatonin receptors , 5. AmonAlthough the etiology of the AIS is unclear, histomorphometric data on iliac crest biopsies and vertebrae of scoliosis patients showed an impaired function of both osteoblasts and osteoclasts , 65. TheThe neuroendocrine hypothesis involving a melatonin deficiency as the source for AIS has generated great interest and controversy. This hypothesis, represented in In bipedal pinealectomized rats a reduction in melatonin, as a consequence of the pineal ablation, was found to cause scoliosis . RecentlNot all data support the hypothesis of the reduction of melatonin as the cause of scoliosis. Melatonin therapy after pinealectomy in young chickens had no effect on the development or progression of scoliosis , and cutBipedal ambulation in mammals is required, associated to low levels of melatonin, to generate scoliosis , 86. TheIn humans, the question of the possible role of melatonin in scoliosis has been addressed using different analytical approaches Melatonin seems to promote bone formation and prevent bone resorption via several mechanisms which include the increase in the osteoblastic activity and differentiation, as well as the reduction in osteoclastic differentiation and activity, and by increasing osteoprotegerin expression and scavenging the free radicals responsible of bone resorption. (b) Melatonin may be an etiologic factor in the postmenopausal osteoporosis, and a therapeutic tool for this pathology, as an adjuvant with conventional treatments such as the administration of estrogens. (c) The recent data concerning the association of melatonin and AIS point toward their possible usefulness as both a diagnostic and therapeutic tool. (d) The experimental evidence on animal models suggests the value of clinical trials to assess the therapeutic possibilities of melatonin in bone diseases."} +{"text": "Molecular pathology, a rapidly expanding discipline connecting pathology and molecular biology, is providing a deeper insight and understanding of the molecular basis of the aetiology and pathogenesis of human disease. This well-laid-out book covers the basic principles of molecular pathology, explains the most important molecular diagnostic techniques in user-friendly language, and describes their applications across a broad range of human diseases and problems, including cancer, hereditary disorders, identity testing, and infectious diseases. The book is divided into 11 comprehensive yet concise chapters, each providing extensive bibliographic references to the primary literature for those wanting to delve deeper into the subject.In the first four chapters the reader is introduced to basic concepts of gene structure and function, epigenetics, Mendellian and non-Mendellian patterns of inheritance, population genetics, types of mutations and chromosomal abnormalities, and modern molecular diagnostic techniques. In chapter five, common inherited diseases such as cystic fibrosis and Huntington's disease are discussed as examples of molecular screening for specific mutated genes or linked DNA polymorphisms now commonplace in clinical laboratories. The material covered in this chapter also includes testing for common mitochondrial and metabolic disorders, and the implementation of newborn and carrier screening programmes. In chapters six, seven and eight, basic concepts of tumour biology are covered, including oncogenes and tumour suppressor genes, programmed cell death (apoptosis) and telomere maintenance, and are reviewed in the context of molecular detection of gene rearrangements, tissue-specific gene transcription and oncogene activation in selected sporadic cancers, haematological malignancies, and familial cancer syndromes. Chapter nine provides a useful introduction to the field of pharmacogenetics and includes examples of genes demonstrating pharmacokinetic and pharmacodynamic variation together with their phenotyping. Chapter ten describes the differentiation of individuals from one another by \u2018DNA fingerprinting\u2019 for purposes of paternity testing, forensic sample identification, and bone marrow engraftment monitoring. The final chapter discusses the diagnosis and monitoring of human immunodeficiency virus and hepatitis C virus infections as examples of how DNA probes for viruses, bacteria, and parasites promise to revolutionise the practice of medical microbiology.Overall the book provides an excellent overview of the ongoing molecular revolution that is now transforming pathology and the practice of laboratory medicine. As well as providing a basic reference text for staff in clinical molecular diagnostic laboratories, it also forms a good basis for tutorials and exam preparations. I would highly recommend this book to scientists and health-care professionals working in the field of pathology, including pathology residents, clinicians, and medical students."} +{"text": "Although the first case of fibrolamellar hepatocellularcarcinoma (FI-HCC) was described by Edmondson in 1956, and later confirmed in fivepatients by Peters, the majority of reports followed those of Berman A case of FI-HCC, which is rarely diagnosed in Mediterranean countries including Turkey,is presented in the following report."} +{"text": "Seasonal variation has been described in the presentation and growth of several malignant tumours, including cancers of the breast, uterus, uterine cervix, urinary bladder, liver, lymphatic system and skin, although the mechanisms are not known. We herein describe a circannual rhythm for thyroid cancer , with significantly more cases presenting during the late autumn and winter. In a subset of these cases (127 papillary carcinomas), significant seasonal variations with highest values in autumn-winter were found for tumour diameter and proliferation indicators (S- and G2M-phase fractions). These results indicate the likelihood of a seasonal factor (or factors) of importance for the regulation and modification of tumour cell proliferation. When further clarified, this might be of relevance for the planning of diagnostic and therapeutic strategies."} +{"text": "Geographical correlations between standardized, mortality ratios (SMRs) of cancers and consumption of different types of alcoholic beverages , of cigarettes, and urbanization were examined for all 46 prefectures in Japan. Suggestive correlations were observed between cancer of the oesophagus in males and both shochu and whisky (r = 0.27 and 0.22 respectively), between cancer of the rectum in males and wine (r = 0.45), and between cancer of the prostate and shochu (r = 0.50). These correlations were also confirmed in the partial correlations between SMRs of cancers and consumption of alcoholic beverages, controlling for the two variables urbanization and consumption of cigarettes. Alhtough cancers of other sites were also correlated with certain types of alcoholic beverages, their associations seemed to be secondary to other factors. The validity of higher-order partial correlations and the problems of correlation study are also referred to."} +{"text": "Nasopharyngeal cancer (NPC) is a unique disease with increasing interest for many physicians due to its unusual etiology, histology, and epidemiology. The recent era of fiberoptic endoscopy now provides the clinician with better tools for the screening, diagnosis, staging, and follow-up of NPC. Theuse of high resolution flexible and rigid nasopharyngoscopy gives the physician an opportunity fora more sensitive examination in a higher proportion of patients. Ultimately, this will allow for earlierdiagnosis of NPC, and improved prognosis and better quality of life for the patients with this disease.Also, by allowing the clinician to perform directed biopsies of the nasopharynx under localanesthesia, fiberoptic nasopharyngoscopy allows a less morbid and more cost-effective approach towardsthis disease, including screening protocols in certain high risk regions of the world."} +{"text": "Founded in 1969, the Organisation of the Islamic Conference (OIC) is comprised of 57 nations that together represent the second largest international organization after the United Nations The information in Schistosoma haematobiumS. haematobium infection is associated with reductions in child growth and development similar to those caused by the intestinal helminths Schistosomiasis is also a common NTD in the Islamic world. Almost one-half of the world's schistosome infections occur in OIC member states, especially in Nigeria, Mozambique, Burkina Faso, Mali, and Cote d'Ivoire Ascaris lumbricoides are capable of withstanding the cold and dry conditions that can occur in these countries. Ascariasis and other intestinal parasitic infections are also highly prevalent among children living in the Gaza strip Indeed, several conflict and post-conflict countries in the OIC stand out for their high prevalence rates of NTDs. In Sudan, the high endemicity of trachoma, hookworm and other intestinal helminth infections, and schistosomiasis were already mentioned. In addition, dracunculiasis (guinea worm) is still prevalent, and more cases of guinea worm occur there relative to any other country The health and socioeconomic effects of the NTDs, including their poverty-promoting and conflict-promoting features, should provide strong incentives to try and control or eliminate these infections in the poorest countries of the OIC. Indeed, through mass drug administration with either low-cost generic drugs or drugs donated by multinational pharmaceutical companies, most of the NTDs listed in Through private donations from the Bill & Melinda Gates Foundation and other foundations, the United States government, the British Department for International Development, and the World Health Organization are working together with public\u2013private partnerships aligned through the Global Network for Neglected Tropical Diseases and several non-governmental organizations, including the Carter Center, to implement and integrate mass drug administration for the most common NTDs in more than one dozen endemic countries The impressive establishment of new and distinguished universities in Saudi Arabia, UAE, Qatar, and elsewhere"} +{"text": "Cryptosporidium parvum.Since the genomic DNA sequence encodes all of the heritable information responsible fordevelopment, disease pathogenesis, virulence, species permissiveness and immune resistance,a comprehensive knowledge of the C. parvum genome will provide the necessaryinformation required for cost-effective and targeted research into disease prevention andtreatment. With the recent advances in high-throughput automated DNA sequencingcapabilities, large-scale genomic sequencing has become a cost-effective and time-efficientapproach to understanding the biology of an organism. In addition, the continueddevelopment and implementation of new software tools that can scan raw sequences forsigns of genes and then identify clues as to potential functions, has provided the finalrealization of the potential rewards of genome sequencing. To further our understanding ofC. parvum biology, we have initiated a random shotgun sequencing approach to obtain thecomplete sequence of the IOWA isolate of C. parvum. Our progress to date hasdemonstrated that sequencing of the C. parvum genome will be an efficient and costeffectivemethod for gene discovery of this important eukaryotic pathogen. This will allowfor the identification of key metabolic and immunological features of the organism that willprovide the basis for future development of safe and effective strategies for prevention andtreatment of disease in AIDS patients, as well as immunocompetent hosts. Moreover, byobtaining the complete sequence of the C. parvum genome, effective methods forsubspecific differentiation (strain typing) and epidemiologic surveillance (strain tracking)of this pathogen can be developed.A lack of basic understanding of parasite biology has been a limiting factor in designingeffective means of treating and preventing disease caused by"} +{"text": "World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm.A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i) therapeutic adherence; (ii) the incidence of the main chronic diseases in old age; (iii) life expectancy without chronic diseases at 60 years of age; (iv) disability adjusted life years lost; (v) years of life lost due to premature mortality, and (vi) years lived with disability.We propose that the implementation of the model active aging framework will permits the empowerment of older adults, which constitutes basic social capital for chronic disease prevention and control in old age. The challenges of populational aging involve everyone. In this regard, the United Nations reported that in 2007 there were 700 million persons aged 60 years and over on the planet, which represents 11% of the entire world population. Likewise, it is projected that this percentage will increase to 15% by the year 2025 and to 22% by 2050 [On the other hand, the World Health Organization (WHO) cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care .The most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia ,4, In thWe observed the principal repercussions of chronic diseases in old age in terms of physical, mental, and social functionality, affecting basic, instrumental, and advanced activities of daily life. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system ,8.In the Second World Assembly on Ageing held in Madrid in 2002, the relevance of active aging was highlighted as a key strategy for achieving the maximum health, well-being, and quality of life (QOL) of older adults, defining this as \"the process of optimizing opportunities for health, participation and security in order to enhance quality of life as people age\" .Active aging refers to the empowerment of older persons in biological, psychological, and social areas, understanding empowerment as the individual's self-promotion, independence, and self-confidence, as well as his/her right to a dignified way of life according to self-imposed values, the ability to stand up for one's own rights, and to be free . Active Social networks refer to the personal, community, and institutional contacts by means of which the individual maintains his/her social identity and receive material, instrumental, emotional, and informative support Figure . In thesThe type of social support that social networks can afford are the material, instrumental, affective, and informative provisions, real or perceived, provided by family, friends, the community, and formal institutions -11.Our research group developed an active aging model for chronic disease prevention and control in old age at the community level, comprising a big-net of social networks of mutual-help of elders in which self-care is a daily practice ,13.Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the development and implementation of a model active aging is reach the empowerment of elderly-dwelling individuals for chronic disease prevention and control in old age at the community through self-care, self-help and self-promotion.A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years, with a significance level of 0.05, a power of 80% and an expected difference in chronic diseases incidence of 50% between The subjects agreed to participate in the study after giving their informed consent. The Ethics Committee of the Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM) Zaragoza Campus approved the research protocol for this study.All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, which will be established actions of self-care as daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age.As a key element, the model establishes the training of gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators and establish self-care and self-promotion actions for elderly well-being and social development.Self-care at the gerontological level refers to the reasoned theoretically based behavior of the individual that allows the elderly adult to decide and act upon the prevention, diagnosis, and treatment of his/her disease, as well as the maintenance of health and maximum enjoyment of QOL, according to his/her sociocultural context, utilizing formal and informal social networks in optimal fashion during aging. Similarly, the mutual-help including reasoned solidarity-oriented behavior that is adopted by a group of elderly individuals who share like problems and whose members are aware of the advantages and commitments acquired on accepting voluntarily to form part of the group. Concerning self-promotion, this involves the actions that an older adult or a self-help group carries out autonomously, in advance, and in optimal form and considers elements and mechanisms of formal and informal social support networks.The model contemplates a Primary Gerontological Health Care Unit (PGHCU), whose purpose is to coordinate the big-net of social networks of mutual-help groups of elderly adults, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and QOL in old age Figure .Mature individuals learn only what they want to learn; (ii)Mature individuals learn only what they are capable of learning; (iii) Mature individuals learn mainly what they teach themselves, and (iv)Mature individuals learn mainly in terms of their experience.The PGHCU linked with Institutions of Higher Education in Gerontology will be responsible for the training of gerontological promoters (GP) following the formal academic structure of a workshop Table and consThe requirements for participating in training courses for GPs are as follows: (i) interest in participating in an intensive training program focused on holistic gerontological development; (ii) 60-74 years of age; (iii) literate; (iv) absence of handicapping illnesses or serious visual or auditory disabilities, and (v) leadership attributes and the ability to coordinate small groups.We will implement a 60-hour workshop that integrated both theoretical and practical aspects (14 weekly sessions). An introductory textbook entitled \"Community Gerontology\" was designed specifically for this aim .Topics for the workshop were selected and approved by a panel of four Gerontologists and took into consideration their basic knowledge on Community Gerontology and age-related changes in the following: biological; psychological, and social aspects; prevention of chronic diseases; healthy lifestyle in the aging period; empowerment, and social networks Table , accordiThe pillars of the model are as follows: gerontological health care; gerontological orientation for families, and gerontological social development.The fundamental objective of GHC is to prevent and detect the diseases of greatest prevalence in the elderly, such as high blood pressure, diabetes mellitus, depression, osteoarthrosis, cognitive deterioration, and osteoporosis, as well as establishing actions of healthy aging for the maintenance, prolongation, and recuperation of physical, mental, and social functionality Figure . The actGPs should possess sufficient knowledge for orienting and training family members to provide basic care for the healthy and ill elderly adult in the home, with the purpose of preventing diseases and/or their complications, in addition to promoting healthy lifestyles for the maintenance, prolongation and recuperation of physical, mental, and social functionality.Among its goals, the model contemplates maximum enjoyment by older adults of their situation of being old. Thus, implantation is recommended of programs of recreation, adaptation, and psychosocial and occupational excelling within an anthropological focus, according to the elderly individual's interests, age, schooling, gender, health state, and socioeconomic situation.The model established flexible general guidelines framed within an active aging paradigm. Therefore, actions for GSD should be adopted by the population in which the model is implemented , as well as by older adult groups of different sociocultural and economic conditions.In 2007, an agreement was signed between the National Autonomous University of Mexico (UNAM) and the Institute for Care of the Elderly in the State of Hidalgo (Mexico) with the objective of implementing a State Active Aging Program according to the model developed at the UNAM (Zaragoza Campus).Among actions implemented within the agreement's framework, we are able to highlight the following: (i) the training of professional personnel of the Institute on the active aging paradigm; (ii) training of gerontological promoters; (iii) the editing of a text on Community Gerontology direct toward elderly adults, and (iv) in 2008, the Institute adopted the Active Aging paradigm as public and strategic policy for care of the elderly.Indicators of the model's impact will be the following: (i) empowerment; (ii) therapeutic adherence; (iii) the incidence of the main chronic diseases in old age; (iv) life expectancy without chronic diseases at 60 years of age; (v) disability adjusted life years lost (DALYs); (vi) years of life lost due to premature mortality (YLL), and (vii) years lived with disability (YLD).Walter (2006) proposes the following seven principles that allow for delineating the components of active aging: (i) participation should contribute to the well-being of the older adult; (ii) it should have a preventive focus; (iii) it should be within the reach of the entire population of elderly individuals, including those who are frailty and dependent, with the degree of participation according to the physical, psychological, and social conditions of the older adult; (iv) it should propitiate the maintenance and strengthening of intergenerational solidarity; (v) it should take into consideration the person's rights and obligations; (vi) it should be participative with empowerment, and (vii) it should contemplate national, local elements and cultural diversity .The following are the pillars of active aging are health, participation, and security: (i) the prevention and control of chronic diseases, as well as maintaining, prolonging, and recuperating physical, mental, and social functionality according to the older adult's age and specific sociocultural context should be considered as fundamental elements with regard to health; (ii) concerning participation, opportunities should be provided that permit older adults to have productive social participation in remunerated and unremunerated activities, in programs linked with social development, work, education, health, cultural and spiritual development, etc., according to elderly persons' rights, capabilities, needs, and preferences; (iii) concerning security, policies should be established that guarantee permanent access to health, alimentation, housing, and well-being for functional older adults, as well as for those requiring instrumental care.On the other hand, active aging as a policy framework constitutes a feasible alternative for substituting the current model, which visualizes the elderly adult as a sickly being and one in decadence, without the possibility of economic and social development. Therefore, the elderly are frequently considered a social and economic burden.The development of community care models within the framework of active aging is a call and a challenge to which we should devote ourselves in all countries. In this regard, we should confront the present hegemonic view of aging within the framework of a structured dependency, which has propitiated a marketing focus in parallel fashion on covering hospital and care needs, developing in parallel great industries of technical, care, and drug industries for aging, which indirectly has negative repercussions on physical, mental, and social functionality . This foOn the other hand, there is an ever greater demand for health care for older adults, outpacing in some cases the resources allocated for this purpose. Thus, there is a need to propose alternative care models that exert a significant impact on cost-benefit and on the QOL of the elderly . In thisIn different studies, the social capital has been recognized of the group of young-old individuals (aged 60-74 years) for active aging, because >80% of this age group are functional and can potentially provide material, instrumental, affective, and informative support to other older adults -24 Figu.We propose that the implementation of the model active aging will permit us to reach the empowerment of older adults for self-care, and consequently prevent and control the diseases chronic, besides its complications.The authors declare that they have no competing interests.VMMN conceived and designed the study, drafted the manuscript. MLMM participated in the design of the study and interviews of the participants. ECM participated in the design of the study and interviews of the participants. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:"} +{"text": "In the spring of 1999 in rural Newfoundland, abortions in goats were associated with illness in goat workers. An epidemiologic investigation and a serologic survey were conducted in April 1999 to determine the number of infections, nature of illness, and risk factors for infection. Thirty-seven percent of the outbreak cohort had antibody titers to phase II Coxiella burnetii antigen >1:64, suggesting recent infection. The predominant clinical manifestation of Q fever was an acute febrile illness. Independent risk factors for infection included contact with goat placenta, smoking tobacco, and eating cheese made from pasteurized goat milk. This outbreak raises questions about management of such outbreaks, interprovincial sale and movement of domestic ungulates, and the need for discussion between public health practitioners and the dairy industry on control of this highly infectious organism."} +{"text": "The Second International Conference of the African-Caribbean Cancer Consortium (AC3) was held on May 12\u201313, 2008 at the Wyndham Miami Airport Hotel & Executive Meeting Center in Miami, FL, USA. The conference was organized by the University of Pittsburgh, Graduate School of Public Health and the University of Pittsburgh Cancer Institute.) was established in 2006 for the study of viral, genetic, environmental, and lifestyle risk factors for cancer in populations of African descent [The AC3 . Session I continued with five additional short presentations of research findings by AC3 members -6.The second general session was chaired by Dr. Camille Ragin from the University of Pittsburgh, US and Dr. Norma McFarlane-Anderson from the University of the West Indies, Jamaica. The keynote address was given by Dr. Raleigh Butler from the University of the West Indies, The Bahamas and was entitled: \"Fact, Frictions and Fractions, HPV the Bahamian Experience\". Dr. Butler presented an overview of the Epidemiology of HPV and related cancers and described the current status of this disease among Caribbean populations. Cervical cancer is the second cause of cancer deaths in the Bahamas, and annual cervical screening is performed in less than 10% of this at risk population. Session II continued with four additional presentations of human papillomavirus (HPV) related studies conducted in Caribbean populations -10.Day one of this conference concluded with two Special Topics sessions. The first, \"Sample Collection, Data Sharing and Confidentiality\" was facilitated by Dr. Emanuela Taioli from the University of Pittsburgh. The participants defined appropriate protocols for collection and storage of data and samples as well discussed the importance of standardization in multi-centered collaborative studies. The second Special Topic, \"Building Infrastructure for Multi-Center Studies\" was facilitated by Dr. Judith Jacobson from Columbia University. During this session the participants discussed decisions and steps necessary for obtaining funding and implementing a collaborative study.The day ended with a dynamic poster session and networking dinner reception, where the participants continued their discussions about their research projects and reconnected with their colleagues and met new ones.This session was chaired by Dr. Michael Okobia, from the University of Benin, Nigeria and Dr. Emanuela Taioli from the University of Pittsburgh, US. Dr. Taioli launched the session as the keynote speaker where she presented the descriptive Epidemiology of Breast cancer among individuals of African ancestry; discussed risk factors for this disease and identified the gaps in research for minority populations. Dr. Taioli also presented some of her current research findings from her studies of African American populations. The session ended with three additional research presentations by AC3 investigators -13.Dr. Elizabeth Quamina Cancer Registry in Trinidad and Tobago and Dr. Wallis Best-Plummer representing the Guyana Cancer Registry in Guyana. The presenters provided data from their corresponding cancer registry and were later joined by Dr. Michael Okobia, from the University of Benin, Nigeria for a panel discussion about the establishment process of cancer registries and the challenges surrounding cancer registration in developing countries.The breast cancer session was followed by a Special Topic discussion on Cancer Registration. There were presentations of cancer statistics by Ms. Veronica Roach from The conference concluded with concurrent breakout sessions where AC3 investigators divided into cancer-specific working groups . During these sessions, AC3 investigators discussed the status of the ongoing collaborative studies and defined future studies.All participants were asked to complete evaluation forms for both meeting dates and 95% of the forms were returned. The majority of the participants (65%) reported that, based on their prior knowledge, they learned more after attending the cancer registration session. In general, participants reported that the conference fulfilled their reason for attending (73%). Eight-five percent were satisfied with the conference content, organization (81%), and overall conference experience (85%).The authors declare that they have no competing interests."} +{"text": "The results of two 5-year studies, for 1974-78 and 1984-88, of cutaneous malignant melanoma (CMM) in Northern Ireland show changes in the presentation of the disease. Although there is some evidence of earlier diagnosis, the rise in incidence has produced an overall increase in the number of cases with advanced disease."} +{"text": "The conference was sponsored by the following units of the University of Illinois at Urbana-Champaign: Center for Zoonoses Research; Department of Pathobiology; Environmental Council; Host-Microbe Systems Theme of the Institute for Genomic Biology; Office of International Programs and Studies; Program in Arms Control, Disarmament, and International Security; and Conservation Medicine Center of Chicago. Proceedings are available at Jonathan Patz, University of Wisconsin-Madison, opened the conference with a presentation about the effects of deforestation and climate on infectious diseases in the northern region of the Peruvian Amazon. Concomitant with new deforestation, the area experienced a sharp (50-fold) rise in malaria incidence during 1987\u20131997, coupled with an invasion by Anopheles darlingi, the most important vector of malaria in South America. A strong relationship has been found between the extent of deforestation, larval sites of A. darlingi, and abundance of adult mosquitoes. The need for a broad-based policy approach to ecology-disease relationships was highlighted.Paul Gibbs, University of Florida-Gainesville, discussed emerging infectious disease trends. The potential overshadowing of recent, naturally occurring emerging diseases and epidemics by a succession of disasters, both natural and manmade, was examined. Dr. Gibbs presented the global factors that have led to the increased emergence of these diseases, a summary of lessons learned, and a broad agenda for action.Alison Weiss, University of Cincinnati, addressed the reemergence of Bordetella pertussis as a notable health threat despite active vaccination programs. She discussed the increased cases of pertussis during the past 25 years and the shift from a whole-cell vaccine to acellular pertussis vaccines, which failed to reverse this increase. Bactericidal immunity, if achievable, was presented as an option for preventing the disease (whooping cough) and transmission of the agent (B. pertussis).Steven Blanke, University of Illinois at Urbana-Champaign, discussed persistence mechanisms of Helicobacter pylori and explored the hypothesis that phase variation results in altered forms of H. pylori that can withstand the gastric environment. Phase variants of a single gene have been found to demonstrate remarkably distinct properties in terms of stress resistance and virulence factor expression.R. Mark Buller, Saint Louis University, presented evidence that human monkeypox is a poxvirus zoonotic disease. The first US outbreak of monkeypox virus infection in 2003, unlike previous outbreaks in Africa, resulted in no deaths and no documented human-to-human transmission. Evidence supports the existence of monkeypox virus strains that differ in virulence and transmissibility for humans.Ricardo Gurtler, University of Buenos Aires, outlined a longitudinal study of the transmission dynamics and control of Trypanosoma cruzi, the causative agent of Chagas disease, in 3 rural villages in northwestern Argentina. Regular monitoring of insect infestations and parasite infections of triatomine bugs was accompanied by demographic assessments of prevalence and infection in humans and dogs before and after the establishment of community-based surveillance in 1992.May Berenbaum, University of Illinois at Urbana-Champaign, discussed biological invasions that resulted in establishment of nonindigenous species, their role in contemporary global change, and their subsequent economic and ecologic costs. Effects on health are disproportionately large, in part because invasive species often owe their success to unique chemical defense mechanisms and because, without coevolved enemies of their own, they can serve as extraordinarily effective disease vectors.Nina Marano, Centers for Disease Control and Prevention, addressed the need for multidisciplinary public policy responses to emerging zoonoses. In particular, she examined the case of highly pathogenic avian influenza in Southeast Asia and presented recommendations for integrated research approaches.A panel consisting of the conference speakers and local experts explored differences between molecular and ecologic studies, between animal and human studies, and between science and public policy. The panel examined strategies for bridging these gaps. Recommendations from this session will appear in a forthcoming Center for Zoonoses Research white paper."} +{"text": "The effects of combinations of dipyridamole, an effective blocker of the salvage pathway of DNA synthesis, and 8 types of anti-cancer drugs on the growth of human T, B and myeloid leukaemia/lymphoma cell lines in vitro were examined. In combinations, dipyridamole and vincristine (VCR), and dipyridamole and vindesine had synergistic inhibitory effects. Dipyridamole reduced the efflux of VCR from cells and enhanced their VCR accumulation in a dose-dependent manner at concentrations of up to 10 microM in the lymphoid cell lines, MOLT-3 and BL-TH, and of up to at least 20 microM in the myeloid cell line, ML-1. Dipyridamole also enhanced the accumulation of VCR in PHA-stimulated and un-stimulated lymphocytes of normal donors, but efflux of VCR was more rapid from normal lymphocytes than from cultured cell lines. It is proposed that combination therapy with dipyridamole plus VCR should be effective in the treatment of leukaemia and lymphoma."} +{"text": "This paper describes an integrated approach to the computerizationof all major disciplines of laboratory medicine and pathology.Installed in the Department of Pathology, Singapore GeneralHospital (SGH), the computer system discussed comprises aRISC-based Data General Aviion 6200 computer and MeditechMAGIC software. The system has been interfaced with thehospital host IBM computer and supports patient informationtransfer, result reporting, phlebotomy management, and compilationof laboratory and financial management reports. The mainfunctions of the system include: on-line and off-line acquisition ofpatient information and test data; preparation of single/combined/cumulative reports; transmission of reports within and betweenlaboratories; instantaneous provision of data in response totelephone enquiries; calculations of quality control/workload/productivity statistics and indices; and generation of billing lists.The computer enables reports to be provided on patient tests resultsin individual wards, at various specialist out-patient clinics, and inthe Accident and Emergency Department of the SGH through theIBM mainframe, as well as to remote printers installed at severalother major hospitals.The use of the MAGIC integrated laboratory informationsystem has resulted in a significant increase in laboratory efficiencyand productivity."} +{"text": "The first-ever National Summit on Neglected Infections of Poverty in the United Stateswas held October 27, 2009, in Washington, DC, bringing together key leaders in publichealth, public policy, and government. Organized by the Eisenhower Institute, the GeorgeWashington University, the Adler School, the American Public Health Association, and theCenters for Disease Control and Prevention, the goal of the summit was to raiseawareness about neglected infections of poverty in the United States and identifyresources and actions to address them.Neglected infections of poverty are a group of chronic and debilitating parasitic andother infections that disproportionately affect peopleliving in poverty. Major neglected infections of poverty in the United States includetoxocariasis, trichomoniasis, toxoplasmosis, cysticercosis, Chagas disease, andcongenital cytomegalovirus infection improve understanding of theimpact and geographic distribution of neglected infections of poverty; 2) enhanceunderstanding of modes of transmission and human ecology of infections of poverty; 3)enhance prevention and promote research and development; and 4) disseminate informationto multiple audiences. Through a wide-ranging and rich dialogue, summit participantsdeveloped 4 priority areas for follow-up. These areas will be pursued by working groupsconvening in early 2010.Outreach and mobilizationData and surveillance needsEconomic impact of neglected infections of povertyResearch and development needshttp://inside.gwumc.edu/niops/ or contactneglectedinfectionsofpoverty@cdc.govFor further information see"} +{"text": "The conference centered on chronic intracranial hypertension (IH) including the latest research and clinical information. It was sponsored by the Intracranial Hypertension Research Foundation and held at the University of Texas Medical School, Houston, on June 21\u201322 The Intracranial Hypertension Research Foundation (IHRF) in Vancouver, Washington, promotes research into the pathophysiological basis of chronic IH and the evolution of better treatment and, ultimately, a cure. IHRF is a multi-functional organization. It not only encourages research, but also facilitates understanding and management of chronic primary and secondary IH, through research, training and education programs worldwide.IHRF sponsors programs for researchers and clinicians, as well as educational conferences for patients and families. The Houston conference was attended by 108 patients and family members who heard presentations by nine clinicians and researchers.Patients asked many questions during extensive panel sessions. The conference also allowed patients to speak about personal experiences with the disorder. IHRF held the first conference on chronic IH in 2006 at the Oregon Health & Science University (OHSU). A wide variety of subjects were presented to enhance patient knowledge and awareness. Patient education importantly improves patient insight about the disorder. It also facilitates active cooperation with their physicians. Understanding limitations of accepted medical and surgical treatment leads to realistic goals in management.Additionally, patient education is vital in controlling health care costs.The opening presentation by Conrad Johanson, Professor of Clinical Neuroscience at Brown University dealt with CSF production in the choroid plexus and its possible role in IH. Covered in the lecture was the structure of the choroid plexus, the dynamic turnover of ions and water in CSF production by the choroidal epithelium, the transport of CSF solute for the brain, and homeostasis of CNS extracellular fluid. A discussion of translational research goals involving the choroid plexus and CSF and possible directions for research in IH concluded the presentation.John McGregor, Associate Professor of Neurosurgery at Ohio State University, spoke on \"Neural Hydrodynamics Disorders: Hydrocephalus, Intracranial Hypertension and the Chiari Malformation. Relationships, Similarities and Differences\" which was followed by two lectures covering CSF shunt and valve technology. The latter two presentations discussed in depth the available technology with details of the features of each device.The conclusion was that despite the numerous designs, the overall success rate for the various shunts and valve equipment are similar. Better designed shunts are greatly needed.The next lecture by Conrad Johanson: \"Current Theories on Causation and Reduction of Elevated CSF Pressures: Implications for Intracranial Hypertension\", began with a discussion of CSF fluid dynamics centering on CSF reabsorption including the controversial arachnoid and CSF lymphatic drainage. The role of neuropeptides such as atrial natriuretic peptide (ANP) in CSF production and the role of growth factors like basic fibroblast growth factor (FGF2) in CSF reabsorption, were identified. The intriguing possibility of peptides as pharmacological agents in controlling intracranial pressure (ICP) was thought provoking and stimulating, especially since no specific drug is available to control production and egress of CSF.Steven Katz, neuro-ophthalmologist and Associate Professor of Ophthalmology at Ohio State University, lectured on the symptoms and signs in idiopathic intracranial hypertension (IIH) and the medical management options. He discussed approaches that work best in his practice. Steven Katz had previously demonstrated the somatostatin receptors 1 and 2 in normal human choroid plexus and arachnoid granulations and thus surmised that somatostatin is involved in CSF production and egress. His preliminary clinical use of octreotide, a peptide that mimics somatostatin, was discussed, including the potential complications of somatosatin analogs to control IH. Steven Katz described his techniques for optic nerve sheath decompression and demonstrated findings from many of his procedures. He attributed excellent outcomes to reduced surgery duration, i.e. especially the time of optic nerve stretching. He emphasized that short exposure and optimal surgical approach lead to minimal diplopia, ptosis and most importantly, minimal vision loss.Marc Criden, neuro-ophthalmologist and Assistant Professor of Ophthalmology at the University of Texas, Houston, presented an updated overview of pediatric IH. In children under 10 years, gender and weight are not the factors they are in adults. He pointed out that many physicians consider IH in children under 10 to be a different disorder because of these characteristic differences. Headaches associated with IH and how best to manage them were discussed by neurologist and neuro-ophthalmologist, Leonard Hershkowitz of Baylor University. He indicated his management techniques that worked well for him.A reception followed in which patients again communicated with the speakers.The 2nd conference day opened with a discussion of the mission and goals of IHRF and a review of IHRF-sponsored research by Emanuel Tanne, Clinical Assistant Professor of Ophthalmology, OHSU and president of IHRF. He pointed out that IHRF works to remove significant obstacles to research: under-funding, under-coordination of effort, incomplete recognition of the life-altering effects of IIH, and low recruitment of researchers in this area. IHRF funded animal model development projects at the University of Chicago and the University of Arkansas. Under investigation is a knockout mouse that develops IH shortly after weaning. Other research areas included joint testing at the University of Utah of a NASA-developed, non-invasive, closed loop ultrasound device to measure ICP in microgravity and an investigation of vitamin A receptors in arachnoid granulations at Ohio State University. IHRF also partners with the Casey EyeInstitute, in regard to the Intracranial Hypertension Registry at the Oregon Health & Science University, Portland. The IH Registry is a relational database management system designed for medical research. Emanuel Tanne discussed ongoing Registry research, including studies in genetics, economics, weight gain and pregnancy. Jessica Tanne, IHRF Director, Communications & Development, discussed raising community awareness, fundraising and the importance of becoming an IH ambassador. Illustrating and discussing their fundraising creativity were Dori Clements and Jacque Tate, both parents of IH children.Clark Sitton, Assistant Professor of Radiology, University of Texas, Houston, discussed types of imaging studies and the goals of imaging in IH. He presented an extensive collection of studies demonstrating pathological findings associated with IH.Bariatric surgery as a possible option in the management of IH was presented by Erik Wilson, Assistant Professor of Surgery, University of Texas, Houston, who covered risks and benefits of bariatric surgery, using his extensive experience as a guide. He also discussed types of procedures available and his personal approach to follow-up and long term goals for patients. Marc Criden presented a new hypothesis to consider for clinical management of chronic IH: establishing target pressures for each patient with IH. The hypothesis arose out of his and Steven Katz's experience with patients at the last IHRF patient conference, where they were impressed by the variety of symptoms and patient reports contradictory to current teaching. They hypothesized that chronically elevated ICP is neurologically damaging, even in patients without significant visual dysfunction or intractable headache. They are presently investigating and evaluating this hypothesis. The final speaker, Kapil Kapoor, resident in ophthalmology at the University of Texas, Galveston, presented his research on hyposmia and IH. He found that patients with elevated ICP have a decreased sense of smell and concluded that other nerves such as the olfactory nerve may be functionally compromised in the setting of IH by a mechanism similar to that of optic nerve compression. Therefore, it may be appropriate to consider IH as a more global neuroanatomic insult of augmented CSF pressure than previously considered.While the intent of educating patients was admirably accomplished by this conference, the conference served as a unique experience for researchers and clinicians to hear from a large group of patients about the nature of their disorders. Therefore, not only did physicians from a variety of sub-specialties have an opportunity to exchange ideas and explore future collaborative projects they also left with a different perspective of chronic IH and a new appreciation of patient-centered conferences as a mechanism to expedite translational CSF research.The author declares he has no competing interests.I am the sole author and have read and approved the final version of this paper."} +{"text": "The well-known association between vte modern molecular techniques vte trials of cancer therapy have defined additional risk factors that compound the thrombotic risk The burden of venous thromboembolism (vte has been associated with a high risk of recurrent thrombosis and of bleeding complications vte are at increased risk of mortality vte prevention and treatment in cancer patients, and sets the stage for future directions in this important domain The treatment of cancer patients for The inherent properties of blood vessels, endothelial cells, adhesion receptors, and soluble plasma coagulation proteins render these structures and molecules important in the propagation of coagulation and the regulation of cancer-cell growth. Perturbation of these components by cancer treatment interventions such as surgery, chemotherapy, and supportive care can further exacerbate prothrombotic properties.vte, as are certain cancer types, including pancreatic, stomach, brain, lung, and hematologic malignancies. In cancer patients, vte is not only a frequent cause of death, it also identifies a patient population with poor prognosis, and it is both clinically challenging and financially costly to treat. As cancer treatment modalities evolve, differences in the added thrombogenic risk for patients also emerge\u2014for example, the addition of anti-angiogenic therapy is associated with one of the highest risks of thrombotic complications.Advanced cancer is more often associated with vte, how should thromboprophylaxis for cancer patients be optimized?Given the strong association of cancer and Current Oncology, patients undergoing cancer surgery and those hospitalized for investigations and treatment of cancer are good candidates for appropriate thromboprophylaxis vte should be considered for long-term low molecular weight heparin therapy, given the more favourable clinical outcomes seen as compared with the outcomes seen with traditional oral anticoagulant therapy.Clearly, as recently reviewed in vte, and participation in good clinical trials evaluating cancer and coagulation should routinely be part of our comprehensive care of cancer patients.The recent guidelines from the American Society of Clinical Oncology underline the importance of optimizing anticoagulation management of cancer patients. The practice of appropriate thromboprophylaxis, up-to-date anticoagulation of cancer-associated"} +{"text": "It was launched on July 2 The specific objectives of i-FAB are to:(i) Increase the profile of foot and ankle biomechanics research within academic, clinical and industry communities(ii) Promote the value of foot and ankle biomechanics research to research users (iii) Develop a coordinated approach to addressing the challenges of experimental and computational biomechanics of the foot and ankle(iv) Enable better coordination of multidisciplinary research(v) Enable more effective coordination of foot and ankle biomechanics research between groups in different countriesA Steering Group has been formed to guide the initial development of the i-FAB community and its activities. The Steering Group seeks to construct a framework for developing i-FAB to meet the needs of the foot and ankle biomechanics community and welcomes input and direction from members.In September 2008, we had our first congress at Istituto Ortopedico Rizzoli, Bologna, Italy, chaired by Dr. Alberto Leardini. A mix of 150 lectures, posters and workshops were presented to 170 delegates from 30 different countries. Highlights included a live operation of a total ankle replacement by Professor Sandro Giannini, hands-on multi-segment foot kinematics demonstration by Professor Maria Grazia Benedetti, and keynotes lectures by Professor Harold Kitaoka , Professor George Arangio (Sailing charted seas: biomechanics and the orthopaedic surgeon), Dr. Mario Lafortune (The role of research in the development of athletic footwear), Professor Peter Cavanagh (Foot complications of diabetes), Dr. Sorin Siegler (Advances in image-based biomechanics of the human ankle) and Dr. Marco Viceconti .in vivo axes of the subtalar and talocrural joints using functional MRI during foot plantarflexion and dorsiflexion [Journal of Foot and Ankle Research [The Best Paper of the Congress was awarded to Dr. Frances Sheehan from the Physical Disabilities Branch of the National Institutes of Health, Bethesda, MD, USA for her paper 'Direct in vivo quantification of the 3D talocrural and subtalar finite helical axes' about a revolutionary non-invasive technique for quantifying the 3D iflexion . Dr. SheResearch and can th to 18th 2010. We anticipate an outstanding program covering both basic and clinical aspects of foot and ankle biomechanics together with a social program that will exploit the resources of the Pacific Northwest.Planning for three i-FAB activities is presently underway: website, 2010 congress, and e-communications. The website and e-communications are the start of a global \"collaborative workspace\" in which all members of the foot and ankle biomechanics community can engage. This collaborative workspace will harness the most recent IT developments for supporting the organisation and coordination of activities across traditional disciplinary boundaries and between groups who are geographically distributed. We are pleased to announce that the 2010 i-FAB congress will be at The University of Washington in Seattle between September 16One exciting goal of i-FAB is to promote and advance research in the field of foot and ankle biomechanics by providing up-to-date consensus based standards for the study and description of foot and ankle kinematics. We have assembled a committee to provide standardised quantitative morphological databases and periodic reviews of the state-of-the-art in foot and ankle kinematic research.i-FAB welcomes members from every community related to foot and ankle biomechanics, from academics, physicians, podiatrists, surgeons, and health professionals, to members of the footwear, orthosis, surgery and related industries. i-FAB has an open philosophy and connecting people across traditional disciplinary boundaries is one of its key objectives. Membership is presently free. Further details regarding i-FAB can be found on our website ."} +{"text": "We examined the liver of adult polar bears, arctic foxes, and rats by gold chloride staining, fluorescence microscopy for the detection of autofluorescence of vitamin A, hematoxylin-eosin staining, staining with Masson's trichrome, Ishii and Ishii's silver impregnation, and transmission electron microscopical morphometry. The liver lobules of the arctic animals showed a zonal gradient in the storage of vitamin A. The density of hepatic stellate cells was essentially the same among the zones. These results indicate that the hepatic stellate cells of the polar bears and arctic foxes possess heterogeneity of vitamin A-storing capacity in their liver lobules. Hepatic stellate cells are located in the perisinusoidal space of Disse and extend their thin fibrillar processes into this space ,2. UnderAlopex lagopus) during the period from August 1996 to September 2001. Three polar bears (Ursus maritimus) were shot in self-defense in February and August 1998. We examined the liver of these animals by gold chloride staining, fluorescence microscopy for the detection of autofluorescence of vitamin A, hematoxylin-eosin staining, staining with Masson's trichrome, Ishii and Ishii's silver impregnation, and transmission electron microscopical morphometry using a division map of liver lobule for a zonal analysis (Figure After having obtained permission to hunt animals from the District Governor of Svalbard, we caught 11 arctic foxes (The liver lobules of the arctic animals showed a zonal gradient in the storage of vitamin A Figure . The graResults of this study indicate that arctic animals possess the intralobular heterogeneity of vitamin A-storage capacity in the hepatic stellate cells.In earlier studies, a specific zonality for intralobular vitamin A-storage was reported. Although our results agree with other reports as to the presence of the heterogeneity of vitamin A-storing lipid droplets in the hepatic stellate cells in the liver lobule ,5, the lThe existence of the intralobular heterogeneity of vitamin A storage would relate to the number of hepatic stellate cells within the each zone or the maturation of hepatic stellate cells itself . HoweverHence, we speculate that the intralobular distribution of CRBP in the liver of polar bears and arctic foxes may also show similar heterogeneity to that in the rats, and have effects on the intralobular heterogeneity of storing vitamin A in the livers."} +{"text": "The search for the infectious agents responsible for cat-scratch disease, bacillary angiomatosis, and related syndromes has a long and often circuitous history. Recognition of the etiologic agents and a new understanding of the fundamental features of the epidemiology and natural history of modern day Bartonella -associated diseases culminate a multipartite story that combines clinical medicine, traditional microbiology, and novel technological approaches to solve a long-standing enigma."} +{"text": "The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age . A relatively high blood triglyceride level was found in patients with breast, lung, rectal , and stomach tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of \"cancerophilia\" (predisposition to cancer)."} +{"text": "British Journal of Cancer (2002) 86, 1528\u20131528. DOI: 10.1038/sj/bjc/6600300www.bjcancer.comCancer Research UK\u00a9 2002 E Edmund Kim and David J Yang. Publishers: Springer-Verlag, 2001. ISBN 0-387-95028-1. \u00a3120.50, $169.00.As the foreword to this book states, our passage into the new millennium gives the opportunity to use the medical achievements of the past 1000 years to develop treatment strategies for the future. It describes and explains the roles that imaging plays in the emergence of new diagnostic and therapeutic procedures.Increased knowledge regarding the genetics and the molecular biology of tumour development offers the potential of new targets of therapy. However, devising methods with which to determine the existence, and the evaluation, of novel diagnostic and therapeutic strategies in cancer remains a challenge. Improved imaging techniques and the radiolabelling of tracers and drugs are making non-invasive imaging of molecular targets possible, thereby facilitating the translation of these scientific breakthroughs into clinical practice.This book provides an excellent review of imaging technologies and their role within oncological treatment strategies. It begins with a basic science chapter giving a very structured and readable background to the molecular genetics of cancer, cancer cell immunology, biochemistry and pathology. This chapter explains DNA replication and the genetic mutations that give rise to the activation of oncogenes and the inactivation of tumour suppressor genes in neoplasia. It discusses the role of cellular immunology, including T-cell and B-cell immunity and cytokine interactions, providing an insight into active and passive immunotherapy in the treatment of cancer. This gives the reader a good platform from which to proceed with the subject of molecular targeting.The following chapters cover the principles of each of the imaging technologies available, and include the techniques of ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and spectroscopy (MRS), single positron emission tomography (SPECT) and positron emission tomography (PET). Each chapter addresses the difficult topic of technique methodology and the authors manage to describe this in a surprisingly straightforward manner. Obviously, some chapters are slightly more complicated than others, but in general the points are made clearly and simply.Having set the scene and discussed the various advantages and disadvantages of each imaging method, the second part of the book gives examples of the ways in which they can be used to image molecular targets utilising, for instance, radiolabelled antibodies and radiopharmaceuticals. Chapter 5 provides an overview of some of the radiopharmaceuticals that target tumours, concentrating on the rationale and the results of these studies.The radiolabelled antibody chapter, Chapter 6, is particularly interesting. It covers the production of monoclonal antibodies from hybridomas, made from the fusion of myeloma cells and B-lymphocytes, through to current phage library techniques. The importance of optimising antibody selection for tumour targeting, in particular the kinetics according to fragment size, is highlighted. Finally, the radioisotopes available for antibody radiolabelling are discussed. The following chapter expands upon this theme by demonstrating the possibility of radioimmunodetection of different tumour-marker expressing cancers using commercially available monoclonal antibody conjugates, such as ProstaScint (Cytogen) for prostate carcinoma, CEA-Scan (Immunomedics) for colorectal cancer and OncoScint (Cytogen) for colorectal and ovarian cancer.The potential value of polymer-drug conjugates and macromolecular contrast media imaged with MRI are described, together with the use of paramagnetic radionuclides to label monoclonal antibodies, and newer contrast agents, to aid in specifically targeting these for magnetic resonance imaging. This, thereby, expands the use from gadolinium-based interstitial agents to agents tailored to specific clinical applications.99mtechnetium-sestamibi scans in SPECT and fluorine-18 fluorodeoxyglucose scanning in PET. The main thrust of these chapters is to describe those radiotracers with established roles in oncology, with suggestions of those requiring further investigation.Dynamic PET images have been likened to displaying \u2018slices of life\u2019, however the expense of performing these scans generally confines their use to academic and teaching medical centres. On the other hand, SPECT is more accessible. Both techniques provide 3-dimensional images of the distribution of radiotracers and the chapters regarding targeted SPECT and PET provide data and images of gallium-67, thallium-201, The final third of the book expands upon the roles of the different techniques for imaging the processes important in tumour development and survival, in particular angiogenesis, hypoxia, apoptosis and signal transduction. The potential for imaging anti-cancer drugs themselves, including anti-sense oligonucleotides, gene delivery and expression, is also discussed. Illustrations are shown and the images and results are discussed providing a vast array of potential and future applications for targeting imaging.Overall, this is a very informative, readable book. The chapter sizes are easily digestible and there is a clear progression through the book presenting a succinct and balanced picture of the methodologies available. The black and white images of the techniques and the targets help to enlighten the reader visually regarding the text. I thoroughly enjoyed reading the book and learning from it. I would recommend it to both the reader with some knowledge wishing to explore the topic further as well as to those wanting a basic introduction and background to the subject."} +{"text": "Acute aortic dissection can occur at the time of intense physical exertion in strength-trained athletes like weightlifters, bodybuilders, throwers, and wrestlers.Rapid rise in blood pressure and history of hypertension are the most common causes of aortic dissection in athletes. It is a very tragic event because of its high mortality rate of about 32% in young patients. We report a case of aortic dissection in a young weightlifter with an extensive intimal tear of the aorta, from the sinus of Valsalva to the abdominal aorta. Acute aortic dissection results from a tear in the intima and media of the aortic wall, with the subsequent creation of a false lumen in the outer half of the media and elongation of this channel by pulsatile blood flow. Dissection of the aorta is associated with a high degree of morbidity and mortality despite continuing improvements in diagnostic and surgical techniques , and hypA 37-year-old Iranian man with a history of hypertension and long history of weightlifting was admitted to our hospital complaining of knifelike retrosternal chest pain, which was abrupt while lifting weight, accompanied by severe sweating and palpitation. Distal pulses were weakly palpable. Electrocardiography showed non-sinus arrhythmia, Wolf-Parkinson-White (WPW) syndrome, and Q in lead III and avf. Echocardiography findings were normal left ventricular size with concentric left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF) of about 55%, dilated ascending aorta of about 56 mm, and mild mitral regurgitation. In addition, the intimal flap in the ascending aorta was seen collapsed. The diagnosis was obtained by computed tomography (CT) angiography, which showed a typical aspect of type A of Stanford classification of aortic dissection fig . The intThe cardiovascular system adapts to exercise. Top-level training is often associated with morphological changes in the heart including increases in the left ventricular chamber size, wall thickness, and mass. The increase in the left ventricular mass as a result of training is called\" athletes' heart\" . MorganrWe strongly advise that athletes with one of the predisposing factors for aortic dissection eschew intense physical exertion. Unfortunately, survival after such dissections is extremely unanticipated because of the lengthy extension of the intimal tear, massive hemorrhage, and organ dysfunction. WPW: Wolf-Parkinson-White; CT: Computed tomography; LVH: Left ventricular hypertrophy; LVEF: Left ventricular ejection fraction; ICU: Intensive care unit; CPR: Cardiopulmonary resuscitation; CPB: Cardiopulmonary bypass.The authors declare that they have no competing interests.AK carried out the surgery and was directly involved in the conception, design and drafting of the manuscript. SS participated in the diagnosis and treatment; also gave critical comments on the results. PY collaborated in the design of the study and was directly involved in drafting and revising the manuscript. All the authors read and approved the final manuscript.Written informed consent was obtained from the patient's family for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal."} +{"text": "The study of cell behavior is of crucial importance in drug anddisease research. The fields of bioinformatics and biotechnologyrely on the collection, processing, and analysis of huge numbersof biocellular images, including cell features such as cell size,shape, and motility. However manual methods of inferring thesevalues are so onerous that automated methods of cell tracking andsegmentation are in high demand. In this paper, a novelmodel-based cell tracker is designed to locate and trackindividual cells. The proposed cell tracker has been successfullyapplied to track hematopoietic stem cells (HSCs) based onidentified cell locations and probabilistic data association."} +{"text": "The main aims of the Society are the organization of an annual scientific meeting and the fostering of Bioinformatics in Italy. The 4th Annual BITS Meeting, , was held in Naples, Italy, on April 26-28 2007, in the \u201cFederico II\u201d Congress Center, in view of the entire gulf of Naples, the Vesuvio, Castel dell'Ovo, the island of Capri and the city seashore. Over 130 scientists actively working in the field or strongly interested in its development met and discussed their work, state of the art and future perspectives. A total of 149 abstracts were accepted and presented in the poster session and 31 of them were selected for oral presentation.The Italian Society of Bioinformatics Structural and functional analysis of genomes; ii) Novel methodologies, algorithms and tools; iii) Molecular evolution and novel algorithms; iv) Biomedical Informatics; v) Large scale analysis of experimental data; vi) Gene expression and system biology and vii) Structural biology and drug design.BMC Bioinformatics supplement. We adopted a stringent reviewing procedure, based on selected Associate Editors handling the process according to their recognized knowledge in specific subjects of Bioinformatics and following a peer review procedure.From these conference sessions, 21 papers were submitted for publication in this After this process, 14 papers were accepted. They cover different aspects of theoretical and applied Bioinformatics, including: i) useful algorithms and tools for sequence analysis aimed at the prediction and characterization of functional motifs in nucleotide and protein sequences, of SNPs affecting protein stability, and of protein interaction networks and protein complexes; ii) curated databases of expression data and of conserved non coding sequences; iii) system biology models and iv) interesting technological breakthroughs for data management and for speeding up large-scale database searches.Whether this will help in encouraging scientists involved in biological and/or medical researches in our country to plan, merge and spread their knowledge by means of Bioinformatics is left to the future and to the availability of national grants specifically devoted to this.In this presentation, we gratefully acknowledge the patience and help of our colleagues around the world who helped in the process of reviewing as Associate Editors:Bert AbbotGill BejeranoAxel BrennickeIdelfonso CasesGino CingolaniLarry CroftManolis DermitzakisChristiane GebhardJerzy JurkaPeter KarpReinhard LabenbacherRoman LaskowskiArthur LeskRodrigo LopezJohn MattickSayan MukerjeeAnnalisa PastoreFrancis QuetierPeter RiceMarie-France SagotMarco SalvettiYves van de Peer and at .The next Annual meeting of the Italian Society of Bioinformatics will be held in Cagliari, September 22\u201326, 2008, in conjunction with ECCB08, the 2008 European Conference of Computational Biology. Further information about BITS2008 will be available on our web site at the address"} +{"text": "The Second Meeting of the British Society for Immunology Tumour Immunology Affinity Group (TIAG) took place at King's College on 17-18 June 1997 and brought together over 100 tumour immunologists from the UK and abroad. In contrast to previous meetings the focus of the meeting was on the role of adhesion in immunosurveillance and tumour dissemination. In addition, recent achievements in the areas of chemokines, cytotoxic T-lymphocyte (CTL) and natural killer (NK) cells, co-stimulation, gene and adoptive immunotherapy were also addressed. The purpose of this report is to outline current trends in tumour immunology."} +{"text": "Sir,In his letter, Dr. Al-Hajoj proposesBCG vaccination of infants was confirmed to have significant protective efficacy against disseminated childhood tuberculosis and tuberculous meningitis. A meta-analysis of 5 randomized control trials and 8 case-control studies showed an average protection of 80% among children vaccinated in infancy. The impaCurrently, BCG vaccine is not given routinely in USA, Canada and parts of western Europe, because of the low disease incidence in these countries . In Saudi Arabia, the incidence of the disease remains moderate , and there is a high influx of foreign workers (including housemaids) from countries with high prevalence of tuberculosis. In these circumstances, exposure of children to the disease is likely to be significant; and therefore, prevention of serious childhood tuberculosis should remain a priority. This emphasizes the need to continue with the current policy of compulsory BCG vaccination of infants in Saudi Arabia. A revision of this policy is justified when the disease incidence declines to low levels."} +{"text": "In a restricted sense, the resource curse is a theory that explains the inverse relationship classically seen between dependence on natural resources and economic growth. It defines a peculiar economic and political environment, epitomised by oil extraction in sub-Saharan Africa.Based on secondary research and illustrations from four oil-rich geographical areas , I propose a framework for analysing the effects of the resource curse on the structure of health systems at sub-national levels. Qualitative attributes are emphasised. The role of the corporate sector, the influence of conflicts, and the value of classical mitigation measures are further examined.Health systems in a resource curse environment are classically fractured into tripartite components, including governmental health agencies, non-profit non-governmental organisations, and the corporate extractive sector. The three components entertain a range of contractual relationships generally based on operational considerations which are withdrawn from social or community values. Characterisation of agencies in this system should also include: values, operating principles, legitimacy and operational spaces. From this approach, it appears that community health is at the same time marginalised and instrumentalised toward economic and corporate interests in resource curse settings.From a public health point of view, the resource curse represents a fundamental failure of dominant development theories, rather than a delay in creating the proper economy and governance environment for social progress. The scope of research on the resource curse should be broadened to include more accurate or comprehensive indicators of destitution and more open perspectives on causal mechanisms. Considering the extreme and deepening subjection of industrialised nations toward fossil energy, this economic approach to the resource curse would thus explain- as a first approximation \u2013 why the case is today nowhere better illustrated than in sub-Saharan Africa, the fastest growing oil-producing region worldwide [et al. [economic mechanisms have been examined as possible explanatory arguments. These explanations classically encompass processes such as: (i) the loss of economic diversification, following the appreciation of the domestic exchange rate caused by exports of natural resources (the 'Dutch disease'), and (ii) the volatility of the price of fossil fuels. Second, resource curse countries are characterised by high corruption levels. The theoretical framework behind this observation relies on the concept of 'rentier state', whereby governments in a capacity to rule in the absence of a functioning tax system are less accountable for misallocation of resources and poor governance. Third, states that rely heavily on oil exports are more likely to adopt authoritarian modes of governance. Fourth, the presence of natural resources increases the risk of civil wars. While this set of findings focusing on politico-economic mechanisms provides essential pieces to the overall picture describing resource curse environments, causal mechanisms and exact interactions are incompletely understood. The initial econometric definition of the 'curse of natural resources' is a useful framework to approach the counter-intuitive observation that economic growth is hampered by the availability of domestic mineral resources. However, this angle of analysis is clearly reductionist, for at least two reasons. First, much of the macro-economic framework (comparing growth performance between countries) is oblivious of sub-national or local differences within countries, and conceals deeper adverse effects for the very populations residing in mineral rich areas. Second, the focus on economic growth to describe the nature of the resource curse assumes that other dimensions are subsidiary to economic factors. Fortunately, some scholars have examined the effect of extractive industries from a broader perspective and used more comprehensive indicators of deprivation than purely economic ones. For example, Gylfason [a and that 'oil dependence is also associated with high rates of child malnutrition; low spending levels on health care; low enrolment rates in primary and secondary schools; and low rates of adult literacy'. More recently, Ross [The soils of most of African countries are rich in mineral, oil or gas resources , and couorldwide . As a coorldwide ,11, Rossorldwide , Karl [1orldwide , and Hum [et al. does not provide so far any comprehensive description of health systems in specific resource curse environments. As a first approach to fill this gap, I carried out secondary (desk) research to identify existing data about health outcomes/impacts and about components of health systems in oil-producing countries located in sub-Saharan Africa. These countries are listed in reference . I extenBased on this compilation of country data and on a review of the resource curse literature, I first propose a possible generic analytical framework Figure to definThe definition of health systems is open to interpretation and, depending on individual points of view or values, it can encompass increasing circles of inclusiveness among activities that define a society , as well as the overlapping category of traditional health practitioners. The latter two categories are popular and probably important in terms of numbers of providers b [The current definition endorsed by WHO draws frviders b , but theviders b and theiAlthough the three core categories considered in the framework provide services based on 'western' paradigms of healthcare and operate within the same geographical boundaries, they are clearly different in their underlying values, operating principles and self-defined legitimacy, as illustrated by examples in Table et al. [While government agencies are well defined by national policies and laws, the category of NPNGO providing health services is heterogeneous, and includes faith-based and humanitarian organisations, both further categorised as national or international agencies. Their defining values are generally altruism or solidet al. have shoIt has become popular for the corporate sector to be engaged in a number of health actions covering a range of public health endeavours, such as: supporting global or regional health initiatives, sponsoring biomedical research, sponsoring non-governmental organisations or, more directly, financing local health projects. As an example, the case of Exxon Mobil illustrates the diversity of such contributions through its involvement in malaria control . Obviousc, resulting in some confusion over its scope [d is a distinct and rather recent operating principle originating from the commercial sector. Definitions of CSR are loose ts scope ,29. CSR ts scope , but CSRts scope . It is ud Figure . This raRelated, but distinct from CSR is the concept of 'social license to operate' (SLO), which is the main operational objective of CSR at community level, giving the corporate industry its share of informal legitimacy and additional operational space Table . How the\"Social investments in local health (...), skills and infrastructure improve the capacity to absorb positive spillovers from and enhance linkages with businesses. The concept of absorptive capacity plays an important and positive role in the theory of FDI and development...At the same time, businesses also have an incentive to make social investments through partnerships over and above the developmental needs of the local people. Such investments will improve local skills, motivation and health of the local workforce, and thus create more efficient labour inputs and higher quality local suppliers on which business become increasingly dependent. Efficient labour inputs and the quality of local suppliers improve business efficiency, while the consent of the local communities provides a 'social license to operate\"' .Lee and Bialous advocateself-regulated norms, and resource curse environments are characterised by poor state governance or deficits in the rule of law. It is therefore important to examine if any international convention would cover norms regulating health systems governance in this context. Article 12 of the International Covenant on Economic, Social and Cultural Rights addresses a number of issues directly relevant to health in resource curse environments. These are specified in General Comment No. 14 issued by the UN Economic and Social Council under 'the right to the highest attainable standard of health' [et al. [A last point to consider here is the nature of health governance regimes under which the corporate sector operates in resource curse environments. By essence CSR entails health' , notably [et al. for inteThe three core categories of agencies introduced so far in the analytical framework Figure entertaiFirst, GOV and NPNGO interact classically through informal trust-based relationships or relational contracts. However, multilateral development agencies are currently promoting more binding relationships through contracting-out of health services, as indicated in the case of Southern Sudan. The benefits of this experimental approach are still disputed ,38. For Second, CES and GOV partnerships in the health sector can be biased by political agendas, at the expense of social achievements. Frynas and Le BThird, the relationship between CES and NPNGO has some underlying complexity. For example, oil companies are unable and unwilling to undertake comprehensive development projects and they are clearly looking for partnerships and joint initiatives to achieve their corporate social responsibilities ,43. For With the notable exception of international humanitarian organisations, the 'tri-sector partnership model' promoted by the corporate sector and multilateral development agencies thus draws from the same categories of actors that define the core elements of the formal health sector in a resource curse environment.Whether implemented under the umbrella of bilateral or multilateral development agencies, the place of ODA-financed health programmes in this context is ambivalent. They dwell upon the core categories of the tripartite health system model illustrated in Figure e [The tripartite health system framework described in previous sections is a dynamic model and it is naturally bound to evolve. Demographic pressure and urbanisation are obvious motors of change for local communities impacted by the resource curse, either through in site infrastructure developments or, more commonly, through migration toward booming urban areas. To different extents, the four areas examined in this paper are undergoing rapid demographic changes, which result in increased and mostly unregulated urbanisation. This is obvious for Luanda, the capital of Angola, and for Port Harcourt, the capital city of Rivers State, Nigeria. In the Doba basin of southern Chad, the oil extraction area of Kom\u00e9 has doubled its population since 1993 . In Soute . Even fre acknowleHarpham and Molyneux have revf and/or to the weapons industry. Sudan [The association between oil extraction and armed violence is well established, and it is classically considered one of the root causes of the resource curse. First, interstate conflicts are a recurrent theme in the history of oil extraction (p. 9.8\u2013y. Sudan (p. 18) y. Sudan (p. 10) y. Sudan addresses an important development issue. However, the theory has been criticised by independent evaluators for its 'lack of appropriate conceptual and empirical framework' g [Using econometric analyses, Collier and colleagues ,60 have ework' g and its ework' g ,63,64. Rework' g ,65,66 prework' g , none ofework' g have shoHaving reviewed the evidence for armed violence as a leitmotiv in the landscape of oil extraction, the key question is: to what extent does violence contribute to adverse health effects in a resource curse environment? Coupland has clarThere are at least three processes through which adverse health effects of industrial development projects can be mitigated at community level, and which would apply directly to oil extraction. These are: health impact assessments, consultations with local communities, and long term monitoring. A Health Impact Assessment (HIA) is an essential part of the broader Environmental Impact Assessment (EIA) process that is now considered standard practice for project proposals submitted to international development agencies . Lee et If one considers that the 'Chad Cameroon Petroleum Development and Pipeline Project' (CCPDPP: see Appendix 1) is a model of environmental and health impact mitigation in oil extraction (due to the oversight of the World Bank Group), the weight given to public health concerns and to HIA as a guarantee of best practices is at best disappointing. While the preliminary HIA had arguably induced some improvements in specific health outcomes , broader systemic health issues raised by the international panel of experts appointed by the World Bank were ignored or dismissed by the Consortium of corporate stakeholders . One of Finally, longitudinal monitoring of health outcomes and impacts of projects such as oil extraction should be standard procedures. Taking again the CCPDPP as an alleged model, there is much scope for improvement in practice, with a need for systematic baseline studies and pre-established public health surveillance mechanisms.primary intent criteria would formally exclude the corporate component (CES) of the core agencies depicted in Figure The presence of extractive industries in oil-rich areas affects directly the health of local populations. Examples of adverse health outcomes and impacts include: direct effects of environmental degradation, increase in road traffic accidents, acceleration of the spread of HIV and of other sexually transmitted infections. In addition, in oil-dependent countries complex systemic effects interact to determine broader consequences on health, such as: higher rates of child mortality, lower life expectancy, higher malnutrition rates or lower spending levels on health care . SimilarAside from direct health effects of oil extraction, Figure marginalised and instrumentalised, not only in the concrete contexts in which extractive industries operate, but also in mainstream development discourses proposing remediation to resource curse situations. Marginalisation of health has been exposed throughout this paper: (i) by the dominance of econometric parameters to define the resource curse, (ii) by the lack of a longer-term analysis taking into account the health consequences of urbanisation and (iii) by the poor weight that HIA and other health mitigation measures carry in the face of economic interests. Instrumentalisation of health appears in: (i) the nature of the operational concept of 'license to operate', (ii) the corporate perspective on HIA as an instrument to secure licenses to operate and (iii) the type of contractual partnerships promoted by multilateral development agencies, including tri-sector partnerships.I argue that health has been h co-authored by Jeffrey Sachs. This is still more troubling as one remembers that the same author has prominently been leading research and political agendas valuing health as a major determinant of economic growth [One might wonder why, with few exceptions, health and other social parameters of well-being have not received more attention in the resource curse literature until recently. Reasons might be historical or methodological, but also ideological. For example, the possibility of health as an explanatory variable is conspicuously absent from a recent authoritative textbook on 'Escac growth .As mentioned in the introduction, initial econometric findings on the resource curse are reductionist in their scope (countries vs. affected communities) and in their perspective . The theoretical foundations of this reductionist perspective obviously reflect mainstream development theories and macro-economic policies supported by international financial institutions. Perpetuating an exclusively economic and political research agenda would carry the risk to see ideologically biased solutions prescribed prematurely, while ignoring other important and neglected dimensions of the resource curse phenomenon. Remediation measures to armed conflict proposed by some analysts of the resource curse are indeed biased toward macro-economic interventions. Bannon and Collier . The country gained independence in 1960 and started oil exploitation in 1958, essentially in the Niger Delta region, where four states account for most of the national production. In spite of such wealth, this is a region where the GNP per capita and educational levels remain below national average, and 70 percent of its 20 million people are living below the poverty line j ,90. The j ,90-92. Dj add to tj ,63. Thisj . Politicj and massj . The Nigk [As shown by Human Rights Watch in the Rk , and in k ,98. Howek ,32,43 ask .With huge reserves of mostly offshore oil and a population of 12.4 million, Angola is one of the richest countries in Africa. Yet, it ranks poorly in terms of social development and it has the highest level of inequality among oil and gas producers. At least one third of Angola's population resides in shantytowns with verThe ruling elite of Angola is opaque and largely unaccountable about national oil revenues amounting to several billion US$ per year. The country is still very much dependent on foreign aid for the vital sectors of health, food relief and emergency assistance. The transition from humanitarian relief to reconstruction has been slow, partly due to obstructions to the work of aid agencies by the Angolan government. The role of oil companies in the social sector is troubling, and Le Billon could coCompared to the Niger delta, Angola thus offers a more straightforward example of the resource curse, devoid of major local and environmental dimensions, while the country at large is still relying heavily on foreign aid and relief agencies for the provision of basic services. For example, excluding landmines action, Angola has appealed for a total of US$ 17,468,992 in foreign emergency assistance in 2007 .l [With the assistance of the World Bank Group (WBG), oil fields have been exploited since 2004 in the Doba basin of southern Chad, through an impressive and elaborate public-private partnership between a consortium of transnational companies, and the governments of Chad and Cameroon. The project includes the development of three oil fields in southern Chad, a 1000-km underground pipeline running through Cameroon, an offshore export terminal, and the construction or rehabilitation of a large number of ancillary infrastructures alongside . The 'Chl ,102,104.l ) is thatth and 9th statutory missions) has repeatedly noted the absence of baseline studies and delays in setting up monitoring mechanisms, in particular with respect to HIV/AIDS prevalence in the project areas. Health impacts of the project will therefore be difficult to determine.The health sector is poorly developed in Chad, due to a lack of qualified medical staff, a lack of management skills at all levels, and a concentration of health services in urban areas . The quem [A glance at a concession map reveals m . As an im has submm (p. 122)m . The exam .g. Acemoglu D, quoted in Banerjee .h. In the book , health i. The following references and considerations about Botswana were kindly suggested to me by one of the reviewers.j. Niger Delta Development Commission (NDDC), 2004: quoted by Idemudia and Ite ; see alsk. For an historical overview, see 'Capital and community: a case study' in Watts .l. For a comprehensive analysis of the CCPDPP, see Gary and Karl . For an m. Letter of Sector Development Policy by Dr. Theophilus Ochang Lotti, Minister of Health. Annex 12, In: Government of Southern Sudan .CCPDPP: Chad Cameroon Petroleum Development and Pipeline Project; CES: Corporate Extractive Sector; CPA: Comprehensive Peace Agreement (Sudan); CSR: Corporate Social Responsibility; EIA: Environmental Impact Assessment; FDI: Foreign Direct Investment; GDP: Gross Domestic Product; GNU: Government of National Unity (Sudan); GOS: Government of Sudan; GOSS: Government of Southern Sudan; GPI: Genuine Progress Indicator; GOV: Governmental health agencies; HDI: Human Development Index; HIA: Health Impact Assessment; LGC: Local Government Council (Nigeria); MPLA: Movimento Popular de Liberta\u00e7\u00e3o de Angola; NPNGO: Non-Profit Non-Governmental Organisations; ODA: Official Development Assistance; SLO: Social License to Operate; SPLM: Sudan People's Liberation Movement; SSA: Sub-Saharan Africa; UNITA: Uni\u00e3o Nacional para a Independ\u00eancao Total de Angola; WBG: World Bank Group.The author declares that he has no competing interests.Table 2. Some key features about selected oil-producing countries.Click here for file"} +{"text": "The theme of the conference was \u201cAdvanced Technology of Radiation Medicine and Medical Physics Practice\u201d. About 650 delegates from India and abroad, including 120 radiological / medical physics students from different universities of India participated in the conference. ICMP-2008 was inaugurated by Dr. Anil Kakodkar, Chairman, Atomic Energy Commission and Secretary to the Government of India, Department of Atomic Energy (DAE). While delivering the inaugural address, Dr. Anil Kakodkar summarized the importance of ionizing radiation in daily life, and the contributions of DAE / BARC toward the cancer control program of the country. He also stated that a sufficient number of trained technical manpower for safe medical applications of ionizing radiation is available in the country. However, there is a need to take the advanced technology equipment to the rural sector, improve the working conditions at rural medical institutions and remunerate the technically trained people adequately. In addition, he emphasised the need to restructure the training modules so that the trained manpower could efficiently use the advanced technology equipment for its intended applications. Shri S. K. Sharma, Chairman, Atomic Energy Regulatory Board (AERB) presided over the inaugural function and released the Souvenir and Book of Abstracts. In the presidential address, Shri S. K. Sharma highlighted the role of AERB in ensuring the safety and security of radiation sources. He also stated that though the radiation safety record in medical applications of ionizing radiation is very good we must be cautious while using advanced technology equipment for radiodiagnosis and treatment. Prof. Bhudatt Paliwal, Director of Medical Physics, Department of Human Oncology and Medical Physics, University of Wisconsin, Madison, USA, presented the keynote address where he described in detail the dosimetry problems associated with organ movements during intensity modulated radiotherapy (IMRT). The keynote address highlighted the feasibility of real-time motion tracking methodology during the delivery of IMRT. Dr. Anil Kakodkar felicitated five Ex-BARC scientists for their contribution to AMPI (See Annexure-1 for their brief bio-data).The International Conference on Medical Physics (ICMP-2008) and the 29One hundred eighty five papers, including the AMPI Ramaiah Naidu Memorial Oration, 29 invited, 35 oral and 120 poster papers were presented during the conference. Shri P. S. Viswantahan, Former Head, Department of Medical Physics, Tata Memorial Hospital, Mumbai, delivered the seventeenth AMPI Ramaiah Naidu Memorial Oration (RNMO). The RNMO award is bestowed on an eminent personality who has a long working experience in the field of medical physics with a good track record of academics, research, and clinical practice. The title of his deliberation was \u201cMedical Physics in India: History, Development, and Activities\u201d. During his talk he described in detail the early days (1943) and the current medical physics activities in the country, including commercially available technology and indigenous developments. He also listed the future directions to deal with hi-tech equipment and emphasized the need for harmonization in medical physics training modules. The key feature of ICMP-2008 was the AMPI-AROI (Association of Radiation Oncologists of India) joint scientific meeting on November 28, 2008, at Nehru Centre, Worli, Mumbai. The joint meeting was the first of its kind, which could be assumed to be the defining moment in the history of medical applications of ionizing radiation in India. Both the clinical and physical aspects of recent radiation oncology, such as, IMRT, IGRT, precision radiotherapy by Cyber Knife, adapted Telecobalt machines and Proton accelerators, Image guided brachytherapy, and indigenous development of radiotherapy technology were presented during the joint meeting. The joint meeting was useful for radiation oncologists, for improving their understanding of medical physics and the technological aspects of recent radiotherapy, while it was equally beneficial for medical physicists to understand the clinical requirements and associated complexities when implementing hi-tech radiotherapy. Panel discussion on \u201cNewer Technologies: Promises and Pitfalls\u201d witnessed the active participation of a large number of medical physicists and radiation oncologists. It was concluded during the discussion that technology is available for high precision radiotherapy and dose escalation, but it should be used discriminately as a majority of cancers require palliative treatment by conventional techniques.The scientific deliberations of ICMP-2008 covered the whole spectrum of medical radiation physics: Radiation Therapy Physics and Devices; Medical Imaging Physics and Devices; Radiation Dosimetry and Standards; Radiation Physics; Radiation Biology; Time Dose Models; Commissioning, Quality Assurance, and Audits; Clinical Aspects of Radiation Oncology; Clinical Aspects of Medical Imaging; Computational Tools in Medical Physics; Education and Training in Medical Physics; and Radiation Protection and Safety. Presentations on recent developments in the technology of radiation medicine and methodology of imaging and radiation therapy were the special attractions. The oral and poster presentations were evaluated for the best Oral and Poster articles. At the end of the conference \u201cImprovement of ImatriXX in terms of spatial resolution and large field acquisition for patient specific IMRT verification\u201d by Arun S. Oinam, Lakhwant Singh, Pradeep Goswami, Anup Bhardwaj, B. S. Rana, S. C. Sharma, from the Radiotherapy Department, Postgraduate Institute of Medical Education and Research, Chandigarh, India, and \u201cDosimetry of in-house designed circular cone for stereotactic treatment using MVCBCT\u201d by Kamlesh Kumar Gupta, V. K. Sathiyanarayanan, Janhavi R. Bhangle, R. Vaitheeswaran, from the Department of Radiation Oncology, Ruby Hall Clinic, Pune, India were declared the best Oral and Poster papers respectively.The overwhelming participation of trades dealing with medical radiation equipment, dosimetry systems, phantoms, computerized treatment planning systems, and treatment accessories was the other attraction of ICMP-2008. A number of recent technological equipments and dosimetry systems (2-D array with high resolution), phantoms (Dynamic phantoms to simulate organ movements), patient immobilization devices (SBRT immobilization systems), and other related products were demonstrated in 32 stalls arranged near the conference venue.In summary, the conference deliberations were useful for radiation scientists, medical physicists, radiation oncologists, radiologists, radiobiologists, dosimetrists, and radiation technologists."} +{"text": "Utilizing data from the California Health Interview Survey (CHIS) 2009, we examine caregiving activities among foreign born and US born Latinos, and US born Non-Hispanic whites ages 18 to 80 who are caring for an adult age 60 or older. Utilizing OLS regression, we first examine the relationship between race, ethnicity, nativity, and age and the amount of caregiving, types of caregiving, and use of long-term care (LTC) services among the population. Next we examine the health, mental health, and economic status of the three caregiver populations. The results find that middle aged and younger foreign born Latinos provide the greatest amount of care and also present with the greatest amount of economic challenges. US born middle- aged Latino caregivers also provide relatively high levels of care and also are more likely than other caregivers to experience health challenges including diabetes, obesity, depression and social isolation."} +{"text": "Bartlett pioneered the use of Extra-Corporeal Membrane Oxygenation (ECMO) for prolonged cardio-respiratory support in critical patients in the 1970's . Early cBurke and McMullan contribute a very extensive and precise review of their experience with Extra-Corporeal Life Support (ECLS) for pediatric heart failure, including the utilization as peri-operative support as bridge to heart transplant. Very appropriately, they present the extracorporeal cardio-pulmonary resuscitation as one of the most significant advancements in the field of ECLS (Burke and McMullan). In addition to a clear list of contraindications, a very detailed list of the potential complications was given, including hemorragic episodes, central nervous system injuries, pericardial tamponade, pneumothorax, metabolic acidosis, seizures, infections, renal failure, failure of the oxygenator, and limb ischemia (Burke and McMullan).Di Nardo et al. contribute review of ECLS, with particular attention to current indications, pre-operative stabilization, peri-operative support and use beyond the peri-operative period .. An important contribution was given with a list of special indications for ECLS: intractable arrhythmias, extracorporeal cardio-pulmonary resuscitation, and use in the presence of \u201cfunctionally\u201d uni-ventricular type of circulation .The contraindications, as well as the details to facilitate the cannulation in neonate and small patients are reviewed .Their very strong message was that every attempt should be done to start ECLS \u201curgently\u201d rather than \u201cemergently,\u201d before the presence of dysfunction of end organs or circulatory collapse Harvey contributed a useful and practical review on cannulation, based on his very extensive clinical experience. Pure cannulation considerations about the design of the available cannulas and the type of required support are discussed (Harvey). For the Veno-Arterial (V-A) support suggestions were given for difficult cannulation, with special considerations particularly for neonates, and for the central cannulation for V-A support. For the Veno-Venous (V-V) support a list of potential complications was presented, with suggestion about their prevention and treatment (Harvey). A separate part was dedicated to the surgical cannulation of the femoral vessels for larger size patients, with attention to the distal limb perfusion, as well as to the vessel sparing cannulation (Harvey). Finally, all aspects related to the need of left heart venting were presented, for both situations of open and closed chest left heart venting (Harvey).Broman and Frenckner contribute an interesting article on the transportation of critical patients on ECMO. After an accurate report of the background, they gave a carefully detailed description of the logistics of the transport, including the requirements for the transport vehicle, the equipment and the personnel (Broman and Frenckner). Special situations were also taken in consideration, such as international transportations, environmental and climate issues, and working environment (Broman and Frenckner).Ryerson and Lequier contribute a review of one of the most important and difficult issues of the ECLS: the management and monitoring of the anticoagulation. They very appropriately started by specifying than anticoagulation per se is more complex in neonates and infants, and anticoagulation on ECLS provides an additional layer of complexity (Ryerson and Lequier). Furthermore, heparin is only an indirect anticoagulant, and the standard monitoring is hugely imperfect. Then they analyzed the role of activated clotting time, activated partial thromboplastin time, anti-Xa assay, viscoelastic testing, and antithrombin replacement (Ryerson and Lequier). Alternative options of anticoagulation were considered, such as direct thrombin inhibitors, new oral anticoagulants, and factor XIIa inhibitors. They provide an useful review on the prevention and management of bleeding and thrombotic complications during ECLS: definition and criteria of significant bleeding, role of antifibrinolytic therapy, activated factor VII, thrombotic complications in the patient and in the circuit, heparin-induced thrombocytopenia, and finally the optimal blood products replacement (Ryerson and Lequier).(Nair and Oishi). After an extensive introduction and explanation of the role of the ECLS in the presence of respiratory issues, they focused on ECLS in patients with \u201cfunctionally\u201d uni-ventricular hearts, discussing the role of V-V vs. V-A support. Special considerations were proposed for patients with \u201cfunctionally\u201d uni-ventricular hearts requiring V-V support because of ARDS: in particular (a) timing of cannulation, (b) type and positioning of the cannula, (c) bleeding, thrombosis and anticoagulation, (d) ECLS flow in these patients, (e) lung rest settings, and finally (f) weaning from ECLS.In the last article of this Research Topic Nair and Oishi report their experience with the management of patients with single-ventricle pathophysiology and acute respiratory distress syndrome (ARDS), with V-V ECLS We strongly believe that this collection of articles on ECMO will be very useful to all people involved in the care of pediatric patients requiring cardiac and/or respiratory support.AFC and TK edited this Research Topic and this editorial was written by AFC.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The use of video-games, either online or offline, has significantly increased, and almost homogeneously, around the globe over the last decades , the USA , Norway , Italy , Greece, Cyprus, and Australia . Online gender specific and face to face data collection procedures were applied, in conjunction with a number of different models and analytical methodologies ranging from Confirmatory Factor Analysis , Mokken analysis , Rash analysis , Classical Test Theory , Complex Regressions , and the PRISMA guidelines for systematic literature reviews (Costa and Kuss). Disordered gaming scales were assessed comparatively , across genders , while the differential functioning of disordered gaming criteria was examined .In this context, the goal of the present special topic-issue is to contribute to the ongoing discussions concerning this phenomenon. The studies included utilized culturally and developmentally diverse, normative samples from Iran Cultural values of independence, competitiveness and hierarchy have been suggested to confound the assessment of the experienced level of absorbance by the gaming activity ; (c) the need of particular emphasis on female gamers and their specialized assessment was emphasized ; (d) a considerable delay in the employment of consistent measurements/ assessment in studies of clinically diagnosed disordered gamers was illustrated (Costa and Kuss); and (e) analogies with the emergence of gambling behaviors among younger individuals became clearer in the context of the broader literature .The findings of this special topic contribute to the extant literature by shedding light to much debated, yet important, aspects of the assessment and measurement of disordered gaming behaviors. Indicatively: (a) the inclusion of gaming motivation as an inherent part of the assessment of disordered gaming behaviors has been supported by Costa and Kuss), while the number of measurement invariance studies, targeting in particular issues of scalar invariance (whether the same scores indicate the same severity) across populations of different genders, cultures, and developmental stages are rare (Stavropoulos et al., assessment and measurement discipline in regards to the officially introduced definitions of DSM-5 (American Psychiatric Association, However, challenges in the field of disordered gaming assessment still remain. Scholars continue to disagree about the nature of the behavior (Kardefelt-Winther et al., All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study.VS and RG contributed to the literature review, the structure, and sequence of theoretical arguments. FM-S contributed to the theoretical consolidation of the current work, revised, and edited the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Social status - the standing of a person or group in the social hierarchy - is part and parcel of social life and a significant determinant of cognition and behavior. Status hierarchies are basis of virtually all human and primate societies and assign different roles and privileges to its members. However, the dynamic nature of social status and the underlying mechanisms in old age are not well understood. Therefore, this symposium addresses questions of how social status is influenced by aging-related changes in roles, life events, self-concept, and images of aging and how social status shapes in response personality, subjective age, prosocial behavior, performance, and well-being in old age. Bellingtier and colleagues examined objective and subjective social status and their connections to subjective age, attitudes towards aging, and awareness of age-related changes. Zhang shows paradoxical association between aging stereotypes and prosocial behaviors toward older adults. Barber and Hamel investigated how stereotypes of reduced physical competence in old age affect the gait performance on easy and difficult tasks. Weiss and colleagues take a cross-cultural perspective on the different sources of social status in China, Germany, and the US showing that generations in contrast to age groups represent a source of high social status in later life. Finally, Kornadt investigates the dynamic interplay of changes in social roles and personality in old age. Together, these presentations enlarge our understanding of the dynamics of social status in old age."} +{"text": "During the workshop, experts discussed the state of the science. The U.S. Food and Drug Administration (FDA) has approved several medications to prevent osteoporotic fractures. These include bisphosphonates (BPs), denosumab, teriparatide, estrogens, and selective estrogen-receptor modulators. BPs are a first line of pharmacologic treatment for most women and men who have osteoporosis. Despite the efficacy of short-term use of BPs and other osteoporosis medications, treatment rates are low and appear to be decreasing. This talk would describe the problem/epidemiology of fracture prevention in the United States; the importance of drug therapy and their effectiveness; the limited evidence regarding long-term use of drug therapies; the questions surrounding the application of drug holidays; and the complex physician and patient factors that impact the use of and adherence to osteoporotic drugs."} +{"text": "The northern coast of Central Java Province, Indonesia, is considered as the critical area of flooding. The area always suffers from flooding because of heavy rainfall and/or sea level rise. Flooding brings a lot of consequences, including people\u2019s suffering, property damage and property loss. A number of efforts have been carried out to manage flood problems, yet the achievement is incomplete without stakeholder involvement. Stakeholders have a very important role in flood risk reduction. A common understanding on the existence and role of stakeholders is important in achieving community resilience. The aim of this article was to analyse interest and cooperation among stakeholders in flood risk reduction. In-depth interviews were conducted to identify and analyse interest and influence of stakeholders in relation to flood risk reduction. MIC-MAC (Cross-impact Matrix Multiplication Applied to Classification) and MACTOR methods were employed to analyse collected data. The results of this study indicated that restoration and humanity are the key objectives with major influence in lowering flood risk. The objectives are critical for the success of flood risk reduction efforts. The Disaster Management Agency is identified as the main stakeholder with the most important role in reducing flood risk in Central Java Province. The Indonesia Disaster Data and Information shows a long-term upward trend in the number of floods in Indonesia, in which 5233 occurrences or approximately 38.99% of the total number of natural disasters occurred between 1815 and 2015. From 2011 to 2015, 368 cases of flooding in the Central Java Province, Indonesia, were reported, and the number has been continuously rising ever since and MACTOR .Cross-impact Matrix Multiplication Applied to Classification is an analytical tool used to analyse the drive power and dependence power of factors and various objectives of stakeholders. The Cross-impact Matrix Multiplication Applied to Classification principle is based on the multiplication properties of matrices. Analysis using MIC-MAC is performed to identify the key factors that drive the system in various categories. Based on their drive power and dependence power, the factors have been classified into four categories which are autonomous factors, linkage factors, dependent factors and independent factors of stakeholders . This quadrant includes objectives that have a weak influence and dependence. The objective is less related to flood risk reduction and may have few relationships that will be eliminated from the objectives of stakeholders in flood risk reduction.Quadrant 2 is dependent factors (weak influence \u2013 strongly dependent). It includes objectives that have weak influence and strong dependence. The objectives in this quadrant are non-independent ones.Quadrant 3 is a linkage factor (strong influence \u2013 strongly dependent). It includes objectives that have a strong influence and strong dependence. They should be determined meticulously as the relationship between goals is unstable.Quadrant 4 is an independent factor (strong influence \u2013 weak dependent). This quadrant includes objectives that have strong strength and weak dependence. The objectives are the key factors in flood risk reduction.The objectives in the upper-left quadrant (restoration and humanity) imply the high influence and low dependence of other variables in flood risk reduction. These objectives have major influence in reducing flood risk. They, thus, become the key objectives that are critical in the success of flood risk reduction efforts. Restoration enables stakeholders to undertake the development, maintenance and improvement of natural resources and/or infrastructures, such as rivers, embankments and floodgates, which have been proven to lower the risk of flooding, while humanity raises awareness and empathy to others. These two objectives have the greatest impact in reducing flood risk.The second most important quadrant is the upper-right quadrant. The two objectives included in this quadrant are main duty and safety. The objective of carrying out the main duty is important for government agencies because it is their main activity as well as a major indicator of the performance of their agencies. The objective of promoting people\u2019s safety is also an important goal for an individual or group or organisation in reducing flood risk.The lower-right quadrant is dependent on weak driver and strongly dependent variables. The objective of this quadrant is the element of awareness, which is a non-independent factor. Image, income, relocation and incentives are also classified in this quadrant. They are the objectives of several stakeholders in conducting flood risk reduction activities.Stakeholders involved in the activities of flood risk reduction have different influences and interests (objectives). Based on the identification and analysis of stakeholders, flood risk reduction activities in the northern coastal area of Central Java Province, Indonesia, were conducted by the Provincial Disaster Management Agency (Badan Penanggulangan Bencana Daerah [BPBD] Jateng), Semarang City Disaster Management Agency (Badan Penanggulangan Bencana Daerah [BPBD] Semarang), Pati Regional Disaster Management Agency (Badan Penanggulangan Bencana Daerah [BPBD] Pati), Pekalongan Regional Disaster Management Agency , Regional Development Planning Agency (Badan Perencanaan Pembangunan Daerah[APPEDA]), Public Health Office (Dinas Kesehatan), Public Works Service (Dinas Pekerjaan Umum), Environmental Services (Dinas Lingkungan Hidup), businessmen, village heads, Search and Rescue (SAR) Team (Tim SAR), Indonesian Military and Indonesian Police , Indonesian Red Cross, farmers, volunteers, fisherman, village community leaders, local community (Masyarakat), Non-government Organisation (NGO) (community), Universities (university), business actors and journalists.Stakeholders in flood risk reduction can be categorised into three groups , Disaster Management Agency of Pati Regency (BPBD Pati) and Disaster Management Agency of Pekalongan Regency are the institutions responsible for disaster risk reduction at regional level and have the highest impact. It means that these institutions have an important role in reducing flood risk in Central Java Province. The BPBD Central Java Province ranks second, followed by community leaders as stakeholders who have a high competitiveness in reducing flood risk in the Central Java Province.The other major findings of stakeholder analysis are convergence and divergence , Semarang City Disaster Management Agency (BPBD Semarang), Pati Regional Disaster Management Agency (BPBD Pati), Pekalongan Regional Disaster Management Agency , Regional Development Planning Agency (BAPPEDA), Public Health Office, Public Works Service (DPU), environmental services, businessmen, village heads, SAR Team, TNI and POLRI, Indonesian Red Cross (PMI), village community leaders, Community, NGO, universities and business actors . StakehoBased on the actor\u2019s preference in objectives and competitiveness, the actors involved in reducing flood risk groups are grouped into four major groups. The first group consists of BPBD Central Java Province, BPBDs at regional level, Health Office, Public Works Service (DPU), environmental services, village heads, SAR and Indonesian Red Cross. The second group consists of universities, farmers, communities, fishermen, community leaders and NGOs (community). The third group includes the business actors and journalists, and the fourth group is the TNI-POLRI.The next finding is divergence. The results of MACTOR analysis show that stakeholders with a high potential of divergence are BPBD, farmers, fishermen and businessmen. The result indicates that these stakeholders have a relatively high probability of conflict or goal difference. On the contrary, university, TNI-POLRI, PMI and SAR have a low probability of conflict. In fact, their position is neutral because they have indirect interests in flood risk reduction activities.Not all actors involved in flood management have an important role in reducing flood risk. Each stakeholder has different objectives in conducting flood risk reduction activities; they are restoration, humanity, safety, income, image, main duty, incentive and relocation. Restoration and humanity are two objectives that have a major influence in lowering flood risk. These key objectives are critical in supporting the success of flood risk reduction. Restoration encourages stakeholders to undertake the development, maintenance and improvement of natural resources and/or infrastructure, such as rivers, embankments and floodgates, which may lower the risk of flooding. Meanwhile, humanity raises the awareness and empathy to others. In general, stakeholders in flood risk reduction can be grouped into three, namely beneficiaries, intermediaries and policy-makers. The Disaster Management Agency (BPBD) as the institution of policy-makers for disaster risk reduction at the regional level appears to have the highest role. The Disaster Management Agency (BPBD) has an important role in reducing flood risk in Central Java Province."} +{"text": "Therapies originating from traditional medical systems are widely used bypatients in both India and the United States. The first India-US Workshop onTraditional Medicine was held in New Delhi, India, on March 3 and 4, 2016, as acollaboration between the Ministry of Ayurveda, Yoga and Naturopathy, Unani,Siddha, and Homoeopathy (AYUSH) of the Government of India, the US NationalCancer Institute (NCI), National Institutes of Health, and the Office of GlobalAffairs, US Department of Health and Human Services. It was attended by Indianand US policymakers, scientists, academics, and medical practitioners fromvarious disciplines. The workshop provided an opportunity to open a dialoguebetween AYUSH and NCI to identify promising research results and potentialtopics for Indo-US collaboration. Recommendations that emerged from the workshopunderlined the importance of applying rational and scientific approaches fordrug development; standardizing traditional medicine products and procedures toensure reliability and reproducibility; promotion of collaboration betweenIndian traditional medicine practitioners and researchers and US researchers;greater integration of evidence-based traditional medicine practices withmainstream medical practices in India; and development of training programsbetween AYUSH and NCI to facilitate crosstraining. Several positive developmentstook place after the thought-provoking deliberations. This makes India one among 12mega\u2013biodiverse countries of the world.Upgrade the educational standards in Indian Systems of Medicines andHomoeopathy colleges in the country,Strengthen existing research institutions and ensure a time-bound researchprogram on identified diseases for which these systems have an effectivetreatment,Draw up schemes for promotion, cultivation, and regeneration of medicinalplants used in these systems, and5Evolve pharmacopeial standards for Indian Systems of Medicine and Homoeopathydrugs.6 Of the threepharmacopeia committees for Ayurvedic, Siddha, and Unani drugs, the PharmacopoeialLaboratory for Indian Medicines, Ghaziabad, has thus far published standards on1,082 single drugs and 302 compound formulations.7 The Ministry of AYUSH has also set up a research portal,managed by the National Institute of Indian Medical Heritage, for disseminatingknowledge regarding AYUSH systems and research updates for academicpurposes.8 The TraditionalKnowledge Digital Library was initiated in 2001 as a collaborative project betweenthe Indian Council of Scientific and Industrial Research, the Ministry of Scienceand Technology, and the then\u2013Department of AYUSH. Managed by the Council ofScientific and Industrial Research, the Traditional Knowledge Digital Librarydatabase contains 34 million pages of formatted information on over 0.29 millionmedicinal formulations of Ayurveda, Unani, Siddha, and asanas of yoga in fiveinternational languages . Access hasbeen provided to 10 international patent offices under a nondisclosure agreement tocheck for prior art while granting patents.9As part of the 12th Five-Year Plan (2012 to 2017), the Government of India launchedthe National AYUSH Mission, which envisages better access to AYUSH services throughan increase in the number of AYUSH hospitals and dispensaries; mainstreaming ofAYUSH through colocation of AYUSH facilities at primary health centers, communityhealth centers, and district hospitals; and ensuring availability of AYUSH drugs andtrained manpower. The plan also aims to improve the quality of AYUSH educationthrough enhancement of the number of upgraded educational institutions, sustainedavailability of quality raw materials, and promoting medicinal plantconservation.10According to the 2012 US National Health Interview Survey, one in three adults in theUnited States used complementary and alternative medicine (CAM) approaches, withnatural dietary supplement products and yoga being the most commonly used CAMmodalities. It has been estimated that in 2006, Americans spent 33.9 billion USdollars out of pocket on CAM products and services.11 For dietary supplements, the FDA\u2019s Center for FoodSafety and Applied Nutrition is responsible for the agency's oversight of theseproducts, and premarket approval is not required for many ingredients that havehistorically been in the marketplace. However, new dietary ingredients do requirepremarket notification with the Center for Food Safety and Applied Nutrition, withsupporting information that the ingredient will reasonably be expected to be safeunder the conditions of use recommended or suggested in the labeling.Several arms of the US Department of Health and Human Services (HHS) address aspectsof TM. Natural products from herbal sources are oftensold as dietary supplements and are readily available to consumers in the US.Because dietary supplements are not intended to treat, diagnose, cure, or alleviatethe effects of diseases, they do not undergo the drug approval process with the USFood and Drug Administration (FDA).12 The NIH Office of Dietary Supplements was created tostrengthen knowledge and understanding of dietary supplements by evaluatingscientific information, stimulating and supporting research, disseminating researchresults, and educating the public to foster an enhanced quality of life and healthfor the US population.13 AnotherNIH institute, the National Cancer Institute (NCI), has at least two programs thatspecifically address traditional medicines. NCI\u2019s Developmental TherapeuticsProgram has empowered its Natural Products Branch to acquire plants, microbes, andmarine organisms through collection contracts encompassing over 25 tropical andsubtropical countries worldwide. The NCI Natural Products Repository, which isconsidered a national resource, includes approximately 80,000 plant samples, 20,000marine invertebrates and algae, and 16,000 microbes.14 The NCI Office of Cancer Complementary andAlternative Medicine is responsible for NCI\u2019s research agenda in CAM as itrelates to cancer prevention, diagnosis, treatment, and symptommanagement.15The US National Institutes of Health (NIH), part of the HHS, comprises 27 differentinstitutes and centers that support biomedical research, including research on manyaspects of CAM. The National Center for Complementary and Integrative Health,formerly the National Center for Complementary and Alternative Medicine, is the NIHagency with a mission to define, through rigorous scientific investigation, theusefulness and safety of complementary and integrative health interventions andtheir roles in improving health and health care.16 State and local governments areresponsible for deciding what credentials practitioners must have to work in theirjurisdiction.In the United States, there is currently no standardized, national system forcredentialing complementary health practitioners, and the credentials varysignificantly from state to state and discipline to discipline.17In April 2015, the Secretary and Joint Secretary of the Ministry of AYUSH, alongwith other associates, visited the HHS and NIH to explore the potential forcollaboration. As an outcome of this visit, AYUSH and NCI proposed a follow-upmeeting as an opportunity for additional discussions. In September 2015, the JointSecretary of the Ministry of AYUSH participated in the First US-India HealthDialogue in Washington DC,18 whereboth sides agreed that they would collaborate on various aspects of TM, includingregulatory assessment and research capacity building. Specifically, the HHS Officeof Global Affairs, NCI, and the Ministry of AYUSH agreed to hold a workshop on TM inearly 2016 to create a roadmap for AYUSH collaborations between India and the UnitedStates and to contribute to health, wellness, and people-centered health care inboth nations.In this context, President Barack Obama and Prime Minister Narendra Modi, in theirIndia-US Joint Statement of January 2015, pledged to encourage dialogue between theUnited States and India on TM.The first India-US Workshop on Traditional Medicine (ayushworkshop.in) was held atthe National Agricultural Science Complex, New Delhi, India, on March 3 and 4, 2016.The workshop\u2019s inaugural session started with a welcome address by JointSecretary Jitendra Sharma (Ministry of AYUSH) and was followed by keynote addressesby Ambassador Jimmy Kolker , H.K. Pande, and Ajit Mohan Sharan ; a special address was providedby US Ambassador to India, Richard Verma, and an address was presented by Shripad Y.Naik . The speakersnoted that the goal of this workshop was to discuss the importance of applyingrigorous scientific methodologies to the study of traditional Indian medicalsystems, using evidence derived from such studies to inform both traditional medicalpractices, appropriately integrating evidence-based traditional practices withmodern (Western) medical practices, and making use of the particular strengths thatIndia and the United States can bring to this endeavor.The workshop was attended by Indian and US policymakers, scientists, academicians,and medical practitioners from various disciplines, including but not limited tonatural product chemistry, pharmacology, biochemistry, cancer biology, immunology,cancer prevention, cancer control and population sciences, medical oncology,radiation oncology, integrative oncology, yoga, Ayurveda, Unani, and homeopathy.The program included specific themes divided into four sessions: (1) TraditionalMedicine in the National Cancer Institute, (2) Traditional Medicine in India(introduced by the Ministry of AYUSH), (3) Strength of AYUSH and Promising AYUSHInterventions for Cancer and Other Areas (presented by AYUSH scientists), and (4)Research Presentations on Alternate Systems and Cancer (presented by US scientists).The second day of the workshop was devoted to group discussions on (1) NaturalProducts Research, (2) AYUSH Systems of Medicine in Cancer: What Holds Promise, and(3) Generating Evidence Toward Market Access for AYUSH Products and Practice.The remainder of this article summarizes the workshop proceedings; recommendationsfrom the first India-US Workshop on Traditional Medicine, including areas thatdeserve additional development in cancer research and management; and possibleresearch areas for Indo-US collaboration. The article also highlights developmentsin the bilateral collaboration since the workshop.19 O\u2019Keefedescribed the work of NCI\u2019s Natural Products Branch and Molecular TargetsLaboratory. The NCI Natural Products Repository is one of the largest and mostdiverse collections of natural products, housing more than 230,000 extracts. Thegrowth inhibitory effects of these extracts and their fractions are tested in theNCI-60 Human Tumor Cell Line Screen, as well as against discrete cancer-relatedmolecular targets. O\u2019Keefe described how the active components in extractsare isolated, identified, and assessed for their mechanism of action. He discussedthe use of analytical techniques, such as liquid chromatography massspectroscopy\u2013mass spectroscopy to help upgrade the Ayurveda, Siddha, andUnani pharmacopeia and bring it on a par with the US Pharmacopeia.The presenters in this session were Jeffrey D. White, MD , Barry R. O\u2019Keefe, PhD , and Ikhlas Khan, PhD . White presented anoverview of CAM use and research in the United States, with an emphasis on cancer.In fiscal year 2014 , NCI supported 212grants for which some component of the research was relevant to CAM . More th Khan explained the US government\u2019s approach to regulating botanical productsas either dietary supplements or drugs. Important issues in the regulatoryassessments of these products are safety, quality, and efficacy. Several aspects ofproduct quality were examined, including standardization, selection of markercompounds, adulteration, and misidentification. Finally, Khan introduced the Indo-USCenter for Research in Indian Systems of Medicine at the University of Mississippi,which has as its mission the facilitation of scientific validation and disseminationof information on Indian systems of medicine through collaborative research.On behalf of the Ministry of AYUSH, Sharma presented a brief overview of AYUSH andAYUSH research programs, including current collaborations with US institutions.Presentations of promising AYUSH interventions for treating cancer included acollaborative study with the Tata Memorial Centre-Advanced Centre for TreatmentResearch and Education in Cancer, Mumbai, which has identified nine medicinal plantswith potential cytotoxic or cytostatic effects against different types of cancers,including cancers of the oral cavity, lung, ovary, colon, and prostate. In addition,a former patient with cancer shared his experience with treatment through the use ofmeditation, yoga, and Ayurvedic medicines, along with a vegetarian diet and simpleliving.The main thrust of this session was that AYUSH interventions/therapies have thepotential to be used for regression of the disease process in cancer, managing itssymptoms and complications, reducing the adverse effects from chemotherapeuticdrugs, improving quality of life, increasing the survival period, and preventingrecurrences and complications. 20Similarly, a presentation by Subhash Padhye, PhD , demonstrated the potential anticancertherapeutic effects of a Unani intervention, black cumin seeds (Nigella sativa). Themajor active component of black cumin is thymoquinone, which demonstrates cytotoxicactivity against pancreatic cancer cell lines by targeting the prolactinreceptor.Chitra Mandal, PhD , discussed a newmolecule, CM-5, a carbazole alkaloid derived from the plant Murraya koenigii(Rutaceae), commonly known as curry leaf or kari patta, which has shown tumoricidalactivity and also increased the efficacy of known cancer drugs in an animal model ofvarious types of cancers at doses that did not cause serious systemic toxicity. CM-5has also been shown to exhibit antiproliferative activity against several pancreaticcancer cells through apoptosis.The utility of yoga in improving the quality of life in patients with cancer washighlighted through two presentations. R. Nagarathna, MBBS, MD, Medical Director,S-VYASA Deemed University, Bengaluru, and Raghavendra Rao, PhD, Senior Scientist andHead, CAM Program, Health Care Global Enterprises, gave a presentation on theintegration of Ayurveda and yoga with conventional Western medicine to relieve thesymptoms of cancer, notably, nausea, vomiting, fatigability, alopecia, diarrhea,insomnia, pain, and the adverse effects of chemotherapy, radiation, and surgery.Ramesh Bijlani, MBBS, MD, Emeritus Professor of Physiology, All India Institute ofMedical Sciences, highlighted the use of yoga as a potential cancer preventionstrategy. G. Geetha Krishnan, BAMS, MD (Ayurveda), Senior Consultant & Head ofthe Department of Integrative Medicine, Medanta Hospital, discussed his work on theuse of yoga and Ayurvedic therapies, such as Panchakarma, to prevent adverse effectsof radiotherapy and chemotherapy, including nausea, vomiting, and insomnia.A pilot study in which metal-based formulations from Ayurveda were used to treatacute promyelocytic leukemia was presented by Vaidya Balendu Prakash of the VaidyaChandra Prakash Cancer Research Foundation in Dehradun. The study, which wasconducted in collaboration with the Central Council for Research in AyurvedicSciences, the Ministry of AYUSH, and the All India Institute of Medical Sciences,provided some evidence for consistent and sustained antileukemic effects.A preclinical study of the anticancer effect of a homeopathic preparation of Thujaoccidentalis was presented by Gaurisankar Sa, PhD, Division of Molecular Medicine,Bose Institute, Kolkata. Results from this study suggested that homeopathicmedicines prepared from Thuja sulfur and Calcarea carbonica in dynamic or potentizeddoses may be able to induce apoptosis in cancer cells through a p53-dependentpathway in various cell lines studied. Jayesh V. Sanghvi, MD (Homeopathy), Director,Nature Clinic Super Specialty Center in Chennai, proposed homeopathy as a singletherapy or as an add-on therapy for relieving pain and other symptoms and adverseeffects of radiotherapy, chemotherapy, and surgery. N. Deepa, M.Pharm, PhD, Vice Principal, College of Pharmacy, Chennai, discussedSiddha interventions derived from aqueous extracts of two plants that showedanticancer properties in preclinical studies. These extracts were shown to becytotoxic to a cancer cell line, apparently through DNA damaging effects. 21Arvind Kulkarni, MD, Director, Radiation Oncology Department, Lady Ratan Tata MedicalCenter, spoke about integrative oncology and highlighted the functioning of theAyurveda Centre in the Integrated Cancer Hospital, which has been established inPune and declared a Centre of Excellence by Ministry of AYUSH. The Centre has donework in evaluating the efficacy of combinations of Ayurvedic drugs in alleviatingdrug toxicity and improving the quality of life in patients with cancer treated withchemotherapy.This session provided examples of relevant US research projects and programs. NagiKumar, PhD, RD, Director, Cancer Chemoprevention, Moffitt Cancer Center, presentedon chemoprevention and treatment of cancers with botanicals. She provided a detaileddescription of the process of drug development with reference to botanicals anddiscussed current challenges for targeted therapies in cancer, as well as theadvantage of a multitargeted approach through botanicals. Limitations of the presentbiomarker-based approaches were also described, along with ways to overcome theselimitations to facilitate botanical drug development.Hasan Mukhtar, PhD, Helfaer Professor of Cancer Research, Director and Vice Chair forResearch, Department of Dermatology, Wisconsin Medical Sciences Center, presented onnatural products for cancer chemoprevention on the basis of lessons learned fromanimal experiments. Studies exploring potentially effective approaches for cancercontrol in humans were discussed. Encouraging findings from these prevention studiesindicate the need for additional investigations of these and other naturalproducts.Guido Pauli, Pharm D, PhD, Professor and University Scholar at the University ofIllinois at Chicago College of Pharmacy, presented on advancing the holisticapproach to traditional plant-based medicine. He elaborated on the need to studynatural products both qualitatively and quantitatively, and presented approaches fora more holistic analysis that captures the complex constitution of natural healthproducts. Although marker compounds for natural products are used widely andglobally, they should be thoroughly investigated and defined with caution.Validation methodology for chemotaxonomic and bioactive markers as well as potentialleads for active pharmaceutical ingredients should be congruent.Day 2 of the workshop began with discussions to identify research areas for Indo-UScollaboration and to summarize the meeting outcomes. The workshop attendees weredivided into three discussion groups: (1) Natural Products Research; (2) AYUSHSystems of Medicine in Cancer: What Holds Promise; and (3) Generating EvidenceToward Market Access for AYUSH Products and Practices.The natural products research group discussed research methods, training needs,prerequisites for material transfer agreements with US NCI and Indianperspectives, intellectual property rights, and National Biodiversity Authorityperspectives on benefit sharing and commercialization.Several recommendations emerged from these discussions:The need to add capacity for conducting research in natural products,including both single herbs and mixtures. Suggestions included buildinga central repository for cell lines, extracts, and fractions, as well asdeveloping infrastructure for translation of validated research intoclinical practice, including incubation of start-up companies.The need for harmonization of pharmacopeias from India and Westernnations, including the United States. Important for such harmonizationis the creation of a centralized laboratory for analytical methodologydevoted to standardized quality control for Ayurvedic preparations. Sucha facility would lead to the development of standard operatingprocedures (SOPs) for herbal and herbomineral preparations.The proposed enhancement of quality control and standardization inAyurvedic preparations would better ensure the reproducibility ofresults among disparate laboratories to increase transferability betweeninstitutes and countries. To support such reproducibility studies, thegroup recommended that the Ministry of AYUSH encourage multicenterclinical studies on interventions for the most prevalent cancers inIndia and the United States. These studies should use a standard formatfor data collection, analyses, and management. Open dissemination of theresults of such clinical trials and evaluation of their power andreproducibility are critical.Additional recommendations included focusing on the strengths oftraditional medical systems such as rasayanas and the development of specialized expertise inintellectual property rights.The overall goal of this group was to identify research gaps and ultimatelydevelop steps for generating evidence and moving research to practice. The groupdiscussed research methods, training needs, and next steps. The focus was onepidemiology studies, palliative care, and support studies. The discussion ledto the following recommendations:Evidence to translate research to practice should be obtained in aculture of collaboration, ensuring communication and cooperation amongall stakeholders, including AYUSH, extramural scientists, clinicians,and pharmaceutical/biotechnology companies. AYUSH activities should bewell integrated, involving both basic scientists and clinical teams.Basic research is needed to generate robust supporting data for claimsregarding the integrity, safety, and efficacy of botanicals that arewell founded , to inform the development andimplementation of clinical trials.There is a critical need to develop guidelines and standard operatingprocedures to ensure product integrity ,including a clear understanding of biology, molecular targets, safety,and indications for use of AYUSH products.Clinical trials should be performed with scientific rigor and includesafety and clinical efficacy studies. Focus areas should includeadjuvant therapy and remission therapy by AYUSH modalities, benefitsfrom such approaches in the form of personalized medicine, andimprovement in quality of life.Mechanisms should be established that encourage the articulation ofresults of TM observations in scientific meetings and their publicationin peer-reviewed journals.With regard to the training and education of the next generation of TMpractitioners, the group felt that joint Indo-US training programs wouldbe mutually beneficial. One particular recommendation was the jointdevelopment of protocols for clinical and basic research. Such protocolsshould consider quantitative clinical parameters.Finally, the formation of US-India activity groups was recommended tocontinue discussions of relevant topics.The overall goals of this group were to identify gaps, define the key role ofresearch, discuss approaches to implementing validation studies, consider therole of rigorous clinical trials, and identify areas for collaboration thatwould ultimately lead to generating sufficient evidence to move research resultsinto clinical practice. Recommendations from this group included thefollowing:Recognize the need to advance basic sciences in AYUSH by establishingcollaborations among basic, clinical, and population science researchteams as well as the private sector and industry.Establish guidelines and standards for product integrity in terms ofbiology, targets, and rigor/reproducibility, including developing SOPsfor product development, validation, batch-to-batch consistency,preclinical models, and clinical trials.Build centralized Good Manufacturing Practice laboratories, usingestablished manufacturing practices for product development and create ahub for making this information, including cost of production ofproducts, available to all users.Establish a regulatory structure to address consistency in standards ofresearch conduct and compliance.Articulate and publish findings of studies conducted using rigorousscientific methodology.Create cross-disciplinary exchange and scholarships, including a platformfor joint India-US conferences and/or symposia, providing trainingopportunities across and within disciplines.After the workshop, the participating agencies agreed to adopt a multidisciplinaryapproach for moving ahead in the intersection of Indian TM and cancer research.Several meetings have been held with representatives of NCI, HHS, National Instituteof Cancer Prevention and Research (NICPR)/Indian Council of Medical Research, theAll India Institute of Ayurveda and the Ministry of AYUSH. All India Institute ofAyurveda has been declared the nodal center to coordinate AYUSH cancer research inIndia. Under the aegis of an MoU signed with NICPR\u2013Indian Council of MedicalResearch, a Centre for Integrative Oncology has been set up in Noida at NICPR whereofficers from each AYUSH system are stationed to collate all information related tocancer research done in AYUSH systems. This center will also coordinateinternational activities, including with the NCI and HHS. The Ministry of AYUSH hasalso signed memoranda of understanding (MoUs) with the United States PharmacopeiaConvention and Pharmacopeia Commission of Indian Medicine and Homoeopathy;Homoeopathic Pharmacopeia Convention of United States and Central Council forResearch in Homeopathy and Pharmacopeia Commission of Indian Medicine andHomoeopathy. This will help in the development and harmonization of pharmacopeiasfor the traditional systems of medicine. The Ministry of AYUSH is also deputingofficers to the National Centre for Natural Products Research, University ofMississippi, for postdoctoral training. A draft MoU between HHS and the Ministry ofAYUSH is in the process of finalization, with the aim of facilitating capacitybuilding and joint academic and research collaborations. These progressivedevelopments will help take forward the shared commitments of the two countries inthe field of TM.In conclusion, the workshop served as an important initial engagement for theMinistry of AYUSH, HHS\u2013Office of Global Affairs, and NCI to discusscooperative activities in areas including research training and research programs.These discussions highlighted the opportunities to develop rigorous scientificportfolios and collaboration, while integrating existing knowledge, clinical bestpractices, and considering regulatory issues that govern the process of bringingscientific results to the benefit of public health.The workshop provided a comprehensive understanding of existing gaps, such asinclusion of rational and scientific approaches for drug development; policies andprocedures that can help develop milestones/expected outcomes; promotion ofcollaborative research; implementation of regulatory structures to ensure productreproducibility; and development of procedures and principles for productvalidation. The workshop also provided the opportunity for NCI and AYUSH researchersto begin engagement that continues as agreements and priorities are formalized.Several important recommendations emerged from the workshop, such as the need forbasic sciences in deepening the understanding of TM; creation of cross disciplineexchange/scholarships; development of centers of excellence; centralizedlaboratories; a platform for joint India-U.S. conferences and symposia to share andacquire knowledge; a hub of standardized information; regulatory structure andcompliance; and development of Good Manufacturing Practice facilities. It would seemhighly beneficial to link together some of the well-established centers in India forbasic, translational, and clinical research with joint projects. Such projectsshould emphasize product supply and encourage industries to participate in productdevelopment. Development of plant biotechnology was another area of interest.Implementing data and procedure optimization via development of SOPs and validationprocedures was highly recommended. Development of training programs for TMscientists and medical practitioners, as well as crosstraining opportunities acrossall relevant disciplines, was also prominent among the recommendations.The first bilateral workshop provided a strong foundation for AYUSH, NCI, and theirpartners to work together on implementing the recommendations for better developmentand promotion of the growth of traditional Indian medicine research, advancing itsevidence-based practice, and defining its role in the care of patients with cancerin an integrated fashion with conventional biomedicine. A Centre for IntegrativeOncology is in place to coordinate interactions on cancer-related research at thenational and international levels. One of the premium institutes of Ayurveda hasbeen designated as a nodal institute for cancer research. Efforts are under way toformalize the collaboration between HHS and AYUSH to advance the research andregulatory capacity of TM."} +{"text": "Adult protective services (APS) and other community-based agencies respond to hundreds of thousands of elder abuse cases each year in the United States; however, little is known about what constitutes success in the context of elder abuse response intervention. This study explored the meaning of elder abuse intervention success from the perspective of victims themselves toward the development of a victim-centric taxonomy of outcomes. Guided by a phenomenological qualitative methodology, this study conducted in-person, semi-structured interviews with a sample of elder abuse victims (n = 30) recruited from APS in the states of Maine, New York, and California, as well as a community-based elder abuse social service program in New York City. To enhance trustworthiness, two researchers independently analyzed transcript data to identify key transcript statements into themes. Outcomes of success were identified across broad domains related to the victim, perpetrator, victim-perpetrator relationship, family system, and home environment. Specifically, common themes represented outcomes related to victim safety, autonomy, social support, and state of mind; perpetrator independence and accountability; and victim-perpetrator separation. For decades, the field of elder abuse has struggled to understand how to define success in the context of community-based intervention from a client-centered perspective. The taxonomy developed in this study provides a comprehensive and conceptually organized range of successful outcomes to serve as infrastructure for the development of meaningful intervention outcome measures. This study represents one of the largest efforts to understand and integrate the perspectives and needs of victims into elder abuse intervention practice/research to date."} +{"text": "Despite the wide recognition of the multifactorial nature of Alzheimer\u2019s disease (AD), mechanisms of the collective influence of genetic and environmental factors on AD remain poorly understood. We used the Cardiovascular Health Study (CHS) and Framingham Heart Study (FHS) data to investigate the effects of genetic and gene-environment interactions on AD prevalence in the association analysis using logistic regression. Based on results of this analysis, we developed several new measures of integrated effects of SNPs, including for specific gene or group of genes, by constructing SNP-specific Interaction Polygenic Risk Scores (SIPRSs), Gene-specific Interaction Polygenic Risk Scores (GIPRS), and Trait-specific Interaction Polygenic Risk Scores (TIPRS), and tested them in the above data. We found strong interaction effects on AD among the SNPs in NRG3 gene and smoking, and among the SNPs in ATM and creatinine. In summary, we developed a new approach to measuring the collective impact of SNPs on complex traits, and discovered significant effects of the newly constructed SIPRS, GIPRS, and TIPRS on AD prevalence. The results of this study open a new opportunity of investigating the joint impacts of genetic and environmental factors on AD and other phenotypes of aging and health."} +{"text": "Following publication of the original article , the autCenter for Disease Control and Prevention, Kisumu, KenyaOriginally the affiliation for Felix Humwa and Vallarie Opollo has been published as:Kenya Medical Research Institute (KEMRI), Kisumu, KenyaThe correct affiliation is:The corrected list of affiliations is included in this Correction."} +{"text": "We demonstrate how application of analytic approaches developed in demography, biodemography, epidemiology, and population studies to Medicare and Medicare-linked data allows to identify causes and mechanisms of disparities in AD/ADRD. Our studies i) confirmed geographic disparities in AD mortality but did not detect them in Medicare data, ii) confirmed racial disparities in AD/ADRD incidence and survival and demonstrated that they can be partly explained by heterogeneity in diagnosis severity and partly by genetic factors, iii) detected unexpectedly strong effects of systemic hypotension, chronic kidney and liver diseases on the risk of AD/ADRD. We concluded that further progress in understanding of mechanisms and causes of the disparities in AD/ADRD is possible by clarifying the role of cause-of-death coding, the effects of comorbidity and their treatment, dynamics in cognition scores before AD/ADRD diagnosis, and genetic factors."} +{"text": "Microbes and Environments, the nitrogen cycle is one of the most important and commonly researched topics in the field of environmental microbiology.If a story was written entitled the \u201cKingdom of Microbial Ecology\u201d, how would the characters and plot be decided? Many microbiologists will agree with the following: the primary story setting involves a magnificent castle (a habitat) in fertile land with bright sunlight (the energy source), and the king and queen are the carbon and nitrogen cycles, respectively. Although this is an unusual way to begin a research highlight article in Nitrogen is among 6 major essential elements of CHNOPS for life and composes the building blocks and intact molecules for metabolism (amino acids and proteins), heredity (nucleotides and nucleic acids), and other important biological functions. Among the essential elements, circulating volumes of biologically available nitrogen and phosphorus are slightly limited in many biospheres of the planet, and, thus, as a whole, the biological demand for nitrogen and phosphorus and their circulation speeds are markedly greater and faster than those for carbon . Further2) and reactive nitrogen processes, nitrogen fixation and denitrification (2 to reactive nitrogens (such as NO) always occurs with lightning, which provides reactive nitrogens to the land and ocean , nitric oxide (NO) and nitrous oxide (N2O), has been recognized in many scientific and social contexts. Nitrification, denitrification, dissimilatory nitrate reduction to ammonium (DNRA), assimilatory ammonication, and anaerobic ammonium oxidation (Anammox) each through the transformation of these intermediate nitrogen metabolites and intermediates in natural microbial communities may be multi-directionally transformed by the complex nitrogen metabolism of various populations in response to intra- and extracellular physicochemical conditions and reaction dynamics through interspecies interactions in coastal eelgrass sediments and suggested that sulfur-oxidizing Gammaproteobacteria and Bacteroidetes populations contribute to N2O removal in eelgrass sediment microbiomes. Siqueira et al. respond to the physicochemical conditions of habitats . Although nitrous oxide reduction (with and without nosZ) is not key for denitrification, the abundance of nitrate reduction (the expression of napA) may be more important. Jang et al.(Bradyrhizobium nitroreducens from rice paddy soil that hosted and co-expressed two types of nitrite reductase genes (nirK and nirS), and the majority of denitrifiers are known to possess and use each of the two types of nitrite reductases. These are also excellent examples of the complexity of the nitrogen cycle in natural microbial communities.In catabolic and anabolic metabolic pathways, the significance of intermediate nitrogen metabolites, such as nitrite ; however, the enzymatic entity that catalyzes the oxidation of hydroxylamine to nitrite, corresponding to hydroxylamine dehydrogenase (Hao) in the case of ammonia-oxidizing bacteria (AOB), remains unclear and alsoet al. demonstra et al. and Nuno (et al. reported unclear . AOA are unclear . Using ti et al. confirmei et al. ; howeverMicrobes and Environments in the last two years have been awarded to studies on the nitrogen cycle. Therefore, the large, fast, and complex nitrogen cycle has attracted the attention of many environmental microbiologists worldwide, and Microbes and Environments has significantly contributed to lifting the veil of secrecy surrounding \u201cthe Queen of the Kingdom of Microbial Ecology\u201d.The MVPs in"} +{"text": "Allopurinol (xanthine oxidase inhibitor) is indicated for the treatment of symptomatic hyperuricemia, the treatment of gout and the treatment and prevention of uric and calcium lithiasis. It is one of the leading drugs for severe toxic dermal reactions, such as Lyell Syndrome (NET), Stevens-Johnson Syndrome (SJS) and Dress Syndrome (Drug reaction with eosinophilia and systemic symptoms). We report the case of a 45-year-old woman who was hospitalized for bullous skin rashes, without pathological history, the patient had generalized erythematous and bullous rash one week after taking allopurinol, prescribed by his rheumatologist for a gout. The diagnosis of bullous Cutaneous reaction due to allopurinol was retained, allopurinol was discontinued and the course was favorable with the disappearance of cutaneous lesions."} +{"text": "The goal of this review is to confer recent advances in our understanding of the brain ISS, including its structure, function, and the various processes mediating or disrupting ISF drainage in physiological and pathological conditions. The brain ISF in the deep brain regions has recently been demonstrated to drain in a compartmentalized ISS instead of a highly connected system, together with the drainage of ISF into the cerebrospinal fluid (CSF) at the surface of the cerebral cortex and the transportation from CSF into cervical lymph nodes. Besides, accumulation of tau in the brain ISS in conditions such as Alzheimer\u2019s disease and its link to the sleep-wake cycle and sleep deprivation, clearance of ISF in a deep sleep via increased CSF flow, novel approaches to remove beta-amyloid from the brain ISS, and obstruction to the ISF drainage in neurological conditions are deliberated. Moreover, the role of ISS in the passage of extracellular vesicles (EVs) released from neural cells and the rapid targeting of therapeutic EVs into neural cells in the entire brain following an intranasal administration, and the promise and limitations of ISS based drug delivery approaches are discussedThe brain interstitial fluid (ISF) and the cerebrospinal fluid (CSF) cushion and support the brain cells. The ISF occupies the brain interstitial system (ISS), whereas the CSF fills the brain ventricles and the subarachnoid space. The brain ISS is an asymmetrical, tortuous, and exceptionally confined space between neural cells and the brain microvasculature. Recently, with a newly developed The brain is made up of neural cells such as neurons, astrocytes, oligodendrocytes, and microglia, the vasculature comprising arteries, arterioles, capillaries, venules and veins, and the interstitial system (ISS) The brain cells are cushioned and supported by two forms of brain-specific fluids, the brain interstitial fluid (ISF) and the cerebrospinal fluid (CSF) , 2 The IThe ISS is circumscribed by the plasma membrane of neurons or glia and the wall of blood vessels Fig. 1)Fig. 1). +/K+-ATPase enzymes in the cell membrane [The constituents of the ISS comprise ISF, ECM, and diffusely distributed interstitial matrix (ISM) Fig. 1)Fig. 1). membrane , 27.The ECM, an abundantly hydrated net-like assembly produced by cells and disintegrated by enzymes, comprises collagen, elastin, glycosaminoglycans, proteoglycans, and glycoproteins such as tenascin, reelin, laminin, and fibronectin , 28-30 . Besidesin vivo using single-photon emission computed tomography (SPECT)/positron emission tomography (SPECT/PET), and magnetic resonance imaging (MRI) will be needed to validate the above possibility.The cerebrospinal fluid (CSF) resides in the subarachnoid space covering the entire surface of the brain and the brain ventricles. The CSF serves as a reservoir for the ISF, and an extensive communiqu\u00e9 between the ISF and CSF helps in the removal of waste products from the brain ISF , 45 Fig. Such anSome exchange of substances also occurs between the ISF and the cytoplasm of neural cells as the plasma membrane of neurons and glia is selectively permeable to specific ions and molecules -55 Fig.. MoreoveThe ISS of the brain is dynamic, which provides a route for cross-talk between elements of the vascular system and neural cells. The role of ISS includes the facilitation of communication between neural cells, processing and integration of information, and coordinated response to changes in the brain environment , 62-66. The ISS also facilitates the passage of neural cell derived EVs into local and distant sites in the brain and to the bloodstream. EVs are broadly classified as microvesicles (MVs) having a size of 100-1000 nm and exosomes (EXs) ranging in size from 30-150 nm. Microvesicles directly bud-off from the plasma membrane of cells , 77 wherThe biophysical and biochemical balance between CSF and ISF is crucial for the metabolism of brain cells and drugs, and hence, continuous exchanges between CSF and ISF are critical . Three pKiviniemi and associates, using ultra-fast MRI techniques have demonstrated that three discrete pulsation processes in the human glymphatic system facilitate the exchange between ISF and CSF . The swiIn conditions such as hydrocephalus, increased ventricular pressure causes high ependymal permeability and enhances the flow from CSF to ISF, which leads to interstitial edema of white matter . HoweverThe pathological changes in conditions such as glioma or stroke can alter multiple aspects of the ISS, which may include changes in geometry, ECM and its components, the constituents of the ISF, and the transport of substances in the ISS , 101. InIn ischemic stroke, studies have shown decreased ISS volume as a result of cytotoxic edema , and incThe failure rate of CNS drugs in both preclinical and clinical studies is much higher than non-CNS drugs , 122. InNonetheless, further refinements are necessary for CED to be translated successfully to the clinic. Notably, a device that avoids the backflow or reflux of injection and mechanical damage to the brain tissue is needed -131. FurMany exciting advances occurred in the past decade regarding our understanding of brain ISS. The new developments in the field include identification of differential ISF drainage in distinct functional segments of the brain, and several routes and mechanisms underlying the drainage of ISF into ventricles and the subarachnoid space. Interestingly, tau accumulation in the brain ISS and sleep deprivation augmenting that process have been identified as one of the factors that facilitate the spread of tau in AD. Additional studies have also shown the promise of the removal of beta-amyloid from the brain ISF for improving cognitive function in AD. On the other hand, ISS-based drug delivery, though promising, needs further development and refinement for a successful clinical application of this approach."} +{"text": "Family members often serve as informal caregivers for the first line of care. The complexity of family caregiving suggests the need to examine the personal and environmental resources that contribute to caregivers\u2019 psychosocial well-being. Informed by the life course perspective, this study investigates the impacts of providing care to a family member on global and daily psychosocial well-being, and the moderating influences of age, gender, marital status, and social support. The sample consists of 1449 participants from Midlife in the United States (MIDUS-II: Main and Diary) survey. Regression and multilevel models results indicated greater global negative affect and daily stressors in caregivers as compared to non-caregivers. In line with the positive correlates of caregiving, caregivers reported greater daily positive events. Age, gender, and marital status significantly moderated the associations between caregiving and well-being. Findings showed that services aimed at family caregivers should take into account of personal resources."} +{"text": "Antimicrobial resistance is projected to become the leading cause of death worldwide, claiming an estimated 10 million lives a year by 2050, primarily in low- and middle-income countries.,Antimicrobial resistance develops in, and is maintained and transmitted across humans, animals and the natural environment. Resistance is an ancient and naturally occurring phenomenon, but anthropogenic antibiotic use since the 1930s has been linked to the increasing occurrence of antimicrobial-resistant microorganisms, particularly bacteria.One of the key guiding principles of the national plans is to use a One Health approach and multisectoral coordination. This principle gives the various collaborating organizations equal status and emphasizes a sense of ownership of the plan.We analysed the 18 national action plans published in English between 2015 and October 2017 to deterBox\u00a01United Republic of Tanzania (2017)Barbados (2017) and Canada (2017)Oman (2017)Denmark (2017) and Sweden (2016)Bangladesh (2017), India (2017), Indonesia (2017), Maldives (2017), Nepal (2016), Sri Lanka (2017), Thailand (2016) and Timor-Leste (2017)China (2016), Japan (2016), Mongolia (2017) and New Zealand (2017),Ten out of 18 action plans followed the World Health Organization (WHO) guidelines and identified five objectives in line with the global action plan on antimicrobial resistance: (i)\u00a0improve awareness and understanding of antimicrobial resistance through effective communication, education and training; (ii)\u00a0strengthen the knowledge and evidence base through surveillance and research; (iii)\u00a0reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures; (iv)\u00a0optimize the use of antimicrobial medicines in human and animal health; and (v)\u00a0develop the economic case for sustainable investment that takes account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions.The most frequent term across all action plans was that,Although most plans have been drafted by multisectoral coordination teams who acknowledge that One Health guides their approach, the predominance of topics around human-animal health and the scarcity of topics around the natural environment suggests that there are more representatives of human-animal health in the coordination teams. The reason for this could be twofold. First, we have an increasing understanding of resistance mechanisms in human-animal systems, alongside better developed surveillance methods, and longer-term collaborations among key agencies, such as WHO, the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE).Antimicrobial resistance is a complex multisectoral challenge. Some progress is being made towards embedding a One Health approach in national action plans on antimicrobial resistance. For example, the national plan of Sri Lanka provides an example of a cross-sectoral approach including expertise from rural economy, fisheries, aquatic sciences, veterinarians and public health, and the national plan of India includes an objective on reducing the environmental spread of antimicrobial resistance. However, our analysis suggests that the first set of national action plans have not been wholly successful in incorporating a One Health approach. The plans have prompted the establishment of multisectoral committees and, in some cases, governance. Yet, while human and animal health feature prominently, the natural environment has yet to be fully integrated into these plans. Since the natural environment is a key source and driver of antimicrobial resistance, as highlighted by the WHO/OIE/FAO Tripartite and by the global action plan on antimicrobial resistance,"} +{"text": "Chronic venous disorders are common vascular pathology of great medical and socioeconomic impact, characterized by a wide spectrum of clinical manifestations occurring with symptoms and/or signs that vary in type and severity. The predominant pathophysiological mechanisms of chronic venous disease start from the development of venous hypertension from shear stress and reflux, leading to endothelial dysfunction and venous wall dilatation. The altered hemodynamic transduces physical signals into harmful bio-molecular pathways, creating a vicious cycle among shear stress, proteolytic remodeling, and inflammatory processes. This intricate network is further exacerbated by the degradation of protective endothelial glycocalyx. In this special issue, at least three main aspects of these interactions are highlighted: the dangerous, the good, and the diverse, which may help to focus attention on the biomolecular mechanisms and the possible targeted therapy of chronic venous disorders (CVeD). Chronic venous disorders (CVeD) are common lower extremity vascular pathologies of great medical and socioeconomic impact , affecting a large part of the population worldwide and significantly decreasing the quality of life of affected patients ..4].The enhanced production, secretion, and activation of several enzymes induced The properties and functions of glycosaminoglycan (GAG) layer, forming a protective barrier in endothelial cells, are critical for the maintenance of water, ions, and protein balance between the intra- and extra-vascular compartments . The cheThe highly negatively charged, unbranched polysaccharide family of GAGs may mediate chemokine mobilization, modulating the recruitment of leukocytes and neutrophils, a vital process in inflammation . InteresIn vitro and in vivo studies have highlighted that the GAGs of endothelial glycocalyx have a profound influence on the vascular wall physiology through: (1) the transmission of shear stress, as mechano-transducer of some hemodynamic stimuli; (2) the maintenance of a selective permeability barrier and a low hydraulic conductivity, like a protective layer for the endothelial cells, both in arteries and veins; and (3) the modulation of blood leukocytes, lymphocytes, and platelets adhesion, limiting extravasation of reactive cells capable of inducing inflammation and proteolysis in blood vessel microenvironment. So, endothelial glycocalyx (and its GAG constituents) represents the good but fragile barrier of both vein and artery wall .The major constituents of the endothelial glycocalyx may be degraded from the endothelial surface under various acute and chronic clinical conditions; a plethora of proteolytic enzymes may have a wide array of potentially destructive capability against vessel GAGs. In fact, other than the well-known matrix metalloproteases, also heparinases, hyaluronidase, and serine proteases , as well as cathepsins, may lead to loss or destruction of GAG from the endothelial surface layer . All theIn this respect, pharmacological agents may dispThe glycosaminoglycans physiologically present as a protective layer and a significant barrier for all endothelial cells , as wellSeveral studies provided evidence that the integrity of GAG compounds of endothelial glycocalyx plays crucial roles and protective functions in several vascular diseases. The loss and/or degradation of glycocalyx prone the vessel wall to the development of inflammatory and proteolytic damages \u201copening the door\u201d for: (a) the mechano-transduction of acute and chronic stimuli; (b) the increased permeability barrier; (c) enhancing harmful adhesion of blood leukocytes, lymphocytes, and platelets; and (d) favoring extravasation of the reactive blood cells capable of induce inflammation and proteolysis in blood vessel microenvironment ,3,14.On the other hand, studies on the GAG-based drugs have demonstrated its \u201cJanus Bifrons\u201d vascular protective properties , throughSeveral veno-active drugs may counteract the hemodynamic, inflammatory, and proteolytic pathologic mechanisms of venous diseases, including all stages of CVeD ,17 but aThe potential of these veno-active and veno-protective drugs is mainly focused to limit the initiation/progression of early stages of CVeD, accelerating also the wound closure in the late stages of CVI, suggesting then a potential utility of GAG-based drugs in endothelial dysfunctions as a promising therapeutic approach for patients suffering of both deep-vein thrombosis and pulmonary embolism, serious and complicated pathologies with significant clinical and epidemiological impact in the elderly reviewed in .An updated consensus highlighted all the clinically complex aspects included in the terminology Chronic Venous Disorders (CVeD), including early clinical pictures which cannot be called simply \u201cdisease\u201d compared to the late stages CVI mainly due to insufficient venous drainage, edema, skin damage, and leg ulcers . This clIt is noteworthy that for resolving CVeD we need to take into account different approaches: on one hand, the ability of pharmacological therapy to target the dangerous biochemical events, on the other hand the positive role of the physical \u201canti-stasis\u201d effects of both compression and/or surgical reflux ablation.The first endothelial alterations induce and guide the subsequent harmful inflammatory and proteolytic cascades, mainly evidenced by the classic hemodynamic CVeD symptomatology .Starting from the primum movens, the complicated network of the CVeD is further exacerbated by the vicious cycle, giving life, over time, to progressive pictures of varying severity, from telangiectasia to varicose veins , to edema and cutaneous trophic lesions up-to venous ulcers (characteristics of CVI), including also venous thromboembolism ,8. It isAn understanding of the hemodynamic-inflammatory-proteolytic biomolecular mechanisms and events may help to orientate the treatment in a more targeted way to the needs of the individual patient suffering of CVeD ,17. The Finally, GAG-based drugs represent the good and the diverse to counteract the dangerous network among hemodynamic, inflammatory, and proteolytic processes occurring from the early stages of symptomatic varicose veins to severe steps of ulcers including the post-thrombotic patients, stigmatizing the fundamental role of the biomolecular mechanisms of endothelium in the management of vascular diseases."} +{"text": "HIV/AIDS continues to be one of the most challenging individual and public health concerns of our days. According to the latest UNAIDS data, in 2018, roughly 37.9 million individuals were infected with HIV globally, while around 770,000 people died of AIDS-related illness . Gene thStill, different challenges remain in anti-HIV drug therapy/prophylaxis, and these include the following, among others: (i) the onset of severe adverse effects leading to the discontinuation or interruption of therapy or even prophylaxis ,9; (ii) This Special Issue presents an exciting series of reviews and original research articles from eminent scientists in academia and different nonprofit organizations involved in the development of antiretroviral drug products, focusing mainly on novel strategies for the formulation and delivery of anti-HIV compounds. Innovative approaches towards improved gene therapy and immunotherapy are also addressed. The presented reports provide not only interesting overviews and opinion on recent developments in the broad field of antiretroviral therapy/prophylaxis and drug delivery, but also describe the development of new products that are currently tracked for clinical testing.The Special Issue starts with an interesting review by Tsukamoto at Kindai University, Japan, on strategies explored for curing HIV infection using a combination of gene therapy and host immunization . In partIn the first original research study included in the Special Issue, the group of Veiga at the Complutense University of Madrid, Spain, provides details on the development of mucoadhesive tablets for the vaginal delivery of tenofovir, in the context of topical PrEP . The comStill in the area of prophylaxis, the team led by Banga at Mercer University and CONRAD, USA, propose a new transdermal delivery system for tenofovir alafenamide, a nucleotide reverse transcriptase inhibitor . The silco-glycolic acid)-based nanoparticles were developed as carriers for the co-delivery of griffithsin and dapivirine, two potent candidate microbicide compounds. Studies in vitro showed that the proposed formulation not only featured interesting technological properties (including biphasic drug release), but also allowed a synergistic antiretroviral effect to be obtained. In another paper pertaining to the application of nanotechnology against HIV infection, Grande et al. reviewed the literature for nanocarriers of reverse transcriptase inhibitors [Rohan and colleagues at the University of Pittsburgh, Magee-Womens Research Institute, University of Louisville and International Partnership for Microbicides, USA, contributed an interesting study that further endorses the potential of nanotechnology-based microbicides . In theihibitors . In thisPharmaceutics possible.I hope that researchers involved in the fields of antiretroviral drug delivery and anti-HIV therapy/prophylaxis may find useful and stimulating information here that can be translated into their own ongoing and future work. A final word of appreciation is due to all the contributing authors, anonymous reviewers, and editorial staff at MDPI for making the publication of this Special Issue of"} +{"text": "Food insecurity or insufficiency, among other factors, is triggered by structural inequalities. Food insecurity is an inflexible problematic situation in South Africa. The country has a custom of evidence-based decision making, stocked in the findings of generalized national household surveys. Conversely, the deep insights from the heterogeneity of the sub-national analysis remain a principally unexploited means of understanding of the contextual experience of food insecurity or insufficiency in South Africa. The data present the food insufficiency status with special focus on adult and children. The data also reveal the adult and children food insufficiency status across the provinces in South Africa. The data contains socioeconomic and demographic characteristics as well the living condition and food security status of the households. A questionnaire was administered to a household to elicit information on household members. The survey covers all legally recognized household members of households in the nine provinces of South Africa. The survey does not cover collective living quarters such as student hostels, old-age homes, hospitals, prisons, and military barracks but specifically on households. The General Household Survey (GHS) collects data on education, health and social development, housing, access to services and facilities, food security, and agriculture.The data in In In the same vein, the data in 2The dataset employed is the General Household Survey (GHS), 2016. The dataset was compiled based on stratified two-stage design, and a total of rural and urban 21,218 households were interviewed containing 72,604 respondents. The dataset were coded in SPSS software 22 version which the descriptive part of the research such as mean, frequency, standard deviation were carried out. In addition, the inferencial statistics were carried out on STATA package 13 using the FGT index to classify the respondents into food secured or otherwise. The dataset was robust and representative enough to generalize on the household food sufficiency status of South Africa.Acknowledgements"} +{"text": "Adults aged 70 and older have the highest suicide rates in most countries across the globe . Prevalence may increase as the Baby Boomers transition into older adulthood . Disease and disability increase risk for late-life suicide, thus identifying opportunities to intervene within the network of services utilized by older adults with illness and disability could reduce suicide risk. This symposium will explore the impact of disease and disability on late-life suicide risk, and present novel ideas for intervention and prevention. Emphasizing the conference theme, we will discuss prevention points spanning networks of care, including mental health and social services, and long-term care. Dr. Bower will frame the scope of the problem by presenting findings of age-stratified associations between physical illness and suicide attempt among older veterans using secondary data from a retrospective case-control study of veterans. Ms. Lutz will present findings on the relationship between disability and suicidal thoughts from a clinical trial of problem-solving therapy. Dr. Lane will discuss management and identification of suicide risk factors during the transition from independent living to long-term care through the lens of a case-series. Dr. Fullen will present preliminary findings from a novel, randomized controlled trial of a community-based suicide prevention training program for nutrition service volunteers. Dr. Yeates Conwell, Co-Director of the Center for the Study and Prevention of Suicide and Director of the Geriatric Psychiatry Program at the University of Rochester Medical Center, will serve as the discussant."} +{"text": "Cushing\u2019s syndrome (CS) is a set of clinical symptoms which occur as a result of hypercortisolemia. Endogenous ACTH-dependent CS related to an ectopic ACTH-secreting tumour constitutes 12%\u201317% of CS cases and is one of the most common causes of paraneoplastic syndromes. This study presents a case of a 31 year-old man with diabetes, hypertension, rosacea, purple stretch marks and hypokalemia. Findings of diagnostic procedures include high concentrations of cortisol and ACTH, pituitary microadenoma and a tumour in the anterior mediastinum. Dynamic hormone tests determined the source of excess hormone secretion and ectopic ACTH-dependent CS was diagnosed. Due to increasing symptoms of superior vena cava syndrome, an emergency resection of almost the whole tumour was performed, with only a small part of the upper pole left because of the proximity of large vessels and a risk of damaging them. On the basis of histopathological tests, an atypical carcinoid tumour of the thymus was identified. Immediately after the surgical procedure, there was a significant reduction of clinical and laboratory traits of hypercortisolemia, yet, during the 46 weeks of postoperative observation, despite chemotherapy, the progression of residual masses of the tumour occurred with metastases and increased hormone indices. The presented case shows and discusses the differentiation of ACTH-dependent hypercortisolemia and its causes, difficulties in surgical therapy and chemotherapy, as well as prognosis for atypical carcinoid of the thymus, which is a rare disease. Cushing\u2019s syndrome (CS) is a set of clinical symptoms which occur as a result of hypercortisolemia. An excessive concentration of cortisol in the body can have either exogenous or endogenous aetiology. In most cases, its origin is iatrogenic. The incidence of this rare disease is 0.7\u20132.4 cases in a million of the population in a year ,2. ThereA smoking 31-year-old man with 1.5-year history of poorly controlled hypertension treated with angiotensin inhibitor and calcium channel blockers and a 6-month history of diabetes with metabolic imbalance treated with intensive functional insulin therapy and with metformin was admitted to the Clinic of Endocrinology, Diabetology and Internal Medicine of the Regional Specialist Hospital in Olsztyn. The patient was admitted as he manifested clinical and laboratory features of hypercortisolemia and body weight loss of about 18 kg in 6 months, swelling of lower limbs, decreased muscular strength/power, mood changes and lower back pain.2, WHR 0.86, conjunctival hyperaemia, oedema, erythema and lividity of the skin on the neck and face, dilated neck veins, spread papulopustular rosacea, purple stretch marks on the hips and thighs, amyotrophy of proximal limb muscles . After fThe first descriptions of CS concerning ACTH-secreting tumours not located in the pituitary gland come from 1928 . The terThe patient was diagnosed with ACTH-dependent CS on the basis of hormone tests: high concentrations of ACTH and cortisol with a rigid circadian rhythm and no suppression of cortisol secretion in 2 mg dexamethasone suppression test. Imaging tests showed both a tumour of the anterior lobe of the pituitary gland as well as a massive tumour in the mediastinum. Both lesions could have led to hypercortisolemia, thus, differentiation of ectopic and pituitary overproduction of ACTH was made. Both very high concentrations of ACTH as well as no response in the CRH test unambiguously confirmed ectopic ACTH secretion. Moreover, a significantly increased concentration of chromogranin A suggested neuroendocrine nature of the tumour in the mediastinum, which was confirmed in the histopathological tests of postoperative material, in which traits of an atypical carcinoid of the thymus were found. The ACTH ectopy was ultimately confirmed by normalization of its concentration on the second day after the operation. A neurogenic tumour of the thymus is a rare malignant primary carcinoma of the thymus which taA CT scan of the chest with contrast is a test of choice in the case of neuroendocrine tumours of the thymus. It reveals a large irregular or patchy mass in the anterior mediastinum, with a heterogenous contrast enhancement and foci of necrosis in the central section of the tumour, at times with microcalcifications. Histological differentiation of neuroendocrine tumours of the thymus includes three categories: low grade of malignancy (well differentiated G1 neoplasms), intermediate grade of malignancy (moderately differentiated G2 neoplasms), and high grade of malignancy (poorly differentiated G3 neoplasms). The majority of thymic tumours belong to the group of well differentiated neoplasms . ImmunohUntil 2016, the total number of cases of neuroendocrine tumours of the thymus was about 400 , while aThe treatment of choice in cases like the one presented here is early total operative resection which, iACTH-dependent hypercortisolemia requires deep diagnostics to know the real aetiology of the disease. When diagnosing ectopic ACTH secretion syndrome, it should be remembered that its cause may be very rarely occurring atypical carcinoid tumour of the thymus\u2014a neoplasma with extremely poor prognosis. The procedure of choice is complete surgery, which is only possible in some cases. Adjuvant treatment is chemotherapy, radiotherapy, and in the case of expression of somatostatin receptors, SST receptor analogues. The grade of histological malignancy, the size of the tumour, non-complete resection, no expression of SST receptors, distant metastases, progression of residual mass of the tumour and concentrations of particular hormones can be additional very unfavourable prognostic factors, as in the presented case."} +{"text": "The first speaker is Dr. Thomas Ferris the Center Director of the NSF Center for Health Organization Transformation (CHOT). Dr. Ferris will provide a high-level overview of CHOT and provide the audience with a greater understanding of its history, funding, partners, and accomplishments. In this section, the mission, annual research model, and the I/UCRC planning integration framework will be reviewed and discussed. The NSF CHOT is the only Industry-University Cooperative Research Center (I/UCRC) focused on innovations in healthcare delivery in the nation. CHOT researchers work alongside the Industry Advisory Board (IAB) to conduct research that supports the implementation of evidence-based transformational strategies within the healthcare sector. During this symposium, Dr. Ferris will discuss some of the challenges and opportunities that can arise from these partnerships. More importantly, in this section will speak to how value is created through these collaborative efforts and how ultimately this can improve health outcomes."} +{"text": "West J Emerg Med. 2019 March;20(2):409\u2013419Best Practices for Evaluation and Treatment of Agitated Children and Adolescents (BETA) in the Emergency Department: Consensus Statement of the American Association for Emergency PsychiatryGerson R, Malas N, Feuer V, Silver GH, Prasad R, Mroczkowski MMErratum inWest J Emerg Med. 2019 May;20(3):537. Pediatric BETA Consensus Guideline Working Group members should not be included in full author list. The author list has now been corrected on this erratum.AbstractIntroduction: Agitation in children and adolescents in the emergency department (ED) can be dangerous and distressing for patients, family and staff. We present consensus guidelines for management of agitation among pediatric patients in the ED, including non-pharmacologic methods and the use of immediate and as-needed medications.Methods: Using the Delphi method of consensus, a workgroup comprised of 17 experts in emergency child and adolescent psychiatry and psychopharmacology from the the American Association for Emergency Psychiatry and the American Academy of Child and Adolescent Psychiatry Emergency Child Psychiatry Committee sought to create consensus guidelines for the management of acute agitation in children and adolescents in the ED.Results: Consensus found that there should be a multimodal approach to managing agitation in the ED, and that etiology of agitation should drive choice of treatment. We describe general and specific recommendations for medication use.Conclusion: These guidelines describing child and adolescent psychiatry expert consensus for the management of agitation in the ED may be of use to pediatricians and emergency physicians who are without immediate access to psychiatry consultation.PMCID: PMC6404720 [PubMed - indexed for MEDLINE]"} +{"text": "Despite an established positive link between social wealth, health, and social capability among older adults, the effect and mechanisms among these factors are understudied. This paper uses the WHO Study on Global Ageing and Adult Health (SAGE) data and a mediation analysis method, combing social capital theory and a social capabilities approach, to provide new evidence on the effects of financial resource, physical function, and cognitive function on the social capabilities of older adults (aged 55 and above) in China and the possible mediating role of social network in this relationship. The descriptive analysis results show that urban older adults , on average, had lower freedom of expression, lower sense of living safety, and less frequent community participation, while having better self-perceived health, higher physical and cognitive functions, more household income, and higher educational background than their rural peers . The Baron and Kenny\u2019s mediation analysis results show that social networks accounted for a substantial proportion of the effects of wealth and health on social capabilities, but wealth and health still had strong, positive direct effects of its own. Higher mediating effects of social networks were found in the association between functions and social capabilities of freedom of expression (9.46%) and sense of safety (36.33%) among rural older adults. Results of this study urge for further social policies and intervention programs to enhance older adults\u2019 social capabilities, including social cohesion, sense of trust and safety, physical and mental functioning, and subjective well-being."} +{"text": "Understanding the immune system is of paramount importance for the prevention and treatment of disease as well as the development of novel immunotherapies and immunodiagnostics in the framework of precision immunology and medicine. Recently, the advent of high-throughput biological methods has provided unprecedented insight into the molecular mechanisms underlying immune cell dynamics. The immense complexity of innate and adaptive immunity spanning several orders of spatial and temporal scales may, however, only be grasped by a systems computational immunology approach\u2014specifically, by developing powerful computational approaches, which process, model, and integrate these big immunological data.Original Research , 5 Methods , 5 Technology Reports , 4 Reviews , 1 Hypothesis and Theory (Cohen and Efroni), and 1 Perspective .This Research Topic was designed to give a comprehensive overview of current methods and applications of computational immunology for the dissection of mammalian immunity. Twenty-nine articles are included in this Research Topic, and are categorized into the following types: 13 Davidsen and Matsen;Schramm and Douek;Yermanos et al.), study the inference of immunoglobulin germline genes and polymorphisms , shed light on immunoglobulin light chain characteristics , compare immune repertoires in aging and disease , and improve and/or develop novel computational tools for clustering immune receptor sequences , immune repertoire benchmarking and error correction . Furthermore, storage and standardization of immune receptor data were advanced by the development of a webserver for immunoglobulin analysis pipelines , a new database of epitope-specific B-cell and T-cell receptors , and guidelines for immune receptor data format standardization . The antigen targets of immune receptor repertoires were investigated in works on B-cell epitope prediction and antigen presentation (Gfeller and Bassani-Sternberg).These papers address a broad range of conceptual challenges in computational immunology. The majority of papers focus on the development and application of computational tools for immune repertoire analysis. Specifically, they elucidate B-cell receptor phylogenetics and somatic hypermutation , plasma cell ontogeny , and regulatory T-cell proliferation . Immune cell signaling was investigated for cytokines , the immune synapse , and macrophage function .In addition to immune receptor biology, the dynamics of immune cells were explored for germinal center B cells (Cohen and Efroni).Finally, a conceptual paper summarized the similarities between the mammalian immune system and supervised machine learning (We would like to express our deepest gratitude and appreciation to all the authors who contributed papers, and to the reviewers and editors without whose invaluable work the publication of this Research Topic would not have been possible.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This collection focuses on innovative approaches and analytical advancement in drugs of abuse testing and monitoring. Substance abuse negatively impacts all facets of society. Drug testing programs have been developed in many jurisdictions to service law enforcement agencies for drug intelligence, criminal justice systems for prosecution of drug-related crimes, and the health industry for harm minimization.Klingberg et al. investigated the mass fragmentation during the collision-induced dissociation process of a series of synthetic opioids including fentanyl derivatives, AH series opioids, U series opioids, W series opioids and MT-45, and identified a number of common fragments that can potentially be used as markers to indicate the presence of a particular synthetic opioid class of compounds within a sample.One significant challenge in drugs of abuse testing is the continuous emergence of new psychoactive substances (NPS) in the illicit drug market. Routine methods of analysis are no longer effective in screening NPS due to the lack of structural information and commercial reference materials which are needed for performing targeted analysis of these NPS. Scientists are developing non-targeted approaches to overcome this difficulty. In this regard, the use of high-resolution mass spectrometry (HRMS) operated in data dependent acquisition (DDA) mode or more often data independent acquisition (DIA) mode has drawn a wide interest among forensic toxicologists and chemists to advance the non-targeted approach for NPS detection based on interactions of the compounds with CBSteuer et al. reviewed the recent development of metabolomics approaches for drugs of abuse testing based on the monitoring of changes in small endogenous molecules in response to drugs of abuse consumption and to specimen manipulation. Based on the limited number of studies reported in the literature, the authors conclude that metabolomic approaches possess potential for detection of biomarkers indicating drug consumption. More studies, including more sensitive targeted analyses, multi-variant statistical models or deep-learning approaches are needed to fully explore the potential of omics science in drugs of abuse testing, especially in testing consumption of unknown NPS.Xu et al. studied the metabolism of AMB-FUBINACA, another indazole-3-carboxamide-type SCRA, using both human liver microsomes and zebra fish systems, and discovered a number of unique metabolites to be used as potential poisoning markers for drug monitoring purpose. Diao and Huestis reviewed the advantages and disadvantages of multiple metabolic approaches for investigating SCRA metabolism, including the human hepatocyte incubation model, human liver microsomes incubation, in silico prediction, rat in vivo, zebrafish, and fungus Cunninghamella elegans models and recommended the use of the human hepatocyte model when possible.Adding to the challenge of detecting the use of a large number of NPS available in the illicit drug market is the limited understanding of their biotransformation following consumption. Many NPS such as SCRAs undergo extensive metabolic transformation in the body and drug monitoring needs to target not only the parent drugs but also their metabolites. Studying the metabolism of these compounds is also important to better understand the toxicity of NPS as many NPS metabolites are also pharmacologically active and contribute to the overall toxicity of the parent drugs. Chen et al. reported the development and validation of a simple, rapid, and sensitive LC-MS/MS method for chiral analysis of selegiline and its metabolites desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine in dried urine spots. Busard\u00f2 et al. developed a comprehensive LC-MS/MS method for quantifying fentanyl and 22 analogs and metabolites in whole blood, urine, and hair.Another important aspect of the collection covers the development of sensitive analytical test methods for the detection of drugs of abuse in a variety of biological matrices. In summary, this collection covers Research Topics representative of a number of important research focuses in the area of drugs of abuse testing. Speedy, sensitive and accurate detection of drugs of abuse, including NPS, is part of the crucial steps in the fight against substance misuse and its associated crimes and harms.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.SE was employed by company Elliott Forensic Consulting. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Microorganisms are the prominent sources of valuable products ranging from large to small molecules . Most of these small molecules termed as \u201csecondary metabolites (SM)s\u201d are inessential to the producer for their growth and development. However, these SMs have significant applications in human and animal health Demain, . BesidesPham et al. have summarized the biological activities and applications of a variety of small molecular medicines and biologics. The manuscript has reviewed the diverse microbial systems used for the production of these biomolecules along with the versatile engineering strategies of such microbial platforms. Generally, each of the microbial strains can produce multiple compounds, but it can produce only subsets of these compounds under specific growth conditions. Therefore, variations in cultivation parameters can elicit the production and discovery of new SMs. For example, by changing cultivation parameters such as temperature, salinity, aeration, and even by altering the shape of the flasks, the production profile from a microbial platform can be altered approach. They have presented the role of variation in medium, cultivation conditions, use of epigenetic modifiers, and co-cultivation in the discovery of novel secondary metabolites from diverse microbial sources utilizing OSMAC approach .Escherichia coli is reported as the most common cell factory for the production of both small molecules and biologics. The clear understanding of its physiological and genetic characteristics, fast-growth even in minimal salts medium, and availability of easy genetic manipulation techniques has established it as first-choice production host . The metabolic engineering approach utilizing gene over-expression cassette for enhanced production of nucleotide diphosphate (NDP)-sugars was utilized for generating the salicylate glucoside and other glycosylated variants . Similarly, the gene-silencing approach was employed for enriching the titer of 3\u2032-phosphoadenosine-5\u2032-phosphosulfate (PAPS), which is donor substrate for sulfation of natural product (NP) precursors. Hence, by inhibiting the degradation of PAPS mediated by repression of PAPS reductase (cysH) and optimization of different sulfate donors significantly enhanced the production titer of naringenin-7-sulfate . Ribosomally synthesized and post-translationally modified peptides (RiPPs) are special class of NPs with diverse structures and bioactivities, and thus possess a complex biosynthetic mechanism. Different aspects for heterologous expression of RiPPs in E. coli have been reviewed by Zhang et al.E. coli, some of the non-lethal Gram-positive bacteria including the native producer strains such as actinobacteria or heterologous hosts [generally recognized as safe (GRAS)] such as Bacillus and Corynebacterium are used as excellent cell factories in industries. Actinobacteria are characterized as the most prominent producers of thousands of bioactive molecules, particularly small molecular medicines such as commercially available antibiotics and anticancer-drugs by modulation by a number of global positive and negative regulatory genes, and genes encoding drug efflux pumps. Further the optimized strain was used for production of NPs of diverse nature such as actinorhodin, murayaquinone, hybrubins, piericidin A1, dehydrorabelomycin, and actinomycin D. Generally, the production of SMs in Streptomyces is controlled by a complex regulatory network that involves pathway-specific, pleiotropic, and global regulators, which tune the expression level of biosynthetic genes in response to a variation in diverse physiological and environmental conditions and its associated protein (Cas9) has enabled the multiplexed genome engineering of actinomycetes including Streptomyces. Tao et al. have reviewed the application of CRISPR/Cas9 based genome editing in Streptomyces for discovery, characterization, and production of NPs. The recent advances in heterologous expression of RiPPs in Streptomyces have been presented by Zhang et al.Due to the presence of endotoxins in products obtained from Gram negative bacteria as Bacillus species has an ability to adapt to varying environmental conditions and capacity for high production yield , hence they are crucial industrial microorganisms. Further, the application of recent advances in metabolic engineering, enzyme/pathway engineering along with the synthetic biological tools have contributed to ameliorate the production titer from these microorganisms. Yang et al. utilized enzyme engineering of homogentisate dioxygenase for production of enhanced production of melanin. Similarly, a metabolic engineering approach was utilized for enhanced heterologous production of 2-deoxy-scyllo-inosose in Bacillus subtilis. Unlike E.coli and Bacillus, Corynebacterium has significant ability to utilize a variety of carbon sources has great prospects for simulating the connection between the genomics and metabolomics to generate the intelligence in these super hosts, so that they can sense the environment condition, and respond rationally.Taken together, all these papers illustrate the applicability of engineering of microbial platforms for the production of small molecular medicines to complex biologics. However, in case of all of these microbial cell factories the industrial scale titer, yield, and productivity is generally difficult to achieve. The major constraint is unavailability of abundant information about their metabolic behavior, unavailability of appropriate genetic engineering tools, or complication in redesigning appropriate flux balance for diverting primary metabolites to target molecules (Bhan et al., DD wrote the manuscript. E-SK and MK revised and corrected the manuscript. The final draft of the manuscript was finalized and approved for publication by all the authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In 2013, the outbreak of wild poliovirus (WPV) in the Horn of Africa (HOA) triggered an aggressive, coordinated national and regional response to interrupt continued transmission. Kenya, Somalia, Ethiopia, South Sudan, and other HOA countries share a range of complex factors that enabled the outbreak: porous and sparsely populated borders, insecurity due to armed conflicts, and weak health systems with persistently under-resourced health facilities resulting in low-quality care and low levels of immunization coverage in mobile populations. Consequently, the continued risk of WPV importation demanded cross-border and intersectoral collaboration. Assessing and addressing persistent communication gaps at the subnational levels were necessary to gain traction for improved immunization coverage and surveillance activities. This article describes a systematic approach to institutionalizing processes of dialogue and facilitation that can provide for a sustainable and effective joint cross-border health platform between Kenya and Somalia. It examines an operational model called the Cross-Border Health Initiative (CBHI) to support joint intercountry collaboration and coordination efforts. To evaluate progress of the CBHI, the authors used data from population coverage surveys for routine immunization and supplemental immunization activities (for polio), from acute flaccid paralysis (AFP) surveillance, and from plans developed by border districts and border health facilities. The project-trained community health volunteers have been a critical link between the hard-to-reach communities and the health facilities as well as an excellent resource to support understaffed health facilities. The authors conclude that the CBHI has been effective in bolstering immunization coverage, disease surveillance, and rapid outbreak response in border areas. The CBHI has the potential to address other public health threats that transcend borders. In 2010, the first WPV importation into the European region since the region was declared polio-free in 2002 resulted in 476 confirmed cases: 458 in Tajikistan, 14 in Russia, three in Turkmenistan, and one in Kazakhstan. In Africa and Asia, 11 new importations into six countries were observed in 2010; 30 WPV importations during 2008\u20132009 resulted in 215 WPV cases in 15 African countries during 2009\u20132013. Across six African and Asian countries, 11 new importations were recorded in 2009\u20132010.3For more than three decades, humankind has pursued the possibility of a \u201cpolio-free world.\u201d4 In Somalia, the first importation occurred during 2005\u20132007, resulting in more than 200 cases of paralytic polio.5 Likewise, in Kenya, two cases in Garissa County were reported in 2006, 19 cases in Turkana County in 2009, and one case in Rongo district in 2011. Somalia experienced a polio-free period from 2007 to 2013.5 This period of calm was upset when an outbreak of WPV type 1 (WPV1) rattled the Horn of Africa (HOA).6 In May 2013, the Somalia Ministry of Health (MOH) and the WHO reported a confirmed WPV1 case in a child from Mogadishu (Banadir region). Subsequently, in May 2013, eight additional WPV1 cases were confirmed in Somalia: seven in the Banadir region and one in the Bay region.7 Just 3 weeks after the initial polio cases were detected in May 2013 in Somalia, Kenya reported its first case across the border in the Dadaab refugee camp. As a result, five people were paralyzed by polio, including young adults, in the northeastern part of Kenya.8 Polio quickly spread from Somalia to its neighboring countries of Ethiopia and Kenya. By April 2013, the case count stood at 223: 199 cases in Somalia, 14 in Kenya, and 10 in Ethiopia. All the Somalia polio cases belonged to cluster N5A,Kenya and Somalia have not been spared from the impact of WPV importation.9 At the same time, the Global Polio Eradication Initiative entered a new phase, with a significant reduction in cases in endemic countries and a heightened recognition of the risk for the international spread of the virus.10 To combat the threat of an international outbreak, the WHO declared polio a public health emergency of international concern in May 2014 and issued recommendations requiring proof of polio vaccination for travel to and from countries experiencing polio cases.10 Frequent cross-border movement of the high-risk mobile populations between Kenya and Somalia and the low level of population immunity in the region continue to be major contributing factors to the spread of poliovirus and the risk of ongoing transmission.11The 2013 HOA outbreak vividly confirmed that \u201cAll countries will continue to have some level of risk for WPV outbreaks as long as endemic circulation continues in Afghanistan, Nigeria, and Pakistan.\u201d12In 2014, Kenya\u2019s MOH requested the United States Agency for International Development (USAID)-funded CORE Group Polio Project (CGPP) Kenya and Somalia HOA Secretariat based in Nairobi, Kenya, to initiate polio eradication activities in five counties along the Kenya\u2013Somalia border deemed at high risk for poliovirus importation. It was clear that effective immunization activities across borders and migration pathways were essential to improve immunization rates. Under the leadership of the respective MOHs of Kenya and Somalia and in collaboration with the WHO, the CGPP began holding cross-border meetings in October 2014\u2014a significant and instrumental move that would shape a systematic, unified, and well-coordinated response in the form of the Cross-Border Health Initiative (CBHI).Objectives arising from the 2015 cross-border meetings targeted improving collaboration between the health and administrative authorities of border regions through enhancing acute flaccid paralysis (AFP) surveillance sensitivity, increasing coverage of supplemental immunization activities (SIAs), and improving coverage and access to quality routine immunization services in the HOA border regions. Before the formation of the CBHI, cross-border committee meetings were first initiated by the WHO in collaboration with the Intergovernmental Authority on Development (IGAD) under the \u201cHealth for Peace Initiative\u201d in 1996. However, these cross-border committees were formed in only a few selected sites and the meetings were ad hoc, resulting in limited capacity for implementation, monitoring, accountability, resource allocation, and sustainability of cross-border polio eradication activities. To address these gaps yet keeping and reaffirming the same set of valuable original objectives, the CGPP Kenya and Somalia HOA Secretariat over a 1-year period transformed the ad hoc cross-border meetings into a full CBHI in October 2015. The secretariat subsequently established more CBHI committees in Kenya and Somalia. The work of the committees funded by the CGPP set the course for the eventual full implementation of the CBHI.13 Cross-border coordination bridges the disease surveillance gaps by forming partnerships among institutions, agencies, and communities in cross-border areas. Specifically, the CBHI works to ensure the vaccination of all cross-border populations, to support the detection of cases of AFP, to conduct joint case investigations of transborder AFP and WPV cases, and to synchronize all polio SIAs.The overarching goal of the CBHI is to reach every child with polio vaccine.In October 2015, the CGPP established a total of seven CBHI committees in five polio high-risk countiesIn Kenya, the government-led committees consisted of representatives from the five counties and subcounties. At the county level, the representatives included the director for health, the disease surveillance coordinator, the Expanded Program on Immunization (EPI) coordinator, the health records and information officer, and the community health strategy focal person. At the subcounty level, representation included subcounty coordinators and disease surveillance or EPI officers. In addition, the CGPP implementing partner officers, WHO and United Nations Children\u2019s Fund (UNICEF) county coordinators, and officers from border administration, immigration, and security completed the committee membership.In Somalia, the committees consisted of regional and district medical officers and a regional EPI coordinator. Similar to the Kenya committees, representation included the CGPP implementing partner officers, WHO regional and district coordinators, UNICEF field staff, and officers from border administration, immigration, and security.To reach high-risk mobile populations, the CGPP, in collaboration with the local authorities and CBHI, identified and profiled both formal and informal crossing points and communities at borders, transit hubs, and migratory routes. This exercise was beneficial; after developing detailed micro-planning to identify and document all border towns, villages, and settlements and their inhabitants, it was possible to estimate the number of children in the catchment areas. Moreover, the major transit points in the area provided pertinent information about population movement patterns, whereas joint mapping of border crossing points and border communities served to improve micro-planning for country-specific and joint country cross-border activities. The CGPP\u2019s non-governmental organization (NGO) implementing partners and local health authorities mapped 11 border health facilities, 161 formal/informal border crossing points, and 372 villages along the border as shown in To guide the CBHI committee members, the CGPP Secretariat in coordination with the MOH wrote a terms-of-reference document to structure regular meetings and outline roles for reporting and for the implementation of action plans. This document defined how to develop the agenda, meeting reports with outcomes, and implementation of activities arising from the meeting. Cross-Border Health Initiative committees followed activity work plan templates to ensure monitoring and accountability through joint supportive health facility visits. The project trained and provided the committees with selection criteria for recruiting community health volunteers (CHVs), whose primary focus was to ensure efficient and sustainable community-based surveillance, and with secondary responsibilities of supporting the committee and health facilities to conduct community mobilization for routine immunization and polio campaigns. In turn, the committees provided training materials for border health facility staff and border CHVs, including reporting forms based on the Integrated Disease Surveillance Response Framework to identify key diseases.The government-led high-level, intercountry cross-border forums and CBHI committee meetings funded by the CGPP and other partners have served as critical communication and community engagement platforms to raise issues of the risk of polio importation in the HOA. The respective local health authorities have owned the CBHI and provided the leadership in its implementation. As a result, the CBHI has led to improved immunization coverage and increased AFP detection among high-risk mobile populations, limiting the importation of WPV across borders.14 who serve as a link between the hard-to-reach nomadic communities and the health facilities. The committees, with funds from the CGPP, trained the CHVs to conduct social mobilization, perform community-based surveillance on vaccine-preventable diseases, report suspected AFP cases from the community, promote routine immunizations, and track immunization defaulters. Community health volunteers reported all suspected AFP cases from conflict-prone and insecure areas inaccessible to trained health workers. A key success of the committee\u2019s work has been the recruitment of CHVsThe risk of persistent threat of WPV importation demands cross-border collaboration and coordinated interventions. In response, the CGPP, in collaboration with the respective country\u2019s MOH and WHO, supported more than 70 local and international cross-border meetings in the HOA to highlight this risk see . These mThe CBHI has expanded access to polio vaccination for high-risk mobile populations in under-resourced areas. The strategic and systematic collaboration of the cross-border health committees has improved access to vaccination for children on the move at formal and informal border crossing points, enhanced tracking of nomadic pastoralist communities, and improved reporting of suspected AFP cases. 15Major obstacles to polio eradication efforts in the HOA and specifically at the security-compromised border areas have been inadequate health infrastructure, limited funding, poor health workforce management, and low-quality skills of health workers. There are inadequate government services in the border areas as the presence of government and NGO workers is restricted because of security risks, especially kidnappings. Polio funding has been critical to supporting the expansion of other health services.The government EPI and surveillance officers carry out their activities through direct, personal contact on a regular basis to guide, support, and assist designated health-care facility staff to become more competent in their immunization and disease surveillance services. In coordination with the National Vaccine and Immunization Program and the Disease Surveillance and Response Unit of the respective government, the CGPP mentored the immunization and surveillance managers on a monthly and quarterly basis to conduct on-the-job training of the service providers, which had a positive impact on the immunization program indicators and on the provision of all services in general. In the border areas of the HOA, the CGPP has provided technical and logistic support for district/subcounty training on the Reach Every District strategy, local micro-planning, data quality self-audits, and supportive supervision of routine immunization at health facilities and outreach sites.Cross-border coordination and scaled-up efforts of community-based surveillance activities to combat polio have contributed to positive AFP surveillance indicator trends; improvements are particularly significant in the hard-to-reach border areas . The geoThe second row of maps shown in Multiple challenges have compromised the AFP surveillance efforts. A strike by health workers in Kenya in 2017 affected service delivery, particularly in the border counties of Turkana and Marsabit. The protracted conflict in South Sudan created an influx of refugees across the border in Kenya, further complicating surveillance efforts. The maintenance of biological specimens is referred to as the reverse cold chain. Maintenance of the reverse cold chain remains a significant barrier. Although stool sample collection rates are high, transportation of quality samples is still a problem due to poor infrastructure and impassable roads. Other operational challenges faced by the project were the high cost of programming due to the difficult terrain (poor roads and insecurity) and the occasional border closures hampering the cross-border work. However, some of these challenges were overcome by working closely with community leaders, building the capacity of the community through the CHVs to conduct the cross-border work, integrating the polio interventions with other cross-border activities undertaken by NGOs, and leveraging their presence and expertise. These partnerships created synergy and reduced the cost of programming. The CGPP closely coordinated with the IGAD, the regional intergovernmental body, and the respective immigration departments to address challenges with border access.17 The CGPP in the HOA has focused on improving access to vaccination services in high-risk mobile populations that straddle common borders. The CBHI in Kenya and Somalia has contributed to improved population immunity among cross-border communities, and it has created and maintained an active AFP surveillance system in these vulnerable regions that includes a community-based surveillance component. The CBHI has supported the collaboration of countries and border districts to develop early warning and response systems as well as the harmonization of cross-border vaccination and surveillance activities.3The CGPP has demonstrated the value of an institutionalized approach that is collaborative and coordinated. This important strategy is adaptable to address other communicable diseases that transcend borders.The communities that straddle the border of Kenya and Somalia are homogenous, sharing a common language and culture that allow for easier collaboration for teams on both sides of the border.The contribution of communities through participation in the cross-border health committees and the community-based surveillance by CHVs has magnified the CGPP\u2019s credibility and ownership among border communities.The cross-border forums have heightened sensitization and advocacy for cross-border issues, leading to high-level political commitment and support from the respective government health authorities and renewed interest and support from the United Nations partners.Frequent cross-border committee meetings have improved opportunities for communication, stronger partnerships, joint regional advocacy, effective management of challenges, and the facilitation and implementation of collective outbreak response activities.Cross-border meetings have proven to be crucial at the local level, providing a forum to exchange information and carry out synchronized action for health service activities, including disease-control and eradication activities.The CBHI has become vital for closely monitoring vaccination status to reduce the risk of WPV importation by those crossing the border. Effective communication among the cross-border committees and border authorities, coordinated immunization activities, and sharing of AFP surveillance data have led to an improved, in-depth understanding of the dynamics of cross-border threats of WPV importations.18The diverse committee representation of the stakeholders has ensured wide sharing of information across the borders.Implementation of the CBHI in Kenya and Somalia has strengthened information flow through monitoring and evaluation of joint action plans.19The border health facilities have conducted mapping and profiling of cross-border populations for routine immunization and SIA micro-planning in hard-to-reach border villages and in high-risk populations that include those residing in \u201cno-man\u2019s land\u201d villages, immigrants and pastoralists, and nomadic populations.online supplement). The guide promotes internal and cross-border partnerships between border health operational units to identify and address the health issues of border populations, identify and document transit routes and hubs, and monitor population movements between borders which can affect cross-border transmission of communicable diseases, including polio.20The capacity built through these committees, although specific to polio eradication, can serve other health initiatives, including the identification of emerging infectious disease threats with epidemic or even pandemic potential and other diseases that continue to challenge fragile health systems. This knowledge has been captured in the CBHI Operational Guide management. In Mandera County, the health committee worked together on a cholera outbreak in 2016. In addition, the Kenyan counties that border Somalia have merged their county development integrated plans with cross-border county action plans and widened the role of their CBHI committees to address other diseases. The CBHI is now an integral part of the operational health plans of border health units and the annual work plans of the participating county departments of health, thus ensuring sustainability of the CBHI after the end of the project. A manual that is used to guide the work of the CBHI is available as an online supplement to this article.As a testament to the power of collaboration, the CBHI\u2019s domain has expanded to integrate the control of other infectious diseases.The CBHI has improved access to health services, particularly for the immunization of nomadic pastoralists. In partnership with other government departments and NGOs that provide nomadic communities with livestock, education, drought management, and internal security, the CBHI has successfully tracked the movement of the nomadic populations to vaccinate missed children\u2014something that was unheard of before the CBHI. Even with the CBHI in the HOA, the long border between Kenya and Somalia remains porous and dangerous. The limited health infrastructure on the border there poses a significant challenge to effective cross-border collaboration. The CGPP will continue to build on the lessons of the CBHI to combat importation of WPV across the borders and will continue its search for new and innovative solutions.19 the CBHI is an important step for \u201cplanning for the end of all polio.\u201d21 The CBHI demonstrates the coherent impact of CBHI committees to engage across borders and across sectors (such as veterinary services and surveillance for zoonotic diseases) to capitalize on already existing synergies. The work of the committees as part of the CBHI could be adapted for other health interventions that require strong partnerships to achieve similar goals.In an acknowledgment that \u201cPolio will not end everywhere until everywhere ends it,\u201d22 The CBHI has been critical in reaching underserved, high-risk mobile populations with oral polio immunizations and other health services. Building on the success of the CBHI in Kenya and Somalia, this article highlights the value of the systemic process of institutionalizing the intervention so that it will continue beyond the eradication of polio. Integration of the CBHI committees into the country-driven County Integrated Development Plans has given particular attention to the often marginalized, security-compromised, and neglected border areas, raising coverage and potentially reducing inequities in immunization services. This integration has enhanced accountability and commitment through resource allocation and sustainability of the CBHI, leading to a gradual improvement in AFP surveillance and in routine immunization uptake in border areas. The CBHI has provided an in-depth understanding of the threat of disease importation, and it has built a cross-border framework for tackling cross-border challenges.Poliovirus circulation is most persistent in high-risk areas deprived of essential health services.23 hence the need for political commitment under the premise of the cross-border governance framework of the IGAD that could institutionalize the CBHI and standardize regional surveillance reporting tools.20 Effective, robust cross-border coordination of polio eradication activities requires a high level of political commitment, solid coordination, and mobilization of cross-border communities and their leaders.24 The potential of strong cross-border collaboration for health that the CGPP\u2019s CBHI has initiated holds great promise not only for contributing to the final eradication of polio but also for addressing other public health priorities.It is essential, however, to acknowledge the everyday challenges faced by HOA countries. The frequent movement of mobile populations in geographic areas that are unsafe for immunization workers makes the achievement of high levels of immunization coverage difficult and increases the threat of re-importation of the WPV and other communicable diseases,Supplemental materials"} +{"text": "Osteotomies are the established surgical procedure for the deformity of the lower limb induced by osteoarthritis (OA) of the knee and ankle. Closed-wedge (CW) and open-wedge (OW) high tibial osteotomy (HTO) are extra-articular surgery, which aim to shift the mechanical axis from medial to slightly lateral and reduce the overload in the medial compartment of the varus deformed knee by extra-articular correction. However, varus deformity of the knee with the teeter effect, which could be accompanied with subluxation and thrust due to the medial-lateral soft tissue imbalance, is not resolved only by the shift of mechanical axis. The depression of the medial tibia plateau, so-called pagoda deformity, is the intra-articular deformity, which could potentially cause the teeter effect and involves intra-articular incongruency. In such case, the osteotomy with novel concept should be developed to overcome the issues, both the imbalance of soft tissue and intra-articular deformity. Tibial condylar valgus osteotomy (TCVO) is an intra-articular osteotomy, which improves the joint congruency of the medial-compartment knee OA with subluxation and/or intra-articular deformity and also provides better joint stability. A similar argument is raised in the treatment of the ankle OA. Low tibial osteotomy (LTO) is an extra-articular surgery to correct malalignment of lower leg. Distal tibial oblique osteotomy (DTOO) is a novel surgery to improve the bony congruency of the ankle OA. In DTOO, the distal tibia is cut obliquely from the proximal medial to the distal lateral in the coronal plane and towards the center of the tibiofibular joint to improve the bony congruency of the ankle joint. Tibial condylar valgus osteotomy (TCVO) and distal tibial oblique osteotomy (DTOO) can correct intra-articular deformity of knee and ankle, respectively. The rationale and indication of TCVO and DTOO for the treatment of the lower limb by reconstructing the joint congruency are discussed. Deformity of the lower limb induced by osteoarthritis of the knee or ankle causes the adverse effect on daily living due to gait disturbance, which could cause abnormal posture, as well as local problem such as pain. Various surgical procedures have been performed such as femoral, tibial osteotomies, and hip and knee arthroplasties to overcome these issues. Osteotomies are the established surgical options for the treatment of lower limb.Osteoarthritis of the knee is a representative disease, which involves malalignment of the lower limb with the joint degeneration. Arthroplasty of the knee, involving total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), is established as surgical procedures with good clinical results \u20133. ArounThe concept of traditional HTO has been the extra-articular correction of the alignment, aiming at the reduction of the overload in the medial compartment of the varus deformed knee by shifting the mechanical axis from medial to slightly lateral. On the other hand, deformities of the lower limb are affected by several factors. The bony deformity and soft tissue balance are the different issues relating to the malalignment. Varus deformity in OA of the knee without excessed medial loosening of soft tissue could be corrected by usual HTO, which is the extra-articular correction with transfer of the mechanical axis. However, the varus deformity of the knee with the teeter effect, which is the medial-lateral soft tissue imbalance, is not resolved only by the shift of mechanical axis to lateral. The depression of the medial tibia plateau, so-called pagoda deformity, is the intra-articular deformity, which could cause intra-articular incongruency and the teeter effect. In such case, the osteotomy with novel concept should be developed to overcome the issues, both the imbalance of soft tissue and intra-articular deformity; otherwise the relief of the pain and disability would not be achieved.For the treatment of osteoarthritis of ankle joint, the same argument exists as the correction of the varus knee. Low tibial osteotomy (LTO) for osteoarthritis of ankle joint has been performed to change the load distribution on the ankle joint by changing the extra-articular alignment , 10. HowConsidering the correction of lower limb alignment, regardless of cause of mal-alignment, such as post-traumatic, degenerative, or congenital, we need to consider two kinds of deformities: extra-articular and intra-articular deformity. Extra-articular deformity can be discussed under static loading condition, and intra-articular deformity should be discussed under dynamic loading condition.Extra-articular deformity in frontal plane is evaluated by the measurement of the standing long-leg AP view. Theoretically, there are 728 kinds of extra-articular deformity, and these deformities can be accurately corrected by using hexapod system. Evaluation of intra-articular deformity should be evaluated by dynamic motion of the contours of the bone facing in the joint. Tibial condylar valgus osteotomy (TCVO) and distal tibial oblique osteotomy (DTOO) can correct intra-articular deformity of knee and ankle, respectively.Traditionally the degree of extra-articular deformity of the frontal plane has been expressed as the degree of deviation from the mechanical axis of the lower extremity Figure . The mecThe frontal plane knee joint orientation line of the distal femur is drawn as a line tangential to the most distal point on the convexity of the two femoral condyles. The frontal plane knee joint line of the proximal tibia is drawn across the subchondral line of the two tibial plateaus. The angle formed between joint orientation lines on opposite sides of the same joint is called the joint line convergence angle (JLCA) . The ankThe deviation from the normal of the lower extremity alignment can be evaluated by the joint orientation angles, such as MPTA, LDFA, LPDA, etc. measured with the full leg standing frontal X-ray image of the lower limb Figure . MalaligAngular deformity has four types: varus/valgus deformity at the frontal plane and procurvatum/recurvatum deformity at the sagittal plane. Similarly, there are four kinds of deformities in translation and axial deformities. Consequently, there are 728 patterns of extra-articular deformities.The angular deformity correction of lower limb can be achieved using hinges set on center of rotation of angulation (CORA) of the connecting rods by Ilizarov technique . CurrentIntra-articular deformity means joint congruency. Joint congruency is defined as the fittings of two opposing joint surfaces as they relate to one another considering the spatial contour of each bone at their interface.In theory, joint congruency can be mainly explained by three factors: contours of bone, functions of ligament, and integrity of articular cartilage and meniscus. Incongruency of the joint immediately causes joint instability or abnormal joint kinematics resulting in the secondary osteoarthritis in the future. For example, mal-union of tibial plateau fracture and/or knee ligament injury such as anterior cruciate ligament and/or collateral ligaments causes easily knee instability and secondary osteoarthritis of the involved knee with joint incongruency .Two primary biomechanical purposes of the articular cartilage are lubrication and shock absorption. The articular cartilage provides a smooth lubricated surface for low friction articulation and acts as a remarkably efficient shock absorber , 20.From the view point of joint congruency, it is considered that the effect of articular cartilage as the shock absorber is not large because the thickness of articular cartilage is thin as 1 \u2013 4\u2009mm. Rather in the cartilaginous element, the menisci may be more important because they have a large effect of filling the gap of the joint . HoweverHigh tibial osteotomy (HTO) is intended to transfer the mechanical axis from medial to slightly lateral to the midline of the knee to decrease the load and subsequently delay osteoarthritis (OA) \u201324. TherOn the other hand, tibial condylar valgus osteotomy (TCVO) developed by Chiba G et al. in 1989 and published in 1994 is an operation that corrects intra-articular deformity , 33 Fig and 7. TThe same argument holds for distal tibial oblique osteotomy (DTOO) and low tibial osteotomy (LTO) for osteoarthritis of ankle joint. LTO is an operation of an attempt to change the load distribution on the ankle joint by changing the extra-articular alignment. However, if instability of the talo-tibial joint exists , improveOn the other hand, DTOO developed by Teramoto in 1994 is an operation to improve the bony congruency of the ankle joint . DTOO coAlthough osteotomies are effective in managing malalignment of knee and ankle arthrosis, determination regarding the type of osteotomy should be based on the pathology in each patient. The cause of deformity of the knee varies, which involves intra- and extra-articular or the combination of them. Center of the deformity may also vary. Soft tissue balance should be another critical issue for the selection of optimal osteotomy type. Traditional HTO should be an optimal strategy to overcome the malalignment in OA of the knee; however, the excessed medial-lateral soft tissue imbalance and intra-articular deformity are not solved by this surgical procedure. Tibial condylar valgus osteotomy (TCVO) should be an optimal option to overcome these issues that improves intra-articular deformity followed by acquisition of medial-lateral stability of the knee, not lower limb alignment. Although LTO is the good treatment for the deformity in OA of ankle by the extra-articular correction of alignment, treatment for incongruency and instability for OA in ankle is the remaining issue of this surgical technique. Distal tibial oblique osteotomy improves the bony congruency of the ankle joint by the oblique osteotomy.Tibial condylar valgus osteotomy and DTOO that correct intra-articular deformity of knee and ankle are the optimal osteotomies for OA with intra-articular deformity and instability."} +{"text": "Evidence-based programs (EBPs) offer proven ways to promote health and prevent disease among older adults in their communities. EBPs are based on rigorous study of the effects of specific interventions or model programs, demonstrate consistently positive changes in important health-related and functional measures, and have tools in place to maintain program access, quality, and efficiency across diverse settings. The University of North Carolina at Chapel Hill\u2019s Center for Health Promotion and Disease Prevention (UNC HPDP), in partnership with the Evidence-Based Leadership Collaborative (EBLC), has established a review process and Review Council to identify new community programs that meet the evidence-based program criteria established by the Administration for Community Living (ACL), one of the chief U.S. federal agencies responsible for aging programs. Approved programs are then eligible for Older Americans Act Title III-D and other discretionary funding to support organizations that deliver EBPs to improve older adult health. The review process assesses the effectiveness, outcomes, and evaluation of the program, information about program implementation, training, and other key elements for successful program dissemination. The Review Council consists of national leaders with expertise in program research, evaluation, and implementation. The review process is supported by the ACL-funded National Chronic Disease Self-Management Education and Falls Prevention Resource Centers. This session will describe the ACL evidence-based health promotion program criteria that must be met for approval; an overview of the review process; and how researchers can submit their programs for review. Time will be allowed for questions, discussion, and research to practice implications."} +{"text": "Participation in active transportation by older persons has been associated with higher quality of life and longevity. Efforts across the United States to increase active transportation by older adults have lacked meaningful input by older adults, are non-theoretical and have had inconclusive results. This paper describes the findings from Phase 1 of the Safe Routes to Age in Place project, a collaboration between Age-Friendly Franklin County, The Ohio State University (OSU) and the University of Texas-Arlington (UT-A), funded by the Ohio Department of Transportation. The aim of the study is to increase the options and safe utilization of active transportation by older persons in three pilot neighborhoods in Franklin County, Ohio utilizing community-based participatory action research strategies with a customized data collection app, MyAmble. The purpose of Phase 1 was to engage city and regional planning students, government officials and older adults to identify \u201chot spots\u201d in the three pilot neighborhoods. Heat mapping of community data including locations of densely-populated vulnerable older adults, fixed transportation routes, bus stop signage and benches, shared bike stations, bike routes, paratransit routes and pedestrian crash data was completed. Maps were used to identify areas of focus and discussions with municipal leaders and older adult residents further refined target areas to be used in the second phase of the study. Older residents completed walk audits using the MyAmble app and identified issues with sidewalks, crosswalk timers and bus stops. Implications related to age-friendly communities and active transportation are offered."} +{"text": "Non Western therapies have played a vital role in dealing with a variety of crisis such as physical, emotional and existential over the last few centuries . Since the introduction of Western medicine in India as early as the eighteenth century, the two systems of medicine have coexisted and influenced each other. Mutual recognition of the therapeutic values of the two systems was further bolstered when American medicine recognized the role of alternative therapies as viable option for healing in the early eighties. The purpose of this paper is to examine the roles two kinds of healers (western and non- western) play in the Asian Indian Hindu context. For this qualitative study, 30 physicians (trained in Western medicine) and 5 sadhus (holy men) were interviewed in the city of Allahabad, during the Kumbh Mela. Open ended questions ranged from: a) field of practice (physicians), sadhus (mystics), b) years of practice, c) number of patients/followers, d) treatment offered (physician \u2013surgery or medications), sadhus , e) adverse reactions. In-depth interviews were recorded and transcribed by two researchers from Hindi to English and coded into themes. Results indicate that about a quarter of Western trained physicians not only sought assistance from the sadhus for their emotional/spiritual issues, but also referred patients with terminal disease. Besides individual consults, the mystics conduct lectures on climate change, on holistic diet, meditation, yoga practices, and healing. Social workers need to assess the value Hindu immigrant families in United States attach to Non-Western therapies."} +{"text": "Healthcare providers (HCPs) are recognized as one of the cornerstones and drivers of health interventions. Roles such as documentation of patient care, data management, analysing, interpreting and appropriate use of data are key to ending vaccine-preventable diseases (VPDs). However, there is a great deal of uncertainty and concerns about HCPs\u2019 skills and competencies regarding immunization data handling and the importance of data use for improving service delivery in low- and middle-income countries (LMICs). Questions about the suitability and relevance of the contents of training curriculum, appropriateness of platforms through which training is delivered and the impact of such training on immunization data handling competencies and service delivery remain a source of concern. This review identified and assessed published studies that report on pre- and in-service training with a focus on HCPs\u2019 competencies and skills to manage immunization data in LMICs.An electronic search of six online databases was performed, in addition to websites of the WHO, Global Alliance for Vaccines and Immunization (GAVI), Oxfam International, Save the Children, Community Health Workers Central , UNAIDS and UNICEF. Using appropriate keywords, MeSH terms and selection procedure, 12 articles published between January 1980 and May 2019 on pre- and in-service training of HCPs, interventions geared towards standardized data collection procedures, data documentation and management of immunization data in LMICs, including curriculum reviews, were considered for analysis.Of the 2705 identified references, only 12 studies met the inclusion criteria. The review provides evidence that shows that combined and multifaceted training interventions could help improve HCPs\u2019 knowledge, skills and competency on immunization data management. It further suggests that offering the right training to HCPs and sustaining standard immunization data management is hampered in LMICs by limited or/lack of training resources.Pre-service training is fundamental in the skills\u2019 acquisition of HCPs; however, they require additional in-service training and supportive supervision to function effectively in managing immunization data tasks. Continuous capacity development in immunization data-management competencies such as data collection, analysis, interpretation, synthesis and data use should be strengthened at all levels of the health system. Furthermore, there is a need for periodic review of the immunization-training curriculum in health training institutions, capacity development and retraining tutors on the current trends in immunization data management. Human resources for health, also known as the health workforce, is one of the building blocks proposed by the World Health Organization (WHO) Health Systems Framework and is central to achieving universal health coverage (UHC) and enhancing the achievement of the Sustainable Development Goals (SDGs) , 2. HoweHigh-quality vaccine coverage and vaccine-preventable disease (VPD) surveillance data are needed to monitor the performance and impact of the Expanded Programme on Immunization (EPI), which aims to reduce infant and child mortality and morbidity. However, inconsistent and inaccurate recording and reporting of these data limit the ability to accurately monitor EPI coverage and remain a source of concern particularly in LMICs. Due to poor and sub-standard measurement and errors in vaccination records, reliability and validity of reported data on immunization coverage are highly questionable. Additionally, incomplete and incorrect data entry and poor documentation of coverage, as well as double entries by HCPs, have decreased the reporting quality \u20137. CapacAttempts to bridge the gaps associated with poor data quality, which are often attributed to insufficient technology rather than the people who drive the system, have led to the implementation of complex health information systems (HIS), including web-based solutions. Nevertheless, these still require human capacity and capability. Persistent challenges identified with these systems include inadequate human resources, insufficient capacity of HIS staff at all levels of the health system, high staff-attrition rates, inadequate training, unstandardized job descriptions, limited HIS development planning and lack of established HIS career path and accredited training programmes .Competency can be defined as a combination of knowledge, skills and abilities needed to perform a specific task in a given context , which cThere is a great deal of uncertainty and concerns about HCPs\u2019 skills and competencies regarding immunization data handling and the importance of data use for improving service delivery. It is unclear whether HCPs\u2019 training curriculum and modalities are appropriate and optimal for improved skills and competencies in data collection procedures and management . QuestioThis scoping review seeks to identify and assess published studies that report on pre- and in-service training with a focus on healthcare providers\u2019 competencies and skills to manage immunization data in LMICs. For the purpose of this study, we assessed available interventions (on improving immunization data documentation and reporting), pre- and in-service training and compared reports on which modality best informs good-quality immunization data collection and management in LMICs.We conducted an exploratory research and systematically mapped available literature on specific topics relating to HCPs\u2019 competencies in immunization data management. Key concepts of pre- and in-service training were identified, and sources of evidence and gaps in the research were also highlighted . This apAll categories of health personnel qualified as healthcare providers (HCPs) involved with immunization data management, such as doctors, pharmacists, nurses, midwives as well as community HCPs were included.In addition, studies on interventions that include any training or capacity-building activities related to standardized data collection procedures and management of immunization data, including curriculum reviews, were considered. As the purpose of this study was to assess and compare pre- and in-service training of HCPs on standardized data collection procedures in immunization services, we assessed interventions that were measured and evaluated. Hence, the study design and outcomes of included studies were left intentionally broad, and a meta-analysis was not appropriate at this stage.Published articles on pre- and in-service trainings of HCPs, healthcare professional curriculum, on-going training and interventions geared towards standardized data collection, correctness, consistency, data reporting and recording and management of immunization data were included. We also included all studies assessing the effect of pre- and in-service training of HCPs in data management improvement, including data collection, entry, completeness, accuracy and timeliness, as well as training on standardized data collection and maintenance in immunization services, interventions on capacity building, improving skills and competencies in data collection and management in immunization services. All studies evaluating educational curriculum, pre- and in-service trainings of HCPs; capacity development on immunization data competencies in data recording and reporting, data analysis, interpretation, synthesis and presentation of immunization data; and interventions and on-going capacity development on standardized data collection and management in immunization services in LMICs were included.In addition, studies on HCPs\u2019 responsive training programmes on immunization data and district-level data improvement programmes conducted in LMICs according to the World Bank Group 2012 classification were incComprehensive search terms and strategy based on the \u2018Population\u2013Concept\u2013Context (PCC)\u2019 framework for scoping reviews were devThe search terms included keywords and Medical Subject Headings (MeSH) together with corresponding synonyms and associated terms, which are summarized in Table Articles were considered relevant if they were about healthcare providers\u2019 capacity development on data collection and quality in immunization programmes in LMICs. All citations were imported into Thomson Reuter EndNote X7 software, and duplicate citations were removed manually. A two-stage screening process for eligibility was conducted, and articles that met the inclusion criteria were selected. In the first stage of screening, two authors (Eunice Turawa (ET) and Edward Nicol (EN)) independently reviewed titles and abstracts of the citations to identify relevant articles. These results were then compared, and discrepancies resolved. As part of the second-stage screening for review, the full text of all potential eligible studies were retrieved, and two authors (ET and EN) independently reviewed the articles for eligibility for inclusion in the review; discrepancies were resolved through discussion, and when consensus was not reached, the third author (George Bonsu (GB)) intervened. Studies that did not meet the eligibility criteria were excluded at this stage. Articles that could not be obtained through online databases were also excluded from the final analysis. A data extraction form was developed according to pre-specified eligibility criteria. To ensure the reliability and consistency of the extraction form, two authors (EN) and (ET) independently piloted the extraction form using the first 20 articles. Results were compared, and the extraction form amended accordingly. At every stage of study selection and data extraction, discrepancies were resolved through discussion and contribution from the third author (GB).Using a pre-designed data-charting form, key and relevant information was identified and systematically extracted from each article that met the inclusion criteria. Following the transfer of the data into an excel spreadsheet, two authors (EN and ET) reviewed the extracted information and selected key focus areas for this review and categorized the information according to the training modules, method of assessment and outcome assessed. The two review authors grouped the outcomes into thematic heading, using the following categories: type of training, authors and titles, study setting, population, method of training and outcome of training (comments/relevant findings). Other useful available information in each article was extracted for clear and deeper understanding of the study.Data were summarized according to key components and definitions used for categorizing data. For each study, we categorized training or interventions evaluated and the outcomes into four levels based on the Kirkpatrick model .As shown in Fig. Key concepts of all studies that met the inclusion criteria were systematically summarized to provide a comprehensive but concise descriptive map of the nature and breadth of research on pre- and in-service training of HCPs\u2019 competence on immunization data handling and to identify obvious research gaps. The research objectives were used to identify and evaluate the evidence gaps. All 12 included studies were from LMICs; four studies were from sub-Saharan Africa, one from Asia and five were multi-country studies including Angola, Bolivia, Chad, the Democratic Republic of Congo, Ethiopia, Cameroon, Ghana, Lesotho, Madagascar, Malawi, Mali, Mexico, Niger, Nigeria, Senegal, South Sudan, Tanzania, Uganda, Zambia, Zimbabwe and the Philippines Table . The parOne third (33%) of the included studies , 24, 32 Sub-standard or lack of knowledge on supervision and monitoring is a major problem among the tutors. While basic knowledge on the principles of immunization is above average, student clinical practice was poorly supervised due to clinical supervisors\u2019 lack of skill and knowledge. One of the studies showed that only three of the seven medical training colleges in Kenya have the updated WHO EPI prototype curriculum , and thaNine of the 12 identified studies were on in-service training , 26\u201332. One of the major problems in HCP training is the lack of appropriate equipment and teaching aids and updated reference manuals and curriculum . Evidence shows that the majority (75%) of the pre-service training institutions lacked the necessary equipment and tools needed for practical demonstrations and knowledge of current EPI theory and practice .This review found that the curriculum, especially in pre-service institutions, is not responsive to current needs and is often outdated and usually only updated every 5 years , 30, 32.Although Hussein et al. reportedHealth information systems (HISs) are recognized as a useful tool in improving data management and access to essential data from multiple sources, but lack of the required skills to operate HIS and convey data information to the target audience has been a major bottleneck among immunization HCPs . Ward etAlthough routine follow-up and accountability are still a challenge, monitoring and evaluation of HCPs\u2019 activities, supportive supervision and development of specific, measurable, achievable, realistic and time-bound targets are essential for improving health providers\u2019 knowledge and competencies.Supervision can also lead to more efficient and effective data handling by HCPs. Effective supervision is difficult to achieve because there is no clarity on the most effective approach to supervision activities and the design and implementation of supervision. There is also no comparative intervention strategy that establishes a clear standard for performance, quality assessment and improvement in immunization data management , 30. EveRowe et al. also ideGood-quality immunization data are crucial for effective policies on vaccine-preventable disease, and in particular the reduction and prevention of under-five morbidity and mortality. However, the task of collecting and managing these data in LMICs rests mostly on HCPs who often lack the necessary skills and competencies to effectively function in these roles . CapacitFindings from this scoping review provide evidence that shows both pre- and in-service trainings are essential for the development of HCPs\u2019 competence in immunization data management, and analysis at all levels of the health system. The evidence shows that although pre-service training is fundamental, it does not adequately prepare HCPs, especially clinicians, with the necessary skills and competencies to collect, analyse and use data. This is due to a number of reasons, which include the inadequacies of the training curricula, which are not responsive to current needs, such as the changing trends in technology and preventive healthcare services, since the training curricula are often outdated , 30, 32.More importantly, the training institutions are not adequately equipped to train HCPs on data skills as the majority of the tutors and clinical instructors at pre-service training institutes lack sufficient skills and knowledge to enable adequate translation of knowledge . ContinuWard et al. highlighIn the systematic review by Vasan et al. , which lThese findings are consistent with the study by Whittaker et al. , which lThe strength of this review lies on the comprehensive nature of the search strategies used to identify the studies, which involves a range of methodologies that support exploratory review. The review extracted studies on HCPs\u2019 capacity development on data collection and quality in immunization programmes in LMICs. However, the restrictions placed as a result of the selection criteria could potentially bias the findings. Our search terms were restricted to low- and middle-income countries and specifically on the expanded programme immunization (EPI), and the review relied only on open access articles or those accessible through the electronic database and search engines, and those articles published in English, thereby possibly omitting some useful articles on the subject.This scoping review has highlighted the challenges faced by HCPs in terms of competencies and skills to perform immunization data management tasks, which have been attributed to insufficient pre-service training. Even though pre-service training is fundamental in the skills acquisition of HCPs, they often require additional in-service training and supportive supervision to effectively function in immunization data management tasks.Other issues around poor data management also stem from errors in processing data, limited use of already generated data, poor standardization of immunization data collection tools and processes such as registers, as well as ill-defined target population. These will require progressive implementation and uptake.Immunization is one of the most cost-effective ways to save lives, improve health and ensure long-term prosperity. Achievement of the aim of the Astana Declaration on primary health care to meet all people\u2019s health needs across the life course through comprehensive preventive and promotive care will require strong immunization programmes with well-trained and motivated workforce.Continuous capacity development in immunization data management competencies such as data collection, analysis, interpretation, synthesis and data use, and efforts to improve data quality should be strengthened at all levels of the health system using the minimum health information competencies framework. Additionally, all new hires require orientation by employers in data management before they commence work.Furthermore, there is a need for periodic review of the immunization-training curriculum in health training institutions, capacity development and retraining of tutors on the current trends in immunization data management such as the use of mobile technologies. The web district health information system (DHIS2) and tool like the WHO Immunization Information System (WIISE) are useful tools in improving immunization data management and use; however, these also require skilled workforce."} +{"text": "Here, we will review the recent literature regarding the interactions between columnar epithelial cells and neutrophils, with an emphasis on intestinal epithelial cells, structural aspects of neutrophil transepithelial migration, molecular determinants of neutrophil-epithelial cell interactions, as well as modulation of these pathways. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.Inflammatory diseases of mucosal organs as diverse as the lung, kidney, and intestine, inevitably require the intimate interactions of neutrophils with columnar epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets for the treatment of mucosal inflammation. Elegant"} +{"text": "To investigate the rule of kidney-tonifying method in Chinese medicine for the treatment of bone marrow suppression (BMS), in order to provide evidence and references for the clinical application of herbs and formulae. Collecting and sorting the information about the treatment of BMS related to kidney-tonifying (Bushen) method in Chinese medicine literatures on databases including Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), establishing a database of BMS treating formulae after radiotherapy and chemotherapy with traditional Chinese medicine (TCM) kidney-tonifying method, and finally applying the relevant theories and techniques of data mining to analyze the medication rules of it. A total of 239 formulae and 202 herbs were included in this database, in which the herbs occurred 2,602 times in general. The high frequency herbs included Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), and Ligustri Lucidi Fructus (Nvzhenzi). The main herb categories were deficiency-tonifying herbs, blood-activating herbs, dampness-draining diuretic herbs, heat-clearing herbs, and digestant herbs. Deficiency-tonifying herbs accounted for 64.60% of the total number. A total of 8 clustering formulae are summarized according to cluster analysis and 26 herb suits association rules are identified by Apriori algorithm. The treatment of BMS is mainly based on the method of invigorating the spleen and tonifying the kidney and liver to strengthen healthy qi, supplementing with blood-activating herbs, and dampness-draining diuretic herbs to eliminate pathogenic factors. BMS is one of the major side effect that is produced during the treatment of cancer patients with radiation, chemotherapy and drugs, which affect seriously patients' radio- and chemotherapical process and even led to treatment failure, which has become a major and difficult problem in clinical practice , 2. Acco kidney-tonifying, 239 related formulae were retrieved, upon which a database of BMS formulae was established and was standardized and classified according to the standard name and Chinese medicine classification of People's Republic of China Pharmacopoeia (2015 Edition) [ Chinese Medicine Dictionary [By collecting and collating the literatures on the databases including CNKI, CBM, VIP database, and WANFANG database about the treatment of BMS after radiotherapy and chemotherapy in Chinese medicine and inputting them to the NoteExpress literature management software and eliminating the literatures which do not meet the requirements, such as reviews, thin sample or not representative cases, and proven reports and animal experiments, this study established a data information collection form and entered the filtered prescription information into it. When the data was collected and sorted, a total of 621 effective formulae were gained to build a database of Chinese medicine treatment of BMS. By inputting the keywordEdition) and Chinctionary .A database of BMS treatment with kidney-tonifying formulae was established with the application of Excel 2013 and was converted into the format required by the data mining software. Programming and modelling the data with R language are done according to the data characteristics of Chinese medicine medication rules, within which the core herbs were clustered by Hierarchical clustering algorithm. For example, Vania M. Youroukova et al. analyzed the phenotype of severe bronchial asthma by using cluster analysis and obtained four clusters that provided reference for clinical treatment . The AprAmong the 239 formulae included in the analysis, there were 202 herbs of Chinese medicine included, and their occurrence frequency was 2, 602 times. Of the highest frequency was the herb Astragali Radix (Huangqi), which occurs 184 times, with a frequency rate of 7.07%. The second was Atractylodis Macrocephalae Rhizoma (Baizhu), whose frequency was 129 times (4.96%); the Ligustri Lucidi Fructus (Nvzhenzi) ranked the third with 125 times and (4.80%). And the top-nine herbs, respectively, are Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), Lucidi Fructus (Nvzhenzi), Angelicae Sinensis Radix(Danggui), Lycii Frucyus(Gouqizi), Codonopsis Radix (Dangshen), Poria(Fuling), Rehmanniae Radix Praepapata (Shudihuang), and Spatholobi Caulis (Jixueteng), whose frequencies all exceed 95 times, with their frequency rate higher than 3.65%, and their cumulative frequency reached 41.12%. Herbs with a frequency more than 18 times are shown in One hundred and eight high-frequency herbs with a frequency of 9 or more were categorized in this study. The details of herb categories and frequency are shown in Thirty-eight core herbs mentioned above were clustered by Hierarchical clustering algorithm in R language and were divided into 4-10 classes by system clustering. Considering Chinese medicine theory, 8 categories are more appropriate in this study, and they were named as cluster one to eight subsequently. The clustering details are shown in In this study, the R language data mining software was applied for modeling, and the Apriori algorithm was used to analyze the association rules of the core herbs above. The parameters were set as support degree \u226520% and confidence level \u226585% , upon wh(1) The method of strengthening the spleen and tonifying the kidney is the most common method for treating BMS in kidney-tonifying method. The herbs used in the tonifying kidney are mainly sweet, bitter, and pungent, rather than salty which is the corresponding flavor of the kidney in Chinese medicine theory and is different from the general idea that herbs salt in flavor are mainly used in kidney-reinforcing therapies and is more practical for clinical use . The herThe top nine frequent herbs are all deficiency-tonifying herbs apart from Poria (Fuling), the dampness-draining diuretic herb and Spatholobi Caulis (Jixueteng), the blood-activating herb. Although the two herbs are not classified as deficiency-tonifying herbs, they are often used in combination with deficiency-tonifying herbs to prevent the stagnation caused by deficiency-tonifying herbs. A former study shows that alfalfa polysaccharides and their derivatives have the effects of anticancer, anti-inflammatory, antioxidant, and antiviral activity biological activities and are good for health . In in vAccording to the relevant techniques and theories of data mining and the analysis of medication rules of applying kidney-tonifying method in treating BMS after chemoradiotherapy, it is revealed that this kind of treatment is based on the method of strengthening spleen and tonifying kidney, replenishing liver and kidney and combined with invigorating healthy qi, and also applied methods include dampness-draining and blood-activating to eliminate pathogenic factors. With the help of data mining techniques and theories, this study has summarized the medication rules of kidney-tonifying method in treating BMS after radiotherapy and chemotherapy, which can facilitate TCM diagnosis, treatment, and experimental research, and would be helpful for BMS patients."} +{"text": "According to the recent report of the World Health Organization (WHO), the global burden of non-communicable diseases (NCDs) has been rising over the last century, with the leading causes of disability being depression, diabetes, cardiovascular diseases (CVDs), and certain cancers . BesidesNumerous epidemiological studies have demonstrated the association between oxidative stress and NCDs. Oxidative stress is commonly known as an imbalance in the production of reactive oxygen species (ROS) and the biological antioxidant defense system. Over the last years, exogenous antioxidants have received great attention because of their potential beneficial effects toward human health. Contained in foods commonly consumed in all populations worldwide, antioxidants represent an attractive explanation of their beneficial effects. However, antioxidants are contained not only of fruits and vegetables, which are characteristic components of healthy dietary patterns, but also in other plant-derived foods, such as tea, coffee, and cocoa. Therefore, the evaluation of dietary habits of a population, and in particular the intake of antioxidants and adherence to healthy dietary patterns is crucial. Indeed, several studies explored the dietary intake of antioxidants and antioxidant-rich foods in a Mediterranean area, as well as their association with fluid and beverage intake ,5,6, demMoringa oleifera leaves [Accumulating epidemiological evidence have demonstrated the association between both antioxidants and antioxidant-rich foods intake and human health. For instance, recent meta-analysis and cohort studies showed that high consumption of antioxidants and antioxidant-rich foods is associated with decreased risk of overall and CVD-related mortality , certaina leaves , coffee a leaves , mulberra leaves , and broa leaves .Nevertheless, nowadays studies exploring the possible effects of antioxidants toward human health, should take into consideration the differences in dietary intake of polyphenols in various populations, differences in food processing (loss of phenolic content), absorption, bioavailability, and metabolism of polyphenols. The study by Khairallah et al. focused on the antioxidant effect of phenolic extracts from polyphenol-rich potato, demonstrating that the colonic microbial digestion of potato-based polyphenols could lead to improved colonic health, as this process generates phenolic metabolites with significant antioxidant potential .Several molecular mechanisms may account for the beneficial effects of polyphenols. The antioxidant effects of dietary polyphenols can be attributed to the regulation of redox enzymes through reducing reactive oxygen species (ROS) production and modulation of the II-phase enzymes responsible for the cellular oxidative response. Indeed, the study by Marmouzi et al. showed that antioxidant compounds from hybrid oat lines prevent against hyperglycemia-induced oxidative stress via the modulation of expression of key II-phase enzymes . AdditioFurther evidence from both epidemiological and experimental studies is needed in order to better characterize antioxidants that may exert beneficial effects toward the prevention of chronic diseases associated with oxidative stress and inflammation."} +{"text": "In the last decades the study of older people and social networks has been at the core of gerontology research. The literature underlines the positive health effects of traditional and online social connections and also the social networks\u2019s positive impact on cognitive performance, mental health and quality of life. Aging in a Networked Society is a randomized controlled study aimed at investigating causal impact of traditional face-to-face social networks and online social networks on older people\u2019 health, cognitive functions and well-being. A social experiment, based on a pre-existing longitudinal study (InveCe - Brain Aging in Abbiategrasso) has involved 180 older people born from 1935 to 1939 living in Abbiategrasso, a municipality near Milan. We analyse effects on health and well-being of smartphones and Facebook use , exploiting the research potential of past waves of InveCe study, which collected information concerning physical, cognitive and mental health using international validate scale, blood samples, genetic markers and information on social networks and socio-demographic characteristics of all participants. Results of statistical analysis show that poor social relations and high level of perceived loneliness affect negatively physical and mental outcomes. We also found that gender and marital status mediate the relationship between loneliness and mental wellbeing, while education has not significant effect. Moreover, trial results underline the causal impact of ICT use on self-perceived loneliness and cognitive and physical health."} +{"text": "This descriptive paper aims to describe the design and implementation of a community engaged primary healthcare strategy in rural Australia, the Primary Healthcare Registered Nurse: Schools-Based strategy. This strategy seeks to address the health, education and social inequities confronting children and adolescents through community engaged service provision and nursing practice.There have been increasing calls for primary healthcare approaches to address rural health inequities, including contextualised healthcare, enhanced healthcare access, community engagement in needs and solutions identification and local-level collaborations. However, rural healthcare can be poorly aligned to community contexts and needs and be firmly entrenched in health systems, marginalising community participation.This strategy has been designed to enhance nursing service and practice responsiveness to the rural context, primary healthcare principles, and community experiences and expectations of healthcare. The strategy is underpinned by a cross-sector collaboration between a local health district, school education and a university department of rural health. A research framework is being developed to explore strategy impacts for service recipients, cross-sector systems, and the establishment and maintenance of a primary healthcare nursing workforce.Although in the early stages of implementation, key learnings have been acquired and strategic, relationship, resource and workforce gains achieved. This strategy seeks to address the health, education, and social inequities confronting rural children and adolescents through community engaged primary healthcare service design and implementation. This strategy aligns nursing services and practice to the unique rural context, the principles of primary healthcare [World Health Organization (WHO), et al., The PHCRN:SB strategy, whilst sharing some similarities with contemporary school nursing services an exploration of evidence and theory; (2) the identification of the right health professional with the right scope of practice to provide services to address these findings; and (3) the design and implementation of a potential solution, the PHCRN:SB strategy.Guided by these findings, an exploration of the literature focused on the principles associated with primary healthcare and integrated care and the theories of family-centred care (FCC) and trauma-informed care. Primary healthcare principles include community participation in promoting health and addressing health inequities and cross-sectorial collaborations. Within primary healthcare, resources and actions are directed towards populations that experience the greatest levels of inequities WHO, , in thiset al., et al., et al., FCC locates \u2018the needs of the child, in the context of their family and community\u2019 through the development of collaborative and dynamic models of care service recipient impacts and outcomes; (2) cross-sector systems impacts and; (3) implications for the establishment and maintenance of a rural Australian primary healthcare nursing workforce. Each of these streams has a number of key focus areas. Stream 1 will explore education, health and social impacts for service recipients . Stream 2 will explore strategic, policy, funding and practice impacts on cross-sector systems. Stream 3 will explore impacts for the PHCRNs, the influence of the nursing model of care on nursing practice and pre-registration student experiences within the strategy. Each stream has cross-sector research leaders with responsibility to convene research sub-groups, develop research protocols and collectively contribute to the overarching research agenda.Governance structures play a critical role in promoting the effectiveness and success of healthcare innovations. Governance involves \u2018ensuring strategic policy frameworks exist and are combined with effective oversight, coalition building, regulation, attention to system design and accountability\u2019 WHO, : 86. A cA number of conceptual, cross-sector, health, professional, financial and research learning points have been gained. Conceptually, it became evident early in community consultations that the title \u2018school nurse\u2019 was not considered sufficient in describing the role and scope of nursing practice. Whilst synergies exist between contemporary school nursing practices, strategy aims, and the role of the PHCRNs, significant differences were identified . The title, PHCRN:SB, was adopted to: clarify the role and scope of nursing practice; respond to community perceptions and feedback; and provide a contemporary interpretation of nursing care and practice within a rural Australian and school-based settings.et al., Key cross-sector learning points included the requirement for significant time investments to establish a consensus-orientated (Johnston Despite wide spread support for the strategy, concerns were raised in relation to the potential for the PHCRNs to contribute to service fragmentation, increased referrals and workloads for other services. In contrast, the literature consistently identified the role of PHCRNs in promoting care coordination and integration. Cross-sector stakeholders acknowledge that tensions can be created when new health strategies have the potential to disrupt existing status quos and healthcare arrangements (North West Joint Improvement Partnership, Professionally, challenges have been experienced in attracting suitably qualified registered nurses to the positions. Additional investments have been required to support the appointed PHCRNs in transitioning from hospital-centric and acute care practice to schools-based and primary healthcare practice. Substantial resource, time and education investments have been directed towards nurse preparation for primary healthcare practice, including the enrolment of all nurses in post-graduate primary healthcare coursework.The uniqueness of the opportunity to co-design and contextualise nursing care and practice has been described by nursing executives and academics. Financially, the need to secure sustainable funding to appoint the PHCRNs has been a focus of the collaboration. This focus has been informed by previous experiences of short-term funding, lack of sustainability of new initiatives in rural contexts and levels of community cynicism towards poorly resourced healthcare innovations.Although in the early stages of implementation, strategic, relationship, resource and workforce gains have already been achieved. Strategically, a cross-sector governance committee has been established and convened to provide guidance and executive level endorsement of strategy aims, nursing care and practice approaches. Strategic documents have been developed and endorsed by this committee, including strategy proposal, communication strategy, comprehensive literature reviews, an initial evaluation and research framework, and a new model of nursing care. Relationships across sectors at the executive, senior management and service levels have been established or consolidated with relationship consistency being promoted through structured and routine multi-level committee, management and service meetings. New and sustained resources to fund the five PHCRN positions have been secured through the local health district, contributing to service continuity, consistency and sustainability. All five nursing positions have now been appointed to.et al., et al., Evidence indicates that to effectively address the challenges confronting disadvantaged children and adolescents we need to build supportive services that coordinate care across agencies in the same community, specifically those engaging with the same families. Increasing our understanding of the health needs of children and adolescents, and the application of this knowledge in the development of responsive primary healthcare policies and practices is necessary in establishing safe, health promoting environments and improved health outcomes (Viner et al., As the complexity of health, educational and social needs of rural school students increases, there are calls for greater levels of innovation in the design and implementation of alternative healthcare models that enhance service accessibility, acceptability and sustainability. Social innovations, those that have the capacity to transform the lives of individuals and communities, are required to resolve complex health inequities (Phills"} +{"text": "RECOTOX is a cross-cutting initiative promoting an integrated research to respond to the challenges of monitoring, understanding, and mitigating environmental and health impacts of pesticides in agroecosystems. The added value of RECOTOX is to develop a common culture around spatial ecotoxicology including the whole chain of pressure-exposure-impact, while strengthening an integrated network of in natura specifically equipped sites. In particular, it promotes transversal approaches at relevant socioecological system scales, to capitalize knowledge, expertise, and ongoing research in ecotoxicology and, to a lesser extent, environmental toxicology. Thus, it will open existing research infrastructures in environmental sciences to research programs in ecotoxicology of pesticides. One of the greatest challenges for ecosystem sustainability and human health is currently the ever-increasing pollution of all environmental compartments by chemicals of various types and properties. For many years, the scientific community has emphasized the lack of long-term field- and landscape-scale monitoring of the fate of chemicals in water, soil, air, and biota, and of their negative effects on living organisms. AllEnvi, Aviesan, and Athena, the French alliances that combine the national research potential and coordinate the scientific strategy, created the French initiative on toxicology, ecotoxicology, epidemiology, and social sciences, that underlined these points in 2013 AllEnvi , they liAgricultural systems, subject to frequent and diverse pesticide inputs, have been treated for more than 70 years with pesticides and other biocides to increase crop production and quality and the variable characteristics of the hydroagroecosystems where they are applied require the implementation of interdisciplinary research to address the complex issues of ecotoxicology and environmental toxicology of pesticides at the landscape or territorial scale.https://www.anses.fr/en/content/phytopharmacovigilance).Institutional and professional organizations request integrated methods and models to improve monitoring, assessment, management, and mitigation of both environmental and human health risks associated with pesticides. Indeed, assessing the impacts of these substances on ecosystems, and their possible consequences on human health, in a context of global change and of exposure to multiple stressors, remains a priority issue for policy makers. Under the French legislation, the \u201cphytopharmacovigilance\u201d concept has been erected in order to monitor the adverse effects of pesticides used in agriculture in relation with the granting of their marketing authorizations is a cross-cutting initiative to promote integrated research to respond to the scientific challenges of monitoring, understanding, and mitigating the environmental and health impacts of pesticides and biocides in agricultural landscapes, in agreement with the \u201cEco Health\u201d approach. Here, we describe the scientific and operational objectives of RECOTOX, based on its experimental site network.In that context, RECOTOX that promotes a common culture of spatial ecotoxicology of pesticides that considers the whole chain pressure-exposure-impact. RECOTOX accounts for a wide range of agropedoclimatical situations, in terms of soil-bedrock, agronomic, and climatic-hydrologic characteristics, influencing pesticide sources or biotransformation (retention-degradation) and transfer processes. RECOTOX, therefore, explores the panel of responses to provide systemic and generic outcomes.RECOTOX aims to (i) determine pesticide transfers and mitigation in soil/water/atmosphere, (ii) analyze the effects of pesticides on biodiversity and resilience processes, (iii) understand how farmer practices in interaction with the environmental affect pesticides transfers, and (iv) examine socioeconomic processes such as acceptability of changing practices, costs, or expectations of civil society. Consequently, the scientific community embedded within RECOTOX comprises environmental chemists, hydrogeologists and hydrologists of the critical zone, ecotoxicologists, microbiologists, ecologists and toxicologists, agricultural scientists, and scientists of human, economic, and social sciences. The added value of RECOTOX in terms of skill, knowledge, and tool capitalization in the field of ecotoxicology could be transposed to toxicology, and then promote interdisciplinary and federative research projects, e.g., in the field of phytopharmacovigilance.Promoting an integrated research in ecotoxicology. The first and main action of RECOTOX is to incubate research projects, involving the wide range of scientific and technological expertise of its partners, and making use of the complementarity of their observatories and skills. As a consequence, RECOTOX aims to create general knowledge, synthesis of information, and facilitate the emergence of integrated research in spatial ecotoxicology among its sites. It will also rely on the homogenization of reference documents and integration of existing metadata in a common open information system. RECOTOX will strengthen in selected sites\u2019 existing measurements of practices and uses, transfers, exposure, or impacts in the different compartments , and at the relevant spatial and temporal scales, establish an integrated approach of the pressure-exposure-impact chain. This integrated approach will benefit from ongoing research programs conducted at the concerned research sites, and/or more comprehensive projects to share methods and models previously developed for different sites of the network.Upscaling approaches in ecotoxicology from plot to landscape. One current challenge is to include ecological realism into ecotoxicological studies. A major step is to understand the relationships between chemical releases and mitigation, exposure patterns, and population spatiotemporal dynamics in heterogeneous landscapes, in response to agricultural practices at various spatial and temporal scales. More, there is a lack of more realistic biological indicators in the case of moderate and chronic environmental degradation by pesticides, in particular indicators based on networks of interactions between organisms under the influence of the physicochemical conditions of the environment. Ecotoxicologists, as well as risk assessors, express increasing interest in learning more about both exposure to and effects of chemicals at the landscape scales. RECOTOX will also evaluate the effect of remediation solutions on the measured or expected impacts at the relevant management scales. Here, observation, experimentation, and modeling will be combined.From ecotoxicology to toxicology. RECOTOX aims at developing, in some cases, observational studies to improve the characterization of human exposure and exposome, by collecting environmental samples, data, and information on daily environments of volunteers. Actions may include (i) the identification of pesticide sources; (ii) the selection of sentinel populations, highest-exposed individuals, activities, and behaviors that yield exposures; (iii) the evaluation of the magnitude and frequency of exposure; and (iv) the examination of the exposure\u2013response relationships. Such data are particularly necessary to improve performance of epidemiologic studies and reduce uncertainties in risk assessment. These studies will also enable to share experience with epidemiologists. RECOTOX will also fact to integrate both environmental and human exposure assessments implies organizing the network to develop interoperability of data, metrics, datasets, and methods. An appropriate information system will be devoted to data management from new experiments and also to ensure identification and valorization of acquired data currently managed by different and distributed information systems within each observatory.Communication, exploitation, and dissemination of results. RECOTOX aims at structuring the scientific community in ecotoxicology and developing interactions with toxicologists. RECOTOX will favor interdisciplinary research programs and promote facilities for an integrated approach, and thus contribute to increase the research potential on continental ecosystems. The wide range of scientific and technological expertise of RECOTOX partners may also serve as an educational support for training in the fields of toxicological risks ecosystems (ecotoxicology) and human health.RECOTOX develops cross-cutting actions, presented hereafter, within a current network of 10 sites.http://www.lter-europe.net/lter-europe/infrastructure/networks/national-networks#lter-france), five of which being involved in RECOTOX, will provide a very strong basis for landscape-scale analyses of pesticide distribution within ecosystems, as well as excellent connections with society and stakeholders in general. The Research Infrastructure OZCAR \u201cNetwork of Critical Zone Observatories\u201d (http://www.ozcar-ri.org/) is a network of sites of continental surfaces with instrumentation on soil, subsurface, water, and ice dedicated to continuous measurement in support of knowledge and modeling of water, carbon, and associated elemental cycling, and comprises two sites of RECOTOX. Then, RECOTOX can also benefit from the Research Infrastructure \u201cAnalysis and Experimentation on Ecosystems - France\u201d . AnaEE-France is an integrated network of the major French experimental, analytical, and modeling platforms dedicated to the biological study of continental ecosystems . This infrastructure aims at understanding and predicting ecosystem dynamics under global change. AnaEE-France comprises complementary nodes offering access to the best experimental facilities and associated biological resources and data: the Research Infractructure Ecotrons, and semi-natural experimental platforms to manipulate terrestrial and aquatic ecosystems. AnaEE-France also provides shared instruments and analytical platforms dedicated to environmental (micro-) biology, as well as databases and modeling tools designed to represent ecosystem dynamics in coupling ecological, agronomic, and evolutionary approaches. AnaEE-France is already open to the community of scientists in the field of continental ecotoxicology . Indeed, this infrastructure brings together networks of Biological Resource Centers (BRC) maintaining genetic, genomic, and biological resources produced and characterized by research on domestic animals, crops and model plant species, wild relatives of domestic species, microorganisms relevant for agriculture and macrofauna of the environment, and environmental samples. RECOTOX can particularly benefit from its capacity to maintain a large diversity of well-documented resources, to collect novel resources, to contribute to their characterization, to distribute them, and to manage the related data. RARe can also help the sites of the network in strengthening and organizing their ability to store and secure collected samples and their related data in the long-term.In addition, RECOTOX would benefit from the Research Infrastructure \u201cAgronomic Resources for Research\u201d (AgroBRC-RARe), and its pillar \u201cenvironmental resources\u201d . Indeed, ECOTOX has three main objectives: (i) to encourage scientific thinking within the community of ecotoxicologists, whether they are dealing with aquatic or terrestrial ecosystems; (ii) to contribute to defining a national research strategy in this field; and (iii) to favor scientific production , the international network on Microbial Ecotoxicology which includes sites centered on the design of agricultural systems, allowing reduced agricultural pressure (including pesticides) for the characterization of the determinants and effects of agricultural practices at the local scale,The catchment, landscape, or territory scale, which allows the observation, experimentation, and modeling of various agricultural practices, pollutant dissipation/retention/transformation schemes in both cultivated or non-cultivated landscape components, or various exposures and impacts on continental terrestrial and aquatic ecosystems,The global scale, where it is intended to organize and cross observations and experimentation results obtained on a similar way in several complementary sites.RECOTOX focuses its activities in a network of instrumented sites mostly belonging to recognized Research Infrastructures , managed by research institutes and universities. The sites cover a variety of soil, agronomic, climatic, and socioeconomic situations, which are reflected in the diversity of agricultural practices, land uses, and landscapes, as well as hydrological and biogeochemical conditions. Their main characteristics are presented in Table http://www.zaplainevaldesevre.fr/, Bretagnolle et al. 2, including the forest of Chiz\u00e9, and is a typical rural area with a temperate Atlantic oceanic climate. It includes around 450 farms with high diversity of agricultural strategies with organic farming, conservation farming, and conventional farming. Since 2003, half of the area is designated as a Special Protection Area (NATURA 2000 network) for conservation of remarkable or endangered bird species such as the little Bustard Tetrax tetrax or harriers Circus spp. From 1994 onwards, biodiversity surveys have been carried out every year in 120 to 200 farmers\u2019 fields. Monitoring started with birds and small mammals in 1994, ground-dwelling arthropods since 1995 and then other arthropods , plants since 2005, and soil organisms since 2016. In addition to biodiversity monitoring, farming practices have been monitored by means of farmer interviews (about 150 fields per year) which allow to quantify pesticide uses and analyze the relationships between this use and biodiversity. The ZAPVS also hosts the ECOBEE platform comprises the observatory ORACLE/BVRE Orgeval (http://gisoracle.irstea.fr). Located 70 km east of Paris, the Orgeval catchment supports research on understanding the processes and developing integrative modeling of the hydrological functioning of its small upstream catchment. Started in 1962, the Orgeval catchment is managed by Irstea. This site belongs to the ORACLE observatory (1800 km2) which is composed of the Grand Morin and Petit Morin catchments. The ORACLE observatory gathers many national and international research units in the GIS ORACLE (Group of Scientific Interest) created in 2011. The Orgeval catchment is also part of the \u201cZone Atelier Seine\u201d thanks to the Interdisciplinary Research Program in Environment on the Seine basin (Piren Seine) and it is also part of the IR OZCAR. The ORACLE observatory is dedicated to the improvement of the knowledge on the hydrological and biogeochemical functioning of sedimentary basins in rural anthropized systems. Its objective is the observation and modeling of streamflow and of water and pollutant transfer processes at various scales. It also works on the optimization of data acquisition methods. ORACLE, with its set of nested subbasins and its perennial long-term observations (more than 50 years), allows to address the scaling and global change issues. The Orgeval catchment area covers 104 km2. It is mostly constituted of drained fields and devoted to field crops. It has a direct influence, in terms of quantity and quality, on the flows going from the Marne to the Seine Rivers until the Paris conurbation. On the Orgeval catchment, chronicles of streamflow and water quality data are available since 1962 and 1978, respectively, and the monitoring of pesticides started in 2008, in the context of two projects: Phyt\u2019ORACLE (EC2CO) and PIREN Seine is an environmental research platform created in 2000 and located in the Grand Est region. Currently, the ZAM gathers a Lorraine scientific community around the protection of water resource of the Moselle River. The ZAM covers 15,400 km2 in France and presents a highly contrasted occupation of the territory combined with specific anthropic pressures. The upper part of the basin is dominated by the Vosges Mountains, sitting on acidic soils . The middle and lower parts of the French basin correspond to a succession of cuestas characterized by limestone plateaus with permeable soils and plains with a dominant clay soil. Agriculture, especially mixed farming and livestock farming, is present on the middle part of the basin, which receives regular agricultural inputs . The downstream part of the basin is characterized by increasing urbanization and by the heritage of Lorraine\u2019s industrial past (iron mining and steel industry). Still, throughout its journey, the Moselle River contributes to maintain wetlands areas with a rich biodiversity . The ZAM research actions are structured around five main disruptions linked to geomorphology, land use, and human activities: the acidification of streams and rivers in the Vosges mountains; pesticides and their residues, mainly linked to agricultural activities (http://www.zabr.org/) comprises the Ardi\u00e8res-Morcille experimental site (https://saam.irstea.fr/), which studies the impacts of anthropization, especially wine growing, on river water quality and aquatic ecosystem functioning in order to highlight the key involved processes, biological adaptations, and remediation trajectories. The Ardi\u00e8res-Morcille experimental site belongs to the Rh\u00f4ne Basin Long-term Environmental Research Observatory (ZABR) which comprises a set of observatories and experimental sites devoted to a better understanding and management of the Rh\u00f4ne River basin. The Ardi\u00e8res-Morcille experimental site was set up in 1987 by the Cemagref, the regional service for water use and supply and the Beaujolais Development Committee. It moved in 2007 to the ZABR (which has been labeled SOERE ZA in 2001). Among the other experimental sites and observatories of the ZABR, the Ardi\u00e8res-Morcille experimental site was chosen in priority to be part of the RECOTOX network because of the anteriority and history of the research devoted to the fate and effects of pesticides used in agriculture, and because of the interdisciplinary approach developed along the fate-exposure-impact chain. Researches on the Ardi\u00e8res-Morcille experimental site also contribute to providing operational tools to better understand and implement buffer zones in catchments so as to limit the diffuse agricultural pollutions of rivers . The Ardi\u00e8res-Morcille experimental site consists of two nested catchments: the Morcille catchment (8 km2) and the Ardi\u00e8res catchment (150 km2). Located northwest of Lyon in continental climate, the Ardi\u00e8res-Morcille experimental site is characterized by intensive wine growing. It is representative of the agricultural, soil, and climatic conditions of the central and northern Beaujolais. The first studies (since 1987) started on the Morcille subcatchment which is now equipped with long-term hydrometeorological stations and experimental subsites. The recent studies on the Ardi\u00e8res catchment (since 2011) enable both to address the question of hydrological processes and modeling scaling up and to strengthen the involvement of the economic and social sciences. Four research themes are crossed on the Ardi\u00e8res-Morcille site: observation and modeling of hydric transfers of pesticides; characterization of the chemical contamination of the river; development of knowledge and indicators of the in situ impacts of pesticides on aquatic ecosystems and their recovery capacity (resilience); development of methods and tools to help public decision-makers to understand and use the research results (http://zaaj.univ-fcomte.fr/) is an area of 13,500 km2 that covers a large part of the Jura medium mountains in Bourgogne-Franche-Comt\u00e9 and Rh\u00f4ne-Alpes regions, eastern France. It is composed of grasslands exploited for cheese production, karst and rivers, forests, peatlands and wetlands, and urban areas. ZAAJ observatories are designed to promote long-term interdisciplinary research on the dynamics of the socioecosystems of this territory. They contribute to capitalize on field data and to analyze and promote the results from long-term observation schemes at the interface between ecology, environment, and society. The main researches questioned the impacts of human activities, including those due to environmental contaminants, and their implications in terms of ecosystems health, social economic issues, and biodiversity conservation. They aim to assess the vulnerability of ecosystems and population at risk and to provide predictive and management tools to help maintain ecosystem services and protect population and ecosystems\u2019 health. Among questions related to RECOTOX, we can cite for instance vole outbreak management in grassland agrosystems and side effects on wildlife (http://www.obs-omere.org) is composed of two cultivated headwater Mediterranean catchments: the Roujan catchment (0.91km2) located in France (Languedoc region) and the Kamech catchment (2.63 km2) located in Tunisia (Cap Bon Peninsula). The OMERE observatory was set up in 2002 to understand the impact of agricultural and land management on mass fluxes in typical farmed headwater catchments of the Mediterranean region. Within this main objective, the OMERE aims at studying the natural and anthropogenic drivers of pesticide contamination of soil and water across scales from plot to catchment scales. The observatory helps to address the effect on pesticide transfer of highly variable hydroclimatic conditions characterizing Mediterranean regions , as well of soil type, crop treatment, and land management. The two catchments are similar with respect to environmental and climatic conditions. They differ according to the change in land use and human activities they are submitted to. In the Kamech catchment, cereals, legumes, and irrigated market gardening are mainly cultivated and a progressive intensification of agriculture occurs with a full use of the area available for agriculture and an increasing application of fertilizers and pesticides. In the Roujan catchment characterized by wine growing, intensification of agriculture has already been operated for a few decades and has led to the creation of a network of ditches and human-made slopes. So far, the dynamics of pesticides, mainly herbicides, has been studied in Roujan catchment. Pesticides have been monitored in soil, runoff water, groundwater, and rainfall. In surface waters, the monitoring is performed from plot to catchment scale using a nested network of hydrometric stations. The monitoring design is based on the knowledge of the applied treatments that are also recorded.The agro-hydrological observatory OMERE is an observatory of agricultural pollution in the French West Indies composed of two equipped catchments: one in Guadeloupe and the other one in Martinique. It is dedicated to the study of the fate of pesticides (including chlordecone) in the environment according to agricultural practices. The OPALE observatory in Capesterre-Belle-Eau in Guadeloupe, and the Galion catchment (40 km2) in Martinique. Previously called OPA-C, the OPALE observatory was accepted in the frame of the call for projects of the Chlordecone National Action Plan\u2014catchment (PNAC-BV) in May 2012. This project, lasting from 2012 to 2014 enabled the implementation of equipment in the two catchments thanks to a partnership between the BRGM, CIRAD, IRD, and INRA. The P\u00e9rou-P\u00e8res River catchment in Guadeloupe is located on the edge of the volcano la Souffri\u00e8re. It is composed of ashy soil on a recent geological formation. The Galion catchment in Martinique is located on well-developed soils with old geological formation. Those two sites are typical of tropical conditions with the leaching of soils with a high organic matter content. They enable to cover the main crops specifically of the French West Indies: sugar cane and banana. Therefore, those two sites have been affected by a heavy use of chlordecone between 1972 and 1993. The OPALE observatory aims at monitoring the agricultural practices and surface or groundwater contamination on a small agricultural area is an agroenvironmental observatory on the Vesle catchment. It aims to guide territory stakeholders in the coconstruction of a collective knowledge management device about agricultural practices, in order to help the implementation of actions to improve the water resource quality. OBSERVOX is a territorial observatory of agricultural practices on the Vesle catchment up to the Couraux water catchment area, which covers 700 km2. It was created in 2007 in the frame of the AQUAL objective contract. OBSERVOX consists of five subcatchments. It is carried by the SIABAVE and the scientific part is led by the CReSTIC (Research Center in Sciences and Technology of Information and Communication \u2013 Universit\u00e9 Reims Champagne Ardennes) and the ASTER unity of INRA of Mirecourt. The Seine Normandie Water Agency and the FEDER take part in the cofinancing of the project. In OBSERVOX, two sites are part of the RECOTOX network: the site of Cernay-les-Reims and the site of Sommevesle. The first one covers 37 ha of vineyards localized on the Reims and Berru mountain slope. Approximately 50 farmers work on this site. The second one covers 830 ha of croplands. Those two sites are characterized by a temperate continental climate tending towards oceanic and chalk soils of the Champagne region. This territory is typical of the Champagne region. The OBSERVOX observatory aims to increase knowledge in partnership with territory stakeholders on water resource quality and changing agricultural and wine-making practices, as well as on the factors affecting molecule transfers towards water resource. It has three objectives: access the change in pesticide pressures linked to their use in vineyards and croplands; explain this evolution; link this evolution to analyzed pesticides and metabolites in waters from the Couraux water catchment area. Benefiting from a 10-year monitoring in the Champagne region, the OBSERVOX site is also located in an agricultural area where there is a heavy use of pesticides. Therefore, this site is particularly relevant to study the impact of pesticide use on water resources.The observatory OBSERVOX enables the quantitative evaluation of matter transfer processes in relation to hydrological and agronomic forcing and human activities in vineyards in order to understand, quantify, and predict the hydrological and biogeochemical functioning of an agrosystem in perennial culture. Located 15 km southwest of the town of Colmar in Alsace, the site is one of the observatories of the Laboratory of Hydrology and Geochemistry of Strasbourg . A 43-ha vineyard catchment was equipped in 2003 for the monitoring of pesticides, and then in 2009 for the monitoring of flows and cycles of solutes, including pesticides and metals and integrating an artificial wet buffer zone at the outlet of the 43-ha catchment. The Hohrain\u2019s catchment team is composed of researchers of the LHyGeS and lecturers of ENGEES and EPLEFPA (College for winegrowers), as well as the city of Rouffach and winegrowers in the catchment area. The monitoring of the Hohrain-Rouffach catchment has been developed in the framework of the LIFE Environment project ArtWET (2006\u20132011), the INTERREG IV PhytoRET (2011\u20132014), and the PACOV project , coordinated by the LHyGeS. The Hohrain-Rouffach site is representative of agriculture, soil , and continental climatic conditions of the Alsatian Piedmont. The site is equipped to quantify solute flows at the catchment scale and the vineyard plot (two 1341-m2 plots equipped). The artificial stormwater wetland zone (320 m2 and 1500 m3) located at the catchment\u2019s outlet is studied since 2009 in terms of reactive transport of pesticides and metals at the water/plant/sediment interface. For 10 years, the catchment has served to collect information on water and chemical flows as well as land use data. A specificity of the catchment is that it enables to investigate the plot\u2013catchment\u2013wetland buffer zone continuum is an observatory devoted to the study of diffuse contamination of crop fields by mycotoxins, trace elements, and pesticide residues. It is an agronomic tool created in 2010 in the frame of the Combined Technology Network (CNT) in order to focus on the thematic field of sanitary quality of major agricultural products. Quasaprove is a network of plots whose agropedogeochemical conditions are well known. It enables to perform full-scale tests on hypotheses and models about the sanitary quality of crops in pre- and post-harvest . The Quasaprove network is spread on the whole French territory. It is located in seven INRA sites, two Terres Inovia stations, four ITAB stations, 11 agricultural secondary schools sites, and one Arvalis site in Boigneville. The seven involved INRA sites are as follows: UE Domaine exp\u00e9rimental de la Motte au Vicomte de Rennes, UE 0802 d\u2019Agronomie de Toulouse, UE 1246 Grandes Cultures Versailles-Grignon, UE 1373 Fourrages Environnement Ruminants de Lusignan, UMR EMMAH Domaine St Paul Avignon, UE d\u2019Epoisses, UE Grandes Cultures Innovation Environnement \u2013 Picardie. Quasaprove is led by ACTA and INRA. In the Quasaprove network, seven sites belong to the RECOTOX network. Located in Auzeville in Haute-Garonne, Lusignan in the Vienne, Epoisses in C\u00f4te-d\u2019Or, Le Rheu in Ile et Vilaine, Versailles in the Yvelines, Estr\u00e9es-Mons in the Somme, and Avignon in the Vaucluse; those sites cover a wide range of soil agricultural practices and climate conditions all over the French territory. Conventional and organic croplands are prevailing in the studied sites. These focus on diffuse agricultural contamination in different compartments and try to understand the sources and accumulation pathway of pollutants. The CNT Quasaprove activities deal with scientific and technical questions in relation with the source, fate, and management of contaminants and non-desirable organisms which jeopardize the sanitary quality at every stage of the food chain. The objectives of the CNT Quasaprove are to assess the contamination levels of crops and agricultural soils; quantify the plot trace elements flow and assess the impact of practices on soil contamination; test characterization tools of the trace element availability, test at a field scale the hypotheses and predictive models of the crop contamination risk; keep a sample bank for further analysis on contaminants not yet studied. The Quasaprove network benefits from a chronicle of the exogenous intakes (fertilizers and pesticides). The multicontamination approach is studied in priority. One of its originality is also to take simultaneously into account the soil and plant compartments with the subsequent difficulty to analyze and model transfers.The QUASAPROVE network its quasi monoculture of vines and its relatively homogeneous soils make it possible to select comparative measurement stations; (ii) agricultural practices, moderate to high slopes, and climate characteristics are favorable to pesticide transfer to surface water; and (iii) the wide range of pesticide substances used for vine protection allows exploration of different physicochemical properties and associated pesticide fate. The tested chemical tools were passive samplers as, for example, Silicone Rods (SR) dedicated to hydrophobic to moderately hydrophilic compounds. In total, 28 pesticides were analyzed as well as potential confusing parameters s, nutrients, temperature). In parallel, the biological approach consisted in an in situ study of a range of selected impacts on microbial and invertebrate communities. As an example, the following were measured: (i) leaf litter decomposition, which is mediated by the combined action of natural microbial and invertebrate communities; (ii) fungal biomass within leaf-associated natural microbial communities; (iii) alimentation and acetylcholine esterase inhibition in standardized caged Gammares (Gammarus fossarum). The tools have been applied during June 2014 and June 2015 (corresponding to a period of pesticide application on vineyard) in the Ardi\u00e8res River at three measurement stations from upstream to downstream. The results . Landscape organization can modulate the resistance and resilience of ecosystems to the impacts of anthropogenic disturbances such as soil pollution, particularly by pesticides. Moreover, landscape elements influence the distribution of contaminants, exposure of living organisms, ecological processes related to ecosystem services, and therefore agroecosystem functioning. For instance, the presence of hedges may limit pesticide transfer or a high percentage of organic farming or grassland in a landscape may buffer the negative effect of pesticides. Unraveling the respective influence of landscape organization and pesticide inputs can thus provide recommendations for risk assessors and suggest spatial arrangement that best support multifunctional and resilient agricultural landscapes. However, assessing the pesticide transfer and risk at landscape scale is challenging and requires dedicated infrastructures. The extensive knowledge of land use in the LTSER Zone Atelier Plaine & Val de S\u00e8vre (ZA PVS) as well as available data on farming practices in the area allows investigating how local farming practices and landscape organization affect biodiversity, ecosystem functions, and pesticide transfer. Three projects address this issue in the LTSER ZA PVS: BIOSERV , funded by INRA metaprogram ECOSERV, test this hypothesis that the flows of goods and services that organic farming will benefit crop production and farmers profitability both in organic farming and conventional farming fields through higher regulation services; RESCAPE funded by French Biodiversity Agency on \u201cResistance and Pesticides\u201d research call, with the fees for diffuse pollution coming from the Ecophyto Plan; and PING funded by Metaprogramme SMaCH of INRA aims to assess the impact of landscape features (composition and configuration) and agricultural practices on pesticide transfers in soils and living organisms. All projects use an integrated and interdisciplinary approach. BIOSERV analyzes the effect of landscape composition and their spatial arrangement on biodiversity, key ecosystem services , and farmers\u2019 incomes. RESCAPE and PING establish quantitative links between agricultural management, the spatial distribution of pesticides and the effects of pesticides. The PING project also investigates the link between ecotoxicology and socioeconomy by analyzing the farmers\u2019 decision to use glyphosate and how, based on scientific results , their perception and use of glyphosate may change. In the three projects, several measurements are performed in arable fields (120 fields) and semi-natural elements such as soil sampling for physicochemical characterization and pesticide concentrations, biodiversity monitoring , and ecological functions . In RESCAPE and PING, the spatial distribution of pesticides in soils is also studied through the development of analytical methods (Daniele et al. Several sites already host research projects in the context of the chain pressure-exposure-impact applied to pesticides. The RECOTOX network offers the perspective to extend them and to address new issues. Examples of projects are presented hereafter:The initiative RECOTOX federates in natura sites that develop a common culture in spatial ecotoxicology in the context of the whole chain pressure-exposure-impact applied to pesticides. RECOTOX will provide an added value to existing research infrastructures for environmental research by launching transversal approaches at relevant socioecological system scales, by capitalizing their knowledge and expertise, and seeking complementarity in the fields of ecotoxicology, and to a lesser extent, in environmental toxicology. RECOTOX will generate proposal and partnership that can serve as a framework for project preparation addressed to funding agencies. Finally, RECOTOX is positioned as the French part of a European network to develop for the research on ecotoxicological effects of pesticides."} +{"text": "Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA\u2019s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions. Pancreatic cancer impinges profoundly on mankind and, is one of the most aggressive and fatal malignancies. Pancreatic cancer is the third leading cause of cancer-related deaths in the USA and is anticipated to take the second spot by 2020 ,2. In 20Despite enormous progress in the field of cancer research and treatment, the biomarkers for initiation and progression of pancreatic cancer are still not well-defined. Micro RNA (miRNA) might help to establish a better diagnostic tool for pancreatic cancer. Altered and aberrant expression of miRNA is a hallmark of several human malignancies . Recent In this review, we provide a brief account of the biogenesis of miRNA and its effects on cellular functions and miRNA related studies in pancreatic cancer patients and animal models. We also review existing literature on the role of miRNA in cell cycle and cell proliferation, apoptosis, invasion, metastasis, and cellular signaling pathways. We also explore the use of miRNA as diagnostic, prognostic and therapeutic targets in pancreatic cancer. Caenorhabditis elegans . Re. Re87]. Given the decisive role of miRNAs in various stages of pancreatic cancer, starting from its initiation to progression to metastasis; miRNAs are potential targets for the therapeutic interventions . miRNA-bA separate approach comprises of miRNA antagonists. These are single-stranded antisense oligonucleotides corresponding to target miRNA, synthesized chemically with specific modification to provide high stability, binding affinity, and protection from nucleases ,156. TheThe association of miRNAs with cancer and using these miRNAs as therapeutic targets provides new hope for the effective diagnosis and treatment of fatal pancreatic cancer. Novel data about the biogenesis, regulation, and functions of miRNAs is increasing at an exponential rate. The cardinal regulatory role of miRNAs in key biological processes such as cell survival and proliferation, invasion and metastasis, apoptosis, and drug responsiveness, highlights their potential as diagnostic, prognostic and therapeutic targets. Also, little is known about inter-cellular communication mediated by miRNAs in pancreatic cancer. Moreover, a single miRNA target several genes and a single gene may be targeted by multiple miRNAs resulting in the additive action of miRNAs in the course of the disease. The aberrant expression of miRNAs is strongly correlated with pancreatic cancer, and in at least some cases appears to play a causative role in the establishment and progression of the disease. Restoration of down-regulated tumor suppressor miRNAs and inhibition of up-regulated oncogenic miRNAs holds the enormous prospect for the development of novel effective anticancer therapies or diagnostics. While there has been tremendous progress in the field with ample ongoing progress, there remain some limitations that need to be addressed before employing miRNAs as a therapeutic target. One of the most serious limitations is the potential for off-target effects and levels of toxicity of these chemically modified miRNAs on the healthy cells of the patients. The specific delivery of therapeutics into the pancreatic cancer cells is another consideration. Nonetheless, the recently developed intravenous injections and nanoparticle associated delivery system have shown great promise. Thus far, the progress in the field of miRNAs is impressive, but there is a long way to go. Pancreatic cancer remains a leading cause of mortality but the new body of work on the function of miRNA in cancer provides hope for miRNA-based strategies for early diagnosis, improved prognosis, and better management of clinical systems."} +{"text": "The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. The discovery of NPs provided a fundamental contribution into our understanding of the physiological regulation of blood pressure, and of heart and kidney functions. NPs have also been implicated in the pathogenesis of several cardiovascular diseases (CVDs), including hypertension, atherosclerosis, heart failure, and stroke. A fine comprehension of the molecular mechanisms dependent from NPs and underlying the promotion of cardiovascular damage has contributed to improve our understanding of the molecular basis of all major CVDs. Finally, the opportunity to target NPs in order to develop new therapeutic tools for a better treatment of CVDs has been developed over the years. The current Special Issue of the Journal covers all major aspects of the molecular implications of NPs in physiology and pathology of the cardiovascular system, including NP-based therapeutic approaches. The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. First, the discovery of NPs provided a fundamental contribution for the understanding of the physiological regulation of blood pressure (BP) and of cardiovascular and renal functions . SubsequAs a matter of fact, the NPs system has provided over time a continuous, attractive source of new knowledge and discoveries regarding the pathogenesis, diagnosis, prognosis, and therapy of CVDs. In particular, the opportunity to target NPs in order to design new therapeutic tools for a more effective treatment of CVDs has been developed, ultimately culminating in the introduction of a new class of drugs for the management of HF, the angiotensin receptor neprilysin inhibitor (ARNi) ,6. The continuous interest in this field of biomedical research is documented by accumulating data produced from several expert scientific groups. This issue of the Journal collects some original and review articles on the molecular and biomedical aspects concerning NPs, with a discussion of their current clinical and therapeutic applications. Nppa) or NPRA gene (Npr-1) led to hypertension and marked cardiac hypertrophy, the latter being independent from high blood pressure levels [Npr-1 led to salt-sensitive increases in BP whereas Npr-1 gene duplication lowered BP and protected against high dietary salt concentrations [Nppa, BNP gene (Nppb), and Npr-1 with cardiovascular disorders in humans [The cellular effects of NPs include the regulation of cell proliferation, angiogenesis, apoptosis, fibrosis, and inflammation . Their ae levels . In parte levels , the gentrations . The fintrations ,8. In fan humans ,8,9. Interestingly, NPs control the lipid metabolism through an anti-lipolytic effect . Of noteNppa, Nppb, CNP gene (Nppc), Npr-1, NPRC gene (Nprc), Corin, and Proprotein convertase subtilisin/kexin type 6 gene (PCSK6) are known contributors to hypertension development in experimental models as well as in humans through a decreased function of the system and of its impact on BP regulation [Nppa , that is frequently encountered in the general population , has shown functional deleterious properties that completely diverge from those of the wild type form, which makes this molecular variant a significant contributor to cardiovascular acute events such as stroke and myocardial infarction [Nppa variant (rs5068) is able to reduce the cardiometabolic risk by increasing the circulating ANP level and its beneficial cardiovascular and metabolic properties [Nppa variant (rs5063) was associated to reduced left ventricular mass in hypertension [Nppa support the existence of genetic predictors of cardiovascular risk that contribute to the individual risk profile (as part of the emerging field of predictive medicine).Both the hemodynamic and cellular effects of NPs explain the pathogenetic involvement of NPs in hypertension and related target organ damage. In particular, as discussed in this issue of the Journal, the comprehension of the fine molecular mechanisms underlying hypertension has been largely improved through the dissection of the molecular genetics of the NPs system . Nowadaygulation . Furtherfarction . On the operties . Furtherrtension . OverallNPs represent today well established and useful diagnostic biomarkers in HF, being of particular help for the differential diagnosis of dyspnea in the emergency room . The incHF is often associated to atrial fibrillation (AF), a condition that on its own presents with higher BNP levels ,33. ThisIn the context of HF, a renal dysfunction often develops . As reviewed in this issue by Okamoto R. et al. , BNP is The strength of the relevance of NPs in HF is reinforced by an interesting review article of this Special issue. Specifically, the article by Cao Z. et al. focuses on the role of NT-proBNP/BNP as valuable diagnostic biomarkers of cardiac dysfunction in deceased individuals . This orAn important component of the NPs system is represented by CNP, which acts through either the NPRB or NPRC receptors. CNP is mainly synthetized by endothelial cells and also by cardiomyocytes and fibroblasts. It circulates in the blood at very low amounts, offering a clear example of an autocrine/paracrine mediator within the cardiovascular system . The mosAmong the recent discoveries regarding the NPs system, the one that deserves particular attention is the potential involvement of NPRC signaling in the pathogenesis of pulmonary arterial hypertension . The artThe main therapeutic approaches to treat CVDs involving the NPs system are based on either the development of peptide analogs or the blockade of peptides catabolism ,4. In thAn overview of the strategies aimed at blocking the NPs catabolism through a NPRC blockade, and particularly through NEP inhibition, is presented by Volpe M. et al. . The appOverall, the comprehension of the multiple functional roles of NPs, gained over the last 35 years, makes this hormonal system an essential contributor to the maintenance of the cardiovascular health. On the other hand, a deeper understanding of the complex molecular mechanisms underlying the functionality of NPs has opened a new way to relevant therapeutic innovations. Future years, through the continuous efforts of several research groups, will certainly reveal more insights on this multifaceted cardiovascular hormonal system."} +{"text": "An emerging component of mHealth is the use of tailored mobile applications (app) to facilitate self-management of chronic illnesses, including the mapping of social networks to assist adults living with chronic illnesses to help them be able to identify sources of social support. The purpose of this study is to describe a prototype app to support persons living with dementia (PLWD) in the community and their informal caregivers to map social networks and identify sources of emotional, instrumental, informational, and appraisal of social support. Adapting the Network Canvas open-source software and drawing upon a previously-developed mobile application for adults to self-manage chronic illnesses, we share the key specifications, including health care provider output, preliminary end user feedback, and the pilot protocol designed to test the feasibility. Findings illustrate the importance of leveraging social network data in novel ways to enhance self-management and well-being among PLWD and their caregivers"} +{"text": "Diagnosis, that is, characterization of building materials and assessment of building materials' decay, as well as assessment of environmental loads;Assessment of compatibility and performance of conservation/restoration materials and interventions, both in lab and in situ on building scale;Monitoring of the structure after the application of the most appropriate materials and interventions, to assure sustainability.Protection of built heritage passes through three distinguished steps that involve the following:Scanning microscopy techniques are among the techniques that are used throughout the investigation of the aforementioned processes, and their applicability is increasingly gaining ground. In this framework, the input aspects of the scanning microscopy techniques in the field of built heritage protection are of high importance. The enhancement of our knowledge on the physicochemical and microstructural characteristics of historic and modern building materials and their degradation processes, as well as on the properties of the conservation and repair materials that we need to design in terms of compatibility and sustainability, is vital, and scanning microscopy techniques are key tools towards this direction, with technological advances further increasing their effectiveness.A. Moropoulou et al. review the literature for the use of scanning microscopy techniques in the fields of building materials and cultural heritage, comparing these techniques with other analytical techniques widely used in these fields, regarding acquired information, sample requirements, and major limitations. They also summarize the main advantages and limitations of the most commonly used scanning microscopy techniques in the field of built cultural heritage through numerically comparing the research papers that report their use and findings in bibliography and demonstrate that scanning electron microscopy with energy-dispersive X-ray spectroscopy analysis (SEM-EDX) can be regarded now as a routine and a key role technique, whereas transmission electron microscopy (TEM) is progressively utilized. Distinctive results of SEM-EDX are presented regarding building material characterization, such as stone and mortars; mortar production technology; stone decay diagnosis, as far as it concerns the impact of pollution, salt crystallisation, and biodeterioration; and assessment of cleaning, consolidation, and protection treatments. Furthermore, characteristic TEM results are displayed, revealing the presence of nanostructures in historical mortars, shedding light on their properties and their specific production technology. The use of TEM in the evaluation of the development of advanced nanomaterials, designed in particular for conservation treatments, such as consolidation and antifouling action, is also recorded.M. Stefanidou and E. Pavlidou investigated the role of SEM-EDX in the characterization of historical mortars, not only in relation to their main components but also in relation to their microstructure. It is demonstrated that important information about production technology of mortars and their preservation state can be acquired by SEM utilization. Furthermore, new repair mortars are to be designed with corresponding and compatible properties to the historical ones. In such cases, SEM results about raw material suitability, effectiveness evaluation of nanoparticle addition, and self-healing processes of special mortar additives are presented.In the two following works of L. Ferrazza et al. and A. Gil-Torrano et al., the numerous ways that SEM-EDX can be coupled with several other techniques, in order to ensure the protection of built heritage, are demonstrated.In particular, L. Ferrazza et al. focus on the conservation study of the facade of the Arciprestal Church of Santa Mar\u00eda de Morella in Spain. A vast array of techniques such as ground penetration radar (GPR), X-ray fluorescence (XRF), optical microscopy (OM), X-ray diffraction (XRD), SEM-EDX, and Fourier transform infrared spectroscopy (FTIR) are used for building material characterization and decay diagnosis, while assessment of cleaning and consolidation treatments on architectural surfaces of both stones and polychromes is included. The multidisciplinary character of this work and the importance of SEM-EDX in investigating crusts, patina, and especially pigments and their substrates are highlighted.rd to 4th century AD) and the Caliphal era (10th to 11th century AD). The similarities and variances between the employed materials and technologies of the different eras' wall paintings are investigated through the combined use of OM, SEM-EDX, XRD and \u03bc-XRD, wavelength-dispersive X-ray fluorescence (WD-XRF), and FTIR. The secco technique is used for the manufacturing of both wall paintings under investigation, while the wall paintings of the Roman era present more preparatory layers in comparison to the Arabic ones. Furthermore, red earth and calcite are detected as red and white pigments in the case of Roman paintings, whereas red ochre and calcite are identified as red and white pigments in the case of Arabic paintings.Correspondingly, A. Gil-Torrano et al. investigate the archaeological site of Cercadilla in Cordoba, Spain, regarding the preservation state of wall paintings of the Roman era and heat resistance, whereas microstructure characteristics are examined by SEM-EDS.Last but not least, S. Nicolopoulos et al. demonstrate a combination of ADT and ASTAR orientation/phase mapping techniques in TEM to investigate various materials with emphasis on pigments used in different artefacts, such as amphoriskos, glass tesserae, and Mayan mural paintings. Nanocrystalline mapping of pigments is achieved using the abovementioned TEM electron crystallography techniques. Ancient composite materials are thus thoroughly investigated, since chemical and structural information is acquired at nanoscale. Through this work, multiple scaled impacts are evident regarding the ways of how technological evolution can significantly enhance our knowledge in several areas of interest for the protection of cultural heritage.The protection of built heritage is a vast and fascinating research field where many questions still have to be answered regarding the properties of building materials, as well as the weathering processes that govern their life cycle. Answering these questions will inspire scientists to pioneer in designing novel conservation/restoration and repair materials that will ensure structures' protection and sustainability.In this context, scanning microscopy techniques play a key role in establishing methodologies and protocols towards revealing the past and planning the future. Technological advances further evolve the capabilities and the applicability of scanning microscopy techniques contributing to the sustainable protection of built heritage.Antonia MoropoulouElisabetta ZendriPilar OrtizGeorge Fourlaris"} +{"text": "The Health Resources and Services Administration recently announced a notice of funding opportunity (NOFO) for the Geriatrics Academic Career Award Program (GACA). The purpose of the GACA program is to support the career development of individual junior faculty in geriatrics as academic geriatrics specialists and to provide clinical training in geriatrics, including the training of interprofessional teams of health care professionals. The GACA program is a mentorship model where the awardee is guided through a faculty career development plan, with required project deliverables, over the course of four years. The GACA supported 222 junior faculty members between 1998 and 2006, when it was discontinued. This initial NOFO provides funding for up to 26 awardees in the schools of allopathic medicine, osteopathic medicine, nursing, social work, psychology, dentistry, pharmacy, and allied health. This presentation will provide an up-to-date overview of the program with awardee demographics and project deliverables."} +{"text": "Cancer on the African continent is quickly becoming an overt public health crisis due to an aging population and changes in lifestyle. The World Health Organization (WHO) states that a national cancer-control programme should aim to reduce cancer incidence and mortality and improve quality of life of cancer patients, through a national cancer-control plan (NCCP) that is systematic, equitable and evidence-based. Despite this, only 11 countries in Africa have a current NCCP. Participants in a US National Cancer Institute-supported, multi-year, technical assistance programme for cancer-control planning noted three main opportunities to improve how plans are created and implemented: 1) mobilisation of resources and partners for plan implementation; 2) accurate surveillance data to promote better resourcing of NCCPs; and, 3) sustainable and innovative partnership models to strengthen capacity to implement NCCPs. Most countries in the region face similar challenges in the development and implementation of an NCCP, including inadequate human, technical, and financial resources. Collaborative partnerships increase access to evidence-based cancer-control planning tools, mentoring and technical assistance, and have the potential to bridge the capacity gap and catalyse better implementation of NCCPs. Challenges can be overcome by better leveraging these opportunities to address the gaps that inhibit cancer control in Africa. Cancer on the African continent is quickly becoming an overt public health crisis due to an aging population and changes in lifestyle, including increased tobacco and alcohol use, rising obesity and physical inactivity. Unchecked, the burden of cancer in low- and middle-income countries will increase by more than 60% by 2030 , plaguinThe World Health Organization (WHO) states that a national cancer-control programme should aim to reduce cancer incidence and mortality and improve quality of life of cancer patients, through a national cancer-control plan (NCCP) that is systematic, equitable and evidence-based . A comprEven with multiple calls for strengthened national cancer-control planning measures, a 2018 analysis of the International Cancer Control Partnership (ICCP) portal shows that a total of only 11 countries (20.1%) in the Africa region have a current NCCP . Given tBuilding on the US government\u2019s domestic engagement in comprehensive cancer-control planning , the US In order to understand the challenges and priorities in cancer-control planning for curriculum development purposes, CGH administered baseline surveys to participants of the 2017 ICCLF (response rate 73%) and 2018 ECHO (response rate 77%), prior to each programme's launch, via Google Forms. The most-often identified challenges and priorities can be seen in Participants identified resource and partner mobilisation for NCCP implementation as two of the leading challenges they face . DespiteAn additional barrier is the organisation of national cancer programmes within ministries of health (MoH). In most African countries, the structure is inconsistent, creating an obstacle to mobilise resources and partners for NCCP implementation. National cancer programmes are, at times, part of the NCD programme under the coordination of a cancer-control officer or an NCD programme officer , a standalone cancer-control programme, or one divided across MoH units .Unlike the global HIV/AIDS response, a centralised pool of financial and technical resources does not exist for cancer and other NCDs. Therefore, MoH technical officers must mobilise resources and engage non-governmental implementing partners as a crucial step for successful NCCP implementation. The suboptimal level of coordination of cancer prevention and control within most ministries of health in Africa means that agreement on priorities, which is necessary for partner and stakeholder engagement, is less efficient and thus, impacts funding for the NCCP.Opportunities to make progress in this critical area are emerging. The increasing number of health economists now working on NCDs can support governments in assessing the cost and affordability of interventions to prevent and control cancer and other NCDs . The WHOCancer Incidence in Five Continents (Volume XI), only seven population-based cancer registries from six African countries had sufficient data quality and capture [The collection of data to inform NCCP efforts was the top challenge identified by 2017 ICCLF participants . Robust capture for inclGovernments across Africa have an opportunity to prioritise and resource population-based cancer registries to enable ministries of health to develop, cost, resource, implement and evaluate NCCPs in a way that truly benefits populations. Nigeria is an example of where sustainable and long-standing cancer registries, coordinated under the Federal MoH, have provided national estimates of the increasing cancer burden which allowed decision-makers to subsequently inform policies and most recently, the National Cancer Control Strategy (2018\u20132022). The ability to prioritise which cancers to address will allow for strategic partner engagement toward effective implementation .A primary challenge for cancer-control planning in Africa, and perhaps the most commonly identified in the literature, is the lack of essential health system capacity and infrastructure needed to prevent, detect and treat cancer , 21. HumThere is growing momentum among medical schools and universities in Africa to develop specialised oncology-related diploma courses and fellowships , 23. WhiCancer-care-focused partnerships such as the Academic Model Providing Access to Healthcare in Eldoret, Kenya, Partners in Health in Butaro, Rwanda, and the Fred Hutchinson Cancer Research Center Partnership with the Uganda Cancer Institute, show how a long-standing commitment to collaboration and partnership , 28 can Lancet Oncology analysis of national cancer-control plans, led by the ICCP, WHO, and Union for International Cancer Control, reveals that the number of plans worldwide has increased and the focus is now on successful plan implementation. The authors cite examples from Africa where planning has led to action, both in cervical cancer screening and in population-based cancer registries [Finally, while this paper is focused on challenges specific to cancer-control in Africa, there are lessons to be learnt globally from similar challenges and solutions in other regions, where building research networks with a focus on implementation science questions to inform effective programming have propelled the effective implementation of national cancer-control plans . Additiogistries . These eReduction in mortality and morbidity from cancer are keys to the attainment of the WHO voluntary global target of 25% reduction in premature mortality from NCDs by 2025 as well as the Sustainable Development Goal target of a one-third reduction in premature mortality from NCDs by 2030. In order to achieve cancer-related global targets, a well-organised and resourced NCCP, guided by accurate data on the burden of cancer and related risk factors, is necessary. Most countries in the region face similar challenges in the development and implementation of an NCCP, including inadequate human, technical and financial resources. Collaborative partnerships increase access to evidence-based cancer-control planning tools, mentoring and technical assistance, and have the potential to bridge the capacity gap and catalyse better implementation of NCCPs. There is tremendous opportunity in the continued support of these kinds of partnerships for cancer-control programmes in Africa.The authors have no conflicts of interest to disclose.This project has been funded in whole or in part with US federal funds from the US National Cancer Institute, National Institutes of Health, and under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services or National Institutes of Health, nor does mention of trade names, commercial products, or organisations imply endorsement by the US government.KD wrote or co-wrote the introduction, background and methods, challenges, and opportunities sections, edited and revised the paper. MKC co-wrote the background and methods, challenges, opportunities, edited and revised the paper. PB wrote or co-wrote the conclusion and background, edited, and revised the paper. ELT edited and revised the paper."} +{"text": "The linkages between ecosystem services and poverty alleviation, however, are complex and poorly understood. In many cases, gains in well-being have gone hand-in-hand with rising inequalities and increasing vulnerability of the more marginalised to environmental shocks and stresses. The Ecosystem Services for Poverty Alleviation interdisciplinary research programme aimed to work towards the Sustainable Development Goals2 by giving decision-makers and natural resource users the evidence they need to address the challenges of combining sustainable ecosystem management with poverty reduction. ESPA set out to:The 2005 Millennium Ecosystem Assessmentbuild a strong evidence base on how human use interacts with ecosystem services, and their dynamics and management;develop innovative, interdisciplinary research and methodologies, so decision-makers may predict socio-ecological responses to complex social and economic trends;get research into practice, by engaging with policymakers, practitioners and decision-makers;use international research partnerships to build research capacity around the global South.The scope of ESPA\u2019s research into different dimensions of ecosystem services, and the social and ecological implications of their management, are summarised in This collection highlights a series of ESPA-funded projects contributing original, interdisciplinary datasets and analytical approaches on social-ecological systems in Asia, Africa and Latin America. They cover ecosystems ranging from montane headwater catchments, through arid and semi-arid rangelands, mesic farmlands and wetlands, to coastal deltas, mangrove and island forests. This collection makes available to a wider scientific audience a set of rigorously compiled and carefully curated interdisciplinary datasets characterising interactions in these social-ecological systems. Each dataset offers considerable potential for further analysis both in its own right and in conjunction with new data, not least as baselines for future studies of the impacts of environmental change and interventions. The data descriptor papers presented here fall into two categories. The first focuses on drivers and outcomes of variability and change in the biophysical dimensions of key social-ecological systems, while the second documents the social implications of these changes.et al.3 addresses measurement of the biophysical features underpinning social-ecological systems, in order to inform land use planning and evaluate the impacts of environmental interventions. This paper presents hydrological measurements from multiple paired catchments, encompassing a wide range of ecosystem types and management systems across three major biomes of the Andean montane region and three countries . By comparing intervention and control sites, the study was able to attribute observed effects to particular land use changes, restoration or water harvesting interventions. Datasets document rainfall, streamflow, and catchment shape, drainage, elevation, topography, soils, land cover and land use, including derived indices of change, under different management approaches, in water yield, water balance, streamflow magnitude, timing and flashiness; and ratio of baseflow to total flow. These data can be used to analyse the impact of human activities on watersheds, and to guide decision-making and governance aimed at reducing poverty.Decision-making and resource-use planning need data on changes in environment, resource availability and use, and on the drivers of those changes. The first paper by Ochoa-Tocachi 4, and free prior informed consent procedures adapted to prevailing literacy and local sensitivities.Beyond documenting the spatial and biophysical underpinnings of social-ecological systems, ESPA set out to establish an evidence base on how different groups of people are impacted by and respond to changes in their environment. The second, larger group of papers in this collection deals primarily with datasets reporting the lives, livelihoods and wellbeing of local communities in the face of environmental change or intervention. Stakeholder participation is an essential ingredient of this set of papers. All involve in-depth, two-way participation, with local users shaping the ways research questions are formulated and research undertaken, as well as volunteering the information recorded, and validating those data through their feedback. All employ ethics scrutiny of processes for working with local respondentset al.5 use an initial spatial land cover classification, comprising seven dominant production systems in the Ganges-Meghna-Brahmaputra delta: rainfed or irrigated farming, freshwater prawn or saltwater shrimp farming, and riverine, mangrove or offshore systems. Their household survey datasets then form the basis for analysis of multidimensional wellbeing associated with particular farming, fishing or other livelihoods and social-ecological systems.The different studies illustrate a range of approaches in terms of how to conceptualise relationships between local users and ecosystem services, in terms of research design, and in terms of practical purpose. Adams et al.6 apply a classic formal agricultural research experimental design to allow causal attribution. An initially purposive sample design to choose intervention and matching control sites is followed by random sampling stratified by location and involvement in the subsidy programme, drawing on formal lists of farmers. Where formal lists are not available, projects have to undertake baseline surveys to establish sample frames. These baseline datasets are themselves a rich source of possible investigation. For example, the data collected by Bluwstein et al.7 allow for analysis of the change in wealth rank through time for 13578 Tanzanian households, potentially contributing to our understanding of changing prosperity in rural Tanzania. Subsequent in-depth survey sample datasets include a couple of thousand households.In the other papers, household survey datasets are used to evaluate implications of specific ecosystem services interventions, including conservation agriculture and wildlife management areas, and are structured accordingly. In their study of subsidy payments in Malawi, Bell 7 or asset indices); natural resource use practices; livelihoods and income; perceptions of wellbeing and of its change, both through time and with respect to specific interventions; and in one case5 biomedical status ; perceptions of the interventions and of the benefits (or disadvantages) of involvement. Each of these papers represents a useful baseline dataset against which the implications of future environmental change in general and of current environmental interventions in particular can be measured.Different studies all follow similar principles of questionnaire, survey and interview design, building on mixed methods and using qualitative approaches to establish context, identify key issues and variables to be evaluated. Local language issues are addressed in different ways according to circumstances, but all rely on extensive discussion, training and role play to ensure data collectors share the same in-depth grasp of underlying principles, general thrust and specific meaning of individual terms used and questions asked. All consider quality control issues, with built in checks at various stages. The different studies capture different but overlapping sets of key variables according to their research question. All record household demographic composition and socioeconomic status .Publisher\u2019s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations."} +{"text": "Given a growing body of evidence for the developmental relevance of the perceived experience of aging and for the presence of interindividual variability in the way people experience aging, this symposium examines the determinants and outcomes of various subjective aging constructs. This session will explore the role of various psychological variables in explaining variability in subjective aging experiences. Consequences of various subjective aging concepts on cognitive functioning, emotional and physical well-being will also be discussed. The first two presentations examine Attitudes Toward Own Aging (ATOA). Kornadt, Siebert and Wahl will address the developmental co-dynamics of personality and ATOA across the second half of life. Siebert and Wahl will examine the associations of ATOA with subjective and objective cognitive functioning. The last two presentations focus on awareness of age-related change (AARC). Sabatini, Silarova, Collins, Martyr, Ballard, Anstey, Kim & Clare will present findings from a systematic-review and meta-analysis synthesizing and quantifying associations of awareness of age-related change (AARC) with emotional and physical well-being and cognitive functioning. Finally, Rothermund and de Paula Couto will show how both the experience of positive and/or negative changes (gains and losses) and the presence of positive and/or negative age stereotypes predict individual\u2019s attributions of change to age. This last presentation will also examine how together the presence of change and attribution of change to age predict developmental outcomes. The symposium will conclude with summarizing remarks from the discussant who suggests possible directions for future research on determinants and outcomes of perceived experience of aging."} +{"text": "This narrative review aimed to identify and categorize the barriers and facilitators to the provision of brief intervention and behavioral change programs that target several risk behaviors among the Indigenous populations of Australia, Canada, and New Zealand.A systematic database search was conducted of six databases including PubMeD, Embase, CINAHL, HealthStar, PsycINFO, and Web of Science. Thematic analysis was utilized to analyze qualitative data extracted from the included studies, and a narrative approach was employed to synthesize the common themes that\u00a0emerged. The quality of studies was assessed in accordance with the Joanna Briggs Institute\u2019s guidelines and using the software SUMARI \u2013 The System for the Unified Management, Assessment and Review of Information.Nine studies were included. The studies were classified at three intervention levels: (1) individual-based brief interventions, (2) family-based interventions, and (3) community-based-interventions. Across the studies, selection of the intervention level was associated with Indigenous priorities and preferences, and approaches with Indigenous collaboration were supported. Barriers and facilitators were grouped under four major categories representing the common themes: (1) characteristics of design, development, and delivery, (2) patient/provider relationship, (3) environmental factors, and (4) organizational capacity and workplace-related factors. Several sub-themes also emerged under the above-mentioned categories including level of intervention, Indigenous leadership and participation, cultural appropriateness, social and economic barriers, and design elements.To improve the effectiveness of multiple health behavior change interventions among Indigenous populations, collaborative approaches that target different intervention levels are beneficial. Further research to bridge the knowledge gap in this topic will help to improve the quality of preventive health strategies to achieve better outcomes at all levels, and will improve intervention implementation from development and delivery fidelity, to acceptability and sustainability. Historical commonalities in colonization, assimilation, and ongoing socio-economic disadvantages have made the Indigenous populations of Australia, Canada, and New Zealand more vulnerable compared to their non-Indigenous counterparts, and they experience higher rates of chronic disease risk factors , 2. FromOf significance, the clustering of such determinants tends to be more prominent in socioeconomically-disadvantaged groups, such as Indigenous populations, and the synergistic interaction of such risk factors has been shown to be responsible for detrimental health outcomes including elevated morbidity and mortality among these population groups , 9. As sThere is, indeed, growing evidence highlighting the effectiveness of multiple health behavior change (MHBC) interventions . Among tTherefore, identifying the barriers and enablers to the successful implementation of these beneficial preventive strategies in the three countries, sharing similarities in Indigenous history, health system governance, constitutional agreements, and recognition from the state or provincial governments , 15, shoThe primary objective of this narrative review was to identify the barriers and facilitators to implementing brief intervention and behavioral change programs that target several risk behaviors among the Indigenous populations of Australia, Canada, and New Zealand, and to portray the current state of knowledge on this topic In addition to the highlighted importance of such lifestyle behaviors in the prevention of chronic disease development, the major focus of this review on lifestyle risk factors was in line with the objective of the Queensland Health Aboriginal and Torres Strait Islander Brief Intervention Training Program (B.strong), developed by Menzies School of Health Research . B.stronPreferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines.The review was undertaken in accordance with the With the assistance of a librarian, six electronic databases were searched: PubMed, Embase, CINAHL, HealthStar, PsycINFO, and Web of Science. The search consisted of keywords and subject headings, the details of which are included in an Additional\u00a0file\u00a0Conduct of the search across the six databases retrieved a total of 741 citations.n\u2009=\u20092). Studies were included if (1) they were published in peer-reviewed journals from 2007 to 2018; (2) they discussed at least one facilitator or barrier in terms of brief intervention implementations that addressed SNP risk behaviours; and (3) they included Indigenous peoples in Australia, Canada, or New Zealand. To ensure rigor and relevance, the selection of interventions was guided by the definition of brief intervention by Nilsen et al. where \u2018brief intervention\u2019 encompasses any preventive, patient-focused, and motivational counselling that is performed by healthcare professionals in short timespans, aimed at changing behavioral risk behaviours [A total of 75 peer-reviewed journal articles was selected following the initial abstract and title screening. An additional hand search of bibliographies of articles retrieved from the search was carried out to identify other relevant publications on the subject the study population was not exclusive to Indigenous peoples of any of the three countries; or (2) they did not present MHBC programs .The search identified a large gap in brief intervention studies in Canada and New Zealand, although the same definition of brief intervention is used in these countries. Following consultation with Indigenous health researchers in both Canada and New Zealand, two common explanatory themes emerged based on their expert opinion and on our thorough thematic analysis of the selected studies: (1) although many similar programs may run across countries with Indigenous peoples, there is a large gap in academia in terms of research and publication of peer-reviewed evaluations of such interventions; (2) brief intervention programs in Canada appear to be mostly focused on substance abuse and alcohol management programs.Thus, to include relevant findings from those countries, and to address the scarcity of such programs in terms of the type of intervention in Canada and New Zealand, the search also included studies that focused on community-based and/or family-based interventions that met the same inclusion criteria, if the components of the programs were similar to those for brief interventions. Importantly, this decision drew upon the findings of a study highlighting the effectiveness of community-level strategies in targeting SNP risk factors in comparison with individual-level programs among Indigenous populations .Overall, 22 articles met the criteria for full text review. A sensitive and comprehensive review was conducted of these articles by the authors to ensure their rigor and relevance in meeting our review criteria, and this yielded nine articles for the review Fig.\u00a0. StudiesThe quality of studies was appraised in accordance with the Joanna Briggs Institute (JBI) guidelines, and by utilizing the JBI System for the Unified Management, Assessment and Review of Information (SUMARI) .Thematic analysis was used to synthesize findings and a narrative approach was used to present findings in accordance with the JBI guidelines . To enhaTable\u00a0Studies were categorized by the intervention level reported on in the study. Based on the characteristics of the included studies, the three intervention levels were identified as (1) individually-based brief interventions, (2) family-based, and (3) community-based behavioral interventions which targeted more than one of the chronic disease risk factors of smoking, nutrition, and physical activity. The priorities and preferences of Indigenous populations with regard to MHBC strategies were also presented in a separate category as they could be applied to all three intervention levels while also providing insights into the analysis of the barriers and enablers.One study used a mixed-methods approach to evaluate the performance and organizational capacity of health services in delivering brief interventions on smoking, nutrition, alcohol, and physical activity (SNAP) risk factors across four Aboriginal and Torres Strait Islander medical services in Queensland . Study mThis study found significant inconsistencies and poor quality in the recording of SNAP risk factors and their assessment measures in medical charts . In addiAnother study reviewed brief intervention resource kits targeting SNAP risk factors for Indigenous Australians to assess the content and quality of such resources . The stuCanadian research found that family-based collaboration models were effective in improving the health of an individual within a group (a family) . This isIn New Zealand, a health promotion program called REPLACE was developed to improve healthy lifestyles of Maori populations. Hamerton et al. , presentThe approach recognized the large role small lifestyle changes could play in people\u2019s quality of life over time. Process and short-term outcome evaluation of the intervention showed successful changes at individual, family, and community levels. The evaluation method fostered a face-to-face approach among participants, stakeholders, and project coordinators, and qualitative data were collected over a two-year period by means of participant observation, surveys and interviews, holding focus groups, and monthly staff meeting reports . The majThe Vanguard study was a pilot study of a cohort of 160 Maori participants in the New Zealand Maori Community Health Worker (MCHW) intervention, Data collection was conducted both prior to and during the MCHW intervention. The major study was aimed at improving lifestyle risk factors for diabetes . The intn\u2009=\u2009160) showed a significant weight reduction for participants over the course of the intervention (189\u2009days), compared with baseline data. Several facilitators contributed to the high acceptability of this program among the Indigenous population. First, the intervention was promoted through media, cultural events, and by the majority of the community members. The major focus in intervention delivery was on building trust and respecting family and community relationships. The core of the intervention was based on the key \u2018message\u2019 approach - created to set small success points to further improve perceived control over multiple lifestyle changes. Also, the design of the study included determining barriers and solutions to facilitate such changes. The promotion of preferred types of physical activities (identified by the community) was another enabler for the observed success rates of the program. However, conflicts existed in terms of participants\u2019 dietary preferences (higher fat and protein than recommended in guidelines) and their macronutrient components [The results of the pilot study conducted on the initial study participants (hydrate) .Ngati and Healthy intervention in New Zealand was a community-led diabetes prevention healthy lifestyle intervention program aimed at modifying high risk behavioral factors in areas of physical activity and nutrition: promoting weight loss, increasing exercise and adoption of healthy eating habits over a period of 2\u2009years . The majA Canadian study evaluated the effectiveness of a school-based intervention (Actions Schools! BC) targeting physical activity and nutrition among Indigenous children and youth in three remote Indigenous communities of British Columbia (Canada) . EmployiHealthy Foods North (HFN) was a community-based, multi-institutional intervention to promote healthy lifestyles among the Indigenous populations of the Canadian Arctic (four interventions and two comparison groups in Nunavut and Northwest Territories) . This prA recent Australian cross-sectional study was conducted to identify the determinants of acceptance of MHBC programs for an Indigenous population in Australia. The study had three main objectives: (1) assessing readiness towards high risk lifestyle changes; (2) acceptability of types of MHBC models: synchronously, in a sequence, or separately; (3) preferences for types of support programs, and the socioeconomic determinants responsible for the preferred choices . A totalSurvey results showed that on the client\u2019s readiness to change their lifestyle health behaviors across all risk factors, smoking was the participants\u2019 number one choice for behavior change . Also, tThose who indicated willingness to change at least a single high-risk behavior had a preference for receiving healthcare practitioner help over other types of support, and, in particular, for improving nutrition and physical activity . ReceiviOverall, the findings presented from the reviewed studies highlight the major facilitators and barriers to the implementation of brief interventions that address more than one modifiable risk behavior for chronic disease. Following a thorough thematic analysis, and due to the presence of varying outcome measures for both the quantitative and qualitative data extracted from the studies, the synthesized findings were grouped into four major categories based on the common themes that emerged: (1) characteristics of design, development, and delivery; (2) patient/provider relationship; (3) environmental factors; and (4) organizational capacity and workplace-related factors. To ensure consistency and relevance, the discussion of each theme and sub-theme is supported by data synthesized from the primary studies and their corresponding interventions.To date, in targeting multiple lifestyle modifications, evidence has supported the superiority of behavioral and cognitive methods along with lifestyle counselling over other types of interventions . Some rePriorities and preferences of Indigenous peoples must also be taken into account when considering the target level for a health behavior change intervention. For example, a cross-sectional study that assessed priorities and preferences of Indigenous populations on multiple behavior change found that when Indigenous clients were surveyed about their preferences over the level of support, the majority preferred individual-level supports for SNP health behaviors over family or community level approaches .To analyze the evaluations of design and developmental characteristics of SNAP behavioral interventions among the Indigenous Australian communities, and to assess the interventions\u2019 effectiveness in improving such risk factors, Clifford et al. , conductInvolving communities in the design and planning as pre-implementation steps in developing interventions is a critical factor in ensuring successful delivery and uptake of health promotion programs among Indigenous populations . More spThe Ngati and Healthy intervention, a community-led project which was based on a community development approach and on the collaboration of community health workers and researchers, relied heavily on Indigenous participation and leadership in all phases of the project, including the design and development phase, delivery and implementation . The autHealth promotion programs that are designed and implemented based on Indigenous cultural values have demonstrated higher perceived value among these population groups in targeting behavior change . In addiIn the Vanguard study, the development of intervention constructs based on Maori cultural values, both from the past and the present, was a major contributing factor to the high rate of program acceptability by Maori individuals . FurtherThe quality of design components plays a critical role in enhancing successful implementation . Based oAllocating enough time in primary care visits for health staff to build a relationship with clients can facilitate the delivery of lifestyle brief interventions, and can enhance the assessment of chronic disease risk factors . Both reIn the review of five Canadian community-based interventions for Aboriginal populations including First Nations, Inuits, and Metis, there was no evidence of improved healthy weight outcomes . AlthougIn the HFN project, the results of the study showed that the intervention had a higher impact on healthy eating and behaviors in higher socioeconomic status populations compared with their lower socioeconomic status counterparts . The autIn assessing the organizational capacity of health services to deliver brief interventions for chronic disease risk factors to Indigenous Australians, Panaretto et al. identified several enablers and barriers to the successful delivery of health messages . EnablerOverall, these authors suggest that the barriers could be addressed to a reasonable extent through the development of assessment tools for modifiable risk factors, specifically nutrition and physical activity, along with appropriate training of staff in the delivery of the most recent state of knowledge that is evidence-based on SNAP risk factors, and by adding Adult Health Checks into the routine delivery of care.A process evaluation found that barriers to the implementation of Actions schools! BC included high staff turnover, limited staff knowledge of healthy lifestyle behaviors, and minimal variation in choices. However, the ease of implementation and participant support were potential facilitators of such programs .Despite employing a thorough and systematically-based method in searching databases, it is possible that this review may not have located all relevant Indigenous health promotion brief interventions from Australia, Canada, and New Zealand. The main purpose of this review was to identify the barriers and facilitators to the implementation of brief interventions that target MHBC in areas of smoking, nutrition, and physical activity among the Indigenous populations of Australia, Canada, and New Zealand. Unfortunately, varying outcome measures in behavioral interventions across the different countries limited any higher level or meta-comparison of such interventions. The level of the intervention also varied across different studies, largely due to the inclusion of community- and family-based interventions in addition to behavioral brief interventions.We note that the specific inclusion criteria employed in this review made the limited pool of studies narrower. Firstly, there was a gap in the literature with regards to Indigenous-specific behavioral interventions. Secondly, the fact that the review looked for interventions that targeted multiple risk factors contributed significantly to the narrow body of literature. Thirdly, no brief intervention study targeting nutrition and physical activity was identified in either Canada or New Zealand (to the knowledge of the authors and the experts contacted). All retrieved brief intervention studies in Canada and New Zealand related to addressing substance abuse and addiction . Lastly, the exclusion of grey literature may have significantly limited the retrieved results since many evaluations of health promotion programs and projects are not published in the peer-reviewed literature. This was a common theme suggested by Indigenous health experts contacted throughout the review.In conducting this research, we found a significant gap in the literature for systematic reviews analyzing multiple health behavior change interventions among vulnerable populations. The findings of this review make a contribution to the evidence relating to Indigenous populations in Australia, New Zealand and Canada. Further research is required to evaluate the effectiveness of brief and behavioral interventions for multiple health behavior change for Indigenous populations at different intervention levels. Findings of such research will assist in the development of recommendations and guidelines to inform policy changes and program funding support, and should facilitate the process of effective brief intervention program design, implementation, delivery, and evaluation.This review aimed to identify the enablers and barriers to the implementation of MHBC interventions among Indigenous populations drawing upon evidence from three countries. The high prevalence of chronic disease risk behaviors among the Indigenous populations has stemmed from the interplay of numerous underlying causes including the unique histories of population groups and the range of ecological, cultural and social determinants of health with different levels of impact. These underlying factors can also directly and indirectly hinder the effectiveness of MHBC interventions. Thus, understanding the interrelationships of barriers and facilitators along with their myriad drivers is essential in developing successful preventive health programs. Also, it is important to recognize that, to target successful and sustainable behavior changes in chronic disease risk factors, single-level approaches and interventions are not sufficient. Importantly, based on the findings from this systematically conducted narrative review, MHBC interventions targeting different intervention levels should be optimized by promoting authentic and effective collaboration of different health and educational sectors, organizations, and community members, with a strong emphasis on Indigenous participation and leadership at all stages of program development and implementation. Adding community-based interventions to target chronic disease risk behaviors could improve the outcome and complement the use of individual-based MHBC brief interventions among Indigenous Australian populations . Lastly,Additional file 1. Search Subject Headings and Term Harvesting Table.Additional file 2. PRISMA 2009 Checklist."} +{"text": "In its 2017 report on the status of tuberculosis in the world, the World Health Organization (WHO) estimated that tuberculosis causes about 1.7 million deaths each year, making it the single leading infectious cause of death [A core mandate of WHO is the development of evidence-based policy for public health interventions . The latClinical Infectious Diseases features a series of papers prompted by the scientific debate in the 2017 WHO expert consultation. The authors explore critical issues of uncertainty in tuberculosis therapeutics, some of them of long-standing. Most of the papers refer to findings from hollow fibre infection models (HFIM), which are increasingly employed to investigate the anti-tuberculosis properties of substances at the preclinical stage to complement the more-conventional tools applied to determine drug/regimen efficacy and safety [WHO convened a technical consultation in Geneva in April 2017 to review the latest data on the pharmacology of those tuberculosis medicines used in MDR-TB regimens . The disThis Supplement includes a set of articles coordinated by the University Medical Center Groningen that review the literature on PK/PD data for mainstay components of second-line MDR-TB regimens. These systematic reviews formed part of the preparation for the WHO consultation in 2017, and provide a useful update on the PK/PD parameters that are best correlated with the performance of amikacin, linezolid, and cycloserine .The other papers analyze data from new or completed studies, often employing novel approaches. In 2 separate articles, Deshpande et al and SrivThe exciting new findings in tuberculosis pharmacology and the novel investigative techniques reported in this Supplement are relevant to the continued development of new medicines, both in pre-clinical and clinical studies. Artificial intelligence could help identify complementary medicinal combinations and dosages to optimize the composition of candidate regimens ahead of the start of trials. In clinical practice, PK/PD knowledge is likely to bring the prospect of precision medicine in public health within closer reach of more patients worldwide, especially if linked to drug discoveries and concurrent advances in diagnostics, therapeutics, and digital technologies. The optimization of drug dosages and treatment schedules for drug-resistant tuberculosis require more scientific debate, along with fresh data of better quality from patients receiving treatment. Therapeutic drug monitoring (TDM) may be relevant to MDR-TB care, due to the narrow therapeutic index and inter-patient variation in PK/PD of fluoroquinolones, injectable agents, linezolid, and other second-line tuberculosis medicines. TDM may become more feasible in resource-limited settings with the addition of advancements in specimen transportation and analytic methods based on mass spectrometry. However, the added value of different TDM strategies on clinical outcomes still needs to be confirmed and quantified.The conclusions made in the papers of this Supplement do not represent WHO recommendations on the use of the medicines, or an endorsement of experimental medicines, regimens, dosages, or new methods of diagnosis. Nevertheless, in the absence of a more robust evidence base from trials and other studies, these PK/PD updates may help researchers to optimize their efforts and inform health care practitioners to assist them in making better decisions in the clinical management of tuberculosis. This information also serves as a valuable background to the ongoing updates being made by WHO to its MDR/RR-TB treatment policies ."} +{"text": "Background: The expert panel that conducted the Assessing Surgical Site Infection Surveillance Technologies (ASSIST) project elaborates on the key findings of the health technologies assessment (HTA) report in a series of articles addressing topics from workflow challenges to implementation strategies to new big data analytics tailored to incorporate serial patient-generated health data (PGHD).Conclusion: By reporting on the methodology, with an emphasis on stakeholder engagement, the ASSIST investigators provide the basis for a future deep dive into the next phase of PGHD integration into surgical site infection (SSI) surveillance. Star Trek are now second nature to digital natives, who bring their own devices to healthcare with the expectation that providers will review patient-generated health data (PGHD) and engage via new communication channels. It is now possible to offer expanded, personalized care to patients after surgery, using new data streams and data types via mobile devices to facilitate remote patient monitoring. One of the most compelling use cases for post-operative mobile health tracking is the triage of surgical sites for evidence of surgical site infection (SSI) through review of serial incision photography and symptom reporting.The adoption of smartphones, texting, and patient portals for post-operative care coordination present both challenges and opportunities to the surgeon. Real-time communications that were once the fantasy of Dick Tracy and Although the current standard of care for SSI diagnosis requires in-person physical examination of the surgical site, patient-generated photographs are increasingly submitted to and reviewed by surgical providers via e-mail, text messaging, and electronic health record-based patient portals. Although the current use of telemedicine for post-discharge surgical care has been reviewed systematically, the specific use of mHealth for SSI surveillance and the process of work associated with this activity is highly variable and generally unacknowledged in the medical literature. In September 2017, the Safety and Healthcare Epidemiology Prevention Research Development (SHEPheRD) program [www.cirg.washington.edu/assistPSAGreport [In year one, the ASSIST investigators completed a literature review and a landscape analysis of apps directed specifically at post-operative incision monitoring. Through this initial work, the group also developed a network of stakeholders and conducted key informant interviews to gain additional perspective on real-world use. In May 2018, the group hosted a one-day Patient-Generated Health Data Stakeholder Advisory Group workshop to seek feedback from key opinion leaders on the findings from the HTA process. A report from this workshop is available online at AGreport .Surgical Infections, the expert panel that conducted the ASSIST project elaborates on the key findings of the HTA report in a series of articles addressing topics from workflow challenges to implementation strategies to new big data analytics tailored to incorporate serial PGHD. Acknowledging the rapid development cycle used in design and deployment of mHealth apps, the ASSIST investigators concede that any report from a defined period of time can best be regarded as a biopsy, as the field continues to grow unabated. Even since the conclusion of the project, new clinical trials of mHealth apps for post-operative care have been presented [In this special issue of resented and publresented , and a cresented .The number of mHealth apps increases exponentially each year, and as new apps emerge, older ones may mature and expand or regress into the past with little usage or impact on patient care. Furthermore, some of the apps reviewed may never advance to commercialization, remaining research endeavors for their whole lifespan. But these orphan apps have value, in that the process of development, the features contained, and the implementation trials all frame lessons for future app design, integration and dissemination. Additionally, the data collected can serve as fuel to drive innovation in analytic methods and to incorporate PGHD, especially incision images, into the clinical and surveillance definition standards for SSI. Finally, by reporting on the methodology, with an emphasis on stakeholder engagement, the ASSIST investigators provide the basis for a future deep dive into the next phase of PGHD integration into SSI surveillance.Heather Evans, Medical University of South Carolina; William Lober, University of Washington; Danielle Lavallee, University of Washington; Sheri Chernetsky Tejedor, Emory University, Centers for Disease Control; E. Patchen Dellinger, University of Washington; Traci Hedrick, University of Virginia, Shuai Huang, University of Washington; Dan Pollock, Centers for Disease Control and Prevention; Aven Samareh, University of Washington; Robert G. Sawyer, Western Michigan University; John Semple, University of Toranto; Jyotirmay Sharma, Emory University; Elizabeth Wick, University of California San Francisco; Jenney Lee, University of Washington; Sarah Lawrence, University of Washington."} +{"text": "Elder mistreatment (EM) and the magnitude of its relationship to anxiety may vary depending on definitional criteria. We leveraged data from the PINE Study, a study of 3,157 Chinese older adults in Chicago. EM was measured by 56 items on psychological, physical and sexual mistreatment, caregiver neglect and financial exploitation subtypes. Least restrictive, moderately restrictive, and most restrictive definitions of EM were constructed. Symptoms of anxiety were measured by the Hospital Anxiety and Depression Scale. Least restrictive , moderately restrictive , and most restrictive definitions of EM were all significantly associated with the likelihood of experiencing any anxiety symptoms. The magnitude of associations between EM and anxiety symptoms vary based on strictness of the EM definition. Future research should explore the potential causal relationships between EM and anxiety through longitudinal data."} +{"text": "Cystic echinococcosis (CE) is endemic in many regions of Central Asia putting up almost 58% of population at risk including areas of Mongolia, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, Afghanistan, Iran, Pakistan and western China . PakistaCystic Echinococcosis (CE) is responsible for over US$ 3 billion in expenses globally every year , and theIn Pakistan, lack of research data at molecular and epidemiological level of CE necessitates more focus on this area of research. To best of our knowledge, published data to date show 1611 CE cases in humans from different cities of Pakistan. These published reports are mostly based on data obtained from different areas of the country . There iLimited epidemiological data on CE impedes in devising effective management strategies for its control. Recently a useful ultra-sound-based study of latent CE and AE cases in rural parts of Romania, Bulgaria, and Turkey was reported which adds to the knowledge of global epidemiology of these diseases consisting of 13 countries was established in Chengdu, China in 2017 , but unfMost of the population in Pakistan lives in rural area with unhygienic life styles. If such increasing burden of the disease is left un-checked, it would pose greater threat to animal and public health. The international research cooperation is a needed act of time to combat and root out this silently evolving neglected tropical disease. The seriousness of issue needs to be addressed by international community to make a point for effective control strategies on regional and global level."} +{"text": "Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. Published 20, March 2018The affiliation of Luis A Diaz was incorrect. The correct affiliation is: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, United States. In addition, Luis Diaz would like to declare the following for his competing interests statement:Luis A Diaz (LAD) is a member of the board of directors of Personal Genome Diagnostics (PGDx) and Jounce Therapeutics. LAD holds equity in PapGene, Personal Genome Diagnostics (PGDx) and Phoremost. He is a paid consultant for Merck, PGDx and Phoremost. LAD is an inventor of licensed intellectual property related to technology for ctDNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University. These licenses and relationships are associated with equity or royalty payments to LAD. The terms of all these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. In addition, in the past 5 years, LAD has participated as a paid consultant for one-time engagements with Caris, Lyndra, Genocea Biosciences, Illumina and Cell Design Labs.The article has been corrected accordingly."} +{"text": "For more than 40 years, under the leadership of four editors and two publishers, The International Journal of Aging and Human Development (IJAHD) has featured multidisciplinary scholarship related to aging processes and older adults. With the publication of eight issues a year, with over 800 pages of scientific content, the IJAHD places emphasis upon psychological and social studies of aging and the aged. However, the Journal also publishes research that integrates observations from other disciplines that illuminate the \"human\" side of gerontology. A more recent focus includes midlife development, as well. About half (47%) of the publications in the IJAHD are from international colleagues. This presentation will discuss tips for both international and US-based scholars for ensuring timely reviews and positive decisions for manuscript submissions, including such areas as key words, suggesting unbiased reviewers, formatting, writing mechanics, clearly-articulated methods, and a sound theoretical basis."} +{"text": "Furthermore, populations of African ancestry are substantially under-represented in global research of neuropsychiatric genetics.10 Training events, online courses, and workshops have provided unprecedented learning strategies for medical, bioinformatics, and public health education in LMICs. However, most of the existing training components are often developed without input from prospective trainees, not specifically focused on neuropsychiatric genomics, and convened over a restricted time period. Therefore, a tailored approach, wherein researchers from the targeted populations continuously participate in defining neuropsychiatric training needs, might add value to the established methods through ensuring ownership and effectiveness of research training programmes.To date, advancements in neuropsychiatric genetics research in sub-Saharan Africa have been limited by low capacity\u2014funding availability, appropriate infrastructure, and qualified researchers are under-represented in African institutions compared with counterparts in high-income countries (HICs). To improve representation of African institutions in neuropsychiatric genetics research, researchers and funding bodies should prioritise projects involving collaborations between institutions in HICs and LMICs that contain a capacity-building component. Initiatives such as Human Hereditary and Health in Africa (H3Africa), the International Brain Research Organization (IBRO), and the Wellcome Trust Developing Excellence in Leadership, Training, and Science Initiative (DELTAS) programme have been invaluable in building these collaborations and in providing genomics-related research training opportunities for researchers from African institutions.The Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER) programme seeks to address these limitations. GINGER is a collaboration between the Stanley Center for Psychiatric Research at the Broad Institute of Massachusetts Institute of Technology and the Harvard T H Chan School of Public Health, and several academic institutions in sub-Saharan Africa . Comprising 17 investigators from these countries, GINGER aims to enhance the capacity of neuropsychiatric genetics research in Africa by training early-career researchers in genetics analysis, psychiatric phenotyping, epidemiology, bioinformatics, biostatistics, ethics, and manuscript and grant writing.A unique feature of the 2 year GINGER programme is the active participation of the fellows and African mentors in selection of programme topics on the basis of the individual and collective needs of the fellows and their host institutions. Intra-African networking and collaborations are strongly encouraged to expand the training and capacity-building of the first GINGER cohort and to contribute to innovative research driven by African investigators. Furthermore, the initiative seeks to increase the awareness of key stakeholders and policy makers about the burden of neuropsychiatric disorders in sub-Saharan Africa.The first cohort of GINGER fellows aims to establish an interdisciplinary group of African researchers, with the potential for sustainability beyond GINGER. Through continued conversations, skills building, and collaborative efforts between African institutions, this group will be equipped to produce first-class research equal to that produced in HICs. This Comment, therefore, serves as a call to action to develop and reaffirm the relationships needed to study neuropsychiatric genetics research in Africa. Improved characterisation of the prevalence and molecular causes of neuropsychiatric disorders in Africa might lead to development of population-specific and individual-specific treatment methods. These discoveries might ultimately improve global health-care strategies."} +{"text": "As America ages, an increased interest has been placed on understanding the development and maintenance of autonomy in later life. This is of particular importance given the impact of autonomy on vitality, well-being, and mood within older adults . However, the research examining which aspects of autonomy directly impact successful aging remains underexplored. As such, the current study utilizes the Functional Autonomy Measurement System (SMAF) to better understand which facets of autonomy promote life satisfaction in older adults. Data included assessments of the Functional Autonomy Measurement System and data was derived from the Survey of Midlife in the US Database (MIDUS 3). Participants were primarily White/Caucasian (88.7%) and female (54.0%); with a mean age of 63.64 years (SD=11.35). A series of hierarchical multiple linear regressions revealed that higher levels of Mental Functions predicted increased life satisfaction scores in models adjusted for age, sex, race, marital status, and education and that higher levels of Communication , Activities of Daily Living , Mobility , and Instrumental Activities of Daily Living also predicted increases in life satisfaction scores but to a lesser extent. The present findings suggest that higher levels of autonomy, both physically and mentally, result in higher satisfaction with life; with perceptions of cognitive independence producing the highest levels. Implications of the current findings include increased understanding of the multifaceted nature of autonomy, and provision of recommendations which could increase autonomous behavior in later life, thus increase life satisfaction and promote successful aging."} +{"text": "Researchers, practitioners and policymakers are daily confronted with multiple and competing situations regarding vulnerable older adults and the complex issues that they face in all aspects of their lives. Challenges can arise in the provision of social services, dispensing justice, conducting research, or addressing legal issues. The purpose of this symposium is to discuss dilemmas that vulnerable older adults and concerned others face by elucidating current and future challenges facing this population, particularly in the realms of compromised health (cognitive impairment); effective status (gender); care arrangements (home and community-based services); and abuse, neglect, and exploitation. Teaster and Anetzberger discuss relevant ethical theories and principles as well as a definition of vulnerability. Santos and Nichols-Hadeed report on ethical issues embedded in vulnerable elders\u2019 cognitive status. Bowland and Halaas highlight the intersection of ethics, gender and vulnerable elders. Niles-Yokum and Beaumaster discuss the nexus of ethics and the provision of home and community based services for vulnerable older adults. Heisler considers vulnerabilities of older adults and ethical challenges when addressing elder abuse. Throughout the papers, we weave the ethical principles of autonomy, beneficence, nonmaleficence, and justice."} +{"text": "Countries in East Asia have the largest aging population in the world. The consequences of aging largely depend on whether it is accompanied by a healthy, active, and high-quality life. This symposium aims to gain a better understanding of aging support and determinants of health in the contexts of two major East Asian countries - China and Japan. We will present new research using data from the Fukui Longitudinal Caregiver Study (FLCS) in Japan, and two most important aging surveys in China \u2013 the China Health and Retirement Longitudinal Study (CHARLS) and the Chinese Longitudinal Healthy Longevity Survey (CLHLS), addressing critical topics including retirement, family care, social mobility, and mortality. Song and Smith investigate the impact of hukou change on mental health in later life. Zang examines the effect of a man\u2019s retirement on his wife\u2019s mental and physical health in China. Zhang et al. explore the determinants of mortality in China by conducting a comprehensive analysis of life-course conditions, community characteristics, biological and physical functioning, and disease burden. Zeng et al. compare demographic, socioeconomic, behavioral characteristics and health phenotypes of centenarians in China and Italy. Wakui et al. focus on the emergence of compound caregiving and the relationship of caregiving status to burden, depression, and social support in Japan. The cross-national comparisons will be informative regarding aging in various contexts. We will discuss the potential for further investigations using population-based aging data from different countries."} +{"text": "This thematic issue on advanced simulation tools applied to materials development and design predictions gathers selected extended papers related to power generation systems, presented at the XIX International Colloquium on Mechanical Fatigue of Metals (ICMFM XIX) organized at University of Porto, Portugal, in 2018. Guest editors express special thanks to all contributors for the success of this special issue\u2014authors, reviewers, and journal staff. Fatigue damage represents one of the most important degradation phenomena which structural materials are subjected to in normal industrial operation, which may finally result in a sudden and unexpected failure/fracture. Since metal alloys are still the most used materials for the design of the majority of components and structures intended to carry out the highest service loads, the study of the different aspects of metals fatigue still attracts the permanent attention of scientists, engineers, and designers.The first International Colloquium on Mechanical Fatigue of Metals (ICMFM) was organized in Brno, Czech Republic in 1968. Afterwards, regular Colloquia on Mechanical Fatigue of Metals started in 1972 also in Brno and were originally limited to participants from the countries of the former \u201cEastern Block\u201d. They continued until the 12th Colloquium in 1994 at Miskolc, Hungary, every two years. After a break twelve years long, the Colloquia restarted in 2006 at Ternopil, Ukraine, followed by the ones in 2008 , 2010 , 2012 , 2014 ,4. The XThis special issue approaches the thematic about the limits of the current generation of materials, which are continuously being reached according to the frontier of hostile environments, whether in the aerospace, nuclear, or petrochemistry industry, or in the design of gas turbines where efficiency of energy production and transformation demands increased temperatures and pressures . At the -Environmental assisted fatigue;-Multi-damage/degradation;-Multi-scale modeling and simulation;-Micromechanics of fracture;-Material defects evolution;-Interactions of extreme environments;-Microstructure-based modeling and simulation;-Fracture in extreme environments;-Probabilistic physics of failure modeling and simulation;-Probabilistic optimization;-Advanced testing and simulation;-Life prediction and extension;-Stochastic degradation modeling and analysis;-Low- and high-cycle fatigue;-Artificial intelligence methods.This issue collects selected papers from ICMFM XIX related This section addresses in brief the scientific papers published in this thematic issue on advanced analytical and numerical simulation approaches applied to materials development and design predictions about power generation systems.Zhang\u2019s group from the Harbin University of Science and Technology, Fudan University and Northwestern Polytechnical University (China) developed a fuzzy multi-extremum response surface method (FMERSM) for the comprehensive probabilistic optimization of multi-failure/multi-component structures, where the probabilistic fatigue/creep coupling optimization of turbine bladed disks was implemented\u2014the rotor speed, temperature, and density as optimization parameters, and the creep stress, creep strain, fatigue damage, and creep damage as optimization objectives .Duda, Pach, and Lesiuk presenteKotch et al. from theLiu et al. suggesteOther study related to the influence of thermal\u2013structural coupling on the blisk low-cycle fatigue life reliability analysis was introduced by Zhang et al. , where tNormally, fatigue crack growth relations are usually presented by using a linear-elastic stress intensity factor range, \u0394K. Lesiuk , from th2O, and PF5 adsorbed on Cu(111) and the geometric parameters of the admolecules were confirmed after structure optimization [Chen et al. group from the Changsha University of Science and Technology and Guangxi University (China) presented a scientific work entitled by first-principles study on the adsorption and dissociation of Impurities on Copper Current Collector in Electrolyte for Lithium-Ion Batteries, where the stable configurations of HF, Hmization .Luo et al. research team applied an innovative surface technology, laser shock peening (LSP), to the dual-phase TC11 titanium alloy to fabricate an amorphous and nanocrystalline surface layer at room temperature, for the ultrahigh strain-rate plastic deformation .Xie et al. have preFinally, a Polish\u2013Portuguese team presenteGuest Editors for this thematic issue are pleased with the final result of the published papers and hope that these scientific works can be useful to researchers, engineers, designers, and other colleagues involved in different thematic aspects of the advanced analytical and numerical simulation approaches applied to materials development and design predictions about power generation systems.Additionally, the Guest Editors would like to express gratitude to all authors for their contributions and to all reviewers for their generous work that is fundamental in the dissemination of the scientific finding.Finally, the Guest Editors would also like to express special thanks to the Editorial Board of Materials international journal for help, support, and patience and for their exceptional contributions during this time."} +{"text": "The NIA/NCI ASPREE (ASPirin in Reducing Events in the Elderly) Study was a landmark RCT of 19,114 healthy adults aged 70 (whites) and 65 (US minorities) in Australia and the US that demonstrated lack of effect of low dose aspirin (LDA:100 mg/d) on the novel primary end point of Disability- Free Survival (life free of disability and dementia) over a mean treatment of 4.7 years. Surprisingly, LDA was associated with a trend toward increased all cause mortality, driven by cancer deaths (results published NEJM September 2018). After the LDA intervention was halted in June 2017, ASPREE was extended as an observational cohort follow-on study, ASPREE-XT, to measure potential delayed LDA effects on ASPREE outcomes. The ASPREE study primary results will be summarized, and the rationale for and performance of the novel DFS geriatric outcome discussed. New results of the analysis of dementia as a secondary outcome will also be presented . We will also examine the unexpected increased all-cause mortality attributed to cancer deaths, despite no significant difference between groups for all incident cancer, and effects of LDA on incident metastatic disease. The important implications of the ASPREE results for prescribing LDA for primary prevention in health elderly will be discussed, and the ASPREE-XT study design and progress described. Lastly, the breadth of the ASPREE sub-studies including the Biobank, Brain Imaging studies and Genomics, and opportunities to access the rich ASPREE data and collaborate with ASPREE investigators will be reviewed."} +{"text": "Clock gene.Investigators from Children\u2019s National Medical Center, Wenzhou Medical University, Virginia Tech, University of Colorado, University of Virginia, Georgetown University, University of Maryland, and Brown University performed transcriptome analysis on human epileptogenic tissue and extended the investigation by creating and testing mouse lines with targeted genetic deletions of the Clock gene.Investigators from Children\u2019s National Medical Center, Wenzhou Medical University, Virginia Tech, University of Colorado, University of Virginia, Georgetown University, University of Maryland, and Brown University performed transcriptome analysis on human epileptogenic tissue and extended the investigation by creating and testing mouse lines with targeted genetic deletions of the Bmal1) had been previously shown to alter seizure threshold in mice, the authors of this article evaluated the expression of the Clock gene in brain tissue from patients with intractable epilepsy. They found decreased CLOCK protein in epileptogenic tissue as compared to control tissue. Next, they generated mouse lines with deletion of Clock in cortical excitatory neurons and found that these mice showed diminished seizure threshold and their excitatory neurons exhibited spontaneous epileptiform discharges. The authors also noticed that flox/floxEmx-Cre;Clock mice have defects in dendritic spines similar to spine defects seen in human epileptogenic tissue and that neurons from both the mutant mice and human tissue show decreased spontaneous inhibitory post-synaptic currents.Because one of the genes that make up the molecular mechanism of the circadian clock .If the loss of The author(s) have declared that no competing interests exist."} +{"text": "PageBreak11th European Congress of Entomology. Maurizio Biondi and Michael Schmitt co-organised the Naples meeting and worked together with Caroline S. Chaboo in the editorial committee for RoC8.Volume 8 of Research on Chrysomelidae (RoC8) presents again examples of the attractiveness and the diversity of Chrysomelidae (sensu lato) as subjects of scientific research. The seven papers included here cover taxonomy, ecology, faunistics as well as phylogenetics. Four of these papers are extended versions of talks presented to the Third European Symposium on the Chrysomelidae, held on 5 July, 2018, in Naples, Italy within the frame of the As with the previous RoC volumes, the team at Pensoft Publishers , especially Yordanka Banalieva, did a wonderful job and made the co-operation of editors and publishers a relaxed and rewarding experience. The editors thank our counterparts at Pensoft for this harmonious collaboration. The editors also thank all authors who submitted their high-quality manuscripts and so made this volume another important contribution towards the science of leaf and seed beetles.th International Symposium in Helsinki (Finland) in 2020 and the 4th European Symposium on Crete (Greece) in 2022. The proceedings of these symposia along with submitted papers on Chrysomelidae sensu lato will be published in subsequent volumes of Research on Chrysomelidae, as special issues of ZooKeys.The series of symposia on Chrysomelidae will continue with the 10Michael Schmitt, Caroline S. Chaboo, Maurizio Biondi"} +{"text": "The number of males diagnosed with prostate cancer (PCa) is increasing all over the world . Most paGenerally, well-differentiated PCa cells are androgen-dependent, i.e., androgen receptor (AR) signaling regulates cell cycle and differentiation. Loss of AR signaling after ADT triggers androgen-independent outgrowth, generating poorly differentiated, uncontrollable PCa cells . Once PCDepartments of Nephro-Urologic Surgery and Andrology (Professor Emeritus Yoshiki Sugimura) and Oncologic Pathology (Professor Emeritus Taizo Shiraishi), Mie University Graduate School of Medicine, organized the semi-closed symposium on Biology of Prostate Gland Ise-Shima. This symposium was started in 2002 and was held every four years in 2006, 2010, 2014, and 2018 without any financial support from pharmaceutical companies and chemical industries. Each year, the symposium was attended by 40\u201350 Japanese investigators with expertise and interest in biology of the prostate gland and PCa. The goal of this symposium was to discuss the biological mechanism of the development and progression of prostatic proliferative diseases such as benign prostatic hyperplasia (BPH) and PCa. Several major topic areas were discussed, e.g., the pathophysiology of BPH, the tumor microenvironment of PCa, AR signaling in PCa progression, and the development of PCa detection and diagnosis. This Special Issue includes the major topics discussed at the symposium in 2018.In this Special Issue, we focused on cytobiology of human PCa cells and its clinical applications to develop a major step towards personalized medicine matched to the individual needs of patients with early-stage and advanced PCa and CRPC. We hope that this Special Issue attracts a lot of attention for readers with expertise and interest in the cytobiology of human PCa cells and its clinical applications."} +{"text": "With the life expectancy in China continuing to increase, age-dependent chronic diseases are also likely to increase, as is the number of people with long-term care needs. This study evaluated the Long Term Care (LTC) needs of the Chinese older population and introduced related policy priorities. Using the 2014 and 2016 \u201cChina Longitudinal Aging Social Survey\u201d, this study assessed the physical functions of older adults by measuring their ability to perform Activities of Daily Living independently, compared changes within the two years, and explored other related indicators including, Instrumental Activities of Daily Living, major chronic disease, and mental health conditions. The study also discussed the development of long-term care policies in China and highlighted the priorities of these policies."} +{"text": "Journal of Ovarian Research [Pursuant to a decree of the Tribunal of Catania, First Civil Section, LJ Pharma SRL obtained an ex Parte order. The Judge orders BioMed Central Ltd, in the person of the legal representative pro tempore to implement the remedy of the retraction notice on the study, signed by Isabella and Raffone, \u201cDoes Ovary need d-chiro-inositol?\u201d, published in 2012 in the specialized journal"} +{"text": "Healthcare Technology Letters (HTL) journal dedicated to the joint edition of the 8th Medical Imaging and Augmented Reality (MIAR), the Augmented Environments for Computer-Assisted Interventions (AE-CAI), and the 6th Computer Assisted and Robotic Endoscopy (CARE) workshops. We are pleased to present the proceedings of this exciting scientific gathering held in conjunction with the Medical Image Computing and Computer-Assisted Interventions (MICCAI) conference on October 13th, 2019 at in Shenzhen, China.Welcome to this Special Issue of the IET's Over the past several years, the satellite workshops and tutorials at MICCAI have experienced increased popularity. This year's workshop brings together three communities that joined forces back in February 2019 in light of our common interests in image guidance, navigation and visualization for computer-assisted interventions. MIAR / AE-CAI / CARE 2019 is a joint venture between the prestigious Medical Imaging and Augmented Reality (MIAR) workshop series founded in 2002, the series of MICCAI-affiliated workshops on Augmented Environments for Computer-Assisted Interventions (AE-CAI) founded in 2006 and featured annually ever since, and the Computer Assisted and Robotic Endoscopy (CARE) workshop series, now on its 6th edition. This year's edition of the workshop received 30 submissions and reached over 60 registrants, not including the members of the organizing and program committees, making MIAR/AE-CAI/CARE one of the best received and best attended workshops with more than a decade-long standing tradition at MICCAI 2019.Computer-Assisted Interventions (CAI) is a field of research and practice, where medical interventions are supported by computer-based tools and methodologies. CAI systems enable more precise, safer, and less invasive interventional treatments by providing enhanced planning, real-time visualization, instrument guidance and navigation, as well as situation awareness and cognition. These research domains have been motivated by the development of medical imaging and its evolution from being primarily a diagnostic modality towards its use as a therapeutic and interventional aid, driven by the need to streamline the diagnostic and therapeutic processes via minimally invasive visualization and therapy. To promote this field of research, our workshop seeks to showcase papers that disseminate novel theoretical algorithms, technical implementations, and development and validation of integrated hardware and software systems in the context of their dedicated clinical applications.The objective of the joint workshop has been to attract scientific contributions that offer solutions to the technical problems in the area of augmented and virtual environments for computer-assisted and robotic interventions to provide a venue for dissemination of papers describing both complete systems and clinical applications. The workshop attracts researchers in computer science, biomedical engineering, computer vision, robotics, and medical imaging.The workshop featured a single track that consisted of long and short oral presentations showcasing original research engaged in the development of virtual and augmented environments for medical image visualization and image-guided interventions. To foster networking and discussion, we also provided all authors with the opportunity to present their work as a poster in addition to their oral presentation slot.Healthcare Technology Letters journal. This year's joint workshop received 30 manuscripts spanning a strong geographic representation from Europe, North America and Asia. The review process was rigorous and involved evaluation of each manuscript by three to five external reviewers. Following the first stage of review, sixteen manuscripts were further considered for major or minor revision, and resubmission. Authors were required to submit a response to reviewers and resubmit a revised manuscript that addressed all reviewers\u2019 critiques.All manuscripts submitted to the joint MIAR / AE-CAI / CARE 2019 were held up to journal standards, as the ultimate objective was to publish accepted work in this Special Issue of the IET's Once revised, all resubmitted manuscripts entered a second round of review conducted by the Program Committee, Workshop Chairs, as well as the HTL Managing Editor and Editor-in-Chief to ensure that all reviewers\u2019 critiques were properly addressed in the revised manuscripts and that the quality of the manuscript was appropriate for journal publication. All manuscript were then accepted for publication and forwarded to the journal for production and publication.In addition to the contributed papers, we were pleased to welcome Dr. Kensaku Mori \u2013 Professor in the Graduate School of Informatics and Director of the Information Technology Center at Nagoya University \u2013 who spoke on the development and use of artificial intelligence for endoscopic procedures.On behalf of the MIAR, AE-CAI and CARE 2019 Program and Organizing Committee, we would like to extend our sincere gratitude to all authors, presenters, and attendees for their scientific contribution, enthusiasm, and support. We also extend special thanks to all reviewers for providing detailed and timely critiques of the submitted manuscripts. We also acknowledge the support we received from the MICCAI 2019 Workshop Committee, and the HTL Editorial Office for their dedication to maintaining the high quality of the workshops, and for selecting outstanding manuscripts that fostered exciting discussions at the meeting.Northern Digital Inc. (NDI) for their continued support over the years, and we also welcome and thank Intuitive Surgical as a new sponsor for our workshop. Our sponsors\u2019 generous contributions have enabled us to recognize our authors for their much deserved dedication and scientific enthusiasm through several paper awards. A big thank you on behalf of all awardees and once again, sincere congratulations to all award winners! The award-winning papers appearing in this Special Issue are listed below!et al. Development and Face Validation of Ultrasound-Guided Renal Biopsy Virtual TrainerAndinet Enquobahrie et al. A Marker-less Real Time Intra-Operative Camera and Hand-Eye Calibration Procedure for Surgical Augmented RealityMegha Kalia et al. Determining blood flow direction from short neurovascular surgical microscope videosReid Vassallo et al. An Augmented Reality Mastectomy Surgical Planning Prototype using the HoloLensSara M. S. Amini et al. Learning colon centerline from optical colonoscopy, a new way to generate a map of the internal colon surfaceMohammad Ali Armin et al. A deep learning approach for automatic out-of-plane needle localization for semiautomatic ultrasound probe calibrationLeah Groves Last but not least, we acknowledge our generous sponsors. We thank We hope that you will enjoy reading this Special Issue and we look forward to your continuing support and participation in future editions of the MIAR, AE-CAI & CARE workshops. Their continued success demands our ongoing commitment.Cristian A. Linte, Rochester Institute of Technology, United StatesXiongbiao Luo, Xiamen Medical University, ChinaJonathan McLeod, Intuitive Surgical, United StatesZiv Yaniv, National Institutes of Health and TAJ Technologies, United StatesElvis C. S. Chen, Western University, CanadaMarta Kersten-Oertel, Concordia University, CanadaHongen Liao, Tsinghua University, ChinaYuan Zhang, University of Jinan"} +{"text": "With an ever-increasing human population size, increasing human impacts on the natural environment, and a growing scarcity of freshwater resources, the study of freshwater systems has become one of the most critical areas of focus for environmental scientists. Never before has there been such a need for an integrated understanding of lakes, wetlands, and flowing waters. This understanding must cross the boundaries of traditional disciplines, reach a wide international audience, and strongly facilitate the linkage between scientific discovery and its real-world application."} +{"text": "Journal of the Belgian Society of Radiology (JBSR), issued for the annual symposium of the BSR, again honors our PhD grant recipients. These highly graduated individuals present themselves and summarize their long-standing work and academic careers. In this article the summaries of their doctoral theses are available on the site of the JBSR: https://www.jbsr.be/.In 2017\u20132018, the Belgian Society of Radiology (BSR) continued its efforts to close the gaps of knowledge and disseminate new concepts in radiology. This year\u2019s special number of the Rodrigo Salgado was born on December 8, 1971, in Independencia (Santiago), Chile. After secondary school, he graduated in 1993 with a degree in computer engineering. That same year, he started his medical studies at the University of Antwerp, graduating in 2000 (cum laude). From 2000 to 2005 he fulfilled his radiology residency under supervision of Prof. Dr. A. De Schepper and Prof. Dr. P.M. Parizel at the Antwerp University Hospital.After his residency, he achieved a staff position in 2005 at the radiology department of the University Hospital Antwerp, chaired by Prof. Dr. P.M. Parizel. During the following decade, and continuing through the present, he specialized in non-invasive cardiovascular imaging using CT and MR. Currently, he\u2019s a consultant radiologist at the Antwerp University Hospital and a staff member at Heilig Hart Hospital Lier.Insights into Imaging and the International Journal of Cardiovascular Imaging. In the past, he has been a member of both the executive and scientific board of the BSR. He is the editor of the ESR publication on the International Day of Radiology 2018 (Cardiac Imaging), and congress president of the ESCR 2019 Congress which will be held in Antwerp, 24\u201326 October 2019. Dr Salgado presented and defended an original PhD thesis in 2017 at the Antwerp University entitled, \u2018Non-invasive Imaging for Cardiovascular Interventions: An Evolving Paradigm\u2019.Dr. Salgado is an active member of the Belgian Society of Radiology (BSR), the European Society of Radiology (ESR), and the European Society of Cardiovascular Radiology (ESCR). He is currently the elected president of the non-invasive cardiovascular imaging section of the BSR and member of the executive board of the ESCR, in which he is also chair of the Communication and New Media committee. He is member of the European Congress of Radiology (ECR) 2018, 2019, and 2020 scientific subcommittees for cardiac imaging, and serves on the scientific editorial board of Radiology, Investigative Radiology, European Radiology, European Heart Journal, JACC Cardiovascular Imaging, and the International Journal of Cardiovascular Imaging. He won the Young Investigator Award (YIA) at the Society of Cardiovascular Computed Tomography (SCCT) 2016 conference, Orlando, Florida (2016), with a presentation entitled \u2018CCTA Reproducibility of Coronary Plaque Volume: Sample Size Implications for Clinical Trials\u2019. He has been awarded an NIH and Research Foundation Flanders (FWO) grant for his research. The goal of his research is to use state-of-the-art cardiovascular magnetic resonance (CMR) and emerging cardiovascular computed tomography (CCT) technology to elucidate the relationship between epicardial coronary flow, microvascular dysfunction, clinical risk factors, and adverse left ventricular (LV) remodeling in patients with coronary artery disease (CAD). The unique tissue characterization capabilities of CMR allow for a non-invasive assessment of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH), two markers of microvascular damage. These CMR markers could be used to improve the short- and long-term prognostication of patients after myocardial infarction. Second, emerging spectral dual-energy and photon-counting CCT technology may allow for a more detailed and reproducible assessment of both epicardial blood flow and myocardial perfusion due to a substantial improvement in tissue characterization capabilities, lower image noise, and higher spatial resolution.Rolf Symons completed his medical degree at the KU Leuven in 2013 (highest distinction and felicitations of the jury). During his residency in radiology, he completed his PhD in 2018 in a joint project between the University Hospitals Leuven and the National Institutes of Health (NIH)/Johns Hopkins University (JHU) for a dissertation entitled \u2018The Role Of State-of-the-Art and Emerging Non-Invasive Imaging Techniques in Improving Risk Stratification in Patients with Coronary Artery Disease\u2019 with promotor Jan Bogaert, MD, PhD, and David A. Bluemke, MD, PhD. He authored 28 publications in international peer-reviewed journals and two book chapters with more than 30 presentations at international conferences, including RSNA 2016, 2017, and 2018. He is an active member of the Radiological Society of North America (RSNA), Society of Cardiovascular Computed Tomography (SCCT), and Belgian Society of Radiology (BSR) and a reviewer for numerous journals including"} +{"text": "The Biological Resource Centre for the Environment BRC4Env is a network of Biological Resource Centres (BRCs) and collections whose leading objectives are to improve the visibility of genetic and biological resources maintained by its BRCs and collections and to facilitate their use by a large research community, from agriculture research to life sciences and environmental sciences. Its added value relies on sharing skills, harmonizing practices, triggering projects in comparative biology, and ultimately proposing a single-entry portal to facilitate access to documented samples, taking into account the partnership policies of research institutions as well as the legal frame which varies with the biological nature of resources. BRC4Env currently includes three BRCs: the Centre for Soil Genetic Resources of the platform GenoSol, in partnership with the European Conservatory of Soil Samples; the Egg Parasitoids Collection (EP-Coll); and the collection of ichthyological samples, Colisa. BRC4Env is also associated to several biological collections: microbial consortia , terrestrial arthropods, nematodes , and small mammals. The BRCs and collections of BRC4Env are involved in partnership with academic scientists, as well as private companies, in the fields of medicinal mining, biocontrol, sustainable agriculture, and additional sectors. Moreover, the staff of the BRCs is involved in many training courses for students from French licence degree to Ph.D, engineers, as well as ongoing training. The BRCs of AgroBRC-RARe are grouped in five pillars according to the origin of their resources: animal/crop/forestry/micro-organisms/environment. AgroBRC-RARe is registered on the French national roadmap for Research Infrastructures.Conserving and ensuring the availability of genetic and biological resources, particularly for the purposes of research, conservation of biodiversity, education, and economic valorization, are today major societal and scientific challenges, mainly faced by Biological Resource Centres (BRCs). In that context, AgroBRC is a network of BRCs and collections hosted by several French research institutions INRA , IRD (Institut de Recherche et D\u00e9veloppement), CIRAD , and CNRS , as well as associated to technical and higher education institutions. The leading objective of BRC4Env is to improve the French and European visibility of biological resources maintained by its BRCs and to facilitate their use by a large research community, from agriculture research to life sciences and environmental sciences. Its added value relies on sharing skills, harmonizing practices, triggering projects in comparative biology, and ultimately proposing a single-entry portal to facilitate access to documented samples, taking into account the partnership policies of research institutions as well as the legal frame which varies with the biological nature of resources .Since late 2015, the pillar \u201cBiological Resource Centre for the Environment\u201d BRC4Env . Currently, BRC4Env includes three BRCs: the Centre for Soil Genetic Resources of the platform GenoSol in partnership with the European Conservatory of Soils Samples, the Egg Parasitoids Collection EP-Coll, and the collection of ichthyological samples, Colisa. BRC4Env also comprises other biological collections including microbial consortia , terrestrial arthropods (insects and mites), nematodes , and small mammals Table . These Bhttps://www.brc4env.fr/Associated-platforms) in biochemistry: Biochem-Env in Versailles .The network develops interactions with analytical platforms for the characterization of samples of the platform GenoSol provides a national BRC for soils unique in Europe for the storage and conservation of genetic resources (DNA) and making them available to the scientific community. Most of the stored soil samples come from soil survey networks , environmental research observatories , long-term experimental sites (within French and European networks), and networks of farms. All these sites are involved in scientific questions concerning the environmental assessment of soil uses and management, as well as the impact of global changes. The platform GenoSol is a strategic tool to supply these sites in the long term and monitor soil biodiversity.The Centre for Soil Genetic Resources with the possibility to store soils from non-European countries granted by a quarantine agreement. The GenoSol platform has all the laboratory facilities needed for molecular biology studies in the service \u201cLaboratory of Molecular Analysis and Development.\u201d Indeed, the CSGR will provide DNA extracted from soil sample rather than soil itself, as soil quantity is limited (ca 50\u00a0g per sample). In consequence, the CSGR of GenoSol needs to routinize and automatize DNA extraction from sample in order to provide good-quality DNA.https://www.brc4env.fr/BRCs-and-collections/Environmental-matrices/CEES) hosted by the US1106 InfoSol in Orleans, in the frame of the French Network of Measurement of Soil Quality . The CEES stores an archive of French soils collected within the national soil survey and monitoring programs coordinated by the French Soils Scientific Interest Group (GIS Sol). This collective infrastructure is also supporting French and European research programs and Research Infrastructures such as ICOS, with inputs in expertise and support on sampling strategies and methods, sample collection, preparation and archiving, supply of samples to research programs, and partner analysis laboratories. The first sampling campaign of RMQS occurred from 2000 to 2009 and corresponded to 20,000 samples from 2200 sites. The second sampling campaign began in 2016 and will finish in 2027.GenoSol performs its activities in partnership with the European Conservatory of Soils Samples or restricted storage (access restricted to the soil owner).https://www.brc4env.fr/BRCs-and-collections/Invertebrates/Arthropods/EP-Coll) aims to collect, characterize, maintain, investigate, and share egg parasitoids\u2019 strains, these organisms being useful for biological control, applied entomology, and evolutionary ecology.The Egg Parasitoids Collection the conservation of living collections and (ii) the management of strains\u2019 transfers, the activities of the BRC are (iii) the collection of new strains (species and/or populations); (iv) the characterization of these individuals using morphological, molecular, phenotypic, and ecological criteria; (v) the optimization of sampling, rearing, and management methods; and (vi) the optimization of phenotyping methods.https://www6.paca.inra.fr/institut-sophia-agrobiotech/Infrastructure-PlantBIOs)), with greenhouses and controlled environment chambers for carrying out in vitro and in situ experiments, with official agreement for the manipulation of quarantine insects and nematodes, and all the laboratory needed for morphological and molecular biology studies.The BRC is deposited at the UMR1355 Institut Sophia AgroBiotech (ISA) in Sophia Antipolis, France. ISA is a research laboratory which benefits of an original collective scientific infrastructure PlantBIOs , and thermal biology including the development of a prototype for the evaluation of some key parameters.https://www.brc4env.fr/BRCs-and-collections/Vertebrates/Colisa) results from the merging of historical samples collected by three INRA units and by FBA as part of the AFB-INRA Pole \u201cGest\u2019aqua.\u201d These samples come from long-term monitoring and research activities conducted by these units and from a national catch declaration scheme .The historical collection of fish scales and tissues that have occurred.http://golo.cirad.fr). The network BRC4Env, the CSGR of GenoSol, EP-Coll, and Colisa have been labelled as BRCs by the French organism IBiSA.The network BRC4Env and its BRCs and collections implement a quality management according to the INRA Quality Framework v2 for optimized functioning, continual improvement, and stakeholder satisfaction. They plan to move to national (NF S 96-900) or international (ISO 9001:2015) certification in the next 2\u00a0years. Numerous BRCs and collections ensure the traceability and planning of their animation activities using the software AQ-tools developed by CIRAD , by providing temporal set of samples to scientists holds more than 900 strains . Microalgae and especially Diatoms are known to be excellent indicators of aquatic ecosystem pollution Rimet . This coTrichogramma pour la protection des cultures: Pang\u00e9nomique, Traits d\u2019histoire de vIe et Capacit\u00e9s d\u2019\u00e9tablissement) aims at characterizing the inter- and intra-specific diversity of the Trichogramma species at several levels of investigation .Trichograms of the BRC EP-Coll are relevant biological models for eco-evolutionary investigations and constitute a reservoir of candidate strains (species/populations/genotypes) for biocontrol of the INRA metaprogram SMaCH relies on a part of this Arthropods Collection: sequenced specimens, studied morphologically, preserved with their DNA for traceability purposes The samples of the collection Colisa, carrying DNA, allow genetic characterization of wild fish individuals or population. Via microchemistry, these samples allow to characterize the trophic status and the environmental conditions of life of these animals The Plant-parasitic Nematodes Collection of BRC4Env has been the support of various collaborative European research programs. For example, the pinewood nematode collection has been instrumental in the achievement of some objectives of the FP7/EU-project REPHRAME . Together with additional field sampling, these biological resources have been used to characterize the genetic diversity of nematode populations from both the native and the invaded areas, and to infer the worldwide routes of invasion of the parasite Haemonchus contortus populations, one of the most deadly livestock parasitic nematodes . The molt of this collection towards a more formal BRC has been recently initiated.The collection of animal parasitic nematodes has been established 30\u00a0years ago. It has originally been dedicated to ruminant trichostrongylid to delineate the genetic basis of anthelmintic resistance (Silvestre and Humbert 8)Leptospira, Tatard et al. Trypanosoma, Diagne et al. The CBGP Small Mammal Collection, including specimens (skins and/or skulls) and their corresponding samples , and the Small Mammal Database gathering all the associated information have been the support of a number of studies over the last years. Among others, we may cite the description of the invasion of Senegal by the house mouse , BRCs and collections of BRC4Env will determine the legal status of their accessions and consequences for their introduction and distribution, regarding the Access and Benefit Sharing as well as French and European policies. A case study based on soil samples will be developed during the project, because these resources are not well characterized at the time of sampling in terms of taxonomy.The main objective of BRC4Env is to develop the Information System of the network, currently constituted by shared tools and distributed services among BRCs, by making these tools interoperable and relevant regarding the Nagoya policy. A specificity of BRC4Env is the hosting of living collections of invertebrates. The Information System must provide and share information concerning sampling, rearing, phenotyping and molecular data, and barcoding. Here, we plan to set the following requirements: (i) centralization and standardization of metadata concerning the resources, (ii) secure storage and confidentiality by controlled access, (iii) tools to perform queries (in partnership with applications to be developed by AgroBRC-RARe). A common database for registering the projects hosted by the BRCs of the network will be developed.The Information System of BRC4Env will offer shared information dedicated to the resources hosted by its BRCs. It will also promote and contribute to make easier the access, storage, archiving of datasets, and their subsequent valorization, and provide to end-users access to the productions of the network by subscription to News and RSS feed. Experience gained in other pillars of AgroBRC-RARe in these fields will be used in order to optimize the functional specificities of our IS and to select the most relevant technical solution.Internal practice harmonization. Considering the diversity of BRCs and collections, the network will encourage practice harmonization for improved management and enhanced traceability of its activities within its BRCs and make available a comprehensive set of harmonized procedures. One main objective is the introduction (if necessary), the development, and the support for a common process-based quality management system for continual improvement and stakeholder satisfaction. Taken together, these actions will facilitate the sharing of experience and the identification of best practices within the BRCs and collections of the network. Sharing experience will then make possible to define a common policy for BRC and collections functioning, charters for sample and data access, relationships between BRCs and private partners\u2026Valorization of the activities of the BRCs. The network will produce scientific and perspective papers , illustrating the research questions that a better and beneficial coordination between BRCs can help to tackle, as well as the scientific and technical support they can provide to end-users. The network promotes also the production by the BRCs and collections of technical papers valorizing their expertise and know-how. It will also produce and support an action plan for attending national and relevant international conferences and workshops to increase its national and international visibility.BRC4Env shares two main other objectives in the next future.BRC4Enc is a network structuring the BRCs dedicated to environmental resources in France. It is currently seeking for similar networks of BRCs in Europe and worldwide to be a French component of international networks. Today, environmental resources are mainly taken into account in environmental specimen banking. BRC4Env can offer a frame to host samples and collections specifically addressing ecotoxicological issues."} +{"text": "The European Board & College of Obstetrics and Gynaecology has initiated improvement of the European standards of training in Obstetrics and Gynaecology through the project called \u2018EBCOG-PACT\u2019. In this project, a pan-European curriculum for postgraduate training in Obstetrics and Gynaecology has been developed. The curriculum is societally responsive, and based on the latest medical educational methodology. It consists of the description of outcomes of training for the common Core Curriculum and Electives, the General competencies and soft skills to be trained, and strategies for training of obstetrical skills, gynaecological skills, ultrasound skills and bio-psychosocial and communicative skills. Also, the curriculum provides strategies for assessment through entrustment, a model for portfolio as well as strategies for faculty development and quality management of training. The implementation of the European curriculum in Obstetrics and Gynaecology will provide opportunities for national scientific and professional societies and ministries of health or education to consider modernisation of national or local OBGYN training programs. In the ever more internationalising world of today, with increasing mobility of both patients and doctors, training of the gynaecologist of the future requires high quality curricula that allow for continuous improvement and modernisation. Therefore, the European Board & College of Obstetrics and Gynaecology (EBCOG) has taken up the task to initiate improvement of the European standards of training in Obstetrics and Gynaecology (OBGYN) through the project called \u2018EBCOG-PACT\u2019 (Project for Achieving Consensus in Training). In this project, a pan-European curriculum for postgraduate training in OBGYN has been developed, which is societally responsive, and based on the latest medical educational methodology.Three main reasons clarify why development of a pan-European curriculum in OBGYN, and therefore European harmonisation of training, is needed . PrimariThe PACT project has been executed in close collaboration between European gynaecologists, trainees, educationalists, change managers, midwives, specialized nurses, hospital board members, and last but not least, patient representatives. It was recognised as a valuable strategic partnership for improvement of European higher education by the European Commission, and therefore was awarded an \u2018Erasmusplus\u2019 grant. Partners in this project represented four highly-renowned medical institutions from Denmark, Italy, Czech Republic, Belgium and the Netherlands, as well as organisations representing the societal stakeholders.The project ran between September 2015 and September 2018 and has resulted in several outcomes. The curriculum consists of the description of outcomes of training for the common Core Curriculum and Electives, both developed through a (Delphi) consensus procedure amongst European gynaecologists and trainees . BesidesThe curriculum has been translated and is currently available in seven different languages with two additional languages soon to follow . Also, several national scientific societies have initiated translation of the curriculum in their national language .https://www.uems.eu/areas-of-expertise/postgraduate-training/european-standards-in-medical-training). We are convinced that the implementation of the European curriculum in OBGYN will provide opportunities for national scientific and professional societies or ministries of health and education to consider modernisation of national or local OBGYN training programs.The UEMS council has officially adopted the curriculum as the European Training Requirements (ETR) in the field of Obstetrics and Gynaecology ("} +{"text": "A meeting and course supported by the Vice-Presidency for International Affairs of the Spanish National Research Council (CSIC) and the National Agricultural Research Organization of Uganda (NARO) were held at the National Livestock Resources Research Institute (NaLIRRI) in Nakyesasa, Wakiso, Uganda on September 2\u20139, 2019. The activities were conducted within the collaboration program between the Institute of Game and Wildlife Research and NARO for the development of vaccines and other interventions for the control of cattle ticks in Uganda. Theileria parva), babesiosis (caused by Babesia bigemina), anaplasmosis , and heartwater (caused by Ehrlichia ruminantium), that affect cattle production in Uganda [Tick-borne diseases (TBDs), such as East Coast fever , in coordination with the Government of Uganda and stakeholders , proposeRhipicephalus microplus BM86 or BM95 recombinant antigens and registered in Cuba and Australia in the early 1990s [Antitick vaccines constitute an environmentally sound intervention with demonstrated efficacy for the control of cattle ticks and TBDs ,14. The ly 1990s ,15. Thesly 1990s ,14,15. Ily 1990s . Despitely 1990s . The collaboration between the Institute of Game and Wildlife Research (IREC) and the National Agricultural Research Organization of Uganda (NARO) for the development of vaccines to control cattle tick infestations began with P. D. Kasaija\u2019s arrival at our laboratory at SaBio, IREC to enroll in the Ph.D. program at the University of Castilla, La Mancha in Spain and during the visit of NARO executives to IREC in September 2018 -based vaccine for the control of cattle tick infestations in Uganda. As stated in the letter by the General Director of NARO, Ambrose Agona, the objectives were (i) understanding the institutional framework that supports successful vaccine production, (ii) identifying the best practices in livestock vaccine production, (iii) identifying infrastructural and human resources requirements for vaccine production, and (iv) establishing a lasting partnership and linkages between NARO and IREC for the development, registration, and production in Uganda of a cattle tick vaccine. Bos indicus and crossbred cattle in Uganda, Rhipicephalus appendiculatus, Rhipicephalus decoloratus, and Amblyomma variegatum. Vaccination trials with systemic and oral vaccine formulations are currently ongoing at NaLIRRI with the participation of the Ph.D. student enrolled in the Ph.D. program at the University of Castilla, La Mancha in Spain. This is the first time that vaccines based on SUB antigens are being tried to successfully control multiple cattle tick species. A second meeting between NARO management and IREC representatives was conducted at NaLIRRI in September 5, 2019 to discuss preliminary results of ongoing vaccination trials and future strategies for the control of tick-borne and other diseases affecting cattle health and production in Uganda was discovered in 2002 , and sinAs part of the project, a course was prepared to address the objective of developing the infrastructure and human resources required for the control of ticks and TBDs and vaccine production. The course was intended to build scientific capacity at the NaLIRRI in Uganda at both theoretical and laboratory practical levels and to implement a multidisciplinary approach for the control of infectious diseases affecting humans and animals in Uganda . A speciTick infestation and tick-borne diseases such as anaplasmosis and piroplasmosis are ranked high among the most important cattle diseases for poverty reduction and global trade. However, the list is much longer, including other relevant shared infections such as foot-and-mouth disease (FMD), Rift Valley fever (RVF), brucellosis, and tuberculosis (TB). Often, these shared infections are regarded as \u201cdouble-burden diseases\u201d, the control of which would benefit both human and animal health and livestock production and trade .Mycobacterium bovis and other closely related members of the Mycobacterium tuberculosis complex (MTC). It is a typical multihost shared infection present worldwide in a wide range of domestic and wild maintenance hosts [Syncerus caffer) and the widespread warthog (Phacochoerus africanus) [One of these priority double-burden diseases is animal TB, caused by ce hosts . It is kce hosts . Howeverce hosts . Regardice hosts , and 14%ce hosts . In Uganricanus) . TherefoM. bovis as an immunostimulant in oral vaccination against ticks [The ongoing trials of cattle tick vaccines might provide an opportunity for animal TB control in Uganda. Cattle enrolled in field trials could be tested for TB, possibly using alternatives to the traditional skin test, such as serology, in order to enable single-sampling protocols and facilitate diagnosis in remote regions . Other lst ticks . Given the key role of cattle in Africa as a safety net and a ladder out of poverty, it is important to maximize the contribution of research activities on livestock disease control to global health, wealth, equity, and sustainability .In Uganda, several arthropods are vectors of pathogens of medical and/or veterinary relevance, with mosquitoes and tsetse flies ranking highest as vectors for human pathogens and ticks having a massive impact on livestock production. R. decoloratus being less plastic than the three-host ticks A. variegatum and R. appendiculatus. However, all three species of ticks of relevance for cattle in Uganda can parasitize wild mammals, such as wild bovids, suids, lagomorphs, hedgehogs, carnivores, and small rodents, and a high number of wild bird species [Tick species differ in their host selection plasticity, with highly specialized one-host ticks such as species ,29, as w species . Despite species ,32. Oura et al. highlighConsequently, Uganda faces a potentially increasing wildlife\u2013human conflict to preserve the biodiversity that attracts tourists and supports the services sector of the country, which accounts for 50% of the GDP. Fighting ticks of cattle with acaricides and antitick vaccines would aid but not solve the conflict, which could only be solved by increasing scientific knowledge with a One Health approach that includes humans, livestock, wildlife, and ecosystems together to understand the ecology of ticks and tick-borne pathogens. This would allow designing effective and environmentally friendly prevention and control strategies in the future to control tick infestations and TBDs of cattle in Uganda. This was one of the main topics of the course at NaLIRRI, which was intended to build scientific capacity and increase concern about wildlife as relevant in the life cycle of ticks and tick-borne pathogens in Uganda.Exposure to cattle ticks or acaricides such as organophosphates account for pediatric poisonings in rural Uganda and toxiThe uncontrolled use of this acaricide may lead to environmental damage in aquatic ecosystems, acaricide resistance in ticks, and a possible exacerbation of TBDs . AlthougTherefore, the correct use and application of the most appropriate and effective acaricides, which was recently proposed as one of the key measures to prevent economic losses caused by ticks and TBDs in the cattle industry in Uganda , should The control of ticks and TBDs constitutes a priority for the Government of Uganda to promote economic growth in the country. This challenge requires a multidisciplinary approach to combine different control measures that range from cattle management and the rational use of acaricides to antitick vaccine development and application. Collaboration between research institutions leading research in these areas with those located in the most affected countries is necessary to achieve these goals. The ongoing collaboration project between IREC and NARO is focused on developing and implementing the production and application of SUB-based vaccines for the control of cattle tick infestations in combination with other control interventions. Controlled pen vaccination trials are currently ongoing. Future directions will include (i) characterization of protective immune response in cattle and vaccine antigen design, (ii) development and evaluation of oral vaccine formulations, (iii) building of vaccine production facilities at NARO, (iv) field trials with effective antitick vaccine formation, (v) characterization of animal TB epidemiology and future control options, (vi) study of the ecology and epidemiology of vector-borne diseases for effective control and prevention, and (vii) application of veterinary toxicology approaches to reduce the detrimental effects of acaricides and other compounds on human and animal health and cattle production."} +{"text": "These processes include investigation of bioavailability to assess to what degree and how fast compounds are absorbed after drug administration, elucidation of metabolic pathways, and elimination routes and their kinetics, as well as the interactions of HMPs with synthetically derived drug products. Due to the complex chemical composition of HMPs, the absorption, distribution, metabolism, and excretion characteristics of the bioactive or toxic HMPs remain to be further explored. The difficulty lies primarily in the selection of appropriate biomarkers for detection, quantification of trace constituents, identification of potential drug-drug interactions, and the discovery of active constituents based on metabolic results.Herbal medicinal products (HMPs) are expected to be safe and effective. Nevertheless, evidence-based verification of the safety and efficacy of HMPs is still lacking. Understanding the metabolic profile and In this special issue, investigators contribute original research articles and review articles that would facilitate the understanding of the basic mechanisms as well as the development of new and promising complementary and alternative strategies for the metabolic profiling and pharmacokinetics of HMPs.Integrating pharmacokinetics is a crucial tool to identify the therapeutic agent. The research article by C. Zhang et al. elucidated the pharmacokinetic profiles and disposition kinetics of the administered and generated stereoisomers in the brain and cerebrospinal fluid (CSF) after oral administration of Isorhynchophylline (IRN) and Rhynchophylline (RN). The results demonstrated that, after oral administration, RN showed significantly higher systemic exposure and disposition in the brain and CSF than IRN, indicating that RN would be more appropriate to be developed as a potential therapeutic agent for the treatment of AD.In technology, ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) is still the most popular tool for the pharmacokinetics study of HMPs. The research article by Y. Fu et al. established a simple, sensitive, and reliable UPLC-MS/MS method for quantifying pinosylvin in rat plasma, urine, feces, and various tissues. Nine metabolites of pinosylvin were found in plasma, and glucuronidation, hydroxylation, and methylation proved to be its main metabolic pathways. Sophora flavescens extract with cytochrome P450 (CYP) isoforms in human liver microsomes. The result showed that S. flavescens and its prenylated flavonoids caused significant herb-drug interactions when coadministered or incubated with substrates of CYP2B6, CYP2C8, CYP2C9, and CYP3A4. The research article by N. Temyingyong et al. determined the effect of short-course oral ciprofloxacin on isoflavone pharmacokinetics in healthy postmenopausal women. The results showed that ciprofloxacin administration significantly reduced the absorption of the aglycones of genistein and daidzein.There are many factors affecting the pharmacokinetics of HMPs, among which herb-drug interaction has been frequently studied. The research article by D. Yim et al. examined the selective interaction ofDrug formulation and administration route also significantly affect the pharmacokinetics of HMPs. The research article by P. Smyk et al. elucidated the influence of propolis on ion channels, channels location in cell membrane, and electrical resistance of skin. In this work, a model skin of Ussing chamber proved to be useful for studying the effect of chemicals on transepidermal ion transport.Finally, in addition to herb-drug interaction, the review article by S. Sun et al. summarized other important factors that affect the clinical practice of HMPs, such as herb pretreatment, herb-herb interactions, pathological status, gender, age of patients, and chemical and physical modification of certain ingredients. in vitro and in vivo studies as well as the literature review related to the objective of this special issue.Thus, this special issue included different aspects related to the recent advances in metabolic profiling and pharmacokinetics of HMPs, based on various"} +{"text": "Skin pigmentation represents one of the most peculiar traits of human beings and its alteration as a consequence of pathological conditions has a dramatic impact on the wellness of individuals and their social relationships. Therefore, the possibility of controlling pigmentation by intervention at the different stages of the melanogenic process has represented over the years a most important research target, with many implications for the dermatological and cosmetic fields. One way of reaching such a goal is an in-depth knowledge of the genetics of pigmentation, the mechanism of activation of the melanocortin receptor 1 (MC1R) and the signaling cascade, and finally the expression and trafficking of melanogenic enzymes. In this regard, it is timely that Del Bino et al. [Most of the papers and review articles appeared in this issue provide a contribution along two main lines, that is, a) unraveling hitherto unappreciated aspects of the complex melanogenesis machinery, or b) identifying new compounds or natural extracts with the ability to suppress or stimulate melanogenesis and elucidating their mechanism of action. N-glycosylation occupancy, incorporating the two metal ions and acting on two different steps of melanogenesis, that is, Cu(II) to acquire 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity, or Zn(II) to acquire tautomerase activity. Of particular interest is the review paper by Solano , which rN-acetyltransferase 10, so far considered as a valuable target for cancer and laminopathies, was shown to play a role also in melanogenesis and melanoma growth through regulation of microphthalmia-associated transcription factor (MITF) [In Oh et al., r (MITF) . The evor (MITF) . The posr (MITF) . In Campr (MITF) . Oroxylum indicum seeds) [Polygonum tinctorium flower extract [A series of compounds exhibiting a broad structural diversity have also been investigated for their antimelanogenic activity by much different mechanisms of action, ranging from direct inhibition of tyrosinase, as reported for thiazolyl resorcinols or lipoym seeds) , Bamboo m seeds) ), conditm seeds) , or syntm seeds) , phenylhm seeds) ). It shom seeds) used humm seeds) , Polygon extract ).New strategies for melanogenesis stimulation are presented based on the use of low frequency or pulseThe case of rhododendrol, a skin-whitening ingredient that was reported to induce leukoderma, was reviewed by Ito and Wakamatsu . This prFinally, the opportunities opened by knowledge of the different chemical reactivity of the two major indole intermediates of melanogenesis, 5,6-dihydroxyindole (DHI) and DHICA, for cosmetic purposes were illustrated through examples in the field of hair dyeing and photoprotection . A uniquIn conclusion, the research contributions presented in this issue clearly illustrate how investigation of the basic facets of the melanogenetic process and insight into the mechanism of action of natural and synthetic compounds may offer a valuable tool for the design of efficient and selective strategies for the control of hyperpigmentary disorders or melanin stimulation as required in vitiligo. In this regard, the current status of clinical and molecular aspects of vitiligo treatments is discussed by Bishnoi and Parsad ."} +{"text": "These include accelerated literature searches, analysis and prediction of physical and quantum chemical properties, transition states, chemical structures, chemical reactions, and also new catalysts and drug candidates. The generalization of scalability to larger chemical problems, rather than specialization, is now the main principle for transforming chemical tasks in multiple fronts, for which systematic and cost-effective solutions have benefited from ML approaches, including those based on deep learning . The latter class of ML algorithms is capable of combining raw input into layers of intermediate features, enabling bench-to-bytes designs with the potential to transform several chemical domains. In this review, the most exciting developments concerning the use of ML in a range of different chemical scenarios are described. A range of different chemical problems and respective rationalization, that have hitherto been inaccessible due to the lack of suitable analysis tools, is thus detailed, evidencing the breadth of potential applications of these emerging multidimensional approaches. Focus is given to the models, algorithms and methods proposed to facilitate research on compound design and synthesis, materials design, prediction of binding, molecular activity, and soft matter behavior. The information produced by pairing Chemistry and ML, through data-driven analyses, neural network predictions and monitoring of chemical systems, allows (i) prompting the ability to understand the complexity of chemical data, (ii) streamlining and designing experiments, (ii) discovering new molecular targets and materials, and also (iv) planning or rethinking forthcoming chemical challenges. In fact, optimization engulfs all these tasks directly.Computational Chemistry is currently a synergistic assembly between Patterns are ubiquitous in Chemistry. From the crystalline structures of solid forms to the branched chains of lipids, or the complex combinations of functional groups, chemical patterns determine the underlying properties of molecules and materials, essential to address important issues of societal concern. Artificial Intelligence (AI), and machine learning (ML) in particular, are committed to recognizing and learn from these patterns understanding and controlling chemical systems and related behavior approaches can also be particularly useful to solving a variety of chemical problems, including compound identification and classification, and description of soft matter behavior are critical challenges, that may, however, facilitate the routine implementation of data mining in chemistry and expedite new discoveries.The amount and quality of chemical data generated by experiments and simulations have been the mainstay of the new data-driven paradigm, that establishes the bridge between theory, experiment, computation, and simulation.This review describes, in a critical and comprehensive way, relevant contributions carried out recently and involving the development of chemistry ML approaches. An exhaustive account of the theoretical foundations and applications published in the early years of AI and ML in Chemistry falls beyond the scope of this review. The reader is referred to Lecun et al. , CoveneyUntil 10 years ago, only a few 100 studies on the use of ML in Chemistry were published, resulting from the contributions made over four decades. In 2018, ca. 8,000 articles in the Web of Science database included these keywords, corresponding to an increase in ca. 35% for just one decade. In this review, there is room to mention only a small fraction of these applications.Despite the increasing number of works on the topic, the models proposed and practices carried out by chemists are entailing serious concerns to be able to quickly identify areas that have benefited most from the development and implementation of ML approaches, and those that still lack of such an optimization, as evidenced by the type of outcome, (ii) to identify the most relevant ML outcomes in each sub-field, and (iii) to assess the dynamics of ML outcomes over the 2008\u20132019 period and how these are related, giving rise to relevant research trends.machine learning, type of outcome and the sub-field in which they co-occur . A total of 5,279 contributions on ML in Chemistry, with 81,248 citations, and published between 2008 and June 30, 2019, are found in the worldwide Web of Science database, corresponding to a 4-fold increase over the previous four decades. Considering the compiled data and the selected Chemistry fields , nine different ML outcomes embracing the most frequent chemical challenges are defined, including (i) text mining and system description, (ii) quantitative structure-activity/property relationships, (iii) DFT functionals and interatomic potentials, (iv) generative models and inverse molecular design, (v) molecular screening, (vi) synthesis/characterization of new compounds and materials, (vii) catalytic technologies, (viii) analytical techniques, and (ix) quantum models, algorithms, and quantum sensing. Note how these have a strong relation with the seven overall applications presented above (i\u2013vii).An extensive literature search on ML contributions in 30 Chemistry sub-fields is carried out, using a global set of 270 co-occurring keywords, each composed of three main terms, The heatmap represented in The natural clusters generated from the most important co-occurring relationships are also identified. Considering the dendrogram for the Chemistry sub-fields, it can be observed that these are organized in two main groups, which discriminates, in general, classical Chemistry sub-fields from analytical and biochemical sub-fields. This structure suggests a significant similarity in the type of ML outcomes within each group. Group 1 have benefitted from a significant production on catalytic technologies, DFT functionals and interatomic potentials, quantum models and quantum sensing. The most representative ML outcomes in group 2 are associated to text mining, analytical techniques, generative models and inverse design, molecular screening, structure activity relationships, and synthesis of new compounds and materials. Examination of the similarity between the type of ML outcomes reveals that there are three main groups, corresponding to (i) text mining, analytical techniques, generative modes and inverse design, and molecular screening (group 1), (ii) structure-activity relationships and synthesis of new compounds and materials (group 2), and (iii) catalytic technologies, DFT functionals and interatomic potentials, and quantum models and quantum sensing (group 3).ab initio approaches. However, the computational cost inherent to these classical approximations have limited the size, flexibility, and extensibility of the studies. Larger searches on relevant chemical patterns, have been successfully conducted since several research groups have developed ML models and algorithms to predict chemical properties using training data generated by DFT, which have also contributed to the increase of public collections of molecules coupled with vibrational, thermodynamic and DFT computed electronic properties , shown in Other strong correlations are found between generative models & inverse design and the two abovementioned ML applications, molecular screening (0.95) and text mining (0.93). This can be explained by the fact that many researchers have proposed machine learning frameworks based on a variety of generative models for modeling molecules, which differ in the respective model structure and in the selected input features , and between generative models and inverse design and analytical techniques (0.85). The former relation evidences the significant effort that has been made on applying ML models, in particular those based on accurate DL architectures, to find and select lead molecules , displaying desired properties molecular screening and (0.84), (ii) synthesis/characterization of new compounds and materials (0.78), and (iii) generative models and inverse design (0.75), DFT functionals and interatomic potentials with quantum models and quantum sensing (0.83), and synthesis/characterization of new compounds and materials with analytical techniques (0.79).Both generative models and analytical techniques have been extensively used in the qualitative/quantitative search of patterns underlying chemical systems optimization of reaction parameters and process conditions, e.g., changing the type of reagents, catalysts, and solvents, and also varying systematically, concentration, addition rate, time, temperature, or solvent polarity, (ii) suggestion of new reactions based on critical functional groups, (iii) prediction of reaction/catalyst design, and optimization of heterogeneous/homogeneous catalytic reactions, (iv) acceleration and discovery of new process strategies for batch reactions, (v) establishment of trade-offs in the reaction rate and yield of organic compounds, (vi) description and maximization of the production rate and conversion efficiency of chemical reactions, (vii) prediction of the potential toxicity of different compounds, and also the (viii) rational design of target molecules and guided exploration of chemical space , obtained from automatic and accurate electronic structure calculations Behler, .However, the intricate nature of the configuration space and its exponential dependence on system size and composition, have hampered the screening of the entire set of candidate structures directly by electronic structure calculations Behler, .Despite the usefulness of ML approaches being indisputable, with the promise to modernize molecular simulations, synthesis, materials science, and drug discovery, the respective endorsement and practical aspects in some chemical sub-fields is far from consensual pitfalls of some practices using ML. It has been argued that ML algorithms may lead to overestimated performances and deficient model generalizations, due to their sensitivity to the presence of maze-like variables and experimental artifacts from each molecule with random (Gaussian distributed) numeric strings. It was shown that the predictions were similar to the original ones. Chuang and Keiser have alsThe original assumptions regarding the significance and validity of the random-forest model to describe important and general chemical features were also confirmed , lack of standardization of chemical data, expertise and familiarity with ML and DL in chemistry sectors, and also lack of collaboration opportunities) which confer the ability of DLNs to learn from highly complex data and perform correlation and reduction. This means that the algorithm discovers correlated data, while discarding irrelevant information. Each layer combines information collected from the previous layer, and subsequently infers on the respective significance and send the relevant information to the next layer. The hidden term is used to represent layers that are not direct neighbors of the input or output layers.The process allows constructing increasingly complex and abstract features, by adding layers and/or increasing the number of neurons per layer. However, the use of more than a single hidden layer requires determining error attributions and corrections to the respective weights. This is carried out via a backpropagation, i.e., a backward process starting from the predicted output, and back through the neural network and ML methods in the search for novel molecular components, have also been implemented , contributing to increase knowledge on the interactions within quantum many-body systems and efficiency of DFT-based quantum mechanical modeling methods algorithm has been conducted , can be represented and predicted by ML methods of hybrid DFT per each atomization energy into milliseconds using ML. Cross-validation over more than seven thousand organic molecules yielded a mean absolute error below 10 kcal/mol. The authors have trained the ML algorithm on a set of compounds in a database, comparing the respective matrices to determine differences between molecules, so as to develop a landscape of such differences. Based on the atomic composition and configuration, the unknown molecule can be positioned in the landscape and the respective atomization energy can be estimated by the contributions (weights) obtained from the differences between the unknown and all known molecules , random-forest, kernel ridge regression, and neural networks (graph convolutions and gated graph networks) were tested. It was concluded that out-of-sample errors were strongly affected by the molecular properties, and by the type of representation and regression method. Molecular graphs and graph convolutions displayed better performances for electronic properties, while kernel ridge regression and histograms of dihedrals were suitable for describing energy-related properties [see Faber et al. for detaIn terms of drug development Brockherde et al. have devSpecifically, the algorithm was created and trained on the basis of a small sample set of the molecule under study, and applied to simulate the intricate chemical behavior within selected molecules, including malonaldehyde. A directed learning of the density-potential and energy-density maps was conducted, as illustrated in In more detail, one of the key tasks in atomistic modeling is the prompt and automated analysis of the simulation results, in order to provide a comprehensive understanding of the behavior of individual atoms and target collective properties. The main supervised and unsupervised machine-learning methods directed at classifying and coarse-graining of molecular simulations were recently summarized and discussed in Ceriotti . A schemab initio MD level of accuracy and produced converged MD simulations with fully quantized electrons and nuclei the free-energy and mean force with respect to translation of the molecule, (ii) the free-energy and variance of the mean force associated to molecular rotation, and considering (iii) the mean force being a conservative force field generated by the free-energy, and (iv) a prior energy for preventing deviations of the simulations with coarse-grained neural networks into unphysical state space regions, i.e., states displaying overstretched bonds or clashing atoms, which are captured out of the training data.The proposed strategy also outperformed classical coarse-graining approaches, which generally failed to capture relevant features of the free-energy surface, providing the all-atom explicit-solvent free-energy surfaces estimated with models including just a few coarse-grained beads, in the absence of solvent , and a predictor, which estimates chemical properties from the latent continuous vector representation of the molecule. These representations allowed generating new chemical structures automatically by employing simple operations in the latent space , and applying gradient-based optimization for a oriented-search of functional molecules for ensuring region/chemo/stereo selectivity and obtaining the highest yields, estimating the precise rate, yield and time for the reaction, predicting major/minor product, and also evaluating similarity between reactions modeling, and based on ML techniques, has been proposed for predicting the pre-discharge chemical profiles of ammunition components from the components of the respective post-discharge gunshot residue (Gallidabino et al., The integration of ML-based algorithms in a chemosensor has also pointed out the future of ML and the artificial internet of things applicability, i.e., optimized sensors, linked to a central data analysis unit via wireless (Mayer and Baeumner, Additionally, researchers have used ML to develop tools for predicting catalytic components and dynamics. For instance, the identification and prediction of ligands for metal-catalyzed coupling reaction have been conducted for designing a synthetic economic and ecological route, with the potential to be expanded into a system of pharmaceutical interest (Durand and Fey, Different case studies covering the application of these descriptors, including maps and models and DFT calculations, have been discussed, demonstrating the usefulness of descriptor-oriented studies of catalysis for guiding experiments and successfully evaluate and compare the proposed models (Durand and Fey, Li and Eastgate have desDesigning catalysts using computational approaches is also a major challenge in chemistry. Conventional approaches have been restricted to calculate properties for a complex and large number of potential catalysts. More recently, innovative approaches for inverse design have emerged, for finding the desired property and optimizing the respective chemical structure. The chemical space has been explored by combining gradient-based optimization, alchemical transformations, and ML. These efforts have been duly reviewed in the context of inverse design and relevance to developing catalytic technologies (Freeze et al., One possible approach to inverse design is to use the synthetic accessibility score, commonly used for drug molecules, in the scoring functions of inverse design for ensuring synthetic feasibility. For that purpose, empirical parameters can be used to describe molecules without the cost of using 3D coordinates for an entire structure and without using a model to describe the complex interactions from geometries.The major progress on inverse design relies on optimization algorithms, which govern the process for exploring a specific space, improving identification rates of parameters that allows optimizing the value of the scoring function. For example, the Classical Optimal Control Optimization algorithm, used for global energy minimization, is based on the diffeomorphic modulation under the observable-response-preserving homotopy algorithm, and lead the classical dynamics of a probe particle, driven by an external field for reaching the optimal value of a multidimensional function, by adjusting iteratively field control parameters over the gradient of the scoring function related to the controls. However, the respective use for scoring functions in inverse design applications still remain a challenge (Freeze et al., The application of autoencoders have allowed transforming SMILES representations of compounds into a continuous latent space in order to optimize chemical properties, including synthetic accessibility score and Quantitative Estimation of Drug Likeness. Additionally, by resorting to gradient-based methods the latent space can be intersected to predict new candidate structures for being synthesized and tested.The integration of inverse design, gradient-based optimization and ML is a very promising strategy to shorten the long path toward catalyst discovery (Freeze et al., This review has sought to provide a sample of ML approaches that support the major research trends in Chemistry, especially in computational chemistry, focusing on DLNs. Such an approaches have offered the possibility of solving chemical problems that cannot be described and explained via conventional methods. In the last few years, the application of ML to the optimization and prediction of molecular properties has become very popular, since more researchers are trained and acquired technical skills to develop and use such methods. ML applications are area-dependent and follow, in fact, a more or less obvious pattern. For instance, medicinal chemistry excels in structure-activity relationships. In other words, each sub-field is progressing essentially in activities that belong to its core subjects. It seems that these fields are evolving naturally, and we cannot identify significant disruptive trends.Despite the historical route of ML methods involving the implementation of clustering or dimensionality reduction approaches, to provide a simple, low dimensional, or coarse-grained representations of structural and dynamical patterns of complex chemical systems, the interplay between innovative ML-driven predictions and molecular simulations can be combined to make time-consuming electronic calculations feasible, obtain accurate interatomic potentials on complex systems, and provide a rational design of molecules and materials. However, the convergence between different ML algorithms is a major challenge to achieve a definite progress in the chemistry fields.Unsupervised learning may also contribute to elucidate the operating aspects of supervised algorithms, while supervised approaches may contribute to the formulation of objective metrics to evaluate the performance of unsupervised approaches.In Chemistry DL is still at an incipient stage, particularly in computational chemistry, although the pace of contributions has been increasing very recently. One of the major challenges is the disparity, quality and interpretability of the generated outcomes. Paired with the sophistication and ability of GPU-accelerated computing for training DLNs and the massive growth of chemical information used for training DLNs, it is anticipated that DL algorithms will be an invaluable engine for computational chemistry. DL uses a hierarchical cascade of non-linear functions allowing to learn representations and capture the required features from raw chemical data, necessary for predicting target physicochemical properties.Considering the recent effort on the topic, DL models have been implemented in various Chemistry sub-fields, including quantum-chemistry, compound and materials design, with superior performances to conventional ML algorithms. There is still tremendous room for improved model accuracy and interpretability. While industrial sectors will continue driving many advances, academia will continue playing a critical role in supplying innovative technical and practical contributions, as well as in fostering cross-disciplinary cooperation.TC performed the bibliometrics analysis, collected the relevant studies in the context of the review, structured, and wrote the paper. AP directed the work, contributed to the interpretation of the data, and to the structure of the review. Both authors reviewed the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Professor Christian Weber studied medicine at the Ludwig Maximilians \u2013 University (LMU) of Munich, Germany, the University Hospital Galway, Ireland and Princess Alexandra Hospital, Australia. After receiving his medical degree in 1994, he joined the Center for Blood Research (T. Springer), Harvard Medical School for a postdoctoral research fellowship. Coming back to Germany, he was awarded as junior research group leader in Vascular Medicine at the Ludwig-Maximilians-University and later was appointed as full-time professor and head of Molecular Cardiology at the University Hospital of the RWTH Aachen. As founding Director of the Institute for Molecular Cardiovascular Research in Aachen, he became a prominent and well-known figure in cardiovascular field, launching well-funded hypothesis and opening novel visions on therapeutic strategies for cardiovascular diseases. In 2010, he was appointed as Chair in Vascular Medicine and Director of the Institute for Cardiovascular Prevention, the Ludwig - Maximilians - University of Munich, as well as Chair of the August-Lenz-Foundation.During his career, he published more than 400 scientific articles, with a cumulative impact factor of over 3100 and more than 20 000 citations, achieving the h-index of 74. His activity was recognized and awarded by the German Society of Atherosclerosis Research (W.H. Hauss-Prize), the European Society of Cardiology (Outstanding Achievement Award 2008), the American Heart Association and the Netherlands Organization for Scientific Research (VICI Award). He is the Chief Editor, Editorial Board Member and/or Referee of many prestigious scientific journals, as well as the president and/or important organizer of several scientific meetings. At last, but not at least, he is an appreciated model and mentor for many ambitioned and motivated young scientists.dolor, calor, rubor, tumor and function laesa. Basically, these symptoms can be explained by high production of pro-inflammatory mediators, recruitment of leukocyte subsets and increased vascular permeability. The role of inflammation in cardiovascular disease is immense. For instance, atherogenesis and plaque growth are driven by imbalanced lipid metabolism and chronic inflammatory processes involving the innate and adaptive immune system1. Therefore, studying inflammation is fundamental to understand the complex pathogenesis of cardiovascular disease and to develop novel biomarker panels together with more effective therapeutics.Inflammation is a protective or adaptive response of the immune system against pathogens or tissue damage. The clinical signs of acute inflammation are 2. The research on platelets, chemokine-receptor pairs and heterophilic chemokine interactions during inflammation is intensively developing as well in the recent past3.Before, the central role of monocytes, macrophages and innate versus adaptive immunity in cardiovascular disease have been extensively discussed. Recently, new aspects on monocyte and macrophage heterogeneity with differential subset-specific recruitment and hitherto less appreciated cellular players such as neutrophils, dendritic, mast and regulatory T-cells become more evident4. However, just a fractional amount of the comprehensive experimental data shows indeed relevance in clinical setting. The exact risk-benefit prediction is often obscure and associated with adverse side effects. The versatile experimental animal models are similar but largely not identical to men and the development of new therapeutics takes a long time with numerous clinical phases until approval.The translation of basic research into clinic is a huge challenge with several pitfalls and very heavy responsibility. Unraveling the molecular mechanisms of inflammation could catalyze the development of innovative cardiovascular therapeutics5.The atherosclerosis field is so vast that attempting to comprehensively cover all aspects will be futile. It will be rather crucial for the future to identify key determinants that lead to chronic inflammation in atherosclerosis, to dissect the intriguing diversity of lipid-related pro-inflammatory versus homeostatic and atheroprotective pathways, to review and validate genetic variants contributing to cardiovascular disease and to discuss promising clinical applications of selectively and local targeting inflammation depending on disease stageScience is a cruel mistress, so do not take shortcuts and be prepared for frustration. It will always be \u201cper aspera ad astra\u201d. But on your way, look out for the right mentor. That will help."} +{"text": "Surface properties of biomaterials, such as chemistry and morphology, have a major role in modulating cellular behavior and therefore impact on the development of high-performance devices for biomedical applications, such as scaffolds for tissue engineering and systems for drug delivery. Opportunely-designed micro- and nanostructures provides a unique way of controlling cell-biomaterial interaction. This mini-review discusses the current research on the use of electrospinning (extrusion of polymer nanofibers upon the application of an electric field) as effective technique to fabricate patterns of micro- and nano-scale resolution, and the corresponding biological studies. The focus is on the effect of morphological cues, including fiber alignment, porosity and surface roughness of electrospun mats, to direct cell migration and to influence cell adhesion, differentiation and proliferation. Experimental studies are combined with computational models that predict and correlate the surface composition of a biomaterial with the response of cells in contact with it. The use of predictive models can facilitate the rational design of new bio-interfaces. The natural regeneration process of human tissues is strongly regulated by the interaction of cells with the extracellular matrix (ECM) for controlling adhesion, differentiation, and migration of different cells lines. The mini review is divided in two main sections: the first one will focus on experimental studies on electrospun fibers that provide physical cues for cell growth and differentiation; the second section will discuss computational models to predict cell behavior on micropatterns. Although mathematical models that simulate cell behavior on electrospun fibers are not currently available, the computational approaches here discussed can be adapted, in the future, to electrospun scaffolds and used to elucidate the underlying mechanisms responsible for cell-fiber interaction.Multiple studies have demonstrated that the morphology and roughness of fibers produced by electrospinning influence cell adhesion, proliferation, and orientation (PCL) fibers influences the recruitment of MSCs In vitro tests on human bone marrow MSCs (hBMSCs) revealed that fiber anisotropy modified cells' morphology: polygonal, round-shaped cells without alignment were detected in the random, mineralized regions of the scaffold; while elongated spindle-shaped cells aligned along the fiber direction were visible in the aligned region. Moreover, the aligned fibers significantly up-regulated tendon-specific and tendon-related markers and therefore guided tenogenic phenotypes of hBMSCs; while, the regions with random, mineralized fibers determined the expression of bone-specific markers and consequently hBMSCs osteogenic phenotypes. Although the authors have not elucidated the underlying cell signaling mechanisms, this work demonstrates that electrospun scaffolds with engineered fiber anisotropy are advantageous to achieve region-specific distribution of tendon- and bone-related genes and find potential application in ligament repair and regeneration of bone-ligament connections.Another study has investigated how electrospun PCL scaffolds with a novel random-aligned-random structure can be used to mimic bone-ligament connections and native ligaments by mediating the production of signaling molecules including Wnt3a, and to promote dentinogenesis. Osteogenesis of MSCs has been reported also on random Poly-L-lactic acid (PLLA) fibers, due to cytoskeletal rearrangements and tensions, which in turn influence intracellular mechanotransductive pathways , there is a clear gap in the field which has great potential if correctly pursued. This will open even more possibilities to design and create novel fibrous scaffolds with engineered surface structures (Ziebert and Aranson, Electrospun nanofibers have become vital structures for a plethora of different applications, with the field of biomedical engineering being, arguably, one of the most important. Thanks to the versatility of electrospinning, nanofibrous scaffolds can be tailored and modified to improve their biocompatibility for applications such as tissue engineering, drug delivery and wound dressings. For example, electrospun mats have been used in clinical studies for the treatment of arterial occlusive disease, skin cancer and diabetic foot Table . As discAD and EM contributed to the conception and design of the study. AD and EM wrote the first draft of the manuscript. DT wrote sections of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The Geriatric Interprofessional Team Transformation in Primary Care (GITT-PC) model improves delivery of healthcare to older adults in primary care by training healthcare professionals in team functioning, rapid cycle QI, and evidence based geriatric practice. The program capitalizes on the role of nursing and other healthcare disciplines. To maximize sustainability, it focuses on Medicare-reimbursable visits. This program will focus on the implementation of the Annual Wellness Visit (AWV) through a collaboration between Dartmouth and 3 GWEPs: University of Florida, University of Louisville and the University of Wyoming. The model\u2019s standardized approach to implementation begins with practice assessments and two trainings. The first training focuses on team functioning & rapid cycle QI and the second is a deep dive training focused on the implementation of the AWV. After the training, practices participate in a data-driven, virtual learning collaborative with monthly data collection and learning sessions. Since 2015, the AWV, through the GITT-PC model has been implemented in 14 sites in northern New England, 10 sites in upstate New York, and nationally through five other GWEP awardees across the country."} +{"text": "This article describes the data associated with the research paper entitled \u201cSubjective life satisfaction in public housing in urban areas of Ogun State\u201d by\u00a0Ibem and Amole (2013). A multistage sampling technique and questionnaire were used to extract data from occupants in 517 dwelling units in ten selected government mass housing schemes located in five urban centers in Ogun State, Nigeria. The dataset has 57 different variables describing households\u2019 demographics, dwelling units\u2019 features, supply of basic services, and neighbourhood environment in the residential estates. In addition, it also contains variables used to assess residential satisfaction and satisfaction with life. The Statistical Package of the Social Sciences (SPSS) file, descriptive statistics for all the variables and questionnaire used to derive the data are provided in this article. The dataset will enhance understanding of the main research findings and conclusions. Specifications tableValue of the data\u2022The dataset is valuable as it provides insight into the housing situations of occupants in government mass housing projects in five urban centers of Ogun State southwest, Nigeria.\u2022The data also have value in understanding the standard of living of occupants in selected mass housing schemes developed by the government in Ogun State.\u2022Housing researchers can use the dataset to compare the housing situations of occupants in other government residential mass housing estates and types of urban housing environment.\u2022The dataset can be used to assess the performance of government constructed mass housing schemes in meeting the needs and expectations of end-users.\u2022The data and questionnaire instrument can be valuable in similar studies in the future.1The dataset described in this article was extracted from 517 residents in the (i) Workers Housing Estate, Laderin (ii) Ogun State Housing Corporation Estate, Ajebo (iii) Obasanjo Hill-Top (GRA) Estate (iv) Kemta Extension Housing Estate, Olokota (v) Media Village, Ajebo; and (vi) Otunba Gbenga Daniel Housing Estate, Asero in Abeokuta. Others are the Ogun State Housing Corporation, Idiroko Road, Ota; Otunba Gbenga Daniel-Sparklight housing estate, Ibafo; Ogun State Property Investment Corporation (OPIC) Estate, Agbara and Otunba Gbenga Daniel Housing Estate, Itanrin, Ijebu-Ode in Ogun State, southwest Nigeria The dataset comprises nominal, interval and ordinal data and contains nine demographics variables and 16 objective housing characteristics, including the number of bedrooms, type of residence, location and use of kitchen, type of walling and ceiling materials, window and door types, wall and floor finishes, type of roofing materials, mode of acquisition of residence and state of repair of the buildings, and modes of water supply, main source of power supply, domestics waste disposal arrangement. It also has 31 subjective variables drawn from dwelling units\u2019 characteristics, sources of water and electricity in the dwelling units; physical, social and economic characteristics of the neighbourhood environments as well as management practices in the residential estates, used to investigate residential satisfaction Detailed descriptions of each of these variables can be found in the sample copy of questionnaire instrument, the SPSS file, and residents\u2019 responses to the questionnaire included in the supplementary files and made available in this article.2Very Dissatisfied and ending with \u20185\u2019 for Very Satisfied was used. Similar studies have used this scale of measurement as seen in the previous works by The dataset was sourced from ten mass housing estates constructed between 2003 and 2010 by the Government of Ogun State using the Core housing, Shell, Public-Private Partnerships (PPPs) and Turnkey strategies in Abeokuta, Ota, Ijebu- Ode, Ifo and Agbara. Based on the research by Ibem and Amole A cross-sectional survey involving the administration of pre-tested questionnaire was used to gather the data from residents in the selected estates. This is in line with the approach adopted by previous authors in similar studies In the survey, each of the 15 and 30 housing units occupied in the residential estates developed through Shell and PPPs strategies, respectively, was given a questionnaire to fill, however, while in the residential estates developed using the Core housing and Turnkey strategies, random sampling method was applied in selecting dwelling units for the administration of questionnaire to the occupants. The questionnaire was administered by hand to household heads or their representatives in each of the dwelling units selected in the morning and evening hours of week days and daytime at weekends between December 2009 and February 2010. Although 670 questionnaires were distributed in all the ten estates, 517 questionnaires retrieved were found to have been correctly filled by the respondents. The SPSS software package was used to analyse the data and the responses are presented using tables and figures as shown in the supplementary files."} +{"text": "This initiative, partially supported by public Spanish government funds, was also the promoter of the Spanish Network on Ion Channels (RECI), a multidisciplinary network that includes more than 50 Spanish groups interested on ion channels (www.reci-ionchannel.org). In the present Special Issue, some SICI members, as well as RECI colleagues, wanted to contribute with the most update knowledge of representative ion channel research in Spain for the last 10 years.The Spanish Ion Channel Initiative consortium the composition, structure and role of signaling channel complexes (channelosomes) in health and disease; (ii) the atomic structure of the pore forming subunits, of channel complexes and their dynamics; (iii) the molecular and cellular mechanisms underlying channelopathy phenotypes, as well as the implication of ion channels in the etiology of other human diseases; and, (iv) the discovery of therapeutically useful channel modulators for drug development. SICI has addressed these questions by establishing an integrative and inter-disciplinary ion channel program that brought together complementary skills. SICI pursued innovation through integration by assembling a multidisciplinary team composed of physiologists, biochemists, biophysicists, structural biologists, chemists, and pharmacologists. The major outcome of SICI has been the generation of innovative knowledge in the ion channel arena that has resulted in: (i) ground-breaking, transferable technology; (ii) original ion channel therapeutics for the treatment of human disorders; and, (iii) an integrated educational program on ion channels for graduated and postgraduate students. The integration of ion channel research via the multidisciplinary teamwork has proven to be very productive, as reflected by almost 500 scientific articles produced by the research groups that participate in SICI. In this special issue the reader may find interesting contributions from structure-function studies to cell biology, pharmacology, or physiology of ion channels.Keeping all this in mind, we, the editors of this special issue, thank the contributors for their effort and whish that the lecture of these selected contributions will be enjoyable. These reviews and research papers bona fide reflect the outstanding level of the last 10 years research on ion channels performed by SICI and RECI members."} +{"text": "To assess the impact of scientific and technical training on midwives' abilities in collecting and recording the key performance indicators for fetal growth chart development in limited-resource settings. A descriptive design was used to describe midwives' abilities in timely collecting and recording the minimum data required to estimate fetal weight and develop fetal growth chart. The study was conducted among 19 urban and rural midwives in South Kalimantan, Indonesia, between April 2016 and October 2017. The training provided access to antenatal care information on 4,946 women (retrospective cohort study) and 381 women (prospective cohort study). The average amount of recorded antenatal care data on the key performance indicators of fetal growth assessment has been significantly improved through scientific and technical training. Scientific knowledge and technical abilities have enabled midwives to timely record routine data of the key performance indicators for fetal growth surveillance. Access to this information is vital during different stages of pregnancy. The information can be utilised as evidence-based guidelines to assess fetal risks through fetal weight estimation and to develop fetal growth chart that is currently not available in Indonesian primary healthcare systems. Fetal growth assessment during antenatal care (ANC) is fundamental in preventing potentially adverse pregnancy outcomes. It has been well documented that one of the main objectives of ANC services is to detect the risk of intergrowth abnormalities , 2. The Access to, adequate use of, and systematic analysis of fetal growth information is crucial for monitoring, detecting, and assessing risks linked to neonatal mortality. The access to reliable, complete, and timely information on pregnancy-related outcomes and interventions remains challenging in Indonesia. Thus, leading to non-evidence-based decisions for program planning and allocating resources , 7.Access to the results of fetal growth assessment during routine ANC examinations is essential , 8\u201310. TImprovement of the data availability, consistency, and quality has become one of the world's priority actions in increasing life survival and reducing the burden of care costs for life-threatening situations and disability for newborns , 15\u201317. Midwives are primary practitioners over 87%) in providing ANC service to pregnant women, detecting potential complications and abnormalities through pregnancy to delivery, and providing timely interventions and referrals \u201321. They7% in proAccess to national and local data on individual maternal, fetal, and neonatal health information during ANC remains insufficient, particularly in developing countries. In Indonesia, the difficulty in collecting the data hampered the development of both standard fetal and newborn growth charts . UnrecorThe aim of this study was to assess the impact of scientific and technical training on midwives' abilities in documenting the minimum data required for fetal weight estimation and fetal growth chart development.This research is the continuation of the previously published study, and the details have been provided in Anggraini et al. . The priA descriptive design using quantitative methods was used to achieve the research aim. Midwives' abilities in collecting and recording the minimum data required for fetal weight estimation , 26 and This study used fetal growth assessment tools which are listed in the first column of Descriptive statistics used to assess the performance of routine ANC data collection, particularly in documenting the key performance indicators of fetal growth assessment , are theAs a part of doctoral degree research, this study has obtained research permissions from the Indonesian national, provincial, and local governments and two ethics' clearances from the Medical Research Ethics Committee, University of Lambung Mangkurat (ULM), Indonesia (reference: 018/KEPK-FK UNLAM/EC/III/2016) and the College Human Ethics Advisory Network (CHEAN), RMIT University, Australia (reference: ASEHAPP 19-16/RM no. 19974). Information about the confidential nature of the project and a consent form (written in both Bahasa Indonesia and English) for recruitment to the study were given to the selected midwives and pregnant women (prospective study), who all agreed to participate.The results discussed below are based on information obtained from the participating midwives, who have the average age of 41 years (ranged between 29 and 56 years) and the average working experience of 19 years (ranged between 6 and 36 years). Further details on participants' characteristics are provided in Anggraini et al. .Scientific and technical training has significantly improved the average amount of recorded ANC data on the key performance indicators of fetal growth assessment suggested in In Indonesia, Johnson-Toshach model is natioBefore training, midwives' unawareness on the importance of recording FH is clearly indicated in However, after training, the responsiveness to those data documentation was significantly improved , particuGardosi et al. recommenFigures As with the main database performance, there was significant improvement of midwives' competencies across PHC facilities in documenting the optional databases for individual fetal growth chart development Figures . This waThe awareness by Indonesian midwives, particularly in rural areas, of the importance of documenting FH and FS at a given GA to estimate fetal weight using the current formula has significantly improved after the training . However, the databases' adequacy remained below 70%. A similar trend of low recording of FH (range 36-76%) was also found in rural Australia .Routine and reliable measurement of FH and its documentation at a given GA throughout pregnancy are essential. Although many factors influence the wellbeing of the fetus, FH remains one of the most recommended and accessible predictors to estimate fetal weight and moniThe measurement of FH is a simple and cost-effective clinical activity. It remains an important first-level screening tool, widely used during routine ANC in both high- and low-income settings, particularly in rural areas where ultrasound machines and skilled personnel are not always available , 41. WheBefore training, access to the recommended minimum databases to develop individual fetal growth chart based onThe adoption of the international standard of fetal and newborn growth references , 46, 47 The current utilisation of global reference in Indonesia has deplThe provision of the fetal growth chart during pregnancy is important to assess the viability of the fetus at different stages of pregnancy and to ensure neonatal survival and wellbeing. The chart can be an effective screening tool to assist midwives in analysing and detecting the risks of fetal growth abnormalities such as prematurity and LBW, as part of their role to improve ANC service . Consequth highest for preterm births in the world [Maternal, neonatal, and child health programmes have been initiated and implemented to reduce the mortality rate in Indonesia, particularly due to prematurity and LBW , 52, 53.he world , 55. Thehe world , 13, 56.To the best of our knowledge, the scientific and technical training has, for the first time, equipped the urban and rural Indonesian midwives with the updated scientific knowledge and technology regarding fetal growth assessment during pregnancy. The training has also increased the midwives' awareness on the importance of timely documentation of the key data on characteristics of mother and fetus in the current manual pregnancy registers . In relaScientific and technical training has significantly improved the average amount of recorded ANC data on the key performance indicators of fetal growth assessment during pregnancy. The training has equipped midwives with scientific knowledge and technical abilities to electronically record maternal, fetal, and neonatal health information during pregnancy and delivery. Provision and adequate use of this information during different stages of pregnancy enables fetal weight estimation and promotes the development of fetal growth chart that is currently not available in Indonesian ANC practices, particularly in rural areas. The fetal growth chart is an effective surveillance tool that can assist midwives in capturing, reviewing, and assessing fetal risk factors to end preventable mortality."} +{"text": "Currently, the GHS has three panels consisting of 5000 households of the GHS collecting additional data on agricultural activities, other household income activities, and household expenditure and consumption, among others. This is to improve data from the agricultural sector and the linkage to other facets of households\u2019 characteristics and outcomes. The LSMS data-set, questionnaire, and basic information document are freely available online at: Specifications TableValue of the data\u2022LSMS-ISA data is an integration of longitudinal panel survey into GHS that makes it possible to produce a more comprehensive analysis of poverty indicators on socio-economic characteristics for rural households3\u2022LSMS-ISA data helps in building capacity and the development of sustainable systems for the production of accurate and timely information on agricultural households\u2022LSMS-ISA helps the development of an innovating model for collecting agricultural data\u2022LSMS generates high-quality data, improving survey methods, and building capacity. The goal of the LSMS is to facilitate the use of household survey data for evidence-based policymaking.1The rural households\u2019 survey is important source of development data, but in low- and middle-income countries, the capacity to conduct and analyse them widely differs. The LSMS-ISA helps address these issues with respect to agricultural data The Living Standards Measurement Study-Integrated Surveys on Agriculture (LSMS-ISA), General Household Survey (GHS) Panel is part of a larger, regional project in Sub-Saharan Africa (SSA) to improve agricultural data for analysis. Ethiopia, Mali, Malawi, Niger, Nigeria, Tanzania and Uganda are the seven countries being supported by the World Bank through funding from the Bill and Melinda Gates Foundation (BMGF), to strengthen the production of household-level data on agriculture. This regional project, the LSMS-ISA has the aim of enhancing people\u05f3s understanding of agriculture in SSA, specifically, its role on household welfare, access to agricultural land and poverty reduction 2The survey instruments for this data set is based on LSMS-ISA for the Household Survey Panel sample which comprises of 5000 households were considered to be characteristics at the zonal and national levels which is made up of both the urban and rural areas.Wave 3 GHS-Panel comprises three questionnaires2.1The Household Questionnaire gives data on socioeconomics; instruction; wellbeing (counting anthropometric estimation for kids and kid vaccination); work and work information accumulation alternatives; nourishment and non-sustenance use; family unit nonfarm pay producing exercises; nourishment security and stuns; security nets; lodging conditions; resources; data and correspondence innovation; and different wellsprings of family unit salary.2.2The Agriculture Questionnaire solicits information on the ownership of land and its uses such as farm labour; inputs use; GPS measuring area of land and management of household farmland; machinery used for farming; irrigation; harvesting and crop utilisation; animal holdings and fishing , Table 2"} +{"text": "Dear Editor,Fibroepithelioma of Pinkus (FEP), also known as fibroepithelial basal cell carcinoma, is a rare cutaneous neoplasm. It has a frequency that ranges from 0.2% to 1.4% in a series of basal cell carcinomas.The patient was 69 years old, male, white, and with a history of bone tumor in the left femur at the age of 17 years. He had undergone a surgical intervention and adjuvant radiotherapy. Years later, he noticed the appearance of red-brown, asymptomatic, slowly evolving papules, restricted to the skin adjacent to the surgical scar, in the area previously subjected to radiotherapy. In 2016, the patient sought dermatological treatment. He exhibited discreetly raised translucent erythematous plaques with pigmented inferior borders, located on the upper lateral aspect of the left thigh. He also exhibited some translucent erythematous papules, located near the surgical scar . The hisFEP affects non-photoexposed areas, commonly in the inguinal and lumbosacral regions.The etiopathogenesis of FEP is controversial.5The histopathological features are fundamental for diagnosis. They are described as peculiar and unmistakable, evidencing thin anastomosing strands of basaloid cells, surrounded by abundant stroma, which form a uniform border with the underlying dermis, resembling a honeycomb.The evolution of FEP is slow. It exhibits low local aggression and little risk of metastasis.In the presented case, the patient had multiple FEP lesions excised and is attending regular follow-up appointments at the dermatology service.This case is reported to emphasize the possibility of other etiologies of basal cell carcinomas, such as previous radiotherapy.None declared.Bruna Anjos Badar\u00f3: Conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing and interpreting the data; critical review of the literature; critical review of the manuscript.Lucia Martins Diniz: Approval of the final version of the manuscript; conception and planning of the study; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Ernesto Negris Neto: Obtaining, analyzing and interpreting the data; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied.Elton Almeida Lucas: Obtaining, analyzing and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied.None declared."} +{"text": "The human brain is the most complex organ in the human body. It comprises billions of neurons and supporting cells in a complex network, managing everything from physical functions to thoughts and feelings of humans. Dysfunctions of the complex network caused by both genetic and environmental factors result in many brain disorders. Several large brain projects have been launched, aiming to understand how the brain works in health and disease, including the Human Brain Project of the European Union, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative of the United States, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MIND) project of Japan. These projects gather, organize, and disseminate data describing the brain and related diseases, in the meantime develop brain-inspired computing and data analytics. As an example, the Human Connectome project (HCP) uses cutting-edge brain imaging technologies to map the circuitry of the healthy adult human brain in order to track their susceptibility to change during aging and disorder occurrence. In addition, the HCP will collect DNA samples, demographic information and behavioral data from the subject to investigate the effect on human brain by both genetics and environment. By analyzing the functional magnetic resonance imaging (fMRI) mappings to detect the factors determining face recognition, the code for facial identity comprised of 205 neurons in primate brain was discovered China Brain Project (CBP) has recently been initiated to promote major advances in the basic understanding of brain and address some urgent societal needs on human health ., for the first time, systematically explored the cellular and molecular mechanisms involved in the formation of prefrontal lobes in the development of the human prefrontal cortex (PFC) by single-cell RNA sequencing (scRNA-seq) Technologies for single-cell amplification and sequencing are maturing, which will be applied by more researchers as a routine tool to assess the genome, transcriptome, proteome, and epigenome of single cells to gain biological insights, particularly in brain science. To date, single-cell transcriptome is the most widely used single-cell sequencing technology, especially in model organism mice The underlying causes of neurological and psychiatric disorders, such as Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and major depression, are as important as the principles of how the brain works in normal state. Genome-wide association study (GWAS) has been the primary method to explore the genetic risk of common genetic diseases, like PD. Recently the subpopulations of dopaminergic neurons that are linked to PD in the mouse brain at embryonic and early postnatal time points were characterized by scRNA-seq Brain science has entered a new era of big data with the development of single-cell sequencing technologies, the development of new tools for mapping neuronal connections, the increasing resolution of imaging technologies, and the explosion of nanoscience. Many large brain projects and individual studies have accumulated a huge amount of data related to brain function. Taking the HCP as an example, it released high quality image data from 1100 subjects plus out-of-scanner, behavior-only data from 100 subjects, which have an unprecedented spatial resolution of 1.25\u202fmm and very low structured temporal noise We are facing a real big challenge with the increasingly complex datasets in brain science. First, for each type of data, there is a lack of standard specification for their generation, storage, processing, and utilization, which hampers the comparison and integration of data or results from different research groups. Moreover, most of the data are unstructured, heterogeneous, and generated from different sources. Developing efficient tools to transform them into structured and normalized format is of critical importance. Second, how to integrate all different types of data including medical information, omics data, morphology, and connectivity images to gain a deep understanding of the brain\u2019s role is a bottleneck. In addition, the technologies of the internet, artificial intelligence, augmented reality (AR), and virtual reality (VR) will be gradually applied to the study of brain science. Improved statistical models are needed for reliable inference from these data. Computational strategies are becoming central to virtually everything we do now. Third, storage and processing of such large datasets with high efficiency remain difficult. The rapid rate of data generation requires powerful storage and processing ability. New processing and computing methods as well as storage devices are needed to bridge the increasing gap between data growth and processing power. Advances in neuroimaging, genomics, computational neuroscience, and engineering have ushered us to another great era of brain science, when we are bound to make extraordinary discoveries regarding normal brain activity, disorders of the brain, and our very sense of self.In the era of big data, brain science is a fast-developing field. This special issue provides a glimpse of advances in the field of brain science, mainly focused on genomics and neuroimaging.de novo mutations in developmental disorders with special emphasis on isoform-specific mutations Genomics is at present one of the main workhorses for brain science. We specifically highlight the application of genomics tools to the investigation of brain disorders, including causal mutations, diagnostic biomarkers, and actionable targets. Built upon previous high-throughput sequencing studies, Ludwig et al. derived a model based on microRNAs to detect AD using peripheral blood In the meantime, neuroimaging is increasingly utilized in the investigation of brain function and dysfunction. Liu et al. investigated cognitive dysfunction in type 2 diabetes using functional neural network Through these snapshots, we hope the readers can achieve better understanding of the current status in brain science, especially the challenges we are facing and the road ahead of us.The authors have declared no competing interests."} +{"text": "Gender equality in access to higher education is an important factor in building a sustainable world. Although a good number of countries across the globe have achieved parity in primary education between boys and girls, the target is yet to be widely attained at tertiary level of education. In this data article, empirical data on yearly admissions into accredited tertiary institutions in Nigeria are extensively explored to reveal the existence of gender gaps in the national admission process. Details on the number of candidates admitted into all accredited universities, polytechnics, and colleges of education between 2010 and 2015 were obtained directly from the Joint Admissions and Matriculation Board (JAMB). Gender distributions of admitted candidates are analyzed across the thirty-six (36) states of the federation, the Federal Capital Territory (FCT), and the international students\u2019 category. Gender disparity in admissions into Nigerian tertiary institutions are explored using relevant descriptive statistics, box plots, bar charts, line graphs, and pie charts. In addition, Analysis of Variance (ANOVA) is carried out on the historical data to find out if there are significant differences in the arithmetic means of females and males admitted over the six-year period. Furthermore, multiple comparison post-hoc test results are presented in tables to understand the extent of variations (if any) in gender distribution over the years. The robust data exploration reported in this data article will help national regulatory bodies and relevant stakeholders in policy formulation and decision making towards ensuring equal access to higher education in Nigeria. Specifications tableValue of the data\u2022Thorough evaluation, correct interpretation, and contextual discussion of the data analyses provided in this data article may speed up the achievement of Goals 4 and 5 of the global Sustainable Development Goals (SDGs) in Nigeria.\u2022Various research efforts aimed at achieving SDGs 1, 3, 7, 10, and 11, will be intensified if access is granted to more females into Higher Education Institutions, particularly into Science, Technology, Engineering, and Mathematics (STEM) programs.\u2022The data exploration provided in this data article will call the attention of national regulatory bodies, executives, administrators, and relevant stakeholders to the need for strategic advocacy and promotion of equal access to higher education among all women and men in Nigeria.\u2022Robust data exploration presented in this data article will help the United Nations (UN) to objectively assess the level of gender disparity in access to higher education in Nigeria.\u2022The contribution of this data article will further widen the coverage of evidence-based and reproducible research on gender disparity in higher education. In addition, the utility of the data may open doors for new research collaborations on the trends and patterns of enrollment by gender in higher institutions in sub-Saharan Africa.1Elimination of gender disparity at all levels of education is one of the major global goals in the pursuit of sustainable development across the globe The basic features of the quantitative data on yearly admissions into all accredited Nigerian universities, polytechnics, and colleges of education between 2010 and 2015 were described using eleven (11) different statistical parameters namely: mean, median, mode, standard deviation, variance, kurtosis, Skewness, range, minimum value, maximum value, and the sum. The descriptive statistics of the number of candidates admitted are computed for two gender category and the results obtained are presented in Also, the gender distributions of admitted candidates were analyzed across the thirty-six (36) states of the federation, the Federal Capital Territory (FCT), and the international students\u2019 category. The distributions of enrollment in higher education for the period of six years (2010\u20132015) are shown in The proportions of females and males in admissions into Nigerian tertiary institutions are depicted using pie charts shown in 2Details on the number of candidates admitted into all accredited universities, polytechnics, and colleges of education between 2010 and 2015 were obtained directly from the Joint Admissions and Matriculation Board (JAMB). Gender distributions of admitted candidates are analyzed across the thirty-six (36) states of the federation, the Federal Capital Territory (FCT), and the international students\u2019 category. Gender disparity in admissions into Nigerian tertiary institutions are explored using relevant descriptive statistics, box plots, bar charts, line graphs, and pie charts."} +{"text": "Population aging and longevity in an era of immense environmental instability raises concerns about the precarity of aging and insecurity in later life. From home- and neighborhood-level insecurities to uncertainties generated by climate change or broad economic and sociopolitical upheaval across the globe, the factors contributing to instabilities relevant to older populations are heterogeneous in scale and cause. This symposium focuses on understanding older people\u2019s needs and experiences in the context of unstable social, economic, political, and natural environments. The first paper investigates effects of socio-environmental disruption on the well-being, recovery, and resilience of older adults in Louisiana and Mississippi deeply affected by Hurricane Katrina. The second paper explores the confinement, exclusion, and loss of autonomy, as well as the creative negotiation and sociopolitical reclamation of space, among disabled older adults experiencing houselessness. The third paper discusses filmmaking with formerly homeless older adults as a method to engage marginalized individuals in community-based participatory research and better understand nuanced meanings of \u2018home\u2019. The fourth paper explores how transportation and technology can serve as both facilitators and barriers to accessibility and social connectivity among ethnically diverse low-income older adults. Altogether, the papers critically discuss novel scholarship and applied research in environmental gerontology from the micro to macro scale. The symposium inspires methodological innovation and critical research directions, and informs place-based policymaking to address diverse contexts of aging in place."} +{"text": "International Journal of Telerehabilitation (IJT) is a biannual journal dedicated to advancing telerehabilitation by disseminating information about current research and practices. The journal is PubMed indexed, and was recently accepted into Scopus, with indexing to follow.The International Journal of Telerehabilitation (IJT) explores five diverse topics that fall under the unifying umbrella of telerehabilitation: telehealth privacy and security; the usability of an immersive augmented reality based system with haptics for synchronous remote musculoskeletal examination; parent perspectives of occupational therapy delivered through telehealth; the use of telehealth in early intervention in Colorado; and the use of telerehabilitation as an effective platform to help manage Low-Back Pain (LBP). We thank our authors and are honored to publish their work.The current issue of the multi-disciplinary We are grateful for the generous efforts of the IJT reviewers, many of whom have reviewed prospective IJT articles for over a decade. Sections Editor, William E. Janes, OTD, MSCI, OTR/L has been a very impactful reviewer and support to authors.Thanks also to the publisher of IJT, the University Library System, University of Pittsburgh. IJT is currently sponsored by the Rehabilitation Engineering Research Center on Information and Communication Technology Access at the University of Pittsburgh. The RERC is funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR). Volumes 1\u20137 were sponsored by the Rehabilitation Engineering Research Center (RERC) on Telerehabilitation at the University of Pittsburgh.We cordially invite submissions to the Fall 2019 issue by mid-September 2019. IJT accepts original research, case studies, viewpoints, technology reviews, book reviews, and country reports that detail the status of telerehabilitation.Sincerely,Ellen R. Cohn, PhD, CCC-SLP, ASHA-FIJT EditorJana Cason, DHSc, OTR/L, FAOTASenior Associate Editor"} +{"text": "In Practice, and The World Allergy Organization Journal and chaired by Mariana Castells, MD, PhD, and Pascal Demoly, MD, PhD.This article is one of a series of international consensus documents developed from the International Drug Allergy Symposium held at the Joint Congress of the American Academy of Allergy, Asthma & Immunology/World Allergy Organization on March 1, 2018, in Orlando, Florida, USA. The symposium was sponsored by The Journal of Allergy and Clinical Immunology, The Journal of Allergy and Clinical Immunology: The prevalence of self-reported drug allergy has been reported up to 8% in the general population and thatDHRs have a significant impact on clinical practice, socio-economy, drug development, and public health. Although tremendous progress has been made over the past two decades in the understanding of the mechanisms of drug allergy and hypersensitivity and their management, several unmet needs remain. Several task forces with representatives from the key stakeholders have identified the critical data gaps and opportunities and made recommendations on how to overcome some of the barriers to DHRs research and address research needs , 6, 7. WEpidemiologic risk factors for DHRs are not well characterized and may be influenced by regional/national differences in drug prescriptions. All drugs can induce DHRs, but the incidence and risk factors for individual drugs have been poorly defined. The development of a network that can increase the population size from which to capture data on DHRs would be a major advance. The establishment of such a network would need the concomitant development of unique DHR databases collecting standardised data, the nature of which would have to be defined on the basis of expert consensus. The development of such a database would have huge benefits in validating diagnostic procedures and defining the risk factors associated with DHRs. It would permit personalized analysis at the individual level and the country level , and would allow longitudinal assessment of the safety of new drugs. It would overcome the major limitation of spontaneous reporting, i.e. under-reporting, by engaging interested clinicians involved in the network. It would assess the socio-economic impact of DHRs, drug allergy pathways, and allow follow-up studies .One of the major reason why we are still lacking reliable in vitro tests is due to a lag in the understanding of the mechanisms of most DHRs. Drugs are capable of inducing all the types of immunological reactions described by Gell and Coombs, with the most common being IgE and T-cell mediated reactions . Drugs c(1) identifying the differences in standard management in the field, (2) providing evidence-based data supporting the different approaches, (3) developing potential expert opinion regarding best practices, and (4) designing future pragmatic research and clinical studies to evaluate outcomes. In order to guide and standardize the approach, we asked them to summarize the current knowledge on their topic in terms of (1) what we knew and what we have (most recently) learned, (2) what is (still) controversial and/or done differently in different institutions or geographical areas , (3) what consensus recommendations can be made now? , and (4) list the unmet needs . The individual controversy and consensus statements are being concurrently published [With the above in mind, the editors of The Journal of Allergy and Clinical Immunology, The Journal of Allergy and Clinical Immunology: In Practice, and The World Allergy Organization Journal sponsored the International Drug Allergy Symposium. This symposium, which was held March 1, 2018 during the American Academy of Allergy, Asthma and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in Orlando, Florida, aimed at developing a series of international consensus documents. The controversies were grouped into five categories: 1) Penicillin and cephalosporin testing, 2) Radiographic contrast media, 3) In vitro testing, 4) Testing for delayed reactions, and 5) Drug allergy pathways. The information was presented by team leaders and discussed thoroughly in person and then evaluated by an expanded group of more than fifty experts around the world. Experts were asked to focus on ublished \u201313. ThisThe group on penicillin and cephalosporin testing identifiThe group on radiographic contrast media (RCM) testing classifiThe group on in vitro testing reviewedThe group on testing for delayed reactions identifiThe group on drug allergy pathways identifi"} +{"text": "Despite the well-documented clinical and public health impacts of palliative care on older patients\u2019 end of life experiences, racial and ethnic disparities in palliative care use still remain. However, empirical evidence on the sources of disparities is lacking, particularly for Asian Americans. Given the rapid growth and increasing cultural diversity of the older Asian population in the United States, a systematic review was conducted to provide a comprehensive overview of the best available evidence on the barriers to palliative care use among Asian Americans. Search was conducted using six electronic databases , and all procedures of the study have been guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). A total of 23 studies published in the U.S. since 1998 were included. Individual level barriers to palliative care service use among Asian Americans identified by the study included lack of palliative care knowledge, lack of insurance, cultural beliefs, language barrier, attitude toward death, family centered decision-making. Provider level barriers included lack of training and experience about palliative care, patient-provider discordance in language and culture, and absence of policy or guidance for providers. Although racial disparities in palliative care for Asian Americans were evident, Asian Americans were underrepresented in palliative research. Future research effort should be directed toward the development of culturally sensitive palliative care services and policies that reduce racial and ethnic specific barriers."} +{"text": "The evolution of the various hearing adaptations is connected to major structural changes in nearly all groups of vertebrates. Besides hearing, the detection of acceleration and orientation in space are key functions of this mechanosensory system.The symposium \u201cshow me your ear \u2013 the inner and middle ear in vertebrates\u201d held at the 11th International Congress of Vertebrate Morphology (ICVM) 2016 in Washington, DC (USA) intended to present current research addressing adaptation and evolution of the vertebrate otic region, auditory ossicles, vestibular system, and hearing physiology. The symposium aimed at an audience with interest in hearing research focusing on morphological, functional, and comparative studies. The presented talks and posters lead to the contributions of this virtual issue highlighting recent advances in the vertebrate balance and hearing system. This article serves as an introduction to the virtual issue contributions and intends to give a short overview of research papers focusing on vertebrate labyrinth and middle ear related structures in past and recent years. With the increasing application of high resolution and noninvasive computer tomography since the 1980s, 3D visualization and their respective analyses became essential for anatomical studies of the middle and inner ear.The vertebrate ear combines two main functions: balance and hearing. The vestibular part of the inner ear is the organ of equilibrium detecting head and body movements during locomotion . The semicircular canals (SCs) of the vestibular system detect angular acceleration, while utricule and saccule detect linear acceleration of elasmobranchs of the lateral line receptors and the labyrinth differs anatomically from the derived amniote ear in showing large and bulky stapedial bones (relative to braincase size) capable of the detection of substrate\u2010borne vibrations is the tympanum (tympanic membrane) overlying an air\u2010filled middle ear cavity with ossicles transmitting the sound to the oval window of the inner ear are able to close their external acoustic meatus with a meatal muscle, possibly for protection against mechanical damage or their own sound of nonmammalian amniotes, sounds bouncing off the skin surface are transmitted to the cochlear duct Manley, .In the 19th century, Georges Cuvier describeDiarthrognathus), which possess both functional jaw joints (primary and secondary) at the same time , incus (anvil), and stapes (stirrup) is laterally restricted by the ectotympanic ring and completely detached from the mandible Allin, . Complexe Allin, . The sege Allin, . Even ife Allin, , 1973. De Allin, conductee Allin, and Fleie Allin, .1.2The inner ear (labyrinth) of vertebrates comprises two main functions: (a) balancing of the individual using the ampullae of the three SCs and the sensory field of utriculus and sacculus, and (b) hearing ability with the sensory hair cells of basilar papilla of the lagena of nonmammalian amniotes . The inner ear is composed of a membranous system (membranous labyrinth) filled with endolymphatic fluid enclosed inside a bony endocast (bony labyrinth), filled with perilymphatic fluid. Both fluids differ in their concentration of potassium and sodium and early tetrapods, which remains unossified during embryogenesis (Clack, In jawless vertebrates, the number of SCs varies Retzius, . The vess Clack, . The rous Clack, , which es Clack, .In the 16th century, Bartholomeus Eustachius discovered the cochlear part of the ear, which was denoted by Gabriel Falloppio as \u201ccochlea\u201d in 1561 Gitter, . PolitzeEven though Hyrtl doubted The shape and number of coils of the mammalian cochlea is known to have a strong phylogenetic signal Ekdale, . MonotreThe evolution of the amphibian inner ear on its way to amniotes is controversially discussed Lombard, , 1976. T1.3Since the expanding availability of noninvasive microcomputed tomography anatomical investigations of the middle and inner ear region of extant and extinct vertebrates are of still growing interest to the scientific community addressing complex questions. For example, the evolution of the huge diversity of the membranous inner ear labyrinth morphology, the function of the vestibular system for detecting acceleration and deceleration of the head and related transmission of sensory signals, the evolution of the mammalian coiled cochlea for enhanced hearing capability, and many more. Recently conducted studies focus on phylogenetic signals to contribute to the tree of life and reveal ecological adaptations. The goal of the symposium held at the 11th ICVM was to exchange newly acquired insights, new technical approaches, and exchange of information addressing anatomical meaning of the bony structure of inner and middle ear related structures in the system of vertebrates.There are no Conflict of interests.All authors drafted the manuscript, and gave final approval for publication."} +{"text": "To assess the public health risk to Singapore posed by the emergence of artemisinin-resistant (ART-R) malaria in the Greater Mekong Subregion (GMS).We assessed the likelihood of importation of drug-resistant malaria into Singapore and the impact on public health of its subsequent secondary spread in Singapore. Literature on the epidemiology and contextual factors associated with ART-R malaria was reviewed. The epidemiology of malaria cases in Singapore was analysed. The vulnerability and receptivity of Singapore were examined, including the connectivity with countries reporting ART-R malaria, as well as the preparedness of Singaporean health authorities. Sources of information include international journals, World Health Organization guidelines, data from the Singapore Ministry of Health and National Public Health Laboratory of the National Centre for Infectious Diseases, and the International Air Transport Association.The importation of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore\u2019s vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of such an event is low based on the rarity and decreasing trend of imported malaria incidence.Anopheles vectors in Singapore, imported cases of drug-resistant malaria could cause secondary transmission. Nevertheless, the risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases.With the presence of This risk assessment highlights the need for a continued high degree of vigilance of ART-R malaria locally and globally to minimize the risk and public health impact of drug-resistant malaria in Singapore. Plasmodium falciparum, P. vivax and P. malariae. , which comprises Cambodia, the Lao People's Democratic Republic, Myanmar, Thailand, Viet Nam and Yunnan Province of China, has long been the epicentre of antimalarial drug resistance. since 1982, Singapore is at risk of importation of emerging diseases including artemisinin-resistant (ART-R) malaria. In view of the emergence of resistance across the GMS and the spread beyond its borders, we carried out an analysis to assess the risk of importation and secondary spread of ART-R malaria infection in Singapore.The risk of importation of drug-resistant malaria into Singapore and the public health impact of its subsequent secondary spread in Singapore were assessed following WHO guidance on the risk assessment of acute public health events. gene was performed by the Malaria Reference Centre from the National Public Health Laboratory (MRC-NPHL) by polymerase chain reaction (PCR) amplification and sequencing according to the protocol of Ariey et al. followed by P. falciparum (22%).Among the 290 cases of malaria reported in Singapore between 2013 and 2017, 289 (99.7%) were imported cases, of whom 141 (49%) were work-permit or employment pass holders. The majority of imported cases were from South-East Asia (16%), Africa (16%) and India (62%). Among the cases imported from South-East Asia, most were from Indonesia and Malaysia, which accounted for 8% and 4% of cases, respectively. Most of the cases of malaria reported in Singapore between 2013 and 2017 were caused by P. falciparum cases tested had mutations possibly associated with artemisinin resistance Among cities outside the GMS, Singapore receives the highest number of travellers from the GMS , which was endorsed by all GMS countries. (To prevent global spread of artemisinin resistance, containment efforts have been initiated in the GMS. In 2015, WHO launched the The risk imposed to Singapore by the emergence of ART-R malaria was characterized using the information collected; key factors were considered to assess the likelihood of importation of cases into Singapore and the impact on public health (The risk characterization of likely based on the likelihood of importation and the according minimal consequence suggest that the overall risk of ART-R malaria to Singapore is low. The importation of a case of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore\u2019s vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of importation is considered low based on the rarity and the decreasing trend of imported malaria incidence over the past few years.Anopheles vectors in Singapore, imported cases of ART-R malaria can cause secondary transmission. The risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases as observed in the past local outbreaks of malaria initiated by imported cases.With the presence of P. falciparum cases in Singapore, 5.8% had genetic mutations that may confer resistance to artemisinin. The presence of competent local vectors, the high volume of travel from regions with ART-R malaria, and the presence of foreign workers from neighbouring endemic countries make it possible that drug-resistant malaria could be imported and introduced to Singapore. To reduce the risk of Singapore residents acquiring malaria infections overseas, pre-travel health education, particularly by travel agents, the media and health-care providers, can increase awareness of the risk of contracting malaria overseas so that personal preventive measures can be taken.Singapore is the top destination for travellers from the GMS. Among the imported Secondary spread following an imported case is also possible. However, any spread is not likely to be sustained. Malaria has not re-established itself as an endemic disease in Singapore despite local outbreaks since it was declared malaria-free in 1982. The Singapore health ministry and NEA have implemented comprehensive malaria surveillance and control programmes to detect cases and curb the transmission of local outbreaks.The risk assessment has some limitations. The assessment is based on limited data as the number of imported cases of malaria in Singapore is small. As the risk characterization was defined by the epidemiological and contextual knowledge available currently, conclusions could change as new information emerges. Ongoing studies on genetic mutations, particularly their underlying molecular and cellular mechanisms and their phenotypic manifestations in resistance, could provide a better understanding of an epidemic and facilitate the design of surveillance and control measures. Identification of new molecular markers and improvements in laboratory capability continues to impact disease surveillance as illustrated by the significant progress in global surveillance of artemisinin resistance expedited by the discovery of the molecular marker K13. (In conclusion, in view of the emergence of ART-R malaria in the GMS and its geographical expansion, this risk assessment highlights the need for a high degree of vigilance over the local and global situation to be maintained to minimize the risk and severity of the public health threat of ART-R malaria to Singapore."} +{"text": "Quantifying the impact of climate change and human activities on grassland dynamics is an essential step for developing sustainable grassland ecosystem management strategies. However, the direction and magnitude of climate change and human activities in driving alpine grassland dynamic over the Tibetan Plateau remain under debates. Here, we systematically reviewed the relevant studies on the methods, main conclusions, and causes for the inconsistency in distinguishing the respective contribution of climatic and anthropogenic forces to alpine grassland dynamic. Both manipulative experiments and traditional statistical analysis show that climate warming increase biomass in alpine meadows and decrease in alpine steppes, while both alpine steppes and meadows benefit from an increase in precipitation or soil moisture. Overgrazing is a major factor for the degradation of alpine grassland in local areas with high level of human activity intensity. However, across the entire Tibetan Plateau and its subregions, four views characterize the remaining controversies: alpine grassland changes are primarily due to (1) climatic force, (2) nonclimatic force, (3) combination of anthropogenic and climatic force, or (4) alternation of anthropogenic and climatic force. Furthermore, these views also show spatial inconsistencies. Differences on the source and quality of remote sensing products, the structure and parameter of models, and overlooking the spatiotemporal heterogeneity of human activity intensity contribute to current disagreements. In this review, we highlight the necessity for taking the spatiotemporal heterogeneity of human activity intensity into account in the models of attribution assessment, and the importance for accurate validation of climatic and anthropogenic contribution to alpine grassland variation at multiple scales for future studies. Finally, the relative contribution of climatic and anthropogenic factors to alpine grassland changes can be identified by comparing the trends of NPPH and NPPP , and Aqua climatic force, (2) nonclimatic force, (3) combination of anthropogenic and climatic force, or (4) alternation of anthropogenic and climatic force. These views also show spatial inconsistencies and lack validation. The current challenges in distinguishing climatic and anthropogenic contributions to alpine grassland variation on Tibetan Plateau mainly include the uncertainties in quality of remote sensing products, uncertainties in the accuracy of models, especially for simulating the potential vegetation growth, and overlooking spatiotemporal heterogeneity of human activity intensity. Thus, it is necessary to evaluate the differences among the multiple remote sensing datasets before inputting some of them into the models of attribution assessment, to take the spatiotemporal heterogeneity of human activity intensity into account in the models, and further to improve the accuracy of models. We also proposed a framework for accurate validation of anthropogenic and climatic contribution to alpine grassland variation at multiple scales for future studies.None declared.Zhang Y. and Liu L. designed the study, and Li L. wrote most of the first draft. Wu J., Li S., and Zhang H. contributed to the analysis and interpretation of the results. Zhang B., Ding M., Wang Z., and Paudel B. contributed to revise the manuscript and provided conceptual advice. All authors contributed to final approval for publication.\u00a0Click here for additional data file."} +{"text": "Axial sesamoiditis or osteitis of the proximal sesamoid bones (PSBs) in the horse is described as a rare condition. The cause remains unknown and speculative, with vascular, infectious and traumatic aetiologies implicated. It is specifically associated with injury of the palmar or plantar ligament (PL), also known as the intersesamoidean ligament. Imaging findings are generally rewarding, and radiological changes are typical, if not pathognomonic, for the condition. Lesions consist of bone lysis at the apical to mid-body axial margins of the PSBs, with variable degrees of joint effusion. Radiographic technique warrants careful attention to make a diagnosis, and exposure factors may need to be adjusted. Perineural, intra-articular and intra-thecal anaesthesia does not seem to provide consistent improvement of lameness in these cases, with literature reporting inconsistent findings. Ultrasonographic findings include digital flexor sheath effusion, loss of the normal fibre structure of the PL at its attachment to the PSBs, abnormal echogenicity or change in thickness of the PL, and irregular hyperechoic cortical margins of the axial margins of the PSBs. Scintigraphy, computed tomography and magnetic resonance imaging, although not necessary to make a diagnosis, may add valuable information regarding the location and extent of lesions. The prognosis remains guarded to poor for return to athletic function. The focus of this article is a comprehensive review of the proposed aetiopathogenesis of the condition, the prognosis and a summary of the literature findings with focus on the notable diagnostic imaging features, including radiography, ultrasonography, scintigraphy, computed tomography and magnetic resonance imaging. The PL is a thick collagenous structure firmly attached to the PSBs by a layer of fibrocartilage, creating a firm union between the two bones in the horse is described as a rare condition, with approximately 56 cases reported in the literature, with 32 of these cases described in the past 5 years , may be intermittent and is often of variable duration prior to presentation, with reports ranging from a few days to several months , intra-articular and intra-thecal (DFTS) anaesthesia do not seem to provide consistent improvement of lameness in these cases, with literature reporting inconsistent findings , lateromedial (LM), and two oblique views \u2013 dorsomedial-palmaro lateral oblique (DM-PaLO) and dorsolateral-palmaromedial oblique (DL-PaMO) uptake in the bone phase of the study of most lesions, with the exception of very small or inactive lesions findings have shown abnormal increased signal intensity within the ligament, and/or high signal intensity within the axial aspects of the sesamoid bones on short-Tau-inversion recovery (STIR) or proton density sequences, consistent with inflammation, necrosis or scar formation , infectious (degenerative neutrophilic fluid) and even normal findings described (Wisner et al. Arthroscopy of the palmar MCPJ or plantar MTPJ joint pouch reveals PL damage, consisting of fraying, discolouration and separation from the PSBs, and osteomalacia and osteochondral fragmentation of the axial borders of the PSBs (Dabareiner et al. Histopathological changes of the PL may range from acute to chronic, which is consistent with the duration of clinical signs (Wisner et al. Post-mortem findings usually consist of hyperaemia and defects or fissuring of the PL gliding surface and brown discolouration of the collagenous substance of the ligament (Wisner et al. Debate exists on the long-term outcome and prognosis of axial sesamoiditis. Evaluation of outcome was hampered in the past by several horses undergoing euthanasia without any treatment (Wisner et al. Septic forms generally carry a poor prognosis, and the general consensus appears to be that of a poor to guarded prognosis (Dunkerley et al. The Friesian breed has also been reported to carry an especially poor prognosis (Brommer et al. Axial sesamoiditis is a clinical entity in which the imaging findings are well documented and rewarding, but treatment and long-term outcome are often disappointing, and a poor prognosis can be expected in the majority of cases."} +{"text": "Healthcare Technology Letters (HTL) journal dedicated to the 12th edition of the Joint International Workshop on Augmented Environments for Computer-Assisted Interventions (AE-CAI) and Cerebral Visualization (CereVis). We are pleased to present the proceedings of this exciting scientific gathering held in conjunction with the Medical Image Computing and Computer-Assisted Interventions (MICCAI) conference on September 16th, 2018 in Granada, Spain.Welcome to this Special Issue of the IET's The AE-CAI workshop series dates as far back as MICCAI 2006 in Denmark and has evolved as a forum to discuss the latest developments in Computer-Assisted Interventions (CAI). CAI is a field of research and practice, where medical interventions are supported by computer-based tools and methodologies. CAI systems enable more precise, safer, and less invasive interventional treatments by providing enhanced planning, real-time visualization, instrument guidance and navigation, as well as situation awareness and cognition. These research domains have been motivated by the development of medical imaging and its evolution from being primarily a diagnostic modality towards its use as a therapeutic and interventional aid, driven by the need to streamline the diagnostic and therapeutic processes via minimally invasive visualization and therapy.To promote this field of research, the AE-CAI workshop series seeks to showcase papers that disseminate novel theoretical algorithms, technical implementations, and development and validation of integrated hardware and software systems in the context of their dedicated clinical applications. This year's workshop is a joint effort between two communities \u2013 the AE-CAI community and the CereVis community. We joined forces back in June 2018 in light of our common interests in neuro-navigation and visualization for image-guided neuro-interventions.The objective of the AE-CAI & CereVis workshop has been to attract scientific contributions that offer solutions to the technical problems in the area of augmented and virtual environments for computer-assisted interventions, with CereVis contributions focusing on neuro-navigation and neuro-interventions, and to provide a venue for dissemination of papers describing both complete systems and clinical applications. The workshop attracts researchers in computer science, biomedical engineering, computer vision, robotics, and medical imaging.The workshop featured a single track that consisted of long and short oral presentations showcasing original research engaged in the development of virtual and augmented environments for medical image visualization and image-guided interventions. To foster networking and discussion, we also provided all authors with the opportunity to present their work as a poster in addition to their oral presentation slot.In addition to the contributed papers, we were pleased to welcome two keynote speakers: Dr. Klaus Engel and Dr. Terry Peters. Dr. Engel is an expert in visualization from Siemens Healthineers in Erlangen, Germany and spoke on cinematic rendering from medical imaging. Dr. Terry Peters is a pioneer in image-guided interventions from Robarts Research Institute at Western University in London, Ontario, Canada and spoke on current and future trends in mixed, augmented and virtual reality visualization in medicine.Healthcare Technology Letters journal. This year AE-CAI & CereVis received 20 manuscripts spanning a strong geographic representation from Europe, North America and Asia. The review process was rigorous and involved evaluation of each manuscript by three to five external reviewers. Following the first stage of review, sixteen manuscripts were further considered for major or minor revision, and resubmission. Authors were required to submit a response to reviewers and resubmit a revised manuscript that addressed all reviewers\u2019 critiques.All manuscripts submitted to the joint AE-CAI & CereVis 2018 were held up to journal standards, as the ultimate objective was to publish accepted work in this Special Issue of the IET's Once revised, all resubmitted manuscripts entered a second round of review conducted by the AE-CAI Program Committee, Workshop Chairs, as well as the HTL Managing Editor and Editor-in-Chief to ensure that all reviewers\u2019 critiques were properly addressed in the revised manuscripts and that the quality of the manuscript was appropriate for journal publication. All manuscript were then accepted for publication and forwarded to the journal for production and publication.On behalf of the AE-CAI & CereVis 2018 Program and Organizing Committee, we would like to extend our sincere gratitude to all authors, presenters, and attendees for their scientific contribution, enthusiasm, and support. We also extend special thanks to all reviewers for providing detailed and timely critiques of the submitted manuscripts. We also acknowledge the support we received from the MICCAI 2018 Workshop Committee, and the HTL Editorial Office for their dedication to maintaining the high quality of AE-CAI and CereVis workshops, and for selecting outstanding manuscripts that fostered exciting discussions at the meeting.Northern Digital Inc. (NDI) for their continued support over the years that has enabled us to recognize AE-CAI authors for their much deserved dedication and scientific enthusiasm through several paper awards. We also thank BrainLab for their generous sponsorship of the top papers presented as part of the neuro-imaging/navigation/visualization track encompassed by the CereVis workshop. A big thank you on behalf of all awardees and once again, sincere congratulations to all award winners!Last but not least, we acknowledge our generous sponsors. We thank CereVis Award Papers:by David ShattuckA Multiuser Virtual Reality Environment for Visualizing Neuroimaging Data, by Taylor Frantz; Bart Jansen; Johnny Duerinck; Jef VandemeulebrouckeAugmenting Microsoft's HoloLens with Vuforia Tracking for Neuronavigation, by Reid Vassallo; Hidetoshi Kasuya; Benjamin Lo; Terry Peters; Yiming XiaoAugmented reality guidance in cerebrovascular surgery using microscopic video enhancement, AE-CAI Award Papers:by Gavin Wheeler; Shujie Deng; Nicolas Toussaint; Kuberan Pushparajah; Julia Schnabel; John Simpson; Alberto Gomez HerreroVirtual Interaction and Visualisation of 3D Medical Imaging Data with VTK and Unity, by Long Qian; Anton Deguet; Peter KazanzidesARssist: Augmented Reality on a Head-Mounted Display for the First Assistant in Robotic Surgery, by Ehsan Azimi; Tianyu Song; Chenglin Yang; Omid DianatEndodontic Guided Treatment Using Augmented Reality on a Head-Mounted Display System, by Andrew Speers; Burton Ma; William Jarnagin; Sharifa Himidan; Amber Simpson; Richard WildesFast and accurate vision-based stereo reconstruction and motion estimation for image-guided liver surgery, We hope that you will enjoy reading this Special Issue and we look forward to your continuing support and participation in future editions of the AE-CAI & CereVis workshops. Their continued success demands our ongoing commitment.Cristian A. Linte, Rochester Institute of Technology, USAMarta Kersten-Oertel, Concordia University, CanadaZiv Yaniv, National Institutes of Health and TAJ Technologies, USAYiming Xiao, Western University, CanadaCaroline Essert, University of Strasbourg, FrancePierre Jannin, University of Rennes IJonathan Lau, Western University, CanadaPhilip Pratt, Imperial College London, UKIngerid Reinertsen, SINTEF, NorwayHassan Rivaz, Concordia University, Canada"} +{"text": "The findings of recent research on drinking patterns and problems among African-Americans can be summarized as follows: (1) African-Americans report higher abstention rates than do whites; (2) African-Americans and whites report similar levels of frequent heavy drinking; (3) rates of heavy drinking have not declined at the same rate among African-American men and women as among white men; and (4) variables such as age, social class, church attendance, drinking norms, and avoidance coping may be important in understanding differences in drinking and drinking problem rates among African-Americans and whites. Limitations of the research are described and suggestions are made for possible directions for future research. Alcohol studies on African-Americans make up a small but growing body of research. The limited research that does exist has focused on a number of issues, including patterns and determinants of drinking and drinking problems. This article reviews recent studies examining the drinking patterns and problems of adult African-Americans. Studies of African-Americans have, for the most part, involved comparisons of drinking patterns and drinking problems among African-American and white populations. This review therefore focuses primarily on studies of that type. After discussing drinking patterns and problems among African-Americans, the article describes some of the possible determinants of drinking patterns in that population.The term \u201cdrinking patterns\u201d refers to various styles of drinking, such as abstention or heavy drinking. Categories of drinking patterns frequently are based on indexes of quantity and frequency or on assessments of the volume of alcohol consumed by a person in a given period of time. Unless otherwise noted, terms describing drinking patterns are based on the definitions used in the studies being discussed.National surveys examining the prevalence of drinking in African-American populations indicate that African-Americans report lower rates of alcohol use than whites. In 1997, according to the National Household Survey on Drug Abuse, 53 percent of African-Americans and 68 percent of whites reported drinking in the past year . The difHeavy drinking increases the risk of drinking problems; researchers therefore often focus on heavy drinking when comparing African-American and white drinkers. Data from the National Alcohol Survey show thaPanel studiesTwo of the most widely studied indicators of drinking problems include drinking consequences and alcohol dependence symptoms. Drinking consequences are concrete problems that arise in different areas of a person\u2019s life because of drinking . Alcohol dependence symptoms refer to a set of behaviors and experiences associated with alcoholism or addiction, such as withdrawal and blackouts . Some stLongitudinal surveys have focused on changes in drinking-problem indicators and alcohol-related mortality among African-Americans and whites. Rates of alcohol dependence symptoms and drinking consequences remained stable from 1984 to 1995 among African-American and white men and women see tab, p. 262.Some of the most promising studies on drinking problems have examined the relationships between race, social class, and drinking problems. Studies in this area have focused on two central hypotheses. The first hypothesis is that adjusting for social class may eliminate racial and ethnic differences in drinking problem rates. To summarize, studies comparing self-reported drinking problems in African-American and white populations have yielded mixed results. Some studies have shown that African-Americans report more drinking problems than do whites, whereas other studies have reported no significant differences between the two groups. Higher social class appears to be a protective factor for African-Americans against the effects of race on drinking problems. Continuing research is needed to understand the effects of social class status on drinking problems among African-Americans.For the most part, research on drinking patterns and drinking problems in African-American populations has not been based on theory. Nevertheless, etiological studies of drinking patterns and drinking problems in African-American populations have focused on a wide range of demographic, biological, environmental, and behavioral variables.Sex, age, income, education, and employment status have been shown to be related to drinking patterns and drinking problems in both African-American and white populations a, 1997. In addition to demographic variables, studies also have examined whether a family history of alcohol problems contributes to drinking problems. Two of the studies reviewed for this article reported\u2014and many researchers agree\u2014that a family history of drinking problems is an important correlate of drinking behavior . People Studies have examined the influence of stress, parental and peer attitudes about drinking, drinking norms, and drinking contexts on drinking patterns and problems among African-Americans. To see how stress influenced drinking, Studies have consistently found a positive relationship between drinking and drinking problems\u2014that is, as drinking increases, drinking-related problems increase . IncreasResearch regarding drinking patterns and drinking problems in African-Americans can be summarized as follows:African-Americans report higher abstention rates than do whites.African-Americans and whites report similar levels of frequent heavy drinking.Rates of heavy drinking have not declined at the same rate among African-American men and women as among white men.Variables such as age, social class, church attendance, drinking norms, and coping behaviors may be important in understanding differences in drinking and drinking problem rates among African-Americans and whites.Studies examining the determinants of drinking patterns and problems suggest that demographic and psychological variables may be important in understanding the differences in drinking patterns and drinking problems among African-American and white men and women. Despite the wide range of variables that have been studied, however, notable gaps exist in the research. None of the studies reviewed examined the effects of illicit drugs and tobacco use, the concentration of stores selling alcohol in a given area , or exposure to alcohol through the mass media on drinking patterns and drinking problems. The scant research on alcohol outlet density and media exposure is surprising, given the large number of alcohol outlets in many African-American inner cities and efforts by the alcohol industry to target African-Americans . Future studies should focus on those variables. In addition, few studies have included other ethnic populations, such as Asians and American Indians; those studies are needed to investigate the reasons behind the different trends in heavy drinking patterns for different ethnic groups.Continuing research is needed on the drinking patterns and drinking problems of African-Americans to address current gaps in knowledge. To ensure that interventions and policies to reduce drinking problems in African-American populations are guided by sound research, future studies will need to be theory based; use a wide range of study designs and variables; and include comparisons with other ethnic groups, such as Hispanics, Asians, and Native Americans. Panel studies also are needed to better understand changes in drinking patterns of African-Americans over time."} +{"text": "Wilting disorder is an abnormal condition characterized by weakness and paralysis of the upper and lower extremities. Pathogenesis and treatment target of the disorder are unclear; hence, allopathic treatment is generally used to relieve the symptoms. To investigate the treatment mechanism and effect of Traditional Korean Medicine (TKM) in patients with wilting disorder, we reviewed in vivo studies that focused on the effect of TKM on the main symptoms of wilting disorder and treatment of the diseases that can cause these symptoms. We electronically searched the PubMed, Cochrane, and CNKI databases using the following search terms: (weakness OR motor function disorder) AND . We selected 11 studies that demonstrated the effect of TKM treatment on the main symptoms of wilting disorder. In these studies, inducted models of amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular atrophy, polymyositis, and Guillain-Barre syndrome were used. With regard to treatment, herbal medicine was used in five studies, and acupuncture and bee-venom pharmacoacupuncture were used in three studies each. Future research is needed to determine the effectiveness of TKM treatment in patients with diseases that can cause the main symptoms of wilting disorder. Wilting disorder, also called \u201cWei-syndrome\u201d in Traditional Korean Medicine (TKM), is defined as an abnormal condition characterized by weakness and paralysis of the upper and lower extremities in the Korean Standard Classification of Disease and Cause of Death (KCD classification). The main symptoms of Wilting disorder are loss of muscle tone in the weakened or paralyzed parts, decrease in muscle strength, and decrease or disappearance of reflexes. In the TKM, the cause of wilting disorder is divided into the factors outside of the body and the factors inside of the body. The external factors include the traumatic events or overwork that can damage bones, joints, and soft tissues, fever causing neurologic dysfunction, and disease which have long morbidity period. The internal factors include energy reduction caused by wrong lifestyle or diseases and malfunctioning of viscera such as liver, heart, spleen, lung, and kidney , 2.There have been arguments between TKM doctors about the TKM treatment of wilting disorder, but the mechanisms and treatment effects of each treatment have remained unclear, despite many modern studies on wilting disorder in TKM , 2.The purpose of this study was to review clinical studies focusing on the treatment mechanisms and effects of TKM treatments on wilting disease. A modern study focusing on wilting disorder suggested that diseases such as myasthenia gravis, Guillain-Barre syndrome, amyotrophic lateral sclerosis, paralysis, polymyositis, and muscular dystrophy could manifest clinical signs similar to those of wilting disorder, such as weakness, paralysis, and loss of motion .So we tried to investigate the treatment mechanisms and effects of TKM treatments in these diseases. This study aimed to investigate the research trends of TKM treatment for diseases that can cause wilting disorder through utilizing various databases and analyze the results. This process will provide information and evidences of TKM treatment to treat wilting disorder in clinical practice and designing a clinical research about TKM treatments.We searched the PubMed, Cochrane, and CNKI databases from inception through April 2018. No language limitation was applied. Key search terms were AND (weakness OR motor function disorder) AND .The data were extracted and grouped using a data extraction form that included the animal , the disease model type , the type of intervention, and the outcome measures . The data were extracted primarily by one author and checked by all other authors.We extracted 159 studies by using our key terms and read their titles and abstracts. Out of these 159 articles, 89 records remained after the duplicates were removed. Of these 89 articles, six articles were systematic review or review of literature, and 23 articles were case reports. There were 29 articles not satisfying intervention criteria; and 11 articles were not research studies on the treatment effect. Nine articles were excluded because of improper group-setting. After screening, we selected 11 animal model studies for analysis . We analWilting disorder can occur because of the abnormality of the muscle, neuromuscular junction, peripheral nerve, and lower and upper motor neuron.The main symptoms of wilting disorder include flaccid palsy, muscle atrophy, loss of reflex, muscular fasciculation, muscular contracture, and reaction of degeneration. Diseases that could cause this condition include myasthenia gravis, Guillain-Barre syndrome, amyotrophic lateral sclerosis, multiple sclerosis, paralysis, polymyositis, and muscular dystrophy.Myasthenia gravis is an autoimmune disease that results from abnormality of the neuromuscular junction. The pathogenesis involves the action of antibodies to block or destroy nicotinic acetylcholine receptors at the neuromuscular junction between the nerve and muscles and eventually prevent nerve impulses from triggering muscle contractions. The main symptoms of myasthenia gravis are painless weakness of specific muscles. The weakness becomes progressively worse during physical activity and improves at rest. Several in vivo studies have reported the effectiveness of TKM treatment with curative intent in patients with this autoimmune synaptopathy . In an aThe area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve were significantly increased following acupuncture treatment .Another study investigated the protective role of herbal medicine, Sizunzi decoction, in the neuromuscular junction. Intervention with Sizunzi decoction resulted in the findings of close to normal NMJ structure and significantly increased expression of the acetylcholine receptor and agrin .Amyotrophic lateral sclerosis (ALS) is a disease characterized by abnormal function of the voluntary muscles. This malfunction results from death of the neurons which control voluntary muscles . ALS is Most of the studies have focused on bee venom pharmacoacupuncture at the Zusanli (ST36) acupoint. An animal study investigating the effect of bee venom pharmacoacupuncture on the central nervous system and muscle in an animal model of ALS showed that bee venom treatment at the Zusanli acupoint significantly enhanced motor function and decreased motor neuron death in the spinal cord compared to the control group. Furthermore, this treatment eliminated downstream signaling of inflammatory proteins, such as TLR4, in the spinal cord, and reduced levels of TNF-alpha and Bcl-2 expression in the ALS animal model .In another similar animal study, bee venom treated animals reported decreased expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem; moreover, treatment with bee venom improved motor activity in animals with symptomatic ALS .Another study explored the effect of electroacupuncture treatment at the Zusanli acupoint. This study reported that ALS animal models treated with electroacupuncture showed a decrease in microglial cell activity and TNF-alpha expression in the spinal cord and brain stem. In addition, the treatment significantly improved motor activity compared to that in the control group and reduced neuronal cell loss in the ALS model .In a study investigating the effect of an herbal medicine, Wen-Pi-Tang, on the ALS animal model showed that the Wen-Pi-Tang treatment inhibited neuronal loss in the lumbar segment of the spinal cord of mice. In addition, astrocytes and CD11b positive microglial cell in the spinal cord that increase prior to neuronal loss were significantly reduced in the Wen-Pi-Tang treated group .Multiple sclerosis is a demyelinating disease with three main characteristics: plaque formation, inflammation, and destruction of the myelin sheaths of neurons. The insulating covers of nerve cells in the brain and spinal cord are damaged and this disrupts the ability of parts of the nervous system to communicate, resulting in muscle weakness and motor dysfunction . Apart fIn a study investigating the effect of bee venom in suppression of motor neuron loss and microglial cell activation, bee venom was injected at the Zusanli (ST36) acupoint in the experimental group. As a result, the symptoms of clinical disorder, pathologic changes, inflammatory cell infiltration, demyelination in the central nervous system, and levels of TNF-alfa, and serum nitrates were decreased in the multiple sclerosis model .Another study investigated whether Hyung bangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in the multiple sclerosis model in rats. Onset-treatment with HBPDS alleviated neurological signs, reduced demyelination and the infiltration of microglia and macrophages, and reduced the mRNA expression of proinflammatory cytokines and chemokines in the spinal cord .Guillain-Barre syndrome is a rapid-onset muscle weakness caused by immune system-mediated damage to the peripheral nerve system. The muscle weakness begins in the feet and hands. This often spreads to the arms and upper body with bilateral involvement. The cause and mechanism of this disease is unknown .A study investigated the mechanism of electro acupuncture at the Shu-points of the five zang-organs for treatment of Guillain-Barre syndrome. In this study, electroacupuncture treatment increased the sciatic nerve movement conduction velocity and decreased the abnormal F wave incidence rate of the sciatic nerve in the Guillain-Barre syndrome model group .Duchenne muscular dystrophy is a severe type of muscular dystrophy caused by X-linked recessive gene. The muscular weakness is associated with muscle wasting of the voluntary muscles. The hips, pelvic area, thighs, shoulders, and calves are the first to be affected; subsequently, muscle weakness occurs in the arms, neck, and other areas .A study accessed the effects of herbal medicine on Duchenne muscular dystrophy. This study showed that the Liu-Wei-Di-Huang-Wan (LDW) and San-Lin-Pai-Tsu-San (SPS) can facilitate locomotor activity with the parameters of horizontal activity, total distance, number of movements, movement time, vertical activity, number of vertical movements, and vertical movement time .Polymyositis is a chronic inflammation of muscles related to dermatomyositis and inclusion body myositis. The hallmark of this disease is weakness and loss of muscle mass in the proximal musculature, as well as flexion of the neck and torso .A study investigated the therapeutic effects of Radix Bupleuri and Ramulus Cinnamomi on the polymyositis model. The herbal medicine treatment significantly increased expression of MyoD and myogenin and the function of myosin heavy chain and activated the Akt/mTOR pathway. In addition, the treatment suppressed the TNF-alpha activation .Due to lack of understanding of the cause and mechanism of wilting disorder, allopathic treatment is generally used to relive the patients' symptoms of pain and weakness. We reviewed the in vitro studies focusing on diseases that can cause the symptoms of wilting disorder and reported our results. Our results indicated that TKM was effective in improving the electrophysiological status, histological and biochemical measurement values, and motor function value index, especially in animal models of myasthenia gravis, amyotrophic lateral sclerosis, and multiple sclerosis. However, there was lack of evidence for the TKM treatment effect in the Guillain-Barre syndrome, Duchenne muscular atrophy, and polymyositis models.This study has some limitations. First, the use of limited search strategies returned a small number of studies. However, very few studies have been reported on the effect of TKM on wilting disease. Second, it was difficult to follow a strictly standardized method of analysis because of limited access to complete data from the studies. Future research is required to fully evaluate the effectiveness of TKM treatment in animal models."} +{"text": "Renal cell carcinoma (RCC) is the most common tumor of the kidney. After diagnosis, 20\u201330% of patients will relapse, with a high probability of death from cancer-related causes. The development of non-invasive biomarkers will allow the identification of patients with a high risk of recurrence after radical or partial nephrectomy and will improve the assessment of tumor response to targeted therapy or immunotherapy. The search for non-invasive diagnostic techniques represents one of the most difficult challenges for cancer researchers. The contemporary scenario includes a variety of strategies that share the aim of maximally reducing the impact of the diagnosis on patients' quality of life (QoL). In this context, liquid biopsy offers a promising perspective for cancer diagnosis and monitoring, with several advantages compared to traditional diagnostic procedures . Indeed,The liquid biopsy of circulating tumor cells (CTCs), which belong to the larger family of circulating rare cells (CRC), has been validated and approved by the US Food and Drug Administration (FDA) as a useful prognostic tool in a variety of cancer types . This isIn the last decade, several studies have investigated the clinical and pathological significance of CTC numbers and characteristics in patients with urogenital cancers , 7. In vVon Hippel\u2013Lindau (VHL) gene and include LOH at 3p and epigenetic silencing. VHL inactivation is a crucial event in the majority of clear cell RCC and represents the only ubiquitous event, in contrast from the other genetic and/or epigenetic aberrations reported which are just subclonal \u201319 and tThe collection, identification, enrichment, and analysis of CTC require the use of different methods, including the following: (1) Epithelial or non-epithelial marker-dependent isolation; (2) RT-PCR-based methods; (3) and morphological- and cell size-based detection .The first method consists of the detection of CTCs through epithelial markers, such as the epithelial cell adhesion molecule EpCAM, . EpCAM iCAIX, VHL and Cadherin-6 (CDH-6) . VHL genof cases . On the samples .The third method is built upon size-based blood filtration combined with morphological and genetic analyses. The need to associate different techniques derives from the evidence that cytomorphological classification alone is not sufficient to detect CTCs in RCC patients . InteresThe survival mechanisms underlying the circulation and migration of CTCs depend on multiple factors. Their biological characteristics, genetic alterations, epithelial mesenchymal transition, and cancer stem cell properties are internal factors that influence their survival. Great importance is now also being attributed to the external factors in the bloodstream microenvironment, consisting of platelets, immune cells, cytokines, and circulating tumor microemboli (CTM) .ex vivo expanded CTC lines, administration of digitoxin significantly inhibited the capacity of CTC clusters to generate metastases are being developed to better characterize CTCs. With this method, independent of cell size variation, and free of hypotonic damage as well as anti-EpCAM perturbing, it is possible to karyotype chromosome ploidy of CTCs and phenotype multi-protein expression. Among different cancers, an aneuploid chromosome 8 (tetraploid or polyploid) identified a positive CTC combined with immunostaining-fluorescence tive CTC \u201344. Thistive CTC , 46.A novel straight microfluidic chip technology to focus and capture CTCs has been applied in head and neck cancer patients. The microchip is designed based on inertial migration of cells in a straight microchannel and allow to isolate single CTCs, CTCs clusters, and CTM by a size-based method, with high recovery efficiencies and low background cell contamination , 48.In future years, technical advances should aim to isolate a greater number of CTCs in metastatic patients than in patients with localized disease and to find the same mutations present in the correspondent histologic sample or, especially, in the metastatic cohort. In our opinion, this could be realized by improving the connection between cytomorphological and genetic analyses, thus overcoming the limits of present techniques, which can be challenging and time-consuming. Indeed, the specificity of CAIX and CDH-6 for CTCs in RCC patients is poor and could be increased only by the design of studies focused on comparing CTCs isolated from patients with clear cell and from patients with benign kidney diseases or healthy volunteers.We hope that in future years whole genome, transcriptome, and proteome analyses of single cells could lead to an increase in our knowledge of tumor heterogeneity and acquired drug resistance. In the localized RCC setting, CTCs could have potential as a surveillance biomarker for disease recurrence. Earlier detection of metastatic RCC, prior to the onset of symptoms, may lead to improved clinical outcomes. In patients with metastatic disease, CTC analysis could be used to select patients for biomarker-guided clinical trials. As in colorectal cancers, the mutational profile of metastatic RCC could evolve after treatment progression, developing an acquired resistance to therapy potentially investigable in a non-invasive way with CTCs. Moreover, the introduction of data on CTCs within the TNM classification represents another step forward on the route of personalized medicine for RCC patients.RCC may benefit from the development of non-invasive and reliable biomarkers, enabling early and timely personalized treatment changes. The introduction of CTC analysis within daily clinical practice for patients with RCC seems still far at the moment. However, the advances obtained in the last 5 years in isolating and analyzing CTCs bring optimism about the future therapeutic landscape in RCC patients.RM and MSc: conception and design; MSa, AC, and FM: drafting the manuscript; NB and ABG: review of the literature; LC, SB, and AL-B: critical revision of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "Health systems face increasingly complex challenges, such as the growing burden of chronic noncommunicable diseases, multisource pollution, new epidemics and antimicrobial resistance. These challenges have prompted an important shift in focus from curative care to health promotion and disease prevention, as well as the development of new models of service delivery, financing and governance for primary health care.Global health stakeholders are pushing for renewed commitments to enhance primary health care in the 21st century, in light of the 2018 Declaration of Astana.Achieving the health-related sustainable development goals (SDGs), including universal health coverage (UHC), will not be possible without stronger primary health care.\u2013Most people not covered by essential health services belong to disadvantaged groups. Primary health care can address this issue because it enhances equity and is the most feasible approach to reach people.However, in many low- and middle-income countries, primary health-care systems are weak and do not provide sufficient high-quality, comprehensive, people-centred and integrated care. In addition, the core principles of empowering people and strengthening health systems are often overshadowed by short-term interventions, with countries attempting to meet an overwhelming number of programme-specific targets that are dependent on donor priorities and funding. This situation highlights the need to strengthen comprehensive primary health-care systems based on local priorities, needs and contexts. These systems should be co-developed by people who are engaged in their own health.Implementation and systems reforms of primary health care are also challenged by the lack of contextualized knowledge and scarcity of research on effective and acceptable approaches to strengthen primary health care, especially in low- and middle-income countries. Primary health-care research that is applicable to different health systems settings is needed.Bulletin of the World Health Organization will publish a theme issue on advancing the science and practice of primary health care as a foundation for UHC. The theme issue aims at providing a forward-looking view of the innovations, challenges and shared responsibilities in driving primary health care, and at filling gaps and fostering discussions around what is needed to implement a primary health-care vision towards UHC. To tackle these challenges, the We welcome manuscripts that capture learnings and experience in the implementation of primary health-care policies and interventions as well as the strengthening of primary health-care systems. The ability of countries to fulfil the commitments made in the Declaration of Astana depends on the active engagement of various stakeholders of primary health care. We therefore encourage analysis of challenges, contextualized research, good practices and innovations in enhancing primary health care at the national or sub-national level, with a strong focus on stakeholder engagement and impact on population health and equity. Papers could focus on, for example, multisectoral action for primary health care and equity, implementation research and analysis of health systems reforms, bridging the gaps in workforce, digital health, quality improvement and the contribution of primary health care in advancing UHC and the SDGs.Documenting good practices on effective approaches to engage and empower people, communities, youth and other stakeholders will also be useful to support efforts enhancing the responsiveness and people-centeredness of primary health care. The theme issue will focus on cross-cutting themes and challenges of primary health care affecting all countries, but we also encourage submission of experiences from low- and middle-income countries and conflict-affected and humanitarian settings, as well as comparative cross-country analyses.Bulletin\u2019s guidelines for contributors (available at: http://www.who.int/bulletin/volumes/96/1/18-990118/en/) and the cover letter should mention this call for papers.The deadline for submission is 30 November 2019. Manuscripts should be submitted in accordance with the This theme issue will be launched at the Global Symposium on Health Systems Research in Dubai in 2020."} +{"text": "Long-distance caregiving (LDC) is a growing phenomenon and common experience for caregivers of frail older adults. In fact, 11% of family caregivers in the US live more than two hours distance from the care recipient (CR). Unfortunately, there is a paucity of research on unique experiences of LDCs and the impact of LDC on the mental health of LDCs. This symposium presents findings from the NIA funded Fordham Long-Distance Caregiving Study (R21AG050018) analyzing data of 304 long-distance caregivers (LDCs). The overall study goal was to better understand how LDCs deal with the structural constraint of distance, and to examine LDC consequences and resources. First, Horowitz presents the study background, characteristics of the sample, and provides a description of the unique experiences of LDCs. Next, Cimarolli concentrates on the Sociocultural Stress Process Model applied to LDC. Her study tested the impact of LDC on mental health and investigated resources which could mediate the association between caregiving stressors and mental health outcomes. The third paper presents data related to satisfaction with formal service providers for four subgroups of LDCs based on CR residence and dementia status. Finally, Jimenez focuses on the characteristics of LDCs\u2019 network of other informal caregivers (IC) providing assistance to the CR and factors are associated with more help received from other ICs. Dr. Pruchno, an expert in caregiving research, will discuss study findings. The symposium provides insights into unique experiences of LDCs, the impact of LDC on mental health, and resource use among LDCs."} +{"text": "Drosophila melanogaster are derived from the imaginal discs, epithelial sac-like structures specified in the embryo that grow and pattern during larva development. In the last decades, genetic and developmental studies in the fruit fly have provided extensive knowledge regarding the mechanisms that direct the formation of the appendages. Importantly, many of the signaling pathways and patterning genes identified and characterized in Drosophila have similar functions during vertebrate appendage development. In this review, we will summarize the genetic and molecular mechanisms that lead to the specification of appendage primordia in the embryo and their posterior patterning during imaginal disc development. The identification of the regulatory logic underlying appendage specification in Drosophila suggests that the evolutionary origin of the insect wing is, in part, related to the development of ventral appendages.Appendages are external projections of the body that serve the animal for locomotion, feeding, or environment exploration. The appendages of the fruit fly Molecular and genetic studies in the fruit fly, Drosophila melanogaster, have provided the basis of appendage development and served for comparative analysis with other arthropods . ,19. 8,19lication ,21. The lication ,22,23,24lication ). Thereflication ,22,23.snail (sna) and vg genes, while the VP expresses Distal-less (Dll) and the Sp family members Sp1 and buttonhead (btd) . TDll gene . At the Dll gene ,67 in posterior cells. Compartment boundaries are the source of signaling molecules that organize the pattern and growth of the imaginal disc [After the specification stage in the embryonic ectoderm, each imaginal primordium follows a developmental program in which the same signaling pathways and an increasing number of transcription factors cooperate to pattern the growing epithelium. In this process the size of each disc increases by cell proliferation, and the epithelium is progressively divided into domains of gene expression that confer each territory with particular cell identities. A common aspect of all thoracic discs is their division in A and P compartments conferred by the expression of nal disc . In thisAntp is the selector Hox gene for leg identity that is expressed in the leg imaginal disc but not in the antenna disc. As expected for its selector function, Antp mutant legs are transformed into antenna and Antp ectopic expression in the antenna converts it into leg [hedgehog (hh) which acts as a short-range signal that activates the expression of dpp and wg in the anterior dorsal and ventral halves of the disc, respectively [H15 and midline (mid) and the repression of dorsal genes such as Doc and optomotor blind (omb) [wg mutants all the ventral structures are lost and replaced by a mirror duplication of dorsal ones and the reverse phenotypes are observed for dpp mutants [The third instar leg imaginal disc is roughly circular in shape with the distal-most region of the leg located in the center of the disc, and the most proximal leg segments and the pleura arising from the periphery of the disc. into leg . The legectively . Dpp andectively ,78,79,80nd (omb) ,81. Ther mutants ,78,80,82Dll [dachshund (dac) in the medial domain of the leg disc, whereas high levels of Wg and Dpp represses its expression in the distal tip [Dll and dac expression is maintained in part by autoregulatory mechanisms [hth is restricted to the periphery of the disc by a Wg and Dpp dependent repression mechanism [elbow (el) and no ocelli (noc) genes that act in the leg and the wing discs to repress hth expression, and therefore body wall fates [hth, dac, and Dll, respectively , Bar (B), and rotund (rn) among others [Delta (Dl) and Serrate (Ser) [btd and Sp1 are co-opted later during imaginal development to control the growth and pattern of the leg, in part through the regulation of Ser expression and therefore Notch signaling [dysfusion (dysf), proximal joints such as the odd-skipped gen family of for all joints like dAp-2 , that regulates the expression in a distal to proximal manner of g others ,96 . Beste (Ser) ,100. Notte (Ser) ,102,103 ignaling ,104,105.e dAp-2 and vg [nub and vg is accompanied by the repression of the body wall genes teashirt (tsh) and hth (hth/tsh (notum and hinge) and vg (wing blade) is analogous to the leg disc, where hth/tsh are also restricted to the proximal domain to promote body wall structures that subdivide the thorax and the wing field in dorsal (D) and ventral (V) compartments [vg expression and wing outgrowth [vg in the cells that will become the wing blade [hth and vg subdivide the wing field in the pouch and the hinge [Iroquois-complex (Iro-C) that are repressed in the wing field by Dpp secreted in the A-P boundary and vg . The act and hth [114,115ructures C. It haserritory ,114,116.artments ,117,118.utgrowth . Ap regung blade ,121,122.he hinge ,114,121.boundary [123,124al fates .en expression subdivides the wing disc in two populations of cells, the A and P compartments. The A-P boundary acts a source of positional information where Hh secreted from the posterior compartment activates the expression of dpp in A cells. Dpp and Hh are both required to pattern the wing blade along the A-P axis (brinker (brk) to the lateral domain of the wing [omb and the spalt genes in nested domains [As in the leg disc, A-P axis . Dpp difthe wing ,129,130. domains ,132).hth, spineless (ss), and Antp that converts every antenna part to its corresponding leg segment [The eye-antennal disc (EAD) is formed by different populations of cells located in the cephalic segments that coalesce together . The EAD segment ,134 and sine oculis (so) [distal antenna (dan) and distal antenna related (danr) genes, responsible for the specification of distal antenna identity [Early on larval development (L1) the EAD shows no sign of regional specification and presents uniform expression of several transcription factors including lis (so) A [135,13lis (so) A. Accordo) ,147. Ss identity ,149.Drosophila melanogaster has provided a detailed picture of the molecular mechanisms that lead to the specification and patterning of the adult appendages. Importantly, many of the signaling pathways and transcription factors identified in the fly have similar functions during vertebrate limb development. However, many important questions remain unsolved. First, the target genes and the regulatory networks controlled by the transcription factors that subdivide the appendages along the different axes are still largely unknown. This includes the analysis of the molecular interactions between patterning genes and signaling pathways. Second, further investigation would be required to unravel how the patterning information is translated into cellular behaviors , which are ultimately responsible for the characteristic shape and size of the different appendages of the fly. The use of whole genome techniques such as ChIP (Chromatin Immunoprecipitation) or ATAC (assay for transposase accessible chromatin) assays, coupled with whole genome sequencing is essential to identify the target genes and the regulatory landscapes governed by the patterning transcription factors. In addition, live imaging techniques would provide novel information of the morphogenetic processes and dynamics during appendage specification and formation.In this review, we have discussed how the study of"} +{"text": "Many Latino older adults delay seeking help for symptoms of Alzheimer\u2019s Disease or Related Dementia (ADRD) due to substantial barriers to services. Community-based Natural helpers (NHs) can increase health-related knowledge and can serve as full partners in health education and promotion. This paper presents the process and product of the first phase of a community-based participatory research study to develop a culturally-tailored intervention increasing knowledge about ADRD and services in East Harlem, NY. We describe the results of the initial survey and development of El Barrio SHARE, an intervention that recruits and trains community residents to provide information and referrals about dementia, tapping into natural community networks of people who interact with and have longstanding relationships with older adults in the course of their work. NHs are well-positioned to observe and detect problems, and can link elders to relevant, culturally-sensitive resources, accessible support, and treatment."} +{"text": "Marked erosion with punched-out resorptive lesion and dilatation of joint cleft, on the distal interphalangeal joint, were seen.In addition, bone erosion and narrowing of the joint cleft were seen on carpometacarpal joint."} +{"text": "Somatic embryogenesis (SE) and organogenesis have become leading biotechnologies for forest tree improvement and the implementation of multi-varietal forestry. Despite major advances in clonal propagation using these technologies, many forest tree species, such as conifers, show a low regeneration capacity. Developmental factors such as genotype, the type and age of the explant or tissue, and the age and maturity of the mother tree are limiting factors for the success of propagation programs. This review summarizes recent research on the molecular pathways involved in the regulation of key steps in SE and organogenesis of forest tree species, mainly conifers. The interaction between auxin and stress conditions, the induction of cell identity regulators and the role of cell wall remodeling are reviewed. This information is essential to develop tools and strategies to improve clonal propagation programs for forest tree species. Recalcitrance to somatic embryogenesis (SE), adventitious rooting (AR) from stem cuttings or adventitious shoot (AS) formation is a major limitation for the clonal propagation/micropropagation of elite trees in many woody species, especially forest tree species. Several reviews on the state-of-the-art of the application of these techniques as well as the impacts of recalcitrance and tree domestication on forestry have been published . There aThis review summarizes the results of recent studies on the molecular and cellular mechanisms involved in the regeneration capacity of forest tree species by SE, AR, or AS formation, with special focus on conifers. The interaction between auxin and stress conditions, the induction of cell identity regulators and the role of cell wall remodeling are mainly reviewed. We have focused on the early stages of regeneration, when the transition from a somatic to an embryonic or meristematic cell occurs, in an attempt to highlight factors or common pathways that may be relevant for the control of the recalcitrance.The induction of SE, AR, or AS formation is a multi-factorial developmental process that includes the effects of hormones and chemical and physical factors. Such factors include the composition of media, growth conditions, stress associated with wounding (excision) or the culture environment, and other stress factors . It has The conditions and requirements for the induction of SE, AR, or AS formation vary within and among forest tree species; however, some common pathways can be identified. The most obvious is the absolute requirement for auxin and polar auxin transport during the initiation stage. Plant growth regulators play a central role in both the initiation of pro-embryogenic masses (PEMs) and the differentiation and maturation of somatic embryos. In forest tree species, initiation and proliferation of embryogenic masses (EMs) are induced in the presence of auxin and cytokinin. Withdrawal of these plant growth regulators results in the differentiation of somatic embryos from PEMs. Embryos are subsequently transferred to medium supplemented with abscisic acid (ABA) to induce somatic embryo maturation.Abies alba has been shown to negatively affect embryogenesis initiation and development. This indicates that high levels of endogenous IAA and polar auxin transport are required for resuming proliferation and activating the embryogenic program during cell reprogramming leading to SE. Similar results have been described during SE from adult leaf tissues of Quercus alba have been shown to reduce the level and distribution of auxin in rooting cells 3 and PIN7 was only marginally influenced by time after induction, physiological age, or auxin treatments. However, the expression of AUXIN RESPONSE FACTOR (ARF)6 and ARF8, which promote AR in model species, increased only in rooting-competent parenchyma cells. In addition, expression of ARF17, which inhibits rooting, decreased concomitantly with the increase in ARF6 and ARF8 expression. Auxin was required for localizing changes in gene expression. Recalcitrant mature cuttings showed a diffuse and uniform mRNA signal among all tissue types. The authors concluded that recalcitrance of black walnut to AR resulted from the failure of rooting-competent cells to perceive molecular signals initiated by auxin in mature cuttings. This confirmed the results of earlier studies on AR in conifers, demonstrating that auxin acts as an unspecific signal of preset cell reaction patterns -related homeobox gene family of transcription factors whose expression is associated with specifying apical cell identity during the earliest stages of Arabidopsis embryogenesis , a novel NF-YB subunit of the CCAAT-binding transcription factor that functions as a master regulator of embryogenesis , encoding an AP2/ERF responsive transcription factor involved in promoting cell proliferation and morphogenesis during embryogenesis 3 gene, encoding a B3-domain transcription factor involved in ABA signaling , indicating that it may be involved in cell division and could not be used as a marker of EMs like in white spruce 1-2 and WOX13 genes, the former encoding a LRR receptor-like kinase involved in the induction of SE competence in culture . The large number of differentially expressed genes encoding cell cycle regulators, PCD-related proteins, and BBM and WOX transcription factors suggested that these proteins may play crucial roles in PEMs establishment and development in larch , PrSCR, and SCARECROW-LIKE (SCL) 6, PrSCL6, were significantly reduced or non-existent in adult tissues that had lost the capacity to form adventitious roots, but were maintained or induced after the reprogramming of adult cells in rooting-competent tissues. GRAS gene expression associated with the maturation-related decrease in adventitious root formation in chestnut. Other studies have reported asymmetrical increases in the transcript levels of other members of the GRAS gene family, PrSCL1 were upregulated in embryogenic tissues compared with non-embryogenic ones. This finding indicated that cell wall signaling and intercellular communication play important roles in the acquisition of embryogenic competence and the initiation of SE in this species. Early work on SE in Norway spruce described the importance of the interactions among cells, and the roles of cell wall signaling and chitinase-cleaved forms of AGPs for induction of SE (Abies hybrid cell line, compared with low embryogenic lines. The AGPs progressively accumulated within the extracellular surface matrix network, a structure covering embryogenic cells, during the early stages of embryo development (To understand the molecular mechanisms regulating the role of the cell wall in the initiation of SE, on of SE . An increlopment . They wein vitro protocols, and have similar early embryogenic markers in Q. suber (Q. alba (Cell wall remodeling by increasing pectin esterification and an increase in endogenous auxin occur concomitantly at the early stages of two embryogenesis pathways: microspore embryogenesis; and embryogenesis from immature zygotic embryos. These pathways can be induced by different Q. suber . Similar(Q. alba .Microtubules and microfilaments are involved in cell polarity and the orientation of the cell division plane, cell wall development, intracellular transport processes, the mechanical properties of the plant cell and tissues, and how these tissues interact with the plasma membrane and the cell wall. Therefore, along with the cell wall, these structures may play important roles in the organization of new structures during regeneration. Microtubules and F-actin were both found to be important for embryogenesis in Norway spruce . CytochaEucalyptus (Eucalyptus. The relevance of microtubule remodeling in the maturation-related decline of AR has been demonstrated using microtubule-disrupting drugs, which increased the rooting capacity of adult cuttings of Eucalyptus grandis (Several studies have identified components of the molecular pathways underlying cell wall and cytoskeleton remodeling which are associated with adventitious root formation and the maturation-related decline in AR in pine and calyptus . These a grandis .Flexibility of the interactions between the cell wall, plasma membrane, and cytoskeleton is required to establish new cell polarity, reorient cell division planes, modify growth direction and induce a new morphogenic program. The components involved in these pathways are regulated by auxin, stress or cell identity regulators during induction of SE or organogenesis. In addition, modifications in the cell wall and cytoskeleton result in changes in cell polarity and the polarization of auxin transporters and auxin gradients.SERK was induced by auxin and stress conditions (PpWOX13-like genes were found to be involved in the control of cell wall loosening to facilitate stem cell formation in Physcomitrella patens (Arabidopsis (de novo regeneration. Molecular dissection of the mechanisms underlying regeneration capacity and identification of the genes expressed in common interrelated pathways regulating competence for SE and organogenesis would allow identification of an expressional signature characterizing specific levels of regulation, developmental stages, age, position, timing, type of tissues, clones or genetic traits associated with competence for SE or organogenesis. Cutting-edge technologies for analyzing multigene expression profiling may provide additional prognostic information for competence. Furthermore, the identification of rechanneling and master genes may provide additional tools for the modification of competence. Moving forward in the same direction, a more precise characterization of tissues used in operational programs will allow individualized management after diagnosis.Several interrelated pathways are involved in the plasticity of plant cells for SE or organogenesis in forest tree species Figure . Stress,nditions . Interesa patens . Crosstabidopsis ,b. All tCD-S conceived the idea, gathered data, and wrote the manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "In response to the urgent need to scale up access to antiretroviral therapy, the Global Nursing Education Partnership Initiative (GNCBP), a PEPFAR program administered by the U.S. Department of Health Resources and Services Administration (HRSA), was implemented from 2011 to 2018 by ICAP at Columbia University. Working closely together, HRSA and ICAP partnered with local nursing leaders and ministries of health to strengthen the nursing and midwifery workforce across 11 countries. This multi-country project, developed to address critical gaps in nursing education and training worked across six building blocks of health workforce strengthening: infrastructure improvement, curricula revision, clinical skills development, in-service training, faculty development and building partnerships for policy and regulation to increase the quality and quantity of the nursing and midwifery workforce. As a result, 13,387 nursing and midwifery students graduated from schools supported under GNCBP. A total of 5,554 nurses received critical in-service training and 4,886 faculty, clinical mentors and preceptors received training in key clinical care areas and modern teaching methodologies. ICAP completed 43 infrastructure enhancements to ensure environments conducive to learning and strengthened nursing leaders as best evidenced by the election and formation of Mozambique\u2019s first national nursing council and the NEPI Network. Going forward, efforts to strengthen nursing and midwifery can build on the results of the GNCBP project. Going forward, a new group of African nursing leaders are being supported to advocate for high quality patient-care led through inter-professional collaboration and participation in international efforts championing the critical role of nurses in achieving universal health coverage. To achieve the UNAIDS 90-90-90In response, the Global Nursing Education Partnership Initiative (GNCBP), a PEPFAR program administered by the U.S. Department of Health Resources and Services Administration (HRSA), was implemented by ICAP at Columbia University. Working closely together, HRSA and ICAP have partnered with local leaders to strengthen the nursing and midwifery workforce. This multi-country project, developed to address critical gaps in nursing education and training, was launched in 2011, with the field work completed in September 2017. The GNCBP spanned 11 countries and included two subprojects; the Nursing Education Partnership Initiative (NEPI) and General Nursing (GN). The GNCBP supported local projects, institutions, and networks to expand, enhance, and sustain the nursing and midwifery workforce through NEPI and GN . The purpose of NEPI was to strengthen both the quality and quantity of the nursing and midwifery workforce through strengthened nursing and midwifery education. The NEPI project had five broad objectives: 1) strengthen teaching/learning infrastructure; 2) improve quality and relevance of teaching and learning; 3) improve the capacity of nursing and midwifery faculty; 4) build governance, leadership and administrative capacity within education institutions; and 5) enhance partnerships and networks. With the release in 2014 of PEPFAR 3.0 \u2013 Across the six countries supported by NEPI, a total of twenty-two schools of nursing participated Table . SchoolsA brief description of nursing and midwifery strengthening efforts within each building block is provided below.Faculty development focused on improving the ability of faculty to lead quality education programs and in later years to provide greater support and attention to nursing and midwifery education locally and regionally. Support was provided for a wide array of educational opportunities, including but not limited to, in-service training initiatives, such as nurse initiated and managed ART (NIMART), training in the set-up and use of simulation-based education and training, development of competency-based curricula, the nursing process, as well as tuition support for those nurses pursuing Master\u2019s and PhD degrees. In the final year of NEPI, a leadership webinar series was undertaken, as well as an in-person nursing and midwifery leadership development workshop.Robust nursing education and leadership networks were developed across NEPI-supported institutions and active links to regional and international nursing bodies have been formed through local technical working groups, the \u2018NEPI network\u2019, and through supporting local, regional and international conference attendance.Prior to the NEPI program, nursing schools lacked the basic equipment and supplies including textbooks, journals and lecture halls able to accommodate an increased number of students. WHO, in the 2006 World Health Report, recognized the importance of increasing the size of the health workforce but at the same time improving educational infrastructure . \u201cInsuffNursing and midwifery curricula needed to be updated to reflect nurses and midwives current scope of practice and \u2018real world demands\u2019. We used the backward design to curriculum development was employed throughout the network of schools . EducatoWithin the NEPI project, ensuring that nursing students were both competent and confident was prioritized. Competency-based curricula were coupled with improved clinical skills training through both simulations and supervised clinical practice. The development of simulation-based education (SBE) included the procurement, set-up and training on use of SBE. Training was provided by both the equipment supplier, as well as regional faculty trained in SBE. High, medium and low fidelity equipment were acquired to ensure students had the ability to learn core skills in a controlled practice environment. Mannequins able to simulate routine nursing functions, such as venipuncture and intravenous infusion were complemented with higher fidelity mannequins that could simulate life-threatening conditions, such as emergency obstetric complications. Faculty were trained in the use of a wide range of equipment, including computer aided simulation which allowed dynamic manipulation of the \u2018patients\u2019 condition. Such features enable students to acquire experience and skills to be able to more competently deal with rare events, such as post-partum haemorrhage, as well as allowing faculty to assess student\u2019s competence for real world challenges. In addition to SBE, NEPI country programs strengthened clinical training through preceptor education and training, improved access to rural practice settings, and allowed for the development and use of model wards.Continuing professional development (CPD) included increasing faculty access to HIV competency-based e-learning, with a pilot of Option B+ e-learning at NEPI supported schools in Lesotho, Zambia and Malawi and NIMART in-service training. Local, regional and international nursing conference participation and abstract submission was encouraged. Over the life of the project, NEPI attended and presented as such conferences as ECSACON , Sigma Theta Tau Honor Society of Nursing, the International Council of Nurses (ICN) and the Association of Nurses in AIDS Care (ANAC). With the PEPFAR Pivot, CPD courses and abstracts focused on HIV priority areas.We present results across the six building blocks is presented here. Table The PEPFNursing Now Campaign, which builds on the Triple Impact report championing the critical role of nurses in achieving universal health coverage [By supporting the education and training of over 13,000 new nurses and midwives, the NEPI program has made a significant contribution by increasing both the quality and the quantity of the health-care workforce in sub-Saharan Africa and strengthening the health care workforce\u2019s ability to respond to HIV . In addicoverage .Nurses provide the majority of HIV services in Africa. Epidemic control will not be achieved without a strong nursing and midwifery workforce at the front lines of primary health care. The NEPI project is the first large-scale systematic multi-country investment in Africa to strengthen nursing and midwifery education reflective of clinical practice. NEPI leaders now drive education and practice change at 22 schools of nursing in Africa, equipped with the basic building blocks for quality education. Recent inter-professional collaboration efforts are building partnerships across professions to drive improvement in education, research and service delivery. Yet, much work remains to ensure nursing and midwifery strengthening is sustained and shared with the thousands of nursing and midwifery schools that lack the basic building blocks of high quality education. The critical role of nurses in HIV must continue to be met with substantive investment in nursing and midwifery education."} +{"text": "Equitable access to essential psychotropic medicines at primary level is fundamental to universal health coverage for mental health. It relies upon rational selection, affordable pricing, financial protection and consistent supply systems. Which medicines are selected as essential impacts patient care and the economic sustainability of the health system. Rational selection uses the best available evidence for efficacy, safety and acceptability, and requires the assurance of affordability, obtainability and appropriate usage of the medicines. The process should be reliable, transparent and consultative.The aim of this study is to describe the process of rational selection of essential psychotropic medicines at primary health care (PHC) level, using SSRIs as an example.Population, intervention, comparison and outcome (PICO) questions were developed for a rapid review of SSRIs for depression and anxiety. PubMed, Trip Database and Cochrane Library were searched for evidence, which was critically appraised (graded as per SORT criteria) and synthesised. Good governance principles were maintained using a consensus decision-making process within the constraints of the PHC Expert Review Committee\u2019s terms of reference, confidentiality and conflict of interest policies. Evidence-based medicine principles were used, considering social values of equity, acceptability, comparative cost and relative budget impact analysis.The PubMed search for meta-analyses yielded 588 articles, of which 13 met inclusion criteria. An additional 4 meta-analyses were retrieved from the Cochrane Library and 4 from additional reference lists. A second search specifying an HIV population retrieved 43 articles, of which 3 were included. The evidence for efficacy and harm of 24 papers was critically appraised by the committee. Conflicts of interest were declared, and there was appropriate recusal from the final decision-making, which took place in July 2018.Rapid reviews using an evidence-based medicine framework contributed to the selection of SSRIs for the PHC essential medicine list. This approach is intensive in terms of resources and capacity, requiring adaptation to the South African setting. Important limitations include time pressure and the use of a single reviewer, with possible incomplete database searches and reviewer bias. Nevertheless, the process allows for thorough, consistent and transparent decision-making, and improved capacity is recommended."} +{"text": "While family caregiving of the elderly has long been part of the cultural life of most OECD countries, longer life expectancy combined with low fertility rates has increased the share of the population dependent on current workers and minimized the available population of informal caregivers. The demand for expanded public provision of long-term care (LTC) resulting from this demographic shift prompted reforms in many OECD countries in the 1990s and 2000s. Differences in these reforms provide an opportunity to examine how individual choices between formal and informal care types are shaped by the policy context. I use longitudinal data on elders in three OECD countries, Sweden, Germany, and Japan, to examine LTC decisions under three varied approaches to population aging. The direction of LTC reforms in each country has been shaped by the existing model of care provision and financial constraints. In response to cost pressures, Sweden introduced need-based provision, financial devolution, and market-based approaches to its universal care model. Germany and Japan, in contrast, widely expanded restricted LTC coverage through public LTC insurance models. I use three multinomial logistic models of the LTC decision to test how differing policy schemes influence choices between formal and informal care. Using longitudinal Global Gateway to Aging data for each country, I model the LTC decision in each country as a factor of demographic and need characteristics of the elder experiencing limitations, characteristics of their family, and eligibility for publicly-provided LTC."} +{"text": "For more than a decade, the United States has performed environmental monitoring by collecting and analyzing air samples for a handful of biological threat agents (BTAs) in order to detect a possible biological attack. This effort has faced numerous technical challenges including timeliness, sampling efficiency, sensitivity, specificity, and robustness. The cost of city-wide environmental monitoring using conventional technology has also been a challenge. A large group of scientists with expertise in bioterrorism defense met to assess the objectives and current efficacy of environmental monitoring and to identify operational and technological changes that could enhance its efficacy and cost-effectiveness, thus enhancing its value. The highest priority operational change that was identified was to abandon the current concept of city-wide environmental monitoring because the operational costs were too high and its value was compromised by low detection sensitivity and other environmental factors. Instead, it was suggested that the focus should primarily be on indoor monitoring and secondarily on special-event monitoring because objectives are tractable and these operational settings are aligned with likelihood and risk assessments. The highest priority technological change identified was the development of a reagent-less, real-time sensor that can identify a potential airborne release and trigger secondary tests of greater sensitivity and specificity for occasional samples of interest. This technological change could be transformative with the potential to greatly reduce operational costs and thereby create the opportunity to expand the scope and effectiveness of environmental monitoring. The release of a BTA as an aerosol has the potential to kill thousands of individuals Riedel, . The iniSurveillance for a biological attack currently relies on a combination of public health/clinical surveillance and environmental monitoring. Public health/clinical surveillance involves a combination of syndromic disease surveillance met to discuss the current state-of-the-art technology for 9 h over three consecutive days during a conference on chemical and biological terrorism defense. The participants included past and present DHS program managers tasked with Research and Development to support the Biowatch program, experts who have contributed in various ways to environmental monitoring of BTAs over the entire history of the Biowatch program, and members of other U.S. Government agencies that have participated in prior assessments of the Biowatch program. State government end-users of the Biowatch program did not attend the scientific conference from which this discussion group was assembled. The discussion group was tasked with providing recommendations to address three specific challenges: value and benefit to public health, cost and sustainability, and probability of detection. The consensus recommendations from the discussion group include operational and technological changes that range from incremental to transformative. Implementing these recommendations could lead to a more robust and cost-effective environmental monitoring program.detect-to-warn and detect-to-treat. The two operational modes were originally defined in the context of warning systems for U.S. military personnel . In the detect-to-warn mode, the early cases of illness diagnosed through conventional public health channels provide confirmation of an exposure event. The early cases can also provide additional characterization of the event and the identification of the potential exposure zone that can be used to trigger a larger public health response for soon-to-emerge cases. Detect-to-warn is the easiest mode to implement. Current environmental monitoring for airborne BTAs operates in the detect-to-warn mode (using the definition provided here) but lacks some of the critical elements needed to support a rapid response, namely adequate data or demonstrated approaches to gather supplemental data that can engender widespread confidence among public health officials.The detect-to-warn mode simply alerts public health officials of a high-confidence exposure event and can trigger population-level distribution of MCMs for post exposure prophylaxis if the scale and geographic scope of the attack is reasonably understood. In this mode, the presence of an air borne biological agent of interest must be established with high confidence because MCMs cannot be delivered to a population based on inconclusive or false positive results. Population-level treatment for an unconfirmed threat is too costly in logistics, materials, and possible adverse health events. Adverse health events can occur as a result of potential side-effects or adverse interactions with other medications in a large, physiologically heterogeneous civilian population in which an unknown number may also have varying degrees of immune-suppression.The detect-to-treat mode alerts public health providers of a Bacillus anthracis or Francisella tularensis) or genetic near neighbors that are indistinguishable from the agent of interest by the assays employed. For example, the microorganisms that cause anthrax and tularemia are endemic in the U. S. and can be found in environmental matrices such as soil and water, respectively, that can serve as sources of low numbers of airborne organisms. However, the airborne concentrations or the viability of these naturally occurring agents are likely insufficient to cause human disease as suggested by the absence of reported cases of inhalation anthrax and pneumonic tularemia in areas where Biowatch is deployed. This is particularly significant with F. tularensis because the infectious dose may be <10 organisms may occasionally be found on air collection filters and detected by current assays resulting in false positive results. The Biowatch program reported 149 false positives from 2003 to 2012 in the performance of environmental monitoring is a significant challenge. Like any clinical diagnostic device, the end-to-end performance of an environmental monitoring system must be thoroughly validated under relevant conditions and the benefit must be unambiguous and their likelihood of detection.detect-to-warn mode, but it is essential for surveillance in the detect-to-treat mode. Viability confirms that a BTA of interest was detected that can potentially cause infection. It also enables antibiotic susceptibility testing to confirm the appropriate antibiotic(s) for prophylaxis. An integrated system does not currently exist for routine surveillance of air borne organisms or toxins of interest and simultaneous confirmation of agent viability or toxicity. In currently existing environmental monitoring systems, for example, a 24-h period of collection results in cell desiccation and possibly additional stresses such as denaturation of proteins that pose substantial challenges for the recovery of viable organisms and active toxins. Given that surveillance in detect-to-treat mode can reduce morbidity and mortality to a much greater degree than in detect-to-warn mode, developing an effective approach to reduce the loss of viable pathogens and toxins during aerosol sampling would be a valuable investment.Confirming the viability of an aerosolized pathogen is unnecessary for environmental monitoring in the Any approach to recovering and documenting viable, non-sporulating biological agents and active toxins of interest must address two major problems: (a) desiccation-related loss of viability or stability; and, (b) ability to rapidly distinguish a viable BTA of interest from other viable cells that may be present in a sample.Although desiccation resulting in cellular destruction or protein denaturation is commonly believed to be the cause of cell death and loss of toxin activity in aerosol samples, dehydration is a common method used for long-term preservation of microbial cells or toxins. In aerosol samples, cell death may occur from the rapid re-hydration of cells during assays for viability increasing the probability that one or more detectors are close to the point source where the released agent concentrations are highest, and (ii) increasing the probability that at least one detector will capture an event despite changing air-flow patterns. A denser network would also improve the likelihood that multiple detectors document an event, which can facilitate the characterization of the magnitude and spatial coverage of an event. However, the cost of denser networks is expected to make outdoor environmental surveillance prohibitive. Consequently, the panel recommended abandoning outdoor monitoring because, as currently practiced, outdoor environmental monitoring seems unlikely to achieve its operational goal have been suggested as potential technologies for a reagent-less bioagent sensor (National Research Council, Raman spectroscopy has been evaluated as a potential technology platform for a reagent-less environmental monitoring system (Ronningen and Bartko, Our recommendations are consistent with those from prior expert panels that evaluated environmental surveillance for biodefense (National Research Council, Kevin Anderson, Department of Homeland Security; Tamilselvam Batcha, University of Illinois; Thomas Blake, Centers for Disease Control and Prevention; Steven Blanke, University of Illinois; Catherine Branda, Sandia National Laboratory; Katrina Campbell, Queen's University Belfast; Stephen Casalnuovo, Sandia National Laboratory; Rodrigo Castillo-Garza, United Technologies Research Center; Douglas Cerasoli, U.S. Army Medical Research Institute of Chemical Defense; Jean Challacombe, Los Alamos National Laboratory; James Dillman, US Army Medical Research Institute of Chemical Defense; John Dunbar, Los Alamos National Laboratory; David Franz, NGI; Mark Geisberg, Silver Lake Research Corporation; David Hodge, Department of Homeland Security; Robin Holland, University of Illinois at Urbana Champaign; Hayden Huang, Government Accountability Office; Molly Hughes, University of Virginia; Janine Hutchison, Pacific Northwest National Laboratory; Morten Jensen, Gate Scientific; Justin Kita, Federal Bureau of Investigation; Luther Lindler, Department of Homeland Security; Ronald Manginell, Sandia National Labs; Patrick Martin, Takara Bio USA; Patrick McNutt, U.S. Army Medical Research Institute of Chemical Defense; Eric Merkley, Pacific Northwest National Laboratory; Stephen Morse, Centers for Disease Control and Prevention; William Nelson, Tetracore; Tom O'Brien, Tetracore; Timothy Persons, Government Accountability Office; Segaran Pillai, HHS Food and Drug Administration; Kristian Scaboo, Gate Scientific; Shashi Sharma, HHS Food and Drug Administration; Sushil Sharma, Government Accountability Office; Patrick Stayton, University of Washington; Nicole Steinmetz, Case Western Reserve University; Jane Tang, Department of Homeland Security; Bernhard Weigl, Global Good; David Wunschel, Pacific Northwest National Laboratory.These participants were attending a conference on Chemical and Bioterrorism Defense and were invited as subject matter experts to the independently organized discussions from which this perspectives article arose.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The INTERGROWTH-21st standards, it is essential to assess the feasibility and acceptability of their implementation and their effect on clinical decision-making in a low-resource clinical setting.To scale up the INTERGROWTH-21This study protocol describes a pre-post, quasi-experimental implementation study of the standards at Jacaranda Health, a maternity hospital in peri-urban Nairobi, Kenya. All women with viable fetuses receiving antenatal and delivery services, their resulting newborns, and the clinicians caring for them from March 2016 to March 2018 are included. The study comprises a 12-month preimplementation phase, a 12-month implementation phase, and a 5-month post-implementation phase to be completed in August 2018. Quantitative clinical and qualitative data collected during the preimplementation and implementation phases will be assessed. A clinician survey was administered eight months into the implementation phase, month 20 of the study. Implementation outcomes include quantitative and qualitative analyses of feasibility, acceptability, adoption, appropriateness, fidelity, and penetration of the standards. Clinical outcomes include appropriateness of referral and effect of the standards on clinical care and decision-making. Descriptive analyses will be conducted, and comparisons will be made between pre- and postimplementation outcomes. Qualitative data will be analyzed using thematic coding and compared across time. The study was approved by the Amref Ethics and Scientific Review Committee (Kenya) and the Harvard University Institutional Review Board. Study results will be shared with stakeholders through conferences, seminars, publications, and knowledge management platforms.st training: gestational dating ultrasound, fetal growth monitoring ultrasound, and neonatal anthropometry standards. Following the training, implementation and evaluation of the standards in Jacaranda Health\u2019s clinical workflow will take place from March 2017 through March 5, 2018. Data analysis will be finalized, and results will be shared by August 2018.From October 2016 to February 2017, over 90% of all full-time Jacaranda clinicians (26/28) received at least one of the three aspects of the INTERGROWTH-21st standards and on the process of scaling up global standards in general, particularly in limited-resource settings.The findings of this study will have major implications on the national and global scale up of the INTERGROWTH-21RR1-10.2196/10293 The neonatal period (first 28 days of life) is the most vulnerable time for an infant\u2019s survival. In 2016, 2.6 million neonates died globally representing 46% of all under-five deaths . There aTo make sound clinical decisions and provide quality maternal and neonatal care, clinicians require measurement standards for accurate pregnancy dating, monitoring of fetal growth, and assessment of newborn size and growth . Such stThe date of the maternal last menstrual period (LMP) can be used for pregnancy dating but is often inaccurate or unknown; in these cases, ultrasound is the most accurate method for determining gestational age ,18-20. Ust Project completed a five-year, global, prospective study of growth, health, nutrition, and neurodevelopment. The study followed women and their infants longitudinally from less than 14 weeks gestation until two years postnatal. The project enrolled populations at low risk of adverse outcome in Brazil, Italy, Oman, UK, USA, China, India, and Kenya [st data were compiled to develop new prospective standards to be used to assess pregnancy dating in the first trimester [In 2014, the INTERGROWTH-21nd Kenya ,29. INTErimester and secorimester , fetal grimester (includirimester and ultrrimester ), and nerimester ,17. WithTo scale these standards and affect preterm birth and its complications, including neonatal mortality, it is essential to assess the feasibility and acceptability of implementing these standards and their effect on clinical decision-making, particularly in low-resource clinical settings.st standards over a one-year period at Jacaranda Health, a private, social enterprise maternity hospital in peri-urban Nairobi, Kenya. To our knowledge, this is the first facility-based implementation study of the INTERGROWTH-21st standards in a limited-resource setting. The research design considers stakeholder inputs, the physical and institutional environment, and the health system structure.We aim to assess the feasibility and acceptability of implementing the INTERGROWTH-21st standards in other settings and to inform the translation of guidelines and tools into routine clinical practice.The ultimate aim of the project is to use the results of the study to inform the implementation and scale up of the INTERGROWTH-21st standards at Jacaranda Health. The specific components of the primary objective are to assess the introduction of the INTERGROWTH-21st standards and the training of clinicians at Jacaranda Health, the effect of the implementation of the INTERGROWTH-21st standards on clinical practices at Jacaranda Health, clinicians\u2019 experiences and satisfaction with the INTERGROWTH-21st standards, clinicians\u2019 perceived effect of the standards on the clinical care they provide, and patient experiences and satisfaction with the care they received at Jacaranda Health during implementation of the INTERGROWTH-21st standards.The primary objective is to determine the facilitators and barriers to implementing the INTERGROWTH-21st standards on clinicians\u2019 decision-making and patient outcomes, including the processes for determining gestational age and estimated due date, internal referral to Jacaranda Health clinicians providing high-risk consultations, tertiary-center referral of high-risk pregnant women, and indications for and rates of labor inductions and caesarean sections.The secondary objective of this study is to assess the effect of implementing the INTERGROWTH-21st standards on clinical decision-making and management at Jacaranda Health. Study activities consisted of a 12-month preimplementation phase which included a baseline facility assessment, changes to facility protocols and charting forms, planning work flow adaptations to facilitate implementation of the standards, equipment procurement, training of clinicians, and baseline data collection; a 12-month implementation phase which included the implementation of the INTERGROWTH-21st clinical standards, revised facility protocols and charting forms into routine clinical practice, and data collection; and a five-month post-implementation phase which includes analysis and dissemination.This is a pre-post, quasi-experimental implementation study using quantitative clinical data, focus group discussions (FGDs), in-depth interviews (IDIs), and a short clinician survey. The study describes the feasibility, acceptability, and the effect of implementing the INTERGROWTH-21st researchers at Oxford University and researchers at the Harvard T.H. Chan School of Public Health.This study design was based on a conceptual model created by INTERGROWTH-21st standards and capturing factors that facilitate and challenge that process. Jacaranda Health patients come from densely-populated, peri-urban neighborhoods in northeastern Nairobi, including Kiambu, Thika, Gatundu, and Embakasi districts. These areas are served by many facilities that range from small pharmacies and outpatient care clinics to private and public sector secondary and tertiary hospitals with maternity wards; the services and prices vary substantially across these facilities.This implementation study is currently being carried out at Jacaranda Health, a social enterprise, 18-bed maternity hospital that provides women in peri-urban Nairobi with affordable, safe, and respectful ANC, standard vaginal and cesarean delivery, and postnatal care (PNC) services. Women in preterm labor and newborns with LBW and/or complications are not managed at this facility and are referred to tertiary-level facilities for specialized care. With a model that emphasizes quality and affordable care provided primarily by nurse-midwives , Jacaranda Health provides an ideal venue for evaluating the implementation of the INTERGROWTH-21Pregnant women with a viable fetus presenting for ANC and/or delivery at Jacaranda Health were eligible for the following three elements of the intervention: (1) gestational dating standards for women who present for their initial ANC visit in the first or second trimester ; (2) fetal growth monitoring standards for women who present for an ANC visit in the third trimester (after 26 weeks gestation) and are identified as high-risk based on factors related to their surgical, medical, or obstetric history or current pregnancy; and (3) newborn size at birth standards for all newborns born at Jacaranda Health. We excluded pregnant women with a nonviable fetus in both quantitative and qualitative data collection, women who present for their initial ANC visit in the third trimester (after 26 weeks gestation) for gestational dating standards, and parents of stillborn infants in qualitative data collection. All eligible pregnant women and mothers of newborns described above were eligible to participate in FGDs and IDIs.st training sessions are eligible to participate in FGDs, IDIs, and a short clinician survey. Clinicians who only work in child wellness clinics and not in prenatal or intrapartum care units were excluded.All clinicians delivering ANC and newborn anthropometry who attended INTERGROWTH-21st standards at Jacaranda Health to assess their acceptability and inform their further scale up. The results of the study will be disseminated to providers at Jacaranda Health by study staff at the end of the study.The development of the study design, research questions, and outcome measures did not formally involve patient and public opinions and contributions. However, the study assesses patient and provider perceptions and experiences of the implementation of the INTERGROWTH-21st standards, we conducted a baseline assessment of current facility practices as they relate to our study objectives. Focus was placed on policies and practices related to ANC provision, pregnancy dating, identification and referral of high-risk pregnancies to high-risk care within Jacaranda Health and to tertiary facilities, fetal growth monitoring, newborn size measurement, and indications for and rates of cesarean section and labor induction.Before implementing the INTERGROWTH-21The baseline assessment was conducted through clinic observations; a desk review of written policies; IDIs with Jacaranda Health\u2019s director of clinical operations, clinical programs manager, and clinical educator; a chart review to understand clinician practices and indications for and rates of cesarean sections and labor inductions; an equipment and supply inventory with a focus on ultrasound and newborn anthropometry; and a human resource inventory to understand existing personnel and clinician roles and responsibilities related to clinic flow, pregnancy dating, fetal growth monitoring, and patient counseling. We then adapted ANC protocols to align with the 2002 WHO ANC model . This wost standards. In partnership with Oxford University, we created a computerized calculator to calculate gestational age and fetal growth percentiles: clinicians use the ultrasound machine to measure the required biometrics for gestational dating or fetal growth, input the measurements into the calculator, and then record the resulting gestational age or fetal growth percentiles in the patient\u2019s chart. Additionally, neonatal scales, measuring tapes, and infantometers, chosen in consultation with the INTERGROWTH-21st Oxford team and adjusted based on local availability and resource constraints, were sourced and integrated into clinical practice.A key element of preimplementation activities was ensuring that the hospital\u2019s equipment, protocols, and procedures were updated and adapted for the implementation of the INTERGROWTH-21st standards.We updated Jacaranda Health clinical protocols for standard ANC, high-risk pregnancy classification and subsequent internal and tertiary-center referral, gestational dating, fetal growth monitoring, and newborn anthropometry, in addition to corresponding patient charting forms, to support the implementation and evaluation of the INTERGROWTH-21Clinician job aids were created to facilitate the implementation of the standards and related decision-making algorithms. We also altered clinic flow processes to accommodate the introduction of ultrasound services; a separate room was designated exclusively for gestational dating ultrasounds. In the context of adapting clinical definitions of high-risk pregnancy criteria and processes for both internal and tertiary-center referrals, we trained clinicians to only do activities (like ultrasound) within their scope of practice as determined by the Nursing Council of Kenya.st standards. This was done in collaboration with the original INTERGROWTH-21st Project study team based at Oxford University and Aga Khan University Hospital (AKUH) in Nairobi, Kenya [A main aim of implementation was training Jacaranda Health staff how to use the INTERGROWTH-21i, Kenya -37.st gestational dating ultrasound, fetal growth monitoring ultrasound, and neonatal anthropometry standards. Emphasis was placed on including assessment, identification, and referral of high-risk patients as part of the study design to evaluate operational system capacity to support the implementation of the standards and their clinical implications.From October 2016 to February 2017, we conducted training of Jacaranda Health clinical and management staff on the purpose and use of the INTERGROWTH-21st standards and accompanying adaptations to charting practices and clinical protocols. Of the 23 participants in the training, 22 were nurse-midwives and one was a clinical officer; these staff provide the majority of ANC and PNC at Jacaranda Health.An obstetrician-led half-day training included essential components of ANC, basic obstetric ultrasound skills, and the INTERGROWTH-21st anthropometry trainer from AKUH provided a half-day anthropometry training which included theory, equipment, and techniques needed to perform accurate newborn length, weight, and head circumference measurements. The anthropometry trainer certified clinicians in neonatal anthropometry after they performed length, weight, and head circumference measurements accurately on newborns. One group of 24 clinicians, 23 nurse-midwives and one clinical officer, attended this training. Nearly 90% (24/28) of all full-time and part-time Jacaranda Health clinicians attended these initial trainings.An obstetrician and an INTERGROWTH-21st ultrasound measurements for the first, second, and third trimesters over the course of two weeks. At the end of the two weeks, the sonographer demonstrated proficiency in performing INTERGROWTH-21st measurements as determined by a senior radiologist at AKUH. The Jacaranda Health sonographer then trained a group of six Jacaranda Health nurse-midwives with prior experience in basic obstetric ultrasound during a half-day training on gestational dating ultrasounds. Three of the six nurse-midwives were certified to perform gestational dating ultrasounds after proving competence in performing measurements and calculating estimated delivery date accurately three consecutive times in the presence of the sonographer. This group of three nurse-midwives constitutes over 10% (3/28) of all clinicians.AKUH trained Jacaranda Health\u2019s primary sonographer in INTERGROWTH-21st standards, revised facility protocols, and adapted patient charting forms were introduced into routine clinical practice in March 2017. The clinic work flow adaptations were implemented to facilitate the identification of pregnant women eligible for ultrasound using the new standards and ensure that pregnant women were seen by the appropriate clinician. Work flow adaptations were not needed to implement the newborn size at birth standards since newborn anthropometry was an established part of routine practice.After training was completed and equipment was put into place, the INTERGROWTH-21st standards, three quality monitoring processes were utilized: expert ultrasound image review, weekly clinic stakeholder meetings, and targeted refresher training. Our protocol includes sending copies of de-identified gestational dating and fetal growth ultrasound images to the quality assurance team at Oxford University. The team reviews the images, assesses the quality of each image based on INTERGROWTH-21st guidelines, and provides guidance to Jacaranda Health staff on how to improve ultrasound quality, if needed. Images were sent to Oxford for review every two months via a double password-protected Dropbox folder. The program management team at Jacaranda Health then shared feedback from the Oxford team with the ultrasound providers to strengthen sonography skills and processes. Reinforcement training was provided by Oxford University clinical researchers specializing in sonography midway through implementation to further improve the quality of the ultrasound procedures. Challenges in clinical implementation were discussed by the clinical staff during weekly meetings, which enabled staff to quickly resolve any problems. Lastly, through chart review and observation, the clinical and project management teams had the discretion to identify clinicians who required targeted refresher training and to provide that training at any point during the study. Important project notifications and reminders were administered to all staff at weekly clinical meetings by clinic managers and project management.To ensure the quality of the implementation of the INTERGROWTH-21st standards and (2) uptake of gestational dating ultrasounds, fetal growth monitoring by ultrasound, and newborn anthropometry. These outcomes were explored through the following dimensions: feasibility, acceptability, appropriateness, adoption, fidelity and penetration [The primary study outcomes are (1) clinicians\u2019 and patients\u2019 perception of facilitators and barriers to the implementation of the INTERGROWTH-21etration .The secondary outcomes used to evaluate clinical decision-making include (1) proportion of ANC clients whose gestational age and estimated due date were correctly calculated and documented, (2) proportion of high-risk pregnant women who were referred internally to a high-risk clinician or to a tertiary care facility, (3) proportion of pregnant women receiving gestational dating scans who were induced for labor due to a prolonged pregnancy, and (4) proportion of pregnant women receiving gestational dating scans who delivered via cesarean section.During the preimplementation phase, baseline data were collected for 12 consecutive months (months 1-12) prior to the start of the implementation phase. Data were also collected for 12 consecutive months during the implementation phase (months 13-24). These preimplementation and implementation phase quantitative data come from patient charting forms completed in the two-year period. Qualitative data were also collected during the preimplementation phase (month eight) and the implementation phase (month 16 and month 24). Additionally, a one-time short provider survey was administered during the implementation phase at month 20 to assess clinicians\u2019 attitudes and acceptability of the standards. .We collected outcome data from patient charts and from a clinic log of external referrals for pregnancies and deliveries one year before and one year after the start of implementation.We conducted FGDs and IDIs with participants sampled from two population groups using purposeful and convenience sampling: (1) patients who received ANC and/or delivery care at Jacaranda Health and (2) clinicians who work directly with patients including nurse-midwives, hospital managers, ultrasonographers, and physicians.FGDs and IDIs with patients and clinicians were conducted in the preimplementation phase and twice during the implementation phase. Patients were interviewed to evaluate their perceptions, attitudes, and experiences of receiving an ultrasound for gestational dating and fetal growth, their newborn receiving a growth assessment, and their interactions with clinicians implementing this care. Clinicians were interviewed to evaluate their perceptions, attitudes, and experiences of the introduction and implementation of the new standards as part of their routine clinical practice.The research team developed semistructured discussion guides for both FGDs and IDIs, which were piloted with Jacaranda Health staff and patients. Research assistants conducted all interviews in a private and secure location and took great care to protect the identity and confidentiality of all participants. To encourage patient participation in qualitative interviews, we offered reimbursement for transportation to the facility and free refreshments after the completion of the interviews. All FGDs and IDIs were audio-recorded and transcribed verbatim by an external transcriber; in the instances that participants spoke a language other than English, the transcriber translated the recording to English for the transcript. Hand-written notes taken by the research assistant provided the context for the interviews.st standards, the ease of integration into their workflow, and their perceptions of the effect of the standards on the quality of care they provided.Additionally, a survey (10 questions) was administered by a research assistant to all clinicians during the implementation phase at month 20 via Survey Monkey on an Android tablet. Clinicians were asked to grade their comfort with the INTERGROWTH-21We used a census of clinicians and patients for this implementation study based on the inclusion and exclusion criteria described prior. According to clinic estimates and projections of ANC and delivery care utilization, data for up to 5,000 pregnant women and newborns will be recorded. The total number included in the final analysis will be based on the number of patients who meet eligibility criteria as confirmed at the time of data entry based on indicators in patient charting forms.In each time period, the sample will be stratified into the following three categories: (1) pregnant women who attended ANC at Jacaranda Health and delivered there, allowing analysis of longitudinal ANC and delivery data; (2) pregnant women who attended ANC at Jacaranda Health but did not deliver there, providing ANC data only; and (3) women who did not attend ANC but who delivered at Jacaranda Health, capturing delivery and newborn data only. All clinic managers, physicians, and nurse-midwives who met the criteria are included. Clinician attrition will be documented.Data from patient charts and referral logs were double-entered and managed in REDCap , a securMost implementation and process indicators will be measured and presented using descriptive statistics. We will analyze changes in quantitative outcomes where relevant, by evaluating the difference in response to the indicators between pre- and postimplementation. Measurements of differences in continuous data will be assessed using t-tests for data that is normally distributed; otherwise, a non-parametric test will be performed. Categorical data will be compared using a chi-squared test. Quantitative data will be analyzed using Stata 15 . All datFor each cycle of qualitative data transcription, the transcriber completed transcription of one initial data file and sent it to the qualitative data manager at Jacaranda Health for quality control prior to transcribing the rest of the data files.Qualitative data collected at each stage are being analyzed independently by two investigators using thematic coding in NVivo and compResults of the study will be shared with key stakeholders both in Kenya and globally through a national dissemination meeting, global conferences, an online knowledge management platform, and publications.The Amref Ethics and Scientific Review Committee of Kenya and the Harvard University Institutional Review Board approved all study activities, protocols, and standards prior to the commencement of study activities.Facility-level informed consent was obtained from the Jacaranda Health hospital manager, acting as the facility\u2019s representative, prior to the collection of any implementation data. The facility informed consent emphasized that no patient-identifiable health data would be shared or disseminated beyond the Jacaranda Health team. All FGD, IDI, and survey participants\u2014patients and clinicians\u2014provided written informed consent prior to any interview. Participants were informed that they could withdraw their consent at any time and be removed from the sample.st training: gestational dating ultrasound, fetal growth monitoring ultrasound, and neonatal anthropometry standards. Following the training, the implementation and study of the INTERGROWTH-21st standards as part of Jacaranda\u2019s clinical workflow took place from March 2017 through March 5, 2018. Data analysis will be finalized, and results are expected in August 2018.From October 2016 to February 2017, over 90% of all Jacaranda Health clinicians received at least one of the three aspects of the INTERGROWTH-21st standards and on the process of scaling up global standards in general, particularly in limited-resource settings. The ability to implement a standard methodology of gestational dating, fetal growth monitoring, and assessment of newborn size at birth will result in better data to enable clinicians, researchers, and policy makers to more accurately identify and quantify high-risk pregnancies, preterm birth, and fetal and neonatal growth disturbances. In turn, standardized data that is comparable across global populations empowers researchers and policy makers to better understand and act on distributions of high-risk pregnancies, restricted growth, and prematurity. Lastly, based on this data, clinical practice and resources can be modified to meet the needs of pregnant women and their fetuses and newborns to decrease the incidence and morbidities associated with poor fetal and newborn growth and prematurity.The findings of this study will have major implications on the national and global scale up of the INTERGROWTH-21While Jacaranda Health provides the right environment for this study, the generalizability of our findings needs to be carefully considered when applying lessons learned to other clinical settings. Given that clinic protocols were amended to meet the 2002 WHO ANC guidelines, which affected the criteria for high-risk referral, this change may confound the outcome of the percentage of women who are referred to high-risk care. The study is also limited in its ability to assess the long-term health outcomes of these standards, yet it will inform future research designed to assess them.st clinical standards into a low-resource setting. Due to the dearth of innovative gestational dating tools and burden of preterm birth in low-resource settings, it is particularly important to study the implementation of these standards in this setting. The results of our evaluation will provide useful insights and recommendations for further implementation in similar clinical settings in Kenya and beyond.This will be the first study to assess the feasibility and acceptability of introducing the new INTERGROWTH-21st standards and the resulting impact on short-term clinical decision-making. Lastly, Jacaranda Health is dedicated to health facility quality improvement in peri-urban Nairobi, which makes it an excellent venue for evaluating the implementation of the INTERGROWTH-21st standards and for capturing factors that facilitate and challenge that process.Additionally, the mixed-methods approach used in this study will yield unique insights into the barriers, facilitators, and process of implementing the INTERGROWTH-21"} +{"text": "Dear Editor,In 1923, Masson initially described a process, at that time neoplastic, which consisted of vascular lumen obliteration due to papillary endothelial hyperplasia associated with degenerative changes.None declared.Sergio Emerson Sasso: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Ana Paula Naspolini: Approval of the final version of the manuscript; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the manuscript.Tassiana De Boit Milanez: Obtaining, analyzing and interpreting the data.Guilherme Suchard: Obtaining, analyzing and interpreting the data.None declared."} +{"text": "The Mediterranean climate is characterized by hot dry summers and frequent droughts. Mediterranean crops are frequently subjected to high evapotranspiration demands, soil water deficits, high temperatures, and photo-oxidative stress. These conditions will become more severe due to global warming which poses major challenges to the sustainability of the agricultural sector in Mediterranean countries. Selection of crop varieties adapted to future climatic conditions and more tolerant to extreme climatic events is urgently required. Plant phenotyping is a crucial approach to address these challenges. High-throughput plant phenotyping (HTPP) helps to monitor the performance of improved genotypes and is one of the most effective strategies to improve the sustainability of agricultural production. In spite of the remarkable progress in basic knowledge and technology of plant phenotyping, there are still several practical, financial, and political constraints to implement HTPP approaches in field and controlled conditions across the Mediterranean. The European panorama of phenotyping is heterogeneous and integration of phenotyping data across different scales and translation of \u201cphytotron research\u201d to the field, and from model species to crops, remain major challenges. Moreover, solutions specifically tailored to Mediterranean agriculture are in high demand, as the region is vulnerable to climate change and to desertification processes. The specific phenotyping requirements of Mediterranean crops have not yet been fully identified. The high cost of HTPP infrastructures is a major limiting factor, though the limited availability of skilled personnel may also impair its implementation in Mediterranean countries. We propose that the lack of suitable phenotyping infrastructures is hindering the development of new Mediterranean agricultural varieties and will negatively affect future competitiveness of the agricultural sector. We provide an overview of the heterogeneous panorama of phenotyping within Mediterranean countries, describing the state of the art of agricultural production, breeding initiatives, and phenotyping capabilities in five countries: Italy, Greece, Portugal, Spain, and Turkey. We characterize some of the main impediments for development of plant phenotyping in those countries and identify strategies to overcome barriers and maximize the benefits of phenotyping and modeling approaches to Mediterranean agriculture and related sustainability. Mediterranean countries are important producers of vegetables, legumes, cereals, fruits, olives and olive oil, grapes, and wine. Vegetable production accounts for 13.7% of the EU\u2019s agricultural output with 63.9 million tons of vegetables grown in 2016 . Spain aTotal cereal production (rice included) in the EU reached 309 million tons in 2017, representing 12% of global production . AccordiOutside the EU, Turkey is a major contributor to European and global agricultural production. In 2017, Turkey accounted for approximately 70% (12.6 million tons) of EU tomato production . MoreoveForestry is another economically crucial sector for Europe, in addition to providing environmental sustainability and key ecosystem services. European forests can also help to mitigate the impact of climate change and enable adaptation policies. Indeed, EU forests absorb the equivalent of about 10% of the total annual greenhouse gas emissions from the EU . Forest The Mediterranean region typically experiences long periods of drought and abrupt rainstorms and floods that negatively impact on crop performance as well as the available water and soil resources. The region has typical dry periods combined with high temperatures and a marked inter-annual weather variability, which results in a large and a highly variable demand for irrigation and in higher incidence of pests and diseases . Spain, A more comprehensive understanding of the specific agricultural environment found in the Mediterranean region is required to support rural development and to meet the goals of the EU-Common Agriculture Program of CAP 2014-2020 . More prDigitization of agriculture and expansion of precision farming can reduce costs and minimize the environmental impact of agriculture . For exaPlant phenotyping, based on non-destructive image analysis, data management, and modeling, has emerged as a cutting-edge technology playing an important role in plant and agronomic sciences, namely, to design new crops, characterize the responses of genetic resources to the environment, and improve the breeding and management of crops . Therefore, implementation of such technologies is crucial for sustainable agro-food operations, while optimizing the use of natural resources such as water and soil.https://eppn2020.plant-phenotyping.eu/EPPN2020_installations#/). These high-throughput platforms are generating considerable volumes of data that provide valuable insights for plant/agronomic sciences and plant/crop breeding as evidenced by the increasing number of publications derived from these phenotyping facilities is most commonly used in high-throughput screening, with structural phenotyping and functional phenotyping being investigated in both model species and crops . Top-dowPhenotyping requires networks and interactions of sensor and data bases with biological and agricultural sciences . Phenotyping is also increasingly linked to modeling studies. Phenotyping should ideally be conducted at maximal throughput (number of units processed per unit time), resolution , and dimensionality (number of captured traits). However, in practice, a trade-off between these three phenotyping descriptors must occur due to economic, technological, time, and personnel constraints . The intTo support and accelerate plant improvement, plant phenotyping must be based on more cost-effective technologies and sensors . In thisvs. greenhouse crops, traits of interest) (see www.phenome-fppn.fr/) congregated nine phenotyping platforms, including controlled conditions (two units), semi-controlled conditions (two units), field conditions (three units), and molecular platforms (two units). This panorama contrasts with other Southern Mediterranean countries see . Yet, duest) see . In 2018http://www.plant-phenotyping-network.eu/eppn). The EPPN established a pan-European infrastructure that includes the whole phenotyping pipeline (involving sensors and imaging techniques), data analysis, and interpretation in a biological context and meta-analyses of experiments carried out on different organs and at different scales of plant organization. The EPPN currently operates in 10 countries providing access to 36 different plant-phenotyping facilities to the users. Furthermore, the European Strategic Forum for Research Infrastructure (ESFRI) has recognized plant phenotyping as a priority for the European research area to achieve food security in a changing climate context. Consequently, EMPHASIS was included in the ESFRI Roadmap 2016 (https://www.esfri.eu/roadmap-2016) as a project to develop and implement pan-European plant phenotyping facilities available to the user community. EMPHASIS aims at increasing the integration of major players and users involved in data acquisition, management, storage, and sharing, to provide a more practical use of the available phenotyping data to analyze genotype performance in diverse environments (The quest for tolerant varieties\u2014phenotyping at plant and cellular level) has further contributed to improve networking by facilitating the exchange of researchers, knowledge, skills, and training across countries, thus leveraging the absence of phenotyping facilities within some EU countries.Improved integration of phenotyping and genetic and genomic platforms and resources should facilitate increased understanding of crop performance for the development of more effective breeding strategies and also guarantee improved big data management . To accoronments . EMPHASIronments Figure 2To further enhance the sustainability of agriculture in Mediterranean countries, the establishment of phenotyping facilities remains a timely and indispensable issue. In the following section, we provide a short overview of the major characteristics of the existing phenotyping infrastructure and the knowledge and networks available in Southern Mediterranean countries.Greece and Portugal share rather similar constraints in terms of agricultural production, related to climate change vulnerability and limited investments in innovation and technology. The recent economic crisis had a marked impact on the development and use of modern technologies in the agriculture and agri-food sectors. Therefore, the panorama for plant/crop phenotyping is closely identical in the two countries and will be discussed in parallel.a (chl a) fluorescence, nutrient deficiencies, and infections have most commonly been assessed . In graia fluorescence induction transients open-field facilities to study the eco-physiological dynamics of plant species and specific crops in their natural environment ;(2) semi-controlled climate conditions within modern glasshouse facilities equipped with both contact and remote-sensing phenotyping tools to assess crop physiological performance;(3) fully controlled climate conditions (climate chamber facilities) for molecular phenotyping ; these facilities would complement the existing EPPN network, thus increasing the number of European facilities with fully controlled environmental conditions .Vitis phenotyping . For both Portugal and Greece, low-cost phenotyping approaches (and/or platforms) would be the most feasible way to move forward on the short to medium term, considering current financial constraints.For Greece and Portugal, the exploitation of current plant phenomics and crop-phenotyping technologies and strategies could provide valuable data for improved management of biodiversity resources, fostering crop/cultivar adaptability to climate and resistance against pests and diseases. However, field-phenotyping infrastructures are still unviable due to high costs. Some initiatives have been instigated to implement the use of phenotyping strategies in crop management, particularly using thermal and multispectral imaging alongside ground-based and aerial approaches (e.g. see projects INTERPHENO https://europa.eu/european-union/topics/agriculture_en).Spanish agriculture is highly competitive at both the European and global levels. The country is a major exporter of both fresh and processed agricultural and horticultural goods/products . Nevertha fluorescence, UV induced-multicolor fluorescence , and thermography using low-throughput imaging sensors for chl mography . Some grmography .Plant and ecosystem functions are also evaluated by mean of proximal and remote sensing, as well as diverse ecophysiological measurements . This reThe relationship between photosynthesis and production under drought conditions in Mediterranean crops is of special interest. The production of high-quality wines in Protected Designation of Origin Areas under a full range of climate conditions is particularly important in Spain . In grapXylella fastidiosa is a quarantine pathogen in the EU, and it has been detected in Spain, Italy, France, and Germany (https://www.eppo.int/ACTIVITIES/plant_quarantine/shortnotes_qps/shortnotes_xylella). X. fastidiosa is a threat to multiple crops across the whole Mediterranean analyses was established in 2017 to coordinate and develop plant-phenotyping research within Italy. The PHEN-ITALY network consists of 13 research organizations, universities, and regional agencies led by the National Research Council of Italy (CNR) and Agenzia Lucana di Sviluppo e di Innovazione in Agricoltura (ALSIA) where a large HTPP infrastructure is operating. CNR is a partner within the EMPHASIS-PREP. PHEN-ITALY aims to become the Italian infrastructural node of EMPHASIS. PHEN-ITALY also participates in the EPPN and the activities and projects of the International Plant Phenotyping Network (IPPN). Following the main principles of plant phenotyping (non-invasive and high-throughput measurements), the PHEN-ITALY infrastructure is based on optical systems that include a conveyor system, two imaging stations , and three computer stations to study: (i) the phenotypic background of genetically characterized crops of interest in Italy , (ii) the root to shoot architecture of plants, and (iii) the VOCs emitted by plants as markers of biodiversity and stress. For example, 3D scanning and chlorophyll fluorescence technology have been used to non-destructively assess the physiological and molecular responses to drought of tomato sprayed with a commercial mixture of amino acids and nutrients was grown around Sanliurfa between 10,000 and 12,000 years ago is crucial to understand crop/plant responses to the environment, but such integrated information remains comparatively limited. Moreover, we must identify which traits to phenotype, and at which moment of the plant\u2019s life cycle this should be done in a fast but robust way. These major questions must be addressed along with more specific issues during any investigation. The lack of integrated phenotyping data is a general drawback in plant phenotyping but is of particular importance in the Mediterranean region and related agriculture due to the structural complexity of field cropping systems . The use of non-invasive methods facilitates more objective and repeatable measurements of traits such as plant architecture, fruit quality, and/or the impact of biotic or abiotic stress under field conditions. Moreover, improvements in phenotyping imaging technology are resolving limitations associated with variable backgrounds and light conditions . To effehttps://emphasis.plant-phenotyping.eu/modelling). HTPP platforms and tools offer a new avenue in the parameterization of models to scale up data from molecular and morphological levels to breeding. Integration of phenotyping data with crop growth models can provide the means to evaluate and quantify the usefulness of agronomic practices to optimize resource use, as well as generate genotypes for different environmental contexts such as resilience to climate change. To this end, different classes of G2P (genotype-to-phenotype) models have been shown to help predict complex phenotypic traits as functions of GxExM interaction demand improved selection criteria and phenotyping strategies for both field and greenhouse conditions. To achieve this, we must: (1) define selection criteria for crop and phenotyping traits, according to the specific breeding needs of each country/region; (2) optimize the practical implementation of phenotyping efforts, as a function of the specific conditions of each country; (3) raise financial support among public and private stakeholders, and (4) include HTPP in national research policies for agriculture.Increasing integration of information across HTPP facilities or different biological levels to bring together farmers, the agro-industry, government, and consumers to identify the most adequate strategies to face the adversities associated with climate change in Mediterranean countries . The rolThe rapid (and expensive) development of phenotyping technologies can partly explain the heterogeneous panorama of phenotyping infrastructure within Europe. Indeed, differences in the establishment of infrastructure, budget, knowledge, and technological capacities are apparent when comparing Northern and Southern European countries. There are further differences amongst Mediterranean countries as well. The major ones are apparent in the available infrastructure, availability of qualified labor, dimension of the companies , and priorities of national and international networks. Solutions to the lack of financial resources, a problem common to Mediterranean countries are needed. Public\u2013private partnerships could assist in resolving this lack of investment and foster political will. This public\u2013private approach is already being implemented in some countries through the close cooperation of academic research institutes and commercial-breeding companies.2, etc.). In this way, it will be possible to properly assist breeding and selection of genotypes/phenotypes better suited to the prevailing and forthcoming climatic conditions in the Mediterranean. In parallel, the development of image processing, analysis, and modeling is also crucial to ensure relevant outputs. Interdisciplinary education of young researchers and technicians, from both public and private sectors, will also benefit from the establishment of phenotyping infrastructures.The establishment of phenotyping and phenomics facilities and infrastructures in Southern EU member states is crucial to meet the EU 2020 targets of smart specialization, sustainable growth, and the development of an inclusive and circular economy. Particularly in light of the budget limitations, commonly experienced by Southern European countries, phenotyping infrastructures should rely on simple, lower cost, and rapid methods, which are user-friendly, reliable, and robust. Improved phenotyping approaches will enhance our understanding of crop responses to Mediterranean climate conditions should be encouraged to implement phenotyping technologies in agricultural and climate change scenarios and to further incorporate genetic and molecular approaches to improve crop productivity.All authors wrote the paper and read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "The United States and Mexico differ greatly in the organization and financing of their old-age welfare states. They also differ politically and organizationally in government response at all levels to the needs of low-income and frail citizens. While both countries are aging rapidly, Mexico faces more serious challenges in old-age support that arise from a less developed old-age welfare state and economy. For Mexico, financial support and medical care for older low-income citizens are universal rights, however, limited fiscal resources for a large low-income population create inevitable competition among the old and the young alike. Although the United States has a more developed economy and well-developed Social Security and health care financing systems for the elderly, older Mexican-origin individuals in the U.S. do not necessarily benefit fully from these programs. These institutional and financial problems to aging are compounded in both countries by longer life spans, smaller families, as well as changing gender roles and cultural norms. In this interdisciplinary panel, the authors of five papers deal with the following topics: (1) an analysis of old age health and dependency conditions, the supply of aging and disability services, and related norms and policies, including the role of the government and the private sector; (2) a binational comparison of federal safety net programs for low-income elderly in U.S. and Mexico; (3) when strangers become family: the role of civil society in addressing the needs of aging populations; and (4) unmet needs for dementia care for Latinos in the Hispanic-EPESE."} +{"text": "Methopolophium dirhodum Walk.) is a major pest of maize (Zea mays L.), but little is known about the biochemical interactions between M. dirhodum and its host plant. Thiol compounds and glutathione S-transferase (GST) play a crucial role in the defense responses of maize to biotic stress factors, including aphids. The purpose of this research was to evaluate the impact of M. dirhodum herbivory on the total thiol (TT), protein bound thiol (PT), reduced glutathione (GSH) and oxidized glutathione (GSSG) contents as well as the activity of GST in three varieties of Z. mays , that were classified as aphid-susceptible, aphid-relatively resistant and aphid-resistant, respectively. The earliest and strongest aphid-triggered alterations in the levels of TT, PT and GSH, and the greatest induction of GST activity, were recorded in the resistant P\u0142omyk seedlings in relation to the relatively resistant Ambrozja and the susceptible Z\u0142ota Kar\u0142owa.The rose-grass aphid ( Zea mays L.) is one of the most important crops worldwide and its economic importance is growing \u201378M. dire plants .M. dirhodum attacks are based on the metabolism of thiol compounds, which is evidenced by alterations in the level of total thiols, protein-bound thiols and GSH, as well as by the activity of GST. The fluctuations in thiol content and GST activity were dependent on the maize variety, the number of aphids and the duration of M. dirhodum feeding. The strongest modulation of the antioxidant system related to sulfhydryl compounds was noted in the resistant variety, P\u0142omyk, which highlights the role of thiols in the resistance of maize genotypes to aphids.In conclusion, our experimental results indicate, that the defense mechanisms of maize plants against"} +{"text": "Scientific Reports 10.1038/s41598-017-10365-3, published online 30 August 2017Retraction of: This Article is being retracted at the request of the corresponding author, because the authors did not obtain relevant permissions from the Liver Cancer Laboratory at Xiangya Hospital, Central South University, who is the owner of some of the clinical specimens and related data for the use of these materials in the study.Xiong Lei, Shuai Xiao, and Taiyuan Li agreed to the retraction. The other authors could not be reached."} +{"text": "The International Federation of Pigment Cell Societies (IFPCS) held its XXIII triennial International Pigment Cell Conference (IPCC) in Denver, Colorado in August 2017. The goal of the summit was to provide a venue promoting a vibrant interchange among leading basic and clinical researchers working on leading-edge aspects of melanocyte biology and disease. The philosophy of the meeting, entitled Breakthroughs in Pigment Cell and Melanoma Research, was to deliver a comprehensive program in an inclusive environment fostering scientific exchange and building new academic bridges. This document provides an outlook on the history, accomplishments, and sustainability of the pigment cell and melanoma research community. Shared progress in the understanding of cellular homeostasis of pigment cells but also clinical successes and hurdles in the treatment of melanoma and dermatological disorders continue to drive future research activities. A sustainable direction of the societies creates an international forum identifying key areas of imminent needs in laboratory research and clinical care and ensures the future of this vibrant, diverse and unique research community at the same time. Important advances showcase wealth and breadth of the field in melanocyte and melanoma research and include emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, precision bench-to-bedside approaches, epidemiology, pigment biophysics and chemistry, and evolution. This report recapitulates highlights of the federate meeting agenda designed to advance clinical and basic research frontiers from melanoma and dermatological sciences followed by a historical perspective of the associated societies and conferences. The XXIII IPCC encompassed a series of opening and award lectures, including the IFPCS Presidential lecture and honorary lectures by the recipients of the Fitzpatrick, Lerner, and Seiji Awards. These awards are bestowed by regional pigment cell societies to leading international scientists who have made extraordinary contributions to pigment cell research. There were 8 plenary sessions and 32 concurrent sessions accomplishing a balance between clinical and basic melanoma and dermatology research.In addition to opening lectures, the first day included a plenary session on the evolution of pigmentary systems across the animal kingdom and three concurrent sessions on advances in vitiligo, melanocyte, and melanoma biology as well as disease management. On the second day, two plenary sessions covered fascinating advances in the genetics of coloration in various animal species and in UV light responses and DNA repair. The fourth day included two plenary sessions and four concurrent sessions that emphasized basic biology of melanoma and the latest developments in translational melanoma therapies and resistance. Day five was headlined by a plenary session with keynote speakers on the impact of regenerative medicine on pigmentary diseases and a plenary session on the immunologic control of melanocytes and melanoma. General sessions covered evolutionary biology of pigmentation, developmental biology, genetics, genomic profiling, neuroscience and pigmentation, melanocyte stem cells and regenerative medicine, hair biology, mouse and non-mouse models of pigmentation, melanosome biogenesis and transfer, melanin function and chemistry, and UV signaling in the melanocyte. The program also included three lunchtime poster sessions with presentation of about 200 posters. Importantly, sessions were specifically dedicated to provide mentoring and career opportunities for young scientists, women in science, and underrepresented minorities in science.The basic and clinical melanoma research sessions presented a state-of-the-art picture of immunotherapy, precision medicine, and genomic profiling of skin cutaneous, uveal, mucosal, and acral melanoma . KeynoteMC1R) variants. Dr. Nicolas Hayward delivered analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. In contrast to frequently occurring coding and non-coding mutations in cutaneous melanoma, the Australian consortium resolved structural changes and novel signatures of mutagenesis in acral and mucosal melanomas, not previously identified in melanoma [Highlights included updates on precision dermatology, bench-to-bedside approaches, genome-wide association studies, genetic diversity of pigmentation, and progress in immunotherapy . Dr. Ianmelanoma .A number of presentations also explored the genetic diversity of pigmentation in non-human and non-mouse systems. Dr. Cheng-Ming Chuong presented a novel foray into the world of feather pigment pattern formation, where color patterns important for animal behavior and speciation is modulated by the presence, arrangement, or differentiation of melanocytes . Among mThe International Pigment Cell Conference has emerged as the sole international scientific convention devoted to the study of the normal pigment cell and the advancement of basic, translational, and clinical research on diseases involving pigment cells. The first meeting was held in New York in 1946 and reconvenes on a triennial basis was developed first as the International Pigment Cell Society and then formalized as IFPCS in 1990. With the IFPCS formally acting as a means to provide interaction between the independently formed sister societies, the IPCC meeting was chartered as a main function of IFPCS. The Japanese Society for Pigment Cell Research (JSPCR) was founded in 1984, the European Society for Pigment Cell Research (ESPCR) in 1985, the Pan-American Society for Pigment Cell Research (PASPCR) in 1988, and the Asian Society for Pigment Cell Research (ASPCR) in 2004, each becoming members of IFPCS at that time. Thus, the mission of the IFPCS is to disseminate cutting edge research via the publication of the federation\u2019s journal, The XXIII IPCC, representing the four member Pigment Cell Societies of the International Federation, was hosted by the Pan-American Society for Pigment Cell Research in Denver, Colorado, on 26\u201330 August 2017. 540 registrants from 28 countries participated in the 8 plenary and 32 concurrent sessions. 8 keynote speakers led the program, along with 21 plenary session speakers and 80 invited speakers. A further 103 speakers were chosen from submitted abstracts. The main program was complemented by four pre-conference satellite symposia and four pharmaceutical company sponsored symposia. The annual meeting of the Melanoma Prevention Working Group (MPWG) was hosted for the first time at the IPCC meeting. The MPWG functions under the umbrella of the Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG). The MPWG meeting promoted clinically relevant research focused on key aspects of melanoma prevention and discussed innovative paths forward into clinical trials of chemoprevention agents for high-risk melanoma patients . The comA major program highlight was a dedicated session on advances in basic and clinical research on albinism. Albinism is a rare genetically inherited condition affecting approximately one in twenty thousand people in most world populations. Albinism occurs at relatively high frequency in sub-Saharan Africa. People with albinism experience visual deficits, hypopigmentation, and sun-sensitivity. In less advanced societies, people with albinism may not have access to healthcare specialists, sunscreen, or protective clothes. Moreover, in sub-Saharan Africa, a humanitarian crisis is presently underway affecting patients with this disease . The dedBreakthroughs in Pigment Cell and Melanoma Research. In essence, IPCC 2017 was at once an outreach to all members of the community and a call to stand unified in facing potential funding challenges as a field.IPCC 2017 was planned for late summer, 26\u201330 August 2017 in downtown Denver, Colorado. The strategy for designing and marketing of IPCC 2017 was informed by multiple lines of reasoning. First, with new melanoma therapies providing improvements in medical care, the field has progressed in an increasingly clinical direction, in some ways diminishing the focus on the basic research that has given rise to successful treatment strategies. Inevitably, new strategies will be needed to further advance the treatment of melanoma patients, and without a strong basic research base, these advances will not be possible. Moreover, successes in the translational arena of melanoma need to be duplicated in other key areas of pigment cell research, including vitiligo, melasma, and other pigmentary diseases. Providing a strong conference venue to support basic research in pigmentary diseases and melanoma in essence embraced the true mission of the IPCC meeting and of the IFPCS organization. A second influencing factor in designing IPCC 2017 was the recognition that with the World Melanoma Congress (WMC) associated with the Society for Melanoma Research (SMR) being scheduled for Brisbane in October, the IPCC would be the only major melanoma meeting to be held in the Northern Hemisphere in 2017. Thus a strong focus on melanoma would allow North American clinicians and researchers proximal access to the latest advances in the field. The third factor embraces all who are interested in pigment cell biology and disease by providing a comprehensive format for promoting interchange between such diverse groups of researchers. Thus, the theme of IPCC 2017 was strategically chosen as Initially, a dual focus on pigmentary disease and melanoma seemed to allow maximal opportunity for industry based meeting support. With strong support from the melanoma committee, major pharmaceutical company support was obtained to support the melanoma program. However, it proved more challenging to raise support from companies with an interest in pigment cell function and disease. This was compensated for by outstanding institutional support from groups within the University of Colorado system affiliated with the local organizing committee. Consequently, the meeting was supported by the melanoma related pharmaceutical industry, the University of Colorado, by conference registration fees and even through generous support from speakers, session chairs and attendees.The IFPCS is a vital global umbrella organization for the regional pigment cell societies. Over more than seven decades, the triennial IPCC has been an opportunity for scientist across the globe to gather to discuss recent findings, progress, and ongoing research. Consistently, the federation and local societies have provided the international research community with essential resources on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma.Melanoma to Vitilio: The Melanocyte in Biology and Medicine at Glendan Beach, OR commencing on October 17\u201322, 2018. The IPCC 2020 will be hosted in Yamagata, Japan from 18\u201321 July 2020. The title and focus of the XXIV triennial IPCC will be Integration of Basic Science and Clinical Practice in Pigment Cell Biology.In 2018, the Montagna Symposium on the Biology of the Skin and the Annual meeting of the Pan-American Society for Pigment Cell Research will host a joint conference entitled"} +{"text": "With the rise of older adults and the number of chronic health issues in this population, comes the need for greater collaboration across organizations and health care settings. Age-friendly health systems offer the benefits of providing the best care possible to individuals and families, connect people to specific community resources, and optimize the best access to services and programs. The Gateway Geriatric Workforce Enhancement Program (GWEP) has combined the efforts of Saint Louis University and a rural, critical access hospital to establish a care network across Missouri. Together, this partnership has created a number of services, initiatives, and projects to help older adults maintain independence and offer families ways to take of their loved ones in more effective ways. In this symposium, presenters from Social Work, Marriage and Family Therapy, Geriatric Medicine, Psychology and Nursing disciplines will introduce several areas of this age-friendly network. The four abstracts for this symposium include: 1.) Assessing At-Risk Older Adults through the Rapid Geriatric Assessment, 2.) Cognitive Stimulation Therapy for Individuals with Memory Loss, 3.) Predictors of Falls in Older Adults Across Partner Settings, and 4.) Development of program initiatives such as the Rapid Geriatric Assessment screening, Cognitive Stimulation Therapy, Falls Assessment in Seniors, and Care for Persons with Dementia in their Environments will be covered in detail. At the end of the four presentations, the presenters will highlight the importance of this collaborative network and ways for audience members to consider building an age-friendly network in their community."} +{"text": "The identification and development of cancer biomarkers and targets have greatly accelerated progress towards precision medicine in oncology. Studies of tumor biology have not only provided insights into the mechanisms underlying carcinogenesis, but have also led to discovery of molecules that have been developed into cancer biomarkers and targets. Multi-platforms for molecular characterization of tumors and blood-based biopsies have greatly expanded the portfolio of potential biomarkers and targets. These cancer biomarkers have been developed for diagnosis, early detection, prognosis, and prediction of treatment response. The molecular targets have been exploited for anti-cancer therapy with proven benefits in improving treatment response and survival. However, plenty of research opportunity exists for discovering, developing, and validating cancer biomarkers and targets for improving the clinical outcomes of patients with malignant diseases, particularly those in the digestive system.Pancreatic-hepato-biliary and gastrointestinal carcinoma are among the most lethal human malignant diseases . With thBiomedicines comprises a variety of articles about recent advances in the discovery, characterization, translation, and clinical application of cancer biomarkers and targets in the digestive system. These articles include original research, reviews, case studies, and conference papers. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference in Hershey, Pennsylvania, the new frontiers in various aspects of digestive organ cancers were presented [This Special Issue of resented . In thisresented . The bioresented . In thisresented . MoreoveA number of articles in this Special Issue examine the biomarkers and targets with a focus on cancer in individual organs, including liver. While liver transplantation is a potentially curative treatment of hepatocellular carcinoma, liver graft injury has been identified as an acute phase event that leads to post-transplant tumor recurrence. Lee et al. examined this acute phase event at the molecular level by transcriptomic analysis of liver grafts from recipients with or without tumor recurrence following liver transplantation . This stBesides hepatocellular carcinoma, several articles focus on cancer biomarkers and targets in the gastrointestinal tract. Fonkoua and Yee present a critical review of the molecular characterization of gastric carcinoma by the Cancer Genome Atlas Research Network, the Asian Cancer Research Group, and tumor molecular profiling through expression analysis and genomic sequencing of tumor DNA . These mDespite advances in developing clinically useful biomarkers and targets in gastrointestinal cancers, relatively little progress has been made for patients with pancreatic carcinoma. While early detection of pancreatic carcinoma is critical for improving patient survival, agents that selectively target pancreatic tumor are expected to enhance therapeutic efficacy. In this Special Issue, Matters and Harms present a detailed review of G protein-coupled receptors, which are key target proteins for drug discovery. They further discuss the potential of GPCRs as biomarkers for tumor imaging and targeted treatment of pancreatic carcinoma .Research on discovery and development of cancer biomarkers and targets has been steadily progressing. Rigorous investigation for identification and validation of biomarkers and targets in both preclinical models and clinical studies are expected to generate new opportunities for making a positive impact on survival and quality of life in the patients. The articles in this Special Issue provide an update on the frontiers in gastrointestinal oncology, with a focus on biomarkers and targets in cancers of the digestive system. We hope this Special Issue will help stimulate research collaboration on developing strategies for prevention, early detection, diagnosis, and screening of cancers in digestive organs, as well as improving treatment outcomes and psychosocial support in patients with these malignant diseases. In particular, liquid biopsy for cancer biomarkers and targets has been a major focus of research with translation into clinical applications.Recent advances in plasma-derived extracellular vesicles (EVs) have demonstrated the potential of making a clinically meaningful impact in the field of cancer biomarkers and targets. Analysis of EV-derived molecular markers is complementary to the conventional diagnostic modalities. By application of nano-, micro-, digital-, and microarray-based technologies, multiplex analysis of disease-specific markers is expected to improve the sensitivity and specificity of bodily fluid-based biopsies for diagnosis of cancer. These minimally invasive diagnostic tools that utilize ultra-low sample volume may prove to be economically cost effective for screening of cancer in the high-risk population and even in the general population. In addition to this, increasing evidence has indicated the potential value of blood-based biopsies in combination with tumor molecular profiling for developing predictive biomarkers of treatment response, as well as personalized targets of therapy. Further development, optimization, and clinical validation of these cancer biomarkers and targets will hopefully enable us to attain the goal of precision medicine in cancer of digestive organs."} +{"text": "Click chemistry has great potential for use in binding between nucleic acids, lipids, proteins, and other molecules, and has been used in many research fields because of its beneficial characteristics, including high yield, high specificity, and simplicity. The recent development of copper-free and less cytotoxic click chemistry reactions has allowed for the application of click chemistry to the field of medicine. Moreover, metabolic glycoengineering allows for the direct modification of living cells with substrates for click chemistry either in vitro or in vivo. As such, click chemistry has become a powerful tool for cell transplantation and drug delivery. In this review, we describe some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases. The iEDDA reaction has been used for the visualization of both antibodies and tumor tissues by PET imaging. Rossin et al. applied the iEDDA reaction for the selective cleavage of tumor-bound ADCs for cancer therapy [Since the iEDDA reaction has the fastest reaction rate of the bioorthogonal reactions , its app quality . They syon doses ,97. Theson doses . They sy therapy . First, In this review, we discussed the application of copper-free click chemistry for cell engineering in cell transplantation and drug delivery. Although certain factors remain unclear, including the safety of utilizing copper-free click chemistry and metabolic glycoengineering, these reports suggest that copper-free click chemistry is a powerful tool for cell engineering and drug delivery. As such, high biocompatible and fast copper-free click chemistry and its application in the biological and medical fields can be expected to develop further in the near future."} +{"text": "Recent evidence has suggested that polyphenol-rich foods intake may be associated with decreased risk of chronic diseases. The Special Issue \u201cEffects of Polyphenol-Rich Foods on Human Health\u201d comprised 64 peer-reviewed papers on the most recent evidence regarding the dietary intake of polyphenols and polyphenol-rich foods, as well as their effect toward the prevention and treatment of non-communicable diseases. Original contributions and literature reviews demonstrated the potential protective effects of polyphenol-rich foods and their extracts toward cardiovascular diseases, certain cancers, and neurodegenerative diseases, mostly through anti-oxidant and chemo-preventive properties. Over the last years, polyphenol-rich foods and polyphenols have received great attention due to their potential beneficial effects toward human health. Contained not only in fruits and vegetables, but also in whole-grains, nuts, olive oil and beverages such as coffee and tea, they are characteristic components of healthy dietary patterns . Recent This Special Issue \u201cEffects of Polyphenol-Rich Foods on Human Health\u201d comprises 64 peer-reviewed papers, including 43 original research papers ,48,49,50The Special Issue included systematic reviews and meta-analysis summarizing the level of evidence on both polyphenols and polyphenol-rich foods. In particular, published articles demonstrated that a moderate intake of coffee is inversely associated with the risk of hypertension , and canEpidemiological and clinical studies reported the following associations of polyphenols and polyphenol food extracts: silibinin and non-alcoholic fatty liver disease ,39, resvImportantly, numerous reviews summarized the evidence regarding polyphenols and polyphenol-rich foods and their association with NCDs related to oxidative stress and inflammation, including CVDs, diabetes, hypertension, obesity, certain cancers and neurodegenerative diseases ,69,70,71Several contributions investigated polyphenol metabolism and transformation into bioavailable molecules and underlined the importance of the clarification of the metabolic fate of polyphenols and their bioavailability in order to fully understand the molecular forms responsible for the preventive actions of polyphenols ,35,36,43Polyphenols have been demonstrated to be responsible for the anti-inflammatory and antioxidant properties of potentially functional foods. Numerous studies explored in detail the molecular mechanisms underlying the protective effects of polyphenols, including antioxidant capacity, that can be attributed to the regulation of redox enzymes through reducing reactive oxygen species (ROS) production and modulation of the II-phase enzymes responsible for the cellular oxidative response; other studies explored the chemo-preventive effects of polyphenols, including the elimination of carcinogenic agents, the modulation of pathways responsible for cancer cell signaling and cell cycle progression, and in the promotion of apoptosis ,48,49,50Nutrients for their professional help in the completion of this Special Issue.As a guest editor, I would like to acknowledge all the authors for their valuable contributions and the reviewers for their constructive remarks. Special thanks to the publishing team of the journal"} +{"text": "An ad hoc committee of the National Academies of Sciences, Engineering, and Medicine examined the potential for integrating services addressing social needs and the social determinants of health into the delivery of health care to achieve better health outcomes and to address major challenges facing the U.S. health care system. These challenges, include persisting disparities in health outcomes among vulnerable subpopulations, often defined by a number of factors including age. Presenters will discuss and provide recommendations in the following areas: 1. evidence of impact of social needs care on patient and caregiver/family health and wellbeing, patient activation, health care utilization, cost savings, and patient and provider satisfaction; 2. opportunities and barriers to expanding historical roles and leadership of social workers in providing health-related social needs care and evidence-based care models that incorporate social workers and/or other social needs care providers in interprofessional care teams across the care continuum and in delivery system reform efforts ; and 3. realized and potential contributions of social needs care to make health care delivery systems more community based, person- and family/caregiver-centered, and responsive to social and structural determinants of health, particularly for vulnerable populations and communities, such as older adults and low-income families. Examples for each of the three areas will also be presented."} +{"text": "Otala lactea snails during estivation arrest of transcriptional and translational activity, (ii) depression of metabolic rate, (iii) re-wiring of energy metabolism pathways toward fermentative rather than oxidative routes, (iv) activation of mechanisms involved in both macromolecular repair and detoxification of cellular-derived oxidants toward a reduced state, favoring the production of superoxide radicals , followed by up to 40\u201360% reductions (from 7 to 21 days) , and GPX activities by 53 and 100%, respectively, upon severe hypoxia further understand the molecular mechanisms controlling the hormetic POS phenomena, for example providing evidence for the role of kinases/phosphatases in the improvement of the antioxidant response in hypoxic tolerant species, and (ii) keep searching for the POS-response in nature (Moreira et al., MO, DM, and MH-L worked on the concept of hormesis and its application on the POS theory. DM, TF, and MG contributed with key examples of POS-related studies. MO and MH-L drafted the manuscript, which was reviewed and approved by all authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."} +{"text": "This systematic review aimed to examine the associations between health-related outcomes and the built environment (BE) characteristics of compact metropolitan cities in Korea using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Searching the three Korean academic databases and PubMed, two independent reviewers identified 27 empirical articles published between 2011 and 2016. Data extracted for review included the study characteristics, the variables and measurement methods related to the BE and health-related outcomes, and the findings on the associations between the BE characteristics and health-related outcomes. Vote counting was used to assess the consistency of associations and the direction of associations between the BE characteristics and health-related outcomes. All of the reviewed studies used cross-sectional designs. The objective BE qualities were commonly examined. The BE characteristics associated with health-related outcomes in the reviewed articles included land use, street environment, transportation infrastructure, green and open spaces, and neighborhood facilities. Street environment, transportation infrastructure, and green and open spaces had consistent positive associations with physical health. Mixed land use and neighborhood facilities, however, had inconsistent associations with physical health. Generally, insufficient findings were reported in the association between the BE characteristics and mental and social health. The accessibility of the BE in a compact urban environment was the prominent attribute related to health promotion, health challenges, and health equity. An international comparative analysis of compact cities with different urban contexts and scale is required. Interdisciplinary urban health strategies are recommended based on the associations between the BE characteristics and health-related outcomes. As health promotion strategies targeting policy, system, and environment changes become more important, the built environment (BE) is becoming a key element of interventions . The BE In the Global Report on Urban Health, the World Health Organization (WHO) indicated the influence BE conditions have on public health, notably in the urban context . This iswhat aspects of and how the BE in metropolitan cities affects public health. The impact of BE on public health is a topic that has been studied extensively around the world. Existing literature suggests that mixed land use, street connectivity, public transportation, and green space are positively related to physical activity and weight loss ,7. Furth2, (2) an independent budget management system, (3) public transit infrastructure (subway and bus), and (4) an urban master plan for compact urban design [The Organisation for Economic Co-operation and Development (OECD) recommends that metropolitan cities adopt a compact urban design to solve urban problems caused by high population density and inefficient land use . Metropon design . AccordiThe health status of residents in Korean metropolitan cities is complicated. The following indicators were better than the WHO average in 2016: Life expectancy at birth was 82.7 years, prevalence of insufficient physical activity was 35.4%, prevalence of depressive disorders was 3.0%, and the prevalence of obesity was 26.0% ,14. On tAlthough Korean studies on the BE and health have been conducted since 1978, there have been scare attempts to integrate the results of BE characteristics that affect the health of urban populations. These studies have focused on different BE and health-related variables, and have used different methods and measurement criteria . They alThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework for conducting and reporting systematic reviews . The rev-Studies conducted in Korean metropolitan cities.-Studies that objectively or subjectively measured the BE reported as independent variables.-Studies that objectively or subjectively measured health-related outcomes .-Peer-reviewed and fully published articles.-Published articles written in Korean or English.Studies were selected by applying the eligibility criteria of settings, study design, methods, and outcome measures. Inclusion criteria were: -Studies that objectively or subjectively measured indoor facilities and working facilities reported as independent variables.-Studies that objectively or subjectively measured the natural environment reported as independent variables.-Systematic reviews.-Qualitative studies.-Studies conducted to develop the BE measuring instrument that does not analyze the correlation with health.-Descriptive studies with only bivariate analysis.Exclusion criteria were:Between February and June 2017, we conducted literature searches in three Korean academic databases and PubMed. The search terms were identified from previous related reviews and the Data extracted included the characteristics , the BE variables and measurement methods, health-related variables and measurement methods, and significant and non-significant findings on the correlation between the BE characteristics and health-related outcomes.To include all the BE variables across studies, we listed and categorized each variable and construct of the BE characteristics . The BE Vote counting was conducted to summarize the number of studies reporting significant and non-significant findings and the direction of the associations between the BE characteristics and health-related outcomes. The Cochrane handbook indicates that vote counting may be useful when statistical meta-analysis cannot be applied due to the heterogeneity of measured outcomes .\u201cConsistent association\u201d was defined as 75% to 100% of the significant findings reporting the same direction within the BE characteristics (c.f. <75%: \u201cinconsistent association\u201d) [In order to clarify the direction of association, we classified the findings as positive or negative as a result of the direction of health promotion. The consistency of associations between the BE characteristics and health-related outcomes was determined by five studies or more that reported significant findings to sufficiently indicate consensus .In the first PRISMA stage, 1077 articles were selected . Of thesThe number of publications has increased in recent years. Researchers represented 12 fields of study, primarily urban planning and design (39%). Some studies (14%) involved researchers from two disciplines. Only three studies were conducted by public health researchers (11%). Overall, Korean studies tended toward a mono-disciplinary approach from the perspective of urban planning rather than public health.All studies used a cross-sectional design. The research setting was as follows: 67% in the capital city, 22% in the metropolitan cities, and 11% in both. More than half the studies (56%) had participants of specific age groups, including adolescents (15%), adults (22%), and the elderly (19%), and 44% had participants of all ages. One study used comHealth-related variables were classified according to the physical, mental, and social health domain. Most studies (81%) used physical health-related variables to examine the relationship between the BE and health, including health-related behaviors, illness or death, and perceived health status. The health-related behaviors included moderate or high intensity physical activity, walking, sedentary behavior, and dietary behavior, with walking being the most common ,41,45,46About one-fifth (19%) of the studies examined the relationship between the BE and mental and social health. The mental health-related variables included prevalence of mental illness and levels of depression, stress, and self-esteem. Of these, depression was used in four studies as a measure of mental health ,28,30,37We investigated the associations between the BE characteristics and health-related outcomes. As noted earlier in Mixed land use had an inconsistent association with physical health ; five ouNon-consistent associations were found between mixed land use, mental health, and social health ,43. MixePedestrian-friendly environments had a positively consistent association with physical health . The higher density and shorter distance of welfare centers were correlated with reduced depression . PerceivThis systematic review has clarified the association between the BE and health in compact metropolitan cities. Empirical research on the BE and health in Korean metropolitan scale cities has been conducted primarily in the fields of urban planning and urban design. All studies reviewed were cross-sectional. Among the studies using secondary data, none conducted detailed spatial unit analyses at the community level, which Lee considerThe BE characteristics that affected health were land use, street environment, transportation infrastructure, green and open spaces, and neighborhood facilities, which aligns with previous studies . The BE The health-related outcomes in the included studies focused on physical health, with few studies including the mental and social health domains. This result supports previous findings suggesting associations between the BE and health lacked an integrated view of health and multi-domain considerations . To overIn previous studies, mixed land use has been reported to be a key strategy for compact city policies that contribute to reduced obesity and promote physical activity ,58. HowePedestrian-friendly environments promote walking and social activities of urban residents. In particular, safety and accessibility were important attributes of the pedestrian-friendly environment ,41,43,49Safety and accessibility can serve as factors for cities to stay active for 24-h, but they can lead to negative health outcomes. Koo et al. pointed In our study, transportation infrastructure has been found to be associated with the promotion of physical and social health through public transportation and bicycle use; whereas, automobile use has a negative impact on physical activity and community safety. These findings support the health promotion effect of active transportation that restrains the use of vehicles and promote the use of bicycle and public transportation ,63. In aWe found that the proportion of parks and green spaces was associated with physical and mental health. However, if the green area of the city is excessively large, it would interfere with spatial connectivity and have a negative effect on physical, social, and mental health. This supports the hypothesis that open spaces only promote walking up to a certain size threshold . Some stWhen neighborhood living facilities are safe, close and convenient to use, outdoor activities are frequently performed, opportunities for social relationships increase, and depression decreases. In terms of equitable utilization of community assets, physical and economic accessibility and the spatial distribution of neighborhood facilities are related to health equity. This suggests that the strategic utilization of neighborhood facilities as a daily life condition for local residents can lead to the social participation of vulnerable groups and physical health promotion . In our Overall, we found that BE characteristics in compact metropolitan cities associated to health-related outcomes had accessibility as a common attribute. The accessibility of the BE contributed to health promotion in terms of resource availability. Urban planning and policies for compact cities positively affected walking for travel and physical activity, and promoted social interactions and networks ,48,49,50However, the accessibility of the BE produced some health challenges: 24-h facilities near the residential area increased fatigue and the obesity rate of residents by increasing their nighttime activity and chances of eating later in the evening ,35. MixeThe accessibility of the BE is an important health equity issue. Areas with a low density of public transport and neighborhood facilities tended to worsen the physical, mental, and social health of the residents. In urban areas with low access to the BE, physical activity and walking decreased, obesity increased, and residents had difficulty maintaining and forming social relationships ,42,43. TThe association between the BE and health studied in the Korean metropolitan cities with a compact urban environment was mostly consistent with that found in urban health research conducted at other urban scales. However, there were differences for some health-related outcomes, the criteria for spatial accessibility, and the BE variable of density. These differences were attributed to the dense and complex urban structure of Korean metropolitan cities and the manner in which the decision-making of health behavior interacts with the perceived environment. Therefore, health promotion strategies aimed at environmental change should consider the environmental specificity and the attributes of the perceived environment related to health behaviors.Because this study only examined studies published in peer-reviewed journals, high-quality research published outside of peer-reviewed journals was included in the results. This review was limited to studies published from 2011 to 2016, and some studies might have been left out of the review because of the limitations of the search terms, search criteria, and search databases used. Additionally, quality assessment was not conducted, and all the included studies used cross-sectional designs. The causal assumption and true effects are difficult to determine by synthesizing results from cross-sectional studies.Despite these limitations, due to a systematic review by following PRISMA, the consistency and direction of findings across studies reviewed were rigorously examined. We also identified the BE variables and measurement methods, and health-related variables and measurement methods. These results strengthen the existing evidence for the associations between the BE and health and provide research design and methodological implications for future research on the BE and health.This study systematically examined the associations between the BE characteristics and health-related outcomes in compact metropolitan cities in Korea and identified the health benefits and risks of the particular BE characteristics in such cities. All of the reviewed studies were cross-sectional, the study methods and measurement tools varied, and there was insufficient evidence for the associations between the BE characteristics and social and mental health. Future research is called for to focus on the impact of BE characteristics on mental health and social health in a compact urban context, and to use theoretically sound longitudinal designs.Interdisciplinary urban health strategies are required based on the associations between the BE characteristics, health-related outcomes, and the environmental context. Evidence for the associations between the BE characteristics and health-related outcomes in compact metropolitan cities may provide a greater understanding of the health effects and health behaviors of urban development for compact cities in other countries. A comparative analysis with international studies would contribute to further planning for rational urban development."} +{"text": "Keywords: trauma; intimate partner violence; mental disturbance; torture; corrigendumAt a community-wide level, in the case of torture survivors, the focus should be on violence prevention by way of early identification and support for men at risk; provision of timely work, educational, and financial assistance; and programs aimed at harmonizing the re-entry of the male survivor back into the family and broader community.The references Pease & Flood, 2008 and Vichealth, 2014 were mistakenly added following the paragraph:"} +{"text": "Chitin and chitosan are very abundant natural polymers with distinctive properties, such as bioactivity, biocompatibility and biodegradability, that have inspired a number of basic and applied studies, mostly in biotechnology, medicine, food preservation and agriculture. The interest in these polysaccharides is still quite high and lot of scientists are currently devoting their efforts to improve the knowledge in this field, gather in various scientific societies spread all over the world and organise specific conferences. The same broad interest in chitin and chitosan has been devoted to the various enzymes involved in their hydrolysis and the corresponding enzyme-producing organisms, in particular bacteria and fungi.Research on chitin, chitosan, and related enzymes has led to many basic and applied studies carried out in order to: explore the potential of these natural polymers , investigate the action and perspectives of the various enzymes and to directly apply the chitinolytic organisms. Although the field had been widely investigated, there is still room for interesting research novelties. This Special Issue aimed to provide a platform for the dissemination of the most advanced studies in this field and main topics were: the physics, chemistry, and biochemistry of chitin and chitosan; chitin, chitosan, and chitin-derivatives production; applications of chitin, chitosan, and their derivatives; and the bio-synthesis and bio-degradation of chitin and chitosan.Various scientists participated in this issue dealing with these various topics, and the Editorial Committee sought to accept only peculiar and/or particularly innovative papers, including review papers, covering the various aspects of the issue as follows:Synthesis and Characterization of Glutamic-Chitosan Hydrogel for Copper and Nickel Removal from Wastewater [. Chitosan preparations were treated with various concentrations of glutamic acid resulting in different types of glutamic-chitosan hydrogels that were tested for the removal of copper(II) and nickel(II) from wastewater. The increase of glutamic acid concentration led to a decrease of metal removal efficiency, probably due to a decrease in the pore size of the hydrogels.stewater . ChitosaInhibition of Listeria monocytogenes in Fresh Cheese Using Chitosan-Grafted Lactic Acid Packaging [. Chitosan was grafted with d,l-lactic acid in aqueous media using p-toluensulfonic acid as catalyst to obtain a non-toxic, biodegradable packaging material that was characterized using scanning electron microscopy and other techniques. The grafting in chitosan with d,l-lactic acid produced films with improved mechanical properties. This material successfully extended the shelf life of fresh cheese and inhibited the growth of Listeria monocytogenes during 14 days at 4 \u00b0C and 22% relative humidity. The results were compared to control samples and commercial low-density polyethylene packaging demonstrating that the use of non-toxic chitosan-g-LA for packaging of fresh cheese offers a valid alternative for the preservation and conservation of this product and inhibited the growth of Listeria monocytogenes.ackaging . ChitosaChitosan Nanoparticles as Carriers for the Delivery of \u03a6KAZ14 Bacteriophage for Oral Biological Control of Colibacillosis in Chickens . The useSorption of Cu(II) Ions on Chitosan-Zeolite X Composites: Impact of Gelling and Drying Conditions [. Different typologies of chitosan-zeolite Na-X composite beads were prepared by encapsulation and analysed by a series of methods in order to investigate Cu(II) sorption. The drying method used for the storage of the adsorbent severely affected both the structural properties of the composite and the copper sorption effectiveness. Textural and Cu(II) sorption data indicated that whereas a chitosan coating impaired the accessibility of the microporosity of the zeolite; presence of zeolite improved the stability of chitosan dispersion upon supercritical drying and increased the affinity of the composites for Cu(II) cations.nditions . DiffereThe Psychrotolerant Antarctic Fungus Lecanicillium muscarium CCFEE 5003: A Powerful Producer of Cold-Tolerant Chitinolytic Enzymes [Chitosan and Its Derivatives as Highly Efficient Polymer Ligands [. This review paper covers results of the last decade. Chitosan has a polyfunctional nature permitting its application as a polymer ligand not only for the recovery, separation, and concentration of metal ions, but also for the fabrication of various functional materials. Although unmodified chitosan itself is the unique cationic polysaccharide with very good complexing properties toward numerous metal ions, its sorption capacity and selectivity can be sufficiently increased and turned via chemical modification to meet requirements of the specific applications. The main information supplied by this paper was aimed to demonstrate how different strategies of chemical chitosan modification effect metal ions binding, and to underline the mechanisms involved in ions binding by chitosan derivatives. Ligands . This reAll the published manuscripts have contributed to provide an image of the current and future trends in the development of chitin, chitosan and related enzyme research. The Editorial Committee expects that this Special Issue may help to understand the great potential of this specific research field and encourage further research on this matter."} +{"text": "Typhoid fever is a continuing public health problem in many low- and middle-income countries; however, routine vaccination as a recommended control strategy has not been implemented in the past in most countries. Greater understanding of the typhoid fever burden, the increasing threat of antimicrobial resistance, and licensure of a new generation of typhoid conjugate vaccines (TCVs) were instrumental in paving the way for the World Health Organization (WHO) to issue a revised global policy on typhoid vaccines in March 2018. The new policy follows evidence-based recommendations by the WHO Strategic Advisory Group of Experts on immunization for routine and catch-up vaccination with TCVs and highlights considerations for universal, risk-based, or phased vaccination strategies in different settings. Further, the first WHO-prequalified TCV and Gavi funding for eligible countries make vaccination a realistic control strategy for many affected countries, especially if combined with improved water and sanitation services, strengthened surveillance systems, and appropriate antimicrobial treatment. Salmonella enterica serovar Typhi, include access to safe water, adequate sanitation, personal and food hygiene, health education, appropriate antimicrobial treatment, and vaccination. While water, sanitation, and hygiene (WASH) strategies are powerful tools for typhoid control, the major financial investments required for infrastructure development and maintenance limit WASH solutions in the short to medium term in most typhoid-endemic countries [An estimated 11 to 21 million cases and more than 128 000 deaths from typhoid fever occur annually across many low- and middle-income countries, primarily in South and Southeast Asia and sub-Saharan Africa . Effectiountries , 5. WeigWHO is mandated to provide global vaccine policy recommendations based on a transparent and systematic evidence review process by the Strategic Advisory Group of Experts (SAGE) on Immunization, an independent advisory committee that advises the WHO on the development of policy related to vaccines and immunization , 7. WHO In 2008, WHO updated its policy on the parenteral unconjugated Vi polysaccharide and oral live attenuated Ty21a typhoid vaccines and emphasized their programmatic use to control endemic and epidemic typhoid fever where the disease remained a significant public health problem. Public health use of the Vi polysaccharide vaccine in 2 large demonstration projects in Asia, in 2003\u20132004 and 2010\u20132012, provided evidence of vaccine effectiveness and safety, feasibility of community- and school-based delivery strategies, and acceptability of the vaccine in the target populations , 10. HowSeveral key developments over the last decade refocused attention on the potential for routine vaccine use as a critical public health tool, especially when integrated with WASH and other strategies, for the control of typhoid fever. Crucially, data from the Typhoid Surveillance in Africa Program showed moderate to high disease incidence in some sub-Saharan Africa countries, rivalling rates previously described in parts of Asia . These gSalmonella Typhi, including spread of the H58 haplotype, which has been responsible for much of the recent and current spread of resistant strains [Salmonella Typhi H58 strain with resistance to the traditional first-line antibiotics of ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole, as well as additional resistance to fluoroquinolones and ceftriaxone, in an ongoing outbreak in Pakistan [Second, there has been a growing body of evidence about the threat of antimicrobial-resistant strains of strains and emer strains . ConcernPakistan .Third, the long-anticipated availability of a newer generation of typhoid conjugate vaccines (TCVs) moved closer to reality with licensure in India of 2 Vi-tetanus toxoid conjugate vaccine products in 2008 and 2013. An earlier Vi-rEPA conjugate vaccine had provided extensive clinical trial data that demonstrated safety, immunogenicity, and clinical efficacy of 89.0% over 46 months follow-up in Vietnamese children aged 2\u20135 years . HoweverFocus on typhoid conjugate vaccines necessitated a review of the (hitherto limited evidence on) age-specific burden in infants and children aged <2 years and the key considerations for the optimum schedule and delivery strategies for that age group. Revision of the typhoid vaccine policy followed the standard SAGE process for the development of vaccine recommendations, which incorporates review of the best available evidence on the clinical and epidemiologic characteristics of the targeted disease in different settings; vaccine characteristics and performance; and immunization, economic, health-system, legal, and ethical considerations, as well as social values and preferences regarding the target vaccine. This evidence review is combined with assessment of the quality of evidence on critical policy questions and, where needed, expert interpretation and judgment on specific programmatic questions to guide the resulting public health decision-making . As withThe new WHO policy recommendations reemphasize programmatic use of typhoid vaccines for the control of typhoid fever and specify that among the available typhoid vaccines, TCV is preferred at all ages in view of its improved immunological properties, suitability for use in younger children, and expected longer duration of protection. Recommendations for routine and catch-up vaccination as well as the specific considerations for national decisions on the preferred vaccination strategy are laid out in the WHO position paper .With the first WHO prequalification of a TCV and a de"} +{"text": "Herbal medicines have been used in traditional medical practices for centuries. While practitioners of herbal medicines are often comfortable with the application of such medicines and are also largely convinced by the results they experience with patients, the scientific validity of herbal medicines in research and development is still often questioned. This is partly due to the lack of quality control, identification, and standardization of chemical compounds and drug formulations, as well as the challenges of applying the same methodologies across dissimilar medicinal products. The development of herbal medicine within the framework of evidence-based medicine is relatively new. Applying the methodologies of Western-based pharmaceutical sciences to herbal medicines presents the research community with a complex set of challenges. However, it is essential that herbal medicine research design and conduct be scientifically and ethically sound, while also taking into account the medical philosophies and practices that accompany the use of traditional herbal medicine.Our special issue is focused on the application of modern technologies and methodologies in herbal medicine research and development using the accepted Western scientific and ethical standards. In the last decades, there has been significant progress in advancing traditional herbal medicine research and development, particularly in Asia, where there is an abundance of medicinal plants. As this issue will illustrate, the application of modern technologies and methodologies can have a significant impact on the scientific validity, quality improvement, and standardization of herbal medicines. et al., the extraction of the bioactive ingredient glycyrrhizic acid from Glycyrrhiza glabra was successfully optimized using a mathematical modeling approach. The plant is one of the most widely used traditional medicines in China, mainly for invigorating the spleen, replenishing qi, and clearing away heat and toxic substances to treat diseases such as the weakness of the spleen and stomach, coughs, and phlegm. The authors demonstrated that the combinational method of genetic algorithm and artificial neural networks provides a reliable and accurate strategy for designing and optimizing glycyrrhizic acid extraction from Glycyrrhiza glabra.In the study of L. Yu et al. investigated the association between the proangiogenic mechanisms of Long-Zhi Decoction (LZD) medicated serum on cellular autophagy. The promotional effect of LZD on angiogenesis was examined in vitro using human umbilical vein endothelial cells (HUVECs). Proliferation, migration, and tube formation were assessed in a cell-based assay. A transmission electron microscope was used in the measurement of autophagosomes to determine the extent of autophagy. Immunofluorescence and Western blot were used to determine the autophagy-related proteins of LC3-ll and Beclin-1. The results showed that the LZD-medicated serum increased autophagosomes and the autophagic protein expressions of LC3-ll and Beclin-1. The LZD-medicated serum also promoted the proliferation, tube formation, and invasion of HUVECs. This may suggest that LZD promotes angiogenesis by increasing cellular autophagy.Q. He et al. conducted a preliminary study in a transgenic strain of mice with adenocarcinoma of the mouse prostate (TRAMP) to evaluate the efficacy of the Deep Immune\u00ae (DI) as a prevention strategy to control the progression of prostate cancer. DI is a commercial natural health product consisting of a mixture of eight medicinal herbs. It was shown to stimulate phagocytosis and expression of a panel of inflammatory mediators in cultured macrophages in vitro. In addition, it also increases the tumor-killing ability of both macrophages and TRAMP mouse splenocytes. Daily intake of this herbal product significantly prevented prostate cancer progression, suggesting the possible effectiveness of the immunostimulant herbal products in the prevention of the progression of prostate cancer.P. Liang Candida albicans. Based on the microbiological test, the concentration of 0.05% of thyme essential oil in the oleogel mixture was shown to exhibit an antifungal activity against Candida albicans.G. Kasparaviciene et al. successfully formulated oleogel with thyme essential oil, designed its optimal formulation, and investigated the influence of ingredients on texture parameters of the preparation while also testing for its antimicrobial activity. The formulation optimization of oleogel was designed by means of a response surface model using Design-Expert 6 program, accompanied by texture analysis. The characterization and quantification of components of essential oils and oleogels were performed by GC-FID. The antimicrobial activity of oleogels with essential thyme oil was determined against Gynostemma pentaphyllum (GP) extract on NAFLD. The in vivo results showed that GP extract alleviated fatty degeneration and haptic fibrosis in NAFLD mice. Through a network pharmacology approach and biomedical assay, the potential active components of GP and their intracellular targets for hepatoprotective activity were identified as acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase-1 (CPT-1).Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries. M. Hong et al. conducted a study to explore the potential protective effects and mechanisms of action of et al. performed a systematic review and meta-analysis of the effects of Panax ginseng on obesity in animal models. Sixteen studies were included in the review. The meta-analysis indicated that oral administration of P. ginseng is effective against weight gain particularly in the obesity model induced by high-fat diet. The review showed that while P. ginseng improved serum lipid profile in animal obesity model, its processing method may affect treatment outcomes.H.-S. ParkJ. Zhong et al. performed another systematic review to evaluate the efficacy and safety of Ma-Huang-Fu-Zi-Xi-Xin decoction (MHFZXXD) in patients with allergic rhinitis (AR). The review included six randomized control trials (RCTs) in 576 patients. Despite its long use and recommendation in a clinical guideline for the alleviation of symptoms of AR, this systematic review concluded that there is insufficient evidence to support the use of MHFZXXD alone for routine treatment of AR. Several scientific issues were identified in the included RCTs, indicating that there were various types of biases in each study, including selection, performance, attrition, and reporting bias. In addition, the sample size of each trial was shown to be too small to provide conclusive results.In conclusion, significant progress is seen in the application of Western research methodologies to the evidence-based evaluation of, and further development of, traditional herbal medicines. The research presented in this special issue demonstrates advances in the technologies and scientific strategies for an evidence-based approach to herbal medicines. This offers promise for a more solid and uniformly accepted basis for the confirmation or rejection of the continued use of specific traditional herbal medicines. The employment of these research methodologies also opens new vistas for discovering new chemical compounds and formulations that may support the development of traditional herbal medicine formulations into Western pharmaceuticals. This special issue further provides evidence that modern techniques and methodologies, including mathematical modeling, are not limited in their application to any stage of herbal medicine research and development, assisting both traditional practitioners and Western scientists in addressing challenges to the scientific validity of specific herbal medicines as well as to help further develop these medicines for uses outside their traditional practices and contexts."}